Congenital Heart 22

A Comprehensive Approach to
Congenital
Heart Diseases
http://vip.persianss.ir
A Comprehensive Approach to
Congenital
Heart Diseases
Editor-in-Chief
IB Vijayalakshmi
MD, DM, FICC, FIAMS, FIAE, FCSI, FICP, FAMS, DSc
Professor of Pediatric Cardiology

Sri Jayadeva Institute of Cardiovascular Sciences
and Research, Bengaluru, Karnataka India
Editors
P Syamasundar Rao
MD, DCH, FAAP, FACC, FSCAI
Professor of Pediatrics and Medicine

Emeritus Chief of Pediatric Cardiology
UT-Houston Medical School
Houston, Texas, USA
Reema Chugh
MD, FACC
Consultant
Cardiology/Adult Congenital Heart Disease
and Heart Disease in Pregnancy
Kaiser Permanente Medical Center
Panorama City, California, USA
Foreword
Dr Joseph K Perloff
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A Comprehensive Approach to Congenital Heart Diseases
First Edition: 2013
ISBN 978-93-5090-267-7
Printed at
Dedicated to
Maude Abbott
First to publish An Atlas of Congenital Heart Disease
Madam Helen Taussig
Mother of Pediatric Cardiology
Dr Joseph K Perloff
Master teacher of Congenital Heart Diseases
Dr S Padmavati
A doyenne of Pediatric Cardiology in India
who has inspired many like me to become Cardiologists
Dr IB Vijayalakshmi
My teachers
Dr Lavanya Muhkerjee, Dr Herman W Lipow, Dr Norman J Sissman
Dr Jerome Liebman, Dr Leonard M Linde
My parents
Dr PVB Krishna Rao, Dr Patnana Savithramma
My wife and children
Dr Hymavathi
Dr Vijay Kumar, Dr Madhavi, Dr Radhika
Dr P Syamasundar Rao
Above all
To all the patients
Past, present and future
Who are our best teachers
and
For whom the quest for knowledge continues...
Dr Reema Chugh
Contributors
Abhilash SP MD DM
Assistant Professor of Cardiology
Sree Chitra Tirunal Institute for Medical
Sciences and Technology
Trivandrum, Kerala, India
abhispin@gmail.com
AM Jagadeesh MD
Professor and HOD
of Cardiac Anesthesia
Sri Jayadeva Institute of Cardiovascular
Sciences and Research
Bengaluru, India
Anil Sivadasan Radha
MD DNB(Pediatrics) DNB(Cardiology)
Consultant Pediatric Cardiologist

Department of Pediatric Cardiac Sciences
Apollo Health City, Jubilee Hills
Hyderabad, India
dranil.s.r@gmail.com
Anita Shet MD
Associate Professor
Department of Pediatrics
St Johns Medical College Hospital
Bengaluru, India
anitashet@gmail.com
Anurakti Srivastava
MD(Pediatrics), Fellow (Pediatric Cardiology)

Hyderabad, India
anurakti07@yahoo.co.in
Arjun Kalyanpur ABR
Chief Radiologist
Teleradiology Solutions
Bengaluru, India
arjun.kalyanpur@telradsol.com
Asha Moorthy MD DM
Professor of Cardiology
Sri Ramachandra University
Chennai, India
drashasrmc@yahoo.co.in
James R Bentham DPhil BM BCh BA

Paediatric Cardiology Intervention Fellow
Yorkshire Heart Centre
Leeds General Infirmary
Leeds, UK
bentham@well.ox.ac.uk
Charles W Hoopes
Associate Professor of Surgery
Director, Heart Lung Transplant and
Mechanical Cardiac Support Program
University of Kentucky College
of Medicine, Lexington, KY, USA
Bhanu Duggal MD DM
Associate Professor of Cardiology
Grant Medical College and
Sir JJ group of Hospitals
Mumbai, India
medhawini2k@yahoo.com
Chitra Narasimhan MD FICPC

Assistant Professor of Clinical
Pediatric Cardiology
Bengaluru, India
chitradr@gmail.com
Bhushan Chavan
Junior Consultant in Pediatric Cardiology
Madras Medical Mission
Chennai, India
Biswajit Bandyopadhyay
Head of the Department
Sr Consultant Pediatric Cardiologist
Rabindranath Tagore International Institute
of Cardiac Sciences (RTIICS)
Kolkata, India
bisban@rediffmail.com
Brannon Hyde
Fellow in Cardiothoracic Surgery
University of Kentucky
College of Medicine
Lexington, KY, USA
Biswaranjan Mishra MD DM
Chief Consultant Cardiologist
Eko Imaging Institute
Medical Road, Mangalabag
Cuttack, Odisha, India
drbisumishra@yahoo.co.in
Chandrakant B Patil
Professor and HOD of Cardiology
St Johns Medical College
Bangaluru, India
drcbpatil@gmail.com
Chandrika YR MD
Professor and HOD
Pediatric Anesthesiology
Indira Gandhi Institute of
Child Health
Bengaluru, India
doctoryrc@gmail.com
Debasree Ganguly MD FNB(Ped Card)

Junior Consultant in Pediatric Cardiology
Rabindranath Tagore International Institute
of Cardiac Sciences
Kolkata, India
debasreeganguly23@gmail.com
Deborah J Kozik
Assistant Professor of Surgery
of Medicine
Pediatric Cardiac Surgery
Kentucky Childrens Hospital
Lexington, KY, USA
Devananda NS MS MCh
Consultant and Head
Department of Cardiothoracic Surgery
Manipal Heart Institute
Bengaluru, India
devananda_ns@yahoo.com
Dinesh Choudhary
MD DM Fellow in Cardiac Electrophysiology

Trivandrum, India
drdineshchoudhary8@gmail.com
Duraisamy Balaguru
MBBS DCH MRCP (UK) FAAP FACC
Associate Professor of Pediatrics

Division of Pediatric Cardiology
Houston, Texas, USA
Duraisamy.Balaguru@uth.tmc.edu
English C Flack MD MS
Clinical Fellow
Pediatric Heart Institute
Monroe Carell Jr Childrens Hospital
at Vanderbilt
Nashville, Tennessee, USA
english.c.flack@vanderbilt.edu
Girish Warrier MS MCh(CVTS)
Consultant Pediatric Cardiac Surgeon
Hyderabad, India
Krishnamoorthy KM DM DNB FACC

Additional Professor of Cardiology
Trivandrum, India
kmkm@sctimst.ac.in
Gowrishankar MS MCh DNB

Associate Professor of Pediatrc Surgery
Indira Gandhi Institute of Child Health
Bengaluru, India
bcgshankar@gmail.com
Kumsi Sridhar MS MCh

Professor of CTVS
Bengaluru, India
Harold N Bass MD FACMG

Department of Genetics
Clinical Professor of Human Genetics
and Pediatrics
David Geffen School of Medicine
University of California, Los Angeles
(UCLA) Los Angeles, California, USA
IB Vijayalakshmi
Madhav Hegde MD
Consultant Cardiothoracic Radiologist
Bengaluru, India
docmadhavhegde@gmail.com
Mazeni Alwi
Senior Consultant in Paediatric
Cardiology Paediatric and
Congenital Heart Centre
Institut Jantung Negara
(National Heart Institute)
Kuala Lumpu, Malaysia
muhaneeza@ijn.com.my
Mitesh Shetty
MBBS MS(Medial Genetics-UK) PhD
Consultant
Medical Genetics
Manipal Hospital
Old Airport Road
Bengaluru, India
mitesh@manipalhospitals.com
Maddury Jyotsna MD DM FACC FESC FICC
Additional Professor of Cardiology
Nizams Institute of Medical Sciences
Secunderabad, AP, India
mail2jyotsna@rediffmail.com
MN Krishnan
DM FRCP FACC FESC FSCAI FCSI
Maitri Chaudhuri MD FNB

Manipal Hospitals and Vikram Hospitals
Bengaluru, India
drmaitricee@gmail.com
Professor and Head

Department of Cardiology
Government Medical College
Kozhikode, Kerala, India
dr.mn.krishnan@gmail.com
Marhisham Che Mood

Senior Registrar in Paediatric Cardiology
Paediatric and Congenital Heart Centre
Institut Jantung Negara
(National Heart Institute)
Kuala Lumpur, Malaysia
dr.marhisham@ijn.com.my
Mrutyunjaya Satpathy MD DM
Former Professor of Cardiology
Haripur Road, Dolmundai
m_satpathy03@yahoo.co.in
MD DM FICC FIAMS FIAE FICP FCSI FAMS DSc

Bengaluru, India
docvj@yahoo.com
Jain T Kallarakkal MD DM
Professor and HOD
MBMM Hospital
Kochi, India
doctorjain1973@yahoo.com
Jaydeepa S
Consultant Radiologist
Teleradiology Solutions,
Bangaluru, India
Jayashree Kharge MD DM
Bengaluru, India
khargej@gmail.com
viii
Kiron Varghese MD DM
St Johns Medical College
Bangaluru, India
drkiron@hotmail.com
Kiran VS
Consultant
Narayana Hrudayalaya Institute
of Cardiac Sciences,
Bengaluru, India
drkiranvs@gmail.com
Mark D Plunkett MD
Associate Professor of Surgery
Chief, Division of Cardiothoracic Surgery
of Medicine
Director, Pediatric Cardiac Surgery
Kentucky Childrens Hospital
Lexington, KY, USA
mplun2@email.uky.edu
Mary M Canobbio RN MN FAAN
Lecturer School of Nursing
Clinical Nurse Specialist
Ahmanson/UCLA Adult Congenital Heart
Disease Center
UCLA Transitional Care Program for
Adolescents with Congenital
Heart Disease
University of California Los Angeles
(UCLA)
Los Angeles, CA, USA
MS Aditya MD DM
Nizams Institute of Medical Sciences
Secunderabad, AP, India
aditya.ms11@gmail.com
Munde K
Mumbai, India
drkalyanmunde@yahoo.com
Nagamani AC MD DM
Bengaluru, India
drnagamani_c@yahoo.co.in
Nagesh CM MD DM
Bengaluru, India
drnageshcm@yahoo.com
Narayanan Namboodiri KK
MD DM DNB FIC(Aus)
Narendra Babu M MS MCh

Associate Professor of Pediatrc Surgery
Bengaluru, India
drnarendrababum88@gmail.com
Neeraj Awasthy MD FNB
Associate Consultant
Department of Pediatric and Congenital
Escorts Heart Institute and Research Centre
New Delhi, India
n_awasthy@yahoo.com
Neeraj Raghani MD DM
Mumbai, India
drnirajraghani@yahoo.co.in
Neeru Kaushik MD
Assistant Professor of Pediatrics
at Vanderbilt
Nicholas Hayes MBChB MRCPCH
Locum Consultant in Paediatric Cardiology
Evelina Childrens Hospital
6th Floor, Westminster Bridge Road
London SE1 7EH, UK
Nick.Hayes@gstt.nhs.uk
Nirav Panchani MD DM
Mumbai, India
drniravpanchani@yahoo.com
Nolan Thompson MD
Chief of Service
Department of Psychiatry
Sudhayakumar N MD DM
Amrita Institute of Medical Sciences
Kerala, India
nsudhayakumar@gmail.com
PM Chandrasekhara MD FICC FIACTA

Professor and HOD
Anaesthesia and Pain Management
Sagar Hospitals, Bengaluru, India
pmc.cardiacanaes@gmail.com
Prabhat Kumar MD FSCAI
Professor and HOD of Pediatric Cardiology
Military Hospital (CTC)
Armed Forces Medical College
Pune, India
drprabhat_cardio@yahoo.co.in
Pradeep Vaideeswar
Professor (Additional)
Department of Pathology
(Cardiovascular and Thoracic Division)
Seth GS Medical College,
Mumbai, India
shreeprajai@yahoo.co.in
Prasanna Nyayadhish
Seth GS Medical College and KEM
Hospital, Parel, Mumbai, India
prasannanyayadhish@hotmail.com
Prasanna Simha Mohan Rao MS MCh
Professor of CTVS
Bengaluru, India
prasannasimha@gmail.com
Praveen Jayan JP MD DM
Consultant Cardiologist
Bharath Hospital
Kottayam, Kerala, India
praveenjayan@gmail.com
Ramesh Arora
MD DM FICC FCSI FIMSA FACC
Chief Cardiologist
Metro Heart Institute
Noida, NCR
Ex-Director
Professor and Head
Cardiology Department
Maulana Azad Medical College and
GB Pant Hospital, New Delhi, India
yuktiarora@hotmail.com
Contributors

Trivandrum, India
kknnamboodiri@yahoo.co.in
Pamela D Miner RN MN NP
Nurse Practitioner
Adult Congenital Heart Disease
Ahmanson/UCLA
Adult Congenital Heart Disease Center
University of California Los Angeles
(UCLA)
Los Angeles, California, USA
Ramesh Santhanakrishnan MS MCh DNB

Professor and HOD of Pediatric Surgery
Bengaluru, India
doctorsramesh@gmail.com
Reema Chugh MD FACC
Consultant
Cardiology/Adult Congenital Heart Disease
and Heart Disease in Pregnancy
R Suresh Kumar MD DM FSCAI
Senior Consultant in Pediatric Cardiology
Frontier Lifeline, Chennai and
Dr KM Cherian Heart Foundation
Tiruvalla, India
r.sureshkumar.mmm@gmail.com
Sanjay Khatri MD DNB(Ped) FDNB(Ped Card)
Consultant
Department of Pediatric Cardiology
Fortis-Escorts Heart Institute
New Delhi, India
Sanjeev Kumar Veeredddy
Senior Resident in Cardiology
Seth GS Medical College
and KEM Hospital
Parel, Mumbai, India
dr_rahulreddy@yahoo.co.in
Satish MD DM
Bengaluru, India
reddy7sathish7@yahoo.com
P Syamasundar Rao
MD DCH FAAP FACC FSCAI
Professor of Pediatrics and Medicine

Emeritus Chief of Pediatric Cardiology
Houston, Texas, USA
P.Syamasundar.Rao@uth.tmc.edu
Satish Govindiah MS MCh

Professor of CTVS
Bengaluru, India
satishgovindaiah@yahoo.co.in
ix
Seema Thakur
Senior Consultant
Genetic and Fetal Medicine
Fortis Health Care, New Delhi, India
Sejal Shah
Consultant
Narayana Hrudayalaya Institute of
Cardiac Sciences, Bengaluru, India
sejalshahsuresh@yahoo.com
Shada J Al-anani
Fellow in Pediatric Cardiology
Rush Center for Congenital and
Structural Heart Disease
Rush University Medical Center
Chicago, IL, USA
Shakeel Ahmed Qureshi
Evelina Childrens Hospital
6th Floor, Westminster Bridge Road
London SE1 7EH, UK
Shakeel.Qureshi@gstt.nhs.uk
Shardha Srinivasan MD
Associate Professor of Pediatrics
Director of Fetal Cardiology
Co-director of Echocardiography
American Family Childrens Hospital
University of Wisconsin, Madison, USA
ssrinivasan3@pediatrics.wisc.edu
Shilpa Suresh Mavanoor DNB MCh
Assistant Professor of CTVS
Bengaluru, India
shilpa.suresh@gmail.com
Smita Mishra
Senior Consultant
Escorts-Fortis Health Care
New Delhi, India
smi1@rediffmail.com
Spoorthi Anup Belludi BDS MDS
Professor of Periodontics
Department of Periodontics
KLE Societys Institute of Dental Sciences
Bengaluru, India
S Radhakrishnan MD DM
HOD and Director
Department of Pediatric and Congenital
Escorts Heart Institute and Research Centre
New Delhi, India
samurai43@yahoo.com
Syed T Rizvi MD
Consultant in Psychiatry
Child and Adolescent Psychiatry
Department of Psychiatry
Sridevi Hegde MBBS DCH PhD

Head of Department and Consultant
Medical Genetics, Manipal Hospital
Old Airport Road, Bengaluru, India
sridevi.hegde@manipalhospitals.com
Thomas P Graham MD
Emeritus, Professor of Pediatrics
at Vanderbilt
Srilatha Alapati MD
Assistant Professor of Pediatrics
Division of Pediatric Cardiology
Texas Tech Health Sciences Center
Amarillo, Texas, USA
Tracy Kustwan Livecchi

Licensed Clinical Social Worker
Psychotherapist
Adult Congenital Heart Association
Mental Health Consultant
Westport, Connecticut, USA
Shishu Shankar Mishra
Varsha Kaulgud Mokhasi MD

Professor and HOD
Department of Anatomy
Vydehi Institute of Medical Sciences
Bengaluru, India
varsha_mokhasi@yahoo.com
MD FAIMS MCAM DoCM FCCP FIAE FICC
Professor and Director

Department of Cardiology
Hi-Tech Medical College Bhubaneswar
Sr Consultant Cardiologist
Med N Heart Clinic
drssmishra@yahoo.com
Sunita Maheshwari ABP ABPC(USA)
Senior Consultant
Pediatric Cardiologist
Bengaluru, India
sunita.maheshwari@telradsol.com
Suresh G Rao MS MCh Dip.NB FIACS
Pediatric and Congenital Heart Surgeon
Director, Childrens Heart Centre
Kokilaben Dhirubhai Ambani Hospital
Mumbai, India
raosureshg@gmail.com
Swati Garekar
American Board Certified
(Pediatric Cardiology)
Childrens Heart Centre
Kokilaben Dhirubhai Ambani Hospital
Mumbai, India
swatigar@gmail.com
Vimala J MD DM
Senior Consultant Pediatric Cardiologist
The Madras Medical Mission
Chennai, India
vimalajesudian@gmail.com
Neil Wilson MB BS DCH FRCP FRCP(CH) FSCAI
Consultant Paediatric Cardiologist
John Radcliffe and Childrens
Hospital Oxford
Honorary Senior Lecturer Dept Paediatrics
University of Oxford
Oxford, UK
neilwil1@aol.com
Ziyad M Hijazi MD MPH FSCAI FACC FAAP
James A Hunter, University Chair
Professor of Pediatrics
and Internal Medicine
Director, Rush Center for Congenital
and Structural Heart Disease
Section Chief, Pediatric Cardiology
Rush University Medical Center
Chicago, IL, USA
Ziyad_Hijazi@rush.edu
Foreword
This thousand plus page book is a remarkable achievement that addresses the
seemingly impossible task of the spectrum of congenital heart disease from the
third week of intrauterine life to late end-of-life issues. Three exceptional Editors
were chosen to achieve this goalIB Vijayalakshmi, P Syamasundar Rao, and
Reema Chugh. Together, they represent three generations who have witnessed
the major advances since the first blue baby operation at the Johns Hopkins
Hospital in 1944.
Survival into adulthood and the issues confronting adults with congenital
heart disease have added yet another dimension with Congenital Heart Disease in
Adults now a subspecialty in its own right. In the United States, there are currently
more adults with congenital heart disease than there are infants and children.
An attractive feature of the book is the seamless continuity from embryo, to neonate, child, adolescent, and adult.
Thirteen Sections are written by separate author(s), but the text reads as single-authored.
The first major facility in the English-speaking world dedicated to treating the young was the Hospital for Sick Children
in London established in 1852 with the aid of Charles Dickens. The second major facility was the Childrens Hospital of
Philadelphia founded three years later. The Childrens Hospital of Boston opened in 1869. Until the turn of the 20th century,
however, these institutions were little more than dim lights of hope in the darkness of pediatric medicine.
Where was congenital heart disease? Oslers Principles and Practice of Medicine devoted a scanty five pages to Congenital
Affections of the Heart. Holts Diseases of Infancy and Childhood devoted seven pages to Congenital Anomalies of the Heart.
In 1929, in Eberswalde near Berlin, Werner Forssman performed the worlds first cardiac catheterization on himself. The
department chief warned him not to do it, but Forssman ignored him. A nurse tried to stop him, but he tied her to the
operating table to keep her out of the way. Into his own antecubital vein, Forssman introduced a cannula through which
he passed a 65 cm urethral catheter, and then walked up a flight of stairs to the X-ray department where a photograph
showed the catheter tip in his right atrium. The image revolutionized cardiology. Despite later joining the Nazi party, Nobel
Laureate Forssman died on June 1, 1979.
In 1896, two Viennese scientists, Edward Haschek and TO Lindenthal, injected liquid calcium carbonate into the hand
vessels of a cadaver, producing an image of the vascular system. In the 1930s, George Robb and Israel Steinberg at Bellevue
Hospital in New York developed angiography and perfected angiography as a practical technique. Iodine-based contrast
materials were injected into the blood vessels of rabbits, and in 1937, into human beings. Castellanos, Pereiras, and Garcia
in Havana, visualized the right cardiac chambers in infants and children. The internal structure of the living heart had been
revealed for the first time
In 1956, Cournand, Dickinson and Forssman were awarded the Nobel Prize in Physiology or Medicine for their discoveries
concerning heart catheterization and pathological changes in the circulatory system.
Each of the thirteen Sections of the book is subdivided into beautifully illustrated chaptersSection 1 Embryo to the
Neonate, Section 2 Basics, Section 3 Defects in Atrioventricular Connections, Section 4 Shunt Defects, Section 5 Right
and Left Ventricular Obstructive Lesions, Section 6 Congenital Valvar Lesions, Section 7 Diseases of the Aorta, Section 8
Cyanotic Heart Disease, Section 9 Congenital Cardiomyopathies, Section 10 Congenital Heart Disease in Adults, Section 11
Electrophysiological Issues in Children, Section 12 Miscellaneous, and Section 13 General Issues.
A Comprehensive Approach to Congenital Heart Diseases by IB Vijayalakshmi, P Syamasundar Rao, and Reema Chugh deals
with congenital heart disease from intrauterine life to late end-of-life issues. The book is a tribute to the authors and a rare
gift to the reader.
Joseph K Perloff MD
Streisand/American Heart Association

Professor of Medicine and Pediatrics Emeritus
Ahmanson/UCLA Adult Congenital Heart Disease Center
University of California Los Angeles School of Medicine
Los Angeles, California, USA
Prologue
I began my formal training in adult cardiology and pediatric cardiology,
after completing postgraduate studies in the UK, under the great and
foremost pediatric cardiologist, Dr Helen Taussig at the Harriet Lane
Home, Johns Hopkins Hospital, Baltimore, USA. There could not have
been a more exciting time for the specialty. Dr Robert Gross had ligated
a patent ductus arteriosus (PDA) and the first Blalock-Taussig (BT) shunt
had been performed by Dr Alfred Blalock at Hopkins a few years later. The
clinic at Harriet Lane was full of patients from all over the world. It was
one of the best periods of my life.
Since my return to India, I have been dealing mostly with adult
cardiology, a large pediatric component of rheumatic heart disease,
and with congenital heart disease (CHD) in both children and adults.
Looking back over a half century, the developments in this field are
breathtaking. At the Johns Hopkins Hospital, in the fifties we depended
on auscultation, the electrocardiogram (ECG), X-ray, fluoroscopy (a very
large slice) and cardiac catheterization for diagnosis even in small infants.
Surgery was at that time limited to closed procedures for CHD (BT or
aorto-pulmonary shunts, PDA ligation, coarctation of aorta repair, etc.).
Today, the advent of echocardiography has done away (almost totally)
with cardiac catheterization in babies. Catheter-based interventions for valve stenosis, device closure of atrial/ventricular
septal defects (ASD/VSD) and PDA along with new surgical procedures using the heart-lung machine have revolutionized
both diagnosis and treatment. Fetal echocardiography is helpful in the diagnosis of several malformations and is rapidly
developing. Correction of some CHDs in the fetal stage has begun in a few places around the world. Genetic and molecular
studies are developing in a big way.
The specialty of Pediatric Cardiology is a recognized entity today. However, there is still some pessimism about the
advances. For example, despite surgery, many patients with ASD, VSD develop cardiac arrhythmias later in life. Corrected
tetralogy of Fallot, transposition of the great arteries and coarctation of aorta almost always require reoperations.
I am sure that this book on congenital heart diseases will be useful for physicians, cardiologists, cardiac surgeons and
all students. It will hopefully help in establishing the exact cardiac burden and cost-effective methods for excellence in
pediatric heart care. Dr IB Vijayalaksmi, the co-editors and all the authors need to be congratulated for this venture.
S Padmavati
FRCP (Lond), FRCPE, FAMS, FACC, FAHA,

FESC, DSc (Hon), PhD (Hon)
Founder-President, All India Heart Foundation

Director and Senior Consultant Cardiologist
National Heart Institute
New Delhi, India
Preface
Congenital heart diseases are the most common birth defects among neonates born worldwide. Advancements in
pediatrics, congenital heart surgery, anesthesia, internal medicine and obstetric/gynecology have allowed the majority
of these infants to survive from childhood into adulthood. Systematic categorization and classifications by embryologists/
pathologists had led to a fundamental understanding of these defects and their associated disorders.
It is, therefore, not surprising that most health providers including the specialists in this field are often overwhelmed
by the various congenital heart defects (CHD). For a clinician to understand the entire spectrum of CHD from embryology/
pathology, clinical manifestations, diagnostics tests, management and surgical indications for CHD appears to be an
insurmountable task. From making the correct diagnosis to appropriate management requires considerable knowledge
and experience. In addition, rapid advances in both catheter-based interventions and surgeries for fetus to grown-up/
adult congenital heart diseases (GUCH/ACHD) needs a deeper understanding of the guidelines and appropriate use criteria
(AUC) in order to facilitate proper decision-making by combining the best available scientific evidence with the collective
judgment of physicians/surgeons.
Public awareness and patient education are critical to improvements in health care. Fortunately, web-based resources
and media are making this knowledge more accessible to all. However, the complexities of CHD often make it difficult even
for experts to provide a focused explanation as well as answer all the queries.
Although there are several textbooks on the various aspects of CHD, there are very few that are focused yet comprehensive
to address all aspects of the care required for this special population. For medical/postgraduate students and practitioners,
quite frequently a lot of time is spent in referring to various resources in order to pull together complete diagnostic and
management strategies for one disease!
This book entitled, A Comprehensive Approach to Congenital Heart Diseases is designed to address all the practical aspects
that a health provider needs to know to deliver excellent care to the children and adults with CHD. In this book a wholehearted attempt has been made to cover all aspects from embryology, fetal malformations, pathology, clinical approach,
diagnostic investigations, management issues, current interventions to the surgery/heart-lung transplantation for CHD.
Our A to Z approach addresses transition of care into adulthood, long-term issues facing the adults with CHD including
pregnancy, contraception and gynecological issues. Multiple distinguished authors from all over India and abroad have
made heartfelt contributions to make this book come alive.
Just like the saying goes It takes a village to raise a child", it takes a global effort to care for an individual born with
CHD from womb to tomb. This book hopes to reach a wide global audience comprising but not limited to medical/
postgraduate students, nurse specialists, general practitioners, pediatricians, pediatric and adult cardiologists, as well as
cardiac surgeons.
This book has three editors representing the three generations who have witnessed the major advancements in this
field since the first blue baby operation. We hope to blend the global literature, new technology and our Indian and
international work experience to bring the best to our readers.
As the Editor-in-Chief, I (Dr IB Vijayalakshmi) have enjoyed collaborating with Dr P Syamasundar Rao who brings his
vast experience to this book, and Dr Reema Chugh who is a specialist in adult congenital heart disease/heart disease in
pregnancy in the United States. My special thanks to my associate Dr Chitra Narasimhan for her dedicated and diligent
support. I am extremely grateful to her for working beyond the call of her duties. I am grateful to Dr Pradeep Vaideeswar,
a pathologist par excellence, for writing the pathology section and sharing excellent pictures of pathological specimens
gathered during his distinguished career, and to Dr Prasanna Simha for writing on the surgical management of various
CHDs, and to Mr P Madhusudan for drawing explicit diagrams. We express our sincere gratitude to living legends, Dr S
Padmavati for writing the prologue and Dr Joseph K Perloff for writing the foreword.
As a co-editor, I (Dr P Syamasundar Rao) thank Dr Vijayalakshmi for inviting me to co-edit the book with her and for asking
me to contribute several chapters for this book. I have immensely enjoyed these tasks and feel delighted that I was able to
pass on the knowledge that I acquired from my teachers, Drs Lavanya Muhkerjee (Andhra Medical College, Visakhapatnam,
India), Herman W Lipow (Good Samaritan Hospital, Phoenix, Arizona, USA), Norman J Sissman (Stanford University, Palo
Alto, California, USA), Jerome Liebman (Case-Western Reserve University, Cleveland, Ohio, USA), and Leonard M Linde
(UCLA Medical Center, Los Angeles, California, USA) as well as from many pediatric cardiology and cardiovascular surgery
colleagues that I, over the years, had the opportunity to interact with at Medical College of Georgia, Augusta, Georgia, USA;
King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; University of Wisconsin Medical School, Madison,
Wisconsin, USA; Saint Louis University School of Medicine, St Louis, Missouri, USA and University of Texas-Houston Medical
School, Houston, Texas, USA.
As a co-editor and contributor to the section on CHD in adults and genetic syndromes, I (Dr Reema Chugh) sincerely
thank Dr IB Vijayalaksmi for giving me the opportunity to share the learning and experience that I have gathered from
all my teachers in this fieldDr SK Khanna (GB Pant Hospital, New Delhi, India), Drs Hillel Laks and Alon S Aharon (UCLA
Medical Center, USA) who introduced me to pathology/surgery in CHD; Dr Jane Somerville (Royal Brompton Hospital,
London, UK), Dr Philip A Ludbrook, Kathryn J Junge (Washington University in St Louis, USA), Dr John S Child, Dr Joseph
K Perloff, Mary Canobbio and Pamela Miner (UCLA Medical Center, Los Angeles, USA) for teaching me everything I know
about taking care of the adults with CHD. My deepest gratitude for the inspiration and support received over the years from
all the medical directors, chiefs of medicine, cardiologists, cardiac surgeons, staff, and patients at the Kaiser Permanente
Medical Centers (in Panorama City and Los Angeles), USA. Many thanks to Gloria Tongson, NP, and the sonographers at
the Echo LabPaul Junkel, Sarah Phillips, Terri McAnallen, Albert Amoranto, and Janae Johnsonwho join me every day
in taking care of the adults with CHD. I am grateful to our librarians, Ms Winnie Wong and Ms Hovey Lee for their diligent
efforts to fulfill my literature searches. My special thanks to Drs Harold Bass, Terry Talkin, Indubala Vardhan, Sami Azzam,
Kevin Landa for their editorial guidance, and to Mr Rober B Reber for his expertise as an audio-visual engineer. My sincere
gratitude to my beloved teachers, Sister Michael (Carmel Convent, Udhampur, India) and Mrs Arzoo Baker (La Martinieres
Girls School, Lucknow, India) for instilling in me a lifelong love for learning. Above all, I am indebted to my parents (Colonel
Prem and Sneh Chugh), my sister Gayatri, Dr Rajesh Behl, John and especially my daughter Tanisha, for their unconditional
love and support in this ongoing journey.
We sincerely thank the President of CSI, Dr Ashok Seth and President Elect, Dr PK Deb for getting it officially released by
His Excellency, the Vice President of India Shri Hamid Ansari, during the 64th Annual Conference of Cardiological Society of
India at New Delhi.
My sincere thanks are due to Jaypee Brothers Medical Publishers (P) Ltd, especially Shri Jitendar P Vij (Group Chairman)
and Mr Ankit Vij (Managing Director) who extended full cooperation to prepare this prestigious book and published it
expeditiously.
IB Vijayalakshmi
P Syamasundar Rao
Reema Chugh
xvi
Contents
Section 1: Embryo to the Neonate
1. Development of the Cardiovascular System
Varsha Kaulgud Mokhasi
2. Fetal Circulation
Chitra Narasimhan, Vijayalakshmi IB
16
3. Etiopathogenesis of Congenital Heart Diseases

Krishnamoorthy KM
25
4. Fetal Cardiology
Shardha Srinivasan
43
5. Congenital Heart Diseases with Duct-Dependent Circulation

Smita Mishra, Sanjay Khatri
84
6. Genetics in Congenital Heart Diseases

Sridevi Hegde, Mitesh Shetty
97
Section 2: Basics
7. Examination of the HeartA Comparative External and Internal Anatomy
Pradeep Vaideeswar
119
8. Classification of Cardiovascular Anomalies and their Terminologies

Prabhat Kumar, Vijayalakshmi IB
129
9. Cardiac Malpositions
Sejal Shah
136
10. Heterotaxy Syndrome

Smita Mishra, Seema Thakur
145
11. Bedside Diagnosis of Acyanotic Congenital Heart Diseases

Vijayalakshmi IB, Satpathy M
166
12. Clinical Approach to Cyanotic Heart Diseases

Sudhayakumar N
183
13. Role of Radiography in Congenital Heart Diseases

Madhav Hegde, Vijayalakshmi IB
190
14. Role of Newer Cardiac Imaging in Congenital Heart Diseases

Sunita Maheshwari, Arjun Kalyanpur, Jayadeepa
203
Section 3: Defects in Atriovenous and Pulmonary Arteriovenous Connections

15. Anomalies of Systemic Veins
Jayashree Kharge, Vijayalakshmi IB
213
16. Anomalies of Pulmonary Veins

Prasanna Nyayadhish, Sanjeev Kumar
224
17. Congenital Pulmonary Arteriovenous Fistula

Chandrakant B Patil, Kiron Varghese
243
Section 4: Shunt Defects

18. Interatrial Defects
Shada J Al-anani, Ziyad M Hijazi
253
19. Ventricular Septal Defects

Vijayalakshmi IB, Chitra Narasimhan, Prasanna Simha Mohan Rao
266
20. Atrioventricular Septal Defects

Neeraj Awasthy, Radhakrishnan S
292
21. Patent Ductus Arteriosus

Ramesh Arora, Vijayalakshmi IB
307
22. Aortopulmonary Window

Vijayalakshmi IB, Praveen Jayan, Satish Govindaiah
332
23. Aorticocameral Tunnels

Vijayalakshmi IB, Chitra Narasimhan
337
24. Aneurysm of Sinus of Valsalva

Biswajit Bandyopadhyay, Debasree Ganguly, Kumsi Sridhar
347
Section 5: Right and Left Ventricular Obstructive Lesions

25. Right Ventricular Outflow Tract Obstructions
Suresh Kumar R
357
26. Left Ventricular Outflow Tract Obstructions

Vijayalakshmi IB, Vimala J
366
27. Left Ventricular Inflow Obstructions

Neeraj Awasthy, Radhakrishna S
380
Section 6: Congenital Valvar Lesions

xviii
28. Tricuspid Atresia

P Syamasundar Rao
397
29. Diseases of the Tricuspid Valve

Duraisamy Balaguru, P Syamasundar Rao
414
434
31. Congenital Mitral Valve Diseases

445
32. Mitral Atresia

458
contents
30. Pulmonary Valve Diseases

Asha Moorthy, Jain T Kallarakkal
33. Aortic Valve Diseases 468

Smita Mishra, Neeraj Awasthy
Section 7: Diseases of the Aorta

34. Coarctation of the Aorta
Bentham J, Wilson N
505
35. Interruption of Aortic Arch

Vijayalakshmi IB, Prasanna Simha Mohan Rao
518
36. Vascular Rings, Slings and Other Anomalies

Maitri Chaudhuri
525
Section 8: Cyanotic Heart Diseases

37. Tetralogy of Fallot
Suresh Kumar, Vijayalakshmi IB, Bhushan Chavan
547
38. Pulmonary Stenosis with Interatrial Communication

Vijayalakshmi IB
560
39. Pulmonary Atresia with Ventricular Septal Defect

Anurakti Srivastava, Anil Sivadasan Radha, Girish Warrier
565
40. Pulmonary Atresia with Intact Ventricular Septum

Marhisham Che Mood, Mazeni Alwi
580
41. Double Outlet Right Ventricle

Vimala J, IB Vijayalakshmi, Prasanna Simha Mohan Rao
594
42. Truncus Arteriosus

Duraisamy Balaguru, P Syamsundar Rao
604
43. D-Transpostion of the Great Arteries

Suresh Rao, Swati Garekar
618
44. Congenitally Corrected Transposition of the Great Arteries

English C Flack, Neeru Kaushik, Thomas P Graham
625
45. Common Atrium

Kiran VS, Sunita Maheshwari
639
46. Single Ventricle

Devananda NS, Maitri Chaudhuri
644
47. Hypoplastic Left Heart Syndrome

P Syamasundar Rao, Srilatha Alapati
665
xix
Section 9: Congenital Cardiomyopathies

48. Dilated Cardiomyopathy
Bhanu Duggal, Munde K
685
49. Non-compaction of the Ventricles

Vijayalakshmi IB
697
50. Restrictive Cardiomyopathy

Bhanu Duggal, Neeraj Raghani
712
51. Hypertrophic Cardiomyopathy

Krishnan MN
723
52. Endocardial Fibroelastosis

Mishra SS, Mishra BR
736
Section 10: Congenital Heart Disease in Adults

53. Transitional Care in Congenital Heart Disease
Mary M Canobbio, Reema Chugh
745
54. Management Issues in Adults with Congenital Heart Diseases

Reema Chugh
751
55. Caring for the Adults with Cyanotic Congenital Heart Diseases
Reema Chugh
771
56. Pregnancy, Contraception and Gynecological Issues in Women with

Congenital Heart Disease
Reema Chugh, Pamela D Miner, Mary M Canobbio
57. Exercise and Sports in Adolescents and Adults with Congenital Heart Disease
Reema Chugh
58. Psychosocial Challenges and Psychiatric Issues while Growing Up with
Tracy Kustwan Livecchi, Reema Chugh, Nolan Thompson, Syed T Rizvi
783
812
827
Section 11: Electrophysiological Issues in Children
xx
59. Congenital Heart Blocks and Bradyarrhythmias

Abhilash SP, Dinesh Choudhary, Narayanan Namboodiri
839
60. Tachyarrhythmias
Sathish S
847
61. Invasive Electrophysiology Testing and Devices in Children

Dinesh Choudhary, Abhilash SP, Narayanan Namboodiri
870
Section 12: Miscellaneous

879
63. Cardiac and Extracardiac Masses

Bhanu Duggal, Vijayalakshmi IB
894
64. Lutembacher Syndrome

Nagamani AC, Nagesh CM
908
65. Pulmonary Hypertension

Maddury Jyotsna, Madhavapeddi Aditya
917
66. Congenital Pericardial Diseases

Prasanna Simha Mohan Rao
944
67. Marfan Syndrome

Harold N Bass, Reema Chugh
946
68. Down Syndrome

960
contents
62. Congenital Coronary Artery Anomalies

Nick Hayes, Shakeel Qureshi
Section 13: General Issues

69. Prevention of Congenital Heart Diseases
Sunitha Maheshwari, Kiran VS
971
70. Oral Health Care in Children and Adolescents with Congenital Heart Diseases
Sphoorthi Anup Belludi
979
71. Infective Endocarditis in Congenital Heart Diseases

Anita Shet
995
72. Noncardiac Surgery in Congenital Heart Diseases

Ramesh Santhanakrishnan,Chandrika YR, Narendra Babu M, Gowrishankar
1004
73. Anesthesia in the Catheterisation Laboratory

PM Chandrasekhara, AM Jagadeesh
1009
74. Anesthesia for Surgical Repair of Congenital Heart Diseases

1022
75. Postoperative Issues in Congenital Heart Diseases

Shilpa Suresh Mavanoor, Prasanna Simha Mohan Rao
1061
76. Pediatric Heart and Lung Transplantation

Brannon Hyde, Deborah J Kozik, Charles W Hoopes, Mark D Plunkett
1070
EpilogueIB Vijayalakshmi
1089
Index 1091
xxi
Sec t i on
Embryo to the Neonate
C hapter
Development of the
Cardiovascular System
Varsha Kaulgud Mokhasi
INTRODUCTION
Cardiovascular system begins to develop by the middle of the
3rd week of intrauterine life. Functioning of the heart starts by
early 4th week of intrauterine life. It develops mainly from the
splanchnic mesoderm, which forms the primordial heart. This
is the first major system to start functioning.
PRIMORDIAL HEART
Endothelial strands appear from the angioblastic cords in
the cardiogenic mesoderm by about the 3rd week. These
comprise of myoblasts and blood islands (Figures 1A to C).
These arrange in the form of cords, which canalize to form
two heart tubes. The two tubes unite with the lateral fold of
embryo to form a single tubular heart (Figures 2A to C). Heart
begins to beat by the 22nd to 23rd day. The flow of blood
begins by the 4th week.
through the streak. The cells destined to form the cranial

segments of the heart, the outflow tract, migrate first and
the cells forming the more caudal portions, right ventricle,
left ventricle and sinus venosus respectively, migrate in a
sequential order. The cells proceed toward the cranium and
position themselves rostral to the oropharyngeal membrane
and neural folds. The primordial heart tube is formed by 18
days.
The primordial myocardium is formed from the splanchnic
mesoderm surrounding the pericardial coelom. The heart
is now a thin endothelial tube and is separated from the
primordial myocardium by cardiac jelly. The endothelial
lining becomes the endocardium.
The primitive myocardium develops into the muscular
wall. The mesothelial cells arise from the external surface of
the sinus venosus and spread over the myocardium and form
the visceral pericardium.
Position of the Heart Tube
Development of the Heart

The cardiac progenitor cells lie in the epiblast, immediately
lateral to the primitive streak and from there, they migrate
After the onset of formation of the head fold, the heart and
the pericardial cavity, which were at the cranial end, come
to lie ventral to the foregut and caudal to the oropharyngeal
Figures 1A to C: A. Dorsal view of the embryo; B. Transverse section on the embryo; C. Cephalocaudal section of the embryo
EmBryo to thE NEoNAtE
B
A
C
Figures 2A to C: A. Transverse section of early presomite (17 days) embryo; B. Transverse section of 18 days embryo;
C. Transverse section of 22 days embryo
membrane. The heart will now occupy the thoracic region.

Thus, the heart becomes a continuous expanded tube, consisting
of an inner endothelial lining and an outer myocardial layer.
It receives venous drainage at its caudal pole and begins to
pump blood out of the first aortic arch into the dorsal aorta at
its cranial pole.
The tubular heart develops alternate dilatations and
constrictions. They are from the cranial to caudal truncus
arteriosus, bulbus cordis, ventricle, atrium and sinus venosus.
The truncus arteriosus is continuous cranially with the aortic sac
and aortic arches. The sinus venosus receives three paired sets of
veins, the umbilical, vitelline and common cardinal veins from
the chorion, yolk sac and body wall of the embryo respectively.
The arterial and venous ends of the heart are usually fixed. As the
bulbus cordis and venrticle grows faster, they form a U-shaped
tube called the bulboventricular loop (Figures 3A to D).
The sinus venosus develops lateral expansions, the right
and left horns. The heart elongates bends and gradually
invaginates into the pericardial cavity. The dorsal mesocardium
suspends the heart and the central part disappears and forms
the transverse sinus.
Circulation through the Primordial Heart

4
The myogenic contractions start at the end of 4th week in

utero by coordinated contractions. The blood enters the sinus
venosus from the embryo through the common cardinal veins;
from the developing placenta through the umbilical vein; from
the yolk sac through the vitelline vein. The blood from the
sinus venosus reaches the primitive atrium and is controlled
by the sinoatrial valves. It passes through the atrioventricular
(AV) canal and then into the primary ventricle, bulbus cordis,
truncus arteriosus and finally into the aortic sac. Then through
the aortic arches the blood reaches the dorsal aortae.
Formation of the Cardiac Loop

The straight heart tube normally loops or folds to the right and
this occurs mostly during the fourth week and is completed
by day 28. The cephalic (ventricle) portion of the heart tube
is displaced ventrally, caudally and to the right and the caudal
(atrium) portion of the tube is displaced dorsally, cranially and
to the left. Hence, the looping of the bulboventricular tube
leads the bulbus cordis (prospectively, the right ventricle)
to the right (D-loop) of the initial caudal segment, which is
the primitive ventricle (prospectively, the left ventricle).
Simultaneously, individual regions of the tube are expanding
and differentiating such that by the end of folding the region
of the future atria lies craniodorsal to the future ventricular
region. The cardiac looping is one of the first manifestations
of right-left asymmetry in the developing embryo.
Abnormalities of Cardiac Looping

Dextrocardia is a condition where the heart lies on the right
side of the thorax instead of the left and is caused because the
DEvElopmENt oF thE CArDiovAsCulAr systEm
D
Figures 3A to D: Formation of cardiac loop. A. 22 days; B. 23 days; C. 24 days; D. Frontal view
of heart tube looping inside in the pericardial cavity
heart loops to the left instead of the right. This may coincide
with situs inversus, a complete reversal of the position of all
organs. Situs inversus, which occurs in 1/7,000 individuals, is
usually associated with normal physiology, although there is a
slight risk of cardiac defects. The patients with isomerism have
replication of the right or left cardiac and visceral structures
bilaterally. The spleen reflects the difference between right
and left isomerism with polysplenia occuring in left-sided
bilaterality, left isomerism and asplenia or hypoplastic spleen
in right-sided bilaterality, right isomerism. These patients also
have increased incidence of other malformations, especially
heart defects. The genes regulating sidedness are expressed
during gastrulation.
Partitioning of the Primordial Heart

The single heart tube now starts to partition to form chambers.
The partitioning of the AV canal, the primordial atrium and
the primitive ventricle begins around the middle of the 4th
week and is completed by the 5th week. At the end of the 4th
week, the endocardial cushions from the dorsal and ventral
wall of the AV canal begin to approach each other and fuse
with the right and left AV canals. These are formed from
the endocardial cushions and function as AV valves. The
endocardial cushions are made of specialized extracellular
matrix or cardiac jelly.
Partitioning of the Primordial Atrium

The atrial partitioning begins at the end of the 4th week of
development. The septum primum, a thin crescent-shaped
membrane descends from the roof of primitive atrium
towards the endocardial cushion. A gap, foramen primum,
appears between the free margin of the septum primum and
the endocardial cushion. The foramen primum acts as a shunt
for the oxygenated blood to pass through from the right to
the left atrium. The septum primum merges with the fused
endocardial cushion to form the primordial AV septum.
The perforations produced by programed cell death appear

in the central part of the septum primum, before the foramen
primum disappears. As the septum primum fuses with the
endocardial cushions, the perforations coalesce to form the
foramen secundum and the foramen primum obliterates
(Figures 4A to F).
The foramen secundum ensures free flow of the oxygenated
blood from the right to the left atrium. The septum secundum
grows from the ventrocranial wall to the right of the septum
primum. The septum secundum forms an incomplete partition
between the atria and consequently an oval foramen or

foramen ovale is formed. The cranial part of the septum
primum disappears and the remaining part forms a flap-like
valve of the ovale foramen.
Before birth, the foramen ovale transmits the oxygenated
blood from the right to the left atrium. The left to right flow
is prevented by the septum primum, closing on the septum
secundum (Figures 5A and B). After birth, the valve of the
oval foramen fuses with the septum primum and closes the
ovale foramen. The oval depression in the lower part of
Figures 4A to F: Atrial septum formation by the actively growing ridges
6
A
B
Figures 5A and B: Ventral view of coronal section through the heart showing right and left atrial development
1
B
Figures 6A and B: Dorsal view of the stages of development of sinus venosus. ACV = Anterior cardinal vein;
CCV = Common cardinal vein; PCV = Posterior cardinal vein; UV = Umblical vein; VIT = Vitelline vein
interatrial septum of the right atrium is the oval fossa and is a

remnant of the oval foramen or foramen ovale.
Changes in the Sinus Venosus

Initially the sinus venosus opens into the centre of the right
atrium and its right and left horns are about the same size.
There is progressive enlargement of the right horn due to two
left to right shunts of blood. The first shunt is the transformation
of the vitelline and umbilical veins. The second shunt occurs
when the anterior cardinal veins become connected by an
anastomosis. This communication shunts blood from the left
to the right anterior cardinal vein. This shunt becomes the
left brachiocephalic vein. The right anterior cardinal vein and
the right common cardinal vein become the superior vena
cava (SVC). The right horn, by the end of the 4th week, is
noticeably larger than the left. The sinoatrial orifice moves to
the right and opens in the part of the primitive atrium that will
become the adult right atrium.
The consequence of the two left to right venous shunts
causes the left horn of the sinus venosus to decrease in size
and its importance. The right horn enlarges and receives all
the blood from the head and neck, through the SVC; and from
the placenta and caudal regions through the inferior vena cava
(IVC) (Figures 6A and B).
Initially, the sinus venosus is a separate chamber. The left
horn of the sinus venosus ceases to grow and eventually gives
rise to the coronary sinus (drains blood from the coronary

circulation of the heart muscle) and the small oblique vein
of the left atrium The right horn is incorporated into the right
atrium and the remainder of the right atrium forms the auricle.
The two parts are demarcated internally by a vertical ridge,
the crista terminalis and externally by a shallow groove, the
sulcus terminalis (Figures 5A and B).
The cranial part of the crista terminalis forms the right
sinoatrial valve
The caudal part forms the valves of the IVC and the
coronary sinus
The left sinoatrial valve is incorporated into the interatrial
septum.
Formation of the Left Atrium

The left atrial wall is mostly smooth because it is formed by
the incorporation of the primitive pulmonary veins. The veins
develop as an outgrowth of the dorsal atrial wall to the left
of the septum primum. As the atrium expands, the primitive
pulmonary veins and its main branches are gradually
incorporated into the wall of the left atrium.
Partitioning of the Primordial Ventricle

The septum formation starts in the AV canal and by the end of the
fourth week two cushions of mesenchyme, the AV endocardial
Figures 7A to D: Formation of the atrioventricular canal by the fusion of the endocardial cushions
cushions, appear at its anterior and posterior borders. The AV

canal initially gives access only to the primitive left ventricle
and is separated from the bulbus cordis by the bulbo (cono)
ventricular flange. As the AV canal enlarges to the right, the
blood passing through the AV orifice, now has direct access to
the primitive left as well as the primitive right ventricle.
The two lateral AV cushions appear on the right and left
borders of the canal, along with the anterior and posterior
endocardial cushions. The anterior and posterior cushions
project into the lumen and fuse, resulting in a complete
division of the canal into the right and left AV orifices, by the
end of the 5th week (Figures 7A to D).
Development of the Atrioventricular Valves

The AV endocardial cushions fuse and each AV orifice is
surrounded by proliferations of mesenchymal tissue. The
bloodstream hollows out and thins the tissue on the ventricular
surface of these proliferations to form valves and they remain
attached to the ventricular wall by muscular cords. The
muscular tissue in the cords degenerates and is replaced by
dense connective tissue. The valves consist of connective
tissue covered by endocardium. They are connected to thick
trabeculae in the wall of the ventricle, the papillary muscles
by means of the chordae tendineae (Figures 8A to C). The two
valve leaflets constituting the bicuspid (or mitral) valve forms
in the left AV canal and three valve leaflets constituting the
tricuspid valve forms on the right side.
Clinical Embryology
Heart Defects: The heart and vascular abnormalities is the

largest category of human birth defects, accounting for 1
percent of malformations among live-born infants. The
incidence among stillborns is 10 times as high. It is estimated
that 8 percent of cardiac malformations are due to genetic
factors, 2 percent are due to environmental agents while most
are due to a complex interplay between the genetic and the
environmental influences (multifactorial causes). The classic
examples of cardiovascular teratogens include rubella virus

and thalidomide. Others include retinoic acid (accutane),
alcohol and many other compounds. The cardiac defects have
been linked to maternal diseases such as the insulin-dependent
diabetes and hypertension. The chromosomal abnormalities
are associated with heart malformations and 6 to 10 percent
of newborns with cardiac defects have an unbalanced
chromosomal abnormality. Furthermore, 33 percent of
children with chromosomal abnormalities have a congenital
heart defect, with an incidence of nearly 100 percent in
children with Trisomy 18. Finally, cardiac malformations are
associated with a number of genetic syndromes, including
craniofacial abnormalities, such as DiGeorge, Goldenhar and
Downs syndromes.
The genes regulating cardiac development are being
identified and mapped and mutations that result in heart defects
are being discovered. For example, mutations in the heartspecifying gene NKX2.5 on chromosome 5q35, can produce
atrial septal defects (secundum type), tetralogy of Fallot, and
AV conduction delays in an autosomal dominant fashion. The
mutations in the TBX5 gene result in HoltOram syndrome,
characterized by preaxial (radial) limb abnormalities and
atrial septal defects. The defects in the muscular portion
of the interventricular septum may also occur. HoltOram
syndrome is one of the groups of heart-hand syndromes,
illustrating that the same genes may participate in multiple
developmental processes. For example, TBX5 regulates
forelimb development and also plays a role in septation of
the heart. HoltOram syndrome is inherited as an autosomal
dominant trait with a frequency of 1/100,000 live births.
Mutations in a number of genes regulating production
of sarcomere proteins cause hypertrophic cardiomyopathy
that may result in sudden death in athletes and the general
population. The disease is inherited as autosomal dominant
and most mutations (45%) target the -myosin heavy chain
gene (14q11.2). The result is cardiac hypertrophy due
to disruption in the organization of cardiac muscle cells
(myocardial disarray), which may adversely affect cardiac
output and/or conduction.
Figures 8A to C: Formation of atrioventricular valves and chordae tendinae
Atrial septal defect is caused either by excessive cell

death and resorption of the septum primum or by inadequate
development of the septum secundum. Depending on the
size of the opening, considerable intracardiac shunting may
occur from left to right. The most serious abnormality in this
group is complete absence of the atrial septum. This condition
known as common atrium or cor-triloculare biventriculare,
is always associated with serious defects elsewhere in the
heart.
Occasionally, the oval foramen closes during prenatal life.
This abnormality, premature closure of the oval foramen, leads
to massive hypertrophy of the right atrium and ventricle and
underdevelopment of the left side of the heart. Death usually
occurs shortly after birth.
The endocardial cushions of the AV atrioventricular canal
not only divides this canal into a right and left orifice, but
also participates in formation of the membranous portion
of the interventricular septum and in closure of the ostium
primum. This region has the appearance of a cross, with
the atrial and ventricular septum forming the post and the AV
cushions forming the crossbar. The integrity of this cross is
an important sign in ultrasound scans of the heart. Whenever
the cushions fail to fuse, the result is a persistent AV canal,
combined with a defect in the cardiac septum. This septal
defect has an atrial and a ventricular component, separated by
abnormal valve leaflets in the single AV orifice.
Occasionally, endocardial cushions in the AV canal
partially fuse. The result is a ostium primum defect but there
is closure of the interventricular septum. This defect is usually
associated with a cleft in the anterior leaflet of the mitral
valve.
The tricuspid atresia, which involves obliteration of the
right AV orifice, is characterized by the absence or fusion of
the tricuspid valves. It is always associated with:
a. Patency of the oval foramen.
b. Ventricular septal defect.
c. Underdevelopment of the right ventricle.
d. Hypertrophy of the left ventricle.
The Ebsteins anomaly is a condition where the tricuspid

valve is displaced towards the apex of the right ventricle. The
valve leaflets are abnormally positioned and the anterior one
is usually enlarged. As a result, there is hypertrophy of the
right atrium with a small right ventricle.
Septum Formation in the Truncus Arteriosus and

Conus Cordis
In the truncus, pairs of opposing ridges appear by the fifth
week. These ridges called the truncus swellings or cushions,
lie on the right superior wall (right superior truncus swelling)
and on the left inferior wall (left inferior truncus swelling).
The right superior truncus swelling grows distally and to the
left and the left inferior truncus swelling grows distally and
to the right. Hence, while growing toward the aortic sac the
swellings twist around each other, making the spiral course
of the future septum. Once the fusion is complete, the ridges
form the aorticopulmonary septum, dividing the truncus into
an aortic and a pulmonary channel.
At the same time similar swellings (cushions) develop
along the right dorsal and left ventral walls of the conus
cordis. These conus swellings grow towards each other and
distally to unite with the truncus septum. The fusion of the
two conus swellings causes the septum to divide the conus
into an anterolateral portion (the outflow tract of the right
ventricle) and a posteromedial portion (the outflow tract of
the left ventricle) (Figures 9A and B).
The arterial outlet, at the same time, undergoes a process
of leftward shifting and differential growth that leads to the
disappearance of the bulboventricular flange; the resorption of
the caudal extreme; and leftward shifting of the conus, closer
to the anterior AV canal cushion. The differences in cell growth
of the outlet septum lead to a lengthening of the segment of
smooth muscle beneath the pulmonary valve (conus). This
process separates the tricuspid and pulmonary valves. In
contrast, the segment beneath the aortic valve disappears, so
that there is fibrous continuity of the mitral and aortic valves.
Neural crest cells, originating in the edges of the neural

folds in the hindbrain region, migrate through the pharyngeal
arches 3, 4 and 6 to the outflow region of the heart which
they invade. Here, they contribute to the endocardial cushion
formation in both the conus cordis and truncus arteriosus. The
abnormal proliferation, migration or differentiation of these
cells results in congenital malformations in this region, such
as tetralogy of Fallot, pulmonary stenosis, persistent truncus
arteriosus and transposition of the great vessels. Neural crest
cells also contribute to craniofacial development; hence it is
not uncommon to see facial and cardiac abnormalities in the
same patient.
Septum Formation in the Ventricles

By the end of the 4th week, the two primitive ventricles
begin to expand. This also includes continuous growth of the
myocardium on the outside and continuous diverticulation
and trabecula formation on the inside.
The medial walls of the expanding ventricles become
opposed and gradually merge and this forms the muscular
interventricular septum. If the two walls do not merge
completely, a deep apical cleft between the two ventricles
appears. The space between the free rim of the muscular
ventricular septum and the fused endocardial cushions permits
communication between the two ventricles.
The interventricular foramen, above the muscular portion
of the interventricular septum, decreases on completion of
the conus septum. On further development, the outgrowth of
the tissue from the inferior endocardial cushion along the top
of the muscular interventricular septum closes the foramen.
This tissue fuses with the abutting parts of the conus septum.
Complete closure of the interventricular foramen forms the
membranous part of the interventricular septum (Figure 9C).
Abnormalities of Conotruncal Development
10
The conotruncus is one of the most common sites of

cardiac abnormalities, as it requires normal development
and proliferation of multiple cell types (secondary heart
field, neural crest cells, myocardium , endocardium). There
are many disorders involving the conotruncal region such
as common arterial trunk, double outlet right ventricle,
interrupted aortic arch, transposition of the great arteries,
tetralogy of Fallot and ventricular septal defect. The tetralogy
of Fallot occurs due to an unequal division of the conus
resulting from the anterior displacement of the conotruncal
septum. The persistent truncus arteriosus results when the
conotruncal ridges fail to fuse and to descend toward the
ventricles. The transposition of the great vessels occurs
when the conotruncal septum fails to follow its normal spiral
course and runs straight down. Van Praagh has said that
the growth of the subaortic conal free wall and resorption
of the subpulmonary conal free wall results in transposition
of the great arteries. Also, double-outlet right ventricle is
caused due to the continued persistence and growth of both
the subaortic and the subpulmonary conal free walls, that is,
failure of subsemilunar conal free wall resorption.
Semilunar Valves
As the completion of the partitioning of the truncus, primordia
of the semilunar valves occurs, small tubercles become visible
on the main truncal swellings. One of each pair belongs to
the pulmonary and the aortic channels, respectively. A third
tubercle appears in both channels, opposite the fused truncal
swellings. The tubercles slowly hollow out at their upper
surface, forming the semilunar valves (Figures 10 and 11).
Recent evidence shows that neural crest cells contribute to the
formation of these valves.
Aortic Arch Derivatives

The pharyngeal arches develop during the 4th week and
they are supplied by arteries directly from the aortic sacs.
The aortic arches terminate in the dorsal aorta and six pairs
of arch arteries are formed (Figure 12A). Among them, the
first 2 disappears, when the 6th artery appears. The remaining
arteries will arrange into its final fetal arterial arrangement,
during the 8th week.
The small portion of the first arch artery remains as maxillary
artery. The second pair of aortic arch arteries persists as stems
of the stapedial arteries. In the third pair of arch arteries, the
proximal part forms the common carotid arteries; distal part
joins with the dorsal aorta to form the internal carotid arteries.
The fourth arch artery on left side forms part of the arch
of aorta. The right fourth aortic arch forms the proximal part
of the right subclavian artery. The distal part of subclavian
artery is formed from the right dorsal aorta and the right 7th
intersegmental artery. The left subclavian artery develops
from the left 7th intersegmental artery. As there is differential
growth, the subclavian artery comes to lie close to the left
common carotid artery.
The fate of the fifth pair of aortic arches in 50 percent of the
embryos is rudimentary and it soon degenerates. They do not
develop in the other 50 percent. The proximal part of the sixth
pair of arch artery on the left side persists as proximal part of
left pulmonary artery. The distal part of this arch artery passes
from the left pulmonary artery to the dorsal aorta to form the
arterial shunt called ductus arteriosus.
The proximal part of the right sixth arch artery persists as
the proximal part of right pulmonary artery and the distal part
degenerates (Figures 12B and C). The transformation of the
sixth pair of aortic arches, determines the course of recurrent
laryngeal nerves. On the right, because the distal part of right
sixth aortic arch degenerates, the right recurrent laryngeal
nerve hooks around right subclavian artery, a derivative
of the fourth aortic arch artery. The left recurrent laryngeal
nerve hooks around the ductus arteriosus, formed by the distal
part of sixth arch artery on the left side. As the arterial shunt
involutes after birth, the nerve hooks around the ligamentum
arteriosum and the arch of the aorta.
Figures 9A to C: A and B. Development of the conotruncal ridges; C. Formation of the interventricular septal development
Figures 10A to C: Transverse section through the truncus arteriosus
Figures 11A to C: Transverse sections through the truncus arteriosus at the level of the semilunar valves.
A. At 5 weeks; B. At 6 weeks; C. At 7 weeks
Aortic Arch Anomalies
Aortic Arches and Other Branches of Dorsal Aorta
Since many changes are involved in the transformation of the

embryonic pharyngeal arch system of arteries into the adult
arterial pattern, anomalies occur. Anomalies result from either
disappearance or persistence of parts of the aortic arch arteries.
The aortic sacs arise from aortic arches and terminate in dorsal
aorta, by the fourth to fifth weeks. Initially aorta is paired
and run through the body. Soon, single dorsal aorta caudal to
aortic arches is formed.
11
C
Figures 12A to C: A. Aortic arches and dorsal aortae; B and C. Final form of the aortic arch arteries
Intersegmental Arteries
The dorsal intersegmental arteries carry blood to somites.
The vertebral artery is formed from the dorsal intersegmental
artery in the neck and the intercostal arteries are formed by the
dorsal intersegmental arteries. The lumbar arteries are formed
by abdominal intersegmental arteries. The fifth pair of the
lumbar intersegmetal arteries forms the common iliac arteries.
The lateral sacral arteries form the sacral intersegmental
arteries. The caudal end of the dorsal aorta forms the median
sacral artery.
Fate of the Vitelline

The vitelline arteries pass to the yolk sac and the primitive
gut. The three vitelline arteries that remain are the celiac trunk
to the foregut, the superior mesenteric artery to the midgut and
the inferior mesenteric artery to the hind gut.
Umbilical Arteries
12
The umbilical arteries pass through the connecting stalk and

carry poorly oxygenated blood. The proximal part forms the
internal iliac arteries and the superior vesical arteries. The
distal part gets obliterates and remains as medial umbilical

ligaments.
Clinical Correlates
Arterial system defects: Normally, the ductus arteriosus is
functionally closed through the contraction of its muscular
wall shortly after birth to form the ligamentum arteriosum.
The anatomical closure occurs by the proliferation of intima
by 1 to 3 months.
In the coarctation of the aorta, the aortic lumen below the
origin of the left subclavian artery is significantly narrowed.
Since the constriction may be above or below the entrance of
the two types (preductal and postductal) may be distinguished
(Figures 13A and B). The cause of the aortic narrowing is
primarily an abnormality in the media of the aorta, followed
by intimal proliferations. In the preductal type, the ductus
arteriosus persists; in the postductal type, which is more
common, this channel is usually obliterated. In the latter case,
collateral circulation between the proximal and the distal parts
of the aorta is established by large intercostal and internal
thoracic arteries. In this manner, the lower part of the body is
supplied with blood.
1
B
Figures 13A and B: Coarctation of aorta. A. Preductal; B. Postductal
B
Figures 14A and B: Abnormal origin of the right subclavian artery
The abnormal origin of the right subclavian artery occurs

when the artery is formed by the distal portion of the right
dorsal aorta and the seventh intersegmental artery (Figures
14A and B). The right fourth aortic arch and the proximal part
of the right dorsal aorta are obliterated. With shortening of
the aorta between the left common carotid and left subclavian
arteries, the origin of the abnormal right subclavian artery
finally settles just below that of the left subclavian artery. Since
its stem is derived from the right dorsal aorta, it must cross the
midline behind the oesophagus to reach the right arm. This
location does not usually cause problems with breathing and
swallowing since neither the trachea nor the oesophagus is
severely compressed.
In a double aortic arch, the right dorsal aorta persists

between the origin of the seventh intersegmental artery and
its junction with the left dorsal aorta (Figure 15A). A vascular
ring surrounds the trachea and the oesophagus and commonly
compresses these structures, causing difficulties in breathing
and swallowing (Figure 15B).
Development of Veins Associated with the Heart

The three paired veins drain
vitelline veins return poorly
yolk sac. The umbilical veins
from the primordial placenta.
into the tubular heart. The

oxygenated blood from the
carry well-oxygenated blood
The common cardinal veins
13
Figures 15A and B: Double aortic arch. A. Persistent right dorsal aorta; B. Formation of the vascular ring around the trachea and esophagus
return poorly oxygenated blood from the body of the embryo

(Figure 16).
Vitelline Veins
14
The vitelline veins drain from the yolk sac to the embryo.
After the formation of the septum transversum, the vitelline
veins enter the venous end called the sinus venosus. As the
liver primordium grows into the septum transversum, the
hepatic cords anastomose around the primordia of the hepatic
sinusoids.
The left common cardinal vein is obliterated at 10 weeks
and all that remains of the left sinus horn is the oblique vein
of the left atrium and the coronary sinus. The hepatic veins
drain from the remains of right vitelline vein. The portal vein
develops as an anastomotic network formed by the vitelline
veins around the duodenum.
The right umbilical vein and the caudal part of the left
umbilical vein between the liver and the sinus venosus
degenerates. The persistent left umbilical vein forms the
ductus venosus which is large venous shunt that develops
within the liver.
The cardinal veins are the main venous drainage system
of embryo. The anterior and posterior cardinal veins drain
from the cranial and the caudal part of embryo. They join the
common cardinal vein and enter into the sinus venosus.
The anterior cardinal vein anastomosis forms the left
brachiocephalic vein. The caudal part of the left cardinal
vein disappears. The SVC is formed from the right
anterior cardinal vein and the right common cardinal
vein. The posterior cardinal vein develops as vessels of
mesonephros and the developing transient kidneys. These
veins disappear with these kidneys. The remaining adult
Figure 16: Main intraembryonic and extraembryonic vessels
derivative of posterior cardinal vein is the root of azygos

vein and common iliac vein. The subcardinal veins connect
through the subcardinal anastomosis. It forms the stem of
the left renal vein, the suprarenal vein, the gonadal veins
and a segment of the IVC. The supracardinal veins in adult
form the azygos and hemiazygos veins and part of the IVC
(Figures 17A and B).
Development of the Inferior Vena Cava

The IVC is composed of four segments: hepatic, suprarenal,
renal, and infrarenal. The hepatic segment is formed from the
vitelline vein. The right subcardinal vein forms the suprarenal
segment by formation of the subcardinal-hepatic anastomosis.
The renal segment develops from the right suprasubcardinal
and postsubcardinal anastomoses. It is generally accepted
that the infrarenal segment formed by the right supracardinal
vein.
1
B
Figures 17A and B: Development of inferior vena cava, superior vena cava and azygos veins
ANOMALIES OF THE VENA CAVAE

The anomalies of the vena cavae are double SVC, left SVC,
Absence of hepatic segment of IVC, double IVC, azygos
continuation of IVC etc. These anomalies have been discussed
in chapter 15.
isolated angiogenic cell islets into a complex, four-chambered

structure. The critical period for development of anomalies
is 36 weeks. Hence, knowledge of cardiac embryology is
necessary to understand the congenital heart defects and to
develop strategies for prevention.
The embryological record is almost always abbreviated in
accordance with the tendency of nature (to be explained on
the principle of survival of the fittest) to attain her needs by
the easiest means.
Francis Maitland Balfour
FETAL CIRCULATION
Fetal Circulation has been discussed in Chapter 2.
CONCLUSION
The cardiovascular system is the first functional system in
embryo. The single heart tube begins to beat at 23 days of
development. The entire process of formation of cardiovascular
structures is completed within one month after the first 20
days of embryogenesis. This amazing process transforms
SUGGESTED READING
1. Sadler TW. Langmans Medical Embryology 11th edition.
Chapter 12.
2. Keith L Moore. The developing Human Clinically oriented
embryology, 8th edition.
15
C hapter
Fetal Circulation
Chitra Narasimhan, Vijayalakshmi IB
Introduction
The fetal circulation is the circulatory system of a human
fetus. It refers to a unique system of shunts and pressures
that are present in the fetal circulatory system. It is the first
functional system in the embryo at 21 days.1 The normal
growth and development of the fetus is dependent on an active,
independent metabolism and also on an efficient circulation.
The circulation in the fetus differs from that in the adult. The
human fetal circulation and its adjustments after birth are for
the most part similar to those of other large mammals, although
rates of maturation differ. Congenital heart disease (CHD) is
being diagnosed with increasing frequency during fetal life.
Hence, it is important to know the course and distribution of
the fetal circulation as it enables one to understand the manner
in which various defects influence the normal circulation.
HISTORICAL REVIEW
The first recorded mention of the fetal cardiovascular
circulation was in the second century AD by Galen.2 He
described what was later to become known as the foramen
ovale and its valve, as well as the ductus arteriosus. Nature is
neither lazy nor devoid of foresight. Having given the matter
thought, she knows in advance that the lung of the fetus does
not require the same arrangements of a perfected lung. She has
therefore anastomosed the pulmonary artery with the aorta,
and the left and right atria. He also gave some account
of their postnatal closure. In 1564, Vesalius, in a posthumous
publication, described the first account of the ductus venosus.3
In 1626, Spigel, also in a posthumous publication, noted that
both the fetal ventricles are of approximately equal thickness
and also noted the absence of any direct communication
between the umbilical vessels of the fetus and the uterine
vessels of the mother.4 In 1628, William Harvey introduced
his concept of the circulation of the blood and his account
of the fetal circulation.5 He realized that in the fetus the two
ventricles work in parallel instead of in series as in the adult,

though he denied the existence of any pulmonary circulation
at all in the fetus. It was later in 1938, that Barcroft and Barron
united their experience of fetal physiology with Barclay,
Franklin and Prichards experience in radiography.6 They
described the first records of the course of the circulation
in the fetal lamb. The changes in circulation at birth were
first described by Dawes and coworkers.7 Rudolph and coworkers in 1967 pursued their studies of the fetal circulation
in lambs and the changes at birth, by using more physiological
methods.8-10 The lamb model appears to best reflect human
physiology.11 In 1972, Winsberg was the first to demonstrate
fetal echocardiography.12 In the 1980s, hemodynamic
evaluation by Doppler enabled assessment of the fetal
circulation and in the late 1990s tissue Doppler methods
opened up new possibilities to assess cardiac function. Three
dimensional echocardiography and tissue tracking analysis of
the fetal heart improved the ease and quality of the assessment
of the fetal circulation, particularly in the first trimester.13
UNIQUENESS OF FETAL CIRCULATION

The fetal circulation is unique. There are several anatomical
differences between a placenta supported circulatory system
and an independent postnatal circulatory system.
1. The fetal circulation is an unique example of the economy
of nature. It is optimized to deliver highly oxygenated blood
from the placenta to the vital organs in greatest need (brain,
heart) and deliver the relatively desaturated blood to supply less essential fetal structures.14 The placenta receives
the deoxygenated blood from the fetal systemic organs. The
fetus circulatory adaptations are achieved by both the preferential streaming of oxygenated blood and the presence of
intracardiac and extracardiac shunts. Thus, the fetal circulation can be defined as a shunt-dependent circulation.15
2. The fetal circulation is arranged in parallel. The right
ventricle delivers majority of its output to the placenta for
ANATOMY OF THE FETAL CIRCULATION

The fetal circulation works differently from that of the baby
after birth, mainly because the lungs are not in use in the
fetus. The fetus obtains oxygen and nutrients from the mother
through the placenta and the umbilical cord, while a baby
after birth acquires oxygen from its lungs. The embryo/fetus
is attached to placenta via the umbilical cord. The anatomy of
the fetal circulation is shown in Figure 1.
The deoxygenated blood passes to the placenta via the two
umbilical arteries. These arteries arise from the right and left
internal iliac arteries. The fetal blood is oxygenated in the
placenta and is returned to the fetus via the umbilical veins.
Initially, there is a right and a left umbilical vein and they
empty into the hepatic venous sinusoids. The right umbilical
vein regresses completely, early in fetal life.18
The blood flow in the umbilical vein splits in the liver. Some
of it goes into the hepatic veins and the portal system of the
liver. In fetal lambs, the proportions vary and on an average
about 55 percent (range 2090%) passes through the ductus
venosus. In the human fetus, 20 to 30 percent of the blood flow
2
Fetal Circulation
oxygenation and the left ventricle delivers majority of its

output to the heart, brain and upper part of the body.
3. The oxygenation takes place at a site external to the
fetus, i.e. placenta. There is mixing of venous return and
preferential streaming.
4. The resistance within the placenta is extremely low and this
promotes shunting of blood to the placenta. Thus, there is
low impedance and high flow in the placental circulation.
The placenta is a richly vascularized organ and serves as
the site for oxygenation and nutrient delivery to the fetus
and carries away its wastes. The exchange of materials in
the placenta is via diffusion.
5. There is high impedance and low flow in the pulmonary
circulation.
6. The pressures in the right or venous system are higher than
the pressures in the left or arterial system.16
7. The three cardiovascular fetal shunts, ductus venosus,
ductus arteriosus and the foramen ovale, are essential
distributional arrangements, making the fetal circulation,
a flexible and adaptive system for intrauterine life.17 These
shunts provide blood flow pathways specific to the fetus
and are important for maintaining the parallel circulation.
8. Long-chain fatty acids are the dominant energy source in
the adult, whereas fetal myocardial energy requirements
are primarily met by lactate extraction.
9. The concentration of hemoglobin in the fetal blood is about
50 percent greater than in maternal blood. At a particular
oxygen partial pressure, fetal hemoglobin can carry 20 to
30 percent more oxygen than the maternal hemoglobin.
In addition, the presence of fetal hemoglobin means that
the organs in the fetus are able to extract oxygen at low
saturations.15
Figure 1: Anatomy of the fetal circulation and the oxygen saturations

in the various chambers and vessels. RV = Right ventricle; LV = Left
ventricle
passes through the direct shunt, the ductus venosus (DV).19,20

The fetal DV is a slender trumpet-like shunt, connecting into
the inferior vena cava (IVC), near its junction with the right
atrium (RA).18 The DV and the umbilical vessels are kept open
by the mechanical effect of the flow through them. The better
oxygenated blood from the DV remains on the posterior and
leftward aspect of the IVC and tends to stream separately from
the extremely desaturated systemic venous blood, which is
returning from the lower portions of the body.15,21
On reaching the heart, the IVC blood is effectively divided
into two streams. A highly oxygenated stream is preferentially
shunted through the next shunt in the fetal circulation, the
foramen ovale (FO), into the left atrium (LA). The other stream
passes into the RA where it is joined by the deoxygenated
stream from the superior vena cava (SVC) and this is directed
through the tricuspid valve into the right ventricle (RV). The
mechanical effect of the streaming of the IVC blood into the
LA and the physical relationship of the IVC to the LA, keeps
the FO patent in the fetus.
The preferential shunting of the more highly oxygenated
IVC blood through the FO appears to be due to various
reasons:
1. The angle at which the DV inserts into the IVCRA
junction, directs most of the richly oxygenated blood
across the FO and into the LA.22
2. The crista dividens, forming the upper margin of the FO
(free margin of the septum secundum) overrides the IVC.23
The free edge of the lower margin of the FO, formed by the
17
18
septum primum, is on the left side of the atrial septum and

the FO is kept open by the IVC stream.
3. The IVC valve or the Eustachian valve diverts the IVC
blood stream towards the atrial septum.24
4. It is likely that the higher velocity of the DV bloodstream
(55 cm/s) as compared to the lower velocity of the distal
IVC (15 cm/s) bloodstream contributes to maintaining the
preferential distribution of DV blood across the FO.25
The Eustachian valve and the lower portion of the atrial
septum move in unison during the phases of the cardiac cycle.
They move either to the left to facilitate movement of blood
through the FO or to the right to enhance flow through the
tricuspid valve.26 This preferential streaming of the DV and
the left hepatic venous blood through the FO distributes the
highly oxygenated blood to the LA and this mixes with the
small amount of deoxygenated blood from the lungs, draining
through the pulmonary veins, before entering the left ventricle
(LV) through the mitral valve. From the LV, the ascending
aorta delivers this oxygen-rich blood to the coronary arteries,
the head and neck vessels and the upper extremities. Only a
small portion of left ventricular cardiac output (10%) traverses
the aortic arch and supplies blood flow to the thoracic aorta.27
The most deoxygenated blood returns to the heart from
the upper body through the SVC and from the myocardium
through the coronary sinus. This blood, in addition to the
IVCs anteriorly streamed flow (venous return from the lower
body and hepatic circulation), is directed across the tricuspid
valve into RV and then ejected into pulmonary artery (PA).15
Only about 5 percent or less of the deoxygenated blood from
the SVC flows through the FO into the left atrium in the
normal fetus.25
As the lungs of the fetus are inactive, most of the
deoxygenated blood from the RV is diverted via the third shunt,
the ductus arteriosus (DA), from the PA into the descending
aorta, distal to the left subclavian artery. The muscular DA
is kept open by the active dilatation of both locally produced
and circulating prostaglandins (PGE2 and possibly PGI2). In
the fetus the DA is as large as the aorta. Only a small amount
of the RV output enters the pulmonary circulation, while the
remaining major portion crosses the DA and then into the
descending aorta. The reduced blood flow to the lungs is also
reflected by the relatively smaller branch pulmonary arteries
in utero and a large arterial ductus and descending aorta.
The lower half of the body is thus supplied with relatively
desaturated blood. This blood supplies the abdominal viscera
and the lower limbs and is shunted, via the umbilical arteries,
which branch from the internal iliac arteries, to the placenta for
oxygenation.15,18
In adult anatomy the following remains of the fetal
circulation can be readily recognized.18
1. The medial umbilical ligament on each side, passing from
the superior vesical branch of the internal iliac artery to the
umbilicus, represents the obliterated umbilical arteries.
2. The round ligament or ligamentum teres, lying in the free
edge of the falciform ligament and then in its groove on
the undersurface of the liver, represents the obliterated

umbilical vein.
3. The ligamentum venosum, lying within its fissure on the
undersurface of the liver, continuing as the ligamentum
teres and terminating at the IVC, represents the obliterated
DV.
4. The fossa ovalis on the interatrial septum, which is probe
patent in about 10 percent of normal subjects, represents
the FO.
5. The ligamentum arteriosum, between the aortic arch and
the left pulmonary artery, with the recurrent laryngeal
nerve in close proximity, represents the DA.
PHYSIOLOGY OF THE FETAL CIRCULATION

The fetal circulatory physiology has been based on animal
data. Ultrasound in obstetrics has been used increasingly to
provide physiological data from human fetuses. There are now
a growing number of human studies, which have investigated
the human physiology, with results that are similar, but not
identical to those from animal studies.17 The human fetus
seems to circulate less blood through the placenta, shunt less
through the DV and FO, but directs more blood through the
lungs than the fetal sheep. There are also substantial individual
variations and the pattern changes with gestational age.17
Fetal Blood Volume

The blood volume in the human fetus is between 10 and 12
percent of the body weight as compared with 7 to 8 percent in
the adults.28 This is mainly due to the large volume of blood
in the placenta, which decreases with gestation.
Studies have indicated a volume of 110 to 115 mL/kg,
which is comparable with experimental sheep studies.29 The
fetus, when compared with adults, is capable of much faster
regulation and restoration of the blood volume due to the high
diffusion rates between the fetal compartments.28
Fetal Arterial and Venous Blood Pressure

The human fetal mean arterial pressure was measured to
be 15 mmHg during cordocentesis at the gestational age of
19 to 21 weeks.30 Intrauterine recordings of the human fetal
intraventricular pressure suggest that the systemic systolic
pressure increases from 15 to 20 mmHg at 16 weeks to 30 to 40
mm Hg at 28 weeks.31 The results did not show any substantial
difference between the two ventricles and in the diastolic
ventricular pressure. The umbilical venous pressure, recorded
during cordocentesis and corrected for amniotic pressure,
increased from 4.5 mmHg at 18 weeks to 6 mmHg at term.32
Fetal Cardiac Function

The fetal myocardium is structurally and functionally immature
compared with that of the older child or adult. The structural
Table 1
Showing differences between fetal/neonatal and adult

myocardial physiology
Feature
Fetus/Neonate
Adult
Cardiac output
HR dependent
SV and HR
Starling response
Limited
Normal
Compliance
Less
Normal
Afterload
compensation
Limited
Effective
Ventricular
interdependence
High
Relatively low
2
Fetal Circulation
details of the fetal heart are organized during the embryonic

period. The fetal heart continues to grow and is dependent on
the physical environment including blood flow for its normal
growth. In many ways, the fetal myocardium differs from the
adult myocardium. The fetal myocardium is composed of
nearly 60 percent of non-contractile elements as compared to
30 percent in the adult myocardium.33 Early fetal myocytes
can undergo replication with development of hyperplasia or
an increase in cell number, whereas mature adult myocytes
undergo hypertrophy or increase in cell size. The myofibrils
density increases in early pregnancy, but the contractility
continues to improve during the second half of pregnancy.34
The relaxation properties of the fetal myocardium differs from
those of the adult. This may be due to the diminished function
of the sarcoplasmic reticulum and greater dependence on
the sodium-calcium exchanger process to remove cytosoliccalcium in the fetus.35 Fetal heart is much stiffer than the adult
heart, with impaired relaxation properties relative to the adult.
The stiffnessof the fetal myocardium is also partly due to
the constraint of the pericardium, lungs and chest wall.36 The
stiffness and impaired relaxation of the fetal myocardium is
reflected by the Doppler echocardiography done across the
atrioventricular valves. In the fetus, E : A ratio will typically
be less than 1, as passive early filling is impaired and active
atrial contraction is primarily responsible for emptying the
atrium.37 The E : A ratio is usually >1 in adults.
The fetal heart has a limited preload reserve and hence
a limited capacity to increase stroke volume by increasing
diastolic filling pressure, the RV even less than the left.
Though the Frank-Starling mechanism operates in the fetal
heart, it does so till a point is reached, after which any increase
in preload will result in a plateau without any further increase
in the stroke volume.38 Fetal cardiac output is controlled
entirely by the changes in the fetal heart rate in contrast to the
stroke volume changes in the adult. Thus, heart rate may be the
single most prominent means of increasing cardiac output in
the fetus. There is immaturity of the sympathetic innervations
of the fetal heart as compared to the parasympathetic. Thus,
under stress the fetal cardiac output favors maintenance of the
umbilical blood flow and support of the myocardium, adrenal
and brain.39 The differences between the fetal and adult
myocardial physiology is shown in Table 1.
The pressure difference between the ventricles is minimal
in the fetus as compared to that in postnatal life. This is
because the ventricles in the fetus are pumping in parallel
into the systemic circulation.31 In fetal circulation as the RV
handles 55 percent of the combined ventricular output, it is
larger and more dominant than the LV. This is confirmed on
echocardiographic evaluation of the human fetal heart. The
wall thicknesses of both the ventricles in the fetal heart are
approximately equivalent. As compared to the LV, the RV has
a greater wall stress, which is due to the greater radius to wall
thickness ratio. Hence, the RV exhibits greater sensitivity
to changes in the afterload such as an increase in vascular
resistance, than the LV.40 Any increase in systemic arterial
HR = Heart rate; SV = Stroke volume
pressure can affect both the ventricles, but the RV is affected

to a greater degree than the LV in the developing fetus.41
Thus in situations of increased preload or afterload, the RV
will manifest hypertrophy, dilatation or dysfunction before
the LV.
In the fetal heart, due to the wide communication between
the atria, there is equalization of pressures. Also, due to the
patency of the DA, there is equalization of pressures in the
aorta and pulmonary artery. As the atrial and great vessel
pressures are equal, in the absence of aortic and pulmonic
stenosis, the ventricular pressures are also equal with a systolic
pressure of approximately 70 mm Hg using amniotic pressure
as zero.27
Fetal Cardiac Output and Distribution

In adults, the circulatory system is in series and as there are no
shunts, the LV and RV stroke volumes are equal. In the fetus,
the circulation is in parallel and as a result of the intracardiac
and extracardiac shunting, the stroke volumes of the fetal LV
and RV are not equal. Even though the pressures are equal,
the RV stroke volume is more. This could be explained due
to the differences in afterload of the two ventricles. The fetal
aortic isthmus is narrower than the ascending and descending
aorta and this may functionally separate the upper and lower
body circulation to some extent.25
The fetal circulation is shunt dependent and is much more
complex and hence the cardiac output must be expressed as
the combined cardiac output (CCO).25 The estimated cardiac
output of the human fetus (553 mL/kg/min1) is higher than
that of sheep (450 mL/kg/min1). The CCO is reported to be
210 mL/min at midgestation and 1900 mL/min at 38 weeks
in human fetus (Table 2).42 In addition, the right and left
ventricular outputs are more similar in the humans (56/44)
when compared with that in sheep (66/34).25 Thus, the ratio
of right to left ventricular output, which is about 2 : 1 in the
sheep is about 1.2 to 1.3 : 1 in the humans.37,43,44 This ratio of
the right to left ventricular outputs decreases with advancing
gestation, from 1.3 at 15 weeks to 1.1 at 40 weeks. This is due
19
Table 2
The combined cardiac output and its distribution in normal human

fetuses during the second half of pregnancy42
Percentage of combined cardiac output
at gestational age
Combined
cardiac output
20 weeks
30 weeks
38 weeks
210 mL/min
960 mL/min
1900 mL/min
Left ventricle
47
43
40
Right ventricle
53
57
60
Foramen ovale
34
18
19
Lungs
13
25
21
Ductus
arteriosus
40
32
39
to the fact that the larger human brain requires a higher LV

output than the brain of the sheep.
The RV during fetal life, is not only pumping against the
systemic blood pressure, but is also performing a greater
volume of work than the LV. The RV output is directed
across the main pulmonary artery and the DA, with a small
portion going to the vasoconstricted pulmonary vascular bed.
The human fetal pulmonary flow is larger (mean 1325%)
than that in the classical fetal lamb studies (10%).17 The
remaining major part of the RV output perfuses the descending
aorta, lower part of the body and the placental circulation.
The LV output is directed towards the coronary and cerebral
circulations, with a small portion (10%) crossing the aortic
isthmus to perfuse the lower body. Thus, the high degree of
oxygenated blood returning via the DV and its preferential
intracardiac streaming across the FO is directed to the organs
in greatest need of oxygen delivery for their development i.e.
heart and brain. The placenta receives 50 percent of the CCO
of the fetal heart.45
Oxygen Saturation
20
The oxygen saturations and PO2 are lower in the fetus than that
in the neonates, infants and children.25 This may be due to the
lower efficiency of the placenta to transport oxygen than the
lungs. However, the fetus is able to adapt to these lower levels
due to the presence of fetal hemoglobin. The fetal hemoglobin
P50 in the sheep is considerably lower (~19 mm Hg) than that
of adult blood (~31 mm Hg) and this facilitates greater oxygen
uptake from the placenta. The distribution of the blood to the
various organs and the placenta is advantageous in that the
highly saturated blood goes to the heart and brain and the low
saturated blood goes to the placenta. The lowest saturation
is found in the abdominal IVC and SVC and the highest
saturation is found in the umbilical vein.14 The difference
in the oxygen saturations between the blood leaving the
RV and the LV is only 10 percent, increasing to 12 percent
during hypoxemia. This is mainly due to the large volume of
blood that is shunted through the FO.17 Oxygen saturations in

different parts of the fetal circulation are shown in Figure 1.
Control of the Fetal Circulation

The control of the fetal circulation is extremely complex and
is poorly understood. There are multiple control processes,
which mature and develop with gestational age. Circulating
catecholamines, other circulating hormones and locally
released vasoactive substances, all play a part. The circulating
catecholamines exert their effect through the activation of
both the - and b-adrenergic receptors, which mature during
early gestation, independent of the autonomic innervation
process.
The fetal peripheral circulation appears to be under a
tonic adrenergic influence (predominantly vasoconstriction),
probably mediated by the circulating catecholamines and in
particular by norepinephrine. Other factors such as arginine
vasopressin (AVP) and the renin-angiotensin system may
also have a role.15 In situations of fetal hypoxia, the fetal
circulation responds to the hypoxic insults through the neural
and endocrine responses and to the prominent direct effect
on the cardiac function.39,46 The fetal heart responds to the
hypoxia with bradycardia, unlike tachycardia in adults. All
these responses orchestrate a circulatory redistributional
pattern that maintains placental circulation and gives priority
to the adrenal glands, myocardium and the brain.47
The fetal pulmonary vascular resistance (PVR) is high
and this is multifactorial in origin. In fetal life, the alveoli
are fluid filled and there is increased tortuosity, kinking, high
muscle mass and the high vasomotor resting tone of the small
pulmonary vessels, all of which contribute to the high PVR. The
collapsed fetal lungs have a low resting oxygen tension. The
PVR may also be influenced by the changes in the pH, PCO2
and by the autonomic nervous system.48-50 Many endogenous
and exogenous vasoactive materials also stimulate the fetal
pulmonary vasculature. The DA also contains muscle that is
sensitive to the oxygen tension and vasoactive substances.
The patency of DA in utero is maintained by the low oxygen
tension and the vasodilating effects of prostaglandin E2.15
Transitional Circulation
As the fetus begins its transition to postnatal life, several
important changes occur as the cardiovascular and respiratory
systems adapt to extrauterine life. The fetus has to transit from
a parallel circulation to a neonatal circulation in series. The
major circulatory changes occurring at birth are the elimination
of the placenta, closure of fetal circulatory pathways, increased
pulmonary blood flow and an increase in the LV output. There
is an impressive immediate change at birth followed by a
slow change until an adult type of cardiovascular system is
achieved. This may occur over varying time periods.51
At birth, with separation of the umbilical cord, lungs
must swiftly take over from the placenta as the site of gas
interatrial septum primum and septum secundum results in

formation of an intact atrial partition. Remnants of the closed
umbilical vein are enclosed within the ligamentum teres.1
Fetal Circulation in Congenital

Heart Diseases25,53
Any development of a structural abnormality will modify the
fetal circulation. This will affect the development of other
components and can lead to other defects. The impact of the
defect will depend on its severity and the time of gestation at
which it occurs. The fetal circulation is modified in many of the
defects, but it will not significantly affect the fetal perfusion
and hence the fetal growth and development. This is because
of the parallel fetal circulation and its connections at the atrial
and great arterial level. This allows adequate transport of
blood to the placenta to pick up oxygen and deliver it to the
tissues. Thus, some CHDs are well-tolerated in utero, while
others can result in severe compromise of the fetal circulation
and early fetal death.
The fetal heart functions as a common mixing and pumping
chamber and hence many complex anomalies are compatible
with survival to term. Fetal shunt pathways play important
roles in the pathophysiology of many types of congenital
cardiac malformations. The defects associated with septal
defects like atrial septal defect, ventricular septal defect (VSD)
rarely influence fetal cardiac development. In atrioventricular
septal defects, the obligatory flow from LV to RA will result
in decrease in LV output and an increase in RV output. This
will reduce the flow across the isthmus and can predispose to
coarctation. It is the degree of severity of the atrioventricular
valve lesion and the regurgitation, which will determine the
outcome.
Any interference with blood flow into or out of the LV or
RV is known to interfere with its development. Premature
closure or restriction of the FO or mitral orifice results in LV
hypoplasia as a result of reduced blood flow, which decreases
the LV volume. In these fetuses with under development
of the left side of the heart, the fetal RV and pulmonary
artery are larger than usual reflecting flow redistribution.
The compensatory dilation of the contralateral ventricle
results in normalized CCO. In the fetus with mitral atresia
or aortic atresia, if the FO is sufficiently large and the
DA accommodates the whole of the systemic blood flow,
there will be no significant interference with intrauterine
development and survival, but the problems will occur
after birth as the DA closes. Blood flows retrograde from
the DA across the arch to the ascending aorta. The reduced
flow through the left heart in cases of atrioventricular valve
obstruction (atresia, stenosis) and in aortic atresia can result
in aortic hypoplasia and coarctation. The aortic isthmus is
especially vulnerable to small changes in intracardiac flow
from various congenital defects. This may account for the
relatively high incidence of narrowing or atresia in this
2
Fetal Circulation
exchange. In order for this to occur, PVR must fall rapidly

and this occurs due to an interaction of a number of factors.
There is a gradual reduction in PVR in late gestation.
At birth, after expansion of the lungs, there is a dramatic fall in
PVR and an 8 to 10 fold increase in pulmonary blood flow.15
The first breaths to inflate the lungs are thought to stimulate
pulmonary stretch receptors which mediate reflex dilatation
of the pulmonary vessels. Mechanical distention of the lungs
also promotes local production of prostacyclin, a pulmonary
artery vasodilator, further decreasing PVR. The improved
oxygenation of the blood acts as a vasodilator both directly
and through its ability to stimulate nitric oxide production.52
The reduction in PVR leads to increase in pulmonary blood
flow and an increased venous return to the LA.
As soon as the placenta is removed, there is a dramatic fall
in the flow through the DV and a significant fall in the venous
return through the IVC. The DV closes passively, 3 to 10 days
after birth. Thus, there is decrease in IVC flow, which results
in a fall in venous return to the RA. This in turn means that
less blood enters the RA causing right atrial pressures to fall.
At the same time with an increase in pulmonary blood flow
due to the decrease in PVR, there is increase in the pulmonary
venous return and subsequent elevation in LA pressures.
These two factors allow the pressures in the LA and RA to
equalize. At this point the flap of the FO is pushed against the
atrial septum and the atrial shunt is effectively closed. This
initial functional closure of the FO occurs within minutes
to hours of birth. Anatomical closure occurs later via tissue
proliferation.15
The shunt at the level of the DA becomes bidirectional
with the reduction in the PVR. In addition, there is a dramatic
reduction in the production of prostaglandin E2 (by the
placenta) and an increase in its metabolism (by the lungs).52
This in combination with increased oxygen content in the
blood provides the stimulus for the DA to constrict. The
ductal tissue itself may become less sensitive to the dilating
influences of the prostaglandins. Anything that increases the
PVR, such as acidosis, hypoxemia, polycythemia or lung
disease, may keep the ductus patent. In healthy full term
newborns, functional ductal closure occurs by 96 hours.
This functional closure is followed by anatomical closure
via endothelial and fibrous tissue proliferation by 2 to 3
weeks.15,27 Once the DA closes, pulmonary artery pressures
reduce significantly as the PVR decreases. The pulmonary
artery pressures are approximately one-half of the aortic
pressures within the first 24 hours of life. Further decrease
in the PVR and involution of the pulmonary arteriolar
medial musculature occurs more gradually. The pulmonary
vasculature looks very similar to that of the adult by the age
of 6 to 8 weeks.51
Functional closure of the three shunts typically happens in
the first 48 hours and is followed by tissue proliferation that
results in anatomical closure and formation of the ligamentum
arteriosus and ligamentum venosus, while fusion of the
21
22
region. The increased flow in the DA allows the substrate

for development of a posterior aortic wall ridge opposite
the orifice and usually a narrowing results at this site. Other
CHDs may be associated with decreased flow into the aorta
thus interfering with its development. Thus in the fetus with
tricuspid atresia with transposition, the aorta arises from the
RV. If only a small VSD is present, the RV is small and flow
into the ascending aorta is restricted, resulting in hypoplasia.
Infants with aortic atresia have been reported to show a
high incidence of neurodevelopmental problems due to the
reduced cerebral blood flow during fetal life.
The patency of the fetal flow pathways is very important for
fetal survival when the right side of the heart is underdeveloped,
as in absent right atrioventricular connection with right
ventricular hypoplasia or with severe right ventricular outflow
obstruction (RVOTO), as in critical pulmonary stenosis or
atresia. The size of the FO and the flow through it is larger
than normal. All the venous blood returning to the heart is
directed through the FO to the LA and hence the LV provides
the total output of the heart. Thus, due to the decreased venous
filling into the RV and increased flow and volume into the LV,
the LV size is more than the RV. The DA is smaller in caliber
than normal and is usually more vertically oriented than in the
normal fetus. This is due to the smaller than normal volume
of flow across the DA and then into the branch pulmonary
arteries. Also, as the total CCO is ejected into the ascending
aorta, there is higher flow across the aortic isthmus. The
ascending aorta is large and the aortic isthmus is as wide as
the descending aorta. These changes are also observed with
other malformations that reduce right ventricular output, such
as tricuspid atresia and tetralogy of Fallot (TOF) with severe
pulmonary stenosis.
In a fetus with rapidly developing RVOTO with intact
ventricular septum, RV and LV cannot compensate and the CCO
falls. But if the RVOTO develops slowly, both LV and RV can
compensate and CCO is maintained. If severe RVOTO develops
early in gestation in the fetus with intact ventricular septum,
the DA flow is reversed and carries only 8 to 10 percent of the
cardiac output. The DA will be narrower and will make an acute
inferior angle with the aorta. The DA will remain patent for a
longer duration than normal. In these fetuses with RVOTO with
intact ventricular septum, if significant tricuspid regurgitation
(TR) develops, RV pressure remains low and myocardial
sinusoids and coronary fistula do not develop. But if TR does
not develop, then there is significant RV systolic pressure and if
this occurs early in gestation there is development of coronary
fistula and intramyocardial sinusoids.
In the fetus with isolated aortic or pulmonary stenosis
there is interference with the outflow of the left or right
ventricle respectively and this restricts the stroke volume of
the affected chamber. Ventricular muscle mass increases in
response to the increased systolic pressure. The left or right
atrial pressure does not increase significantly because of the
presence of the FO. Venous return is diverted away from the

ventricle with obstructed outflow and preferentially enters
the ventricle with the greater diastolic compliance. In cases
of critical aortic valve stenosis, congestive heart failure can
occur with hydrops fetalis.
In the fetus, TOF, total anomalous pulmonary venous
connection (TAPVC) and transposition of great arteries (TGA)
are well-tolerated. In TOF, depending on the severity of the
obstruction to the pulmonary blood flow, the aorta will carry a
larger percentage of CCO. Hence, there is a larger amount of
blood flow across the ascending aorta and the isthmus and they
tend to be larger. If the obstruction to the pulmonary blood
flow is very severe, blood flow to the lungs will be supplied
via the DA from the descending aorta (i.e. the reverse of the
normal situation). In absent pulmonary valve syndromes,
pulmonary artery branches are greatly dilated. Significant
pulmonary regurgitation can seriously affect perfusion of the
pulmonary vessels and cause abnormal development of the
intrapulmonary vessels.
In the fetus, TAPVC, may be masked as the pulmonary
venous return is already low. If whole of the pulmonary
venous return drains into the SVC, LV will be totally free
of pulmonary venous blood and hence will be of higher
saturation. LA and LV will be relatively small in TAPVC.
In TGA, the aorta arises from the RV and the pulmonary
artery from the LV. The FO and DA develop normally and
hence there are no major circulatory consequences of this
lesion in utero. Restriction of the FO and the DA is more
likely to be observed in later gestation. The diameter of the
DA will be reduced as a result of both the lower flow through
it and the constrictor effect of the higher oxygen saturation.
The increased pulmonary blood flow will result in greater
return of blood to the LA and this tends to reduce the size
of the FO. The presence of these changes in the fetus is
predictive of early severe hypoxemia postnatally.
Congenital cardiovascular malformations with valvar
regurgitation most often cause elevation in the systemic
venous pressure. The regurgitant atrioventricular valves
can lead to chamber dilation, hydrops fetalis and death.
Atrioventricular valve regurgitation is noted in many fetuses
with Ebstein malformation, some with atrioventricular septal
defect and in pulmonary regurgitation with absent pulmonary
valve syndrome. Some fetuses with obstruction to the LV,
such as with aortic atresia or to the RV output, such as with
DA constriction, may develop increased venous pressure. The
manifestation of the elevated venous pressure is fetal hydrops.
In the fetus with Ebsteins anomaly, severe TR can manifest
as cardiac failure especially if the FO is restrictive. There
is marked enlargement of the RA and the atrialized RV can
cause septal displacement and compromise the LV output.
Functional pulmonary atresia can result and ductal flow
may be reversed. Marked enlargement of the RA can cause
pulmonary hypoplasia.
References
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1991;68:947-57.
42. Rasanen J, Wood DC, Weiner S, et al. Role of the pulmonary
circulation in the distribution of human fetal cardiac output during
the second half of pregnancy. Circulation. 1996;94:1068-73.
43. De Smedt MCH, Visser GHA, Meijboom EJ. Fetal cardiac
output estimated by Doppler echocardiography during mid and
late gestation. Am J Cardiol. 1987;60:338-42.
44. Sutton MG, Plappert T, Doubilet P. Relationship between
placental blood flow and combined ventricular output with
gestational age in normal human fetus. Cardiovasc Res.
1991;25:603-8.
45. Rychik J. Fetal cardiovascular physiology. Pediatr Cardiol.
2004;25:201-9.
46. Iwamoto HS, Kaufman T, Keil LC, et al. Responses to acute
hypoxemia in fetal sheep at 0.6-0.7 gestation. Am J Physiol.
1989;256:H613-20.
47. Kiserud T, Jauniaux E, West D, et al. Circulatory responses to
acute maternal hyperoxaemia and hypoxaemia assessed noninvasively by ultrasound in fetal sheep at 0.3-0.5 gestation. Br
J Obstet Gynaecol. 2001;108: 359-64.
48. Reynolds SRM. Fetal and neonatal pulmonary vasculature in
guinea pig in relation to hemodynamic changes at birth. Amer
J Anat. 1956;98:97-102.
49. Cassin S, Dawes GS, Mott JC, et al. The vascular resistance
of the fetal newly ventilated lung of the lamb. J Physiol. 1964;
171:61-79.
50. Cook CD, Drinker PA, Jacobsen HN, et al. Control of pulmonary blood flow in the fetal and newly born lamb. J Physiol.
1963;169:10-29.
51. Rao PS. Perinatal circulatory physiology: Its Influence on
clinical manifestations of neonatal heart disease. Neonatology
Today. 2008;3:6-12.
52. Zeltser I, Tabbutt S. Critical Heart Disease in the Newborn. In
Pediatric Cardiology: The Requisites in Pediatric Cardiology.
Vetter VL (Ed). Mosby, Inc, US; 2006. pp. 31-3.
53. Rudolph AM. Congenital cardiovascular malformations and
the fetal circulation. Arch Dis Child Fetal Neonatal (Ed).
2010;95:F132-6.
C hapter
Etiopathogenesis of
Congenital Heart Diseases
Krishnamoorthy KM
Introduction
The prevalence of CHD at birth in a population-based

setting is 0.9 percent or one in 110 newborns.2 CHD are very
heterogeneous in anatomy, hemodynamics and recognition
rates. It is difficult to pinpoint one or even a multifactorial
cause for etiopathogenesis in the majority of cases. An
estimated 15 percent of CHD can be traced to a known cause.3
The remaining cases are thought to result from complex
interactions involving environmental exposures, maternal
lifestyle factors and genetic susceptibilities.
There are six supposed pathogenetic mechanisms of CHD

as enumerated below:5
1. Abnormal migration of ectomesenchymal tissue
2. Abnormal intracardiac blood flow
3. Abnormal cellular death (apoptosis)
4. Abnormalities of the extracellular matrix
5. Abnormal targeted growth
6. Abnormalities of situs and looping.
This chapter reviews the etiopathogenesis of CHD and
deals with etiologic factors, which are not genetic. Genetic
factors will be dealt within another chapter. Most of the causes
of CHD discussed occur within the fetal-placental-maternal
environment. They are broadly classified into:
1. Infections
2. Maternal drug exposure
3. Parental medical conditions
4. Parental smoking
5. Parental alcohol intake
6. Vitamins
7. Environmental factors
8. Sociodemographic factors
9. Recurrences of CHD in families.
Studies done in such situations are reviewed. Wherever
data is available, the pathogenesis of CHD is briefly reviewed.
Limitations of such studies are also discussed in the end.
Pathogenetic Mechanisms
Infections
Pathogenesis during cardiac development varies between

the different types of CHD. Hence a particular teratogen will
not increase the risk of all defects. Between 5 to 8 weeks
of gestation, the primitive heart tube undergoes folding,
remodeling and septation that transforms its single lumen
into a four-chambered heart. By the 9th week, the outflow is
divided into two. For a teratogen to act on the embryonic heart
to produce CHD, it has to do so during the 14 to 60 days of
gestation, which is the most vulnerable period.4
Exposure to teratogen produces an estimated 1 percent of CHD.6
Congenital heart diseases (CHD) are the most prevalent and

serious of all recognized structural birth defects. Surviving
infants often require surgery or interventions and lengthy
hospitalizations, and will have a lifetime of disability that
imposes a significant burden on families. Costs associated with
the care of a child with a CHD are significant even in developed
countries,1 particularly when lifetime costs of management
are considered. Advances in medical diagnosis and treatment
have certainly helped to improve the survival of patients with
CHD. The burden of CHD can be further ameliorated through
primary prevention, if the causes are known.
Prevalence of CHD
Maternal Rubella
Maternal rubella was the earliest teratogen identified. This
discovery was important not only in itself, but by stimulating
interest in the etiology of CHD. The rubella virus passes through
the chorionic epithelium to the bloodstream of the fetus. It
has a selective action on the heart and on the three epidermal
structures of the fetus. The cells are severely damaged,

becoming swollen and vacuolated and sometimes destroyed.
Most offsprings (90%) have flow defects, especially patent
ductus arteriosus (20%) and peripheral pulmonic stenosis
(1020%).7 Both occur more commonly in infants with
rubella syndrome than in those with non-rubella CHD.8 Other
defects noted are pulmonary valve abnormalities7, as well as
atrial and ventricular septal defects.7,9 Of particular note, there
is a relative absence of conotruncal, atrioventricular canal,
laterality and single-ventricle defects.
Other Infections and Fever

There are intriguing reports of association of CHD with
maternal fever in the first trimester, including influenza.8,10
A 40 to 80% increase in risk for CHD has been reported10-12 with
some degree of specificity in the outcomes. The association
with febrile illness appears to be more marked for tricuspid
atresia,8 atrial and ventricular septal defects8,10, as well as for
left-sided obstructive defects and transposition of the great
arteries.10,11 Specific defects shown to be associated with
such febrile illness include pulmonic stenosis,8 all right-sided
obstructive defects,10 coarctation of the aorta,10 d-transposition
of the great arteries8 and conotruncal defects.10,11 In a smaller
cohort study, an infant exposed prenatally to high fever had
transposition of the great arteries.13 Mothers with any febrile
illnesses during the first trimester of pregnancy have a 2-fold
higher risk of CHD in the offspring.8,10 A case-control study
found an association of maternal fever with conotruncal
defects among offspring born to mothers, who did not use
multivitamins.14
Hyperthermia in chick embryos causes malformations of
the outflow tract and stenosis of the ventral aorta and aortic
arches.15,16 But in man, the exposure is febrile illness rather
than hyperthermia. Both fever and infection have biological
effects on specific developmental pathways. Apoptosis is
affected by both hyperthermia17 and viruses.18 Apoptosis is
involved in cardiac morphogenesis, e.g. in the development
of the cardiac outflow tract.19 Distinguishing the effect of
hyperthermia from that of underlying infection may be
difficult. Most of the studies have not been able to distinguish
between independent and joint effects associated with
maternal fever, maternal infection and use of medications to
control the fever or infection.
26
includes CHD ranging from ventricular and atrial septal

defects to complex conotruncal defects.21 Extensive review
on this association is available.22
Metronidazole
In the Baltimore-Washington Infant Study, maternal use of
metronidazole during pregnancy was found to be associated
with an increased risk of outflow tract anomalies with normally
related great arteries, as well as membranous ventricular
septal defects.8
Trimethoprim-sulfonamide
An association with CHD was found, when trimethoprimsulfonamide was taken during the first trimester pregnancy
in a case-control study.23 Similar were the observations
in the Hungarian case-control surveillance of congenital
abnormalities.24 Significantly, the risks were reduced if the
mother also took folic acid supplementation.
Isotretinoin
This analogue of vitamin A, used to treat cystic acne, has been
associated with CHD.25 A characteristic pattern of malformation
involving craniofacial, cardiac, thymic and central nervous
system structures is seen. Conotruncal and aortic-arch
abnormalities have been described.25 High maternal intake of
retinol supplements is uniquely associated with transposition
of great arteries, according to one study.26 Like thalidomide,
it produces highly specific and time-dependent effects on
cardiovascular development.27 It may have a deleterious
effect on cephalic neural crest cell activity that results in the
observed craniofacial, cardiac and thymic malformations.25
The frequency of CHD is reduced among offsprings of women,
who discontinue therapy before conception.28
Antiepileptic Drugs
Maternal Drug Exposure
Anticonvulsant drugs are strongly implicated as teratogens.

Their use during pregnancy has been associated with
CHD.2934 Among 69 patients with valproate embryopathy, 26
percent had CHD in a study.31 Ventricular septal defects, aortic
stenosis, pulmonary stenosis and patent ductus arteriosus
were observed. These lesions belong to the category of
abnormalities resulting from altered embryonic blood flow.
Therapeutic Drug Exposure
Fluconazole
Thalidomide
An unusual pattern of CHD in offsprings of mothers treated

with high-dose of fluconazole for meningitis, during the first
trimester has been noticed. One baby had tetralogy of Fallot,
patent ductus arteriosus, pulmonary artery hypoplasia, patent
foramen ovale, while the other had ventricular septal defect
Thalidomide was the second teratogen recognized after rubella.

It was shown to be involved in anomalies of the ventricular
outflow tract more than 50 years back.20 The embryopathy
Lithium
Maternal treatment with lithium carbonate during pregnancy
and the occurrence of Ebstein anomaly have been
associated.36,37 In a voluntary reporting registry, serious CHD
were observed in 8 percent of 225 infants born to mothers,
who had taken lithium during the first trimester of pregnancy.38
One-third of these infants had Ebstein anomaly. But current
data from retrospective, prospective and meta-analysis studies
suggest that lithium is not a known cardiac teratogen.39,40
Hypnotics
The incidence of CHD was increased among infants of
women, occasionally treated with amobarbital.41 The risk for
chronic or high-dose maternal use is unknown.
use of ibuprofen during pregnancy has been associated with

d-transposition of great arteries, membranous ventricular
septal defects, atrioventricular septal defects and bicuspid
aortic valve.46 Ketoprofen47 has been associated with
CHD. Indomethacin has been similarly implicated.48,49
Two studies have associated indomethacin and patent
ductus arteriosus, the risk being maximum, when it is
given within 48 hours of delivery. Patent ductus arteriosus
was more common in infants after maternal indomethacin
administration as a tocolytic. These neonates failed to
respond to postnatal indomethacin to close a patent ductus
arteriosus.50 Infants exposed to antenatal indomethacin
had an increased incidence of patent ductus arteriosus,
were more symptomatic from the ductus, which was more
resistant to medical closure.51
Case reports of persistent pulmonary hypertension and
premature closure of the ductus arteriosus in infants, whose
mothers took other non-steroidal anti-inflammatory drugs are
available like naproxen,52 diclofenac53 and sulindac.48
Female Hormones
One study mentions phenothiazine exposure as a risk factor

for CHD in the offspring.41
Female sex hormones were found to be teratogenic to the fetus

during the period of cardiovascular embryogenesis, for any type of
CHD and specifically for ventricular septal defects.5457 Although
case-control studies58 suggested a risk of CHD in offsprings
from maternal use of oral contraceptives, later reports and metaanalysis did not substantiate this association.59
Narcotics
Clomiphene
Case-control studies29 reported an association of CHD in

offsprings with maternal codeine use during the first trimester
of pregnancy, but with methodological limitations. Other
studies failed to confirm this.42
A similar conflicting data is available for the association

of maternal corticosteroid use and CHD. The BaltimoreWashington Infant Study showed a possible association by
univariate analysis, but not when other variables were taken
into account.44
Maternal use of clomiphene was associated with coarctation of

the aorta and tetralogy of Fallot.8 Among 397 newborns from
women treated with clomiphene in a study, four had ventricular
septal defects.60 This was more than expected and the rate of
all CHD was significantly high. Atrial and ventricular septal
defects, as well as coarctation of aorta were observed in
another study.61 The same authors published their observations
on the incidence of CHD among women, who conceived
after assisted reproductive technology.62 Studies that have
investigated the impact of clomiphene on fetal development
have been criticized for combining the use of clomiphene with
assisted reproductive technology. In fact, the defect categories
that appear to be associated with both clomiphene and assisted
reproductive technology are similar: septal heart defects and
esophageal atresia.61,62 Further, the small number of cases,
inconsistency of some findings with previous reports and the
inability to assess the clomiphene effect separately from that of
infertility alert to a cautious interpretation.
Non-steroidal Anti-inflammatory Drugs
Chemotherapy
A large registry study found a slightly high-risk of CHD for

these drugs, but no drug specificity for CHD.45 Maternal
It is impossible to study the effect of chemotherapy during

pregnancy. Studies on children of mothers, who received
Phenothiazine
Sympathomimetics
There are conflicting reports of association of phenylephrine
with CHD: a case-control study with positive association43
and a large cohort study with negative association.41
Corticosteroids
3
Etiopathogenesis of Congenital Heart Diseases
and pulmonary artery hypoplasia.35 But prospective studies

are not available to draw definite conclusions. The drug
inhibits cytochrome P450 as well as cytochrome c oxidative
and peroxidative enzymes. This results in an increase in
intracellular peroxide generation, which is toxic to the
developing fetus.
27
chemotherapy for cancer in childhood, found CHD in 10

percent of such children.63
Non-therapeutic Drug Exposure

Cocaine and Marijuana
Maternal: A case report suggested that single ventricle may
result from maternal cocaine ingestion.64 Coronary occlusion
in the developing fetal heart due to coronary spasm could have
produced an infarct, which destroyed the right ventricle. This
fetal pathology may be one mechanism that leads to single
ventricle hearts. Data from a case-control study, the Atlanta
Birth Defects Case-Control Study, investigated the role of
maternal cocaine ingestion in the induction of single ventricles
and found no association.65 In this study, even if maternal
cocaine ingestion during pregnancy was a purported cause of
single ventricle, most cases appeared to be unrelated to this
exposure. An increased frequency of CHD was seen among
infants with neonatal toxicology screens showing the prevalence
of cocaine in 1 study, with peripheral pulmonic stenosis as the
leading diagnosis and in far greater numbers than in the general
population.66 Case-control studies have reported an association
of maternal cocaine abuse with increased risk of any CHD,67
heterotaxy68 and membranous ventricular septal defects.8
Paternal: The Baltimore-Washington Infant Study reported
an association of paternal cocaine use with an increased risk
of any CHD and with ventricular septal defects and tricuspid
atresia in particular.8 In this study, it was found that paternal
marijuana use and use of cocaine among older fathers were
risk factors for isolated membranous ventricular septal defects
in offspring.69 The evaluation of these drugs is hampered due
to the concomitant use of tobacco and alcohol and therefore
individual effect is difficult to evaluate. In the Atlanta Birth
Defects Case-Control Study, risk of isolated simple ventricular
septal defects doubled in offsprings with maternal self- and
paternal-proxy reported marijuana use.70 Risk of isolated
simple ventricular septal defect increased with regular
(3 day/week) marijuana use for both maternal self- and
paternal-proxy report. The association was significant for
maternal self-report. Maternal use of marijuana was also
found to be associated with a slight increase in risk for Ebstein
anomaly in the Baltimore-Washington Infant Study.8
Early Lesions
The pattern of CHD encountered with an emphasis on
abnormalities of laterality, looping and conotruncal septation
suggests that maternal diabetes affects cardiogenesis very early,
prior to 7 weeks of gestation.73,74 Experimental embryogenesis
in a medium with high glucose concentrations, shows that the
migratory and proliferative capacity of neural crest cells are
affected.75 Early onset defects like conotruncal anomalies
are thus explained in diabetic pregnancies. The case of two
infants of diabetic mothers, with DiGeorge syndrome and
normal chromosome 22q11, further illustrates that maternal
diabetes may be a pathogenic factor in this anomaly.76 In the
Baltimore-Washington Infant Study, only the early CHD
(defects of primary cardiogenesis) were strongly associated
with maternal diabetes, while those arising later in cardiac
development (obstructive and shunting defects in fourchambered hearts) were not significantly associated.77
Mechanism
Among CHD, 1 percent of CHD can be attributed to maternal

diseases, such as type I diabetes and phenylketonuria.42
It is believed that the abnormal glucose levels disrupt expression

of a regulatory gene in the embryo, leading to embryotoxic
apoptotic cellular changes.78 Variations in glucose metabolism
and/or protein glycosylation, perhaps of genetic origin, affect
the vascular complications of diabetes.79 Vascular alterations
as a common pathway to cardiovascular maldevelopment
might be initiated by aneuploidy and by maternal diabetes.
Both of these etiological factors would explain the occurrence
of early, rather than late CHD. Another postulated mechanism
is an association between excess oxygen radical activity and
disturbed embryogenesis in diabetic pregnancy.80 Adminis
tration of antioxidants to diabetic pregnant rodents can reduce
the risk for diabetes-associated embryopathy.81 A higher
genetic susceptibility towards congenital malformations also
plays a role in diabetic women.82 Pregestational diabetes
increases the risk of CHD83 and is hypothesized to change the
expression of a regulatory gene important for the septation of
the outlet tract of the heart.84
Diabetes Mellitus
Defects
Diabetic mothers have offsprings with CHD.32,54,71 In the

Atlanta Birth Defects Case-Control Study, the absolute risk
for CHD was 5.3 per 100 live births.72 Therapy of diabetes
Laterality and looping defects,3,8 hypoplastic left heart

syndrome,8 non-chromosomal atrioventricular septal defects,8
outflow tract anomalies, tetralogy of Fallot,72,85 transposition
Parental medical conditions
28
mellitus does not affect the risk of malformation in the fetus.

However, the duration of diabetes has a significant effect on
the malformation risk with higher incidence seen in infants of
mothers with a longer duration of diabetes. Paternal diabetes
does not increase the risk. These observations suggest that
maternal diabetes, through its adverse effects on maternal
metabolism, is the responsible factor for the increase of
malformations in the fetus.
Epilepsy
Pregnant women with epilepsy are at an increased risk for
CHD in their offsprings.89,90 Confounding factors like direct
teratogenic effects of anticonvulsant drugs or their indirect
effect on folate metabolism prevent an objective analysis of
the impact of epilepsy on the causation of CHD. As already
mentioned, anticonvulsant drugs are known teratogens.29-34
No specific pattern of CHD seems to be closely related to
these factors, with reported associations involving CHD as a
whole, as well as the common arterial trunk, transposed great
arteries and septal defects.
Phenylketonuria
Untreated maternal phenylketonuria is associated with a > 6
fold increased risk of CHD.91 One study reports an increased
incidence of left-sided obstruction.92 Other defects described
are tetralogy of Fallot, ventricular septal defects, patent ductus
arteriosus and single ventricle. This can be reduced with strict
diet control before conception and during pregnancy.8
Obesity
There is a modestly elevated risk among obese women for
CHD in their offspring.32,93 Another study found a 6.5-fold risk
elevation for aggregate CHD among obese black women.94

A 2-fold increase in risk of aggregate CHD with predilection
for truncus arteriosus and transposition of great arteries has
been reported95 and for a grouped category of defects of the
great vessels.96 Obesity is a complex condition and has to be
studied carefully to minimize the possibility of associations
due to chance and bias. The possibility of confounding by
other factors such as type 2 diabetes, intake of micronutrients
or use of multivitamin supplements have to be borne in mind.
This is because of a hypothetical explanation that undetected
diabetes type 2 may be associated with an increased risk for
CHD.97
Parental Smoking
Maternal
Lesions
Tobacco smoking is one of the major preventable causes of
morbidity and mortality. Its use in pregnancy is a public health
issue and is a human developmental toxicant and potential
teratogen.98 Some studies have reported an adverse effect of
gestational smoking on the risk of CHD (as a group) in the
offspring99-102 or on specific heart defect subgroups,99,100,103
though others have not found any relationship.89 A metaanalysis of studies published between 1971 and 1999 (12
analyses of all CHD and 7 analyses of CHD groups or specific
phenotypes separately) found no association for CHD and
mixed results for analyses of specific groups or phenotypes.99
Reports of positive associations of maternal smoking with
CHD combined100,101 and negative association are available
(Baltimore-Washington Infant Study).8 A similar trend is
seen for associations between maternal smoking and CHD
groups. Positive association has been suggested for atrial
septal defects, atrioventricular septal defects and tetralogy
of Fallot,100 while these were not corroborated by larger
studies such as the Baltimore-Washington Infant Study8 and
a Swedish study.99 In the Swedish population-based study,
unadjusted estimates revealed an increased risk of having an
infant with either truncus arteriosus or atrial septal defects
among women, who smoked.99 Analyses of small case groups
based on the Baltimore-Washington Infant Study data has
shown associations of maternal smoking with single ventricle
and l-transposition of great arteries.68,103 Smoking in early
pregnancy was associated in a dose-dependent manner with
transposition of great arteries with ventricular septal defect
and with pulmonic valve stenosis.8 The effects were seen in
certain, possibly susceptible subgroups, such as older mothers
and those with a history of miscarriages.
Among the congenital defects in a large cohort study on
congenital anomalies in relation to gestational smoking,
only CHD showed a significantly increased incidence in the
tobacco exposed group.101 Maternal and infant characteristics
3
of great vessels,8,72 patent ductus arteriosus8,72 and ventricular

septal defects8,72 are associated with maternal diabetes. There
is a strong predilection for left atrial isomerism86 and visceral
heterotaxia in transposition.87 In the Baltimore-Washington
Infant Study, maternal diabetes was strongly associated with
CHD with significant heterogeneity within these developmental
categories: among laterality defects, diabetes was associated
only with cardiovisceral and atrioventricular discordance; among
outflow tract anomalies, the risk was strongly associated with
normally related great arteries but not with simple transpositions;
and among atrioventricular septal defects, diabetes was
associated with the complete but not with the partial forms.77
The association was strongest among infants with multisystem,
predominantly VACTERL association (vertebral anomalies,
anal atresia, cardiac defect, tracheoesophageal fistula, renal
anomalies, limb defects). The mortality with CHD was more
than double among infants with diabetic mothers compared
to those with non-diabetic mothers. This excess mortality was
due to the associated non-cardiac malformations, prematurity
and low birth weight. Three mothers with insulin-dependent
diabetes mellitus had babies with isomerism. High glycated
haemoglobin levels made the authors implicate poor glycemic
control, although other teratogenic mechanisms associated with
diabetes could not be excluded. Both right and left isomerism
in different parts of the same patient were seen and suggested
the model of random development of laterality following the
interruption of normal developmental processes.88
29
of neonates with CHD were compared with normal neonates

in one study.104 More mothers of neonates with CHD smoked
(40.8% vs 19.7%) during pregnancy. Logistic regression
analysis showed that periconceptional tobacco smoking
was associated with increased risk of CHD in the offspring.
Incidence of neonatal CHD increased with the level of fetal
tobacco exposure, suggesting a dose effect too.
Quantification
Any-time smokers have babies with septal defects, the association being stronger for mothers, who reported heavier tobacco consumption during pregnancy.105 This was independent
of potential confounding factors. Mothers, who smoked > 25
cigarettes/day more often gave birth to babies with right-sided
obstructive lesions.105 The dose-effect relation for CHD was
confirmed in a case-control study.104 Maternal overweight and
smoking may have a synergistic adverse effect on the development of the fetal heart and these women should be strongly
encouraged to stop smoking and to lose weight before becoming pregnant.106
Mechanism
30
Smoking during pregnancy results in deposition of tobacco

constituents in the circulation of mother and hence the
fetus. This serves as serious hazard at all stages of human
development.98 Gestational smoking results in placental
pathologies, preterm birth, low birth weight and structural
malformations in the offspring, abnormal somatic growth
and increased blood pressure in childhood.98 Nicotine and
carbon monoxide have high placental permeability, resulting
in increased concentrations in the fetal circulation compared
to maternal levels.98 Nicotine constricts the uterine arteries,
reducing placental blood flow.107 Carbon monoxide increases
fetal carboxyhemoglobin impairing fetal oxygenation.98 Both
contribute to tobacco-associated fetal hypoxia, which exerts a
teratogenic effect.
Environmental toxin can induce oxidative deoxyribonucleic
acid (DNA) damage, mutations and chromosomal aberrations,
such as DNA strand breaks and aneuploidy.108 They might act
in human seminal fluid as endocrine disrupting agents causing
direct germ line DNA damage or epigenetic changes.108
Smoking is associated with increased oxidative stress,109
which can decrease the functional activity of methionine
synthase through limiting the availability of reduced vitamin
B12. As mentioned in the section on alcohol, homocysteine
accumulates and produces its toxic effects.110
Glutathione S-transferase (GST) polymorphisms were
investigated in a study on mothers of affected children
with CHD.111 The modification effect of susceptibility in
children, who lacked the genetic capacity to produce GSTM1
and GSTT1 enzymes was explored. Paternal smoking
(>15 cigarettes/day) was found to be associated with CHD
risk. An additive risk was present, when both parents were
exposed to the toxins. Both maternal and paternal exposure

to toxins increased the CHD risk in children, who carried the
combined null GST genotypes. Polymorphisms in GST genes
can modify a persons risk of toxicant exposure. It showed
that GST polymorphism might mediate the risks of parental
exposure to toxin for CHD.
Genetic polymorphisms in the nitric oxide synthase (NOS)
gene are associated with birth defects. In a population-based
registry, single nucleotide polymorphisms in the NOS3 gene
among infants with conotruncal defects were more likely to
carry the variant alleles for NOS3 (922A > G), NOS3 (298G
> T) or both and to have mothers who smoked cigarettes
periconceptionally compared with control infants.112 The
gene-environment interaction reported by this study illustrates
the importance of the associations among CHD, maternal
exposure and genetic variants that modify the effect of
exposure on developing hearts.
Paternal
Fathers cigarette smoking has been shown to be more common
among children with ventricular septal defect.113 Other studies
showed that parental smoking, particularly when both parents
were smokers, increased the risk of conotruncal defects.114
It is also believed that male exposure might exert a
teratogenic effect through toxic nicotine compounds adsorbed
to the sperm and transmitted to a woman in the ejaculate. The
contaminant is absorbed by the woman, where it might reach
and adversely affect a current pregnancy or may even remain
in the womans body to influence future pregnancies.108
In all these studies, some residual confounding could
not be excluded. Exposure to environmental smoking was
determined by maternal self-reports, without independent
biochemical validation.
Parental alcohol intake

Maternal
Alcohol abuse is known to be teratogenic and among the effects
seen are CHD.115 Some studies could not find an association.33
Ethanol produces fetal tissue edema and affects the turgor of
the primitive cardiac loop. Alcohol intake is associated with
increased oxidative stress109 that decreases the activity of
methionine synthase through limiting the availability of reduced
vitamin B12. Homocysteine and S-adenosylhomocysteine
are elevated. S-adenosylhomocysteine is a potent product
inhibitor of cellular methyltransferases, which during
organogenesis can alter gene expression, cell differentiation
and apoptosis.110 Homocysteine has embryotoxic effect and
leads to inhibition of DNA methyltransferase reactions, DNA
hypomethylation and altered gene expression.
The first description of fetal alcohol syndrome pointed
at alcohol, as a cardiac teratogen.116 Atrial, ventricular and
conotruncal defects are predominantly seen after maternal
Alcohol use by the father was positively related to the

offsprings risk of ventricular septal defects in one study.113
The authors admit that the data does not indicate strong
associations between paternal attributes and CHD. Because of
this studys imprecision and limited ability to isolate defects
likely to be of paternal origin, further study is necessary.
In a review125 of all major randomized trials and

observational studies from 1992 to 2000, three studies121-123
showed an overall decrease in the risk of CHD in the range
of 25 to 50 percent. This was maximal for conontruncal and
septal defects. A derangement of maternal homocysteine
metabolism and a mutation in the methylenetetrahydrofolate
reductase gene termed C677T are more frequently seen
in selected populations with CHD.126,127 This mutation is
associated with elevated homocysteine levels, which can be
normalized by folic acid supplementation.
In a case-control design, biomarkers of the folate-dependent
methionine and homocysteine pathway were measured among
a population-based sample of women, whose pregnancies were
affected by CHD.110 Case subjects had higher concentrations
of homocysteine and S-adenosylhomocysteine and lower
concentrations of methionine. Methionine is initially activated
by adenosine triphosphate (in presence of methionine
synthase) and converted to S-adenosylhomocysteine.
Homocysteine is elevated among women with a history of
adverse pregnancy outcomes including CHD.128 Increased
S-adenosylhomocysteine is a potent product inhibitor of
cellular methyltransferases, which during organogenesis
can alter gene expression, cell differentiation and apoptosis.
These alterations, if not causally related, are associated with
an increased risk of having adverse pregnancy outcomes,
including CHD. Possible causes for the altered biomarkers
include deficiencies in folate or vitamin B12 or both. Possible
mechanisms by which homocysteine may have an embryotoxic
effect include oxidative stress and secondary accumulation of
S-adenosylhomocysteine, which leads to product inhibition of
DNA methyltransferase reactions, DNA hypomethylation and
altered gene expression.
Vitamins
Indirect Evidence
Folic Acid
While the above studies directly tested the association

between multivitamin use and risk for CHD, other studies
present ancillary evidence of a protective effect of folic acidcontaining supplements on CHD. When pregnant women
took folic acid antagonists, there was a two-fold increased
risk of having babies with CHD. This was reduced among
those, who also took multivitamin supplements containing
folic acid.30 In a study on the effect of multivitamins in
high-risk groups, the increased risk for CHD associated with
febrile illness was reduced among women using multivitamin
supplements around the time of conception and during early
pregnancy.10
Associations with sulfasalazine given to pregnant
mothers and CHD was observed in a case-control study.23
These associations were not seen among mothers, who took
supplemental folic acid. As already mentioned, maternal
use of trimethoprim-sulfonamide has resulted in CHD
in offspring,23 the risk being reduced when folic acid was
supplemented.24
Paternal
Direct Evidence
A Hungarian randomized trial on birth defects showed that
periconceptional use of multivitamin supplements containing
folic acid had a 50 percent overall reduction in risk for CHD.121
It was 25 percent reduction in risk in the Atlanta populationbased case-control study.122 Multivitamin use reduced the
risk in case-control studies: 54 percent reduction in one122
and 30 percent in another.123 For ventricular septal defects, a
population-based case-control study122 showed a 40 percent
reduction and the Hungarian randomized trial showed a 85
percent reduction in risk.121 There was a 30 percent reduced
risk for conotruncal defects in a population-based case-control
study.123 Heterogenecity in this favorable response also has
been reported, with a more apparent trend in risk reduction for
transposition of the great arteries than for other defects of the
cardiac outflow tract.124
3
alcohol consumption during pregnancy.117 In a case-control

study of patients with conotruncal abnormalities and
ventricular septal defects, the effect of maternal alcohol use
was compared with controls.118 Maternal alcohol consumption
during the first trimester of pregnancy was more common
among the mothers of infants with ventricular septal defects
than among those of controls. These mothers consumed
alcohol regularly every week and consumed more than 1 drink
per occasion. Another case-control study examined sporadic
and daily doses of alcohol consumption and reported an
increased risk of CHD, as a group only with the highest level
of maternal alcohol consumption per day (> 92 g/day).119
Increased risks of atrial septal defects118 and ventricular septal
defects120 are associated with any maternal alcohol consumption
in the first trimester, but the dose-response trends in risk have
been inconsistent with a causal association in these studies. In
the Baltimore-Washington Infant Study, heavy consumption
(5 drinks on a single occasion) was linked to increased risk for
small muscular ventricular septal defects; but no statistically
significant associations were detected for atrial septal defect or
membranous ventricular septal defects.8 A similar study from
Finland reported double the risk of atrial septal defects with
maternal alcohol consumption during the first trimester.120
31
Vitamin A
The association between high vitamin A in the diet and/or
supplements and neural crest cell defects (cardiac and noncardiac defects) or outflow tract have been addressed in some
studies. An increased risk of CHD with an intake of more
than 10,000 IU retinol in the form of supplements129,130 and
occurrence of defects of the cardiac outflow tract at dosages
more than 18,000 to 25,000 IU/day in animals have been
described.
environmental factors
Organic Solvents
Maternal occupational exposure to organic solvents, chemicals,
dyes and paints is a signifcant risk factor for CHD and specifically
for ventricular septal defects.54,55,131 The Baltimore-Washington
Infant Study showed that maternal exposure to degreasing or other
solvents was associated with an increased risk of hypoplastic
left heart syndrome, coarctation of the aorta, pulmonic stenosis,
transposition of the great arteries with intact ventricular
septum, tetralogy of Fallot, total anomalous pulmonary venous
return, non-chromosomal atrioventricular septal defects and
Ebstein anomaly.8 Other associations are that of occupational
exposure to organic solvents and increased risk of ventricular
septal defects;118,132 dyes, lacquers and paints with conotruncal
malformations;133 and mineral oil products with coarctation of
the aorta.134 Genetic susceptibility to the effects of solvents and
paints has been suggested.135 Genetic polymorphisms in key
solvent-metabolizing enzymes, glutathione S-transferases, were
found to mediate the risks of solvents and paints for pulmonic
valve stenosis and atrial septal defect.
Chemicals at Workplaces
Hazardous maternal occupation has been implicated in the
causation of CHD in some studies.54 A study investigated the
possible associations between CHD and maternal occupational
exposure to various factors during the first trimester of
pregnancy.136 The cases were taken from infants diagnosed with
CHD, while controls were randomly selected from all normal
births during the same period. Maternal overall exposure to
chemicals at work was more prevalent among the case group.
Among the specific chemical groups, maternal exposure to
dyes, lacquers or paints was significantly associated with the
risk of CHD. Exposure to organic solvents during the first
trimester increased the risk of ventricular septal defects. Work
at video display terminals was more prevalent among the
case group.
32
Washington Infant Study, maternal exposure to herbicides and

rodenticides were linked to an increased risk of transposition
of the great arteries and maternal exposure to pesticides with
total anomalous pulmonary venous return and membranous
ventricular septal defects.8 A recent case-control study
of various end-product uses reported an increased risk of
conotruncal defects with maternal exposure to insecticides.132
The Baltimore-Washington Infant Study, a case-control
study of CHD in liveborn infants, revealed an association
of maternal exposure to herbicides and rodenticides during
the first trimester with transposition of great arteries in their
infants.138 Regarding the dose-response relation, it was found
that the risk was sequentially increased when mothers, who
reported one-time exposures and mothers reporting monthly
exposures were each compared with unexposed mothers. One
study has shown no association of maternal pesticide exposure
at work places with a risk for CHD.136
Air Quality
Studies have addressed the associations of ambient air
pollutants with CHD. A population-based case-control
study139 looked at risks of CHD associated with second
trimester exposure to carbon monoxide, sulfur dioxide,
nitrogen dioxide, ozone and particulate matter less than 10 m
in aerodynamic diameter. There were associations between:
1. Carbon monoxide exposure and increased risk of
ventricular septal defect and tetralogy of Fallot,
2. Ozone exposure and elevated risk of aortic artery and valve
defects, pulmonary artery and valve defects and conotruncal
defects,
3. Particulate matter less than 10 m in aerodynamic diameter
and atrial septal defect,
4. Sulfur dioxide and ventricular septal defects.
The difference is explained by the usage of a different
critical window of exposure in the analysis: gestational monthspecific exposures140 vs mean exposure for the entire period
of susceptibility, from gestational weeks 3 through 8.139
Groundwater Contamination
Contamination of public drinking water supplies by
chlorinated hydrocarbon solvents reportedly was associated
with increased risks for CHD.141143 The risk of CHD was
greater among children of parents, who had contact with areas
that had groundwater contaminated with trichloroethylene
than among children of parents, who had no such contact.141
Another study after evaluating the actual maternal
consumption of home tap water during the first trimester of
pregnancy found an increased risk of CHD.142
Herbicides, Pesticides and Rodenticides
Ionizing Radiation
An increased risk of conotruncal defects was associated

with maternal employment in the agricultural industry with
exposure to chemicals used in agriculture.137 In the Baltimore-
Ionizing radiation is implicated in the pathogenesis of CHD

in a small study.54 The Baltimore-Washington Infant Study
studied associations of CHD with maternal exposure to
ionizing radiation in occupational settings or for medical

evaluations and found no evidence of any associations.8
Studies have linked maternal exposure to chlorination byproducts in municipal water supplies and CHD.144
Other Environmental Hazards

Communities situated near hazardous waste sites or other
sources of environmental pollution had an increased risk of
CHD as a group,145 but the number of exposed cases were
small (n = 3) to draw valid conclusions. Rural residence was
associated with an elevated risk for CHD. This might be due to
the fact that, in this study, a considerable percentage of parents
living in rural areas were factory workers. Other possible
explanations might be exposure to pesticides or herbicides,
higher frequency of respiratory and other infectious diseases
implicated in the etiology of CHD.54
sociodemographic factors
Age
Maternal
Increased maternal age at conception was associated with
increased risk for CHD.131 Other studies reported that, after
excluding cases with chromosomal anomalies, maternal age
was not associated with CHD.4 In the Baltimore-Washington
Infant Study, maternal age was not associated with nongenetic CHD as a group.8 But analysis by specific defects
found that maternal age of more than 30 years was associated
with an increased risk of transposition of great arteries and
Ebstein anomaly. More advanced maternal age (> 34 year)
was associated with an increased risk of bicuspid aortic valve
and atrial septal defects. Young maternal age (< 20 year) was
associated with an increased risk of tricuspid atresia. Analysis
of non-chromosomal birth defects of the Metropolitan Atlanta
Congenital Defects Program found associations of advanced
maternal age (3540 year) with an increased risk of all CHD,
tricuspid atresia and right ventricular outflow tract defects.146
Paternal
With increasing paternal age, an increase in the risk in the
offsprings for atrial and ventricular septal defects and patent
ductus arteriosus has been in one study147 and for pulmonic
stenosis in another.113 Offsprings of men less than 20 years
of age were at higher risk for atrial and ventricular septal
defects. Data from Metropolitan Atlanta Congenital Defects
Program also found an increased risk for atrial and ventricular
septal defects with increasing paternal age after adjustment
Gender and Race

Increased prevalence of left-sided obstructive lesions,
particularly coarctation of the aorta and aortic valve stenosis,
among whites has been reported.149,151 White infants are also
reported to have an increased prevalence of Ebstein anomaly,
atrioventricular septal defects, atrial septal defects,149 truncus
arteriosus, transposition of the great arteries, tetralogy of
Fallot,137,149 patent ductus arteriosus149,152 and hypoplastic
left heart syndrome.152 In the Baltimore-Washington Infant
Study, significant association for membranous ventricular
septal defect was found with African-American race of the
infant.69 Pulmonic valve stenosis was also more prevalent
among African-Americans in the Baltimore-Washington
Infant Study.8 Increased prevalence of transposition of the
great arteries among male infants in the Baltimore-Washington
Infant Study and of atrioventricular septal defects in females
with Down syndrome has been noted.8
3
Water Chlorination Byproducts
for maternal age.148 A matched case-control study showed

that an older paternal age was a significant risk factor for
developing any CHD, atrial and ventricular septal defects and
pulmonary stenosis.54 Other epidemiological studies have
found an association between advanced paternal age and
CHD.147 A prospective study32 and the Baltimore-Washington
Infant Study69 could not find an association between paternal
age and CHD.
Maternal Psychology and Stress

Maternal psychological stress was associated with an
increased risk of conotruncal heart defects in one study.137
A case-control study gave similar results with a stronger
effect among offspring of mothers, who were high school
dropouts.153 Experiencing at least one stressful event during
the periconceptional period was associated with a high-risk of
delivery of infants with conotruncal heart defects. At least one
study has ruled out mothers education level as an association
for CHD.136
Socioeconomic Deprivation
There was an increasing risk with increasing deprivation for
all CHD and for septal defects.154 Other studies have shown
socioeconomic trends of higher risks in lower social classes
for some specific cardiac defects149 and ventricular septal
defects.155
Reproductive History
Birth Order
A birth order of more than the second increases the risk of
having CHD.4,150,156,157
33
34
Bad Obstetric History
recurrences of CHD in families
This is associated with an increased risk of tetralogy of Fallot,

non-chromosomal atrioventricular septal defects, atrial septal
defects and Ebstein anomaly in the Baltimore-Washington
Infant Study.8
Family History as Risk Factor
Assisted Reproductive Technology

A rapidly developing field, this is associated with CHD as
seen in meta-analysis158 and in a controlled, prospective
cohort study.159 This association is observed particularly for
septal defects in a population-based, multicenter, case-control
study.160 From the data of the Paris Registry of Congenital
Malformations, there was a 40 percent increase in the overall
risk of CHD without chromosomal abnormalities in children
conceived following assisted reproductive technology after
taking into account maternal age, socioeconomic factors and
year of birth.62 There were specific associations between
assisted reproductive technology and subcategories of
CHD. Significant increases in the odds of malformations of
the outflow tracts and ventriculoarterial connections and of
cardiac neural crest defects and double outlet right ventricle
were seen. These results for CHD without chromosomal
abnormalities suggest that associations between CHD and
assisted reproductive technology are not due to the association
of the latter with chromosomal abnormalities. This higher
risk for CHD varied specifically, according to the method of
assisted reproductive technology and the type of CHD and
may be due to assisted reproductive technology per se and/or
the underlying infertility of couples.
The confounding factor of an additional mechanism came
into play here. There was no adequate data for folic acid and/
or multivitamins intake for women in this population. Lack
of adjustment for multivitamins use could have resulted
in an underestimation of the risks associated with assisted
reproductive technology:
i. Multivitamins/folic acid intake lowers the risk of
CHD.122
ii. A higher proportion of women, who conceived after
assisted reproductive technology may have had an
adequate multivitamins/folic acid intake.160 Another
compounding factor is the difficulty in distinguishing
between the effects of the underlying subfertility and the
infertility treatments used. It is not decided if the history
of reproductive problems is a proxy for teratogenic
exposures or is an inherent increased susceptibility
for CHD. Gestational losses has been described, both
for general117 and specific defects.83 Further, women
undertaking assisted reproductive technology are likely
to have lower exposure to toxins such as alcohol and
cigarettes and to be of higher socioeconomic status, than
the general population of pregnant women.
Family history of CHD is a known risk factor. Several studies

have reported a higher risk for CHD in first degree relatives of
patients. Offspring of patients with CHD are at a higher risk
of having CHD.161 The prevalence of CHD is 3.1 percent in
offspring of individuals with CHD and 1.3 percent in offspring
of individuals without CHD. The adjusted odds ratio for CHD
to offspring of parents with CHD is 1.73 (95% CI 0.892.44,
p = 0.02).161 The risk is higher if the affected first-degree
relative is a parent rather than a sibling6 and if it is the mother
rather than the father with CHD.1 When the recurrence risk
of CHD was examined using fetal echocardiography in 6,640
consecutive pregnancies, where a first-degree relative had a
CHD, the rate of recurrence for all CHD was 2.7 percen, with
a high concordance for the specific type of CHD (37%), or for
CHD of the same group (44%).162
A population-based study163 found that the same CHD
phenotype showed strong familial clustering in first-degree
relatives, ranging from a 3-fold to 80-fold compared with the
population prevalence. A family history of any CHD among
first-degree relatives accounted for 2.2 percent of CHD in the
population. This relative risk diminished, when the family
history of CHD was in only second- and third-degree relatives.
This suggests that gene mutations may be an underlying cause.
In families where there were two or more recurrences, the exact
concordance rate was 55 percent. Even in these families in
which there was a strong evidence for monogenic inheritance,
the type of heart defect was not always predictable; over
40 percent of index and first affected pregnancy cases were
discordant. Exact concordance rates were particularly high
for isolated atrioventricular septal defects (80 percent) and
laterality defects (64 percent). Minor CHD in the index case
does not exclude more severe disease in recurrences. Major
CHD in the index case does not necessarily imply very severe
CHD in recurring cases. For non-syndromic hypoplastic left
heart syndrome, epidemiologic studies have demonstrated an
increased recurrence risk in the family.163 From a populationbased registry of adults, who survived surgery for selected
major CHD, the recurrence risk among offspring (4.1%) was
significantly greater than among siblings (2.1%).165
The risk of recurrence of CHD in a child having one parent
with CHD is reported to vary from a lowest of 2.5 percent
(atrial septal defect) to a highest of 4.3 percent (ventricular
septal defect).97 The abnormality in the child is often the
same as in the parent or a closely related variant. A parent
with pulmonary stenosis without a Mendelian syndrome,
who has a spouse with no CHD and no other children with
CHD, has a risk to a subsequent child of 3 percent. If the
mother has Noonan syndrome, half of her children will have
this dominantly inherited syndrome and half of those with
(based on the suspected pathogenic mechanism) for CHD was

100 percent. Dizygotic twins are siblings with different genes,
carried together in the same womb. Genetically, they can be
considered as non-twin siblings. Thus, the higher occurrence
of CHD in dizygotic twins could depend on a non-identified
environmental risk during pregnancy.
Consanguinity
Left vs Right-sided Lesions

Left-sided lesions predominate among relatives of patients
with CHD. In the Baltimore-Washington Infant Study, the
sibling recurrence risks of CHD was 3.1 percent overall and
highest among cases with left-sided obstructive heart defects,
notably, hypoplastic left heart, with an 8.0 percent recurrence
rate and coarctation of aorta, with a recurrence rate of 6.3
percent.8 Familial aggregation of left-sided obstructive heart
defects, particularly coarctation and aortic valve stenosis, has
been reported.165,166 Relatives of children with hypoplastic
left heart syndrome have a higher incidence of left-sided
lesions such as bicuspid aortic valve and aortic stenosis.167
Concordant left-sided obstructive CHD (including bicuspid
aortic valve) among siblings, parents and other relatives of
affected probands has been reported in another study.168 Thus,
an apparent familial aggregation of left-sided obstructive
defects is seen and corroborated in studies of echocardiograms
on first-degree relatives.169,170
Twins
The relative risk for CHD in monozygotic twins was much
stronger than in unlike-sex twins, whereas the relative risks
in unlike-sex twins and in singletons with a family history of
any CHD in first-degree relatives were similar.163 The excess
relative risk of CHD in monozygous twins, also reported by
others171 and not in unlike-sex twins indicates that twinning
per se predisposes to CHD, (omit plural) whereas the shared
in utero conditions do not appear to play a role. The relative
risk for CHD in monozygotic twins is much stronger than the
relative risk in unlike-sex twins, whereas the relative risks in
unlike-sex twins and in singletons with a family history of any
CHD in first-degree relatives are similar. The excess relative
risk of CHD in monozygous twins indicates that twinning
per se predisposes to CHD,171 whereas the shared in utero
conditions do not appear to play a role.
In an elegant study on CHD in dizygotic twins,172 the potential
role of genetic and non-genetic factors in the development of
CHD was studied. Dizygotic twins were compared with nontwin patients, who had a sibling with the same or similar CHD.
The recurrence rate among non-twin patients was 4 percen. In
13.6 percent of twins, both siblings had a CHD. Same CHD in
siblings was seen in 55.5 percen of dizygotic twins, while it was
only 6 percent in siblings of non-twin patients. In the 9 pairs
of twins in whom both siblings had CHD, the concordance
A highly inbred population showed a much lower incidence of

CHD.173 Some studies found a relationship with consanguinity
and CHD,54,174-177 but some of those studies were performed
in regions where endogamy is common.174-176 This association
with consanguinity was higher for certain heart defects,
especially ventricular and atrial septal defects.174,175
Mother or Father
The adjusted odds ratio for CHD is higher for offsprings of
affected females than for offsprings of affected males (2.30 vs
1.31, respectively).161 The increased risk for the offspring of a
mother with CHD contrasted to a father with CHD is noted in
other studies.164,178-181 This gender difference has been noted
even for specific CHD, as for example, in Ebstein anomaly.179
Since the etiology of CHD is multifactorial, the threshold for
the penetrance in females could be higher. An affected female
represents an increased genetic burden, transmitting the disease
more often to her offspring.178 Other possibilities could be a
parent of origin effect due to maternally imprinted CHD genes
or involvement of mitochondrial genes in the etiology of CHD.
3
the syndrome will have 25 percent risk rather than 3 percent

recurrence risk. A mother with atrial septal defect, whose
mother and only sibling also have atrial septal defects and
her husband is free of CHD should be considered a high-risk
family until proved otherwise. Inspection of other family
members would reveal a minor limb anomaly, which would
support dominant inheritance.
Limitations
There are limitations in studies on the recurrence of CHD
in family. Patients with more severe CHD may not survive
to adulthood or their handicap prevents them from having
a child. Individuals with a milder defect might be included
more often in such studies. If more severe CHD are associated
with a higher risk to offspring, the estimated relative risk
could be underestimated. Misclassification bias could result
from several factors. Some CHD, such as ventricular septal
defects, resolve spontaneously and are not diagnosed. Higher
proportion of offspring of patients with CHD may undergo
cardiac evaluation including echocardiography, while
offspring of individuals without CHD may not. Asymptomatic
CHD may be diagnosed in this group more often, resulting in
an overestimated relative risk. Further, the group of unaffected
parents may not undergo any cardiac evaluation and a few of
them might have suffered from an undiagnosed CHD.
Interaction of genetic and non-genetic factors

The potential effects of parental exposures on etiopathogenesis
of CHD are of great public and scientific concern. Both genetic
35
and non-genetic environmental factors play crucial roles in

this. It is believed that CHD is caused by the interaction of
genetic and environmental factors182,183 and 30 percent of
some CHD may be attributable to identifiable and potentially
modifiable factors.46 After a teratogenic insult, fetuses may be
unaffected, suggesting that only a subpopulation may be at risk.
In contrast, several syndromic and familial cases of CHD are
caused by rare single-gene mutations that have major effects.
The predisposition to CHD involves multiple factors,
including different genetic loci, epigenetic factors (e.g.
DNA methylation or histone modifications that affect gene
expression), environmental influences, subtle hemodynamic
factors during cardiac development or a combination of these
factors. The common forms of CHD that appear to be sporadic
may be caused by inherited genetic variants that affect protein
expression or function and manifest, as disease only when
combined with additional genetic, epigenetic, environmental
or hemodynamic insults.128 A parent may harbor a genetic
predisposition to a disease (susceptibility allele) and transmit
this genetic risk to the offspring. However, this would result
in CHD only in conjunction with variants in other genetic loci
or with epigenetic factors, resulting in disease penetrance.
The susceptibility allele alone may not be sufficient to cause
disease in offspring (non-penetrance), but the individual
would still be at risk for vertical transmission of increased
risk. A potential disease-susceptibility allele could lead to
disease penetrance or non-penetrance, depending on the size
of the effect of the susceptibility allele and the presence of
second hits that modify the phenotype.
In the Baltimore-Washington Infant Study, significant
associations were found for membranous ventricular septal
defects with paternal marijuana use, cocaine use among
older fathers and African-American race of the infant. These
associations support a multifactorial etiologic hypothesis for
isolated membranous ventricular septal defects.69
Studies on risk factors for CHD

While etiopathogenesis of CHD has been comprehensively
reviewed, it may be noted that there are controversies
and conflicts too. Hence, it is appropriate to look into the
methodology of collection of data in the various studies
described.
Study Designs
36
The ideal study design for the epidemiological approach

to CHD is a randomized clinical trial. Except for prenatal
multivitamin supplements containing folic acid, which
reduce the occurrence of CHD,121,123 there are very few
preventive strategies. Then there are case-control studies.
They identify patients with CHD, select a comparison group
and retrospectively evaluate the risk factors in the two groups.
It requires fewer study subjects, since affected persons can

be ascertained from a few sources; it is also more costeffective. Most of the data on risk factors come from casecontrol studies and the best available information comes from
two large population-based case-control studies specifically
designed to investigate risk factors for CHD in an exploratory
manner. The Baltimore-Washington Infant Study conducted
in the Baltimore-Washington area between 1981 and 19898
and the study conducted in Finland by the National Public
Heath Institute in Helsinki of cases and controls born during
1982 to 1984.131 These larger, population-based studies used
standardized methods for ascertaining and classifying CHD
and methods to minimize potential biases.
Limitations of the Studies

The disadvantages of case-control studies are the potential
for selection bias in assembling the case population, such that
the cases are not representative of all the patients with the
disease. This bias may relate to non-participation in the study
or to incomplete participation and missing information on the
exposure questions. It is possible that women, who conceive
after exposure are more likely to participate in the study.
Further, some studies focus on individuals with severe CHD,
some include all types of CHD.
Then there is the potential for recall bias. Maternal
recollection of periconceptional events may be influenced by
the birth of a child with a congenital malformation, calling to
mind events and exposures suspected as being teratogenic.
Assessment is based on parental recall after the birth of the child.
Most studies on non-genetic factors in the etiopathogenesis of
CHD suffer from recall and interviewer bias. They are based
on retrospective interview data or questionnaires. This could
very often be long after the birth of the infant. This method
of data collection may carry the risk for recall bias and
when interviews are part of routine birth defect registration,
interviewer bias can also be involved.
Patients with more severe CHD may not survive to
adulthood or their handicap prevents them from having a
child. Individuals with a milder defect might be included
more often in such studies. If more severe CHD are associated
with a higher risk to the offspring, the estimated relative
risk could be underestimated. Some CHD may have subtle
symptoms or, for better or worse, be asymptomatic. Some
are strongly age-dependent in manifestations, following the
natural history of the malformation. Some CHD (e.g. small
ventricular septal defects) spontaneously resolve and are not
diagnosed. There is no universal coding or nomenclature
system, hampering communication among scientists.
Further, CHD is not a single disease, but rather a spectrum
encompassing many specific diagnoses, each of which may
be distinct in origin and risk factors. Many fetuses with CHD
die in utero, resulting in a survival bias among the types of
might be due to confounding by the condition for which the

analgesic was taken (e.g. influenza or a febrile illness) and
the apparent protective effect of multivitamin supplement use
might be due not to the use itself, but to the behavior of the
user. The differences in the results of the different studies can
also be attributed to different methodologies used.
Conclusion
Congenital heart defects are a frequest cause of morbidity and
mortality in children and adolescents. They have an impact
on human suffering and economic costs. The challenge for
the future is to prevent CHD through primary prevention.
This can be done through genetic counseling and also health
awareness of the various risk factors.
We know a great deal more about the causes of disease than
we do about the causes of health.
M Scott Peck, TRLT
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3
CHD present among live births. Technological advances

in diagnosis (e.g. echocardiography) have increased the
sensitivity of diagnosis, which makes it difficult to compare
modern and historical studies. If there is a large increase in
the prevalence of any particular malformation in later studies
compared to older ones, it may entirely be due to better
diagnostic methodologies. Higher proportion of offspring of
patients with CHD may undergo cardiac evaluation including
echocardiography, while offspring of individuals without
CHD may not. Asymptomatic CHD may be diagnosed in this
group more often, resulting in an overestimated relative risk.
Further, the group of unaffected parents may not undergo any
cardiac evaluation and a few of them might have suffered
from an undiagnosed CHD.
The data in case control studies refer to the prevalence
of a CHD at birth and may not reflect the true incidence, if
prenatal selection of malformed embryos or fetuses occurs
through spontaneous or selectively induced abortions. For
CHD, the true incidence would need to include occurrences
among spontaneous abortions. A risk factor that causes a
selective loss of embryos with CHD may not be detectable in
a study based on infants born. Therefore, some associations
might be missed in this study. The other alternative, the
prospective studies, are known to detect stronger associations,
but there are difficulties in the case of CHD, since performing
autopsy on stillborn and dead neonates is necessary to rule
out other causes of stillbirth or neonatal deaths (e.g. other
congenital anomalies). But case-control studies identify risk
factors for CHD in fetuses that survive to birth, which is the
group representing the practically important problem. Taking
into consideration the relatively low prevalence rate of CHD
in livebirths, a whole population-based study is required to
obtain an adequate sample size that will not affect the power
of the study with such a multitude of associations.
Variations in live birth prevalence of CHD by time and
place can yield tentative clues about risk factors. Peak rates
of coarctation of aorta was seen in winter in one study,184
plausibly suggesting an infectious source. But, variability
in study designs and methods makes it extremely difficult to
compare prevalence rates taken from different reports and
time periods.
The absence of demonstrable effects may have different
explanations. Studies on the association between risk factors
and CHD may be limited by small numbers and lack of
an appropriate control group. A true association may be
missed, because of low validity in exposure information (e.g.
occupational exposure, where only maternal and paternal
occupation was known). Low validity of the exposure
information may also affect the results, as regular or heavy
and temporary exposures may not be differentiated (e.g.
alcohol abuse). Associations between risk factors and CHD
in observational studies may be the result of chance, bias or
confounding. Confounding is of concern in that an apparent
association between reported analgesic use and a heart defect
37
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exposures interact with polymorphisms in glutathione-Stransferase genes to increase the risk of congenital heart
defects. Teratology. 1997; 55:42A.

136. Tikkanen J, Heinonen OP. Occupational risk factors for
congenital heart disease. Int Arch Occup Environ Health. 1992;
64:59-64.
137. Adams MM, Mulinare J, Dooley K. Risk factors for conotruncal
cardiac defects in Atlanta. J Am Coll Cardiol. 1989; 14:432-42.
138. Loffredo CA, Silbergeld EK, Ferencz C, et al. Association
of transposition of the great arteries in infants with maternal
exposures to herbicides and rodenticides. Am J Epidemiol.
2001; 153:529-36.
139. Gilboa SM, Mendola P, Olshan AF, et al. Relation between
ambient air quality and selected birth defects, seven county
study, Texas, 1997-2000. Am J Epidemiol. 2005; 162:238-52.
140. Ritz B, Yu F, Fruin S, et al. Ambient air pollution and risk of
birth defects in Southern California. Am J Epidemiol. 2002;
155:17-25.
141. Goldberg SJ, Lebowitz MD, Graver EJ, et al. An association
of human congenital cardiac malformations and drinking water
contaminants. J Am Coll Cardiol. 1990; 16:155-64.

142. Shaw GM, Swan SH, Harris JA, et al. Maternal water
consumption during pregnancy and congenital cardiac
anomalies. Epidemiology. 1990; 1:206-11.

143. Dawson BV, Johnson PD, Goldberg SJ, et al. Cardiac
teratogenesis of halogenated hydrocarbon-contaminated
drinking water. J Am Coll Cardiol. 1993; 21:1466-72.
144. Shaw GM, Malcoe LH, Milea A, et al. Chlorinated water
exposures and congenital cardiac anomalies. Epidemiology.
1991; 2:459-60.
145. Croen LA, Shaw GM, Sanbonmatsu L, et al. Maternal residential proximity to hazardous waste sites and risk for selected
congenital malformations. Epidemiology. 1997; 8:347-54.
146. Reefhuis J, Honein MA. Maternal age and non-chromosomal
birth defects, Atlanta-1968-2000: teenager or thirty-something,
who is at risk? Birth Defects Res A Clin Mol Teratol. 2004;
70:572-9.
147. Olshan AF, Schnitzer PG, Baird PA. Paternal age and the risk
of congenital heart defects. Teratology. 1994; 50:80-4.
148. Lian ZH, Zack MM, Erickson JD. Paternal age and the occurrence
of birth defects. Am J Hum Genet. 1986; 39:648-60.
149. Correa-Villasenor A, McCarter R, Downing J, et al. Whiteblack differences in cardiovascular malformations in infancy
and socioeconomic factors: the Baltimore-Washington Infant
Study Group. Am J Epidemiol. 1991; 134:393-402.
150. Torfs CP, Curry CJ, Harris JA. The descriptive epidemiology
of hypoplastic left heart, coarctation of the aorta, and aortic
stenosis. Teratology. 1991; 43:448-9.
151. Storch TG, Mannick EE. Epidemiology of congenital heart
disease in Louisiana: an association between race and sex and
the prevalence of specific cardiac malformations. Teratology.
1992; 46:271-6.
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42
173. Gatrad AR, Read AP, Watson GH. Consanguinity and complex
cardiac anomalies with situs ambiguus. Arch Dis Child. 1984;
59:242-5.

174. Becker SM, Al Halees Z, Molina C, et al. Inbreeding and
congenital heart disease in Saudi Arabia. Am J Med Genet. 2001;
99:8-13.
175. Yunis K, Mumtaz G, Bitar F, et al. Consanguineous marriage
and congenital heart defects: A case-control study in the
neonatal period. Am J Med Genet A. 2006; 140:1524-30.
176. Gev D, Roguin N, Freundlich E. Consanguinity and congenital
heart disease in the rural Arab population in northern Israel.
Human Heredity. 1986; 36:213-7.
177. Jain VK, Nalini P, Chandra R, et al. Congenital malformations,
reproductive wastage and consanguineous mating. Aust NZ J
Obst Gynaecol. 1993; 33:33-6.
178. Nora J, Nora AH. Maternal transmission of congenital heart
disease. New recurrence risk figures and the questions of
cytoplasmic inheritance and vulnerability to teratogens. Am J

Cardiol. 1987; 59:459-63.
179. Connolly HM, Warnes CA. Ebsteins anomaly: outcome of
pregnancy. J Am Coll Cardiol. 1994:23:1194-8.
180. Emanuel R, Somerville J, Inns A, et al. Evidence of congenital
heart disease in the offspring of parents with atrioventricular
defect. Br Heart J. 1983; 49:144-7.
181. Nora J, Nora AH. Update on counselling the family with a
first degree relative with a congenital heart defect. Am J Med
Genet. 1988:29:137-42.
182. Nora JJ. Multifactorial inheritance hypothesis for the etiology
of congenital heart diseases: the genetic-environmental
interaction. Circulation. 1968; 38:604-17.
183. Ferencz C, Correa-Villasenor A. Epidemiology of cardiovascular
malformations: the state of the art. Cardiol Young. 1991; 1:264-84.
184. Miettinen OS, Reiner ML, Nadas AS. Seasonal incidence of
coarctation of the aorta. Br Heart J. 1970; 32:103-07.
C hapter
Fetal Cardiology
Shardha Srinivasan
eOver the past two decades, rapid advances in the field of

ultrasound, in conjunction with developments in surgery,
invasive cardiology and intensive care has revolutionized
the field of pediatric cardiology. With this came the need
for early diagnosis of congenital heart disease (CHD) in an
effort to further improve morbidity and mortality. Ultrasound
has been increasingly applied to the evaluation of the fetal
cardiovascular system allowing for more detailed evaluation
of cardiac structure as well as its function. Over the past decade
or so, fetal cardiology has evolved into a highly specialized
field, based on close collaboration between perinatology and
pediatric cardiology.
Ultrasound provides a unique ability for noninvasive
assessment of fetal heart and cardiovascular system including:
1. The assessment of fetal cardiac anatomy and its alterations
2. The assessment of fetal cardiovascular physiology
3. Assessment of fetal rhythm.
Advances in transducer technology and ultrasound machines
and the resultant improvement in image resolution allows
for evaluation of anatomic details at much greater level and
prenatal detection of most CHD. Early assessment of fetal heart
and serial assessments have provided us with an understanding
of the evolution of certain types of lesions; spurring the
exploration of interventional strategies in some lesions in an
attempt to modify the evolution to more significant heart disease.
Doppler evaluation of the fetal heart and fetal cardiovascular
system has provided us with unique insights into cardiovascular
physiology and fetal compensatory mechanisms to both altered
structure as well as in the setting of noncardiac pathologies and
the pathophysiology of fetal heart failure. Ultrasound has also
contributed significantly to our ability to diagnose, monitor and
manage fetal arrhythmias. Fetal echocardiography now has a
significant role in the management of not just fetal CHD, but
also in several noncardiac fetal pathologies.
Prenatal diagnosis of CHD allows for evaluation of
associated genetic or noncardiac lesions that can impact
outcomes, better counseling and preparation of the family,
planning of pregnancy and delivery options and institution of

appropriate fetal and neonatal management strategies.
IdentIFyIng the Fetus at rIsk For

CongenItal heart dIsease
The incidence of congenital cardiac malformations in
newborns is approximately 5 to 11/1,000 live births.15
CHDs are 8 times more common than Down syndrome for
which there are currently well-established prenatal screening
protocols. Recent studies suggest that the overall incidence has
been stable over the past decade.2,6 CHD may be attributed to
various different etiologies, which can be stratified into three
groups: fetal, maternal and familial risks as outlined in Table
1. However, there are currently no strong markers for fetal
CHD with the highest yield being in the setting of abnormal
cardiac screening views in 42 to 69 percent, followed by fetal
chromosomal abnormalities in 47 to 50 percent and presence
of other extracardiac abnormalities in 4.4 to 9 percent.7,8 A
diagnosis of CHD is established in about 2.7 to 20 percent of
cases referred for a fetal echocardiogram.8,9
Maternal metabolic disorders such as pregestational diabetes
and phenylketonuria are associated with heart defects in fetus.
Though a 3 to 5 times increase in risk for CHD is reported in
maternal diabetes, recent data suggests that this higher risk is
associated with poor control and higher hemoglobin A1c levels
in the periconceptional period. Recent studies have reported
yields of 0 to 7 percent and are likely reflective of the setting
in which the study is performed.8,9 Other maternal risk factors
include exposure to either drugs or viral infections (Table 1)
that may damage the developing heart with resultant CHD and
myocarditis. Fetal dilated cardiomyopathy has been reported
with maternal viral infections.10,11 Maternal autoantibodies
especially anti-Ro and anti-La antibodies can cross the placenta
between 16 to 18 weeks gestation with a risk for fetal heart
block and cardiomyopathy in about 1 to 3 percent cases, but
the majority of these occur in asymptomatic women.
table 1
Embryo to thE NEoNatE
Indications for fetal echocardiography

Maternal
Fetal
Familial
1.

2.

3.

4.
5.
1.
2.
3.

4.
5.

6.
7.
8.
9.
1.
2.
3.

Systemic disease
Pregestational diabetes
Phenylketonuria
Presence of anti-SSA/SSB
autoantibodies
Teratogen exposure
Anticonvulsants
Lithium
Paroxetine
Retinoid
NSAID
Maternal infection
Parvovirus
TORCH
Coxsackie
In-vitro fertilization
Maternal CHD
Abnormal cardiac screen

Increased nuchal translucency
Extracardiac anomaly
Omphalocele
Duodenal atresia
Diaphragmatic hernia
Tracheoesophageal fistula
Cystic hygroma
Situs inversus
Abdominal wall defects
Single umbilical artery
Chromosomal anomaly
Conditions with known risk for heart
failure:
Vascular tumor
Arteriovenous malformation
Cystic adenomatoid malformation
Absence of ductus venosus
Hydrops fetalis
Monochorionic twinning
Fetal arrhythmia
Polyhydramnios
Paternal CHD
Prior child or fetus with CHD
Familial syndromes/single gene defects
Noonan
William
DiGeorge
HoltOram
Marfan
Tuberous sclerosis
CHD = Congenital heart disease; NSAID = Non-steroidal anti-inflammatory drugs; TORCH = Toxoplasmosis, rubella, cytomegalovirus and herpes
44
Fetal chromosomal abnormalities have a high association

with underlying congenital heart defects. 3,12 These include
cases of trisomy 21, 13 and 18 and 22q11 deletion. An
elevated first trimester nuchal translucency (NT) is a marker
for aneuploidy and in the setting of normal chromosomes for
other fetal malformations including CHD.13 In the study by
Hyett et al the prevalence of major CHD increased with an
increase in the NT, from 0.8 per 1000 live births for a NT
less than 95 percentile to 63.5 per 1000 live births for those
with a NT greater than 99 percentile or about 3.5 mm and 55
percent of cases with CHD had an elevated NT between 10
to14 weeks gestation.13 However, the diagnostic accuracy of
increased NT as a predictor of CHD in the general population
has been lower. Based on a meta-analysis, Makrydimas et al
concluded that approximately 30 percent of the major CHD
detected by specialist echocardiography in a chromosomally
normal population, had a NT greater than 99 percentile,
but sensitivity has been lower in other population based
studies.1417 Nonetheless, the prevalence of CHD is 3 to 4
folds higher in the fetus with a NT greater than 3.5 mm and it
serves as an important indication for fetal echocardiography.
Other markers such as abnormal ductus venosus flow patterns
in very early pregnancy as well as the presence of tricuspid
regurgitation in early gestation are being explored as potential
markers for CHD.1820
Fetuses with extracardiac malformations merit a complete
cardiac evaluation. Malformations in more than one
system may indicate a syndrome or chromosomal anomaly.
Abnormalities with a particular association with CHD are

included in Table 1. CHD may rarely present with either
significant tachycardia or bradycardia in the setting of
complex congenital heart defects, though overall incidence is
low. Recent publications indicate a higher risk for CHD in
conditions such as twin-twin transfusion syndrome (TTTS) and
in vitro assisted conceptions.2123 Fetal echocardiograms are
also increasingly being used for assessment of cardiovascular
status and function in noncardiac lesions such as TTTS as well
as conditions associated with altered loading conditions on
the heart such as vascular tumors, diaphragmatic hernia and
congenital cystic adenomatoid malformation (CCAM).
A family history of CHD remains an important indication
for fetal echocardiography not because of high yields, but for
the reassurance that a normal study provides to these families.
Single gene disorders such as microdeletion of chromosome
22 (del 22q 11) have been associated with patterns of CHD
typically involving the conotruncus. Recurrence risks are
higher for certain lesions such as heterotaxy syndromes and
left heart obstructive lesions.24,25
The majority of CHD occurs in the absence of clearly
identifiable risk factors and ideally all pregnancies should
be screened for heart defects in conjunction with the
midgestation anomaly scan.9,2628 There are many published
studies and commentaries outlining the wide variation in
prenatal pickup of CHD variably attributable to differences
in scanning protocol-4 chamber alone versus inclusion of
outflow tract imaging, instrumentation and level of training
limitations of image resolution are particularly important in

these early scans and it is important to keep use of color and
pulsed Doppler to the minimum necessary. Given potential
for evolution of certain lesions through gestation, it remains
necessary to perform a follow-up scan between 24 to 28 weeks
in these cases. Currently, these early scans are mostly limited
to select population at high-risk such as those with abnormal
first trimester screening or where the reassurance is important
as in a family history for CHD.
Fetal eChoCardIogram
technical Considerations
Timing of Scan: The best balance of image definition as well

as timing for counseling is afforded between 18 to 20 weeks
gestation. This allows time for re-evaluation in the setting of
a difficult scan, evaluation of the fetus for possible associated
chromosomal defects and other abnormalities, and time for the
family to consider all options available without being rushed.
Most major CHD can be reliably diagnosed in this time
frame; however, a small number of lesions may evolve later in
pregnancy. From the standpoint of general applicability, this
remains the most favorable time period for assessment of the
fetal heart.
Several studies have demonstrated the feasibility of
obtaining diagnostic scans in the early fetus, as early as 11
to 13 weeks of gestation in skilled hands for major CHD
such as ventricular hypoplasia, transposition of the great
vessels as well as atrioventricular canal defects.20,3840 The
Though ultrasound techniques for fetal evaluation are welldefined, the fetal heart poses several differences that make it more
challenging. Firstly, the fetal heart is small and often measuring
only a centimeter or two. Thus, high image resolution is needed
to enable visualization of the cardiac structures in enough
detail. However, the fetus may be situated at varying depths
from the maternal abdomen depending on maternal habitus,
amniotic fluid volume and gestation age, necessitating imaging
in the far field in some instances. Secondly, the fetal heart is a
dynamic structure with heart rates typically ranging from 120 to
160 BPM, hence high frame rates (typically 50 to 100 Hz) are
necessary for optimal temporal resolution. Finally, the fetus by
virtue of its mobility frequently changes its presentation with
respect to the transducer and hence a good understanding of
the cardiac anatomy in three dimensions is necessary for the
performance and interpretation of fetal echocardiography.
4
FEtal Cardiology
of sonographers.27,2933 Inclusion of outflow tracts improves

detection of conotruncal lesions, which have a high likelihood
of being ductal dependent.28,34 Improvement in pickup rates
with regional training programs is well-demonstrated in
several European countries.35,36 However, recent studies
continue to demonstrate a wide variability in referral patterns
for fetal echocardiography as well as pick up of cardiac
abnormalities on routine scanning.30,31,37 Table 2 outlines the
anticipated abnormality by different views.
table 2
Expected findings on screening images in different congenital heart diseases

Diseases
TAPVR
Tricuspid atresia
Ebstein anomaly/ TV dysplasia
Mitral valve dysplasia
AVSD (balanced)
Primum atrial septal defect
Hypoplastic left heart
Aortic stenosis
Pulmonic stenosis
PA/IVS
Coarctation
Large perimembranous VSD
Malalignment VSD
L-transposition of great vessels
D-transposition of great vessels
Tetralogy of Fallot
Double outlet right ventricle
Truncus arteriosus
Vascular ring
Interrupted aortic arch/no VSD
Interrupted aortic arch/VSD
Four chamber view
Outflow tracts
Three vessel/trachea view
PA
A
A
A
A
A
A
PA
PA
PA
PA
PA
N
A
N
N
N
N
N
N
N
PA
A
PA
A
N
N
A
PA
PA
A
PA
PA
A
A
A
A
A
A
PA
PA
A
PA
A
PA
A
N
N
A
PA
PA
A
PA
N
PA
A
A
A
A
A
A
A
A
A = Abnormal; AVSD = Atrioventricular septal defect; N = Normal; PA = Possibly abnormal indicating cases where in a subtle abnormality may be present,
but could be missed on screening scans or where the presence of an abnormality depends on the severity of lesion; PA/IVS = Pulmonary atresia with
intact ventricular septum; VSD = Ventricular septal defect;
45
To achieve the above requirements a balance between

penetration and the maximal possible lateral resolution is
needed. Most current ultrasound machines used for fetal
imaging provide transducers with a range of imaging
frequencies, with typical frequencies used being the 4 to 10
MHz range. Lower frequencies along with use of harmonic
imaging may be needed in the setting of increased fetal depth
or poor insonation characteristics. Linear array transducers
or phased array transducers with dynamic focus may be
used. Postprocessing should be set to improve frame rates by
judicious use of dynamic zoom and optimal depth with low
persistence and spatial averaging. Endocardial definition is
enhanced by the use of relatively high dynamic contrast and
appropriate grayscale map. Use of color flow mapping tends
to drop frame rates and it is especially important to set a small
region of interest and optimize color scales. Finally, given
the dynamic nature of the heart, the capacity to record and
display real time images along with still frames of Doppler
and M-mode recordings, is critically important.
Four dimensional evaluation using spatiotemporal image
correlation (STIC) technology is now possible. Inherent
limitations are imposed by the temporal resolution and motion
artifact. With the inclusion of color flow information good
diagnostic accuracy for detection of major CHD has been
demonstrated.4144 The ability to analyze the data set offline,
may have an important impact on improving accessibility of
cardiac screening to remote sites. As with other techniques
there is a learning curve to the process and often a
combination of techniques and postprocessing is required
to achieve good diagnostic capability. Fetal movements and
arrhythmia continue to be issues. Inter and intraobserver
variability approaching 96 percent has been demonstrated for
the assessment of fetal cardiac volumes.45
normal Fetal echocardiogram
46
It is important to evaluate the fetal heart in a segmental

fashion with the goal towards establishing situs, segmental
connections and alignments as well as functional assessment
(Figures 1 and 2). Fetal position, as well as motion may not
allow for these to be assessed in a sequential fashion as in
postnatal studies; hence, it is important to have a mental
or written checklist to make sure that all components are
understood at the end of the study. Poor visualization or
incomplete visualization should prompt a repeat study.
Scanning the fetal heart requires small controlled movements.
The importance of assessment in a segmental fashion as
well as assessment of morphologic characteristics of various
cardiac structures cannot be stressed enough; especially in
the diagnosis of congenital heart defects where in seemingly
minor issues may alter prognosis and surgical approach, such
as associated obstructed total anomalous pulmonary venous
return.
evaluation of Fetal Position and right-left orientation

It is critical that all fetal cardiac assessments begin with
evaluating fetal position and establishing fetal right versus
left. Once the fetal stomach is identified as being correctly
positioned to the fetal left, it then serves as a useful landmark
to reorient oneself through the scan with fetal movements.
Though there are algorithms that have been outlined for the
same,46 the easiest method is to establish fetal lie and thus the
fetal left and right. This is best done by identifying the fetal
head and aligning the transducer along the spine of the fetus
to establish the craniocaudal axis of the fetus and then turning
the transducer 90 percent to obtain a transverse scan through
the abdomen and thorax.
transverse scans and the extended

Cardiac screening Views
A series of transverse scans starting from the upper abdomen
to ascertain situs, to the chest outlining the four chambers of
the fetal heart and then to the mediastinum visualizing the
outflow tracts and great vessels, provides for a comprehensive
screening technique (Figure 1). Initially advocated by Yagel
et al, this provides a template for sequential segmental
evaluation of cardiac anatomy as noted in Figure 2.47 It should
be noted that these imaging planes represent a continuum and
small movements separate one view from the other.
1. Abdominal situs: The transverse scan across the upper
abdomen of the fetus helps to establish the abdominal situs.
Normal landmarks (Figure 1: plane A and Figure 3A)
include:
Spine posterior
Stomach bubble to left
Pulsatile descending aorta anterior to spine, slightly left
of midline
Inferior vena cava slightly anterior to right of descending
aorta
Scanning cranially the cardiac mass is noted with apex
to left
The inferior vena cava passes anteriorly to drain into the
base of right atrium.
Besides this, the umbilical vein is noted looping
away from the stomach and the ductus venosus can be
identified as a small vessel connecting the umbilical vein
to the inferior vena cava. Color flow evaluation shows low
velocity accelerated continuous flow pattern.
Alterations in abdominal situs or right/left symmetry
may be the first clue to associated heterotaxy. The presence
of a prominent venous structure posterior to the aorta may
be seen in setting of interruption of the inferior vena cava
with either an azygos continuation (right posterior vessel)
(Figure 3B) or hemiazygos continuation (left posterior
vessel). In these cases, the flow in the vein is cephalic,
4
FEtal Cardiology
a
Figure 1: Schema for extended cardiac screening. A series of
transverse scans through the fetal chest and upper abdomen constitutes
the extended cardiac screening as advocated by Yagel et al. Plane A
is through the upper abdomen of the fetus showing abdominal situs.
Scanning cephalic one gets the four chamber view in Plane B, the left
ventricular outflow tract in Plane C, right ventricular outflow tract and
three vessel view in Plane D and the three vessel tracheal view in Plane E.
AA = Aortic arch; DA= Ductal arch; LVOT = Left ventricular outflow tract;
RV = Right ventricle; RVOT = Right ventricular outflow tract; S =
Spine; St = Stomach; T = Trachea. Note: It is a very small movement
between planes C, D and E
coursing behind the heart to drain into the respective

superior vena cava. Caudal flow or flow towards the
abdomen will be seen in setting of infradiaphragmatic
anomalous pulmonary venous connection. Note should be
made of a rightward descending aorta, which may be seen
in cases of situs inversus or heterotaxy.
2. Four chamber view: The four chamber view of the heart
is visualized by obtaining a transverse scan of the fetal
thorax just above the level of the diaphragm (Figure 1:
Plane B). It is important to train ones eyes to recognize
morphological characteristics of the different cardiac
segments. The fetal heart occupies about a third of the fetal
thorax and is situated with the cardiac axis at about 45 15
percent to the axis of the chest. The heart is situated more
horizontal than in postnatal life, allowing for side-by-side
visualization of the right and left inflows in the same plane
(Figures 4A and B).
Figure 2: Segmental analysis of cardiac anatomy. A stepwise approach

to the evaluation of the different cardiac segments is recommended in
evaluation of the fetal heart. At each level it is important to evaluate
for the presence or absence of a structure as well as variations in
size and function. For example, a small hypoplastic left ventricle, a
well-developed but poorly contractile right ventricle in some cases
of pulmonary atresia with intact ventricular septum. In addition,
it is important to ascertain the connections between the different
segments in terms of alignment as well as function. For example,
double inlet left ventricle, where in both atrioventricular valves are
aligned to the left ventricle, discordant atrioventricular connections in
L-TGA or failure to demonstrate pulmonary venous connection in the
four chamber view, etc. The extended cardiac screening as shown
in Figure 1 helps readily identify variations and further supportive
information is obtained from supplemental views in terms of the shortaxis and sagittal scans
47
Figures 3a and b: Transverse scan through the upper abdomen: A. Normal situs: The fetus was in breech position with stomach (St) to the left
and cardiac mass (not shown) was to the left. Normal relation of the aorta (solid white arrow) and IVC is noted; B. Interruption of the IVC with
azygos continuation. In this case there was isolated dextrocardia with the cardiac apex pointing to the right (not shown). A prominent azygos
vein is noted as a venous structure, posterior and to the right of the descending aorta (solid while arrow). IVC = Inferior vena cava; LT = Fetal
left; S = Spine; St = Stomach.
48
Landmarks include:
Spine is posterior
Descending aorta is noted anterior to spine and slightly
to left of midline
Anteriorly, the cardiac mass lies with apex to left and
occupies about a third of the chest
Cardiac axis of about 45 degrees to the line bisecting the
thorax
Four chambers with a intact crux in the center: right =
left (in midgestation)
Right atrium is anterior and receives the superior and
inferior vena cava
Left atrium is posterior and receives the pulmonary
veins (The space between the left atrium and aorta is
free of vascular structures at this level)
Foramen flap towards the left atrium
Right ventricle is anterior and is identified by the
tricuspid valve and presence of moderator band at the
apex
Tricuspid valve is slightly offset towards the apex and
has septal attachments
Left ventricle is posterior and receives the mitral valve
Mitral valve is septophobic or lacks attachments to the
septum and attaches slightly higher than the tricuspid
valve
Normal valve motion
Normal myocardial squeeze and echogenicity
Normal heart rate with atrioventricular synchrony
Additional evaluation includes color flow and Doppler
evaluation of the valves and septum.
Early in gestation there is relative equality of the two sides

though there may be mild right sided prominence past
28 30 weeks gestation and this becomes more prominent
in late gestation. The four chamber view may be projected
either horizontally or vertically depending on the angle
of imaging. The perimembranous septum is normally the
thinnest part of the interventricular septum and is prone
to dropout on two dimensional imaging. In these cases,
assessing the septum in a horizontal orientation to maximize
lateral resolution of the transducer and use of color flow
mapping will help resolve the issue (Figure 4B). However,
given relatively equal pressures between the two ventricles
and the limitations of resolution may result in missed
diagnosis of a ventricular septal defect (VSD), especially in
early scans and with poor imaging windows. Abnormalities
in cardiac position may be noted in setting of extracardiac
malformations with cardiac displacement, heterotaxy with
or without associated cardiac displacement. A change in
cardiac axis is an important marker for associated cardiac
defects as well as extracardiac malformations with resultant
cardiac shift. The differential features and common causes
are outlined in Table 3.
3. Outflow tract view: Scanning cephalic or towards the
fetal head from the four chamber view shows the origin of
the aorta from the left ventricle (Figure 1: Plane C). Slight
rotation of the transducer in such a way as to lengthen the
interventricular septum will result in opening of the left
ventricular outflow tract (LVOT) and better visualization
of the aortic valve (Figures 5A to C). Note is made of the
following:
4
FEtal Cardiology
Figures 4a and b: Normal four chamber view of the heart: A. 2D image: The heart occupies about a third of the chest and the interventricular
septum forms about a 45 angle with the line bisecting the thorax. The right ventricle (RV) is the anterior ventricle and is identified by the
moderator band in the apex and apical offset of the tricuspid valve. < marks the crux of the heart with an intact and normal offset of the
atrioventricular valves noted. The pulmonary veins (PV) (arrows) and foramen flap are related to the left atrium; B. HD-flow demonstrates flow
in the pulmonary veins (arrows) and the interventricular septum is intact. The right and left heart are approximately equal in size in both cases.
LT = Fetal left; RT = Fetal right
Figures 5a to C: Left ventricular outflow tract views: A. Normal heart: the aorta arises from the left ventricle and there is septoaortic continuity
(arrow) and the interventricular septum is aligned to the anterior wall of the aorta. There is also aortomitral continuity; B. The aorta arises
normally from the left ventricle but there is lack of septoaortic continuity (arrow) and color flow confirmed a subaortic ventricular septal defect
(not shown); C. In this case there is lack of septoaortic continuity (arrow) and in addition the aorta straddles the ventricular septum and is more
aligned to the right ventricle in setting of a malalignment ventricular septal defect. Ao = Aorta; LT = Fetal left; RT = Fetal right
Aorta arises from the left ventricle and is situated in the

center of the heart
Aortomitral continuity is present
Aortoseptal continuity is present
Interventricular septum appears intact
Cranial scanning opens the pulmonary valve and
pulmonary artery
Normal valve motion is noted
Color and Doppler evaluation is performed.
4. The 3 vessel view (3VV) and the 3 tracheal view (3VT):

Extending the scan further cranially into the mediastinum
of the fetus demonstrates the three vessel view and its
continuation into the tracheal view. This view outlines the
great vessels and their relationship in the mediastinum.
These are easily obtained by a slow cranial sweep from
the four chamber view (Figure 1: Plane D and E). A slight
rotation of the transducer will help lay out the vessels.
49
50
table 3
Variations in cardiac position and axis: distinguishing features and common causes
Description of fetal heart
Possible causes
Levocardia
Majority of cardiac mass in left chest:

Normal
1/3rd to right of midline (RA) and 2/3rd in
left chest
Apex to left
Cardiac axis 45 15%
CA 1/3rd of TA
Mesocardia
Cardiac mass: Midline

Axis: ~90
Apex midline
Extrinsic shift: CHAOS

Abnormal looping: Atrioventricular
discordance
Heterotaxia
Dextrocardia
Majority of cardiac mass in right thorax

Apex to right
Situs inversus totalis

Heterotaxia
Isolated dextrocardia
Dextroposition
All of cardias mass in right thorax

Apex to front/left
Cardiac size often small
Mass in LEFT thorax with extrinsic

push: e.g. Left DH, left pleural effusion,
CCAM
Mass in right thorax: Right
lung agenesis or hypoplasia with
compensatory increase in left lung
Levoposition
All of cardiac mass in left thorax

Apex to front
Cardiac size often small
Mass in RIGHT thorax with extrinsic

push: e.g. DH, pleural effusion, CCAM
Mass in left thorax: Left lung agenesis
or hypoplasia
Left axis shift
Majority of cardiac mass in left thorax

Axis > 60 to midline
Cardiac size: Normal or enlarged
Apex to left
Shift of ventricular septum:

Right ventricular enlargement/
hypertrophy
Left ventricular hypoplasia
Milder forms of extrinsic shift
Right axis shift
Majority of cardiac mass in left thorax

Axis < 30 to midline
Size normal or increased
Apex left or midline
Shift of ventricular septum:

Right ventricular hypoplasia
Left ventricular enlargement
Milder forms of extrinsic shift
CCAM = Congenital cystic adenomatoid malformation; CHAOS = Congenital high airway obstruction; DH = Diaphragmatic hernia
abnormalities in number, size, alignment and flow in the

components of each of the views (Figures 6 and 7).
sagittal Planes
1. Aortic and ductal arch view: Scanning in the thorax
along the long axis or parallel to the spine provides the
sagittal images of the fetal heart. Due to the shadowing
effects for the spine it is important to approach the heart
slightly from the one side of the fetal spine. This window
profiles the superior vena cava-inferior vena cava (SVCIVC) view, identifying the great veins as they enter the
right atrium. Aortic arch forms a candy cane with cranial
head and neck vessels while the ductal arch is much more
shallow reminiscent of the American hockey stick
(Figures 8A and B). Given embryologic origins the aortic
arch is slightly cranial to the ductal arch, though in cases
of severe arch hypoplasia this may be difficult to reliably
demonstrate. The right pulmonary artery can be seen
posterior to the ascending aorta and superior vena cava
(Figures 8A and 9A). The foramen ovale is well-profiled in
this view (Figure 9A). In the abdomen, the ductus venosus
can be identified as it connects to the IVC in the liver.
Short-axis images of the ventricles can be obtained and
the ventricular function and mitral valve papillary muscles
identified (Figure 9B).
2. Short-axis images: Given horizontal positioning of the fetal
heart short-axis images of the ventricles can be obtained
either from a relative fronto/sagittal position or from a
transverse scan plane orthogonal to the four chamber view
depending on fetal position. The mitral valve, papillary
muscles, function, pulmonary valve, branch pulmonary
arteries and the ductal arch are well seen.
4
FEtal Cardiology
Landmarks include:
Cranial sweep from the left outflow view opens the
pulmonary valve and pulmonary artery
Pulmonary valve is anterior and connects to the right
ventricle
Pulmonary artery gives off lateral branches
There is a subpulmonary conus or muscle and lack of
continuity with the tricuspid valve
The two great arteries cross each other with the
pulmonary valve being anterior and to the left of the
aorta
The three vessels are seen from right to left: The right
superior vena cava, the ascending aorta and the main
pulmonary artery
Ascending order in size with: The superior vena cava
ascending aorta main pulmonary artery.
Scanning cephalic from here gives the tracheal view
(Figure 1: Plane E):
Pulmonary artery continues into the ductal arch
Aorta continues to the aortic arch
The aortic arch is slightly cephalic to the ductal arch
The ductal arch and aortic arch come together to form a
V with apex at the descending aorta
Three vessels are seen from right to left with ascending
order in size: The right superior vena cava the aortic
arch the ductal arch
Trachea is noted slightly posteriorly between the
superior vena cava (SVC) and the aortic arch
Further, cephalic innominate vein is noted crossing
from left to right to join the SVC.
Abnormalities in the 3 VV and 3 VT are important clues
for the presence of underlying conotruncal malformations
and variations in arch anatomy. It is important to assess for
Figures 6a to C: Three vessel view demonstrating normal right ventricular outflow tract and variations in size. A cross-section through
the fetal thorax demonstrating from fetal left-to-rightcross-section of the main pulmonary artery (PA), ascending aorta (Ao) and superior
vena cava (SVC). The branch pulmonary arteries are noted (arrow heads) arising from the PA in each case. A. Normal 3 vessel view.
Note: Gradually increasing size from SVC to Ao to PA and normal arrangement in a line; B. Dilated PA in a fetus with valvular pulmonary stenosis.
The ascending aorta is normal in size; C. Diminutive main PA with small confluent branch pulmonary arteries in setting of pulmonary atresia.
Lt = Fetal left; S = Spine.
51
Figures 7a to d: Three vessel tracheal view: A and B. Demonstrate normal three vessel tracheal view in the upper mediastinum of the fetus in
2D and with color flow mapping. Vessels from fetal right to left are superior vena cava (SVC); aortic arch (AA); ductal arch (DA). Note: The V
formed by the DA and the AA as they come together at the descending aorta to the left of the trachea (T). The direction of flow should be similar
in the two arches; C and D. The AA is noted to the right of the trachea while the DA passes to the left of the trachea and thus the V is disrupted
in this fetus with a right AA
a
52
Figures 8a and b: Normal sagittal views of the fetal arches: A. Aortic arch (*) demonstrating a candy cane with presence of cranial directed
head and neck vessels (arrow). Note: Right pulmonary artery (RPA) posterior to the ascending aorta. This view also profiles the foramen
ovale (FO). Descending aorta runs parallel to the spine (S); B. Demonstrates the pulmonary artery arising from the right ventricle (RV) and the
ductal arch (*) which is shallow and lacks the head and neck vessels. The aortic valve (AV) is seen in cross-section in the middle of the heart.
4
FEtal Cardiology
Figures 9a and b: Normal sagittal short-axis image of the heart: A. Profiling the superior vena cava (SVC) and the sinus venosus atrial septum.
The foramen ovale (FO) is well profiled with the primum atrial septum bulging into the left atrium. The right pulmonary artery (RPA) is related to
the posterior aspect of the SVC. The inferior vena cava can be seen as it enters the right atrium from the abdomen but is not well profiled in the
current image; B. Extending the scan into the ventricles provides a sagittal short-axis image of the ventricles and profiles the mitral valve (MV)
and papillary muscles. Note: The stomach (St) is related to the left ventricle in this view. RV = RIght ventricle; S = Spine
Quantification
diagnosis of specific Cardiac defects
In early and midgestation there is usually right-left symmetry

that allows for qualitative assessment. However, in cases
of doubt, formal measurements of various structures in the
fetal heart can be performed. Routine measurements of
key structures has the advantage of allowing the operator
to become familiar with norms by experience and serial
determination allows tracking of growth of structures in case
of abnormalities. Z score graphs for various fetal cardiac
structures are now published.4852 Several studies have
also demonstrated the utility of tracking Z scores or growth
for predictive value in certain defects.5356 However, it is
important that there be standardization of technique within the
lab and for use of normative data.57
Fetal diagnosis of congenital heart defects is in general

skewed towards more serious defects given that the majority
of defects are picked up on routine screening. Most significant
cardiac defects can be reliably diagnosed prenatally with some
limitations. It is very important to adopt a segmental approach
to the assessment of cardiac anatomy (Figures 1 and 2). In a
simple fashion, this involves assessment of the following:
1. Abdominal situs and atrial anatomy:
a. Solitus: Normal atrial and venous arrangements. The
atrial appendage morphology may occasionally be
seen well enough to aid in the diagnosis. Variations to
systemic and pulmonary venous return may be seen in
isolation in the absence of situs abnormalities.
b. Situs inversus: Mirror image arrangement.
c. Abnormal situs: Includes cases of right and left atrial
isomerism as well as situs ambiguous. There is a high
association of complex congenital heart defects.
2. Atrioventricular connections:
a. Concordant: Normal right atrium to right ventricle and
left atrium to left ventricle.
b. Discordant: Right atrium to left ventricle and left atrium
to right ventricle or inverted connections.
c. Univentricular connections: Where in there is connection
to one ventricular chamber and includes: Double inlet
(both atrioventricular valves aligned predominantly to
Color and doppler evaluation

Color flow and Doppler evaluation are an important part of the
anatomic and functional assessment of the fetal heart (Figures
4B and 10). As with postnatal assessment they are sensitive to the
angle of insonation, gain, velocity settings. For pulse Doppler,
it is important to use small sample volumes and low velocities.
Color Doppler evaluation aids in anatomic assessment in some
cases with poor 2D definition. Characteristic flow patterns are
noted across the different valves and vascular structures and
are outlined in Figures 11A to I.
53
Figures 10a to F: Fetus with critical aortic stenosis and dysplastic mitral valve: A. Four chamber image shows a massively dilated left atrium
(LA) and an enlarged left ventricle. The right heart appears smaller and squished; B. Sagittal image showing retrograde filling of the aortic
arch. Note: Good-sized left ventricle; C. Color and pulsed wave Doppler demonstrated severe mitral regurgitation; D. Mitral stenosis; E. The
foramen ovale demonstrated continuous high velocity flow (in this case left to right flow) consistent with restriction; F. The tricuspid valve shows
a monophasic filling pattern, likely to be secondary to restriction to right ventricular filling secondary to altered septal geometry
54
one ventricle), common inlet (common atrioventricular

valve aligned to one ventricle) or single inlet (atresia of
one valve either the mitral or tricuspid valve).
It is important to look carefully at the atrioventricular
valves for presence of straddling attachments, which
may change surgical management towards a single
ventricle approach even though there are two effective
ventricles. Similarly, the size of the inflow may have a
significant impact on surgical approach. For example,
a small tricuspid valve annulus that is well below -3 Z
scores may rule out a two ventricle repair even in the
presence of an otherwise reasonable sized right ventricle
in setting of severe pulmonary stenosis/atresia with an
intact septum.
3. Ventriculoarterial (VA) connections:
a. Concordant: Normal, i.e. right ventricle to pulmonary
artery and left ventricle to aorta.
In the normal heart, the great arteries cross each other
and their relationship is such that visualization of one
great artery in long axis will show a cross sectional view
of the other. The ability to show the long axis of both great
arteries at the same time or parallel orientation of great
vessels suggests abnormal connections and/or alignment.
b. Discordant: Right ventricle to aorta and left ventricle

to pulmonary artery or transposed. As noted, this will
result in a parallel orientation to the great vessels on
ultrasound (Figures 12A and B).
c. Double outlet: Where in the majority of both great
vessels arise from one ventricle, more commonly an
anatomic right ventricle.
d. Single outlet: Where in there is only one outlet from the
ventricular mass. These include aortic atresia (small aorta
and large pulmonary artery) and pulmonary atresia (small
pulmonary artery and normal aorta) and a single large
outlet as in cases of truncus arteriosus where in a single
large outflow vessel gives rise to the coronaries, head
and neck vessels as well as pulmonary arteries. A wide
variation in size and morphology of the atretic valve can be
seen and in some cases may hamper distinction between a
true truncus and tetralogy of Fallot with pulmonary atresia.
Careful attention to the origin and relationships of the
pulmonary arteries and head, neck vessels from the single
vessel is needed to make the diagnosis in these cases, to
help plan surgical intervention and outline prognosis.
Ultimately, the impact of complex heart defects depends on
the ability of the fetus to tolerate the hemodynamic alterations
FEtal Cardiology
i
Figures 11a to i: Doppler profiles across different sites in the fetal cardiovascular system: A. Atrioventricular valves demonstrate a biphasic flow
pattern. E wave corresponds to passive filling during early diastole and A wave to augmented filling with atrial systole; B. Ductus arteriosus
and aortic arch show systolic forward flow with low velocity forward flow in diastole; C. Hepatic veins and inferior vena cave demonstrate a low
velocity bimodal forward flow pattern. S wave corresponds to annular motion with ventricular systole, diastolic (D) forward flow with ventricular
filling and a transient A reversal wave is noted with atrial contraction; D. The main pulmonary artery and aorta show systolic forward flow pattern;
E. Normal ductus venosus flow also demonstrates these three components except that forward flow is maintained during atrial systole and
presents as a decrease in velocity rather than A reversal. F. The proximity of the branch pulmonary artery and pulmonary vein allows for
simultaneous sampling of the two. High resistance forward flow pattern is noted in the branch pulmonary artery (PA) and is shown above
the baseline in F with pulmonary venous flow below the baseline; G. The umbilical vein (UV) shows continuous low velocity forward flow.
The umbilical artery (UA) demonstrates pulsatile flow with a systolic peak with continuous forward flow in diastole. With increasing placental
resistance there is a gradual decrease in diastolic flow velocity in the UA; H. The middle cerebral artery also shows a systolic peak with low
velocity forward flow into diastole. Conditions associated with cerebral vasodilatation will result in higher diastolic velocities; I. The foramen ovale
shows predominantly low velocity flow from the right atrium (RA) to the left atrium (LA) with a transient flow reversal
55
Figures 12a and b: Parallel orientation of the great vessels in setting of D-transposition of the great vessels.
The pulmonary artery arises from the left ventricle and the aorta from the anterior right ventricle
Figures 13a to C: A. Four chamber view demonstrating a dilated coronary sinus (CS). The interventricular septum appears intact in this view;
B. Outflow tract view demonstrating origin of the aorta (Ao) and lack of septo-aortic continuity secondary to a large subaortic ventricular septal
defect (arrow head); C. Three vessel tracheal view demonstrating presence of four vessels: right superior vena cava (RSVC); aorta (Ao);
pulmonary artery (PA); left superior vena cava (LSVC); trachea (T). The LSVC can also be visualized as a vessel to the left of the pulmonary
artery in B
56
in utero and its ability to have a successful transition to neonatal

circulation. In the fetal circulation, the right and left hearts are
working in parallel rather than in series as after birth. There
exists the potential for flow redistribution across the foramen
ovale as well as ductus arteriosus. Obstruction or resistance
to flow through one ventricle allows for redistribution of flow
across the foramen and the ductus arteriosus to the other.
Hence, right heart obstruction or high afterload states on the
left ventricle may present with relative enlargement of the
right ventricle and vice versa. Similarly, one may see flow
reversal in the ductus arteriosus with right heart obstructive
lesions and flow reversal in the ascending aorta with lesions
that impact left ventricular output.
sPeCIFIC lesIons
1. Systemic venous abnormalities: Variations in systemic
venous anomalies can be easily detected on fetal
echocardiograms. A dilated coronary sinus is often the clue
to look for an associated left superior vena cava (LSVC).
The presence of a LSVC can be easily confirmed in the high
mediastinal or 3 VV and tracheal views by the presence of a
fourth vessel leftward to the pulmonary artery (Figure 13).
Though this variation has no hemodynamic significance,
it is often noted as an associated finding in left heart
lesions and should prompt a careful review of the left heart
structures including the mitral valve and arch and may
prompt a follow-up evaluation to assess in utero growth of
Figure 14: Total anomalous pulmonary venous return: Four chamber

view showing presence of pulmonary vein confluence (arrows) in
the space between the left atrium (LA) and descending aorta (Ao).
Note: The LA and left ventricle are well-developed in this case.
RA = Right atrium; S = Spine. (Image courtesy: Dr Bettina Cuneo)
circulatory patterns. The normal atrial septum in the fetus

is characterized by the presence of the foramen flap, which
opens towards the left atrium and demonstrates low velocity
flow from right to left with a transient left to right flow in
late diastole.58 The foramen ovale also serves as an obligate
shunt in the setting of congenital heart defects such as right
and left heart obstructive lesions, transposition of the great
arteries and also total anomalous pulmonary venous return.
Prenatal restriction of the foramen ovale has been reported
in 6 to 22 percent of cases in these settings and is associated
with poorer outcomes both in fetal and postnatal life.5961
It can be a true emergency in the delivery room in some
cases and has important implications for delivery planning.
The presence of restriction may be indicated by a bulging
tense appearing foramen with either restricted motion or
hypermobile motion, straight septum with small opening
by 2 dimensional imaging, the presence of turbulent flow
across it by color Doppler and elevated velocities in excess
of a 1 m/sec,6264 (Figure 10). The appearance of the atrial
septum will vary depending on the underlying lesion.
Left heart obstructive lesions are associated with a higher
incidence of left atrial hypertension.61,65
Atrial septal defects: The presence of a normal foramen
ovale in fetal life precludes diagnosis of secundum atrial
septal defects in fetal life. Rarely, the absence of a foramen
flap and a T artifact may clue one to the presence of
one. Sinus venosus defects are typically high or low in
proximity to the venous inflow and may be diagnosed in
sagittal images profiling the atrial septum (Figure 9A).
A primum atrial septal defect is readily detected on fetal
echocardiograms and occurs either in isolation or in setting
of a complete endocardial cushion defect (Figure 16). This
is described in greater detail below. Lack of atrial septation
may result in a common atrium and is often associated with
a common atrioventricular valve (CAVV).
Ventricular septal defects: Larger VSDs may be diagnosed
in fetal life based on a dropout in the ventricular septum in
at least two views. Color flow mapping demonstrating very
low velocity bidirectional flow helps to distinguish from
small dropouts due to poor lateral resolution. Malalignment
and outlet defects may not be seen in the standard four
chamber view unless one images the outlet septum in
relation to the outflows (Figure 13). These defects are
often associated with abnormalities of the outflow tracts.
The lack of septoaortic continuity should prompt a closer
assessment with color. The lack of apical offset of the
tricuspid valve may present a clue to an underlying small
inlet VSD confirmed by color flow imaging. Ventricular
septal defects are very common in postnatal life and though
often seen in isolation, they may also exist as part of an
underlying syndrome.
Endocardial cushion defects: Complete endocardial
cushion defect includes a primum atrial septal defect with
an inlet ventricular septal defect and a CAVV, however,
4
FEtal Cardiology
the left heart. Systemic venous anomalies may be found in

isolation, but are also often a part of more complex lesions
as seen in heterotaxy (Figure 3B). A careful evaluation for
situs abnormalities is warranted.
2. Pulmonary venous anomalies: Include variations in return
such as total anomalous pulmonary venous connection
(TAPVC) and partial anomalous pulmonary venous
connection (PAPVC) or pulmonary vein atresia. Pulmonary
venous Doppler show characteristic changes in setting of
high left atrial pressures and have been well-characterized
(Figures 15A to D). Obstructed total anomalous pulmonary
venous drainage can be a true surgical emergency in the
delivery room. It is important to identify at least one vein
from each lung as entering the left atrium on screening scans
to avoid missing diagnosis of total anomalous pulmonary
venous return. Subtle features suspicious for TAPVR
include mild right heart enlargement in setting of RV: LV
disproportion as well as the presence of a vascular structure
in the space between the left atrium and the descending
aorta on four chamber views (Figure 14). Rarely, a cor
triatriatum may mimic this picture. Pulmonary venous
anomalies are also often seen in the setting of heterotaxy
and may have a significant impact on outcomes in single
ventricle physiology. Partial anomalous pulmonary venous
return is often missed on prenatal scans unless an effort is
made to delineate all four veins in each study.
3. Atrial and ventricular septal abnormalities:
Prenatal restriction of the foramen ovale: Patency of the
foramen ovale is critical to the maintenance of normal fetal
57
1
a
Figures 15a to d: Change in pulmonary venous tracing with increasing left atrial pressure in setting of
restriction at the foramen ovale in left heart obstructive lesions: A. Normal pattern with S, D waves and lower
A velocities; B to D. With increasing left atrial pressure there is an increase in A reversal and a decrease in
D velocities till a biphasic pattern with a forward S and reversed A wave (D)
58
incomplete forms may be present. This defect is easily

detected based on the absence of the crux in the center
of the heart in four chamber views. Presence of a CAVV
results in the two atrioventricular valves being at the
same level and lack of apical offset of the tricuspid valve
(Figure 16). Endocardial cushion defects are commonly
seen in the setting of aneuploidy especially trisomy 21 and
as part of a more complex CHD in the setting of heterotaxy.

The lesion may be balanced or unbalanced or favoring
one or the other ventricle with resultant hypoplasia of
one ventricle and associated outflow abnormalities.66,67
Significant atrio-ventricular valve insufficiency is
associated with a higher risk for fetal hydrops and fetal
demise especially in the setting of heterotaxy syndromes.
4. Tricuspid valve abnormalities: Tricuspid valve abnormalities may range from subtle minor abnormalities with
mild tricuspid insufficiency to significant abnormalities
such as tricuspid valve dysplasia with thickened leaflets,
Ebstein malformation with mild to severe downward
displacement of the septal leaflet with associated stenosis
and regurgitation, tricuspid valve hypoplasia and stenosis
to atresia.68 The tricuspid valve plays an important role in
fetal circulation given that fetal right ventricle functions
against systemic pressures. The normal tricuspid valve
in the fetus is usually fully competent and any trivial
insufficiency is usually limited to early systole.69,70
Pan-diastolic tricuspid regurgitation is abnormal and
suggests either an underlying abnormality or an alteration
in right ventricular afterload. Significant right heart lesions
are often associated with abnormalities in venous flow
patterns suggestive of elevated right atrial pressures and
are not predictive of outcomes in this setting.71
Severe tricuspid valve stenosis or atresia is often seen
in the setting of a single left ventricle. As in cases of
pulmonary stenosis, even cases that appear not quite severe
in early second trimester, may progress in severity with lack
of right ventricular growth and resultant single ventricular
physiology in late gestation and serial evaluation during
pregnancy is necessary.54,72,73
Ebstein malformation of the tricuspid valve involves
varying degrees of apical displacement of the valve and
resultant enlargement of the right atrium secondary to
4
FEtal Cardiology
Figure 16: Balanced complete common endocardial cushion defect:

Note: Lack of X at crux. The normal offset of atrioventricular valves
is lost and a common atrioventricular valve is noted separating the
ventricular septal defect (arrow) from the primum atrial septal defect
(dashed arrow). Note: Pulmonary vein draining into the left atrium
(arrow head). The ventricles are equal in size. DAo = Descending
aorta; LV = Left ventricle; RA = Right atrium; Rt = Right.
atrialization of the right ventricular inflow and right

ventricular hypoplasia. This is a lesion where in fetal
physiology is detrimental and is associated with a high
incidence of fetal heart failure.74,75 The inability of the right
ventricle to generate enough pressure to open the pulmonary
valve mimics pulmonary atresia (functional pulmonary
atresia). Demonstration of some degree of pulmonary
insufficiency by color flow is often a clue towards some
patency of the pulmonary valve. These neonates may
initially demonstrate a ductal dependent pulmonary blood
flow physiology till a drop in the pulmonary vascular
resistance allows for better ventricular ejection.
5. Pulmonary valve abnormalities: Include pulmonary
stenosis, atresia and absent pulmonary valve syndrome or
dysplastic pulmonary valve. Milder forms of pulmonary
valve stenosis are common in the postnatal period, but are
often missed in midgestation scans. Subtle findings such as
a thickened valve, mildly dilated main pulmonary artery
along with the presence of mild regurgitation of the valve
by color Doppler, with or without elevation in Doppler
velocities, may indicate the presence of an underlying
abnormality (Figure 6). In utero progression may result in
severe stenosis or rarely atresia.
In pulmonary valve atresia, there is no demonstrable
flow across the pulmonic valve and there is ductal
dependent pulmonary blood flow, and the ductus arteriosus
demonstrates reversal of flow, i.e. from the aorta to
the pulmonary artery (Figures 17A and B). The branch
pulmonary arteries are typically small but confluent in
cases with an intact ventricular septum. Branch pulmonary
artery abnormalities are in general more likely in the
setting of pulmonary atresia with a VSD, which falls in
the realm of tetralogy of Fallot and is discussed later.
Pulmonary atresia with intact septum is associated with
varying degrees of right ventricular and tricuspid valve
hypoplasia ranging from a very small hypoplastic right
ventricle along the lines of a single ventricle, to those
where in a tripartite right ventricle is noted and prenatal
decision making in terms of a two ventricle versus single
ventricle repair becomes challenging.53,54,72,73 Important
issues in these cases include the morphology and size of
the right ventricle as well as tricuspid valve growth. The
range of surgical options are described in chapter 40 in this
book. Coronary sinusoidal connections can be suggested
prenatally by presence of to-fro flow along the surface of
the heart and presence of a dilated proximal coronary.
Rarely, a dysplastic pulmonary valve may be noted with
a combination of severe stenosis and insufficiency. In these
cases there is right ventricular enlargement. As with other
volume loading conditions there is a risk for hydrops and
fetal loss in these cases.
6. Mitral valve abnormalities: Isolated mitral valve abnormalities are unusual and are usually seen in the setting of
associated abnormalities of the left ventricle and aortic
valve. The combination of a dysplastic mitral valve with
59
Figures 17a and b: Double outlet right ventricle with severe pulmonary stenosis: A. Origin of both great vessels from the right ventricle (RV).
A small pulmonary artery (PA) is noted crossing anterior to the aorta (Ao); B. Sagittal images show a small curlicue ductus arteriosus (DA) with
reversed flow feeding small confluent branch pulmonary arteries (PA). LV = Left ventricle, S = Spine
60
associated stenosis and severe regurgitation presenting

with severe left ventricular and left atrial dilatation and
ineffective left ventricular ejection is usually associated
with poor outcomes.76,77 This lesion is characterized by a
high risk for prenatal restriction at the level of the foramen
ovale given elevated left atrial pressures; associated right
heart failure due to impairment of right ventricular filling
in the setting of a dilated hypocontractile left ventricle
(Figure 10). There is a high risk for hydrops in these cases.
In utero intervention in terms of balloon dilatation of the
foramen ovale has been attempted in some cases. It is often
difficult to distinguish this from severe aortic stenosis with
secondary mitral valve insufficiency. The aortic valve
though small will often show low velocity laminar forward
flow in these cases. In many situations associated with
mild left ventricular hypoplasia, the mitral valve lesion is
often the limiting factor for a two ventricle repair. A cleft
in the mitral valve may be seen in setting of an endocardial
cushion defect and is best seen in the sagittal images of the
left ventricle with the mitral valve en-face.
7. Aortic valve disorders: Include stenosis, atresia and
associated left ventricular abnormalities. The left ventricle
may be dilated or hypoplastic or may show evolution from
one to the other in later gestation. Isolated mild aortic
valve stenosis in the setting of an otherwise normal left
ventricle may be difficult to diagnose in fetal life. Clues
include subtle dilation of ascending aorta, thickened aortic
valve leaflets on 2D imaging and aliasing of color flow
across the valve and elevated flow velocities across the
valve by Doppler or subtle right ventricular enlargement.
These findings may be subtle in the early second trimester

scan and may be missed, especially on screening studies.
More severe stenosis may be associated with altered flow
patterns across the distal arch with retrograde filling being
noted in the transverse arch with or without associated arch
hypoplasia (Figure 10B).
The combination of a hypoplastic left ventricle with
varying degrees of aortic valve stenosis/atresia and
mitral valve stenosis/atresia with aortic arch hypoplasia
constitutes hypoplastic left heart syndrome. However,
many different combination of lesions may share the
physiology and surgical options. For example, a dysplastic
mitral valve may preclude a two ventricle repair even
though the left ventricle and aortic valve may be deemed
adequate.66,7779 Significant aortic stenosis and variations
of hypoplastic left syndrome result in a ductal dependent
systemic circulation (Figure 10B).
8. Conotruncal lesions: Common lesions include tetralogy of
Fallot, truncus arteriosus, transposition of the great vessels
and double outlet right ventricle amongst others. All of
these lesions share defects in septation of the conotruncus
or formation of the aorticopulmonary septum and are often
associated with a malalignment type VSD (except simple
D-transposition of great vessels). Interrupted aortic arch
with a VSD falls in the same category, but is discussed
with arch anomalies given that a VSD is not universally
present. Associated chromosomal abnormalities, including
22q11 deletions and aneuploidy, have been reported in
17 to 26 percent of cases and may affect counseling and
outcomes.3,8082 The outflow tract, 3 VV and tracheal
4
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Figures 18a and b: A. Truncus arteriosus. A single outflow or truncus (Ao) is noted that gives rise to the branch pulmonary artery (arrow) and
head and neck vessel (**); B. Three vessel view in a fetus with pulmonary atresia and bilateral superior vena cava (SVC). Confluent small branch
pulmonary arteries (arrows) noted in close proximity to the large aorta (Ao). Closer assessment reveals a small hypoplastic main pulmonary
artery segment wrapping around (arrow head) to the left of the aorta. S = Spine
views are important in the evaluation of the conotruncus

and great vessels with supplemental information from the
sagittal and transverse scans.8385
Tetralogy of Fallot: It is associated with anterior
deviation of the conal septum with resultant aortic override,
malalignment VSD and varying degrees of sub- and valvar
pulmonary stenosis. The right ventricular hypertrophy
is a normal feature in fetal life. This lesion is associated
with varying degree of hypoplasia of the pulmonary
arteries (Figure 6C). With severe outflow tract obstruction
and with pulmonary atresia the pulmonary blood flow is
ductal dependent and there is reversed flow noted in the
ductus arteriosus.86 Rarely, in the setting of pulmonary
atresia, the lesion may be mistaken for a truncus arteriosus
(Figures 18A and B). Color flow evaluation of the arch in
sagittal views may reveal the presence of aortopulmonary
collaterals. A variant of this defect is tetralogy of Fallot
with absent pulmonary valve syndrome. This lesion,
characterized by aneurysmal dilated branch pulmonary
arteries and a dilated right ventricle in the setting of severe
pulmonary insufficiency, has poorer fetal and postnatal
outcomes.87 Severe air trapping may be seen in postnatal
period, in the setting of tracheobronchial compression
from the dilated pulmonary vessels and hence these fetuses
are best delivered at a tertiary care center.
Transposition of the great vessels: These include D-loop
transposition and L-loop transposition of the great vessels.
From the standpoint of fetal echocardiogram both these
defects show a parallel orientation of the great vessels, with
lack of crossing of the aorta and pulmonary artery in the

outflow views, along with a posteriorly placed pulmonary
vessel that shows lateral branching (Figure 12).
D-transposition of the great vessels is characterized
by atrioventricular concordance and ventriculoarterial
discordance. Four chamber views are normal however,
outflow tract views reveal parallel great vessels. The 3
VV/tracheal views are abnormal as the ductal and aortic
arch will superimpose and result in lack of the normal V
seen in the tracheal view. Though well-tolerated in fetal
life this results in significant desaturation after birth and
significant hypoxemia can result especially in the setting
of poor mixing at the atrial and ductal level. In about 13
percent of cases there can be in utero restriction at the level
of the foramen ovale with resultant failure to resuscitate in
the delivery room or early neonatal death in unrecognized
cases. A hypermobile foramen, restrictive foramen
flow and diastolic reversed flow in the ductus arteriosus
have been suggested as predictors for an urgent balloon
septostomy.64,88
L-loop transposition of the great vessels is characterized by the presence of atrioventricular and ventriculoarterial discordance, which results in physiologically corrected
flows. The clinical picture is dictated by the associated
lesions, which are reported in upto 85 percent of cases and
include VSDs, left atrioventricular (tricuspid valve) abnormalities, pulmonary and subpulmonary stenosis, heart
block and arch abnormalities.89,90 There is an incremental
risk for complete heart block in this setting and this may
61
62
often be the presenting feature in fetal life. Echocardiography reveals an abnormal four chamber view with the right
ventricle being posterior and parallel outflows, with the
aorta being situated anterior and to the left of the pulmonary artery.
Double outlet right ventricle: In this defect both great
arteries arise from the right ventricle (Figure 17). The
clinical picture is dictated by the variable relation of the
great vessels to each other, the relationship of the VSD to
the great arteries and presence or absence of stenosis of
one of the semilunar valves. Relative hypoplasia of one of
the ventricle may be seen. A systematic approach to outline
the connections and alignment of the different cardiac
segments is needed to elucidate the physiologic effect of
the lesion. It is particularly important on prenatal scans
to identify the fetus at risk for ductal dependent systemic
circulation as in the setting of aortic stenosis and arch
hypoplasia or as is more commonly seen, ductal dependent
pulmonary circulation in the setting of severe pulmonary
stenosis or atresia. Outcomes depend on the subtype and
association of chromosomal abnormalities.91
Truncus arteriosus: It results from failure of aorticopulmonary septum to form completely. This is characterized
by the presence of a single large vessel that overrides the
ventricular septum and gives rise to both the aorta and
the branch pulmonary arteries (Figure 18A). Important
differential includes tetralogy of Fallot with pulmonary
atresia and aortic atresia with a VSD. 22q11 deletion
may be found in 30 to 40 percent cases.92 Associated
abnormalities include a right aortic arch, interruption of
the arch, truncal valve stenosis and regurgitation. Inability
to document head and neck vessels from the only arch and
the presence of a larger than normal first head and neck
vessel that is directed straight up should raise suspicion of
ductal continuation of the aorta. A dysplastic truncal valve
with severe stenosis or insufficiency may adversely affect
prognosis.
9. Aortic arch and ductal abnormalities: The addition
of the three vessel and tracheal views have significantly
added to the assessment of the variations in ductal and
aortic arch anatomy including lesions such as interruption
of the aortic arch, aortic arch hypoplasia, variations in
arch sidedness, variations in ductal morphology including
ductal aneurysm, and vascular rings (Figure 7).
Type B interruption demonstrates ductal continuation
of the descending aorta and a straight appearance to the
ascending aorta. There is a high association with a malalignment VSD, various degrees of subaortic obstruction
and 22q11 deletion.
Isolated coarctation of the aorta is difficult to reliably
diagnose in fetal life in the absence of arch hypoplasia.
The redistribution of flow results in relative prominence
of the right ventricle. Though there are other causes for
right ventricular prominence, presence of right heart
enlargement in the second trimester was associated with

arch abnormalities in 60 percent of fetuses in one series.93
Markers including the presence of isthmic hypoplasia or
a Z score of less than -2, presence of a posterior shelf and
an isthmus to ductus diameter ratio less than 0.74.56,94
Fetal diagnosis of a coarctation remains very challenging,
especially in the third trimester due to the normal presence
of right ventricular prominence and tortuosity of the
ductus arteriosus in late gestation and variable postnatal
presentation.95
The ductus arteriosus has a major role in fetal circulation
acting as a conduit of most of the fetal systemic blood flow
to the lower body with aortic isthmus only seeing about 7
to 10 percent of the combined cardiac output. Inadequate
forward flow from the right heart results in flow reversal in
the ductus arteriosus from the aorta to the pulmonary artery
and serves as a marker for ductal dependent pulmonary
blood flow in postnatal period (Figure 17B). Similarly, in
cases of inadequate left ventricular cardiac output there is
retrograde filling of aortic arch from the ductus arteriosus
and hence a marker for ductal dependent systemic blood
flow (Figure 10B). Prenatal restriction of the ductus has
been reported in the setting of both a normal heart as well
as setting of CHD.63 It may result from maternal exposure
to medications such as indomethacin and its analogues
and has been reported with high dietary polyphenol
exposure.9698 Narrowing may be noted on 2D imaging
along with turbulent color flow and elevated diastolic flow
velocities across the ductus and results in right ventricular
hypertrophy, enlargement and progressive tricuspid
regurgitation. If no correctable cause is noted then early
delivery may be indicated with resultant improvement
in right ventricular function. Elevated ductal flow may
be seen in high output states.99 Ductal constriction is
associated with a decrease in pulsatility index (PI) of less
1.9, where as high output states result in as elevated PI. In
utero ductal restriction in the setting of underlying CHD
such as transposition of the great arteries is associated with
a poorer outcome and serial evaluation through pregnancy
is recommended to adjust delivery management.
The ductus arteriosus is often smaller and curlicue in
the setting of conotruncal lesions associated with severe
right ventricular outflow tract obstruction (Figure 17B).
Diastolic flow reversal in the ductus arteriosus in setting
of transposition of the great arteries may be a marker
for prenatal restriction of the atrial septum and has been
associated with persistence of pulmonary hypertension in
the newborn.63,64
10. Complex CHD: A segmental approach is critical to
the diagnosis of complex CHD, with a view towards
establishing the anatomic diagnosis along with the
functional consequence. Heterotaxy syndromes are often
associated with significant cardiac defects that include
variations in systemic and pulmonary venous return,
Cardiac diverticulum and aneurysms are rare lesions

affecting the ventricles or atria that may be noted on fetal
echocardiograms. Aneurysm are thin walled, lack myocardium,
have a wide attachment to the ventricle and tend to fill with
ventricular systole, while a diverticulum has a narrow neck, has
myocardium and contracts in synchrony with the ventricle.103,104
A ventricular diverticulum may be idiopathic or seen in the
setting of herniation of a part of the ventricle through an anterior
chest wall defect as with pentalogy of Cantrell. It may be difficult
to prenatally distinguish between the two. They may present in
association with pericardial effusion, needing pericardiocentesis
in setting of cardiac dysfunction or if progressive, to prevent
lung hypoplasia; cardiac arrhythmias or rupture with fetal death.
In utero as well as postnatal resolution has been described.105
Cardiomyopathy: Fetal cardiomyopathy may have a diverse
presentation and may result from many different causes
as in postnatal life. Fetal anemia and myocarditis may
mimic dilated cardiomyopathy. A picture of hypertrophic
cardiomyopathy may be idiopathic or seen in the setting of
Noonan syndrome in the fetus, severe uncontrolled diabetes
mellitus in mother, right ventricular hypertrophy in the
recipient twin in TTTS. Non-compaction cardiomyopathy
may coexist with arrhythmias and complex CHD in
heterotaxy syndromes.
limitations of Fetal echocardiograms
Though a high degree of diagnostic accuracy has been

achieved with a comprehensive fetal echocardiogram,
several lesions may be difficult to diagnose or missed in the
prenatal period given inherent limitations of fetal physiology
and resolution by ultrasound. These include small VSDs,
isolated minor valvular lesions, secundum or sinus venosus
atrial septal defects, partial anomalous pulmonary venous
return, isolated coarctation of the aorta and importantly late
gestational changes in form or function.
FEtal Cardiology
cardiac looping and outflow abnormities. In these cases,

the risk for associated rhythm abnormalities, malrotation
of the intestines and abnormal splenic function may
impact postnatal management and should be addressed at
the time of counseling.
11. Miscellaneous heart defects: Intracardiac massesA
range of cardiac tumors may present in fetal life.
Rhabdomyomas are the most common followed by
teratomas, fibromas and hemangiomas amongst others.100,101
Cardiac consequences may occur due to effects of the tumors
on blood flow across the valves resulting in obstruction to
blood flow or regurgitation of the valve; local impact on
the myocardium resulting in poor contractility or irritability
and cardiac arrhythmias; local effects such as development
of pericardial effusions and tamponade. Serial monitoring
of cardiac function, tumor size and its hemodynamic impact
is needed during pregnancy. Rhabdomyomas may regress
after birth, but are associated with tuberous sclerosis in up
to 80 percent of cases and the postnatal course is dominated
by the neurologic consequences of the same.102 If identified
prenatally, formal genetic counseling and evaluation for
tuberous sclerosis is indicated.
Echogenic foci appear as discrete echo-bright or echogenic
spots in the submitral or subtricuspid valvular apparatus and
move with the cardiac valves, are often noted on routine scans.
They are thought to represent areas of ectopic calcification or
fibrosis. It is important not to mistake them for cardiac tumors.
These do not affect cardiac function.
In utero Course and ImPlICatIons For

delIVery PlannIng
The main goal of prenatal diagnosis is to afford adequate
counseling to families with regards to implications of the
cardiac lesion and to plan follow-up, delivery and neonatal
care. A positive impact on survival has been shown only in
certain lesions, however, several studies have shown an
improvement in preoperative variables.106109 Data suggests
that one in three infants with a potentially life-threatening
lesion leave the hospital undetected.110,111 Fetal diagnosis of
CHD in general, tends to be on the severe end of the spectrum
given that most are picked up on screening studies. There is in
general a higher risk for fetal loss in the setting of chromosomal
abnormalities especially with Turners syndrome.
In general, fetal CHD is well-tolerated in fetal life given the
presence of shunts at the level of the foramen ovale and the
ductus arteriosus. Obstructive lesions involving one ventricle
are compensated by redirection of flow across the foramen
ovale to the other ventricle. As long as the combined cardiac
output is relatively maintained by the other ventricle the fetus
does well. Congenital heart defects that are poorly tolerated in
fetal life include those associated with:
Prenatal restriction at the foramen ovale with or without
associated CHD
Prenatal restriction at the level of the ductus arteriosus with
or without associated CHD
Significant valvular insufficiency (e.g. Ebstein malformation, absent pulmonary valve syndrome)
Poor myocardial function (e.g. myocarditis, myocardial
non-compaction, heart failure)
Arrhythmias: both tachy- and bradyarrhythmia, especially
in the setting of associated CHD
Associated placental insufficiency and intrauterine growth
retardation.
Progression of lesions
The potential for progression of fetal heart disease has an
important bearing on prenatal counseling with regards to
prognosis and planning of prenatal and neonatal management.
This progression may happen at many levels such as:
63
Progressive increase in degree of stenosis or resultant

atresia of valves
Lack of growth of a chamber or vessel with resultant ductal
dependent systemic or pulmonary blood flow. This may
ultimately change surgical options with potential need for
a univentricular repair rather than biventricular repair.
Progressive regurgitation of a valve with risk for fetal
hydrops and implications for delivery
Development of significant restriction at the level of the
foramen ovale and/or ductus arteriosus with implications
for timing, type and place of delivery; given potential need
for urgent intervention and high risk for fetal and early
neonatal demise
Myocardial dysfunction may develop with resultant fetal
heart failure
Development of fetal arrhythmias needing medical management or impacting timing of delivery
Progression or regression of a cardiac tumor.
Fetal Cardiac Interventions

As our understanding of the in utero progression of certain
lesions evolve, there has been an attempt to alter or limit the
progressive changes by in utero intervention. On a broader
slate, prenatal interventions include the use of transplacental
antiarrhythmic medications in fetal arrhythmias or use of
Digoxin for inotropy. However, in terms of progressive structural
lesions most of the recent advances have been in the setting
of percutaneous fetal cardiac interventional procedures. Fetal
open cardiac surgery has been limited by the high incidence
of preterm labor in these cases.112 With closed interventional
approach, a high degree of technical success has been achieved
especially in left heart lesion. The success in prevention of a
single ventricle physiology is dependent on case selection,
timing of intervention and the underlying diagnosis and these
are evolving. Methodological advances are being made. A
handful of centers across the world are involved in a systematic
approach to these lesions given ethical considerations. Several
recent publications have addressed the technical aspects, case
selection as well as world-wide results.113116
Interventional approach has been applied to primarily three
subsets:
Balloon Valvuloplasty of the Aortic Valve
64
For aortic stenosis with a normal or large left ventricle and

poor function, with a view towards promoting growth of
the left ventricle and thus prevent the need for a single
ventricle repair. Inclusion criteria which reflect predictors for
development of HLHS includes: critical aortic stenosis as the
dominant lesion, presence of retrograde flow across the arch,
monophasic mitral inflow pattern, normal sized or dilated left
ventricle with diminished function, right to left flow at the
foramen ovale.55,79,113,115 There appears to be an improvement

in hemodynamics with growth of the inflow and outflow,
but growth of the left ventricle itself is not as robust. Fetal
mortality is about 10 percent. A threshold scoring system
for prediction of a biventricle outcome has been developed
by the Boston group in an effort to predict a two ventricle
outcome.55,116
Creation or Enlargement of Inter-atrial Communication

In utero restriction of the foramen ovale is associated with
poor postnatal outcomes secondary to poor oxygenation and
chronic left atrial hypertension with resultant pulmonary
venous hypertension. Technically, this is more challenging
given the small atria. Though successful in utero stenting of the
atrial septum has been reported, however an improvement in
outcomes has not been clear, given the small numbers. Timing
of intervention, size of defect created and relief of associated
significant aortic stenosis may all have an impact.114,116,117
Pulmonary Valvuloplasty
Pulmonary atresia with intact septum or highly restrictive
VSD is associated with varying degrees of right ventricular
hypoplasia and tricuspid valve involvement, which is often
the limiting factor to a two ventricle repair. In utero dilatation
of the pulmonary valve has been successfully performed and
improvement in right ventricular growth demonstrated on
follow up.114,118,119 The procedure is technically challenging
and case selection and technological advances is a subject of
current investigation.
delivery Planning
In general, delivery is best done as close to term as possible
in the setting of complex congenital heart defect to avoid
complications of associated lung disease of prematurity.
However, these decisions have to be made on a case by
case basis, weighing the risk benefit ratio of continuing the
pregnancy to those of prematurity.
Type of delivery is usually dictated by obstetric needs
except in certain situations such as:
Concerns for poor myocardial reserve in the fetus in setting
of heart failure or hydrops where in the stress of a vaginal
delivery may not be well-tolerated.
Fetal arrhythmias such as complete heart block or tachyarrhythmias where in monitoring of fetal well-being in
labor may be difficult
Presence of anterior abdominal or chest wall defects.
Significant prenatal restriction at ductal or atrial level
where in immediate postnatal intervention is contemplated.
An early delivery may be considered in some cases in
the setting of progressive hydrops, especially in the setting
FunCtIonal assessment oF Fetal CardIaC

FunCtIon and Fetal heart FaIlure
The systematic application of ultrasound and Doppler to
the evaluation of the fetal circulatory state has provided us
with a unique insight into fetal circulatory system and its
compensatory mechanisms to conditions associated with
cardiovascular stress. Clinical features suggestive of congestive
heart failure after birth can be elucidated based on changes in
cardiac function and Doppler parameters in the fetus.
The fetal circulation is a parallel circulation characterized
by the presence of shunts across the foramen ovale, ductus
arteriosus and the ductus venosus. Though early in gestation,
the relative outputs of the two ventricles are similar, the
right ventricle contributes to an increasing proportion of the
combined cardiac output after midgestation; estimated to

be about 60 percent at about 38 weeks.120,121 The combined
cardiac output in the human fetus is estimated to be about 425
to 550 mL/kg/min.122 Heart failure in the fetus manifests as
features of increased central venous pressures characterized
by fluid accumulation and diminished cardiac output with
associated decentralization of flow. Hydrops fetalis is defined
as the presence of two or more of the following: pleural or
pericardial effusion, ascites or skin edema.
4
FEtal Cardiology
of right heart failure where in the fetal physiology is more

detrimental to cardiac function as in Ebstein malformation
or severe prenatal ductal constriction, intractable arrhythmias
not responsive to medical management, progressive placental
dysfunction and markers for poor fetal well-being or for
maternal causes.
Factors predictive of the need for neonatal intervention and
planned delivery include:
Prenatal restriction at the level of foramen ovale or ductus
arteriosus
Obstructed pulmonary venous return
Ductal dependent systemic or pulmonary circulation or
potential for the same
Poor myocardial function and heart failure
Presence of fetal hydrops
Uncontrolled arrhythmias: Tachyarrhythmia or bradyarrhythmia.
Most congenital heart defects are well-tolerated in the
delivery room and the stabilization of ductal dependent
lesions can be achieved with the use of prostaglandin E1
(PGE1) infusion. However, the presence of restrictive fetal
pathways, obstructed pulmonary venous return, airway
obstruction or severe myocardial dysfunction may present as
true emergencies in the delivery room and arrangement for
delivery at a tertiary care center with availability of immediate
interventional, surgical or ECMO support, depending on the
underlying issues is critical.
Other lesions that are not ductal dependent such as
a complete common atrioventricular canal that is wellbalanced, VSDs or conotruncal lesions that are not clearly
ductal dependent are managed differently in different settings,
depending on the standard of care available locally. The
availability of teleconferencing and the ability to read studies
remotely and availability of PGE1 has made it easy to stabilize
neonates locally and allow for transport in a timely fashion if
needed.
etiology of heart Failure

Heart failure in a fetus may result from one or a combination
of physiologic factors in a variety of clinical settings both
cardiac and non-cardiac as outlined in Box 1.
Secondary cardiac dysfunction has now been recognized in
a variety of extracardiac conditions. Volume overload occurs in
the setting of fetal anemia, arteriovenous malformations as in
vein of Galen malformation, vascular tumors as in hemangiomas
and sacrococcygeal teratomas, congenital absence of the
ductus venosus when associated with an extrahepatic vascular
shunt. Studies have shown that a combined cardiac output of
greater than or equal to twice the normal indexed combined
cardiac output result in the evolution of hydrops and this may
box 1: Causes of fetal congestive heart failure

1. C
ongenital heart disease associated with valvular
insufficiency:
Ebstein malformation and tricuspid valvular dysplasia
Mitral valve dysplasia
Absent pulmonary valve syndrome and severe pulmonary
stenosis
Dysplastic common atrioventricular valve
In utero constriction of ductus arteriosus or foramen ovale
Dysplastic truncal valve
2. Fetal arrhythmias:
Sustained tachyarrhythmia with HR > 220/min
Sustained bradyarrhythmia with FHR < 55/min
3. High output states:
Fetal anemia: Maternal parvovirus infection, immune mediated
Vascular tumors: Sacrococcygeal teratomas, placental
chorioangioma
Arteriovenous malformation: Vein of Galen
Agenesis of ductus venosus
4. Extrinsic cardiac compression:
Diaphragmatic hernia
Congenital cystic adenomatoid malformation
5. Primary myocardial dysfunction:
Fetal cardiomyopathy
Fetal myocarditis
Intracardiac tumors (also cause valvular dysfunction)
6. Recipient in twin-to-twin transfusion syndrome
7. Severe uteroplacental insufficiency (IUGR)
65
Figure 19: Pathophysiology and cardiovascular manifestations in twin-twin transfusion syndrome. The recipient twin is subject
to a mixed physiology secondary to volume overload as well as pressure overload secondary to transmitted vasoactive
mediators from the donor twin with resultant right ventricular cardiomyopathy and associated left ventricular dysfunction.
LV = Left ventricle; MR = Mitral regurgitation; RV = Right ventricle; RVOTO = Right ventricular outflow tract obstruction;
TR = Tricuspid regurgitation.
66
influence decision to intervene.123125 Cardiovascular findings

include cardiomegaly, atrioventricular valve regurgitation and
abnormal Doppler. Extrinsic compression on the heart may
impede venous return and affect myocardial contractility
and result in heart failure as in diaphragmatic hernia and
CCAM.126
Conditions associated with a high afterload such as
placental dysfunction and the recipient twin in TTTS can result
in cardiac failure. In the fetal circulation, the right ventricle is
particularly susceptible to the effects of high afterload imposed
by placental insufficiency and this may result in ventricular
hypertrophy, altered diastolic function and systolic dysfunction.
TTTS complicates about 10 to 15 percent of all monoamnioticdichorionic (MoDi) pregnancies. It is characterized by a mixed
picture of volume overload in the setting of a high afterload
in the recipient fetus (Figure 19). The presence of placental
vascular communications allows for the transmission of
vasoactive mediators secreted by the donor fetus in response
to hypovolemia. Progressive right ventricular dysfunction
results, with associated left ventricular dysfunction, tricuspid
insufficiency with progression to hydrops consistent with an
acquired cardiomyopathy.123 In utero therapy with laser ablation
of placental vascular connections can lead to stabilization and
improvement in cardiac status and outcomes. Acquired subpulmonary stenosis and evolution to pulmonary atresia has
been reported. Findings of right ventricular cardiomyopathy
are absent in stage 1 and 11 of the Cincinnati modification of
the Quintero classification and allows for a trial of expectant
management with or without amnioreduction.22,127,128
evaluation of Fetal Cardiac Function and

Changes in Fetal heart Failure
Evaluation of fetal heart function involves a comprehensive
and systematic assessment of the fetal cardiovascular system
including the following:
Cardiac function
Assessment of hemodynamic consequences:
Venous Doppler
Arterial Doppler
Signs of congestive heart failure: Evaluation for hydrops
Assessment of fetal cardiac function and myocardial
performance: Several parameters help in the assessment
of cardiac function (Figures 20A to E). Cardiac outputs
can be calculated using Doppler data (Figures 21A and B).
Atrioventricular valve inflow patterns in the fetus typically
show A wave dominance with an E/A ratio of less than 1.
Increasing stiffness of the ventricle is reflected in the presence
of a monophasic inflow pattern characterized by A wave
alone. Elevated filling pressures result in increasing atrial flow
reversal in venous Doppler. Vector velocity mapping has been
applied for assessment of fetal myocardial properties recently
and has the advantage of being angle independent though it is
affected by frame rates.129 Myocardial performance index has
been used as a measure of global function and can be altered
with systolic or diastolic dysfunction.130,131 Alterations in
myocardial performance index (MPI) have been reported
in the setting of CHD, altered afterload as in diabetic
pregnancies and TTTS. Progressive ventricular dilatation
and hypertrophy in the setting of elevated afterload, results
4
FEtal Cardiology
E
Figures 20a to E: Methods used in assessment of cardiac performance: A. Systolic function can be estimated qualitatively by assessment
of wall motion by 2D and can be quantified by calculating fractional shortening (FS) based on M-mode recordings; B. Presence of valvular
insufficiency with a normal valve suggests diastolic dysfunction and can help assess ventricular pressures; C. Increasing ventricular stiffness and
elevated filling pressures results in loss of passive filling and augmented atrial filling with a resultant monophasic inflow pattern; D. Method for
calculating myocardial performance index (MPI) by inflow outflow Doppler. ICT = Isovolumic contraction time; IRT = Isovolumic relaxation time;
SEP = Systolic ejection period; E. Tissue Doppler assessment for assessing diastolic properties. Supplementary information on fetal heart rate
and rhythm is obtained by M-mode as well as Doppler evaluation
in atrioventricular valve insufficiency. The presence of holosystolic tricuspid insufficiency is abnormal and merits close
follow-up. Normalization of afterload as seen with reversal
of ductal constriction with cessation of indomethacin therapy
or s/p laser ablation in setting of TTTS results in a prompt
improvement in degree of tricuspid regurgitation and can be
used as a marker for improving hemodynamics.
Venous dopplers
Studies in both animals and human fetuses have shown that
alterations in central venous blood flow patterns accurately
reflect changes in hemodynamics. Normal venous flow
patterns in the systemic veins show biphasic forward flow;
corresponding to the S wave with ventricular systole and D
wave during early diastole followed by a transient negative or
67
Figures 21a and b: Measurement of right ventricular cardiac output (RVCO): A. Short axis image demonstrating the right ventricular outflow
tract, measurement of pulmonary annulus diameter (D) and placement of Doppler sample; B. Pulmonary artery Doppler signal is used to
measure velocity time integral (VTI) and heart rate (HR). Formula for calculation of cardiac output using above parameters. Left ventricular
cardiac output (LVCO) can be calculated from measurement of aortic annulus and Doppler flow velocity across the left ventricular outflow tract.
Combined cardiac output equals LVCO + RVCO
A reversal in association with atrial contraction. In the ductus

venosus, atrial contraction results in decreased flow velocity
but maintains forward flow. Normal umbilical vein shows
non-pulsatile flow. Increasing central venous pressure leads
to progressive increase in a wave reversal starting from the
hepatic veins and IVC through the ductus venosus and hence
to the umbilical veins with increasing severity.132,133 Early
venous Doppler changes indicative of high filling pressures
may be seen normally in the setting of CHD associated
with right heart obstructive disease, but should be nonprogressive in these states.134136 Similarly, tachyarrhythmias
result in abnormal venous Doppler tracing but should show
normalization during sinus rhythm. Persistence of abnormal
venous Doppler tracings in sinus rhythm is thought to be
indicative of underlying myocardial dysfunction. Doppler
indices used are noted in Box 2.
Similar changes may be seen in the pulmonary veins in
the setting of elevated left atrial pressures. Normal pulmonary
venous flow shows low velocity forward flow with a S and
D peak and cessation of flow in atrial systole. Increasing left
atrial pressure results in flow reversal in the pulmonary veins
with atrial contraction and a decrease in diastolic forward
flow, ultimately resulting in a biphasic to-and-fro pattern
with absent D velocities.65,137,138 Left atrial hypertension
and restriction at the level of the foramen ovale has been
associated with poor outcomes.59
68
arterial doppler
Arterial Doppler can be obtained at several sites including
the semilunar valves, great arteries and their branches
box 2: doppler indices

Commonly used venous doppler indices:
1. Preload index (IVC): Peak A velocity/peak S velocity
2. Pulsatility index for veins (DV): Systolic-diastolic (a) velocity/
time averaged maximal velocity
3. Percentage reverse flow: Time velocity integral (S+D)/time
velocity integral A reversal
Commonly used arterial doppler indices:
1. SD ratio: Systolic/diastolic ratio
2. Pulsatility index (PI): Systolic velocitydiastolic velocity/
mean velocity
3. Resistive index (RI): Systolic velocitydiastolic velocity/
systolic velocity
4. Cerebroplacental ratio: Middle cerebral artery PI/umbilical
artery PI
D = Diastolic; DV = Ductus venosus; IVC = Inferior vena cava; S = Systolic.
including the middle cerebral artery (MCA) and the umbilical

cord. Evaluation of the arterial Doppler patterns enables
the assessment of features of decentralization of flow and
assessment of the fetoplacental unit. Fetal hypoxia results in
cerebral vasodilatation as a brain sparing response, which
results in a decrease in MCA PI due to increase in diastolic
flow velocity, in the setting of increased PI in the umbilical
artery.139 This results in an increase in cerebroplacental index
(Box 2). Fetal anemia results in an increase in MCA peak
velocity. The healthy placenta is a low resistance circuit and the
umbilical artery shows a systolic peak with continued forward
flow in diastole. With progressive placental dysfunction, there
is initially a decrease in diastolic flow velocity followed by
cessation and then reversed flow in diastole implying a high
table 4
Cardiovascular profile score.

Feature
Normal
1 point
2 points
Hydrops
None (2 points)
Ascites or pleural effusion or

pericardial effusion
Skin edema
Venous Doppler
(Umbilical vein)
(Ductus venosus)
UV
UV
UV pulsations
FEtal Cardiology
Cardiovascular profile score (10 points = normal)
DV (2 points)
DV
Heart size (Heart area/chest
area)
0.35 (2 points)
0.35 - 0.50
> 0.50
< 0.20
Cardiac function
Normal TV and MV
RV/LV S.F. > 0.28
Biphasic filling (2 points)
Holosystolic TR or
RV/LV S.F. < 0.28
Holosystolic MR or
TR dP/dt < 400 or
Monophasic filling
UA (2 points)
UA (AEDV)
UA (REDV)
Arterial Doppler
(Umbilical artery)
A normal score is 10 in absence of abnormal signs and reflects two points for each of the five categories. Abnormal finding in each
category results in loss of one or two points as marked. A decreasing score indicates worsening heart failure. Reproduced with
permission from reference 144. AEDV = Absent end-diastolic velocity; dP/dt = Change in pressure over time of TR jet; DV = ductus
venosus; LV = Left ventricle; MR = Mitral regurgittion; MV = Mitral valve; REDV = Reversed end-diastolic velocity; .RV = Right
ventricle; SF = Shortening fraction; TR = Tricuspid regurgitation; TV = Tricuspid valve; UA = Umblical artery; UV = Umblical vein.
placental resistance.140 Finally, underlying CHD may impact

arterial flow patterns especially in left heart obstructive lesions
and should be taken into account.141143
A fetal cardiovascular profile score has been proposed
by Huhta and colleagues as outlined in Table 4.144 A normal
score would be 10 with a decrease in the score with each
additional abnormality. A decreasing score has been shown
to be predictive of poor outcome in the setting of placental
insufficiency and primary heart defects.145,146
Fetal arrhythmIas
Fetal rhythm disturbances account for about 10 to 20 percent of
referrals to fetal cardiologists.147,148 Most of these are benign and
consist of transient irregularity in rhythm and are well-tolerated.
However, persistent tachycardia and bradycardia may result
in fetal heart failure and in utero demise. Transplacental drug
therapy has been used effectively, especially in the management
of fetal tachycardia, providing an impetus for comprehensive
assessment of the fetal rhythm in an effort to improve outcomes
in these fetuses. Normal fetal heart varies with gestational age,
but in general ranges from 120 to 160 BPM. Normograms have
been published and are available for reference.149,150
assessment of Fetal rhythm

Ultrasound is the mainstay in the clinical evaluation and management of rhythm disorders in the fetus. Fetal echocardiography allows for a comprehensive assessment of the fetus
including:
Assessment of underlying rhythm and elucidation of
mechanism of arrhythmia
Evaluation for associated cardiac malformations
Serial evaluation/assessment for evidence of heart failure
and tolerance of arrhythmia
Response to therapeutic intervention.
The assessment of underlying rhythm by ultrasound
depends on the extrapolation of electrical events based on its
mechanical consequence in terms of myocardial contraction
(M-mode, tissue Doppler), its physiologic correlate by
assessing Doppler flow patterns or a combination of the
two (color M-mode) (Figure 22). The goal is to establish
the chronologic relationship between atrial and ventricular
contraction and their rates, thus inferring the underlying
rhythm. Mechanical PR interval can be measured using
Doppler techniques and helps to assess A-V conduction times.
(Figures 22 A and B).
69
Figures 22a to d: Common modalities used in arrhythmia assessment: A. Simultaneous inflow and outflow Doppler obtained with Doppler gate
positioned in the left ventricular outflow tract. Each atrial contraction results in A wave in mitral inflow and ventricular ejection results in flow
into the aorta (V). Mechanical PR interval is measured from beginning of mitral valve A to the beginning of ventricular ejection (parallel lines);
B. Superior vena cava (SVC): Aorta or SVC and aortic flow signal. Atrial contraction results in A reversal in the SVC tracing and ventricular
ejection in flow in the aorta V. Lines denote measurement of mechanical PR interval or A-V conduction time; C. Anatomic M-mode showing atrial
contractions (A) followed by ventricular contractions (V); D. Color encoded M-mode showing atrial contractions on M-mode (A) followed by flow
in the aorta documented by color Doppler (E). This allows for optimization of M-mode to record the low amplitude atrial contraction
m-mode
Alignment of the M-mode along the atrium and ventricle allows
for simultaneous recording of the atrial and ventricular wall
motion. The quality of the tracings is significantly affected by
maternal insonation characteristics, fetal position and motion,
which may limit the ability to achieve proper alignment. It
is often difficult to obtain good quality tracings of one or the
other chamber and atrial signals may be of low amplitude in
setting of hydrops. Color encoded M-mode overcomes some
of these issues. In this, the M-mode cursor is optimized to
record atrial signals. The color Doppler gate is set over aorta
or the LVOT and flow in the aorta (from ventricular ejection)
is superimposed on the M-mode. (Figure 22D). The ability to
obtain dual anatomic M-mode tracings on the newer machines
may circumvent some of these issues (Figure 22C).
doppler evaluation
70
Pulsed Doppler recording of simultaneous inflow and outflow

signals in the LVOT can be used for characterizing the rhythm.
The mitral valve A wave results from atrial contraction and
is followed by the systolic ejection wave in the left ventricular
outflow from ventricular contraction (Figure 22A). However,
this method is not usable in the setting of high heart rates,
which result in fusion of E and A waves and also when atrial

contraction occurs simultaneous with ventricular contraction
or against a closed atrioventricular valve.
Simultaneous sampling of the ascending aorta and the SVC
as it enters the right atrium, demonstrates the relationship
of the atrial contraction (A reversal in SVC) to ventricular
contraction (forward flow in aorta) (Figure 22B). Using
this technique one can assess chronological relationships to
ascertain the rhythm and measure ventriculoatrial (VA) and
atrioventricular (AV) time intervals to further characterize
the tachycardia.151 It is important to optimize Doppler gate
as well as gain settings to allow for visualization of buried
events or A waves superimposed on ventricular ejection. This
technique can be used from other sites such as the pulmonary
vein and pulmonary artery and descending aorta and IVC.
The transmission of the A reversal to the ductus venosus and
hepatic veins helps to identify atrial contraction sequence.
Tissue velocity imaging using either annular Doppler or
simultaneous sampling of an atrium and ventricle has been
shown to permit reliable arrhythmia assessment.
Ultrasound also plays an important role in the assessment
of fetal compensation to the arrhythmia. Hydrops is easy to
recognize, however assessment of fetal well-being in the
prehydropic state may be challenging as current methods of
assessment for heart failure are heavily dependent on Doppler
Fetal electrocardiogram (FeCg) and

magnetocardiogram (FmCg)
Fetal electrocardiogram (ECG) recordings are hampered by
low amplitude signals, especially from the atrium, secondary
to the insulating properties of vernix. Recent publications have
outlined its use in a clinical setting for rhythm analysis but in
limited settings.152,153 Fetal magnetocardiogram, which involves
processing of the magnetic signals that go hand in hand with
electrical signals, has been successfully applied to the study
of fetal rhythm and has provided valuable insights into the
electrophysiological assessment of fetal arrhythmias; especially
those associated with abnormal repolarization.154156 However,
it is currently available only at a few centers worldwide and its
lack of portability and need for a magnetically shielded room,
limits its applicability in the clinical arena.
types of arrhythmias
Irregular Rhythms
These are common and usually noted in the obstetric office as
either extra beats or skipped beats. Causes include:
Premature atrial contractions

Premature ventricular contractions
Mobitz type I or intermittent type II second degree block.
Atrial premature beats are fairly common in the late
second trimester and third trimester of pregnancy and are
often self-limiting. They may be conducted to the ventricle or
blocked with a resultant extra beat or skipped beat on Doppler
(Figure 23B). Persistent blocked atrial bigeminy will present
as fetal bradycardia (Figure 24B). It is important to assess the
A-V relationship closely to rule out underlying conduction
defects (Figure 24). Most are self-limiting, however, there
is a 2 to 3 percent risk for sustained tachycardia especially
in those with multiple or frequent blocked extrasystoles with
a resultant low heart rate.157 Hence, management includes
weekly, auscultation of the fetal heart in an outpatient till
resolution and for any tachycardia. If they persist to term,
then a neonatal EKG is recommended to assess for underlying
pre-excitation.
Ventricular premature beats are occasionally seen in fetal life
and are diagnosed by a premature contraction of the ventricle
in the setting of a regular atrial rate (Figure 23C). Though they
are often benign, they may occur in the setting of increased
myocardial irritability as with myocarditis, tumors or long QT
syndrome and these should be ruled out on the basis of a full
echocardiographic evaluation and detailed history. Postnatal
evaluation is recommended with a baseline ECG.
Disorders of A-V conduction may present with an irregular
rhythm. In Mobitz type I block, there is gradual prolongation
4
FEtal Cardiology
evaluations, which show baseline abnormalities while in

tachycardia. Persistence of abnormal venous Doppler in sinus
rhythm, progressive valvular insufficiency and decreased
myocardial contractility may all provide clues.
Figures 23a to C: Superior vena cava/aorta (SVC-Ao) tracings in two fetuses with ectopic beats: A. 2D image showing a pulse Doppler sample
gate over the SVC and aorta to obtain simultaneous tracings; B. Conducted atrial ectopy. Atrial beats are denoted by arrows, solid arrows
denoting sinus beats and dashed arrows ectopic or early beats. Atrial ectopic beat (dashed arrow, a) results in early ventricular beat (V); C.
Ventricular ectopic beats. Regular atrial rhythm is noted (solid arrows), however, ventricular rhythm is irregular secondary to ventricular ectopic
beats (V); Solid arrows denote sinus atrial beats, dashed arrows and a denote early/ectopic atrial beats, V ventricular ejection and V premature
or early ventricular ejection
71
C
Figures 24a to C: M-mode tracings from three fetuses with irregular rhythm: A. Fetal bradycardia secondary to 2:1 Mobitz type II block. Atrial
rhythm is regular and every other atrial impulse (arrow) results in a ventricular contraction (V); B. Fetal bradycardia secondary to blocked atrial
bigeminy. Every other atrial beat (arrow) is premature and is blocked (dashed arrows). Ventricular ejection results in flow in the aorta (E); C. Color
mode demonstrating Mobitz type I block. Arrows denote gradual prolongation of conduction time from atrial contraction to ventricular ejection (E)
and a non-conducted atrial impulse (dashed arrow)
of the mechanical PR interval culminating with a nonconducted atrial impulse (Figure 24C). In intermittent Mobitz
type II second degree heart block, the baseline mechanical
PR interval is stable (normal or prolonged) but occasional
atrial impulses are non-conducted. This should prompt an
evaluation for presence of maternal SSA/SSB antibodies and
for familial channelopathy. This has occasionally been reported
in otherwise normal pregnancies with a good prognosis in
general.158160
Fetal tachycardia
72
Fetal tachycardia is diagnosed at ventricular rates greater

than 180 to 200 BPM. Associated CHD may be seen in about
10 to 12 percent cases. A broad classification based on A-V
relationships includes:
Sinus tachycardia
Supraventricular tachycardia with 1 : 1 A-V relation
Atrial flutter
Ventricular tachycardia.
Sinus tachycardia with heart rates greater than 180 BPM
may result from a variety of conditions such as maternal
pyrexia, hyperthyroidism, fetal anemia, etc. It is characterized
by 1 : 1 A-V relationship, long VA interval and a variable heart
rate that gradually increases and decreases.
Supraventricular tachycardia includes different types of
tachycardia with 1 : 1 A-V relationship. The most common
mechanism is atrioventricular re-entry either along an
accessory pathway (AVRT) or nodal re-entry (AVNRT)

accounting for about 70 percent of cases. Heart rates are
typically in the 220 to 280 BPM range, with sudden onset and
rapid termination of tachycardia. SVC/Ao tracings show a
short VA interval due to rapid depolarization of the atrium via
the accessory connection (Figure 25A). Medications that affect
the nodal refractory period or the pathway characteristics are
often effective in termination of tachycardia. At birth about 10
percent will have WolffParkinsonWhite syndrome (WPW).
The presence of a long VA interval indicates either an ectopic
atrial focus or permanent junctional reciprocating tachycardia
(PJRT) (Figure 25B). PJRT can be incessant and often requires
polydrug therapy for control.
Atrial flutter is characterized by much faster atrial rates in
the range of 350 to 500 minute with ventricular rates in 180 to
250 range in the setting of 2 or 3 : 1 conduction (Figure 25C).
Ventricular response may be irregular. Initiation of drug therapy
may result in abrupt drop in fetal heart rate due to high grade
AV block and is often mistaken for fetal distress resulting in
an emergency cesarean or mistaken for sinus tachycardia
depending on ventricular rates. A quick evaluation by bedside
ultrasound will clarify the situation. A third of the cases may
coexist with supraventricular tachycardia (SVT) in the setting
of an accessory connection.161,162
Ventricular tachycardia or junctional ectopic tachycardia
is characterized by a ventricular rate that is greater than the
atrial rate. The atrial rate is usually normal with a ventricular
rate ranging from 160 to 300 BPM. These are rare, but
4
FEtal Cardiology
C
Figures 25a to C: Superior vena cava and aorta tracings in three fetuses with tachy cardia. Arrows denote atrial contraction, V = Ventricular ejection.
Ventriculoatrial interval is measured from beginning of aortic flow to beginning of atrial flow reversal and atrioventricular time interval from beginning
of atrial flow reversal to beginning of next ventricular ejection; and is denoted by parallel lines. A. Short VA tachycardia. Note: Retrograde atrial wave
buried at the end of aortic flow (V); B. Long VA tachycardia in a fetus with atrial ectopic tachycardia; C. Atrial flutter with 2:1 conduction. A ventricular
ejection is present for every two atrial beats
may be seen in the setting of myocarditis, tumors, familial

channelopathy such as long QT syndrome (LQTS) as well as
immune-mediated heart block. It is not possible to characterize
ventricular repolarization abnormalities by ultrasound and this
requires fetal ECG or magnetocardiography (MCG) to define the
fetal QTc.163164
management
The management of fetal tachycardia varies from center to
center. General guidelines are presented here (Figure 26).
Management options depend on the gestational age at diagnosis,
the frequency of tachycardia intermittent versus incessant,
mechanism of tachycardia, presence or absence of hydrops and
maternal and fetal well-being. Hydrops may result in upto 50
percent of cases and risk increases with incessant tachycardia
(>50% time), younger gestation age at onset, diminished
cardiac function in sinus rhythm and those with structural heart

disease.165167 Options include close observation, transplacental
drug therapy and if that fails or in setting of hydrops, direct
fetal therapy may be considered. Preterm delivery is avoided if
possible except if the fetus fails therapy and is of a sufficiently
advanced gestational age and there is a clear advantage to
therapeutic options postdelivery.
Medications that have been used for transplacental therapy
of tachyarrhythmia include digoxin, flecainide, sotalol,
amiodarone, propranolol, and propafenone, procainamide
and verapamil in the past.168 Most SVT can be successfully
managed by transplacental therapy. In the absence of hydrops
most centers will initiate therapy with digoxin which has
reported success rate of 60 to 80 percent in absence of hydrops
though therapeutic efficacy drops in setting of hydrops.169,170
Digoxin is often used for its beneficial effects on fetal heart
function. The second line of medications includes flecainide
73
Figure 26: Potential algorithm for the diagnosis and management of fetal tachycardia. 1. Presence or absence of suspicion for LQTS based
on history and FMCG/FECG if available. 2. Any of the drugs listed may be used with or without magnesium. Both sotalol and flecainide has
been used as first line or second line therapy with some studies suggesting better efficacy of sotalol for fetal atrial flutter. AET = Atrial ectopic
tachycardia; AF = Atrial flutter; A-V = Atrioventricular relationship; CAT = Chaotic atrial tachycardia; LQTS = Long QT syndrome; PJRT =
Paroxysmal reciprocating tachycardia; SVT = Supraventricular tachycardia includes both atrioventricular re-entry (AVRT) and atrioventricular
nodal re-entry tachycardia (AVNRT); V-T = Ventricular tachycardiaimplies absence or presence of.
74
or sotalol with success rates approaching 60 to 85 percent

and in some centers amiodarone. Studies suggest comparable
efficacy of both with flecainide having better efficacy with
SVT and sotalol with flutter.171178 Direct fetal therapy
is limited to fetuses with poor response to transplacental
medications in setting of heart failure and prematurity. The
risk of adverse outcomes and fetal mortality approaches 15
to 30 percent167,171 in setting of hydrops and 0 to 10 percent
without.167,170,179 Other morbidities include risk for cerebral
injury and also prematurity.167,176,180 Upto two-third of
cases may have recurrence of arrhythmia in the neonatal
period. Cases of atrial flutter have low recurrence rates post
cardio version in the neonatal period, unless associated with
underlying pre-excitation.151,167
Ventricular arrhythmias are rare and when incessant
have been managed with transplacental administration of
magnesium, lidocaine, mexiletine, beta-blockers and amiodarone.148,181
A cardiology assessment of the mother to look for contraindications to therapy, as well as monitoring for adverse effects
of the medications is critical. This involves multidisciplinary
care involving the perinatologist, pediatric cardiologist and
adult cardiologist to help coordinate care and monitoring of
mother and fetus.
Fetal BradyCardIa
Fetal bradycardia is defined as a persistent fetal heart rate of
less than 110 BPM. Transient fetal bradycardia is often seen
during ultrasound evaluations and demonstrates a brisk return
to normal heart rates with release of pressure. Differential
diagnosis of fetal bradycardia includes:
Sinus bradycardia
Blocked atrial bigeminy
2 : 1 atrioventricular block
Complete heart block.
4
FEtal Cardiology
Figures 27a and b: Left atrial isomerism with complete heart block: A. 2D image with common atrioventricular valve separating the atrium (A)
and ventricle (V). The ventricular walls are thick and non-compacted. A pericardial effusion (E) is present; B. Simultaneous Doppler in descending
aorta and azygos vein demonstrating complete heart block along with sinus bradycardia. The atrial rate (A) was 110 with a ventricular rate (V)
about 55 and the two are dissociated as evidenced by varying A to V relation.
Sinus bradycardia demonstrates 1:1 AV conduction in

the setting of a slow atrial rate. Sinus bradycardia may be
seen in the setting of left atrial isomerism. In the setting of
a normal heart it may be associated with channelopathies
as in SCN5A mutation, LQTS and in setting of maternal
SSA/SSB antibodies, sick sinus syndrome and IUGR in
fetus.148,159,182 Sinus bradycardia in setting of LQTS in fetus
may be subtle with mean heart rates just below the 3 percent
in the 120 to 100 range in late gestation.183 In blocked atrial
bigeminy (BAB) every other beat is an atrial ectopic beat that
is non-conducted to the ventricles and the resultant ventricular
rate is usually slower than in sinus bradycardia (Figure 24B).
It is usually associated with a good prognosis.
Complete or third degree AV block presents with a
regular atrial rate and slow ventricular rate in the setting of
AV dissociation (Figures 27A and B). Second degree AV
block presents with a regular or irregular rhythm, while first
degree AV block manifests a regular rhythm with a prolonged
mechanical PR interval. Isolated conduction abnormalities
have been reported in setting of a normal heart.160 Complete
AV block is seen in the setting of CHD or with a structurally
normal conduction system. Associated congenital heart defects
include left atrial isomerism and congenitally corrected
transposition of the great vessels. Prognosis remains very poor
in the setting of associated isomerism with only a 10 percent
survival in this setting.158,184 Therapy in these cases is generally
ineffective and includes use of beta agonists to increase fetal
heart rate and also digoxin to improve contractility.185
The risk for immune mediated heart block is about 2 to
3 percent in setting of maternal SSA and/or SSB antibodies.
This risk increases to about 16 to 20 percent in setting of
a prior affected child suggesting that the cardiac effects are
secondary to an interaction between environmental factors
with positive antibody status. The risk is highest between 16
to 26 weeks of gestation, but CHB may be detected beyond
this time period and progression in postnatal period has been
reported. The spectrum of immune medicated disease has
evolved and suggests a generalized myocardial inflammation.

Findings reported include patchy areas of increased
echogenicity, atrial endocardial fibroelastosis, valvular
insufficiency, chordal rupture, tachyarrhythmia including
junctional tachycardia and torsade and sinus bradycardia
and heart defects.186189 Hydrops may result in setting of
low non-reactive FHR below 50 BPM as well as myocardial
dysfunction.158,185,190 Once set CHB is generally thought to
be irreversible even with steroid therapy with rare cases of
reversal being noted.191,192 In contrast, second degree heart
block may show stabilization or rarely reversal.193 Recent
data suggests that CHB may set in suddenly and the finding
of PR prolongation to 3 Z scores is not predictive for onset
of CHB.194,195
management oF autoImmune heart BloCk

Optimum evaluation schedule for fetuses at risk is not
entirely clear. Many centers will offer weekly or biweekly
monitoring of cardiac function and mechanical PR interval in
setting of maternal antibodies to SSA/SSB through 24 or 26
weeks.196,197 Evaluation should include assessment for function
and valvular insufficiency. Pharmacotherapy includes use of
beta- agonists such as terbutaline to augment fetal ventricular
rates below 55 BPM, dexamethasone or beclomethasone to
limit inflammation and ongoing damage and intravenous IVIG
in an attempt to decrease circulating antibodies.168,189,190,193,
196,198,199 Antenatal steroid therapy has associated risks of
oligohydramnios, neurologic concerns in the developing brain
and maternal glucose intolerance. Indications are not clear, but
it is suggested that steroid therapy be reserved for cases with
progressive heart block, evidence of endocardial fibroelastosis,
valvular insufficiency myocardial dysfunction or ongoing
features of heart failure. IVIG has been used in some fetuses
non-responsive to steroids. Prophylactic IVIG given through
pregnancy in high-risk pregnancies did not prevent CHB in
doses used.200202 Survival in the setting of immune mediated
75
Figure 28: Potential algorithm for diagnosis and management of fetal bradycardia: AV = Atrioventricular, (-) denotes absence and (+) presence of
congenital heart disease (CHD); LQTS = Long QT syndrome; IVIG = Intravenous immunoglobulin. 1. Assessment for long QT syndrome includes
a detailed family history, parental ECG and evaluation of fetus with FMCG/FECG where available. 2. Steroids used include dexamethasone or
beclomethasone
complete heart block has improved from around 70 percent to

now greater than 90 percent on recent reports.196,203 Figure 28
outlines a general approach to the evaluation and management
of fetal bradycardia.
Future dIreCtIons
Ultrasound has significantly advanced our understanding of
fetal cardiovascular physiology. Recent work with the use of
fetal ECG and MCG point towards the presence of possible
fetal repolarization changes and potential arrhythmias in the
stressed fetus with underlying CHD.154156 Technological
advances resulting in improvements in the ability to obtain
fetal ECG and MCG at the bedside are needed. It is likely
that assessment of fetal cardiovascular status by ultrasound
will play a more important role in several non-cardiac
conditions as well as providing guidance for invasive
procedures. Prenatal detection rates for CHD remains poor
76
and it is important that regional programs dedicated to local

sonographer training and support be developed. Hand-inhand with the technological and therapeutic advances, it is
important to keep a focus on ethical issues, which are unique
in this setting, with the potential of harm not only to the
mother and fetus, but in cases of twin gestation to all three of
them! 3D and 4D ultrasound will likely play a more prevalent
role in remote diagnosis of CHD and assessment of cardiac
function.41,44
Medicine is a science of uncertainty and an art of probability.
Sir William Osler
aCknowledgments
I would like to thank our sonographers Tim Heiser, Janet
Klobuchar and Barb Trampe, for their dedication and help with
the image acquisition.
reFerenCes
4
FEtal Cardiology
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83
C hapter
Congenital Heart Diseases with

Duct-dependent Circulation
Smita Mishra, Sanjay Khatri
Introduction
Congenital heart diseases (CHDs) with major structural
alterations like pulmonary atresia or transposition of great
arteries (TGA) are usually compatible with fetal life. However,
these defects have serious manifestations once a baby is born.
To comprehend innate abnormality in a baby born with a
certain heart defect, one has to understand fetal circulation
and its disparity from postnatal circulation, which is described
in detail in Chapter 2.
The ductus arteriosus (DA) or Botallo duct, is a normal
structure in the mammalian fetus, that diverts about 80 to
90 percent of the right ventricular output directly to reach
into the descending aorta.1,2 The DA is a large vessel in
the fetus and its size is equal to the main pulmonary artery
(MPA) and the descending aorta. Typically, only about 9 to
10 percent of the right ventricular (RV) output passes through
the pulmonary vascular bed and 30 percent of the total right
atrial (RA) inflow directly enters into the systemic circulation
via the patent foramen ovale (PFO) into the left side of the
heart to enter the ascending aorta and get distributed in the
upper part of the body. The circulation of a smaller volume
of blood in pulmonary circulation results in smaller branch
pulmonary arteries.13 The fetal circulation can be considered
as parallel with two intertwining shunts through PFO and DA.
Furthermore, the fetus enjoys the freedom from commitment
of arranging gaseous exchange by active brea
thing efforts
and has parasitic dependence on the placenta and maternal
circulation for the oxygen.13
With the onset of birth, a fetus becomes an independent
newborn. With the first few breaths, the inflated lungs start
functioning independently. The pulmonary and the systemic
circulations are now two distinct entities. Systemic venous
blood reaches the pulmonary vascular bed via the right atrium,
right ventricle, and the pulmonary artery, while the pulmonary
venous blood reaches the left side of the heart, so that it can
be distributed into the systemic circulation. Therefore, there
is natural elimination of the role of the PFO and PDA in a

newborn baby.
Embryology
Embryologically, the DA is a remnant of the distal sixth aortic
arch and connects at the junction of the MPA and the left
pulmonary artery (LPA) to the proximal descending aorta.
The left subclavian artery arises from the descending aorta
near this junction.12
Natural History of Ductus arteriosus

In the natural history of postnatal ductus, spontaneous closure
is the rule. Normally, in healthy term infants, the functional
closure of the DA occurs in about 15 postnatal hours. However,
true anatomical closure, in which the ductus loses the ability
to reopen, may take several weeks.14
Cassels et al defined the true persistence of the PDA when
it persists in an infant beyond 3 months of age.5 The ductus
closure occurs by abrupt contraction of the muscular wall of
the DA secondary to increase in the partial pressure of oxygen
(PO2), with the commencement of the first breath. This was
demonstrated by multiple experiments in the 1940s and
subsequently was confirmed in clinical studies. Although the
neonatal ductus appears to be highly sensitive to the changes
in the arterial oxygen tension, the actual reasons for the
closure or persistent patency are complex. It involves perinatal
manipulation of ductal musculature by the autonomic nervous
system and chemical mediators.1,2,5
Morphology and Physiology of Ductus

Arteriosus
Normally, the ductus is a muscular artery, which shows
morphological variation in accordance to the gestational age of
the fetus. Few reports based on the histology demonstrated that
Role of Prostaglandins in Patency of Ductus:

Historical Review3438,41
Coceani and Olley et al established that the dilation of the
ductus is possible by infusion of prostaglandin (PGE1) in fetal
lambs.19 The PGE1 was beneficial in opening the ductus and
raising the systemic arterial oxygen saturation in neonatal
patients with duct-dependent congenital heart defects.2224
Prolonged administration of PGE1 infusion provides a window
period before going for the surgical creation of a palliative
systemic to pulmonary artery anastomosis or total correction.
Clyman et al demonstrated that the PGE1 is effective as a duct
dilator, even in the presence of normal arterial oxygen tension.
Subsequently, prostaglandins were used successfully to
achieve ductal patency in babies with interrupted aortic arch
and coarctation of aorta.2627 In a study involving 56 centers,
PGE1, was used in 492 infants with ductus-dependent
CHDs. PGE1 provided effective palliation for the 385
infants out of which 107 babies were acyanotic and had leftsided obstructive lesions.28 Clinical improvement occurred
in about 80 percent in both cyanotic and acyanotic babies.
In the infants with aortic coarctation and interruption,
descending aortic blood pressures increased and the pressure
differences across the DA decreased markedly.28
According to McNamara, the period of 1946 to 1982 saw
the revolution in pediatric cardiac care due to the evolution
of the methods to keep open the PFO and PDA. Successful
medical manipulation of PDA also became the routine practice
in the same period.29
Dilemma of Managing Patent Ductus Arteriosus

in Sick Newborn Units
Usually, babies born before achieving the desired gestational
age have patent ductus. These preemies have early congestive
heart failure and become symptomatic. The prostaglandin
inhibitors can be used to treat them medically. Some of
them may need catheter or surgical intervention. The duct-
dependent CHDs (DDCHDs) must be ruled out before

attempting closure of PDA.
Patent Ductus Arteriosus Dependent

Ductus-dependent lesions are a special group of CHDs,
which have life-threatening propensities. These are either
isolated severe obstructive lesions like coarctation of aorta
or critical pulmonary stenosis or they can be more complex
(Table 2). These defects are responsible for life-threatening
hemodynamic effects. The two shunts, PFO and PDA play
a unique role, since they do not have effective valves and
depending on the pressure of the adjoining chambers or great
arteries, they can shunt blood in either direction. Only the
duct-dependent lesions will be discussed in this chapter.
Classification of Duct Dependent Congenital

Heart Diseases1,2,4,31,32
The duct-dependent CHDs can be divided into three categories
(Table 2, Figures 1A to C):
Duct-dependent Pulmonary Circulation

The lungs are underperfused in these babies. The patent
ductus diverts the partially saturated systemic blood towards
the pulmonary circulation to improve the overall saturation.
Rarely, a widely open duct may raise the PaO2 above 49 mm
Hg. Therefore, the concentration of oxygen, to start ductal
constriction, is seldom achieved by oxygen supplementation. It
is observed that in babies with pulmonary atresia, who survive
for several days or weeks, the PaO2 remains in the range of
35 to 40 mm Hg. It is not known whether it is related to this
physiological balance or whether it is due to poor development
of the ductus, so that it cannot accommodate a higher flow. The
severely hypoxic babies who have very low pulmonary blood
flow, are the least benefitted by oxygen administration.4,31
Furthermore, the administration of 100 percent oxygen only
increases the dissolved oxygen level. It is most unlikely that
these babies can have their PaO2 level to the threshold level for
ductal constriction (Table 2 and Figure 1A).31
5
congenital heart diseases with duct-dependent circulation
the duct had a minimal thickening of the internal elastic lamina

and media in the first 3 to 6 months. Remarkable changes were
seen in structure after the seventh month of gestation.6,7
The patency of the arterial duct is ensured by the low
oxygen content of the fetal blood and the vasodilating action
of the prostaglandins, mainly due to the prostaglandin E2.8
Takizava et al published an article about the role of nitric
oxide and prostaglandin on ductal patency in fetus.9 They
concluded that endogenous nitric oxide has a major role in
regulating the patency of the DA in earlier fetal stages, while
dilator prostaglandins may play a role in the near-term fetus
(Table 1). The duct is vulnerable to antenatal administration
of prostaglandin inhibitors like indomethacin or other nonsteroidal anti-inflammatory drugs (NSAIDs) which can cause
premature duct closure in fetus.1,2,4,10
Duct-dependent Systemic Circulation

Obstructive left-sided lesions are responsible for the decreased
perfusion to the body. In the condition like critical aortic
stenosis, a generalized low perfusion pressure prevails leading
to hypoperfusion and acidosis of the vital organs including
the brain and kidney. The aortic stenosis leads to pressure
overload of the heart. The neonates of this group, who have
PFO and duct, clinically present with hepatomegaly and right
ventricular dominance. The duct in such cases becomes not
only a decompressing channel, but also provides volume and
85
86
Table 1
Regulators of ductal patency

Agents
Effect on ductus arteriosus
Possible role
PGI2 (Prostacyclin I2)
Dilatation of duct
Vascular endothelium produces PGI2 as a primary derivative of arachidonic

acid. It is a potent vasodilator and inhibitor of platelet adhesion to the
endothelium and acts through the Gs-protein pathway. Therefore, it is
antithrombotic. These actions are similar to those of endothelium-derived
nitric oxide. Unlike PGE1 and 2, exogenous PGI2 is not effective in
ductal relaxation in low doses. Though PGI2 is not as strong as PGE2.
It may be responsible for prolonged patency of ductus in cyanotic
babies. One of the studies has shown that the persistent high levels
of plasma-6-keto PGF1, a stable hydrolysis product of prostacyclin,
in the study group of cyanotic babies, while PGE2 levels showed no
difference in cyanotic and non-cyanotic groups.11 PGI2 is also used in
treatment of primary pulmonary hypertension.1,2,4,1217
PGE2 (Prostaglandin E2)
Dilatation of duct
PGE2 generally acts as a vasodilator by stimulating the Gs-protein

pathway. Though PGI2 is produced more than PGE2, ductal rings
are more than 1,000 times sensitive to PGE2 than PGI2. The level
of PGE2 falls down fast and reaches adult levels within 3 hours.
Newborns with lung disease fail to achieve this fall in PGE2 levels, as
it does not get metabolized in the lungs.829
Nitric oxide
Dilatation of duct
NO synthetase is present in ductal epithelium and vasa vasorum. It

possibly contributes to the ductal patency in early gestational age.14,9
Oxygen
Constrictor of duct
An arterial partial pressure of oxygen (PaO2) level of >45 mm Hg and

<17 mm Hg induces constriction of the duct. The oxygen inhalation
with high fraction of inspired oxygen (FIO2) may induce duct closure
in duct-dependent systemic circulation, but in duct-dependent
pulmonary circulation it may not be achievable as pulmonary
circulation is low in pressure and the shunt across the duct is always
left to right. Aortic PaO2 cannot reach to higher level even with 100
percent FIO2.4
Adenosine
Relaxes ductal muscle
Possible prenatal role in the patency of the duct.1,2,4
Calcium
Promotes oxygen-induced
constriction
Possibly oxygen, via adenosine triphosphate (ATP) route, induces cell membrane depolarization and closure of K+ channels. This
opens voltage-dependent Ca++ channels, increase the intracellular
Ca, which then induces duct constriction.4
Norepinephrine/epinephrine
Constrictor of duct
Can enhance the oxygen-induced constriction. Ductal wall has

sympathetic nerve ending.1,2,4 It may have some regulatory role
in utero.
Cholinergic stimulation
Constriction of duct
It can lead to ductal constriction. Also, it can enhance the sensitivity

towards oxygen-induced duct constriction.1,4
Acetylcholine
Constrictor of duct
Can enhance the oxygen-induced constriction, but no established

individual role.1
Bradykinin
Constrictor of duct
Can enhance the oxygen-induced constriction, but no established

individual role.1
Non-steroidal antiinflammatory drug (NSAID)
These agents are cyclooxygenase (COX 1 and

2) inhibitors. Act as duct
constrictor.
Can cause premature ductal closure in fetus. Have therapeutic role

in medical closure of duct in preterm newborns with PDA.1,2,4
Light
Inhibits constriction
Prohibit PDA closure in preterm newborns.4 Rosenfeld et al (1986)

recommended shielding of chest of preterm baby during phototherapy.
Thromboxane/leukotrienes/
mono-oxygenase metabolite
of arachidonic acid
May have some supportive

role in ductal constriction
induced by NSAID or O2
The role is not well defined.4
5
C
Figures 1A to C: The diagrammatic representation of duct-dependent circulations: A. Pulmonary atresia/ventricular septal defect; B. Hypoplastic
left heart syndrome; C. Transposition of great vessels. Ao = Aorta; LA = Left atrium; LV = Left ventricle; PA = Pulmonary artery; RA = Right
atrium; RV = Right ventricle.
Table 2
Classification of the CHDs with duct dependent circulation

Lesions which will depend on flow
via the ductus arteriosus to maintain
pulmonary circulation (Figure 1A)
Lesions which will depend on the flow

via the ductus arteriosus to maintain
systemic circulation (Figure 1B)
Lesions where the systemic and

pulmonary circulations are separated so
that mixing site is needed (Figure 1C)
Pulmonary atresia with or without

ventricular septal defect (VSD)
Critical pulmonary stenosis
Tricuspid atresia
Tetralogy of Fallot (severe form)
Few selected cases of Ebsteins anomaly
of the tricuspid valve
Critical aortic stenosis
Transposition of the great arteries.
Coarctation of the aorta

Interruption of aortic arch
Hypoplastic left heart syndrome
perfusion pressure for the whole body. Echocardiographic

evaluation shows characteristic reverse filling of the arch and
ascending aorta.
In interrupted aortic arch and severe coarctation of aorta,
the perfusion is less in the lower part of the body and it is
reflected by the heightened blood pressure in the upper limb

and the head. This differential response of blood pressure is
primarily due to the renal response to hypoperfusion. The
opening of the duct in such situations would provide perfusion
volume and pressure for the lower extremities. Furthermore,
87
hypoplastic left heart syndrome (HLHS), leads to complete

intracardiac mixing of pulmonary and systemic venous blood.
The pulmonary artery is the single outlet for the total cardiac
output. When pulmonary vascular resistance (PVR) falls in
the early postnatal period, pulmonary blood flow (Qp) is
diverted to the lungs and the Qp, which increases, often at the
cost of the systemic (Qs) and coronary blood flow. This Qp :
Qs mismatch imposes three physiological consequences:
1. Excessive Qp leads to pulmonary edema and tachypnea
and hence augments the overall metabolic rate
2. Excessive Qp results in an added volume load to the single
ventricle resulting in ventricular dysfunction and valvar
regurgitation, and
3. Qs may fall, leading to diminished oxygen delivery (DO2),
acidosis, necrotizing enterocolitis, renal and hepatic
dysfunction and other complications.30,3335 The chemical
manipulation keeps the duct patent giving enough
opportunity to stabilize the baby before surgery, but it also
makes patient vulnerable for unbalanced Qp : Qs and its
tribulations (Figure 1B and Table 2).
Duct in Transposition Physiology: A Site for Mixing

Transposition of great vessels with intact ventricular septum
is a common cyanotic CHD. In this condition, the aorta gets
connected to right ventricle and pulmonary artery to the left
ventricle leading to parallel circulation, where the systemic
venous blood would reenter into the systemic artery, bypassing
the lungs. Similarly, pulmonary venous blood evades systemic
circulation and reenters into the pulmonary artery. It leads to
high oxygen saturation in the pulmonary arterial blood and
severe systemic hypoxemia. A good sized PFO or atrial septal
defect is required to accomplish the proper mixing of blood
at the atrial level. The balloon atrial septostomy in a tertiary
cardiac care center provides a non-surgical palliation for sick
neonates. However, ductus helps in oxygenation by redirecting
desaturated aortic blood towards the lungs. It also provides
site for mixing, as bidirectional shunting occurs in presence
of pulmonary arterial hypertension.4,31,32 A restrictive PFO
may scuttle the advantage of patency of the duct in some cases
(Figure 1C and Table 2).
EFFECT OF HYPOXEMIA SECONDARY TO DUCTAL

CONSTRICTION IN DUCT-DEPENDENT congenital
heart diseases3031
88
The mechanism responsible for the response to hypoxemia are

complex and the effects are the result of interacting influences
(Figure 2). The main mechanisms involved are:
1. Chemoreflex responses.
2. Hormonal effects.
3. Direct local vascular responses.
4. Baroreflex response.
The peculiarities of neonatal response to hypoxemia are:
Figure 2: Effect of hypoxemia in duct-dependent CHD31
a. Modest rise in heart rate unlike in adults, where

tachycardia is the rule.
b. Hypoxic hypometabolism leading to decreased oxygen
consumption and core temperature.
c. Lactic acidemia.
d. Onset of hypoglycemia: Occurs secondary to increase in
anaerobic glycolysis and can cause additional problem
of energy supply.
e. The PaCO2 does not rise. It can be related to the fact
that CO2 readily diffuses across the alveolar-capillary
membrane. Lactic acid metabolism is depressed and
hence production of CO2 at tissue level is less.
The relative insensitivity of peripheral chemoreceptor in
the early postnatal period probably explains the fact that the
infants with cyanotic CHD with marked hypoxemia and who
do not have significant increase in respiratory efforts, do not
have bradycardia and may appear comfortable.
Differential Diagnosis14,30
We know that DDCHDs are associated with systemic
desaturation and central cyanosis. The central cyanosis can
be present clinically in conditions like persistent pulmonary
hypertension of the newborn (PPHN), primary pulmonary
disease, sepsis and methemoglobinemia. Many other
conditions can simulate DDCHDs like choanal atresia,
Pierre Robin sequence, vascular ring, diaphragmatic hernia,
acyanotic CHDs with shunt reversal, chest infections, neonatal
sepsis, hypothermia and hypoglycemia.
Clinical Presentation
The infants with duct-dependent circulation have imminent
risk of life-threatening events. These events usually coincide
Table 3
Clinical examination, X-ray chest and electrocardiogram (ECG) findings in duct-dependent congenital heart diseases (CHDs)14
Clinical findings
X-ray chest
ECG
Hypoplastic left heart

syndrome
Single S2, breathing effort,

pulse amplitude, perfusion,
+/ SM
Pulmonary arterial markings are

increased, cardiomegaly
LV force usually, develops RAE,

RAD
Transposition of great
arteries (IVS, VSD)
Split S2 +/, murmur +/
Pulmonary arterial markings,

+/ cardiomegaly with narrow
mediastinum (i.e. egg on a
string)
Develops RAE, RAD, RVH
Tricuspid atresia
with PS
Single S2, PSM/ESM
Pulmonary arterial
markings, +/ cardiomegaly
Left axis deviation/LVH
Tetralogy of Fallot
with severe PS
or PA
Single S2, ESM

+/ boot-shaped heart
Single S2 continuous murmur,
Pulmonary arterial markings
Left sternal edge, back and axilla and heart size
Develops RAE, RAD, RVH
Pulmonary atresia
intact ventricular
septum
Single S2, continuous murmur in

axilla, back, front
Pulmonary arterial markings
QRS axis 0 to 80, RV forces may

be absent
Coarctation of aorta
Feeble or absent lower limb

pulses, decreased lower limb
blood pressure, soft ESM in
back +/, click and S3 +/,
differential cyanosis, shock like
picture mimicking sepsis
Heart size, Pulmonary venous

hypertension, pulmonary edema
RVH , LVH or Biventricular

hypertrophy
Critical aortic stenosis
Shock like picture, poor pulses

and perfusion, ESM +/-, click +/-,
S3, single S2
Heart size,
pulmonary edema
QRS axis corresponds to +90 and

+100 LVH, T-wave abnormalities
Critical pulmonary
stenosis
ESM, click, single

S2, most have
cyanosis
Normal or
pulmonary arterial
markings, RAE
QRS axis 0 to 90,

develops RVH
Diagnosis
ESM = Ejection systolic murmur; IVS = Intact ventricular septum; LVH = Left ventricular hypertrophy; PA = Pulmonary atresia; PS = Pulmonary stenosis;
PSM = Pansystolic murmur; RAD = Right axis deviation; RAE = Right atrial enlargement; RVH = Right ventricular hypertropy; SM = Systolic murmur; VSD
= Ventricular septal defect;
with the time of ductal constriction or closure (Table 3). These

babies often present in the first few days of life with incremental
cyanosis. The neonatal cyanosis becomes more conspicuous
due to their higher hemoglobin levels. The central cyanosis
is dependent on absolute concentration of deoxygenated Hb
and is more than 3 grams/L in arterial blood and more than 5
grams/L in capillary blood. A polycythemic neonate with Hb
of >20 grams/L will have evident cyanosis at the saturation of
85 percent. On the contrary a neonate with Hb of 8 grams/L
will show it only when saturations falls below 70 percent. Also
babies with higher fetal Hb level will have late visible cyanosis.
Very sick babies usually have cyanotic spell or congestive heart
failure and circulatory collapse without clinical cyanosis. An
inaudible murmur must not be criteria for exclusion of CHD in
these patients and some times, the deterioration of the clinical
condition with disappearance of murmur is a pointer for an
urgent intervention. The patient may have additional clinical
features. There is a probability of involvement of multiple
organs like kidney, brain or skeletal system, which may add up
to the morbidity and mortality. Hence a detailed examination

and parental counseling is required.
Management
Assessment
The general condition of babies with DDCHD is so critical
that urgent resuscitation and stabilization becomes the
primary goal. Nevertheless, once baby is stable one must try
to confirm the diagnosis in the following steps:
1. Confirmation of presence of central cyanosis: First of
all, central cyanosis must be confirmed by monitoring
saturation with pulse oximetry (PO) and subsequently with
arterial blood gas analysis. A sample from the right radial
artery is preferable. Monitor pre- and postductal oxygen
saturations. If there is a difference of saturation in upper
and lower limb of more than 3 to 7 percent, the chances
of having ductal flow from the pulmonary artery to aorta
89
are high. In first few hours, differential saturation may be

fallacious due to high pulmonary artery pressure and patent
duct.
2. Applying hyperoxia test: The test is based on the
principle that in the absence of fixed cardiac shunts, 100
percent oxygen will increase alveolar PO2, leading to an
increase in pulmonary venous and systemic arterial PO2.
In cyanotic CHD (e.g. decreased pulmonary blood flow or
TGA), little or no rise in PaO2would be expected after
breathing 100 percent O2 (Table 4). However, the same
finding may occur in infants with significant pulmonary
hypertension, if significant right-to-left shunting persists
through extrapulmonary shunts (ductus arteriosus and
foramen ovale).
The baby must be kept in 100 percent oxygen for 10
minutes. Before and after the oxygen inhalation, an arterial
blood gas analysis must be done and saturations must be
tested. Usually the PO2 in arterial blood gas (ABG) is the best
parameter to interpret the hyperoxia test, but many centers
may not be having facilities for ABG analysis (Table 5). One
can see for the rise in saturation by 10 to 20 percent and this
can give a clue about the diagnosis.
Validity of Use of Pulse Oximetry in Routine

Screening for Congenital Heart Disease34
Ten studies (44,969 newborns, 71 severe defects) evaluating
the usefulness of neonatal PO screening in timely detection of
CHD, were reviewed. PO showed a high specificity (99.99%)
and the overall rate of detection of 15 individual defects with
PO was 72 percent (range 46100%), exceeding that of the
clinical examination, 58 percent (986%). Similar results
were obtained for cyanotic CHD (89%vs69%, respectively).
Without PO, discharge of apparently healthy infants with

unknown CHD was 5.5 times and 4.1 times more likely in
cyanotic CHD and all serious CHD, respectively.
Pulse Oximetry: Implications of Differential

Pre- and Postductal Saturation
Pulse oximetry should be documented at preductal and
postductal sites to assess for differential or reverse differential
cyanosis. If the preductal saturation is higher than the postductal saturation (3 to 7% difference), differential cyanosis
exists. Oxygenated blood from the pulmonary circulation
enters the descending aorta through PDA. In Sweden the use
of PO and clinical examination led to an increased sensitivity
of 82.8 percent and specificity of 100 percent for the ductdependent lesions.35
Goals of Management3033
1. To establish the diagnosis after initial stabilization, resuscitation with or without ventilator support.
2. Intubation is indicated when baby presents with apnea,
Table 5
Target arterial blood gas (ABG) analysis in hypoplastic left heart

syndrome38
pH*
7.257.35
PaO2*
3545 mm Hg
PaCO2*
3545 mm Hg
Target saturation
7585%
Fraction of inspired oxygen (FiO2) can be kept as low as 21 percent. If

saturation is < 70 percent then FiO2 can be increased. Avoid hyperventilation
and alkalosis.
Table 4
Interpretation of the hyperoxia test3032

PaO2 (mm Hg) at FiO2 = 0.21
(% saturation)
PaCO2 (mm Hg)
Normal
70 (95)
> 300 (100)
35
Pulmonary disease
50 (85)
> 150 (100)
50
Neurologic disease
50 (85)
> 150 (100)
50
Methemoglobinemia
70 (95)
> 200 (100)
35
< 40 (< 75)

< 40 (< 75)
4060 (7593)
< 50 (< 85)

< 50 (< 85)
< 150 (< 100)
35
35
35
#Cardiac
disease
*Parallel circulation
**Mixing with restricted PBF
***Mixing without restricted PBF
90
PaO2 (mm Hg) at FiO2 = 1.00

(% saturation)
PaO2 = Arterial partial pressure of oxygen; FiO2 = Fraction of inspired oxygen; PaCO2 = Arterial partial pressure of carbondioxide; PBF = Pulmonary blood flow
*D-Transposition of the great arteries with intact ventricular septum.
**Tricuspid atresia with pulmonary stenosis or atresia, pulmonary atresia or critical pulmonary stenosis with intact ventricular septum, tetralogy of Fallot,
or Ebstein anomaly.
***Truncus arteriosus; total anomalous pulmonary venous return; single ventricle, hypoplastic left heart syndrome.
#The ratio of fetal to adult hemoglobin varies from infant to infant and the proportion of each hemoglobin affects the oxygen saturation. Thus, if a baby has
mostly adult hemoglobin, central cyanosis (arterial saturation 7585%) will be observed when the PaO2falls below 50 mm Hg. In contrast, if the baby has
mostly fetal hemoglobin, central cyanosis may not be observed, until the PaO2drops well below 40 mm Hg. Thus, infants with a high proportion of fetal
hemoglobin may have a serious reduction in oxygenation before cyanosis is clinically apparent.
f. The babies with transposition physiology are severely

hypoxemic and may have PO2 < 20 mm Hg, high PCO2
in the absence of lung causes and severe metabolic
acidosis. They can be treated with emergency balloon
atrial septostomy and PGE1 infusion.14
4. Finally, blood samples must be sent for blood counts, Hb,
CRP, culture, electrolytes, sugar, urea, crea
tinine, liver
enzymes and screening for metabolic disorders to identify
the co-morbid conditions.
CYANOTIC NEONATES WITH SPECIAL ISSUES

Hypoplastic Left Heart Syndrome: Special Challenges of
Preoperative Management
The HLHS is a fatal disease, with 90 percent of patients dying
within the first month of life without some sort of intervention.
This is the group where special management strategies are
needed to control hyperoxia. A patient with mild to moderate
restriction at PFO may have left atrial hypertension and hence
pulmonary venous and arterial hypertension leading to little
check on pulmonary overflow and hyperoxia. The group of
HLHS with no or severe restriction of PFO may present with
circulatory collapse and shock and might need resuscitation
and medical or catheter intervention. The biggest task in
a baby with HLHS is to keep the balance between the Qp :
Qs. Prostaglandins, vasoconstrictor drugs, oxygen inhalation,
all will decrease pulmonary vascular resistance and increase
pulmonary blood flow (PBF) at the expense of systemic
circulation.
5
shock or circulatory collapse, severe metabolic acidosis.

Intubation in HLHS is done, if evidence of pulmonary
overcirculation are present like arterial saturation more
than 90 percent and systemic hypoperfusion.
3. To minimize the hypoxemia:
a. Prostaglandin infusion: Prostaglandins have established
role in maintenance of ductal patency. Prostaglandin E1
and E2 both can open up the closing duct. Routinely
PGE1 is used for pharmacological palliation of duct
dependent neonate (Table 6).829
b. To increase the fraction of inspired oxygen (FiO2) once
ductal patency is maintained. Moreover, PCO2 levels
should also be optimized between 35 to 45 mm Hg, with
or without ventilation, to achieve the balance between
Qp : Qs. (Table5)3033
c. One must not try to achieve complete abolition of
cyanosis and a saturation of 75 to 85 percent can be
adequate to avoid tissue hypoxemia and eventual lactic
acidosis.3033 Monitoring of babies on prostaglandin
infusion is shown in Tables 6 and 7.
d. Intravenous fluid resuscitation, 10 ml/kg isotonic
saline or colloid and then optimization of fluid therapy
according to the status. If hemoglobin is less than 12
gm% blood transfusion can be given to improve the
oxygen carrying capacity.
e. By maintaining the acid-base balance, one can correct
acidosis. It has been established that PO2 less than
32 mm Hg can be associated with severe metabolic
acidosis due to hypoxemia at tissue level and onset of
anaerobic metabolism, which further deteriorates the
oxygen uptake and its release at tissue level. It also
leads to fall in core temperature, as thermogenesis is
affected. As we know that therapeutic goals vary in the
three categories of duct-dependent circulation, a fine
tuning of systemic and pulmonary vascular resistance
must be achieved with the customized use of ventilatory
parameters, vasodilators and vasoconstrictors.
Strategies to Keep Qp : Qs Low3640

1. By keeping FiO2 low (21%).
2. By increasing PaCO2. It is well known that CO2 is a
potent pulmonary vasoconstrictor and it can be increased
by giving supplemental inspired PaCO2. This approach
Table 6
Prostaglandindoses, preparation, monitoring37

Drug
Doses
Preparation
Monitoring
Prostaglandin E1
Vial :1 ml (500
mcg)
Starting dose: 0.050.1

mcg/kg/min
Maintenance: 0.0020.05
mcg/kg/min
500 g in vial (1 ml) dissolved in 49 ml

of 5% dextrose to make concentration
10 g/ml. In most infants, the ductus will
reopen within 30 minute to 2 hour after
starting PGE1. Once the ductus has
opened, the maintenance doses can be
started.
During the infusion close monitoring

of heart rate, oxygen saturation, blood
pressure, respiratory rate, and core
body temperature is required.
a. Stable infants on PGE1: Side effects
like apnoea, profound bradycardia,
or severe hypotension, recurrent
or prolonged apnoea may require
ventilatory support.
b. Critically sick infants: PGE1 infusion
MUST not be stopped and managed
by providing intensive care support.
91
Table 7
Side effects of prostaglandins4856

Side effects
Detailed description
Apnea
Usually dose related. Less common if dose is < 0.01 mcg/kg/min.
Hyperthermia
Occurs in 1014% of patients treated with PGE1
Cutaneous vasodilation (resulting in flushing and edema)
Occurs in approximately 10% of infants, with bradycardia in 7% and

hypotension in upto 4%
Seizures
Incidence is about 4%
Tachycardia
3% usually dose related
Diarrhea
2%
Sepsis
2% (dose and duration related)
Respiratory depression, arrhythmias, congestive heart failure, < 1% (rare side effects)
wheezing, gastric regurgitation, bleeding, anuria, hematuria,
thrombocytopenia, peritonitis, hypokalemia or hyperkalemia,
hypoglycemia and jitteriness
92
Necrotizing enterocolitis
In preterm, prolonged and higher doses > 0.5 mcg/kg/min
Hyperostosis
5060%, if PGE2 used for prolonged period
Gastric outlet obstruction
In 67% (after prolonged use)
Intimal tears within the pulmonary arteries and changes in

vessel muscularity. Aneurysmal dilatation and vessel wall
edema
These changes may be dose related, occurring more frequently

when higher infusion rates are used to maximize pulmonary blood
flow
for increasing PaCO2 is preferred over hypoventilation,

which may lead to atelectasis. It has been demonstrated
that the hypercapnic acidosis (HCA) increases oxygen
deliveryby 44 percent. Furthermore, there is evidence that
HCA is a lung protective strategy that preserves pulmonary
mechanics, attenuates lung protein leakage, reduces
pulmonary edema and improves oxygen deliveryin an
animal model of lung injury.
3. PVR can be increased by decreasing the concentration of
inspired oxygen and by adding supplemental nitrogen gas
to attain a FiO2 of 17 to 19 percent. Additionally, PVR can
also be increased by maintaining the hematocrit greater
than 40 percent, a state that optimizes oxygen-carrying
capacity and increases the viscosity of the blood.
Ebsteins anomaly is optimally stabilized on prostaglandin to

support pulmonary blood ow. As PVR falls, a trial of weaning from prostaglandin must be done and the clinical pattern
of response must be assessed. Usually surgical management
strategies are based on tricuspid valve regurgitation and degree of cyanosis. If cyanosis alone is the dominant symptom, a
systemic to pulmonary artery shunt alone is performed.
However, when poor right ventricular function in association
with severe tricuspid regurgitation is present, right ventricular
exclusion by patching the tricuspid valve is the best option.
This is one condition where actively pulmonary vasodilatation is attempted, if weaning of PGE1 fails. Trial of nitric
oxide has been attempted in many centers. Sildenafil also was
tried successfully in few case reports.45
Newborn with Severe Ebstein Anomaly of Tricuspid

Valve: Issue of PGE1 Infusion4145
Total Anomalous Pulmonary Venous Connection:

Effect of Prostaglandins4648
The Ebstein anomaly is not only a tricuspidvalve disease, but

also disease of the right ventricle and rightatrium, or right heart
disease. Of all neonates with the diagnosis of Ebstein anomaly,
20 to 40 percent will die in a month. Like in HLHS, the presurgical and surgical management of critically ill neonates and
younginfants with Ebstein anomaly remains challenging. The
problems which can influence the overall outcome are diminutive and dysfunctional right ventricle, severity of tricuspid regurgitation, severity of right ventricular outflow obstruction,
size of pulmonary arteries, severity of pulmonary hypertension
and dysfunctional left ventricle. The symptomatic neonate with
Routinely, cyanotic CHDs with severe hypoxemia can be put

on prostaglandin infusion without any harm before sending
them to a tertiary cardiac care center, when facility for
echocardiography is not available and exact diagnosis cannot
be made. However, there are some concerns regarding its use
in total anomalous pulmonary venous connection (TAPVC)
espcially the obstructed type. PGE1 could produce adverse
effects by two mechanisms:
1. By increasing the cyanosis and hypoxemia of systemic
circulation: When the pulmonary arterial pressure is higher
than that in the aorta, dilatation of the DA may result in
PROSTAGLANDIN E1: SIDE EFFECTS

Prostaglandins are great rescuers for babies with ductdependent circulation. However, PGE1 infusion is not totally
safe. The problems are associated with gestational age and
type of lesions. Mc Elhinney et al followed-up 643 babies
with complex congenital anomaly and they found 3.3 percent
incidence of necrotizing enterocolitis and it showed high
correlation with prematurity and little higher PGE1 infusion
rate (> 0.5 mcg/kg/min).51 There is risk of apnoea requiring
ventilation particularly in premature, low-birth-weight (LBW)
newborn.4856
Transport of a Baby with Duct-dependent

Congenital Heart Disease38,57
Early diagnosis and optimization of blood biochemistry,
adequate oxygenation, if required ventilation and prostaglandin
infusion to maintain the adequate Qp : Qs ratio is important.
In tetralogy of Fallot (TOF) physiology, usual goal in a case
of duct-dependent pulmonary circulation is to do modified
Blalock-Taussig shunt or ductal stenting. In duct-dependent
systemic circulation, a ductal stenting or high-risk modified

Norwood procedure is expected. In transposition physiology,
if baby fails to stabilize, a balloon atrial septostomy could be
the first interventional procedure before the switch operation.
All of these methods, have some procedure related morbidity
and mortality, as well as financial implications. The neonatal
transport from remote parts of India also has significant risk.
Hence, besides securing intubation, central and peripheral
line, prostaglandin, dextrose, electrolytes, fluid infusions,
temperature optimization, antibiotics coverage, one needs to
do detailed parental counseling before transporting the baby.
INTERVENTION IN DUCT DEPENDENT congenital

heart diseases: DUCTAL STENTING
With growing interest in catheter interventions and persistent
high mortality related to shunt surgery, efforts were made to
explore the new possibilities to maintain the ductal patency.
Moreover, arterial duct stabilization with a high-flexibility
coronary stent is an effective alternative in high-risk surgical
candidates or whenever short-term pulmonary blood flow
support is anticipated. It seems highly logical to try to keep
the duct open rather than going for a surgical alternative
with prosthetic material. We know prostaglandins are highly
effective at maintaining duct patency medically in the short
term. They become less reliable and have more side-effects if
given long-term. Ductal stenting at cardiac catheterization was
first described in the early 1990s.58 Even though technique of
stenting has not changed appreciably in the past 15 years, stent
and balloon technology is becoming better. With the future
advancement and training, one can think of better outcome of
this promising and life-saving procedure (Table 8).
5
an increase in right-to-left shunt and would increase in the

degree of cyanosis.
2. By direct pulmonary vasodilatation leading to altered Qp :
Qs: Usually it might be expected that the ductus response
to PGE1 would predominate and cyanosis may be expected
to worsen.
Very rarely PGE1 has an ameliorating effect on infradiaphragmatic TAPVC by relaxing the ductus venosus and thus
relieving the obstruction.
Table 8
Recommendation for ductal stenting (a scientific statement from the American Heart Association)61
1. Recommendations for patent ductus arteriosus (PDA) stenting for the purpose of augmenting pulmonary blood flow
Class IIa
It is reasonable to stent an anatomically suitable ductus arteriosus in an infant with cyanotic congenital heart
disease (CHD) who has >1 source of pulmonary blood flow (antegrade pulmonary blood flow or collateral blood
flow), but who requires additional pulmonary blood flow from the stented ductus for a relatively short period of
time (36 months) (Level of Evidence: B).
Class IIb
It might be reasonable to stent an anatomically suitable PDA in an infant with cyanotic CHD whose sole
source of pulmonary blood flow is the ductus (Level of Evidence: C).
Class III
Ductal stenting should not be performed in an infant with cyanotic CHD who has obvious proximal pulmonary
artery stenosis in the vicinity of the ductal insertion (Level of Evidence: C).
2. Recommendations for a hybrid approach to hypoplastic left heart syndrome (HLHS) and complex single ventricle
Class IIa
It is reasonable to perform hybrid stage I palliation, consisting of right and left pulmonary artery banding,
PDA stent implantation and creation of an unrestrictive atrial communication, by combining transcatheter
and surgical techniques without cardiopulmonary bypass as an alternative to conventional surgery in
neonates with HLHS or complex single ventricle, in high-risk surgical candidates and as a bridge to heart
transplantation (Level of Evidence: B).
Class IIb
Hybrid stage I palliation may not be indicated in a patient who has significant retrograde aortic arch
obstruction at the time of initial diagnosis that might be further compromised by placement of the PDA stent.
This decision should be a collaborative decision between the interventional cardiologist and a congenital
heart surgeon (Level of Evidence: C).
93
Advantages of Ductal Stenting

1. Eliminating the need for neonatal palliative surgery.
2. Reducing the number of operations required.
3. Optimizing the time of definitive surgical correction.
Procedure59,60
Ductal stenting is done in the catheterization laboratory under
general anesthesia. Angiography is done to demonstrate the
anatomy and to measure the length of the arterial duct. IV
heparin (50 U per kg) must be given. Cefazolin 30 mg per kg
is administered prior to stent implantation, followed by another
two doses at the interval of 8 hours. Prostaglandin infusion can
be stopped several hours before the procedure, so that duct can
have grip over stent. Prostaglandin inhibitors can be used in
selected cases.
The antegrade approach through femoral vein or retrograde
approach through femoral artery can be used. For antegrade
approach in a case of pulmonary atresia, perforation of
pulmonary valve would be required.
The procedure for stent implantation has to be individuali
zed, since origin and morphology of the duct varies in
different CHDs. In patients with pulmonary atresia with
intact interventricular septum, the approach can be either
antegradely through the pulmonary artery after the perforation
of atretic valve or it can be done retrogradely. In patients with
pulmonary atresia with VSD also, the approach has to be either
antegrade or retrograde. For better support during delivery of
the stent, a 4F long sheath (Mullin) can be used. After entering
pulmonary artery, by using an end-hole catheter, a 0.014
coronary wire is introduced via arterial route to cross the DA.
Over this wire, the delivery system with the coronary stent
may be advanced into the duct. After confirming the correct
position of the stent across the duct, the balloon is inflated in
order to deploy the stent. Post stenting, anticoagulation and
prevention and management of the restenosis are important.
Acetylsalicylic acid, 1 to 3 mg/kg/day, is started for as long as
stent patency is required. Stent restenosis can be treated with
ballooning and restenting.
Modifiers for Success of the Procedure5961
94
The success of procedure depends on the type and length of

PDA, type of stents and experience of operator. A stented duct is
more comparable with a central shunt, which has no restriction
at the aortic end. Usual size of surgical shunt in neonate is 3
to 4 mm. The final lumen within the stent, will depend on the
stent diameter at the time of implantation. The diameter of
lumen decreases by contraction of the vessel wall leading to
tissue prolapse through the stent struts. This process starts after
few hours of stent placement. Further decrease in size of lumen
is secondary to endothelial hyperplasia. The stents design and
material determines the cross-sectional area, strut thickness
and radial force. The stent characteristics like larger metallic

cross-sectional area, thicker struts, and smaller cell area give
good scaffolding with limited tissue prolapse. However, these
properties reduce the flexibility and conformability of the
stent, and are known to enhance in-stent restenosis rate in
coronary arteries. Balloon redilatation or additional stent can
be deployed to avoid residual stenosis. The radial force and
side-branch accessibility are no issue for a stent deployed in the
arterial duct. A thin but complete layer of endothelium forms
over the stent as early as 1 month. Neoendothelial proliferation
plays an important role in duct-dependent pulmonary blood
flow. There could be gradual fall in oxygen saturation as the
duct becomes compromised by neoendothelium.
Alwi and colleagues demonstrated that PDA stent
accelerates pre-existing stenosis of the pulmonary arteries,
primarily in the LPA. They concluded that the stent metal
grid provokes intense neointimal proliferation and fibrosis in
the ductal tissue encircling the pulmonary arteries.60 Because
the pulmonary artery implants at the LPA origin, the higher
incidence of stenosis in this branch can be explained by the
concomitant effect of the pulmonary coarctation and the
neointimal hyperplasia. Fortunately there are attempts to evolve
novel technologies. The innovative methods like rapamycincoated drug eluting stents have been experimented in newborn
pigs successfully.
The palliation obtained from ductal stenting, is less reliable
and of shorter duration than that expected from a surgical
aortopulmonary shunt. In HLHS, a more complex hybrid
approach (selective pulmonary artery bandings without
cardiopulmonary bypass followed by percutaneous PDA stent
implantation and balloon dilation of the atrial septum) was done
by Akinturk et al in 2002 with little better results.61 However,
duct stenting in HLHS as a part of combined procedure, is still
an unpredictable and technically demanding procedure and not
recommended as Class I indication.
Bioengineering in Duct Patency

Transfection is the delivery of DNA, RNA, proteins, and
macromolecules into the eukaryotic cells. Based on the belief
that a protein called fibronectin, the concentration of which
increases in the advanced stage of gestation, is responsible
for closure of the duct, the gene for a fibronectin 'decoy'
was introduced directly in utero in the ductal tissue to keep
ductal patency in animal experiments. Percutaneous postnatal
transfection of gene for PG in ductal tissue also ensured
prolonged patency of duct. These and several other projects
are underway to get the safest technique to keep duct open.2
Conclusion
Duct-dependent congenital heart diseases are life-threatening
cardiac emergencies and need to be recognized as early as
possible. Medical intervention with prostaglandin infusion
They do certainly give very strange, and new fangled, names

to diseases.
Plato
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11. Hammerman C,Aramburo MJ, Bui KC. Endogenous dilator
prostaglandins in congenital heart disease. Pediatr Cardiol.
1987; 8:155-59.
12. Clyman RI, Heymann MA, Rudolph AM. Ductus arteriosus
responses to prostaglandin E1 at high and low oxygen concentration. Prostaglandins. 1977; 13:219-23.
13. Olley PM, Coceani F, Bodach E. E type prostaglandins. A
new emergency therapy for certain cyanotic congenital heart
malformations. Circulation. 1976; 53:728-31.
14. Clyman RI, Sangstad D, Mauray F. Reactive oxygen
metabolites relax the lamb ductus arteriosus by stimulating
prostaglandin production. Circ Res. 1989; 64:1-8.
15. Elliot RB, Starling MB, Neutze JM. Medical manipulation of

patent ductus arteriosus. Lancet. 1975; 1:140-2.
16. Heymann MA, Rudolph AM, Silverman NH. Closure of
the ductus arteriosus in premature infants by inhibition of
prostaglandin synthesis.N Engl J Med.1976; 295:530-3.
17. Silove ED. Pharmacological manipulation of the ductus
arteriosus; Archives of Disease in Childhood. 1986; 61:827-29.
18. NadasAS.Patent ductus revisited.N Engl J Med.1976; 295:
563-5.
19. Coceani F, Olley PM. The response of the ductus arteriosus to
prostaglandins. Can J Physiol Pharmacol. 1973; 51:220-25.
20. Silove ED, Coe JY, Shiu MF, et al. Oral prostaglandin E2 in
ductus dependent pulmonary circulation. Circulation. 1981;
63: 682-88.
21. Silove ED, Roberts DGV, Giovanni JVD. Evaluation of oral
and low dose intravenous prostaglandin E2 in management of
ductus dependent congenital heart disease. Archives of Disease
in Childhood. 1985; 60:1025-30.
22. Elliott RB, Starling MB, Neutze JM. Medical manipulation of
the ductus arteriosus. Lancet. 1975; 1:140-42.
23. Heymann MA, Rudolph AM. Ductus arteriosus dilatation by
prostaglandin E1 in infants with pulmonary atresia. Pediatrics.
1977; 59:325-9.
24. Heymann MA, Berman W Jr, Rudolph AM, et al. Dilatation
of the ductus arteriosus by prostanglandin E1 in aortic arch
abnormalities. Circulation. 1979; 59:169-72.
25. Lang P, Freed MD, Rosenthal A, et al. The use of prostaglandin
E1 in an infant with interruption of the aortic arch. J Pediatr.
1977; 91:805-07.
26. Freed MD, Heymann MA, Lewis AB, et al. Prostaglandin E1
in infants with ductus arteriosus-dependent congenital heart
disease. Circulation. 1981; 64:899-904.
27. McNamara DG. Twenty-five years of progress in the medical
treatment of pediatric and congenital heart disease. Journal of
the American College of Cardiology. 1983; 1:264-73.
28. Robin H, Steinhorn MD. Evaluation and management of the
cyanotic neonate, Clin Pediatr Emerg Med. 2008; 9:169-75.
29. Rudolph AM. Oxygen uptake and delivery. In Congenital
Diseases of the Heart: Clinical-Physiological Considerations.
Futura publishing House, UK. 2001; 85-119.
30. Marino BS, Fine KS. Cardiology. In Blueprints Pediatrics
(Blueprints Series) 3rd edition. Marino BS, Fine KS, McMillan
JA (Eds). Blackwell publishing 2004; 16-26.
31. Costello JM, Franklin WH. Preoperative and postoperative care
of infants with critical congenital heart diseases. In Averys
neonatology: pathophysiology and management of the newborn
6th edition. MacDonald MG, Seshai MMK, Mullett MD (Eds).
Lippincott Williams & Wilkins, Philadelphia, USA. 2005; 710767.
32. Valmari P. Should pulse oximetry be used to screen for
congenital heart disease? Arch Dis Child Fetal Neonatal Ed.
2007; 92:F219-F24.
33. Granelli A, Wennergren M, Sandberg K, et al. Impact of
pulse oximetry screening on the detection of duct dependent
congenital heart disease: a Swedish prospective screening
study in 39,821 newborns. BMJ 2009; 338:a3037.
34. Liske MR, Aschner JL. Counterpoint: hypoxia is not the
optimal means of reducing pulmonary blood flow in the
preoperative single ventricle heart. J Appl Physiol. 2008;
104:1836-8.
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babies need to be supported with inotropes and ventilation,
which needs to be customized according to the type of
lesion. Ductal stenting can obviate need for shunt surgery.
Mostly such babies can undergo successful cardiac corrective
intervention at an appropriate time.
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of the Newborn, 8th edition. Taeusch HW, Ballard RA, Gleason CA (Eds), Elsevier 2004; 888-895.
36. Shan F, Shekerdemian L, Millar J, et al. Early management of
infants with hypoplastic left heart syndrome. Hhs. 2008. doc;
http://www.rch.org.au/emplibrary/picu/HLHS.pdf.
37. Day RW, Barton AJ, Pysher TJ.Pulmonary vascular resistance
of children treated with nitrogen during early infancy.Ann
Thorac Surg.1998; 65:1400-4.
38. Dessardo S, Ahe V. Preoperative management of hypoplastic
left heart syndrome. SIGNA VITAE. 2009; 4:12-15.
39. Kinouchi K,Okawa M,Fukumitsu K. Perioperative management of two neonates with severe Ebsteins anomaly with pulmonary atresia. Masui. 2000; 49:1274-7.
40. Jaquiss RD, Imamura M. Management of Ebsteins anomaly
and pure tricuspid insufficiency in the neonate. Semin Thorac
Cardiovasc Surg. 2007; 19:258-63.
41. Bove EL, Hirsch JC, Ohye RG, et al. How I Manage Neonatal
Ebsteins Anomaly. Semin Thorac Cardiovasc Surg Pediatr
Card Surg Ann. 2009; 12:63-65. http://cardiopedhnn.
comfypage.com/site/UserFiles/Ebstein-Neonatal-Sx.pdf.
42. Pham P, Hoyer A,Shaughnessy R. A Novel Approach Incorporating Sildenafil in the Management of Symptomatic Neonates
with Ebsteins Anomaly. Pediatric Cardiology. 2006; 27:61417.
43. Aggarwal S, Chintala K, Humes RA. Sildenafil use in a
symptomatic neonate with severe Ebsteins anomaly of the
tricuspid valve. Am J Perinatol. 2008; 25:125-28.
44. Chang AC, Burke RP. Anomalous pulmonary venous connection. In Pediatric cardiac intensive care, Chang AC, Hanlay
FL, Wernovsky G, Wessel DL (Eds). Williams and Wilkins,
Toronto. 1998; 223-28.
45. Bullaboy CA, Johnson DH, Ajar H. Total anomalous
pulmonary venous connection to portal system: A new role for
prostaglandin E1. Pediatric Cardiology. 1984; 5:115-16.
46. Product information. Prostin VR Pediatric. The Up John
Company; Kalamazoo, MI. January 1995.
47. Host A, Halken S, Kamper J, et al. Prostaglandin E1treatment
in ductus dependent congenital cardiac malformations: a
review of the treatment of 34 neonates. Dan Med Bull. 1988;
35:81-84.
48. Kramer HH, Sommer M, Rammos S, et al. Evaluation of
low dose prostaglandin E1treatment for ductus dependent
congenital heart disease. Eur J Pediatr. 1995; 154:700-07.
49. McElhinney D, Hedrick H, Bush D, et al.Necrotizing

enterocolitis in neonates with congenital heart disease: risk
factors and outcomes. Pediatrics.2000; 106:1080-87.
50. Lewis AB, Freed MD, Heymann RA, et al. Side effects of
therapy with prostaglandin E1in infants with critical congenital
heart disease. Circulation. 1981; 64:893-98.
51. Sone K, Tashiro M, et al. Long-term low dose prostaglandin
E1administration. J Pediatr. 1980; 97:866-67.
52. Kaufman MB, El-Chaar GM. Bone and tissue changes following
prostaglandin therapy in neonates. Ann Pharmacother. 1996;
30:269-74,277.
53. Peled N, Dagan O, Babyn P, et al. Gastric-outlet obstruction
induced by prostaglandin therapy in neonates. New Engl J
Med. 1992; 327:505-10.
54. Heffelfinger S, Hawkins EP, Nihill M, et al. Pulmonary vascular
changes associated with prolonged prostaglandin E1treatment.
Pediatr Pathol. 1987; 7:165-73.
55. Transfer of Babies with Duct Dependent Congenital Heart
Disease. Neonatal transfer service. NHS. http://www.neonatal.
org.uk/documents/1457.pdf.
56. Rosenthal E, Qureshi SA, Kakadekar AP, et al. Comparison
of balloon dilation and stent implantation to maintain patency
of the neonatal arterial duct in lambs. Am J Cardiol. 1993;
71:1373-76.
57. Gewillig M, Benson LN. Stenting the Neonatal Arterial Duct
in Duct-Dependent Pulmonary Circulation: New Techniques,
Better Results. J Am Coll Cardiol. 2004; 43:107-12.
58. Djer MM, Alwi M. Stent implantation into ductus arteriosus:
a new alternative of palliative treatment of duct-dependent
pulmonary circulation. Paediatrica Indonesiana. 2004;
44(1-2).
59. Boucek MM, Mashburn C, Kunz E, Chan KC. Ductal anatomy:
a determinant of successful stenting in hypoplastic left heart
syndrome. Pediatr Cardiol. 2005; 26:200-5.
60. Alwi M. Initial results and midterm follow-up of stent
implantation of patent ductus arteriosus in duct dependent
pulmonary circulation. J Am Coll Cardiol. 2004; 44:438-45.
61. Akinturk H, Michel-Behnke I, Valeske K, et al. Hybrid
transcatheter-surgical palliation: basis for univentricular or
biventricular repair: the Giessen experience Pediatr Cardiol
2007; 28:79-87
62. Feltes TF, Bacha E, Beekman RH, et al. Indications for Cardiac
Catheterization and Intervention in Pediatric Cardiac Disease:
A Scientific Statement From the American Heart Association
Circulation. 2011; 123:2607-52.
C hapter
Genetics in
Sridevi Hegde, Mitesh Shetty
The first reference in history to the presence of congenital

heart disease (CHD) comes from a Babylonian tablet, which
dates back to around 4,000 BC. The description mentions;
When a woman gives birth to an infant that has the heart
open and has no skin, the country will suffer from calamities,
which might refer to ectopia cordis (Figure 1).
Leonardo da Vinci, was the first to describe a congenital
heart defect in humans in his Quaderni de Anatomia.1
Congenital heart disease is the leading cause of infant
morbidity in the western world, but only in the past 10 years its
etiology has been understood. Recent studies have uncovered
the genetic basis for some common forms of the disease and
provide new insight into how the heart develops and how
dysregulation of heart development leads to disease.2 In this
day and age, about 85 to 95 percent of the children with CHD
survive into adulthood due to better surgical and non-surgical
Figure 1: Ectopia cordis
techniques.3,4 Therefore, the number of adults with a CHD

is on the rise. Once these patients enter the reproductive age
group, knowledge of heritability of such defects is essential.
Isolated congenital heart defects are most frequently sporadic.
Despite the sporadic nature, a genetic component is still very
likely to contribute to the occurrence of these defects and there
is a higher recurrence risk among siblings and offspring of
patients with CHD.5,6 CHD, being a complex trait, is thought
to be multifactorial.7 Even though, extensive knowledge of the
genetic control of cardiogenesis in animals is available, this
has not been translated into an equivalent amount of clinical
knowledge of the genetic determinants of CHD in humans.
EmbryoloGy
Congenital heart diseases arise from abnormal heart development during embryogenesis, so understanding how the heart
forms normally is important. The heart is the first organ to form
in an embryo and must function to support the rapidly growing
embryo before it has the opportunity to shape itself into the
four chambered organ (Figures 2A and B). The combination
of complex morphogenetic events necessary for cardiogenesis
and the superimposed hemodynamic influences may contribute
to exquisite sensitivity of the heart to perturbation. The fraction
of congenital heart malformations, that are hemodynamically
compatible with the intrauterine circulation form the spectrum
of CHD, that is observed clinically.8
The earliest cardiac progenitors arise from lateral plate
mesoderm, controlled by a cascade of interacting transcription
factors. Discovery of a second heart field (SHF) led to
rethinking of the origin and patterning of the embryonic heart.
The SHF is medial and dorsal to the early differentiating
cardiomyocytes that comprise the cardiac crescent, and
gives rise to a large portion of the heart, including the outflow
tract, right ventricle and most of the atria. The SHF is further
subdivided into a number of lineage pools, which contribute
either to anterior structures (such as the outflow tract) or
posterior components (such as the atria).9
b
Figures 2a and b: Heart development. [Reprinted with permission from Macmillan Publishers Ltd. Nature, Bruneau, 2008, P 946] (A = Artery;
AO = Aorta; AS = Atrial septation; CC = Cardiac cushions; FHF = First heart field; LA = Left atria; LV = Left ventricle; OT = Outflow tract; PA =
Pulmonary artery; RA = Right atria; RV = Right ventricle; SHF = Second heart field; SV = Sinus venous; V = Ventricle, VS = Ventricular septum)
98
allele have similar cardiac abnormalities to those seen in

HoltOram syndrome, with septal defects and atrioventricular
(AV) conduction block.12,14 Mouse TBX20 is expressed in the
cardiac crescent, and in some cells of the SHF. In the heart
tube, it is expressed in myocardium and in endothelial cells
associated with the endocardial cushions; this latter expression
persists with further development, as myocardial expression
weakens. TBX20 interacts directly with TBX5, NKX2-5, and
GATA4.14 TBX20 null mouse embryos have hypoplastic,
unlooped hearts. Expression of TBX20 is required for normal
levels of NKX2-5 expression.16 Notch signalling pathway,
NOTCH1 is expressed in the endocardium of the great vessels
of the heart, where it is thought to be important for epithelial
to mesenchymal transition and valve formation. Individuals
with NOTCH1 mutations have a spectrum of defects, including
AS, ventricular septal defect (VSD), Tetralogy of Fallot (TOF)
and, in one patient, mitral atresia, double outlet right ventricle
(DORV) and hypoplastic left ventricle. NOTCH1 also represses
a bone related pathway, which might explain calcifications in
the cardiac valves of patients with NOTCH1 mutations.2
6
GENEtics iN coNGENital hEart DisEasEs
Human genetic studies have identified numerous genes

that are responsible for inherited and sporadic congenital heart
diseases. Most of these genes encode transcription factors
that regulate specific events in heart development, such as
ventricular septation or outflow tract morphogenesis. A core set
of evolutionarily conserved transcription factors (NK2, myocyte
enhancer factor 2 [MEF2], GATA, TBX and HAND) control
cardiac cell fates, the expression of contractile protein-encoding
genes and cardiac morphogenesis.10 In turn, these transcription
factors regulate one another and many other transcription factors
are involved. Of these, MEF2 is the key myogenic transcription
factor, involved in the differentiation of all types of myocyte. In
turn, it is under regulation by NK2 homeobox genes, particularly
tinman in Drosophila and its orthologous in mammals. The
homeodomain factor NKX2-5 is a key transcription factor in
cardiac development.11 It is expressed in cardiac progenitor cells
of both the first and second heart fields. Expression continues in
the primary heart tube and in the looping heart, in the outflow
tract, ventricles, common atrium and the proximal horns of
the sinus venosus. Expression continues in muscular layers of
the heart throughout the remainder of embryogenesis and into
postnatal and adult life.12 The absence of NKX2-5 is catastrophic
to heart development in the mouse embryo, resulting in complete
failure of cardiac morphogenesis, chamber formation and
outflow tract development. NKX2-5 acts as a part of pathway,
in which it physically interacts with a set of other transcription
factors to activate target genes. For example, the zinc finger
transcription factor GATA4 (one of a group of genes named
because their protein products bind to the nucleotide sequence
GATA) physically interacts with NKX2-5. When coexpressed,
their effect on the transcription of some cardiac genes is
synergistically augmented.12 GATA4 protein is regulated by
other co-transcription factors including the friend of GATA (Fog)
proteins. GATA4 null mouse embryos have severely disrupted
cardiac development, with failure to form the primitive heart tube
among other severe developmental abnormalities.13
The T-box genes are a group of transcription factors, which
share a highly conserved 180 a-amino acid DNA-binding
domain called the T-box.14 Of the seven or more T-box genes
expressed in the developing human heart, TBX1, TBX5
and TBX20 have been implicated in human CHD. TBX1 is
important in the SHF and subsequently the outflow tract,
consistent with its role as the major determinant of the cardiac
phenotype in velocardiofacial syndrome (characterized by
conotruncal malformations).15
There is evidence that TBX5 functions as part of the
NKX2-5 pathway.12,16 Mouse TBX5 associates directly with
NKX2-5 and GATA4, synergistically stimulating chamberspecific genes in later stages of cardiac development. TBX5
is specifically expressed in the FHF, at the cardiac crescent
stage and later in the primary heart tube. TBX5 null mouse
embryos are severely dysmorphic and fail to undergo cardiac
looping. Interestingly, mice heterozygous for a TBX5 null
EtioloGy
Most of the congenital heart defects are sporadic. The major
genetic cause for congenital heart defects includes the following:
a. Chromosomal disorders and single gene disorders
constituting eight percent.
b. Two percent of environmental teratogens.
c. Ninety percent multifactorial disorders.17
Multifactorial means both genetic and environmental
factors interact, to interfere with the development of the heart.
Increased incidence of CHDs has been noted with intrauterine
viral infections, maternal drug and alcohol consumption
during first trimester of pregnancy and pregnancy-induced
systemic maternal disease.18
Chromosomal Aberration
The association of CHDs with chromosomal anomalies
varies between 4 to 12 percent.19 The following are common
chromosomal abnormalities associated with CHD.18,20
Trisomy 21 (Down Syndrome)

Down syndrome is also known as trisomy 21 because of the
extra copy of chromosome 21. It was first described by John
Langdon Down in 1866. It is the most common cause of
human birth defects. It is associated with a delay in cognitive
ability, physical growth and a particular set of facial features.
At least 40 percent of children with Trisomy 21 will have
heart disease; furthermore, 50 percent of those children
with heart abnormalities will specifically be affected with
atrioventricular septal defect (AVSD) (Figures 3A to D).
99
D
Figures 3a to D: Baby with Down syndrome and karyotype of Trisomy 21
Trisomy 18 (Edward Syndrome)

Edward syndrome was first described by John H Edward in
1960. This is the second most common autosomal aneuploidy
after Down syndrome. Majority of the fetus carried to the
term will be stillborn. Common features of trisomy 18
are strawberry-shaped head, microcephaly, micrognathia,
clenched hand, crossed leg, rocker bottom feet, renal problem,
mental deficiency and CHD. Common CHDs include VSD,
AVSD, double outlet right ventricle and hypoplastic left heart.
Trisomy 13 (Patau Syndrome)
100
Patau syndrome was first observed by Thomas Bartholin in

1657 but chromosomal defect was confirmed by Dr Klaus
Patau in 1960. It is associated with holoprosencephaly,
meningomyelocele, cleft palate, polydactyly, overlapping

fingers, omphalocele, mental deficiency and CHD (Figures
4A and B). Common CHDs include atrial septal defect (ASD),
VSD, patent ductus arteriosus (PDA) and cardiac malpositions
especially dextrocardia (6%).
45, X (Turner Syndrome)

Association between short stature and abnormal ovarian
development was described by Rossle in 1922. This was
explained with webbed neck and cubitus valgus by Turner in
1938. It is a chromosome abnormality in female, where one
of the sex chromosome is missing. Common CHDs include
VSD, coarctation of the aorta (COA), bicuspid aortic valve,
hypoplastic left heart, mitral valve prolapse and idiopathic
aortic root dilatation.
b
Figures 4a and b: A. Baby with Trisomy 13 and B. Karyotype Trisomy 13
Tetrasomy 22q (Cat Eye Syndrome)
Tetrasomy 12p (PallisterKillian Syndrome)
Usually the result of additional copy of chromosome 22,

triplicate or quadruplicate of the critical region 22 pterq11. It
is characterized by coloboma of iris and anal atresia. The CHDs
association is found to be 30 percent in patients with total
anomalous pulmonary venous drainage as a major problem.
One of the patient at the time of anomaly scan showed
marked hypoplasia of both ears with preauricular ear tags and
moderate degree of micrognathia (Figure 5). Detailed fetal
echocardiography showed slight discrepancy in the cardiac
ventricles. Based on this ultrasonography (USG) finding,
amniocentesis was carried out, which revealed tetrasomy 22q
(Figures 6 and 7). After genetic counseling, the couple opted
to terminate the pregnancy. Postnatal examination of the fetus
confirmed the ultrasound findings and in addition there was
anal atresia.
Pallister-Killian syndrome is due to extra isochromosome

12p, which is seen mainly in skin fibroblast. It is characterized
by hypotonia, skin pigmentary changes, diaphragmatic defect,
mental deficiency and CHD. The CHDs association is found
to be in 25 percent of the patients that includes VSD, COA,
PDA, ASD and aortic stenosis (AS).
Chromosome Deletion Syndrome

Deletion 22q11.2 Syndrome (OMIM: 611867)
Deletion 22q11.2 syndrome comprises of three major
syndromes: DiGeorge syndrome (DGS), Velocardiofacial
syndrome (VCFS) and conotruncal anomaly face syndrome
(CTAFS). The incidence of this syndrome is estimated to
101
Figure 5: 4D fetal image showing preauricular tag and retrognathia
Figure 6: Karyotype: Tetrasomy 22q
Figure 7: Mosaic trisomy 22q and tetrasomy 22q
Figure 8: Microdeletion of 22q11 region FISH report
102
be at least 1 in 4,0006,000 livebirths, but this might be an

underestimation as many cases with mild features may remain
undiagnosed.2123
In 1965, DiGeorge described a patient with hypoparathyroidism and cellular immune deficiency secondary to thymic
hypoplasia, which was expanded later with inclusion of
dysmorphic feature, 3rd and 4th branchial arch defect.
In 1978, Shprintzen and colleague described VCFS or
Shprintzen syndrome with cleft palate, cardiac defects,
velopharyngeal incompetence and prominent nose. In 1980,
Takao and colleague reported conotruncal anomaly face
syndrome or Takao syndrome with outflow tract defect. It was
subsequently determined that all of them have a deletion of
chromosome 22q11.2. Burn and Goodship20 suggested that a
useful acronym would be CATCH: cardiac defect, abnormal
facies, T-cell deficit due to thymic hypoplasia, cleft palate,
hypocalcemia. Various diagnostic terms have been assigned to
the constellation of features of DiGeorge syndrome including
VCFS, 22q11.2 deletion syndrome, Takao syndrome and
CATCH 22. All of these terms are now acknowledged to
represent variant manifestations of the same entity, as all these
syndromes are caused by the same 22q11.2 microdeletion
(Figure 8) and demonstrate an extensive overlap of phenotypes.
Dysmorphic facial feature were small mouth, retrognathia,
elongated face, narrow palpebral fissure, facial palsy with
squared nasal root and pinched nares (Figures 9A and B). Other
abnormalities include slender hyperextensible fingers, renal
anomaly, hypothyroidism, hearing loss with mild to severe
learning problem. Skeletal differences are possible, including
mild short stature and, less frequently, abnormalities of the
spinal bones. Mortality and morbidity after corrective surgery
for congenital heart defects is higher in these patients than
in those with isolated congenital heart defects. Mortality of 8
percent of cases due to cardiac defect before six months of life
has been reported. Hypotonia in infancy is frequent. Speech
b
Figures 9a and b: DiGeorge syndrome. A. Mother and B. Child
6
b
Figures 10a and b: Children with Williams syndrome
development is often delayed and impaired with almost

always hypernasal voice. Additionally, affected children are
more likely to have attention deficit hyperactivity disorder
(ADHD) and developmental disorders such as autism that
affect communication and social interaction. Hypocalcemia
may present with seizure activity, but responds promptly to
replacement therapy and becomes less apparent with age. The
immune deficit also resolves with time and is often less evident
than in the original case. Later in life, they are at an increased
risk of developing mental illnesses such as schizophrenia,
depression, anxiety and bipolar disorder. A variety of cardiac
malformations are seen particularly affecting the outflow
tract. These include TOF, interrupted aortic arch (IAA), VSD,
trucus asteriosus (TA), right aortic arch and aberrant right
subclavian artery.
This disorder has an autosomal dominant inheritance
pattern. Familial cases of DGS have been described in 6 to 28
percent, but usually DGS occurs sporadicaly and results from
a de novo deletion, which occurs most often as a random event
during the formation of reproductive cells (eggs or sperm) or
in early fetal development 22q11.2 microdeletion.24 Although
the penetrance of a 22q11 deletion is nearly 100 percent, the
severity of the disorders is variable.
WolfHirschhorn Syndrome (OMIM: 194190)

WolfHirschhorn syndrome is due to deletion of the terminal
segment of chromosome 4p (Figures 12A and B). There is
an increased incidence of cleft lip, palate, seizures and heart
disease (30%).
Alagille Syndrome (OMIM: 118450)

Alagille syndrome is characterized by prominent forehead,
deep set eyes, thin nose, butterfly vertebrae, arcus juvenilis
with pulmonary artery stenosis (Figure 13). It is caused by
Williams Syndrome (WilliamsBeuren Syndrome)

(OMIM: 194050)
Williams syndrome was first described in 1961 by Williams
and is characterized by learning disability, malar flattening,
periorbital fullness, heavy sagging cheeks, short nose with
hypercalcemia and supravalvular aortic stenosis (Figures 10A
and B). It is caused by the deletion of the elastin (ELN) gene
from a specific region of chromosome 7q11.23 (Figure 11).
103
Figure 11: Microdeletion at 7q11 FISH report
b
Figures 12a and b: 4p deletion. A. Karyotype report and B. FISH report
the deletion of the JAGGED1 gene from a specific region of

chromosome 20p11.2.
Single Gene Disorder

Noonan Syndrome (OMIM: 163950)
Noonan syndrome was first described in 1962. Children with
this syndrome have specific features such as valvar pulmonary
stenosis (PS), short stature, mild learning difficulties and
dysmorphic appearance (Figure 14). The cardiac disease
seen in this syndrome includes PS, ASD, PDA, VSD and
asymmetric septal hypertrophy. It is caused by mutation of
PTPN11 gene, which is linked to chromosome 12q24.1.
Figure 13: Pulmonary artery stenosis in Alagille syndrome
HoltOram Syndrome (OMIM: 142900)

HoltOram syndrome was first describe by Holt and Oram
in 1960. It is characterized by upper limb defect, narrow
shoulders and cardiac anomaly (Figures 15A and B). Cardiac
anomaly in majority includes secundum ASD with occasional
reports of VSD, AVSD and TA. It is caused by mutation of
TBX5 gene, which is linked to chromosome 12q24.1.
Ellis-van Creveld Syndrome (OMIM: 225500)
104
Figure 14: Hypertelorism, short-webbed neck, and low hairline

in a child with Noonan syndrome
Ellis-van creveld syndrome (EVC), shows skeletal dysplasia

characterized by short limbs, short ribs, postaxial polydactyly,
dysplastic nails, teeth and short upper lip bound by frenule to
alveolar ridge (Figures 16 to 18). CHDs occur in 60 percent
of affected individuals that are diseases of primary atrial
septation; single atrium and hypoplastic left heart syndrome.
It is caused by mutation of EVC gene, which is linked to
chromosome 4p16.
b
Figures 15a and b: HoltOram syndrome familial ASD. A. Child with HoltOram syndrome
and B. X-ray shows clubbed hand, absent radius, hypoplastic 1st metacarpal
Figure 16: Baby with Ellis-van Creveld and polydactyly of hands
Figure 18: Adult showing short upper lip bound

by frenula to alveolar ridge
Kabuki Syndrome (OMIM: 147920)

Kabuki syndrome is caused due to mutation in the MLL2
gene and is characterized by distinct facial anomalies,
variable degrees of mental retardation, CHDs and skeletal
malformation. CHDs occur in 50 percent of affected individual,
which include ASD, VSD, TOF, PDA, transposition of great
arteries (TGA), aortic coarctation, single ventricle with
common atrium and right bundle branch block.
metabolic Disorder
Pompe Disease (OMIM: 232300)
Figure 17: Child with Ellis-van Creveld syndrome
Pompe disease is an inborn error of metabolism and is caused

by an accumulation of glycogen in the lysosome due to
deficiency of the lysosomal acid alpha-glucosidase enzyme.
105
There is accumulation of glycogen in certain organs and

tissues. It is manifested as hypotonia, generalized muscle
weakness, feeding difficulties, failure to thrive, cardiomegaly
and hypertrophic cardiomyopathy.
Zellweger Syndrome (OMIM: 214100)

Zellweger syndrome is characterized by hypotonia, high
forehead, flat facies, hepatomegaly and CHDs like PDA
and septal defect. It is caused by defects in number of PEX
genes.
SmithLemliOpitz Syndrome (OMIM: 270400)

SmithLemliOpitz syndrome is characterized by severe
learning disability, failure to thrive, cleft palate, bitemporal
narrowing, anteverted nares and syndactyly. Fifty percent
will have CHDs like AVSD or ASD. It is due to severe
defect in cholesterol biosynthesis resulting in deficiency
of 7-dehydrocholestrol reductase (DHCR7) gene, which is
mapped to chromosome 11q1213.
GEnES ASSoCiAtED witH CHD

Most of the isolated congenital heart defects do not show
a typical Mendelian inheritance pattern, but as mentioned
earlier a genetic component is very likely to contribute
(Table 1).
NKX25 (omim: 600584) NK2 Homeobox 5/CSX

Homeobox genes have been found to play a crucial
role in regulating tissue specific gene expression. The
cardiac homeobox protein NKX2-5 is essential in cardiac
development and mutations in CSX (cardiac-specific
homeobox which encodes NKX2-5) cause various congenital
heart malformations. The earliest molecule marker of the
cardiac lineage is NKX2-5 in vertebrates. It is one of the
members of NK2 family of homeobox genes and a homolog
of the Drosophila tinman.25 It has highly conserved regions
of DNA binding, protein-protein interactions, nuclear
translocation, and regulation of other transcription factors.
Their homeodomains have a tyrosine at position 54,
making it the most unambiguous feature of this class and
is a useful classification tool.26 Mutations in this gene have
been reported to cause ASD, VSD with atrial ventricular
block, TOF and tricuspid valve abnormalities. Mutations in
this gene can also cause congenital hypothyroidism, nongoitrous type 5, a non-autoimmune condition.27
Turbay and group28 mapped the CSX gene to chromosome
5q35, close to the junction with band 5q34.
Pauli and group29 described a distal 5q deletion, with
karyotype del(5)(q35.1q35.3), in a 7-year-old girl who, in
addition to ASD and PDA, had ventricular myocardial noncompaction. Fluorescent in situ hybridization (FISH) analysis
showed that this deletion included the locus for CSX. Thus,
they suggested that some instances of ventricular myocardial
table 1
Genes causing different types of CHDs with their chromosomal region in humans18
106
Gene
Chromosome locus
Type of defects
CSX / NK-X2-5
5q35
ASD, VSD, AV block, TOF, Ebstein malformation and

Tricuspid valve abnormalities
GATA4
8p2223
ASD,VSD, AVSD, pulmonary valve thickenings
TBX5
12q24.1
ASD, VSD, AVSD,TOF, HLHS, AS
dHAN DeHAND
4q33 and 5q33 respectively
AS
IRX4
5p15.3
SV
JAG GED1
20p12
TOF
Elastin
7q11
AS
TFA P2B
6p12
PDA
Fibrillin
15q21
AA
AA = Ascending aorta; AS = Aortic stenosis; ASD = Atrial septal defect; AV = Atrioventricular; AVSD = Atrioventricular septal defect;
HLHS = Hypoplastic left heart syndrome; PDA = Patent ductus arteriosus; TOF = Tetralogy of Fallot; VSD = Ventricular septal defect
GATA4 (omim: 600576)

GATA4 is a transcription factor which is characterized by a
highly conserved binding domain of two zinc fingers. It is
expressed in the heart and is essential for mammalian cardiac
development, localized to chromosome region 8p23.1. In
mice, germline ablation of the gene encoding GATA4 results

in abnormal ventral folding of the embryo, failure to form a
single ventral tube and lethality. Besides heart development,
GATA4 is involved in the formation of multiple organs, such
as intestine, liver, pancreas and swim bladder in zebrafish
as well as gastric epithelial development in mouse through
interaction with factor of GATA (Fog) cofactors.36 The
mutation in GATA4 gene diminishes DNA-binding affinity
and transcriptional activity. GATA4 is capable of synergizing
with other transcription factors such as NKX2-5, dHAND and
TBX5 to activate cardiac-specific gene expression.
There are published deletions involving chromosome
8p23.1 range from large terminal deletions that are easily
detectable by routine chromosome analysis and small
interstitial deletions that are best identified using FISH or
molecular techniques such as array comparative genomic
hybridization (aCGH). Lubs and Lubs described37 first case
of an individual with a partial deletion of distal chromosome
arm 8p and CHD. Brcker-Vriends and group38 described
two patients with partial monosomy of the short arm of
chromosome 8. The chromosomal abnormality of partial
monosomy of 8p was initially not considered. They stressed
upon the importance of cytogenetic investigations in all infants
with major congenital heart defect and facial dysmorphism or
microcephaly or both.
Devriendt and group39 reported the prenatal diagnosis at
30 weeks of gestation of a del(8)(p21.3pter) in a growthretarded fetus with an unbalanced AVSD and a hypoplastic
right ventricle. Pehlivan and group40 provided evidence that
GATA4 may be involved in the etiology of some congenital
heart defects. They performed FISH analysis using a GATA4
probe on five patients with interstitial deletions of 8p23.1.
Hemizygosity for GATA4 was seen in the four patients with
CHD but not in the patient without known cardiac anomalies.
The authors proposed that haploinsufficiency of GATA4 may
contribute to the CHD observed in some patients with del(8)
(p23.1).
Reddy41 described a case with del(8)(p23.1) in amniocyte
culture with normal cardia. Similar deletion was revealed in
fathers karyotype. The karyotype from the prenatal case was
compared with the previous four cases of 8p23.1 deletions in
his laboratory to see if there was a discernible difference in
the size of the deletion. The deletion in the proband seemed to
involve a more distal 8p23.1 breakpoint. In the father's high
resolution chromosomes (550850 band level), the breakpoint
appeared to be 8p23.1 approximately 23.2 and FISH studies
using an 8p telomeric probe confirmed a terminal deletion.
Interstitial deletion of sub-band 8p23.1 was associated with
phenotypic abnormalities and distal 8p23.2pter deletion
was found in apparently normal individuals, therefore, 8p23.1
appears to be the critical region for clinical abnormalities.
Bhatia and group42 reported the prenatal diagnosis, at 18
week gestational age of a del(8)(p23.1pter) in a fetus with
an AV canal, persistent left superior vena cava and hypoplastic
right ventricle detected by sonographic imaging. Some of the
6
non-compaction may be caused by haploinsufficiency of

CSX. They reviewed four other cases with deletions in the
same region of 5q and pointed out that two of them had atrial
septal defects and one had a cardiomyopathy. Gibbons and
associates30 presented an infant girl with an interstitial deletion
of chromosome bands 5q33 to 5q35 inherited from a maternal
interchromosomal insertion ins(8;5)(p23; q33q35), which was
confirmed by FISH. She had increased tone, microcephaly,
short neck, apparently low-set ears, micrognathia, camptodactyly, mild rocker bottom feet and hammer toe. Cardiac
anomalies included a large VSD, PDA pulmonary hypertension
and hypoplastic right ventricle. Schafer and group31 described
two male sibs with partial monosomy of chromosome 5
[46,XY,der(5)inv ins(1;5)(p32;q35.4q34)]; maternally derived
from a balanced insertion of 1 and 5 [inv ins (1;5)
(p.32;q35.4q34)]. One sibling had microcephaly, cleft lip and
palate, facial anomalies, ASD and VSD, camptodactyly the
4th and 5th fingers and developmental delay. The other sibling
showed microcephaly, facial anomalies, ASD, hypotonia,
primary optic nerve hypoplasia and developmental delay. Both
had only one copy of the cardiac specific homeobox CSX gene.
Schiffer and group32 described a boy with complex heart
defect, club feet, adducted thumbs and facial dysmorphic
features. Karyotype identified an abnormal chromosome 5q
suspected to be an interstitial deletion (5)(q33q35). Breakpoints
of the deleted segment were confirmed as del(5)(q33.3q35.2)
by multicolor FISH using two sets of combinatorially labeled
band specific yeast artificial chromsome (YAC) clones.
Baekvad-Hansen and group33 described a 15-year-old boy
with Ebstein anomaly, ASD, AV conduction defect and
microcephaly. He had an apparently balanced paracentric
inversion of chromosome 5, with the karyotype 46, XY,
inv(5) (q13q35) de novo. Further mapping of the chromosome
breakpoints using FISH revealed a 2.2 Mb microdeletion at
the 5q35 breakpoint, which spans 16 genes, including the
cardiac homeobox transcription factor gene NKX2-5. They
also suggested presence of a new microcephaly locus within a
2.2 Mb region at 5q35.1-q35. 2. Rauch and Dorr34 described a
larger terminal deletions including chromosomal bands 5q35.
1 and 5q35. 2 cause a more severe phenotype significant CHD,
microcephaly, profound developmental retardation or early
death due to respiratory failure. A heart defect is explained by
haploinsufficiency of the NKX2-5 gene at 5q35.1.
Bjrnstad and Leren35 have identified a mutation in the
NKX2-5 gene on chromosome 5q35 responsible for autosomal
dominantly inherited ASD in the oval fossa combined with
disturbances of AV conduction in seven patients spanning four
generations.
107
common features reported with partial monosomy of 8p include

growth and mental retardation, impulsive and aggressive
behaviour, congenital cardiac defects, diaphragmatic hernia
and in males, genital abnormalities. Devriendt and group43
have performed genotype-phenotype correlations in nine
unrelated patients with a de novo del 8p. In five patients, a
uniform interstitial deletion of approximately 6 Mb in 8p23.1
was detected. One patient carried a large terminal deletion
encompassing this commonly deleted region. All these
patients have a similar phenotype, with a CHD, microcephaly,
mild developmental delay, intrauterine growth retardation,
and a characteristic behavioral phenotype. Features that have
been recognized more recently are a characteristic behavioral
phenotype, hypospadias, and seizures.44 The del(8p)
phenotype often is relatively mild, without associated facial
dysmorphism or other major internal malformations.45-47
They defined an 8p heart defectcritical region spanning a
10-cM segment defined distally by D8S1706 and proximally
by D8S1759 and they suggested the transcription factor
GATA4 as a candidate gene.
Giglio and group48 narrowed this region by studying
12 del(8p) patients, including 6 new cases, 7 of whom had
CHDs. Patients with 8p deletions distal to D8S1706, at
approximately 10 cM from the 8p telomere, did not have
CHD, whereas patients with a deletion that included the more
proximal region suffered from the spectrum of heart defects
reported in patients with 8p distal deletions. The 5-cM critical
region is flanked distally by D8S1706 and WI-8327, both at
approximately 10 cM and proximally by D8S1825, at 15 cM.
Second DiGeorge Syndrome locus (DGSii)

(omim: 601362)
108
The DiGeorge syndrome and velocardiofacial syndrome may

present many clinical problems, including cardiac defects,
hypoparathyroidism, T-cell immunodeficiency and facial
dysmorphism. They are frequently associated with deletions
within 22q11.2, but a number of cases have no detectable
molecular defect of this region. Bourrouillou and group49
described a case of monosomy 10p with microcephaly,
antimongoloid slant of the palpebral fissures, low-set ears,
prominent anthelix, congenital heart disease and abnormalities
of the limbs. Schuffenhauer and group50 described a
20-month-old girl with DGS and a monosomy 10p13pter
and a trisomy 10q26qter due to a meiotic recombination of
a maternal inversion (10)(p13q26). The proposita's phenotype
demonstrates typical features of the del(10p) syndrome,
which include mental retardation, abnormally shaped skull,
hypertelorism, low nasal bridge, micrognathia, dysmorphic
low set ears, short neck, foot abnormalities and cardiac defect.
Daw and group51 stated that a number of single case reports
with deletions of 10p suggested genetic heterogeneity of
DGS. They compared the regions of hemizygosity in four
patients with terminal deletions of 10p (one patient with
hypoparathyroidism and three with DGS) and one patient

with VCFS and a large interstitial deletion. FISH analysis
demonstrated that these patients had overlapping deletions at
the 10p13/10p14 boundary. They concluded that the results
strongly support the hypothesis that haploinsufficiency of a
gene or genes within 10p (DGSII locus) can cause the DGS/
VCFS spectrum of malformations.
Schuffenhauer and group52 performed FISH and
polymerase chain reaction (PCR) analyses in 12 patients with
10p deletions, nine of them with features of DGS and in a
familial translocation 10p;14q associated with midline defects.
The critical DGS2 region was defined by two DGS patients
and mapped within a 1-cM interval including D10S547 and
D10S585. The other seven DGS patients were hemizygous
for both loci. The breakpoint of the reciprocal translocation
10p;14q mapped at a distance of at least 12 cM distal to
the critical DGS2 region. Interstitial and terminal deletions
described in these patients were in the range of 10 to 50 cM
and enabled the tentative mapping of loci for ptosis and hearing
loss, features that are not part of the DGS clinical spectrum.
Lichtner and group53 reported a new case with the high
dynamic range (HDR) phenotype: hypoparathyroidism,
deafness and renal dysplasia. They were found to have partial
monosomy for 10p due to terminal deletions with breakpoints
between D10S585 and D10S1720. By comparison with data
previously published on patients with DGS/VCFS associated
with 10p monosomy, they concluded that this is a contiguous
gene syndrome. Hemizygosity for a proximal region can cause
cardiac defects and T-cell deficiency; hemizygosity for a more
distal region can cause hypoparathyroidism, sensorineural
deafness and renal dysplasia.
Berend and group54 tested 412 patients, 54 were found
to be deleted for the DGSI locus on chromosome 22 (13%),
and a single patient was found deleted for the DGSII locus on
chromosome 10 (0.24%). The patient with the 10p deletion
had facial features consistent with VCFS, plus sensorineural
hearing loss, and renal anomalies. Cytogenetic analysis
showed a large deletion of 10p [46, XX,del(10)(p12.2p14)]
and FISH using a 10p telomere region-specific probe
confirmed the interstitial nature of the deletion.
Lichtner and group55 constructed a deletion map of partial
monosomy 10p patients and narrowed the critical region
DGCRII to about 300 kb. The genomic draft sequence of this
region contains only one known gene, BRUNOL3 ( NAPOR,
CUGBP2, ETR3). In situ hybridization of human embryos and
fetuses revealed as well as in other tissues a strong expression
of BRUNOL3 in thymus during different developmental
stages. BRUNOL3 appears to be an important factor for
thymus development and is therefore a candidate gene for the
thymus hypoplasia or aplasia seen in partial monosomy 10p
patients. Many patients with the mild end of the DGS/VCFS
spectrum have been referred to the cytogenetics laboratory
by the physicians for FISH for the deletion on 22q11.2 and
high resolution G-banded analysis has been requested for only
DiGeorge Syndrome locus (omim: 188400; 600237)

Most cases of DGS result from a deletion of chromosome
22q11.2 (DiGeorge syndrome chromosome region or DGCR).
Several genes are lost including the putative transcription
factor TUPLE1 (TUP-like enhancer of split gene-1), which is
expressed in the appropriate distribution. Molecular biology
studies revealed that approximately 90 percent of patients
have a typically selected region of 3 Mb, which encompasses
an estimated 30 genes, whereas about 8 percent of patients
have a smaller nested deletion of 1.5 Mb, which encompasses
24 genes.56
Halford and group57 reported that TUPLE1 gene is an
attractive candidate for the central features of the syndrome.
This putative transcription factor shows homology to the
yeast transcription factor TUP and to Drosophila enhancer
of split. It contains four WD40 domains and shows evidence
of expression at the critical period of development in the
outflow tract of the heart and the neural crest derived aspects
of the face and upper thorax. Lamour and group58 isolated a
cDNA that encodes a protein of 1,017 amino acids, designated
HIRA (histone cell cycle regulation defective, Saccharomyces
cerevisiae, homolog of, A) on the basis of its homology to
the HIR1 and HIR2 transcriptional repressors of S. cerevisiae.
HIRA encompasses the entire TUPLE1 protein with an
additional 207 internal amino acid residues and an extra 44
N-terminal residues, a result of an alternative start codon.
Thus, TUPLE1 cDNA appears to represent a truncated version
of the HIRA cDNA. Demczuk and group59 reported the
isolation and cloning of a gene encoding a potential adhesion
receptor protein in the DGCR. They designated the gene
DGCR2 and suggested DGCR1 as a symbol for the TUPLE1
gene. Haploinsufficiency of the TBX1 gene is also responsible
for most of the physical malformations. There is evidence that
point mutations in the TBX1 gene can also cause the disorder.
De la Chapelle and group60 suggested that DiGeorge
syndrome may be due to a deletion within chromosome 22 or
partial duplication of 20p, based on finding the syndrome in
members of a family with a 20;22 translocation. Specifically,
they observed DGS in four members of one family and
demonstrated monosomy of 22pter-q11 and 20p duplication.
Their interpretation that DGS might result from monosomy for
22q11 was confirmed by Kelley and group61 in three patients
with translocation of 22q11-qter to other chromosomes.
Greenberg and group62 observed partial monosomy due

to an unbalanced 4;22 translocation in a two-month-old male
with type 1 TA and features of DGS. The asymptomatic
mother showed partial T-cell deficiency and the same
unbalanced translocation with deletion of proximal 22q11.
The recognition of the importance of 22q11 deletion grew
with improving techniques. Greenberg and group63 found
chromosome abnormalities in five of 27 cases of DGS, three
with 22q11 deletion though only one of these was an interstitial
deletion. Wilson and group64 reported high resolution banding
(more than 850 bands per haploid set) in 30 of 36 cases of
DGS and demonstrated nine cases of interstitial deletion. All
other cases were apparently normal. Use of molecular dosage
analysis and fluorescence in situ hybridization with probes
isolated from within the deleted area revealed deletion in 21
of the 22 cases with normal karyotypes65 giving pooled results
of 33 deleted among the consecutive series of 35 cases.
Gowde and Patel66 screened families with congenital heart
disease for chromosome 22 microdeletion; of the 105 patients
screened six had microdeletion.
The VCFS has an extremely expansive phenotypic
spectrum. More than 180 clinical features, both physical and
behavioral, have been described. No single clinical feature
occurs in 100 percent of cases and there is no reported case of
the syndrome that has all or even most of the clinical findings.
The phenotype therefore shows markedly variable expression.
The diagnosis is therefore defined by the deletion of DNA from
chromosome 22 at the q11.2 band spanning the region that is
regarded as the critical region. Other molecular genetics tests
will clearly become widely available in the near future, such
as microarray analysis and Multiplex ligation dependent probe
(MLPA), but at the current time, FISH is widely available,
relatively cost effective, and highly accurate.67
Volpe and group68 reported 141 cases of malformations
of the outflow tracts or interrupted aortic arch (IAA) from
1150 prenatal cases of heart defects diagnosed over a period
of 10 years. 22q11 microdeletion was detected in 28 out of
141 fetuses (19.8%). IUGR, additional aortic arch anomalies
and thymic hypoplasia were significantly more frequent in
fetuses with 22q11 microdeletion. Most often, intrauterine
growth restriction (IUGR) appeared to be associated with the
worst prognosis. Prenatal ultrasound thymus examination,
showed 75 percent sensitivity and 94 percent specificity. The
combination of these two predictors, namely, thymus defects
and IUGR associated with additional aortic arch anomalies
was more than 90 percent sensitive and 100 percent specific.
A wide variety of non-cardiac malformations such as overt
cleft palate, renal and limb abnormalities, neural tube defects
and polyhydramnios are identifiable prenatally, and have
been reported to occur in association with 22q11.2 deletion
syndrome.69,70 Few authors have raised the possibility of
considering prenatal 22q11.2 deletion studies in the event
of non-cardiac USG findings. In a recent review on genetic
counseling for 22q11.2 deletion syndrome, McDonaldMcGinn and Zackai71 argued that, such findings lead to
6
those patients with a more severe presentation, although the

most effective method for detecting all possible cytogenetic
abnormalities would be to perform a complete chromosome
analysis along with the FISH studies. Other chromosomal
abnormalities can help in detecting new gene loci similar to
all other genes, which were identified based on chromosomal
abnormality. Even though the deletion on 10p is relatively rare
deletions of DGSI and DGSII result in similar phenotypes,
and hence, it is still beneficial to screen patients referred for
DGS and VCFS for both DGSI and the DGSII loci.54
109
systematic prenatal diagnosis of aneuplodies, the addition

of 22q11.2 deletion studies to standard cytogenetics
should be considered. Similarly, isolated increased nuchal
translucency (NT), a powerful marker of fetal CHD and
aneuploidies or isolated without major CHD do not deserve
deletion testing.72-74 Increased NT, polyhydramnios, IUGR,
pulmonary arterial abnormalities, aortic arch anomalies
and thymic hypo/aplasia were found to be more frequent in
fetuses with deletion.68,75 In a study of 95 fetuses with CHD
in which the status for 22q11.2 deletion was known, Chaoui
and group76 concluded that the marker thymic hypo/aplasia
performed with a sensitivity of 85 percent and a specificity of
97 percent. Bretelle and group77 proposed to take advantage
of these observations to set out guidelines to improve the
prenatal detection of 22q11.2 deletion syndrome in fetuses
with normal hearts (Flow chart 1).
These results suggest that deletion studies could be justified
in fetuses with non-cardiac prenatal USG findings that have
been reported in association with 22q11.2 deletion syndrome.
22q11.2 microdeletion is one of the primary conditions
leading to intrauterine growth retardation and congenital heart
malformation.78 Therefore, high-risk fetuses showing growth
retardation and malformation should receive screening for
22q11.2 microdeletion. FISH test of the key gene TUPLE1 is
still considered the gold standard for the diagnosis of 22q11.2
microdeletion syndrome.79
Indian postnatal studies of chromosome 22 microdeletions
for isolated CHD showed the microdeletion in 6/105
(5.71%)80 and 4/23 (17%)81 patients.
Flow chart 1: Decisional chart proposal for prenatal 22q11.2 testing
according to ultrasound finding (US) and aneuploidy screening tests77
Flow chart 2: Genes on 22q11 and 22q13 regions
Source: Image from Kreatech website
The genetic predisposition to cardiac malformation may be

influenced by in utero environmental or genetic background.
The importance of genetic factors in the cause of congenital heart
defects has been shown by previous studies.82,83 Microdeletion
of chromosomal region 22q11 is an important cause of
selected conotruncal cardiac defects of the heart and account
for about 6.9 to 68 percent of cases.8488 Prenatal diagnosis
of chromosome 22q11.2 microdeletion by FISH analysis was
first reported in 1995.89 Since then, numerous studies have
confirmed the high occurrence of 22q11.2 microdeletion after
prenatal detection of cardiac anomalies.68,77,79 Three genes
namely TUPLE1, TBX1 and N25 are responsible for 22q11.2
deletion syndrome (Flow chart 2).
The prevalence of 22q11.2 microdeltion is more in prenatal
period than the postnatal period.90 Perhaps, this difference
may be accounted for by perinatal death of fetuses/neonates
due to very complex CHD forms and/or low birth weight68 or
termination of pregnancy after detection of microdeletion in
our country.
PrEnAtAl DiAGnoSiS
110
In the literature, transabdominal amniocentesis in the third

trimester has been reported by Prochownick, Von Schatz
and Lambl in 1877 and Schatz in the 1890. The first use of
amniotic fluid examination in the diagnosis of genetic disease
was reported by Fuchs and Riis in 1956, in their seminal
article in Nature. They determined fetal sex from cells
found in amniotic fluid, basing on the presence or absence
of the Barr body.91 The determination of fetal sex led to the
prenatal management of patients with haemophilia A in 1960
and Duchenne muscular dystrophy in 1964. Steele and Breg
Chorionic Villi Sampling

Chorionic villi sampling (CVS) is the removal of a small
part of placenta tissue (chorionic villi) from the uterus. CVS
can be done through the cervix (transcervical) or through the
abdomen (transabdominal) (Figure 19). The techniques are
equally safe, when done by an experienced fetal medicine
specialist, although miscarriage rates are slightly higher when
done through the cervix. Prior to procedure, an abdominal
ultrasound is performed to determine the position of the
uterus, the size of the gestational sac and the position of
the placenta within the uterus. Under aseptic precaution,
the transabdominal procedure is performed by inserting a
needle through the abdomen and uterus into the placenta.
Ultrasound is used to help guide the needle and a small
amount of tissue is drawn into the syringe. Apart from the
risk of miscarriage, there is a risk of infection and amniotic
fluid leakage. Random studies have demonstrated that the rate
of fetal loss following first-trimester transabdominal CVS is
the same as with second-trimester amniocentesis. There is
an association between chorionic villus sampling, before 10
weeks and fetal transverse limb abnormalities, micrognathia
and microglossia. It is therefore imperative that chorionic

villus sampling is performed only after 11 weeks and before
15 weeks by appropriately trained operators.95
Amniocentesis
Amniocentesis is a prenatal procedure, in which small amount
of amniotic fluid, which contains fetal tissues, is extracted
from the amnion or amniotic sac surrounding a developing
fetus. Amniocentesis is performed between the 15 to 20
weeks of pregnancy. Under aseptic precaution, with the aid of
ultrasound guidance, a fetal medicine specialist punctures the
sac in an area away from the fetus and extracts approximately
20 ml of amniotic fluid. Apart from a risk of miscarriage, there
is a risk of infection, injury to the fetus and amniotic fluid
leakage. It is also possible at 10 to 14 weeks of gestation.
However, randomized studies have demonstrated that after
early amniocentesis the rate of fetal loss is about 2 percent
higher and the incidence of talipes equinovarus is 1.6 percent
higher than after first-trimester CVS or second-trimester
amniocentesis. Amniocentesis should not be performed before
15 weeks.95
6
very importantly demonstrated in their seminal paper in the

Lancet in 1966 that cultured, amniotic fluid cells were suitable
for karyotyping.92 The year 1966 is an important milestone
in prenatal diagnosis, as this year saw the introduction of
amniotic fluid cell culture. Geneticists could advise on the
degree of risk and the avoidance of pregnancy, but it was an
evident that genetic counseling had little impact without fetal
diagnosis. The emergence of amniocentesis and amniotic
cell culture for fetal chromosomal and metabolic disorders
in 1966 changed this practice forever.93 In 1974, Hobbins
and Mahoney reported a technique for obtaining fetal
erythrocytes for prenatal diagnosis of hemoglobinopathies.94
Important trends in practice are revealed by the survey, such
as the gradual change from transcervical to transabdominal
chorionic villi sampling from 1982 to 1986.
Cordocentesis
Cordocentesis, also sometimes called percutaneous umbilical
cord blood sampling (PUBS), is a highly specialized prenatal
test that examines blood from the fetal umbilical cord. An
advanced imaging ultrasound determines the location for
needle insertion into the placenta and the needle is guided
through the mothers abdomen and uterine wall into the
fetal vein of the umbilical cord, where a fetal blood sample
is removed. It can be done at 18 week of pregnancy or
later. This test carries a significant risk of complication and
includes blood loss at the puncture site, infection, premature
rupture of membranes and the rate of fetal loss is higher than
amniocentesis.96
Cytogenetics
Figure 19: Transabdominal chorionic vill sampling.

[Reproduced from counseling aids for geneticists, 3rd edn, GGC (1995)]
Cytogenetics is the study of chromosomes, which are carriers

of the gene. A normal human karyotype contains 22 pairs of
autosomes and one pair of sex chromosomes. The year 1956
is considered as beginning of modern human cytogenetics.
Before this the human chromosomes numbers were believed
to be 48 and XX-XY mechanism of sex determination was
assumed to work in same way as it does in Drosophila. Due
to improvement of technique, Tijo and Levan discovered that
human chromosome number is 46. Historians have divided
the discipline of human cytogenetics into five erasthe
dark ages, the hypotonic period, the trisomy period, the
banding era, and the molecular era.97,98
During the Dark Ages(prior to 1952) mammalian
tissue culture techniques were used for arresting cells during
division. The Hypotonic Era(started in 1952 by TC Hsu)
denotes the use of a solution with a lower salt concentration
111
than the cells, it contains. This causes the cells to absorb

water through their membranes and swell (but not burst).
The swollen cells allow the chromosomes to readily separate,
making them easier to count. During the trisomy period:
Cytogeneticists discovered patients with an additional
copy of a small chromosome, e.g. Trisomy 21 (Down
syndrome), Trisomy 13 (Patau syndrome) and Trisomy 18
(Edward syndrome). Numerical abnormalities involving
sex chromosomes (the X and Y chromosomes) were also
described for the first time and such as Turner syndrome
and Klinefelter syndrome. Further advances in technology
led to banding techniques (hence the banding era), which
brought out horizontal bands of differential staining intensity.
The most recent developments in cytogenetics have led to
the molecular era. Advances in the use of DNA probes
have allowed cytogeneticists to hybridize these probes to
chromosomes and determine if a specific DNA sequence
is present on the target chromosome. This has been useful
in detecting abnormalities beyond the resolution level of
studying banded chromosomes at the microscope, and also in
determining the location of specific genes on chromosomes.
Recent advances in cytogenetic techniques made a valuable
contribution toward the practice of modern medicine.97,98
The FISH is a molecular cytogenetics technique that allows
identification and detection of the gene of interest within its
natural environment of chromosomes, cells or tissues. The
basic principle involved in this technique is natural affinity of
base pairing of nucleotide sequences with the complementary
sequences. Pardue and Gall99 reported the hybridization of
radioactive DNA probes for repetitive sequences to mouse
and drosophila chromosomes. In 1981 Harper and Saundres
reported an improved technique for in situ hybridization
allowing detection of unique DNA sequence along human
metaphase chromosome spread.100
The FISH allows rapid analysis of chromosome copy number
in interphase cells of amniotic fluid, chorionic villi, cord blood
and peripheral blood samples. It has been extensively applied
in cancer cytogenetics to confirm various translocations. It is
also used for detection of microdeletion (less than 5 million
base pairs size) syndromes like DiGeorge syndrome, Prader
Willi Syndrome, etc. Various types of FISH probes such as
centromeric, -satellite, locus specific, telomeric, subtelomeric
and whole chromosome painting probes are available.
GEnEtiC CounSElinG
112
Genetic counseling is a communication process to aid people

understand and adapt to the medical, psychological and
familial implications of genetic contributions to disease. This
process integrates the following-interpretation of family and
medical histories to assess the chance of disease occurrence
or recurrence, understanding alternatives for dealing with
recurrence risk, choosing a course of action best suited to the
patient based on their values and family goals and to make
the best possible amendment to the disorder in an affected

member.101
During genetic counseling, emphasis is placed on respecting
the experiences of the patients and/or family and on patient
autonomy in decision making so that an informed decision is
made. A psychotherapeutic component of genetic counselling
is desirable as the occurrence of a genetic condition can have
a family-wide impact and the clinician or genetic counselor
should provide acceptance and empathy, but should never
play God. Genetic counselling should be non-directive,
presenting all information to the patient in a non-judgmental
and neutral approach. This will enable the patient to make a
decision best suited to their situation.
In cases where congenital heart defects are picked up
prenatally, it is important to address the immediate concerns
of the couple. The most important issues to discuss during a
prenatal visit are accuracy of prenatal testing, risks of prenatal
testing, recurrence risks for the couple and family and most
importantly, what to expect, when undergoing prenatal
diagnosis. It is easy to assume what needs to be addressed
during the session, however, it is important to identify
the expectations and issues, the patient is facing. In our
experience, the least important issues during the initial genetic
counselling session with the couple are pregnancy termination
options, discussions as to whether the couple should have
another child and other reproductive options. It is optimum if
these issues are addressed during the follow-up session.
Testing in the form of prenatal diagnosis should be
offered for an etiological diagnosis and its implication in the
management and prognosis of the condition. In cases where
the cardiac defect is not amenable to surgical correction, the
investigations will help in providing information in the form
of recurrence risks for future pregnancies. In developing
countries, where affordability of health care is an issue for
majority of the population, the genetic counselor should be
supportive of the couples decision to undergo termination
of pregnancy, where the long-term prognosis, in absence of
appropriate medical intervention, is poor.
SummAry
Antenatally diagnosed cases of CHD should be investigated
for karyotyping and for 22q11.2 deletion syndrome. Increased
NT, IUGR and other non-cardiac malformations of 22q11.2
deletion syndrome should be screened carefully for thymus
hypo or aplasia and fetal echo for cardiac defects including
vascular ring. Chromosome analysis along with the FISH
studies to be carried out in patients with the DGS/VCFS
spectrum. Other chromosomal abnormalities can help in
detecting new gene loci similar to all other genes, which were
identified based on chromosomal abnormality. Even though
the deletion on 10p is relatively rare deletions of DGSI and
DGSII result in similar phenotypes, and hence, it is still
beneficial to screen patients referred for DGS and VCFS for
ConCluSion
Individual with congenital malformations place a heavy burden
on the society and affected families. Primary prevention of
genetic diseases is emerging as an important area to improve
quality of life and to prevent disease burden. Hence, the
causes of birth defects and developmental disabilities should
be found. The primary focus of antenatal care has been health
of the mother during pregnancy and safe delivery of the child.
Fetal medicine is now emerging as an equally important
component of the antenatal care. Hence, the scope of antenatal
care needs to be enlarged to include fetal health.
The completion of the human genome project has
provided a range and depth of information. It has brought
lot of importance and challenge to understand the genetic
disease. Further challenges include utilizing this information
to improve diagnosis and treatment of children with CHDs.
We need to extend the ability of fetal medicine specialist to
find heart defects as early as possible so that, they can be
treated while the heart is still forming.18 In near future whole
genome sequencing will not only be achievable, but also come
within reach for advanced clinical diagnostic testing. Whole
genome sequencing will generate a lot of new information and
interpreting these results will be difficult. There is a need to
identify approaches and means to translate knowledge into
effective intervention. This information can be translated
through Preimplantation genetic diagnosis (PGD) and gene
therapy. PGD will help in selecting the normal embryos and
prevention of the termination of the pregnancy and physical
and emotional trauma associated with it. Gene therapy will
help in correcting the defect at the gene level.
If someone feels that they never made a mistake in their life,
then it means that they had never tried a new thing in their
life.
Einstein
ACknowlEDGmEnt
We wish to thank Dr I B Vijayalakshmi, Professor of Pediatric
Cardiology, for sharing some of her clinical images.
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6
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Sec t i on
2
Basics
C hapter
Examination of the Heart

A Comparative External
and Internal Anatomy
Pradeep Vaideeswar
Understanding the normal anatomy of the heart forms an

important basis in the diagnosis of various congenital and
acquired diseases of the heart through investigative modalities.
Examination of the external surface of the heart often provides
clues to the inner pathology, which may alter the pattern of
further dissection or operative techniques. The features to

be seen on external examination would be the orientation,
cardiomegaly, appearance of anterior and posterior surfaces,
chamber and vascular morphology and appearance of the
epicardial surface.
ORIENTATION (fIguRES 1A ANd B)
Figure 1A
Figure 1B
Most pathologists or for that matter even anatomists are guilty

of using inappropriate descriptive terms in the gross analysis
as we continue to orient the heart in an upright position like a
valentine heart.
This is the true anatomic position of the heart. The
atrial have an anteroposterior relationship and are fixed
within the thorax by the systemic and pulmonary venous

connections. The axis of the ventricles is tilted laterally
to the left from base to apex, extending anteriorly and
slightly inferiorly; the atrioventricular junction follows the
ventricular orientation.
BAsics
EXTERNAL SuRfACES
Anterior (figure 2)
Figure 2
The anterior surface of the heart shows the right and left atrial appendages (RAA, LAA) and the great arteries (AoAorta,
PT pulmonary trunk) towards the base and most of the right ventricle (RV) and small part of the left ventricle (LV) towards
the apical aspect. The atria and ventricles are separated by their respective atrioventricular grooves that are filled with adipose
tissue (which increase with age and/or weight of the patient). The apex points to the left and is formed by LV. The normal great
arterial relationship is constituted by anterior and left position of PT, relative to ascending aorta. The surface anatomy of left
anterior descending artery (LAD) offers an excellent guide to position of interventricular septum.
Posterior (figure 3)
120
Figure 3
The posterior surface shows body of the atria, right and

left pulmonary veins (RPVs, LPVs), longitudinally placed
coronary sinus, inferior caval vein (IVC), larger portion of LV
and a small portion of RV. It is to be noted that coronary sinus
lies in most of the posterior left atrioventricular groove and
also that all chambers, meet at a common point (*), which is
the crux of the heart.
Right Atrial Morphology (figures 4 and 5)
In the external anatomy, the most characteristic features of the atria are their appendages. The RAA is large and triangular with a
broad base. It is to be noted that the entire anterior atrial wall is formed by the appendage, which is characteristically pectinated.
Figure 5
The caval veins enter the right atrium (RA) at an obtuse angle
or nearly in alignment with superior vena cava (SVC) being
anterior to the IVC. Demarcating the extensively pectinated
appendage from a smooth walled venous component of RA
is sulcus terminalis (dotted line). Important in this area is the
location of sinoatrial or SA node. This is an elliptical structure
(black ellipse), which occupies a lateral position at superior
cavoatrial junction. It sits as a wedge of specialized tissue
subepicardially, not occupying the full thickness of atrial wall.
Rarely, it is disposed in a horse-shoe shape at the junction or
may be discernible to the naked eye.
ExAminAtion oF thE hEArtA compArAtivE ExtErnAl And intErnAl AnAtomy
Figure 4B
Figure 4A
121
Left Atrial Morphology (figures 6 and 7)
BAsics
Figure 6A
Figure 6B
In contrast to RAA, LAA resembles a crooked little finger with crenellations and a distinctive narrow junction with main atrial
chamber. It is located more superiorly than RAA, overlying the left main coronary artery to reach the root of the PT.
122
Figure 7
There is no obvious demarcation between the LA chamber

and the entry of the pulmonary veins. On the posterior aspect,
LA appears like a pillow with veins entering into its corners.
The right upper PV passes behind SVC junction with RA,

while the right lower vein passes behind the intercaval area
(Figure 8A). The left veins enter the LA more superiorly as
compared to right veins (Figure 8B).
Figure 8A
Figure 8B
Figure 9
The above figure 9 shows the relationship of various structures at the base of the heart.
123
Cardiomegaly (figures 10A and B)
BAsics
Figure 10A
Figure 10B
The heart may be small in size, normal or enlarged. The cardiomegaly may be graded as mild, moderate or marked. More
importantly, it is important to assess the chamber or chambers responsible for the change. On the right image, there is mild
cardiomegaly, but there is marked enlargement of the RV so that the interventricular septum (as delineated by LAD, arrows) is
pushed towards the left and even the apex is formed by RV. The epicardial surface is inspected for the presence of increase in
adipose tissue, thickening, tortuosity of coronary vasculature and presence of fluid or exudates.
INTERNAL ANATOMY
Right Atrium (figures 11 to 14)
124
In general, the chambers are described with respect to their

size, texture of endocardium and thickness of their walls. The
atrial chambers possess body, venous component, vestibule
and appendage. The body of RA is virtually non-existent. The
vestibule is part of the cavity above the tricuspid valve.
The atria are separated by the interatrial septum (IAS),
which is obliquely placed. In the postero-superior location,
there is an infolding of the atrial wall, which is filled with
adipose tissue. This is designated as Waterson groove.
In the RA are important landmarks. The true extent of the
IAS is confined to the floor of the fossa ovalis (FO) or the oval
fossa with its muscular anteroinferior rimlimbus FO.
In the venous component are openings of SVC, IVC and
CS. The IVC and CS openings are guarded by their respective
Eustachian and Thebesian valves. These sometimes can be
fenetrated. The smooth-surfaced sinus venarum is delineated
from the rough portion of RAA by the second landmark, crista
terminalis or terminal crest (TC).
Figure 11
Figure 12
The crista terminalis originates from the septal wall and

sweeps like a twisted C. It passes anterior to the opening of
the SVC, descending posterolaterally and then anteriorly to
skirt the right side of the orifice of IVC.
The internal anatomy of RA also provides the landmark of

triangle of Koch, an established guide to the location of the
atrioventricular conduction tissues. The Eustachian ridge
containing the tendon of Todaro forms the posterior border
while the tricuspid annulus (at the attachment of septal leaflet
of tricuspid valve [TV]) forms the anterior border. At the base
of this isosceles triangle is the CS opening and at the apex, the
central fibrous body. Around the apex are present compact and
transitional portions of atrio-ventricular node (AV node). This
pierces the central fibrous body as the penetrating portion.
Despite its position in the center of the heart, the node is an
epicardial structure.
Left Atrium (figure 15)
Figure 13
Figure 14
Figure 15
The distal ramification of TC towards CS is part of the lower

RA wall called flutter isthmus. It is quadrilateral in shape
bordered by the Eustachian valve and Eustachian ridge
posteriorly, tricuspid annulus anteriorly and CS superiorly.
In sharp contrast to RA, the topography of LA is almost

featureless. The pectinate muscles are confined to LAA.
Remaining portion appears smooth with thick pearly white
endocardium. The septal aspect is usually marked by shallow,
irregular pits.
125
Atrioventricular Valves (figures 16 and 17)
BAsics
The atrioventricular valves are described on the basis of their

annuli, commissures, leaflets, chordae and papillary muscles.
Figure 16
The TV has three leaflets: anterior (ATL), septal (STL) and

posterior (PTL) and hence three commissures: anteroseptal,
posteroseptal and anteroposterior. The leaflets are anchored to
the RV endocardium via the chordae tendineae to the papillary
muscles. The anterior group is constant, while the posterior is
usually developed and the medial is occasionally developed.
Ventricles (figures 18 to 22)
Figure 18
The RV is coarsely trabeculated with a thin compact portion

that measures 0.5 to 0.7 cm. The trabeculation extends even
into the outflow tract.
Figure 17
126
The mitral valve (MV) has two leaflets: anterior (AML) and
posterior (PML) and two commissures: anterolateral and
posteromedial. The AML has a greater width and appears a
little tongue-shaped. The subvalvular apparatus is represented
by delicate chords attached to fairly constant anterior and
posterior group of papillary muscles.
Figure 19
The LV is finely trabeculated with a thick compact portion

measuring about 1 cm. The septal surface is smooth and
covered by the thicker endocardium (Measurements: Usually
taken 1 cm below the arterial valves).
The morphology of the RV lends itself to subdivision into

three components. The inlet component extends from
tricuspid annulus to attachments of the tendinous chords. The
trabecular or sinus portion extends from chordal attachments
to apex, while the outlet portion is present beyond the septal
band. The septal band or trabecula septomarginalis (TSM)
is an important landmark in the RV. Note another muscular
band connecting the TSM to the base of the anterior papillary
muscle (APM). This is the moderator band (MB).
Figure 21
Similar subdivisions (inlet, trabecular and outlet) can be

applied to the sigmoid muscular interventricular septum IVS.
Asterisk marks the membranous portion of the IVS. On the
right side, the roof of this septum is formed by attachment of
anteroseptal commissure.
Additional muscular bands are seen in RV

outflow tract. The TSM divides into its anterior
and posterior limbs and assumes a Y shape.
Clasped between the two limbs is the crista
supraventricularis or parietal band connecting
the RV free wall to IVS. Please note that PV is
separated from TV by the ventriculoinfundibular
fold, while the arterial valves are separated by
the outlet septum.
Figure 22
Figure 20
127
BAsics
Arterial Valves (figures 23 and 24)

The arterial valves are described with respect to their annuli,
cusps and commissures. The valves are characteristically
three-cuspid; cusps are semilunar and translucent. The spaces
enclosed by the cusps and proximal artery are sinuses of
Valsalva.
Figure 24
Figure 23
In PV, the cusps are one anterior and two posterior.
The cusps of AV are two anterior and one posterior. The

right and left coronary arteries arise from two anterior sinuses.
Hence, cusps are designated as right coronary cusps (RCC),
left coronary cusps (LCC) and non-coronary cusps (NCC).
A discontinuous ridge, seen above the arterial ostia, is called
as the sinotubular junction. On the left side, the membranous
IVS (asterisk) is sub-aortic and has its roof formed by the
adjoining portions of the RCC and NCC. Also, note that there
is fibrous continuity between the adjoining portions of NCC/
LCC and AML. The AML is called the aortic leaflet of the
MV, while PML is the mural leaflet.
The road to medical knowledge is through the pathological museum

and not through an apothecarys shop.
William Withey Gull
128
C hapter
Classification of Cardiovascular
Anomalies and their Terminologies
Prabhat Kumar, Vijayalakshmi IB
Introduction
Pediatric cardiology and management of congenital heart
diseases has seen a sea of change in the last 75 years. Since
the time Dr Maude E Abbott categorized 1,000 malformed
hearts,1 different systems of classification and nomenclature
have been described. The variation is mainly based on the
importance given by the researcher either to embryogenesis,
atrial sidedness, morphology and position of ventricles and
great arteries or on surgical anatomy. Till date, there is no
uniform system of nomenclature because with the development
of every new classification, newer terms have been added, but
older terms have not been dropped. The need for a commonly
acceptable nomenclature cannot be underestimated. There are
many different combinations of lesions observed in pediatric
cardiology practice where description and an individual place
for them in the classification is a must.
Earlier descriptions and classifications of congenital heart
diseases by Richard Van Praagh and Maria Victoria de la Cruz
were based on topographic arrangement of the atrium, ventricle
and great arteries, thus developing the concept of concordance
and discordance. The concept of detailed description of the
heart has revolutionized and has become more rational, since
the development of cross-sectional echocardiography. The
system of sequential segmental analysis by Anderson et al now
takes into consideration all possible variations of relations, not
only between the two atria, ventricles, great arteries, but also
between the atrioventricular and ventriculoarterial junctions.2
It is important that the system we use for description should
have more clarity and the concept of sequential segmental
analysis appears very appropriate at this time.
Cardiac position in the chest and visceral sidedness is

first defined, i.e. on the left or right side. Each region of the
heart is then evaluated in the direction of blood flow, i.e.
beginning with systemic and pulmonary blood flow, both
atria, atrioventricular valves, ventricles, semilunar valves and
great arteries. It is not as simple as it looks on description.
To diagnose the simplest lesions to the most complex
lesions, all the chambers of the heart are to be recognized by
their morphological features rather than according to their
position, e.g. morphological left atrium in a normal heart can
be identified by pulmonary veins, while a right-sided atrium
will have systemic veins draining into it, but that is not the case
in malformed hearts. In case of total anomalous pulmonary
venous connection, left atrium has to be identified by the
other constant morphological features such as appendicular
morphology. Similarly, ventricles are identified based on their
trabecular pattern, attachment of the valve leaflets, etc. Great
arteries are identified based on their branching patterns. Apart
from the identification of individual chambers, their relations
with each other is to be identified. The major abnormality in
several cardiac malformations is that the cardiac chambers are
not present at their anticipated locations. Thus, each chamber
has to be identified on the basis of their morphological features
and then they are to be described as morphologically left or
morphologically right, irrespective of their locations. Term
single is applied to a chamber or valve when the corresponding
contralateral structure is totally absent, while the term common
is used when bilateral components are present, but septation
is absent, e.g. tricuspid atresia with single inlet ventricle,
common atrium, etc. Cardiac chambers are largely defined by
the anatomic landmarks on septal surfaces.
Sequential segmental analysis
SITUS
In this system of analysis, heart is considered a segmented

structure represented by three building blocks or regions, i.e.
atria, ventricles and great arteries. Each region is partitioned
into a left-sided component and a right-sided component.
The situs or sideness or position, applies to structures/organ

systems that are not bilaterally symmetric. It describes the
position of the cardiac atria and viscera in the system. The
visceroatrial situs refers to the position of the atria in relation
Basics
to the nearby anatomy (including the stomach, liver, spleen,

and bronchi).3 Three different anatomic configurations may
be observed: situs solitus (normal), situs inversus (inverted
or mirror image of normal), or situs ambiguous (ambiguus).
Situs solitus is the normal anatomic configuration, with
the right atrium and the larger lobe of the liver on the right
side; the left atrium, stomach, and spleen on the left side.
There is a right-sided trilobed lung and a left-sided bilobed
lung (Figure 1A). The morphologic right bronchus is short,
wide and its first branch is eparterial (bronchus is above the
right pulmonary artery). The morphologic left bronchus is
long, thin, curved and is hyparterial (bronchus is below the
left pulmonary artery).
Situs inversus is an exact inversion of anatomic configura
tion that is seen in situs solitus (Figure 1B). The morphologic
left atrium is to the right of the morphologic right atrium and
the larger lobe of the liver is on the left, the stomach and spleen
are on the right side of the body. The left lung is trilobed with
an eparterial bronchus and the right lung is bilobed with a
hyparterial bronchus. The atrial situs always corresponds to
the visceral situs with situs solitus and situs inversus.
Situs ambiguous is when the situs is uncertain. It is
neither situs solitus nor inversus. Situs ambiguous may
manifest with various abnormal visceroatrial configurations
that are associated with extracardiac anomalies (e.g. splenic
abnormalities, biliary atresia, and intestinal malrotation) as
well as cardiac anomalies. Two subsets of situs ambiguous are
well recognized: right isomerism (asplenia) and left isomerism
(polysplenia). In right isomerism, bilateral trilobed lungs,
a large symmetric liver, absence of the spleen (Figure 1C),
and total anomalous pulmonary venous return are frequently
observed. Left isomerism is usually indicated by bilateral
bilobed lungs (Figure 1D), interruption of the inferior vena
cava, multiple spleens (Figure 2) and pulmonary veins that
A
130
drain into both right and left atrium.3 In situs ambiguous the
stomach can be either on the left, right or in the midline.
Morphological features of various

cardiac chambers
Atria
Each atrium has three components, i.e. an appendage, a
venous component and a septum, which separates the two
atria. The appendage, because of its characteristic external
features distinguishes the morphological right and left atrium.
The appendage is the only component, which is universally
present to determine the type of atrium. The appendage of the
right atrium is triangular with a broad base. Internally, right
atrium has numerous pectinate muscles and a terminal crest
(crista terminalis). Left atrium has a pyramidal or fingershaped, small appendage with several lobes. The main body
of the left atrium is smooth walled.
In situs solitus, i.e. the left atrium is on the left of the right
atrium. If there is a mirror image of this arrangement, it is
called situs inversus. Rarely, the atria and appendage do not
have such lateralization and the two appendages are mirror
image of each other, thus both the appendages are either
morphologically left type or of right type. It is important to
note that the morphology of the appendages is closely related
to the arrangement of the thoracic and abdominal organs.
Atrial isomerism is thus a part of heterotaxy syndromes in
which lungs and atria have isomerism, while the abdominal
structures are jumbled up. Generally, isomerism of left atrial
appendage is associated with polysplenia, interrupted inferior
vena cava, while right atrial isomerism is associated with
absence of spleen. Though these associations are common,
they are not the rule. Structure of the appendages, atria,
Figures 1A to D: Schematic diagram showing the various characteristic features of different types of thoraco-abdominal situs:
A. Situs solitus; B. Situs inversus; C. Right isomerism; D. Left isomerism
Great Arteries
Figure 2: Coronal image of computed tomographic angiogram in a

2-year-old girl with left isomerism shows bilateral long, thin, curved
left bronchus (2 black arrows) with polysplenia indicated by 3 white
arrows. (Image courtsey: Dr Madhav Hegde)
visceral situs and orientation of the vessels at the diaphragm

should be clearly defined.
Ventricles
Normal ventricle has three parts: inlet, trabecular and outlet.
Inlet portion has the atrioventricular valve, its tension apparatus
including the papillary muscles. Trabecular portion extends
from the papillary muscles to the apex. Outlet portion is the part
of ventricle from apex to the valves leading to the great vessels.
Trabecular portion of the ventricles differentiates the two
ventricles for identification. The right ventricle has coarse
trabeculations whereas left ventricle has got fine trabeculations
and is smooth walled.
Atrioventricular valves always go with the ventricles, i.e.
tricuspid valve will always be with the right ventricle and
mitral valve with the left ventricle. Identification of valves
helps in defining the morphology of the ventricle. Tricuspid
valve is identified by typical attachment of the septal leaflet
to the interventricular septum. Mitral valve does not have any
attachment to the septum. Its anterior and posterior leaflets are
attached with the two papillary muscles within the ventricle.
At the atrioventricular level, tricuspid valve is positioned
more closer to the apex in comparison to the mitral valve.
This feature is very well-defined in the four chamber view of
echocardiography.
Two great arteries, i.e. aorta and pulmonary artery normally

arise from the left and right ventricles respectively. Valves of
these vessels cannot be differentiated by their structure. The
vessels are identified by their branching pattern. Aorta as it
ascends, gives rise to three branches from the arch, while the
main pulmonary trunk bifurcates early into two pulmonary
arteries. Aortic sinuses are also identified by recognizing
the origin of the coronary arteries from them. The problem
comes when only one arterial trunk is identified. It could be
due to atresia of one of the major great vessels, i.e. aortic
atresia or pulmonary atresia. Common arterial trunk or
truncus arteriosus is defined as the vessel which arises from
the ventricle and has a common arterial valve. It supplies the
coronary, systemic and pulmonary arteries directly. In one of
the types of truncus (type IV), the pulmonary trunk is absent
and the pulmonary blood supply comes from the collaterals
arising from the descending aorta. Such a type of arterial trunk
is called solitary arterial trunk.4
The characteristic differentiating features of right and
left atrium, ventricles and the two great arteries are given in
Box 1.5
8
Classification of Cardiovascular Anomalies and their Terminologies
When the morphologic right ventricle is on the right side

of the morphological left ventricle, the bulboventricular loop
is defined as D (dextro) loop. When the morphological
left ventricle is on the right side of the morphological right
ventricle, it is l (levo) loop. The cardiac apex pivots to the
hemithorax opposite to the bulboventricular loop. Hence,
when there is atrioventricular concordance; with situs solitus
and D looped ventricles, the apex goes to the left hemithorax
and with situs inversus and l looped ventricles, the apex
goes to the right hemithorax. When there is atrioventricular
discordance, the apex is facing downwards. The convexity of
the aorta points towards the morphological right ventricle.
Atrioventricular Junction and

Atrioventricular Valves
Atrioventricular junction is the union of atrium and ventricle
and its analysis will involve atrial arrangement with respect
to left and right atrium, their connections to ventricles
and morphology of the valves. Morphological left and
right atrium in respect to each other may be lateralizedmeaning morphological left atrium is located to the left and
morphological right atrium is on right side or they could be
mirror image, where they are located on opposite sides or
there may be isomerism.
The atrioventricular valve is formed of fibrous tissue and
connects the atrium to the ventricle. Valves tend to travel
along with their respective ventricles, thus tricuspid valve will
always be present with the morphological right ventricle and
mitral valve will always be with morphological left ventricle.
If morphological left atrium is connected to the morphological
131
Basics
Box 1: Morphological features of various cardiac chambers and great arteries

Atria
Right atrium
Left atrium
Appendage
Triangular
Finger-like
Appendageal orifice
Wide
Narrow
Sulcus and crista terminalis
Yes
No
Pectinate muscles
Extend to atrioventricular junction
Do not extend to atrioventricular

junction
Fossa ovalis with limbus
Yes
No
Right ventricle
Left ventricle
Trabeculation
Heavy and irregular
Fine and relatively regular
Trabecular septomarginalis
Yes
No
Moderator band
Yes
No
Septal attachment of the atrioventricular

valve
More apical
More basal (cranial)
Chordal attachment to the IVS
Yes
No
Aorta
Main pulmonary artery
Course
Long arching
Branching
Branches
Origin of coronary arteries

Cephalic and other systemic arteries
Pulmonary arteries
Ventricles
Great Arteries
IVS = Interventricular septum
132
left ventricle then this connection is called concordant, while

if this connection is inappropriate, means left atrium is
connected to the morphological right ventricle and vice versa,
it is called discordant.6
The morphology of atrioventricular valves should be
defined well. One of the two atrioventricular valves may be
absent, while in another situation there can be overriding and
straddling. Both straddling and overriding are associated with
ventricular septal defects. In straddling, the atrioventricular
valve has part of its chordal apparatus attached across the
ventricular septum into the other ventricle, while in overriding
only the opening of the valve sits across the septal crest.
Malformed hearts where both the atria connect with only
one ventricle is categorized under univentricular connections.
Most of such cases have two ventricles, but only one ventricle
is of normal size and has inlet, body and outlet components.
In such cases, the other ventricle is hypoplastic and usually
lacks the inlet portion. Larger ventricle may be morphological
right ventricle or morphological left ventricle and respectively
named as double-inlet right ventricle or double-inlet left
ventricle.
Similarly in the group of univentricular connections, one
of the atrioventricular valve may be atretic and thus one of
the atria is not connected with the ventricle. Thus, the term
tricuspid valve atresia and mitral valve atresia has evolved

for malformed hearts where one of these valve is atretic. In
such univentricular hearts, the corresponding ventricle, i.e.
in tricuspid atresia, right ventricle or in mitral valve atresia,
the left ventricle may be hypoplastic. The connection can be
discordant also in cases where the atrium can be connected
to a dominant left or dominant right ventricle. Rudimentary
ventricles are usually malformed and their morphology
is defined by explaining the morphology of the dominant
ventricle. Thus, if the dominant ventricle is morphologically
left ventricle, hypoplastic ventricle will be the right ventricle
only.
Ventriculoarterial Junction
Ventriculoarterial junction is the junction of ventricles and
arterial segments, where the connections could be concordant
or discordant. Concordant connection is when the aorta is
arising from the left ventricle and the pulmonary trunk is
arising from the right ventricle. Discordant connection is
when these vessels are arising from the opposite ventricles.
Transposition is a term used when the great vessels have
discordant connection with regard to the ventricle. The
combination of concordant atrioventricular connection and
8
Figure 3: Types of human heart: segmental sets and alignments. Heart diagrams are viewed from below, similar to a subxiphoid twodimensional echocardiogram. Cardiotypes depicted in broken lines had not been documented when this diagram was made. The aortic
valve is indicated by the coronary ostia; the pulmonary valve is indicated by the absence of the coronary ostia. Braces { } mean the set
of. The segmental sets are explained in the text. Rows 14 and 6 have ventriculoarterial (VA) concordance. Row 5, transposition of the
great arteries, has VA discordance. Rows 7 and 8 have double-outlet RV and LV, respectively. Columns 1 and 3 have atrioventricular
(AV) concordance, {S, D, -} and {I, L, -}, respectively. Columns 2 and 4 have AV discordance, {S, L, -} and {I, D, -}, respectively. Ant
= Anterior; Inf = Infundibulum; L = Left; LA = Morphologically left atrium; LV = Morphologically left ventricle;. Post = Posterior; R = Right;
RA = Morphologically right atrium; RV = Morphologically right ventricle; (Courtesy: From Foran RB, Belcourt C, Nanton MA, et al. Isolated
infundibuloarterial inversion {S, D, I}: a newly recognized form of congenital heart disease. Adapted from Am Heart J 1988;116:13371350, with
permission)
133
Basics
134
discordant ventriculoarterial connection gives rise to complete

transposition of great vessels. The combination of discordant
connection at atrioventricular junction and discordant
ventriculoarterial connection (double discordance) gives rise
to congenitally corrected transposition.
When both the great arteries arise from one ventricular
chamber, the ventriculoarterial connection is considered
as double outlet. It can be from right ventricle or from left
ventricle.
Morphology of ventricular outflow tract is different in
left and right ventricle. Right ventricular outflow tract has
muscular infundibulum, while there is fibrous continuity
between the arterial and atrioventricular valve in the left
ventricle.
The spatial relation of both the great vessels to each other
also needs to be defined. Two trunks usually have spiral
relation, but can be parallel to each other in transposition
physiology. Anteroposterior and right-left relation of aortic
and pulmonary valves to each other also requires to be defined,
as this would help in surgical management.
Complete transposition of the great arteries in an abbreviated

form can be described as (S, D, D ), i.e. S = situs soilitus,
D = D loop, D = D transposition. Similarly, after segmental
analysis, all types of segmental connections can be described
in an abbreviated form (Figure 3).9 It is important that the
description of complex cardiac anomalies in whatever way we
do, should be easier to understand and describe.
SEGMENTAL TERMS DEFINED AS ABBREVIATIONS
Conclusion
The segmental terms can either be defined in full or can be

written as abbreviations.7 The types of visceroatrial situs
are solitus (S), inversus (I), or ambiguous (A). The types of
ventricular situs are solitus or D-loop ventricles (D), or inverted
or L-loop (L). The types of great arterial situs are solitus (S),
as in solitus normally related great arteries and inversus (I)
as in inverted normally related great arteries. When the great
arteries are abnormally related, the right sided (dextro or D)
location of the aortic valve relative to the pulmonary valve
is symbolized as D and the left-sided (levo or L) location of
the aortic valve relative to the pulmonary valve is symbolized
as L. D-malpositions of the great arteries are considered to
be solitus or non-inverted malpositions, the aortic valve
normally being right-sided in situs solitus. L-malpositions of
the great arteries are considered to be inverted or mirror image
malpositions because the aortic valve is left-sided relative to
the pulmonary valve, as in situs inversus totalis. In anterior or
A-malpositions of the great arteries, the right-left location of
the aortic valve (directly anterior to the pulmonary valve) is
equivocal (neither right nor left). Hence, A-malpositions may
be regarded as of uncertain situs (situs ambiguous of the great
arteries).8
For example, a normal heart without abbreviations can
be defined as: situs solitus of the viscera and atria, D loop,
solitus normally related great arteries. In an abbreviated
form it will be represented as (S, D, S), i.e. S = situs solitus;
D = D loop; S = solitus normally related great arteries. A
mirror image dextrocardia or an inverted normal heart in an
abbreviated form will be described as (I, L, I), i.e. I = inversus,
L = L loop, I = inverted normally related great arteries.
In routine practice, most of the hearts with congenital

heart diseases will have usual location in the chest, the
chambers will have normal relationships with concordant
atrioventricular and ventriculoarterial connections. Still in
all patients without making any assumptions, analysis should
be made by segmental approach so as to make detailed and
correct anatomical delineation without missing any defect.
Segmental analysis is quite helpful and is the most accepted
method of analyzing complex cardiac defects in detail, which
is understood by all concerned. This method overcomes the
older controversial nomenclature in most of the situations thus
making description much simpler and practical.
Defining the associated malformations

Sequential segmental analysis defines the chambers of the
heart and the connections of various segments of the heart,
but many a times, associated malformations are the ones
who have a major impact on the clinical presentation.10
Apart from defining the position of the heart in the chest and
defining the apex pointing to left or right, pulmonary venous
anomalies, various types of atrial septal defects, anomalies of
atrioventricular valves, ventricular septal defects, anomalies
of aortic arch and coronary anomalies, etc. They also require
to be defined well for complete diagnosis and management.
Science is the systematic classification of experience.

George Henry Lewes
References
1. Abbott ME. Atlas of congenital cardiac disease. New York:
American Heart Association. 1936.
2. Anderson RH, Becker AE, Freedom RM, et al. Sequential
segmental analysis of congenital heart disease. Pediatr Cardiol.
1984; 5(4):281-7.
3. Lapierre C, Dry J, Gurin R, Viremouneix L, Dubois J, Garel
L. Segmental approach to imaging of congenital heart disease.
Radiographics. 2010; 30:397-411.
4. Ho SY. Cardiac morphology and nomenclature. In: Diagnosis
and Management of Adult Congenital Heart Disease
Philadelphia: Elsevier; 2011, pp. 5-13.
5. Yoo Sj, MacDonald C, Babyn P. Sequential segmental
approach to congenital heart disease. In: Chest Radiographic
Interpretation in Pediatric Cardiac Patients, 1st edition. Yoo Sj,
JF, Lock JE, Fyler DC (Eds). Nadas Pediatric Cardiology. 2nd

edition. Saunders, Pennsylvania. 2006, pp.39-46.
9. Foran RB, Belcourt C, Nanton MA, et al. Isolated
infundibuloarterial inversion {S, D, I}: a newly recognized
form of congenital heart disease. Am Heart J. 1988; 116:
1337-50.
10. Anderson RH. Terminology. In: Anderson RH, Baker EJ,
Macartney FJ, Rigby ML, Shinebourne EA, Tynan M (Eds)
Pediatric Cardiology, 3rd edition. Philadelphia, Churchill
Livingstone; 2010, pp.3-16.
8
MacDonald C, Babyn P (Eds). Thieme Medical publishers,

New York, 2010, pp. 22-30.
6. Edwards WD. Classification and terminology of cardiovascular
anomalies. In: Moss and Adams Heart Disease in Infants,
Children, and Adolescents: Including the Fetus and Young
Adults, 7th edition. Lippincott Williams and Wilkins; 2001,
pp. 118-39.
7. Van Praagh R. Terminology of congenital heart disease.
Glossary and commentary. Circulation. 1977; 56:139-43.
8. Van Praagh R. Segmental Approach to Diagnosis. In: Keane
135
C hapter
Cardiac Malpositions
Sejal Shah
Cardiac malposition is defined as the location of the heart

anywhere other than its usual position in the left hemithorax
or location of the heart in the left hemithorax when other
organs are in an abnormal position such as situs inversus.
Cardiac malpositions include dextrocardia, mesocardia,
isolated levocardia, pericardial defects and ectopia cordis.
Dextrocardia
Incidence
Dextrocardia is defined as a right-sided heart with a base
apex axis directed rightward resulting from a variation in
cardiac development and not used as a general term indicating
any heart in the right chest.1 The malposition is intrinsic
to the heart and not caused by extracardiac abnormalities.
Dextrocardia should be differentiated from secondary cardiac
dextroposition, which is defined as displacement of the heart
to the right secondary to extracardiac causes such as right lung
hypoplasia, right pneumonectomy or diaphragmatic hernia.2
Dextrocardia occurs in approximately 0.01 percent of live
births1 and 0.008 percent of pregnancies.3 In a retrospective
review of all cases of dextrocardia, the number of cases of
situs solitus, situs inversus and isomerism were found to be
similar.3 Cardiac malformations were more common in the
situs solitus (96%) and isomerism group (100%) compared
to situs inversus group (25%).3 Cardiac malformations were
complex in the situs solitus and isomerism groups.3
Types
1. Dextrocardia mirror image: This is true dextrocardia
occurring with abnormal situs (situs inversus or ambiguous),
most common of which is situs inversus totalis.
2. Dextroversion dextrocardia: This type of dextrocardia
occurs with situs solitus. Here, the cardiac apex fails to pivot
to the left and the heart appears to have twisted to the right.
The morphological right atrium is to the right and morphological left atrium is to the left or the morphological right
atrium is to the right and posterior and the morphological
left atrium is to the left and anterior, hence the term situs
solitus, pivoted is used.2 The morphological left ventricle
is relatively anterior and right ventricle lies to the right. It
is frequently associated with atrioventricular discordance.
Embryology
At 22 to 23 days of gestation, the primitive cardiac loop normally
bends towards the right forming a D-loop (the morphological
right ventricle is to the right of morphological left ventricle)
(Figure 1A). During the next 10 to 12 days, the apex of the
heart gradually migrates from the right side of the thorax to its
normal location in the left hemithorax. Lack of this normal left
ward migration of the cardiac mass explains the development
of dextrocardia with situs solitus (dextroversion). Conversely,
in situs inversus with L-loop (Figure 1B), the apex of the heart
swings from the left hemithorax to the right, which explains
the development of dextrocardia with situs inversus. Failure of
the shift of the apex of the heart to right hemithorax in L-loop
can result in the development of levocardia with situs inversus
(levoversion). If the shift of the apex remains incomplete, it
results in mesocardia.
Incidental detection is common with mirror image dextrocardia in normal intracardiac anatomy on chest X-ray done as
a screening test or for other medical disorders. In rest of the
situations, the intracardiac anatomy would decide the type of
presentation.
Physical appearance: Poland syndrome is reported with
situs solitus dextrocardia. It has absence of a pectoralis major
muscle, ipsilateral syndactyly, brachydactyly and hypoplasia
of a hand.4 Goldenhar syndrome is reported with complete
9
Figures 1A and B: A. The primitive heart tube normally loops to the right forming a D-bulboventricular loop, which is associated with heart being
in the left hemithorax; B. If the loop is to the left, it results in a L-bulboventricular loop where the apex of the heart swings from the left thorax to
the right. LA = Left atrium; LV = Left ventricle; RA = Right atrium; RV = Right ventricle
situs inversus, which is characterized by oculoauricular

vertebral dysplasia and hemifacial microsomia.5
On examination, check for chest asymmetry with right
chest bulge. On percussion, gastric tympany, hepatic dullness
and cardiac dullness will give a clue about the dextrocardia
and situs. On auscultation, if prominent sounds are in the right
anterior hemithorax compared to the left, suspect dextrocardia.
Investigations
Chest Roentgenogram
Before reading the chest X-ray, it is important to check the
marker (L or R). Chest X-ray is useful in demonstrating the
position of the heart, location of liver and stomach to determine
the visceral situs (Figures 2A and B). It is important to check
for a curvilinear shadow in the right lung resembling scimitar.
Secondary dextroposition can be suspected if the right lung
appears hypoplastic (Figure 2C).
Electrocardiogram
It will show the P vector directed leftward and inferiorly in
situs solitus of the atria and rightward in situs inversus. In situs
inversus with dextrocardia (mirror image), there is reversal
of the QRS pattern in lead aVR and aVL. Hence, the major
QRS is negative in lead one and aVL. The septal q waves
depend on the looping of the ventricles in dextrocardia. The
frontal QRS axis has a right ward shift or right axis deviation.
In left precordial leads, a gradual reduction in the height of
the R-wave voltage in QRS complex (Figure 3A). Hence, it is
necessary to obtain additional right precordial leads (V3R to
V6R) (Figure 3B).
Echocardiography
This non-invasive and convenient technique would be the
gold standard to determining the type of dextrocardia, the
intracardiac anatomy and physiology.
It is important to start the examination from subcostal
view.6 The segmental approach will enable us to understand
the cardiac position and the anatomy of major cardiovascular
segments (visceral situs, atrial situs, ventricular looping and
relationship of great arteries).
Cardiac Position and Base to Apex Axis

When the heart is located in the left chest, right chest or
midline, it is said to have levoposition, dextroposition or
mesoposition respectively. When the cardiac axis (from base
to apex) is oriented to the left, right or inferior, it is levocardia,
dextrocardia or mesocardia respectively. This base to apex
axis is best defined by subcostal view (Figures 4A to C).
Subcostal 4-chamber view, when the cardiac apex is to the
right of midline, major axis of the heart is aligned from the
left shoulder to right hip, the morphological right atrium is to
the right of morphological left atrium (atria are in their normal
position or shifted slightly to the right) it is dextroversion.7
When the major cardiac axis is between the left shoulder
and the right hip, with the cardiac apex in the right fifth or
sixth intercostal space at anterior axillary line and the right
atrium is to the left of left atrium, it is dextrocardiasitus
inversus.7 Though the major cardiac axis in dextroversion
and dextrocardia situs inversus is the same, the angle is
more shifted to the right in dextrocardia situs inversus. In
dextroposition, though the heart is shifted to the right of
midline or in the retrosternal area with morphological right
137
Basics
atrium to the right of morphological left atrium, the major axis

of the heart is normal, to the left.
The position of the transducer is important to obtain the
apical and parasternal views. For dextrocardia situs inversus,
the apical view is obtained by putting the transducer in the
right fifth/sixth intercostal space in the anterior axillary line
with the plane of sound oriented in a similar way as subcostal
4-chamber view (Figures 5A and B). At the right secondthird intercostal space, the plane of sound is oriented from
the left shoulder to the right hip for parasternal long axis view
and parasternal short axis from right shoulder to the left hip
(Figures 5C and D). With dextroversion, the apical view is
obtained by placing the transducer usually just to the right
of the sternal border. The parasternal long axis is done with
the plane of sound oriented in the mirror image direction of
normal just to the right of sternum. The parasternal short axis
is obtained with the normal orientation of the plane of sound
as the atria are positioned normally and the great arteries arise
normally from the ventricles. For dextroposition, the apical
and parasternal views are obtained just to the right of the
sternal border with the usual orientation of the plane of sound
summarized in Table 1.
Associated Intracardiac Abnormalities
138
Figures 2A to C: Chest roentgenogram showing the apex of heart

to the right side of chest. A. With the liver on the right, indicating
dextrocardia with situs solitus. Note that the lung fields are oligemic;
B. With a midline liver, indicating dextrocardia with situs ambiguous;
C. With the right lung hypoplastic and shift of trachea to the right side,
likely dextroposition
1. Intracardiac abnormalities are common in dextrocardia

situs solitus. 70 percent of these patients have associated
congenital heart diseases including ventricular septal
defect (VSD), atrial septal defect, coarctation of aorta,
anomalous pulmonary venous connections and complete
atrioventricular septal defect.8 When associated with
atrioventricular and ventriculoarterial discordance, the
incidence of associated congenital heart diseases is high
and it includes ventricular septal defect, pulmonary
stenosis, double outlet right ventricle, double inlet left
ventricle with smallish morphological right ventricle
giving rise to aorta, pulmonary atresia, common
atrioventricular septal defect, mitral atresia, Ebstein
anomaly of tricuspid valve and anomalous systemic
pulmonary venous connections.8-10
Scimitar syndrome is uncommon, but a welldescribed entity. The diagnosis of Scimitar syndrome
rests on the demonstration of partial anomalous
pulmonary venous return (scimitar vein) of usually the
right lung (entire or the lower portion) to the inferior
vena cava.11 It is associated with abnormal right lung
lobation and right lung hypoplasia (virtually 100%, with
widely varying degrees of hypoplasia); dextroposition
of the heart; hypoplasia of the right pulmonary artery
(60%); systemic arterial blood supply to the right lower
lung from the infradiaphragmatic aorta (60%); secundum
ASD (40% overall, 8090 % in the infantile variant);
right-sided diaphragmatic hernia (15%) and horseshoe
lung. The infantile Scimitar syndrome, in addition to its
9
B
Figures 3A and B: Electrocardiogram in a 8-year-old with situs inversus, dextrocardia. A. P wave is negative in lead one and aVL and upright
in lead aVR with absent R wave progression in left precordial leads; B. Right precordial leads show the progression of the R wave
Figures 4A to C: Subcostal 4 chamber view on echocardiogram showing. A. The apex of heart to the left side indicating levocardia; B. The
apex of heart to the right side indicating dextrocardia; C. The apex of heart appears to be in the midline with vertically positioned interventricular
septum, which is characteristic of mesocardia
high incidence of ASD, has an association with a litany

of cardiovascular anomalies including ventricular septal
defect, patent ductus, hypoplastic aortic arch, coarctation,
tetralogy of Fallot, anomalous origin of the left coronary
artery and truncus arteriosus.11
Scimitar syndrome can present in infancy with severe

symptoms, i.e. respiratory distress and severe pulmonary
arterial hypertension and has worse prognosis or can
present in older children with recurrent respiratory tract
infections and a murmur.
139
Basics
D
Figures 5A to D: Shows probe positions for mirror image dextrocardia. A. Subcostal 4 chamber view is done in the conventional way;
B. Apical view is obtained by placing the transducer on the right side of chest, in fifth or sixth intercostal space near the anterior axillary line with
the plane of sound directed in a similar way as subcostal 4 chamber; C. Parasternal long axis view is obtained at the right second-third intercostal
space, the plane of sound is oriented from the left shoulder to the right hip; D. Parasternal short axis has the plane of sound from right shoulder
to the left hip and is obtained by rotating 90 clockwise from parasternal long axis view
140
Table 1
Clues to differentiate types of dextrocardia on echocardiogram

Dextroposition
Dextroversion
Dextrocardia
RA, RV on right
side of LA, LV
RA, RV on right
side of LA, LV
LA on the right of
RA
Isolated levocardia
Major axis of heart

pointing left
Major axis of heart

from left shoulder
to right hip
Major axis of heart

from left shoulder
to right hip
Entire heart to
right of midline/
retrosternal
Apex to right of
midline
Apex in right fifth

intercostal space
Transducer to right,
usual orientation of
plane
PLAX plane in
mirror image,
PSAX normal
orientation
PLAX and PSAX in

mirror image
When there is situs inversus or heterotaxy with levocardia,

it is considered a malposition. Isolated levocardia is rare.
The morphological right atrium is to the left and posterior
and the morphological left atrium is to the right and anterior,
hence the term situs inversus, pivoted is used.2 Most of these
cases have been found to have atrioventricular discordance,
ventriculoarterial discordance or double outlet right ventricle
and right anterior aorta.8,18
LA = Left atrium; LV = Left ventricle; PLAX = Parasternal long axis view; PSAX
= Parasternal short axis view; RA = Right atrium; RV = Right ventricle
2. Situs inversus with dextrocardia is known to have much

less incidence of intracardiac abnormalities. It usually
occurs without coexisting congenital heart disease.12
Associated anomalies included ventricular septal defect,
tetralogy of Fallot, pulmonary atresia, complete atrioventricular septal defect, secundum ASD and atrioventricular
concordance with ventriculoarterial discordance.13 Atrioventricular with ventriculoarterial discordance is rare, but
when present is associated with ventricular septal defect
with pulmonary stenosis.13 Rarely, isolated ventricular
inversion is seen (atrioventricular discordance with ventriculoarterial concordance).13
However, they are at a greater risk for pulmonary
diseases than the general population. The most common of
these is Kartagener syndrome (KS). KS is an autosomal
recessive disorder14 characterized by dextrocardia,
bronchiectasis, sinusitis15 and infertility.16
Treatment
Treatment must depend on the associated lesion seen. Readers
are requested to refer to the corresponding chapters for
management.
Mesocardia
When the heart and the cardiac base-apex axis is directed to
the midline of the thorax or with ventricular apices equally
directed to both the right and left sides, it is called mesocardia.
In other words, mesocardia is defined as a condition in which
the longitudinal axis of the heart lies in the midsagittal plane,
with the heart possessing no distinct apex.17 The atria lie sideby-side and posterior to the ventricles with the atrial septum
in an anteroposterior plane. The ventricles are anterior, more
or less side-by-side (Figure 4C). Most of the mesocardia have
9
situs solitus, though situs inversus and ambiguous has also

been seen. The types of the heart found in mesocardia are
same as those found in dextrocardia and levocardia.17
Congenital pericardial defects

Congenital defects of pericardium are uncommon and difficult
to diagnose clinically. They are commonly detected as an
unexpected finding during surgery or autopsy. The incidence
was found to be 0.044 percent among patients who underwent
cardiovascular surgery.19 Pericardial defects are due to
defective formation of the pleuropericardial membrane or
septum transversum.20
It could range from minor partial defects to total absence of
the pericardium.20 Two types of congenital pericardial defects
have been described: a complete form where there is absence
of the pericardium on one side of the heart, left or right and
a partial form, where the defect is localized to a certain area
of the heart. Complete agenesis is not compatible with life.
Left-sided pericardial defects are more common.20,21 Rightsided defects, diaphragmatic defects and total absence are
rare. Pericardial defects have been described with congenital
cardiac defects,19,2224 though it is unlikely that they share the
same pathogenic mechanisms.
The genetic cause for abnormal development of pericardium
is not clear. GATA4 gene is considered a candidate gene for
pericardial defects.25
Symptoms
Most of the defects are asymptomatic.19 Sometimes, there
may be associated symptoms, some of which may be lifethreatening. There can be chest discomfort, recurrent
respiratory tract infections, palpitations, dizziness, syncope,
dyspnea or dysrhythmias.19 Gatzoulis et al found the chest
pain commonly as paroxysmal, sharp, stabbing (mimicking
coronary artery disease), of short duration, commonly in left
precordium and sometimes postural in nature, i.e. the pain
increases in supine or left lateral recumbent position and is
relieved in semi-upright position.26 Sensation of shifting
heart was also noticed by Gatzoulis et al.26 Awareness of heart
beats have been noted especially when patients are lying on
the left side.21
141
Basics
In partial left-sided defects, there can be herniation of

the ventricles through the patent pleuropericardial foramen
resulting in strangulation of the ventricles and sudden death or
herniation of the left atrial appendage. In right-sided defects,
herniation of the right lung into pericardial space can cause
superior vena cava (SVC) obstruction. In diaphragmatic
defects, greater omentum can herniate into pericardial space
causing cardiomegaly.
Cause of chest pain in congenital absence of pericardium
is unclear. It has been suggested to be multifactorial.26 It
could be due to herniation of left atrial appendage, torsion
of the great vessels due to increased heart mobility, lack of
pericardial cushioning, tension on pleuropericardial adhesion,
pressure on the pericardial rim or constriction of the coronary
arteries by fibrous bands.
Diagnosis
Physical examination usually does not provide any evidence
for the diagnosis of pericardial defect. The apical impulse may
be hyperactive and displaced to the left. A systolic ejection
murmur can appear at the left sternal border.
The electrocardiogram is usually normal, though in
complete defects may show a right axis deviation and
clockwise rotation probably due to anomalous rotation of the
heart. Incomplete right bundle branch block pattern has also
been reported in complete form of absent pericardium.26
Chest X-ray was found to be diagnostic in 90 percent of
patients.26 With a complete left pericardial defect, the heart
is shifted to the left resulting in loss of the right heart border
and the left heart border has bulges at the aortic knob, the
pulmonary artery or the left ventricle. A part of the lung may
insert between the aorta and pulmonary artery or between the
diaphragm and the inferior border of the heart. With a partial
left defect, there may be prominence of the pulmonary artery
or the left atrial appendage.
In echocardiogram, the apical windows are laterally
displaced. For parasternal views, lateral placement of the
transducer might be needed.
In the current era, computed tomography (CT) scan or
magnetic resonance imaging (MRI) of the chest can confirm
the diagnosis and give information regarding the extent of the
defect.
Treatment
142
Asymptomatic complete absence of the pericardium and

small defects require no intervention. Partial forms of
pericardial defects may require surgical intervention,
especially when symptomatic. Surgery is indicated for
debilitating symptoms and for herniation with parital absence
of pericardium. Surgical options include enlargement of the
defect to avoid the risk of strangulation and closure with a
flap of mediastinal pleura. Symptomatic benefit is reported
with decrease in the severity and frequency of pain in all

patients after surgery.26
EctopiA cordis
Ectopia cordis is a rare congenital malformation where there
is complete or partial displacement of the heart outside the
thoracic cavity. The estimated prevalence of ectopia cordis is
0.079/10,000 births and more frequently seen in females.27
Ectopia cordis may be classified into cervical (5%),
thoracic (65%), thoracoabdominal (20%) or abdominal (10%)
types.2830 The thoracic and thoracoabdominal types are the
most common followed by abdominal and cervical types of
ectopia cordis.31 The heart is found completely uncovered,
covered with a serous membrane or with skin.28
Ecopia cordis is usually associated with Cantrell pentalogy
or a variant of Cantrell pentalogy with sternal defect.32 Cantrell
pentalogy is characterized by a midline supraumbilical
abdominal wall defect/omphalocele, a defect of the lower
sternum, a deficiency of the anterior diaphragm, a defect in
the diaphragmatic pericardium and congenital intracardiac
defects.33
Pathogenesis
Complete or incomplete failure of midline fusion of lateral
folds has been proposed to result into ectopia cordis. Early
rupture of the chorion and/or the yolk sac causing compression
of the thorax and preventing midline fusion has also been
proposed as mechanical cause for development of ectopia
cordis.34 Early rupture of the amnion with formation of fibrous
amniotic bands also has been postulated.35,36
Associated Anomalies
Variety of congenital heart diseases have been seen to be
associated with ectopia cordis, though ventricular septal defect,
atrial septal defect, tetralogy of Fallot and diverticulum of the
ventricle are the most common.31,37 Other congenital anomalies
like abdominal wall defects, cranial and facial malformations,
cleft lip and palate, anencephaly, hydrocephaly, neural tube
defects, pulmonary hypoplasia, genitourinary malformations
and gastrointestinal defects are seen with ectopia cordis.3840
The complexity of the associated congenital cardiac defect
contributes to poor prognosis.37 Trisomy 18 and Turner
syndrome have been reported with ectopia cordis.4145
Management
As ectopia cordis can be detected antenatally and is commonly
opted for termination due to a low survival rate, it is becoming
uncommon in clinical practice. Surgical correction requires a
staged approach including coverage of the heart, placement of
the heart into the thorax and sternal/thoracic reconstruction.37
Conclusion
A sequential segmental approach with an understanding of the
possible malpositions with their associations would greatly
facilitate the diagnosis of congenital heart disease.
The doctor is often more to be feared than the disease.
French Proverb
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33. Laberge JM. Defination of pentalogy of Cantrell. Commentary
on Araujo Junior et al: diagnosis of pentalogy of Cantrell by
three-dimensional ultrasound in third trimester of pregnancy
(Fetal Diagn Ther 2006; 21:544-7). Fetal Diagn Ther. 2008;
23:168.
34. Kaplan LC, Matsuoka R, Gilbert EF, et al. Ectopia cordis and
cleft sternum: Evidence of mechanical teratogenesis following
rupture of the chorion or yolk sac. Am J Med Genet. 1985;
21:187-99.
9
Intracardiac repair is commonly performed after the first stage

operation.38 Operations for thoracoabdominal ectopia cordis
carry extremely high-risk with only few survivors of thoracic
ectopia cordis.46
143
Basics
144
35. Van Allen MI, Myhre S. Ectopia Cordis thoracalis with

craniofacial defects resulting from early amnion rupture.
Teratology. 1985; 32:19-24.
36. Bieber FR, Mostoufi-zadeh M, Birnholz JC, et al. Amniotic
band sequence associated with ectopia cordis in one twin. J
Pediatr. 1984; 105:817-9.
37. Amato JJ, Zelen J, Talwalkar NG. Single stage repair of
thoracic ectopia cordis. Ann Thorac Surg. 1995; 59:518-20.
38. Hornberger LK, Colan SD, Lock JE, et al. Outcome of patients
with ectopia cordis and significant intracardiac defects.
Circulation. 1996; 94:32-7.
39. Hochberg J, Ardenghy MF, Gustafson RA, et al. Repair of
thoracoabdominal ectopia cordis with mucocutaneous flaps
and intraoperative tissue expansion. Plast Reconstr Surg. 1995;
95:148-51.
40. Diaz JH. Perioperative management of neonatal Ectopia
cordis: report of three cases. Anest Analg. 1992; 75:833-7.
41. Bick D, Markowitz RI, Horwich A. Trisomy 18 associated with

ectopia cordis and occipital meningocele. Am J Med Genet.
1988; 30:805-10.
42. Fox JE, Gloster ES, Mirchandani R. Trisomy 18 with Cantrell
Pentalogy in a still born infant. Am J Med Genet. 1988; 31:
391-4.
43. King CR. Ectopia Cordis and chromosomal errors. Pediatrics.
1980; 66:328.
44. Soper SP, Roe LR, Hoyme HE, et al. Trisomy 18 with ectopia
cordis, omphalocele and ventricular septal defect. Case report.
Pediatr Pathol. 1986; 5:481-3.
45. Garson A, Hawkins EP, Mullins CE, et al. Thoracoabdominal
ectopia cordis with mosaic Turners syndrome. Report of a
case. Pediatrics. 1978; 62:218-21.
46. Morales JM, Patel SG, Duff JA, et al. Ectopia cordis and other
midline defects. Ann Thorac Surg. 2000; 70:111-4.
c hapter
10
Heterotaxy syndrome
Smita Mishra, Seema Thakur
IntroductIon
Box 1: Terminologies
Visceral heterotaxy or heterotaxy syndrome (HS) results

from embryological failure to establish normal left and
right asymmetry. As a consequence, there is an unusual
spatial arrangement of thoracic and/or abdominal organs in
relationship to each other and this does not predict a final
clinical or physiological outcome.
This chapter analyses the dilemma in nomenclature,
management options of diverse lesions, long-term management
of asplenia and primary ciliary dyskinesia (PCD). It also deals
with embryological and genetic aspect of the disorder.
IncIdence15
In general, the incidence of HS is 1/10,000 to 20,000
livebirths. It usually occurs sporadically. Although familial,
X-linked, autosomal recessive and dominant occurrence
are reported in literature, the recurrence rate in the same
family is just below 5 percent.5 The incidence tends to
be as high as 3 percent in neonates with congenital heart
disease (CHD) and 30 percent in babies dying with cardiac
malposition.15 In a large cohort study at least 6.3 percent of
patients with PCD had heterotaxy. The prevalence of CHD
with HS is 200 fold higher in PCD than general population
(1: 50 vs 1:10,000). Hence screening for PCD is required in
the HS patients.7,8
termInologIes16
The important terms related to heterotaxy syndrome are given
in Box 1.
embryology and genetIcs

Embryologically, the timing of origin of the disorder can be
ascribed to the 5th week of gestation or Streeter horizon.13
This is the time when important developmental events like
Situs solitus (SS): The normal left-right anatomical arrangement recognized in relation to the visceroatrial position.
Situs inversus (SI): Complete reversal of asymmetrical structures in the thorax and abdomen. It occurs in approximately 1
in 8,00025,000 individuals.
Situs ambiguous (SA): If right and left patterns of ordinarily
asymmetrical structures like liver, spleen, atrial appendage,
bronchus, etc. are unidentifiable and discordant.
It is recently defined as an abnormality in which, there
are components of situs solitus and situs inversus in the
same person. Situs ambiguous, therefore, can be considered
to be present when the thoracic and abdominal organs are
positioned in such a way with respect to each other as to be not
clearly lateralized and thus have neither the usual or normal,
nor the mirror-imaged arrangements. (Nomenclature Working
Group, 2007).
Heterotaxy (Synonyms: Heterotaxy syndrome (HS) or
visceral heterotaxy): Heterotaxy is defined as an abnormality
where the internal thoracoabdominal organs demonstrate
abnormal arrangement across the left-right axis of the body.
Isomerism of right atrial appendage (IRAA): When both
atrial appendages are morphologically right atrial appendage
and cardiac and non-cardiac thoracoabdominal viscera show
abundance of right-sided morphological features like bilateral
trilobed lung, eparterial bronchi or absence of spleen.
Isomerism of left atrial appendage (ILAA): When both
atrial appendages are morphologically left atrial appendage
and cardiac and non-cardiac thoracoabdominal viscera show
abundance of left-sided morphological features like bilateral
bilobed lung, hyparterial bronchi or presence of multiple spleen.
Polysplenia syndrome: It can be defined as a subset of
heterotaxy with components of bilateral left-sidedness, usually
associated with multiple spleens.
Asplenia syndrome: It can be defined as a subset of heterotaxy with components of bilateral right-sidedness, usually associated with an absence of the spleen.
Ivemark syndrome: It is a term that, historically, is synonymous with asplenia syndrome. Other synonyms have been
used for HS with asplenia including asplenia syndrome, bilateral right-sidedness sequence and splenic agenesis syndrome.
BASIcS
bending and septation of cardiac loop and conotruncus,

growth of endocardial cushion, location of lungs, rotation of
gut, pulmonary venous connection to the roof of left atrium
(LA) and development of spleen takes place.9,10
Over 100 genes have been identified as important in leftright asymmetry in animal models.1117 The heterogeneity
of genes related to HS, combined with a prediction of
reduced penetrance and variable expressivity, makes clinical
molecular diagnostics challenging. Patients with Trisomy
13 or Trisomy 18 have been reported to have heterotaxy. A
number of submicroscopic chromosomal deletions, including
22q11.2 (DiGeorge/velocardiofacial syndrome [VCFS]), have
been identified in patients with heterotaxy.11,12 The majority
of mutations identified have been shown to have reduced
penetrance and variable expressivity, indicating multifactorial
causation. Environmental modifiers such as maternal diabetes,
maternal cocaine use and monozygotic twinning have all been
associated with heterotaxy spectrum defects.15
The X-linked form of heterotaxy, HTX-1 (OMIM# :306955)
is caused by mutations in a zinc finger transcription factor,
ZIC3. X-linked heterotaxy, caused by mutations in ZIC3, is the
best understood genetic cause of heterotaxy.16,17 Interestingly,
mutations in this gene can cause classic heterotaxy or isolated
congenital heart defects. In one family, three of nine female
carriers exhibited situs inversus. Approximately, 1 percent of
sporadic heterotaxy cases (male and female) and greater than
75 percent in familial X-linked heterotaxy cases are due to
ZIC3 mutations.17
Heterotaxy patients without mutations in ZIC3 have been
screened for mutations in genes involved in the conserved
nodal signal transduction pathway.18 The mutations have been
identified in genes encoding the ligand (NODAL), ligand
coreceptor (CFC-1), receptor (ACVRIIB), transcriptional coactivator (FOXH1) and midline inhibitor (LEFTYA) within
the nodal signal transduction pathway.12,19
The PCD disorders are characterized by abnormalities
of ciliary structure and function and are most commonly
autosomal recessive. Heterotaxy with PCD is caused by
mutations in DNAH5 and DNAH11 genes.20
HIstorIcal background and nomenclature

asplenia, is a teratologic syndrome of visceral symmetry
Ivemark 195522
146
The first case on record of this combination of anomalies

is that of Martin (1826), who described the necropsy findings
of a case of septal defect, transposition of the great vessels
and agenesis of the spleen. In 1955, Biorn Ivemark (1955)
published his landmark paper, which included analyses
of all the cases from the published literature, as well as his
own 14 cases, in which he postulated that it was possible to
have teratogenic effect of some genetic factor on splenic and
cardiac development because development of spleen, division

of atrioventricular canal and the conotruncus, somewhat
coincide in fetal life.16,2124 The polysplenia initially was
overlooked as a marker of one more subset of HS till Moller
et al (1967) published another breakthrough paper of their own
findings and correlated it with previously published literature.
They found that these polysplenic patients had a tendency for:
1. Cardiac malposition.
2. Interruption of inferior vena cava (IVC) with azygos
continuation.
3. Partial or total anomalous pulmonary venous connection to
the venous atrium.
4. Bilateral superior vena cava
5. Defects in the atrial and ventricular septa
Additionally, they reported presence of extracardiac
abnormalities that was:
1. Partial or complete abdominal heterotaxy
2. Abnormality of pulmonary lobulation
3. Symmetrical liver.23
These evolutionary findings fueled further debate regarding
the terminology of HS and splenic morphology.
The terminological address of spectrum of HS evolved
slowly. Evidently it needed a large numbers of publications
and extensive discussions to reach to a consensus so that
current nomenclature and terminology could prevail.16
controversies in nomenclature2527
It had been the convention over the years to describe these
characteristic groups of HS in terms of asplenia and polysplenia.
Afterwards, it was clear that these splenic morphological
abnormalities are vacillating, henceforth cannot be reckoned
as a sole pennant of HS. Subsequently, attention was drawn
towards the unique morphological resemblance of two
atrial appendages (Figures 1A to C). Umera and Anderson
et al highlighted that description of the morphology of the
appendages as well as the venoatrial connections, were more
conclusive than anything else. As it was pointed out by Van
Praagh, Andersons group themselves changed their stand
later, by advocating the inner anatomy of appendages as the
basis of diagnosis rather than the outer morphology. Now
there is a consensus regarding the description of HS on the
broader basis rather than diagnosing it as right atrial (RA) or
LA isomerism and isomerism of atrial appendages is to be
accepted as a real anatomic entity (See Box 1).
recommendations of nomenclature Working group for

Pediatric and congenital Heart disease (2007)6
This group reviewed the nomenclature, definition and
classification of heterotaxy and emphasized more on sequential
segmental analysis (Table 1). The few of the recommendations
are as follows:
10
HeTeRoTAxy SyndRome
c
Figures 1A to c: Computed tomography (CT) angiography 3D reconstruction: A. Normal right and left atrial appendages in a case of situs solitus,
dextrocardia, corrected transposition of the great arteries (TGA); B. Bilateral right atrial appendage in dextrocardia with corrected TGA and;
C. Isomerism of left atrial appendage. (Courtsey: Apoorva Goyal, Francis B). LAA = Left atrial appendage; RAA = Right atrial appendage.
Table 1
Nomenclature and segmental analysis in heterotaxy5,6,25,27
Segments
Variables
Atrial situs
S (solitus), I (inversus), A (ambiguous) X (unknown)
Ventricular loop
D (right handedness), L (Left handedness), X (unknown)
Arterial relationship
N (normal), S (solitus), I (inversus), D (D-malposed), L (L-malposed), A (anterior aorta), X (unknown)
AV connection
Concordant, discordant, biventricular and mixed, double inlet and absent connections (right or left),
univentricular heart
AV valve
Two perforate valves, one single perforate valve with an absent atrioventricular connection, one perforate
along with one imperforate valve, a common valve or an absent valve with a so-called unguarded orifice,
straddling of valve, overriding of valve >50%, 5090%, >90%
VA connection
Concordant, discordant, single outlet (common arterial trunk), single outlet via aorta (pulmonary atresia),
single outlet via pulmonary trunk (aortic atresia, DOLV, DORV)
VA valve
Over-riding, imperforate valve, absent AV/PV
Cardiac position/apex
Dextrocardia, levocardia, mesocardia, dextroversion, levoversion, bifid apex
AV = Atrioventricular; DOLV = Double outlet left ventricle; DORV = Double outlet right ventricle; PV = Pulmonary valve; VA = Ventriculoatrial.
147
BASIcS
1. Description of cardiac and non-cardiac thoracoabdominal

structures: The cardiac anatomy and associated cardiac
malformations, as well as the relationship and arrangement
of the remaining thoracoabdominal organs, must be
described separately.
2. Splenic morphology: Less than perfect association between
the state of the spleen and the form of heart disease implies
that the splenic morphology should be investigated in all
the forms of heterotaxy. The splenic morphology should
not be used to stratify the form of disease within the heart
and the form of the cardiac disease should not be used to
stratify the state of the spleen.
3. Malrotation of gut: Intestinal malrotation is another
frequently associated lesion that must be considered.
abnormalItIes of tHoracoabdomInal
organs In Heterotaxy syndrome
As mentioned above, the HS needs to be evaluated based on
segmental analysis of the heart and a individualized approach
to other organs. To accomplish it, the morphological
method described initially for cardiac evaluation by Lev
et al and subsequently by Van Praagh and his associates,
must be followed. This principle states that structures should
be identified according to the component part that is most
universally present.2731
The first step in the assessment of the cardiac anatomy
is to locate and identify the LA and RA. Anatomically, the
atrial chamber differentiation based on the morphology of
atrial appendages are not reliably identifiable at ultrasound or
radiologic imaging and the localization of non-cardiac organs
is more helpful in determining the atrial situs. These noncardiac organs are:
1. Thoracic levelright and left bronchus and lungs.
2. Abdominal levelliver, spleen, descending aorta and the
inferior vena cavae (Figure 2).
It is apparent from the various analyses, (Table 2), that
none of the findings are sacrosanct for isomerism of right
atrial appendage (IRAA) or isomerism of left atrial appendage
(ILAA) and can be shared by either of groups. In general, IRAA
group usually presents with severe cardiac malformations
whereas ILAA present with extracardiac malformations. With
this basic understanding now we precede to the rest of chapter
and analyze:
A. Cardiovascular system
B. Extracardiac thoracoabdominal organs.
anatomical configuration of cardiovascular system

and segmental analysis5,6,2831
Cardiac Position
148
The cardiac position is variable and all kinds of cardiac positionslevocardia, dextrocardia or mesocardia, can be seen in
either of the groups. Discordant ventricular apex and stomach

relationship predicts a complex CHD.
Venoatrial Connection5,6,2833
Systemic venoatrial connections: The most important clue
of morphological RA is its connection with IVC or absence
of it (IVC interruption), which can be delineated by various
imaging modalities. We will see in further analyses that there
may be exceptions to this rule.
Isomerism of right atrial appendage: Abnormal systemic
venoatrial connections are the integral part of the syndrome.
IRAA is usually associated with bilateral superior vena cava
(SVC). The coronary sinus (CS), which collects systemic
venous blood from the persistent left superior vena cava
(LSVC) and cardiac veins, is usually absent. The cardiac veins
and persistent LSVC directly drain into either of the atrium.
IVC can drain into either of the atrium or centrally. The IVC
and aorta tend to remain juxtaposed on either sides of the
midline (Figure 3A). The hepatic veins may drain into the IVC
or occasionally anomalously to either of the atrium. Usually
the left hepatic vein drains into the left sided atrium, which
represents the morphological left sided IVC (Figure 4A).
Isomerism of left atrial appendage: Generally, isomeric
hearts with ILAA are associated with bilateral SVC and
have interrupted IVC. The suprarenal (hepatic) part of IVC
is missing here and hepatic veins may form a confluence
or drain individually into the either of the atrium. The
infrahepatic part of the IVC remains intact. Moreover, sizeable
number of patients may have missing coronary sinus. The
echocardiographic diagnosis of ILAA is based on the absence
of hepatic portion of IVC in the subcostal transverse section
and demonstration of ascending dilated retroaortic venous
channel (azygos/hemiazygos venous system). In ILAA, the
hemiazygos vein is usually present bilaterally and may drain
into the CS, RSVC or LSVC (Figures 3B and 4B). However,
the interrupted IVC can be seen in the IRAA as well as in
patients with normal or non-isomeric hearts. Figure 3C is
demonstrating a rare case of ILAA with intact IVC draining
into the floor of the left-sided atrium.
Pulmonary venoatrial connections3335: In IRAA, any type
of total anomalous pulmonary venous drainage or connection
(TAPVD or TAPVC) is common because true morphological
LA is absent in this group. Commonly, this connection is
obstructed irrespective of the site of drainage.
In ILAA, pulmonary veins try to drain to the respective
isomeric atrium and partial anomalous pulmonary venous
drainage (PAPVD) or TAPVD due to malaligned interatrial
septum is more common.34
McCartney et al analyzed 45 necropsy specimens and
found that 32 out of 34 had TAPVD in IRAA group. One
patient had a short obstructed channel draining the pulmonary
venous confluence to the atrium. In ILAA group 7 out of 11
had PAPVD and none had TAPVD.29
10
HeTeRoTAxy SyndRome
Figure 2: Inferior vena cava (IVC) and abdominal aorta (Ao) at the level of diaphragm defining atrial situs (L1 vertebra).
ILAA = Isomerism of left atrial appendage; IRAA = Isomerism of right atrial appendage.
Atrial Anatomy1,5,6,2131
The RA has three basic parts: the appendage, the vestibule
and the venous component. The right atrial appendage has the
shape of a blunt triangle, with a wide junction to the venous
component across the terminal groove. The appendage also
has an extensive junction with the vestibule of the RA; the

later structure is the smooth-walled atrial myocardium that
inserts into the leaflets of the tricuspid valve. The most
characteristic and constant feature of the morphology of the
RA is that the pectinate muscles within the appendage extend
around the entire parietal margin of the atrioventricular (AV)
149
BASIcS
junction. The venous component of the RA extends between

the terminal groove and the interatrial groove. It receives
the superior and inferior caval veins and the CS. The RA is
identified by its connection to IVC, atrial appendages, limbus
fossa ovalis, opening of the CS, eustachian and thebesian
venous valves.
The LA also has three basic components: The appendage,
vestibule and venous component. Unlike the RA, the LA
appendage is a finger like, trabecularized structure, which
lies over the left AV groove. It has a limited junction with
the vestibule and the pectinate muscles are located almost
exclusively within the appendage. Obviously, externally
mirror imaged atrial appendages are not seen universally and
inner morphology of the appendages define the isomerism
(isomerism of junction of the atrial appendage).
In IRAA, the defects like common atrium with a strand of
atrial tissue straddling the atrial cavity or large primum atrial
septal defect (ASD) preponderate.
In ILAA, intact atrial septum, sinus venosus ASD, patent
foramen ovale (PFO) and secundum ASD are commonly
seen.4,5 As mentioned above, the malaligment of atrial septum
is often seen in ILAA and forms the basis of cardiac PAPVD
to RA and ASD.
Atrioventricular Connection, Ventricles, Ventricular Loop,

Atrioventricular Valve46,2331
150
Figures 3A to c: Computed tomography (CT) angiography: A. CT

angio at T12, L1 level. Isomerism of right atrial appendage; right juxtaposition of inferior vena cava (IVC)/Abdominal Ao. Central liver; B.
CT angio at T12, L1 level. Isomerism of left atrial appendage; azygos
continuation of IVC behind the abdominal Ao. Central liver and; C.
CT angio at T12, L1 level. Isomerism of left atrial appendage; intact
suprarenal IVC in left isomerism. Central liver. (Courtsey: Apoorva
Goyal, Francis A)
The AV relationship in HS is defined as mixed instead

of being called concordant or discordant. Furthermore,
frequently AV connections may not be biventricular. In IRAA,
the AV relationship is more complex.16,2331
The right ventricle (RV) is described as tripartite structure
having three componentsinlet, cavity and outlet and its cavity
is triangular, which contains the moderator band and coarse
trabeculations. The inlet of RV is guarded by trileaflet tricuspid
valve. The septal leaflet has relatively lower attachment with
the interventricular septum (IVS) than the mitral leaflet. RV
is anteriorly placed than the left ventricle (LV) and there is
tricuspid-pulmonary valve discontinuity. The LV is elliptical
and relatively posteriorly placed chamber. Its inlet is guarded
by the bicuspid mitral valve (MV) and its outlet has a tricuspid
AVV, which maintains the fibrous continuity with MV. The
LV aspect of the IVS is smooth and the LV cavity has fine
trabeculation. It also has MV subvalvar apparatus attached to the
anterolateral and posteromedial papillary muscles at the LV free
wall. Unlike the atrial anatomy, the morphologic identification
of ventricles is less problematic on echocardiography. However,
this may not be easy in presence of common AV junction or
unbalanced ventricles. Also in presence of grossly unbalanced
ventricles, the inner morphology becomes difficult to decipher.
However, the ventricular looping and morphology follow the
usual normal or abnormal pattern (D or L loop) of evolution
and morphologically ventricles are never isomeric. It is not
uncommon to find univentricular heart with indeterminate
ventricular morphology.
10
HeTeRoTAxy SyndRome
Figures 4A and B: Isomerism of; A. Right atrial appendage, left-sided (HV) draining into left-sided atria. B. Left atrial appendage, ascending
azygos vein beside the descending aorta drains into right superior vena cava (RSVC). (Courtsey: Apoorva Goyal, Francis A)
The most common abnormality found in HS is common

AV junction or the so called atrioventricular canal defect
(AVCD). This has also been called endocardial cushion defect
or atrioventricular septal defect (AVSD). These defects
have varying degrees of incomplete development of the AV
septal tissue adjacent the AV valves along with spectrum
of abnormalities of the AV valves themselves. Partial
AVSD or incomplete AVSD has an ostium primum ASD
and abnormal left AV valve. Typically the left AV valve
in this subset differs from the normal MV. It is guarded
by three leaflets and has a cleft essentially facing the IVS.
Complete AVSD (CAVSD) has both defects in the atrial
septum just above the AV valves (ostium primum ASD) and
defects in the ventricular septum just below the AV valves.
In CAVSD, the AV valve is one valve that bridges both the
right and left sides of the heart, creating superior (anterior)
and inferior (posterior) bridging leaflets. Transitional or
intermediate AVSD is in-between and has two distinct
orifices, but also has an ASD just above and a ventricular
septal defect (VSD) just below the AV valves. The VSD
in this lesion is often restrictive. The AV valves in all the
three forms may be grossly abnormal, often regurgitant and
prognosticate a suboptimal surgical outcome.
In IRAA, CAVSD and common AV valve with common
orifice is frequently associated. The tethering and type of
straddling of the superior and inferior bridging leaflets
forms the hemodynamic basis for complex AV connections,
abnormal flow pattern, resulting in developmentally
unbalanced ventricles. Sometimes, in the absence of AVSD,
various degree of overriding, straddling of AV valves may lead
to serious consequences. The aforesaid complex intracardiac
anatomy is the substrate for univentricular or Fontan type
repair in majority of cases of IRAA.
In ILAA, partial or transitional AVSD with two distinct AV

orifices, is common. However, presence of normal AV junction
with or without shunt lesions is not uncommon in ILAA.
Cardiac structure in ILAA may be completely normal or may
have simple heart defects. VSD is the usual finding in HS.
In IRAA, preponderance of common AV junction
predisposes for a true large inlet VSD, but other types of
isolated or additional defect like, perimembranous, outlet,
doubly committed and muscular, can be present.
In ILAA, an inlet VSD may be present as a part of AVSD.
Because common AV junction in this group usually manifest
as partial or transitional AVSD, inlet VSDs is less frequent in
comparison to the IRAA. Other varieties of VSD can be seen
in this group.
outflow in Heterotaxy5,2325,36,37
The conotruncal abnormalities are frequent associations of
HS. The outflows can be obstructed, partially or completely in
both IRAA and ILAA.
IRAA, is usually associated with right ventricular outflow
tract (RVOT) obstruction and pulmonary valve anomaly.
In ILAA, on the contrary, the left ventricular outflow tract
(LVOT) obstruction is common.
Besides, both the groups in HS may be associated with
abnormal ventriculoarterial connection like transposition and
double outlet right or left ventricle (Table 2).
Conduction System
Patients with IRAA may be associated with bilateral
sinoatrial (SA) node. However bilateral presence of SA node
is not a universal finding as was shown by Ware et al who
151
BASIcS
demonstrated the presence of bilateral sinus nodes in only

54 percent of the cases.38
In ILAA, bilateral absence of sinus nodes is seen frequently.
Ware et al documented bilateral absence of SA node in
25 percent of cases with left isomerism.38
The pathways for AV conduction in hearts with isomerism
of the atrial appendages are conditioned both by ventricular
topology and by the AV connections. No pathognomonic
variation is seen in HS.
In D-loop ventricle, an AV node is in its regular position,
with a posteroinferior penetrating bundle, which is further
posteriorly deviated in presence of AVSD. In L-loop ventricle,
the conduction system simulates to that of congenitally
corrected transposition of great vessels, i.e. either an anterior
AV node is seen or a sling of conduction tissue is seen along

the crest of IVS, connecting an anterior and posterior AV node.
Pattern is almost same when RV is the dominant ventricle, but
if LV is dominant with RV as a small ventricle, the AVN is
anterior and lies in relation to the LVOT.4,5
Coronary Arteries in Heterotaxy

Umera et al reported abnormal patterns in branching of the
coronary arteries, associated with abnormal ventricular
architecture. The morphologically LV/RV arteries were
frequently lacking in those hearts with a dominant ventricle
and a rudimentary or incomplete ventricle. A solitary coronary
artery was seen in 13 percent of cases.39
Table 2
Usual morphological features in heterotaxy
152
Clinical and morphological

features
Isomerism of left atrial appendage
Isomerism of right atrial appendage
Heart position
Levocardia: 5075% dextrocardia: 210%
Levocardia: 63%, rest dextro or mesocardia
Systemic veins
Absence of intrahepatic portion of IVC with

Bilateral SVC: 5060% cases and absent
azygos/ hemiazygos venus system continuation coronary sinus in 78% cases.
to SVC. Hepatic veins may form confluence
and drain into right/left sided atrium or in the
floor of common atrium in 9096% of cases.
Bilateral SVC: 40% cases and absent coronary
sinus in 3055% cases.
Pulmonary veins
PAPVC: 4060% with ipsilateral veins draining

into respective atrial chamber. TAPVC 1012%
usually due to malalignment of atrial septum.
Scimitar syndrome 1%
TAPVC > 50%, up to 40% case have

obstructed vertical vain
Atria
Both atrial appendages are both atrial

appendages are morphological LAA: Long
narrow and pectinate muscles restricted upto
the base of appendage and not going beyond.
No crista terminalis, fossa ovalis is often
absent. Large ostium primum defect in 5065%
cases. However, fenestrated fossa ovalis, intact
atrial septum, sinus venosus ASD also have
been reported.
Both atrial appendages are both atrial

appendages are morphological RAA: Broad
base, thumb like in little anterior plane and
pectinate muscle extending beyond the base
of appendage.
Bilateral crista terminalis, fossa ovalis is
often absent. Common atrium or large ostium
primum defect in majority of the cases, isolated
or as a component of complete AVSD.
Atrial septum/atrioventricular
(AV) junction/valve
Common AV junction, partial AVSD with two

distinct AV orifices and cleft in left component
of AV valve. Ostium primum ASD is frequent
as a part of partial AVSD. Other kind of ASDs
(secundum/sinus venosus can also be seen.
Common AV valve associated with complete

or partial AVSD 8090%. Common atrium
where single strand runs through cavity or a big
secundum ASD along with ostium primum ASD
(like common atrium) has been reported.
AV connection
Univentricular connection: 1040%
Univentricular connection > 72%
RVOT/LVOT
Pulmonary stenosis/atresia: 2830%

LVOTO: 40% (coarctation of aorta 16%;
AS 10%)
Pulmonary stenosis/atresia: Up to 8090%,

LVOTO uncommon
VA connection
Are abnormal in 50% patients. TGA: 16%,

DORV: 32%, DOLV: 7%
Abnormal ventriculoarterial connection

discordant, double oulet or single outlet:
9096%
Significant CHD
Less frequent
> 98%
Conduction system
Sinus node may be absent
There may be two sinus node

Contd...
10
Contd...
Isomerism of left atrial appendage
Isomerism of right atrial appendage
Lungs and bronchi
Symmetrical, left bronchus and left lung

morphology bilaterally (90%)
Congenital lobar pneumonia
Symmetrical, right bronchus and right lung

(trilobed) morphology bilaterally (90%)
Spleen
Majority multiple (88%), absent (5%); single in

few
Majority-absent (80%) few: single (17%)

multiple (4%)
Liver
Symmetrical (2570%), right-sided

or left-sided
Symmetrical (majority of cases)
Stomach
May be placed in center, right or left

hypochondrium
May be placed in center, right or left

hypochondrium
Bowel
Malrotation of gut, volvulus

Malrotation of gut, short dorsal mesentery:
Short mesentery-13% other abnormality: jejunal 19%. Cephalic migration of colon
atresia
Duplication of bowel
Pancreas
Truncated/annular can be seen more often
Rare
Gallbladder
Biliary atresia 11% usually biliary abnormalities

are seen like mirror image branching,
quadruplicating or ciliary atresia, cholelithiasis
Usually no biliary abnormalities
HeTeRoTAxy SyndRome
Clinical and morphological

features
Percentages listed are approximations based on review of references22,2931,34,3639,49,50,52,53

ASD = Atrial septal defect; AVSD = Atrioventricular septal defect; DOLV = Double outlet left ventricle; DORV = Double outlet right ventricle; IVC = Inferior
vena cava; LAA = Left atrial appendage; LVOTO = Left ventricular outflow tract obstruction; PAPVC = Partial anomalous pulmonary venous connection;
PS/PA = Stenosis or atresia; RAA = Right atrial appendage; RVOT/LVOT = Right/left ventricular outflow tract; SVC = Superior vena cava; TAPVC = Total
anomalous pulmonary venous connection; TGA = Transposition of the great arteries; VA = Ventriculoarterial.
Other Cardiopulmonary Manifestations

in Heterotaxy Syndrome
Many other cardio-pulmonary anomalies like pulmonary
hypertension and portopulmonary shunt, have been described
but can not be associated consistently with HS. There are
isolated reports of association of pulmonary emphysema,
non-compacted LV, scimitar syndrome, isolated pulmonary
sequestration and bronchomalacia, mostly in ILAA group.4043
anatomical arrangement and structure of extracardiac

thoracoabdominal organs in Heterotaxy
Lungs and Bronchial Anatomy4345
The ratio between left (bronchus sinister) and right
bronchial (bronchus dexter) length is usually 2 : 1. Also the
branch pulmonary arteries (PAs) are in a unique relationship
with the ipsilateral bronchi. Accordingly, the first branch of
the right bronchus can be described as eparterial or that
of the left bronchus as hyparterial.4547 The lungs differ
from each other in the number of their lobes, consequently
the bronchi differ in their mode of subdivision (Figures 5A
to D). The right lung has three lobes, one oblique and one
horizontal fissure. The left lung has two lobes, one major
oblique fissure. These features can be appreciated in plain
chest roentgenogram.4547
In IRAA, the lungs are trilobed bilaterally and are connected

to eparterial bronchi. Both the branches of pulmonary artery
show the morphological pattern of right PA as they travel
below and anteroinferior to the bronchus on both the sides to
enter into the respective hilum. The corresponding bronchus
enters underneath the PA after giving rise to its first branch
(eparterial branch). The ratio of the length of bronchi measured
from bifurcation of trachea to the origin of first branch from
bronchus, remains <1.5.
In ILAA, both the bronchi have the same length and the
first branch of both the bronchi arise most distally (hyparterial
bronchus), after they pass beneath the respective branch PA.
Hence, branch PA are the morphological left PA, bilaterally.
Predictively, the lungs are bilobed and isomeric in this setting.
Van Meirope et al suggested that the chest roentgenogram
in anteroposterior or posteroanterior view can be best way
of knowing atrial situs, as it always corresponds to tracheobronchial tree.44 This conventional thinking is not valid
absolutely and evidences to contrary, i.e. atriobronchial
discordances, are cropping up.4447
Yet, in clinical settings, loss of bronchopulmonary
asymmetry is most easily discernible and useful clue to the
diagnosis of HS.
In a recent publication, the five thoracic features in 306
postmortem specimens were assessed to evaluate bronchoatrial relationship and its validity as a marker of atrial situs.
The results showed a good, but variable predictive value of
153
BASIcS
Figures 5A to d: Computed tomography (CT) angiography reconstruction: A. Isomerism of right bronchus. Distance of the origin of first bronchus
bilaterally. Early branching; B. Isomerism of left bronchus. Delayed origin of first branch; C. Isomerism of right atrial appendage:: pulmonary
artery (PA) branches (white arrow) passing anterior to both bronchus till the first branch of bronchus originates; D. Isomerism of left atrial
appendage:: Pulmonary artery first branch arising before the first branch of bronchi and crossing over the bronchus. (Courtesy: Apoorva Goyal,
Mr Francis)
each criterion. Morphological features of bronchi, lungs and

branch pulmonary artery are given in Table 3.
abdomen in Heterotaxy
Liver 5,6,2426,49,50
The liver normally has two lobes. The right lobe is usually
approximately six times larger than the left. It occupies the
right hypochondrium, The left lobe is smaller and more
flattened than the right. It is situated in the epigastric and left
hypochondriac regions. The liver in HS, is often centrally
placed or may remain in right or left hypochondrium.
Spleen
154
The absence of spleen can be the indicator of IRAA and

presence of multiple spleens indicates ILAA. Nevertheless,
with the growing understanding of HS, we know that splenic
morphology may vary and cannot predict the presence of
either types of isomerism accurately.
Morphology of spleen in ILAA5,6,4854: The splenic mass

is usually divided into fairly equally sized 2 to 6 masses or
splenules. Usually these splenules are 1 to 6 cm in diameter,
which together equals to the mass of a normal spleen
(Figure 6). Infrequently, there may be several small spleens
adjacent to either one or two larger spleens. The location of
these splenules may be along the greater curvature of the
stomach, in the left or right upper quadrant of abdomen. A
single-bilobed spleen is a rare variant. The polysplenia results
from incomplete fusion of the splenic mesenchymal tissue. We
will discuss functional status of the spleen later in the chapter.
malrotation of gut
Normally, in visceral situs solitus the duodenojejunal junction
(DJ) lies towards the left of midline, at the level of L1-L2.
Essentially, the stomach and DJ junction are on the same side
of spine. Intestinal malrotation can be broadly defined as the
congenital abnormal position of the DJ junction. It is usually
accompanied by abnormal bowel fixation by mesenteric
bands or absence of fixation of portions of the bowel, leading
10
Table 3
Morphological features
HeTeRoTAxy SyndRome
Morphological features of bronchi, lungs and branch

pulmonary artery47
Percentage of positive prediction
(Specimen: 306; heterotaxy: 56)
Lung lobation
77%
Lengths of main bronchi
77%
Ratio of left to right (L/R)

bronchial lengths (<1.5)
90%
Relationship of bronchi to
ipsilateral pulmonary artery
> 95%
Number of cartilage rings in

each main bronchus
77%
to increased risks of bowel obstruction, acute or chronic

volvulus and bowel necrosis. This abnormal position is
because of failure of normal counterclockwise rotation of the
midgut by 270, during the embryologic development. The
rotational abnormality of gut can be best attributed to nonrotation, incomplete rotation or rarely reverse rotation of gut
in stage 1 of development. This rotation takes place around the
superior mesenteric artery (SMA). So, normal inferior and left
position of DJ junction will not be attained and cecum does
not reach to the right lower quadrant. The mesentery in turn
forms a narrow base as the gut lengthens on the SMA without
rotation and this narrow base may lead to midgut volvulus
in many patients (Figure 7A).5,51,55,56 Barium examinations
under fluoroscopy and getting upper gastrointestinal series is
helpful.6,56
Pancreas in Heterotaxy
Pancreas is a centrally placed single organ, which has three
distinct partsthe head, neck, body, and tail extends between
the curves of duodenum to spleen. The abnormalities of
pancreas are seen in ILAA. In many cases, the tissue from
the head of pancreas forms a semicircle around the duodenum
and is known as annular pancreas; pancreas is called truncated
when only head or head and small body is present (Figure
7B).51,57
Gallbladder and Biliary Atresia

Gallbladder is an unpaired organ, which is placed under the
surface of the right lobe of liver. In heterotaxy it may be placed
in the midline. In ILAA, it may be absent or can be associated
with biliary atresia. Davit et al have described specific gene
mutations associated with ILAA and biliary atresia.5,51,54
other systemic manifestations in Heterotaxy5,6,8,3538

Besides the above mentioned structural and positional
abnormality of thoracoabdominal viscera, some other
Figure 6: Computed tomography (CT) angiography: Isomerism of left

atrial appendage: Intact inferior vena cava (IVC) (rare) with multiple
spleens (SPL) and ransverse liver. (Courtsey: Apoorva Goyal, Mr Francis)
structural anomalies are also seen in either of heterotaxy

groups.
Central nervous system (CNS)encephalocele, neural
tube defects, porencepalic cyst, cerebellar agenesis.
Axial skeletonhemivertebra, sacral agenesis.
Genitourinary/adrenalhypoplastic or absent kidneys,
cystic kidney, hydroureter, hypospadias, duplicated uterus,
vaginal atresia, bicornuate uterus, ovarian cysts.
Craniofacialcleft lip/palate agnathia, micrognathia,
choanal atresia, laryngeal cleft
Endocrinalfused or horseshoe adrenal, absent adrenal.
clInIcal evaluatIon
Babies with HS present very early with critical illness and
are clinically unstable for various reasons like:
1. Severe cardiac diseases presenting with congestive heart
failure or severe hypoxia due to association with obstructed
TAPVC, outflow obstruction or large shunt lesions, AV
regurgitation.
2. Associated tachyarrhythmia or bradycardia (AV block).
3. Extracardiac problems like volvulus, biliary atresia.
4. Severe sepsis.
Clinical signs may include: abnormal heart rate and rhythm,
low volume or differential pulses, abnormal or differential
blood pressure in all four limbs, cyanosis, abnormal cardiac
apex, with or without cardiomegaly, single second heart
sound, with or without ejection or pansystolic or continuous
murmur. In older children with ILAA, second sound may be
wide, variable or fixed. Abnormal positioning of liver dullness
or stomach tympanic sound may occur. Also, there may be
abdominal distention.
155
BASIcS
B
Figures 7A and B: A. Barium meal. Malrotation of gut. Right-sided stomach, duodenojejunal (DJ) junction to the left;
B. MRI scan. Truncated pancreas (ILAA). Part of body and tail is missing. Area is empty near splenic artery
No characteristic clinical finding can be narrated, as, a

number of intracardiac abnormalities are associated with the HS.
According to intracardiac anomaly clinical findings will vary.
routine Work-up
According to the severity of symptoms, a detailed clinical
as well as laboratory work-up must be planned to ascertain
the cardiac diagnosis and to see the functional status of renal,
hepatic, splenic and other systems.
chest radiograph: Predictors of asplenia syndrome

Besides providing the usual information on cardiopulmonary
status, there are certain findings in chest X-ray which suggests
the presence of HS.
Trinavarat et al evaluated six such findings in a series of
30 prediagnosed patients of asplenia syndrome and found
bilateral minor fissure in 53 percent, bilateral eparterial
bronchi in 53 percent, symmetrical transverse liver in 30
percent, ipsilateral side of liver and stomach in 30 percent,
ipsilateral side of minor fissure or eparterial bronchus and
stomach in 33 percent, contralateral side of minor fissure or
eparterial bronchus and liver in 23 percent. They found atleast
two positive findings in 28 out of 30 patients.58
electrocardiogram5,59,60
156
Electrocardiogram in HS must be evaluated for rate, rhythm,

accessory pathways and AV conduction.
Usual ECG abnormalities are:
1. Abnormal P-wave axis (bilateral SA node or absent SA
node and position of atria).
2. Bradycardia/junctional rhythm/blocks.
3. Abnormal left axis deviation.

4. Abnormal Q waves (single ventricle or ventricular
inversion).
5. Accessory pathway.
The atrial situs, ventricular hypertrophy patterns can
be assessed by evaluating axis and voltage of P, QRS and
T waves. In postoperative period, one can see varieties of
rhythm abnormalities (Figure 8A).
The characteristic ECG of ILAA shows an aberrant P-wave
axis, progressive slow heart rate, multiplicity of atrial rhythm,
AV block and junctional escape rhythm. Overall complete AV
block is observed in one-tenth of cases of left isomerism.5,60
Figure 8B shows low atrial focus in a patient with ILAA.
This patient underwent a double switch operation successfully,
but had a slow junctional rate postoperatively. The patient
needed a permanent pacemaker implantation.
In IRAA, ECG may show multiple atrial rhythms and
a variable P-wave axis. The changing P-wave axis is due to
bilateral sinus node with switching over of pacemaker function.
In few cases, there might be dual QRS axis due to the
presence of dual AV node and sling of conduction tissue. Reentry tachycardia can be seen in these circumstances.
One of the case series consisting of cases with ILAA
showed mean frontal P-wave axis of 30 to 90 in 70
percent of subjects. Additionally, in half of the cases, atrial
rate was below the second percentile. Only 10 percent cases
had it persistently low. About 40 percent of cases showed a
tendency for recurrence. The junctional escape rhythm was
seen in 42 percent.60
The abnormalities in ECG may also be related to
intracardiac defects and QRS axis may deviate superiorly with
a counterclockwise or clockwise loop and may show abnormal
ventricular dominance. An abnormal cardiac rhythm can also
be noticed in fetal life.61
10
HeTeRoTAxy SyndRome
B
Figures 8A and B: A. Postfontan IRAA supraventricular tachycardia and; B. ECG in ILAA: a junctional beat follows
the atrial ectopic then low atrial foci is taking over
echocardiography5,62,63
computed tomography scan
Echocardiography is the best modality to understand

anatomical and hemodynamic effects of the prevalent
structural heart diseases in HS. It can be done by transthoracic
or transesophageal route. Numerous series of images can be
displayed through multiple windows. Since the orthogonal
planes of the heart are different from the major axes of the
body, it is conventional to describe the window of access as
well as the reference plane. The availability of the subcostal
windows in babies and small children are a great advantage,
because they enable the examiner to produce innumerable
sequential images in desired orthogonal planes and hence
provide opportunity to follow the anatomical course of veins
and arteries, to study atrial and ventricular septum despite
their obliquity and to identify the diverse placement of the
cardiac valves.
The diagnosis of HS by echocardiography is based on the
abnormal placement of the descending aorta and IVC in the
subcostal short-axis view. We have seen that this relationship
is unpredictable at times. The identification of morphology
of the atrial appendages is not possible always (Figures 9A
to F).
The computed tomography (CT) scan and angiography

are used routinely for complex HS. The radiation to the
babies and children remains a constant worry. Otherwise, it
requires less time for acquisition of images unlike magnetic
resonance imaging (MRI) or conventional angiography.
Our own experience with this modality is excellent. CT
gives outstanding 2D and 3D imaging of atrial appendages,
systemic and pulmonary veins, aorta and its branches,
collaterals and pulmonary arteries. Additional morphological
information about the bronchial anatomy, lung lobulation and
position of the abdominal viscera can be obtained accurately.
The abdominal contrast CT is also needed to understand gut
morphology (Refer: Figures 1A to C; 3A and B; 4A and B; 6
and 7A and B).64,65
magnetic resonance Imaging

MRI gives excellent images of the cardiovascular system. It
can create moving images of the heart throughout its pumping
cycle. Therefore, unlike the CT scan, MRI can do a functional
assessment of the heart. It can demonstrate abnormalities
157
BASIcS
Figures 9A to F: Echocardiography in heterotaxy syndrome: A. Atrial situs: IRAA. Juxtaposed (IVC)/Abdominal Ao on right side of spine; B. Atrial
situs: ILAA. Interrupted IVC/Az continuation; C. IRAA, complete (AVSD). Indeterminate ventricle; D. Subcostal modified coronal view. Common
(AV) valve; E. ILAA. Interatrial septum. (ASD) secundum; F. ILAA. Left SVC to roof of LA. Coronary sinus is absent
of thoracoabdominal structures, extracardiac abnormalities

and can help in delineation of visceral situs abnormalities.
Nevertheless, it cannot define extent of pectinate muscles
in atrial appendages. Perhaps MRI is the best modality for
better assessment of complex anatomical and functional
abnormalities after surgery.5,66
conventional angiography and catheter Intervention
158
As a diagnostic modality, conventional angiography is losing

its place. Still, this is the only modality, which gives triple
opportunity to obtain the anatomical details, hemodynamic
data and to intervene. One such catheter interventions is the
coiling of major aortopulmonary collaterals, usually done
before or after the surgical intervention. The hypoplastic
branch pulmonary arteries can undergo balloon angioplasty
and stenting. Donna et al reported successful device
closure of post-fenestrated Fontan in 154 cases, out of
which 14 patients were with HS (Figures 10A and B).68
The completion of Fontan with percutaneous intervention
is an attractive and upcoming possibility.69 The congenital
extrahepatic portosystemic shunt (CEPS) is another

interesting entity found in ILAA with interrupted IVC. In this
condition, pulmonary hypertension often coexists, though
liver is functionally normal. The percutaneous closure of
abnormal channels in CEPS is possible.70 Neonatal catheter
interventions and palliative procedures are routine like balloon
atrial septostomy, ballooning of obstructive lesions, ductal
stenting.71 The systemic venous abnormalities may pose
special problems. Interrupted IVC in ILAA may complicate
a simple ASD device procedure. The electrophysiological
procedures can also be difficult in operated and non-operated
patients.
management
The HS is associated with spectrum of malformation and
malfunctioning of thoracoabdominal organs and needs
customized management plan. The goals of management are:
1. Diagnosis and management of malformations.
2. Infection control.
3. Parental counseling.
10
HeTeRoTAxy SyndRome
B
Figures 10A and B: Post-extracardiac Fontan surgery: LPA stenting in a 13-year-old boy
medical management7276
Usually, the babies presenting early have severe malformations
and need hospitalization and urgent intervention. Besides
clinical and routine bedside investigations, pulse oximetry
must be used to record basal saturation in both right upper and
lower limbs (Table 4).
InterventIon In Heterotaxy
catheter Intervention
The catheter interventions can be done before or after the
surgical intervention, as diagnostic or palliative procedures.
Rarely catheter interventions can be definitive procedure.
surgical Intervention5,34,7785
Majority of cases with right isomerism need surgical
intervention for their survival. Usual urgent surgical
interventions are required for TAPVC repair or for palliative
procedure like pulmonary artery banding or modified
Blalock- Taussig shunt. Majority of the patients with IRAA
need bidirectional Glenn shunt or total cavopulmonary
connection (TCPC). For few patients with IRAA and majority
of the patients with ILAA, biventricular corrective procedures
like AVSD repair, double switch with or without conduit can
be done.7785 These interventions are age dependent and are
usually done in stages. The ILAA group may require a late
intervention. Recently, with growing experience, surgeons
are less inclined to do univentricular repair.7781 Hence,
many centers are opting for biventricular or one and half
ventricular repair for the patients who initially underwent
bidirectional Glenn shunt. Hoashi T et al published a case
series of 9 patients,82 with previous Fontan procedure

(n = 3) or bidirectional Glenn shunt (n = 6) with intent for
a later Fontan procedure. Five of them had one and half
ventricular repair and 4 had biventricular repair. Two early and
one late death were reported in the series at a median followup of 27 months (range, 3.399.8 months). All survivors were
in New York Heart Association functional class I. Another
advancement reported recently is, early direct hepatic vein to
azygos anastomosis without cardiopulmonary bypass.83
Results of Surgical Intervention in Heterotaxy Syndrome

The outcome of HS in unoperated cases varies from early
demise to prolonged and productive life. The surgery is the
most important tool to modify the natural history.
By and large, IRAA is common in males and has high
mortality and morbidity.5,85 The patients with ILAA can be
associated with less severe cardiac malformation and have
better prognosis.4,5,8589 The adverse outcome patients with
ILAA, may be the result of severe extracardiac malformations.
Gilljam et al reported 18 percent mortality in babies with
normal heart.77
Nonetheless, neonates requiring early surgery have over
all, poor outcome. Complete AV septal defect, AV valve
regurgitation are independent risk factor against favorable
short term and long term results.22,58,67 In IRAA, presence
of complex CHD in association of pulmonary stenosis/
pulmonary atresia and extracardiac obstructive TAPVC,
invariably foretells poor survivability.85 Factually, all patients
may not be operated due to complexity of lesions or they die
before any intervention can be planned.
However, the technical improvement in diagnostic
modalities and concomitant improvisation in surgical
159
Table 4
BASIcS
Medical management of heterotaxy syndrome (cardiac disease*)7276

critical with cyanosis (rule out obstructed
TAPVc**)
Prostaglandin infusion
Suspecting cyanotic spell: follow the protocol for management of
cyanotic spell. Sedation, morphine, beta-blocker (esmolol, metoprolol)
infusion, IV fluid, sodabicarb and oxygen, blood transfusion or
ventilation if needed. Refer for surgery or PDA stenting, BAS.
critical baby with congestive heart failure
Decongestives, diuretics, digoxin, ACE inhibitors. Fluid restriction.

Blood transfusion, if required. Refer to PA banding, if required. BAS, if
transposition is suspected.
Recognition and treatment of fulminant sepsis
Prompt recognition of infection. Investigate and treat with appropriate

antibodies.
management of rhythm
Bradycardia: Atropine, isoprenaline, pacing for bradycardia.

Tachyarrhythmias: Antiarrhythmic, pharmacological or electrical
cardioversion.
* Other system must be evaluated, a cyanosed baby may be critical because of non-cardiac problems like volvulus.
** Surgical emergency.
techniques have increased the number of patients undergoing

either univentricular or biventricular repair.
Noritaka Ota et al reported a retrospective review of
institutional database from 1997 to 2010 and recognized 60
consecutive patients with IRAA having single ventricle. They
found that 5-year survival was 53.8 percent before 2003 and
81.7 percent after 2004 (p = 0.035) and identified persistent
AV valve regurgitation of more than moderate degree (p =
0.04) as a factor associated with late mortality.86
One of the recently published retrospective studies has shown
increased postoperative morbidity and mortality in 87 patients
with CHDs with HS in comparison to that of CHDs without
HS. They found prolonged postoperative hospital stay (17 : 11
days), prolonged mechanical ventilation (11 : 4 days), increased
number of tracheostomies (6.9% : 1.6%), increased use of
ECMO (12.6 : 4.9%) and postsurgical deaths (16.1 : 4.7%).87
bIventrIcular rePaIr In Heterotaxy syndrome

a surgIcal cHallenge
160
To achieve biventricular repair in IRAA is a surgical challenge.

Nevertheless, world over, the recent trend amongst the
surgeons is to attain a biventricular repair, whenever possible.
Lim et al reported the series of 371 patients with HS.
91/371 (24.5%) patients underwent biventricular repair from
1990 to 2007. Median age at repair was 6.8 months with a
range of 5 days to 22 years. LA isomerism was present in
73% (66/91) and right atrial isomerism in 10 percent (9/91),
with indeterminate atrial anatomy in 17 percent (16/91).
Combined lesions were common, occurring in 99 percent
of patients, which included systemic venous anomalies
in 82 percent (75/91), pulmonary venous anomalies in
28 percent (26/91), endocardial cushion defects in 39
percent (36/91), transposition complexes 16 percent (15/91),
AV discordance in 10 percent (10/91), double outlet right
ventricle (DORV) (3/91), tetralogy of Fallot (TOF) in

3.2 percent (3/91) and hemitruncus in 2.1 percent (2/91).
Operations included double switch repair, physiologic repair,
arterial switch and the Rastelli procedure. Separation of
systemic from pulmonary venous return included intra-atrial
baffle in 48/91 patients and extracardiac grafting in 2/91.
Average follow-up was 44.9 plus or minus 57.5 months
(3 days189.3 months). Kaplan-Meier estimated survival
was 93.4% at 10 years; unbalanced complete AV canal was
the only risk factor for mortality (P = .006). Subsequent
procedures were common with a 10-year freedom from
reoperation or reintervention of 38% 7.5%. Arrhythmias
occurred in 36 (39.6%) patients; bradyarrhythmia in 27
(29.7%) and tachyarrhythmia in 15 (16.5%). Freedom from
any arrhythmia was 53.9% plus or minus 6.7% at 10 years.88
These results are better than the previously published
series about surgical outcome in patients with ILAA. In
the series published by Gilljam et al, 87 percent cases
underwent biventricular repair and combined 15 years
survival was less than 50 percent.77 This difference may be
due to patient selection strategies because incriminated risk
factors had been congenital AV block, aortic coarctation,
single ventricle, billiary atresia and other gastrointestinal
malformations.77,79,84,88
PreventIve strategIes and Prenatal dIagnosIs

The genetic testing and counseling has some role to play, but a
definitive primary preventive strategy is yet to be found. When
we discuss the outcome of HS, the possibility of diverse outcome
always pre-exists. Additionally, the risk of sepsis in asplenic
patients or abnormal ciliary system in ILAA may influence
the outcome. Antenatal fetal echocardiography is the solitary
preventive strategy in routine use. The natural elimination by
spontaneous abortion has been noticed in many studies.
Streptococcus pneumoniae is the most common pathogen causing septicemia in asplenic children followed by
Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus and other streptococci.
The splenic malfunction is diagnosed by presence of target
cells, Howell-Jolly, Heinz, Pappenheimer bodies and pitted
erythrocytes in peripheral smear. The pits or pox on the red
cell surface, ability to clear 51Cr-labeled heat damaged red
cells, SPECT-CT done with 99mTc-labelled, heat altered
autologous erythrocyte scintigraphy are the advanced methods
to know the functional status of spleen.96,97
long-term management of asplenia/Hyposplenia7680

The four component of medical management are:
1. Antibiotic prophylaxis.
2. Appropriate immunization.
3. Very aggressive management of suspected infection.
4. Parent education.
Identification notes and written instructions must be
given to asplenic patients (Box 2). The recommendations are
Box 2: Asplenia or hyposplenia: Prophylaxis against

bacterial infection97101
Heterotaxy In adultHood
It is rare to have adult patients afflicted with HS probably
because severity of malformations makes them less capable to
endure life. However, few of case reports and small case series
have been reported. Majority of these patients had ILAA and
less severe cardiac malformations.49,92,93
The association of IRAA with asplenia leads to deficient

body defense mechanism. Besides, absence or inappropriate
functional abilities of spleen in ILAA are also known.
Thus, functional evaluation of the spleen is mandatory in
heterotaxy syndrome for an appropriate management plan.
The functional evaluation of spleen, bacterial prophylaxis and
infection control protocols are guided by experience gained in
splenectomized patients.
effect of asplenia/Hyposplenia9495
Risk of bacteremia is highest in absence of spleen. The bacteria

transmitted by human or animal bite, protozoal infestations
like malaria or babesiosis can be dangerous.
Universal immunization of IRAA patients with the

pneumococcal conjugate (PCV7) below 2 years and/or
polysaccharide vaccine (PPC23) above 2 years and influenza
vaccine can improve the morbildity.81 Reimmunization is
recommended for children who received pneumococcal
vaccine before 24 months of age
Children up to 5 years should also receive all doses of
Haemophilus influenzae type b vaccine. Unimmunized
children >5 years should receive 1 dose
Patients should also receive quadrivalent meningococcal
vaccine.
Antibiotic prophylaxis
functIonal status of sPleen In

Heterotaxy syndrome94101
10
HeTeRoTAxy SyndRome
Berg et al examined their database retrospectively and found

that in 32 of 35 fetuses had prenatal diagnosis of cardiosplenic
syndromes. 22 fetuses had left isomerism. Their main prenatal
ultrasound features were interrupted IVC (n = 21), CAVSD
(n = 15), viscerocardiac heterotaxy (n = 15), persistent
bradyarrhythmia (n = 12) and fetal hydrops or nuchal edema
(n = 12). 12 pregnancies were terminated, 2 fetuses were
stillborn and 8 infants survived. 10 fetuses had right isomerism.
Their main sonographic features were juxtaposition of
the descending aorta and IVC (n = 7), CAVSD (n = 7), left
persistent SVC (n = 6) and viscerocardiac heterotaxy (n = 6). In
this group there was 1 stillbirth, 5 infant deaths and 4 survivors.
They suggested that diagnosis of left isomerism should be
strongly suggested in the presence of a combination of at least
two of the following:
1. Complete atrioventricular septal defect or other structural
heart disease.
2. Interruption of IVC with azygos continuation.
3. Early fetal heart block.
4. Viscerocardiac heterotaxy.
Right isomerism should be suspected in the presence of a
combination of at least two of the following:
1. Structural heart disease, namely CAVSD.
2. Juxtaposition of IVC and descending aorta.
3. Viscerocardiac heterotaxy.89
Lin et al reported a series of 25 fetal diagnoses who were
diagnosed and managed on the basis of antenatal diagnosis.90,91
However, in their series isomerism of left atrial appendage
was twice as common as isomerism of right atrial appendage.
Regardless of vaccination status, children with splenic malfunction must be on antibiotic prophylaxis before 2-month
of age. Oral administration of penicillin V potassium is
recommended at a dosage of 125 mg twice a day until
3-year of age and at a dosage of 250 mg twice a day after
3-year of age. Children who have not experienced invasive
pneumococcal infection and have received recommended
pneumococcal immunizations may discontinue penicillin
prophylaxis after 5-year of age.
Some experts recommend that asplenic patients have
access to stand-by antibiotics (Amoxicillin with or without
clavulanic acid), which can be initiated with higher doses
schedule at the first sign of infection (fever, chills or
malaise). The initiation of stand-by antibiotics is not a
substitute for seeking immediate medical attention at the
onset of an illness cannot be overemphasized.7980
Asplenic patients have a high-risk to develop severe
malaria with very high peripheral blood parasite counts.
They should be given appropriate prophylaxis if travelling
to endemic areas.
161
BASIcS
extrapolation of the guidelines for the patients who underwent

spleenectomy for some medical reasons.
conclusIon
Heterotaxy syndrome, also known as incomplete lateralization
disorder, is now a well known entity of cardiac and non-cardiac
positional and structural anomalies. Demonstration of isomeric
atrial appendages, the juxtaposed abdominal aorta and IVC or
interrupted IVC, radiological evidence of isomeric bronchi
and numeric abnormalities of spleen, abnormal placement
of liver, helps in clinching this diagnosis. The meticulous
examination of all thoracoabdominal organs is essential before
making the management plan. The cardiac anomalies need
to be described by unbiased segmental analysis to deal with
the diversity of cardiac lesions. Identifying genetic etiology
will improve the overall management, prognostication and
recurrence risk assessment. Finally, functional assessment
of ciliary and splenic functions is essential to prevent lifethreatening infections.
Symptoms, then are in reality nothing but the cry from
suffering organs.
Jean Martin Charcot, translated from French
acknoWledgments
I want to express my special gratitude to Dr Rajesh Sharma,
Director and Head of Department of Pediatric Cardiac
Surgery for allowing me to access the data of his patients, to
Dr Aoorva Goyal, Sr Consultant and Mr Francis, Technician
from the Department of Radiology for helping me in retrieving
the CT angiographic images and to Dr Sanjay Khatri, Dr
Ashish and Dr Maitri Chaudhary for giving me their collection
of information. I am thankful to Ms Paramita Mishra and Mr
S. Balakrishnan for their help in editing.
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C hapter
11
Bedside Diagnosis of Acyanotic

Vijayalakshmi IB, Satpathy M
Introduction
The bedside diagnosis and detailed evaluation of the congenital
heart diseases (CHDs) in infants and children is an absolute
clinical necessity. Despite the tremendous advancement in
the various interventional invasive procedures and complex
cardiac surgeries for CHD, the success of these procedures
mainly depends on the early and precise diagnosis. Hence, the
accurate bedside diagnosis is no longer an academic curiosity,
as in the past, when there were hardly any treatment modalities
available.
There is a considerable variation in the presentation at
different ages (newborn to late adulthood), because the
manifestations mainly depend on the severity of the basic
lesion or the associated lesions. With the advent of fetal
echocardiography, CHD can be detected prior to birth thus
preparing not just the clinicians to manage these patients, but
the family too.
The newborn period extends up to the first month and
infancy up to the first year of life. When a clinician evaluates a
newborn or an infant in distress, it is important to differentiate
between cardiac and non-cardiac causes. It is very important to
exclude non-cardiac causes having structurally normal heart,
which can produce cardiorespiratory distress either during the
newborn or infancy period. At the same time, the physician
should not be complacent if a newborn is apparently normal,
because some complex cyanotic heart diseases remains
asymptomatic with no murmur for a brief period.
For a reasonably good clinical diagnosis the clinician
should pay careful attention to the traditional systematic
examination and must know the normal parameters and its
variations, according to the age group of the patients, so that
the abnormal findings can be easily detected and analyzed
methodically.
The systematic approach to CHD includes the following:
1. Detailed antenatal and postnatal history.
2. Systematic physical examination: Which includes gen-
eral examination, followed by detailed examination of

the cardiovascular system by inspection, palpation, percussion and auscultation. The examination of the respiratory system and abdomen should be done in a methodical
manner.
3. Electrocardiography (ECG)
4. Chest X-ray
5. Echocardiography
6. Computed tomography (CT) angiogram and cardiac magnetic resonance imaging (MRI) in selected cases
7. Invasive procedures like cardiac catheterization and angio
cardiography, if needed.
The diagnosis of CHD represents the summary of applied
clinical logic. Appropriate data should be extracted and
analyzed. When correct inferences are drawn from accurate
history, close observations with sharp clinical acumen,
diagnosis emerges with gratifying frequency.
Congenital heart defects are classified into two broad
categories: acyanotic and cyanotic congenital heart disease.
The acyanotic defects may further be subdivided into shunt
lesions and non-shunt lesions, which are further sub divided
into obstructive and regurgitant lesions (Table 1).
Acyanotic congenital heart diseases may present with signs
of congestive heart failure and/or heart murmurs that are heard
during physical examination and can manifest any time during
infancy or early childhood. Most of these patients present
during the first 6 months of life, when the shunt or obstruction
overwhelms the cardiac compensation and function. The
Nadas criteria can be applied for the diagnosis of CHDs
(Table 2). Presence of one major and two minor criteria are
essential for the diagnosis of CHDs.
HISTORY
Eliciting correct history or complaints from the parents or
reliable attenders during infancy is essential and cannot be
overemphasized in the evaluation of infants and children with
11
Table 1
Classification of acyanotic congenital heart diseases

Types
Defects
Shunt lesions
Pretricuspid
Atrial septal defect

Secundum
Sinus venosus
Primum
Coronary sinus type
Partial anomalous pulmonary venous drainageone vein or
entire drainage on right or left side (hemianomalous venous
drainage)
Post-tricuspid
Ventricular septal defect

Common atrioventricular septal defect
Shunts at great vessel level
Patent ductus arteriosus
Aortopulmonary window
Rupture of sinus of Valsalva aneurysm
Obstructive lesions
Aortic stenosis, subaortic obstruction, supra-aortic obstruction

Pulmonary stenosis, infundibular stenosis
Coarctation of aorta/interruption of aorta
Left ventricular inlet obstructions (parachute mitral stenosis,
supramitral ring, cor triatriatum)
Regurgitation lesions
Mitral, tricuspid, pulmonary, aortic

regurgitation
Non-shunt lesions
Table 2
Nadas criteria for the diagnosis of congenital heart diseases

Major criteria
Minor criteria
1. Systolic murmur of grade

34/6
Systolic murmur grade 2/6
2. Diastolic murmur
Abnormal second heart sound
3. Congestive heart failure
Abnormal chest X-ray
4. Cyanosis
ECG abnormalities
Abnormal BP
Presence of one major and two minor criteria are essential for diagnosis of
congenital heart diseases
suspected cardiovascular disorders. But, in our country due to

low literacy rate, eliciting proper history from the parents or
relatives can be difficult for the clinicians.
Presenting Complaints
The magnitude of the shunt or the severity of the obstruction
determines the clinical presentation and symptoms. Suspicion
of a congenital heart defect should be raised by the presence
of:
1. Feeding difficulties
2. Tachypnea
3. Sweating
4. Subcostal recession
Table 3
Causes of congestive heart failure in acyanotic congenital heart

diseases according to age
Age
Causes
1st day of life
Large arteriovenous fistula, congenital

severe pulmonary regurgitation (volume
overload of right ventricle), premature infant
having large PDA, pinpoint aortic stenosis
with hydrops fetalis
1st week of life
Coarctation of aorta, critical aortic stenosis,

critical pulmonary stenosis
1st month of life
Coarctation of aorta with large PDA, large

VSD, large PDA, AV septal defect
6 month of life
Any of the above conditions, VSD with PDA

or without PDA, anomalous origin of the
left coronary artery from pulmonary artery,
aortoventricular tunnels
1 year of life
Large VSD, AV septal defect
Bedside Diagnosis of Acyanotic Congenital Heart Diseases
Lesion
AV = Atrioventricular; PDA = Patent ductus arteriosus; VSD =

5. Recurrent respiratory infections

6. Growth impairment in the infant
7. Exercise intolerance
8. Easy fatigability or murmur in the older child.
The age of presentation with heart failure also gives a clue
regarding the type of acyanotic CHD (Table 3).
167
Basics
Symptoms
Feeding Difficulties
Feeding difficulties is a common symptom in significant
acyanotic CHDs. In infants, feeding itself is a form of exercise
or effort. An infant with heart failure has the inability to
complete feeds within 15 to 20 minutes, sucks less volume
of milk (< 3.5 ounces per feeding), gets tired easily and takes
frequent feeds (less than 2 hours). The infant has increased
breathing or tachypnea and perspiration during feeds. As the
feeds are inadequate they become irritable and cry excessively.
This suck-rest-suck cycle continues round the clock. Children
with respiratory distress and poor cardiac output due to heart
disease cannot be fed well, as it requires considerable effort to
suck, resulting in easy fatigability and failure to thrive.
Respiratory Distress
Respiratory distress is the most prominent sign of heart failure
caused by significant left-to-right shunting in infancy. Symptoms of respiratory distress include tachypnea or rapid breathing
(respiratory rate > 60/min in newborn and > 50/min in infants)
and intercostal and subcostal chest retractions. In very sick
infants, grunting and nasal flaring can also be present. Dyspnea
is manifested in infants by rapid breathing with retractions and
grunting. Older children may complain of shortness of breath.
Easy Fatigability
Fatigue on exercise or exercise intolerance must be distinguished from dyspnea, as it has a different physiologic basis.
It is a difficult symptom to interpret because of other factors,
such as motivation or amount of exercise an individual can perform. In an infant, it is seen as poor ability to suck and feed.
In older children, heart failure may be manifested as exercise
intolerance; difficulty in keeping up with peers during sports
or need for a nap after coming home from school and poor
growth. Eliciting a history of fatigue in an older child requires
questions about age-specific activities, including stair climbing, walking, bicycle riding, physical and competitive sports.
Repeated Lower Respiratory infections

Recurrent pneumonia has been defined as two episodes of
pneumonia in 1 year or three episodes in any time frame.
Respiratory infections, particularly pneumonia, are frequently
present in infants and less commonly, in older children with
cardiac anomalies, especially those associated with increased
pulmonary blood flow (PBF) or left-to-right shunt.
Growth Retardation or Failure to Thrive

168
Growth retardation is common in many children, who present

with other cardiac symptoms within the first year of life. Failure
to thrive is defined as weight < 3rd percentile for age. Usually,

the rate of weight gain is more delayed than that of height
gain. It is probably related to the inadequate caloric intake due
to breathlessness during feeding and to the excessive energy
requirements of congestive cardiac failure. If weight is severely
affected, a more general dysmorphic condition should be
suspected.
Chest Pain
Chest pain or angina is rare, but not unknown in infants and
children. Chest pain is a common and benign symptom in
older children and adolescents, estimated to occur in around 70
percent of school-going children. Chest pain may be the first
complaint that points to an unsuspected anatomic heart defect.
Pain associated with palpitations, dizziness and panic attacks
may be the presenting symptoms in some patients, who have
mitral valve prolapse (Barlow syndrome). These patients are
usually associated with a midsystolic click and occasionally an
apical mid-to-late systolic murmur. In patients, who have left
ventricular outflow tract obstruction (LVOTO) in the form of
stenosis of the aortic valve, subaortic valve area, supra-aortic
valve area or coarctation of the aorta, may present with chest
pain and associated with dizziness and fatigue. It can occur
in severe aortic stenosis or possibly in pulmonary stenosis
due to demand-supply mismatch resulting in myocardial
ischemia. Chest pain in association with exercise intolerance
and fatigue may be the initial presenting complaint of patients,
who have hypertrophic or dilated cardiomyopathy. Chest pain
due to myocardial ischemia can occur in patients, who have
abnormal coronary artery anatomy, including congenital
anomalies of the coronary artery, coronary artery fistulas and
stenosis or atresia of the coronary artery ostium and have been
recognized in infants with an aberrant left coronary artery. In
infants, it can present with excessive crying or irritability
associated with pallor or sweating. Chest pain can also occur
with very rapid paroxysmal tachycardia.
Syncope
Syncope is a transient loss of consciousness due to generalized cerebral ischemia, which usually is followed by rapid
and complete recovery. In rare instances, anoxic seizures may
result. Syncope may be preceded by palpitations, lightheadedness, dizziness, weakness, pallor, nausea, cold sweat, blurred
vision or hearing loss.
Syncope may result from impaired response of the
autonomic nervous system or from cardiac structural defects,
especially those obstructing blood flow, or from cardiac
arrhythmias. History of syncope on mild to moderate exertion
indicates severe aortic stenosis, hypertrophic cardiomyopathy
(HOCM), severe pulmonary hypertension or complete
transposition of the great vessels (CTGV). In CTGV, syncope
is due to significant bradycardia. The relatively uncommon
long QT syndrome is an especially worrisome cause of
syncope. Non-cardiac mechanisms, which cause syncope
Peripheral Edema
Pretibial and presacral edema are late developments in
the child with congestive circulatory failure, apparently
due to the difference in tissue turgor. When peripheral
edema due to heart failure does develop in an infant, it
first appears periorbitally, and is usually preceded by other
manifestations such as tachypnea, tachycardia, dyspnea and
liver enlargement.
Meticulous history is the corner stone for the diagnosis of

some diseases. The common symptoms of acyanotic CHD
and their pathophysiological basis is given in Table 4. The
grading of severity of heart failure in adults as proposed by
the New York Heart Association Class (NYHA) is universally
accepted. However, it is difficult to grade or apply these
classifications in children, especially infants. A common
system followed is the one advocated by Ross (Table 5).
Family History
A detailed family history at times is rewarding in CHD. If
one parent has a congenital heart anomaly, the risk of the
child having one (frequently the same type) can be as high
Table 4
Pathophysiology of common symptoms

Symptoms
Pathophysiology
Tachypnea
PBF will cause engorged vasculature resulting in interstitial edema. This is due to the
transudation of fluid under increased pressure across the capillary walls, which is faster
than the lymphatic clearance). This also acts as a barrier for proper gaseous exchange,
rendering the process less effective. To compensate for this the respiratory rate is due
to stimulation of the J (juxtacapillary) receptors in the alveolar interstitium, adjacent to the
pulmonary capillaries, due to the interstitial edema.
Dyspnea or shortness of breath
Occurs due to pulmonary congestion or interstitial edema from either left-sided cardiac
failure or other conditions raising pulmonary venous pressure or from oxygen diffusion
and hypoxemia. Left ventricular failure causes LVEDP and pulmonary venous pressure.
This causes a high back pressure in the pulmonary vessels and transudation of fluid into the
interstitial tissue, making the lungs less compliant. The child has to work harder to breathe.
Chest retractions
tidal volume and pulmonary compliance with expiratory airway resistance due to
interstitial lung water results in work of breathing, which is manifested as tachypnea,
intercostal and subcostal chest retractions. Wet and stiff lungs encourage secondary
infection. In very sick infants, grunting and flaring of alae nasae can also be present. PBF
may also result in compromise of the airways, leading to atelectasis and emphysema.
Feeding difficulties
Feeding itself is a form of exercise or effort. Children with respiratory distress and poor CO
due to heart disease cannot feed well as it requires considerable effort to suck resulting in
easy fatigability and failure to thrive. Also, as the feeds are inadequate, they are irritable.
Sweating
Inappropriate sweating is due to the release of catecholamines. In an infant, sweating

particularly while feeding is a reliable sign of overt or impending heart failure.
Recurrent respiratory infections
As a result of PBF the engorged pulmonary arteries compress the adjacent bronchi and
bronchioles leading to:
1. Microatelectasis, which leads to stasis of secretions. Atelectasis may also occur,
particularly in the right upper or middle lobe, in these children.
2. There is also goblet cell hyperplasia which causes increased mucus secretion. Both
these cause stagnation of mucus which forms a nidus for infection.
3. Coupled with this, there is the defects in clearance of airway secretions due to
abnormalities of the respiratory mucus or defects in the mucociliary function causing
reduced ciliary movement. This may be due to structural defects of cilia or secondary to
various infections.
4. These children also have decreased immune mechanism and they may be associated
with syndromes, which make them more prone to infections.
5. In addition, increased number of respiratory infections occurs due to blood pooling in the
lungs which is likely to prompt bacterial growth.
Contd...
11
in school-going children are vasovagal (neurocardiogenic),

orthostatic, breath holding and hyperventilation. Other causes
of syncope are metabolic, neurological and psychological
disorders.
169
Basics
Contd...
Symptom
Pathophysiology
Fatigue or exercise intolerance
Mainly due to the poor CO and increased energy consumption by an overworked heart.
Poor weight gain or failure to thrive
Mainly due to increased caloric demands due to increased work of breathing and overworked
myocardium with increased energy consumption to maintain an adequate CO combined
with poor intake. The child due to poor CO, tires easily during feeding and is unable to take
a full feed and also the rapid respirations diminish the time available for swallowing. There
is also secretion of anorexic hormones that limit the volume of feeds. The child has poor
appetite, frequent respiratory infections and poor absorption of nutrients from the digestive
tract. The poor CO and poor feeding due to shortness of breath and the elevated metabolic
expenditures associated with increased respiratory effort and myocardial work, leads to
decreased nutritional intake and/or increased catabolism.
Angina/chest pain
Demand to supply mismatch resulting in myocardial ischemia.
Syncope
May result from impaired response of the autonomic nervous system or from cardiac structural defects, especially those obstructing blood flow or from cardiac arrhythmias.
CO = Cardiac output; LVEDP = Left ventricular end diastolic pressure; PBF = Pulmonary blood flow.
Table 5
Modified classification of heart failure by Ross

Types
Features
Class I
No limitations or symptoms
Class II
Mild tachypnea or diaphoresis with feeding in

infants
Dyspnea on exertion in older children
No growth failure
Class III
Marked tachypnea or diaphoresis with feeds or

exertion
Prolonged feeding times
Growth failure from congestive heart failure
Class IV
Symptoms at rest with tachypnea, retractions,

grunting or diaphoresis
as 10 percent. When a first cousin has a congenital heart

anomaly, the risk of a sibling having one is approximately 2
percent. With no family history of CHD, if the firstborn has
a congenital heart lesion, the risk of a second child having a
congenital heart lesion is 2 to 3 percent, slightly higher than
the risk for the general population.
Maternal History
170
A maternal history of acute illness or exposure to drugs

especially in the first trimester or any chronic illness in the
mother may provide an etiological information. The history
should include:
a. Exposure to drugs (lithium, phenytoin, thalidomide)
b. Alcohol intake
c. TORCH infections especially rubella
d. Maternal diseases like diabetes mellitus, systemic lupus
erythematous, phenylketonuria
e. Exposure to radiation.
Box 1: Risk factors for CHD

Maternal History
Diseases
Diabetes mellitusVSD/hypertrophic cardiomyopathy,
pulmonary stenosis, PDA, TGA
Systemic lupus erythematosuscomplete heat block
PhenylketonuriaVSD, ASD, PDA
Infections/Ingestions/Exposure
Infections
RubellaPDA, pulmonary artery branch stenosis, congenital rubella syndrome
Mumpsendocardial fibroelastosis
Coxsackie virus, Cytomegalovirus, herpesvirus (in late
pregnancy)myocarditis
Drugs
AmphetaminesVSD, PDA, ASD, TGA
Phenytoin (Dilantin)PS, AS, CoA, PDA
TrimethadioneVSD, PS, TGA, TOF, HLHS
LithiumEbsteins anomaly
Retinoic acidconotruncal anomalies
Valproic acidASD, VSD, AS, CoA, pulmonary atresia with
intact IVS
Progesterone and estrogenVSD, TOF, TGA
Ingestions/Exposure
Alcohol (fetal alcohol syndrome)VSD, PDA
Marijuana, cocaineVSD
SmokingPDA, prematurity
AS = Aortic stenosis; ASD = Atrial septal defect; CoA = Coarctation of
aorta; HLHS = Hypoplastic left heart syndrome; IVS = Interventricular
septum; PDA = Patent ductus arteriosus; PS = Pulmonary stenosis;
TGA = Transposition of great vessels; TOF = Tetralogy of Fallot;
VSD = Ventricular septal defect
The most important contributory factors for development

of CHD are given in Box 1. In most instances, however, no
specific contributory factors can be identified.
11
PHYSICAL EXAMINATION
Figures 2A and B: A. Hypertelorism, distinctive webbed neck, low set

ear, small chin, malocclusion of teeth and wide-spaced nipples in a
Noonan patient; B. Short neck with low set ears with abnormal auricle
and low hairline in a 3-year-old Down syndrome patient
General Appearance
A wide spectrum of extracardiac malformations occur in 15-45%
of cases with CHD. Extracardiac malformations can give a clue
towards certain CHD. One should look for physical deformities
like polydactyly, fingerized thumb (Figure 1), which may
indicate atrial septal defect (ASD) or ventricular septal defect
(VSD). Hypertelorism distinctive webbed neck, low set ears,
micrognathia, malocclusion of teeth, with wide spaced nipples
are some of the features seen in Noonans syndrome (Figure
2A). Short neck or with low hairline is seen in Down syndrome
(Figures 2B). Mongoloid facies with transverse simian crease
on the palm, hypotonic and hyperflexible limbs are also other
features of Down syndrome (Figures 3A and B). Elfin facies
indicate Williams syndrome (Figure 4). Child having moon like
Figure 1: Hypoplastic radius with fingerization of thumb with,

polydactyly and syndactyly in 12-year-old boy with atrial septal defect
The following are several specific features that should be

observed and evaluated on examination of the patient:
1. Does the patient show signs of distress (e.g. tachypnea,
shortness of breath, clamminess or diaphoresis)?
2. Is the child responsive, interactive, happy or irritable?
3. Is there any change in color (e.g. pallor or cyanosis)?
4. Are there any dysmorphic features?
5. Are there any obvious skeletal abnormalities of the
chest, back or extremities? Is there a precordial bulge or
asymmetry of the chest?
6. Is the patient age appropriate for height and weight?
7. Is the patient developmentally delayed in motor skills,
speech or cognition?
The clinician must have a background knowledge of the
changed fetal to neonatal physiology. Careful inspection with
overall perception of the patient is very informative. The
physician should watch the activities of neonate or infant as
whether they are normal, listless or irritable.
Figures 3A and B: A. Mongoloid facies in a 1-year-old with Downs

syndrome; B. Palm of a 3-year-old child with Downs syndrome showing transverse simian crease
Figure 4: Elfin facies in a 12-year-old boy of Williams syndrome with

supra-aortic stenosis showing patulous lips and malocclusion of the
teeth
171
Basics
D
Figures 5A to D: Marfans syndrome: A. Steinberg thumb sign; B. Murdoch-Walker wrist sign; C. ArachnodactylyAbnormally long and
slender fingers on the left in comparison to normal fingers on the right; D. Kyphoscoliosis with deformed ear
Box 2: Common clinical syndromes associated with CHD

Down syndrome (Trisomy 21)ECD, VSD, ASD
Turner syndrome (XO)Coarctation of aorta in females, PS in
males, AS
Marfan syndromeDissection of aorta, aortic aneurysm, AR,
MVP
Rubella syndromePDA, PS, pulmonary artery branch
stenosis
Noonan syndromePS, ASD with/without PS
DiGeorge syndromeAortic arch anomaly, Conotruncal
anomaly
Holt-Oram syndromeFamilial ASD, VSD
172
Fanconi syndromePDA, VSD

Thrombocytopeniaabsent radiusASD, TOF
Rubinstein-Taybi syndromePDA
Ellis-van Crevald syndromeSingle atrium
Kartagener syndromeDextrocardia
Williams syndromeSupravalvular aortic stenosis, peripheral
PS
Laurence Moon Biedl syndromeVSD, TOF
Carpenters syndromePDA, VSD
Smith-Lemili-OpitzVSD, PDA
Goldenhar syndromeTOF
Multiple lentigenes (Leopard)PS
Fetal alcohol syndromeVSD, ASD, TOF
AR = Aortic regurgitation; AS = Aortic stenosis; ASD = Atrial septal defect; ECD = Endocardial cushion defect; MVP = Mitral valve prolapse;
PDA = Patent ductus arteriosus; PS = Pulmonary stenosis; TOF = Tetralogy of Fallot; VSD = Ventricular septal defect
Respiration
Respiratory distress is the most prominent sign of heart failure
caused by significant left-to-right shunting or obstructive
lesions in infancy. In newborns and infants, it is diagnosed by
tachypnea, altered depth of breathing, intercostal, subcostal
retraction, flaring of alae nasi, grunting, stridor and apneic
spells. Apneic spells are more common if central nervous
system (CNS) is involved. The respiratory rate and heart rates
vary with age (Table 6).
Arterial Pulse
Palpating the pulse is one of the simplest, oldest and yet the
most informative of all clinical examinations. The arterial
pulse is the abrupt expansion of an artery resulting from the
sudden ejection of blood into the aorta and its transmission
throughout the arterial system. Routine examination in
infants involves the brachial and femoral arteries. In the
adolescent, the carotid artery is added, in adults the radial,
popliteal, posterior tibial and dorsalis pedis pulses are
11
Table 6
Respiratory rate and heart rate at different age

Age
group
Respiratory rate
(per minute)
Tachycardia
Heart rate
Bradycardia
Newborn
4060
> 160
< 100
Infants
up to 30
> 120
< 90
14 years
2426
> 100
< 60
Adolescents
1820
> 100
< 60
routinely examined. The carotid pulse is palpated for pulse

contour, the femoral pulse is palpated for pulsus paradoxus.
The information to be gained from the examination of arterial
pulse includes rate, rhythm, character and symmetry (between
left and right side).
On simultaneous palpation, if femoral pulse is delayed,
weak or absent in comparison to the brachial or radial pulse
(radio-femoral delay), it indicates coarctation of aorta (CoA)
or interrupted aortic arch. Also, if there is any discrepancy in
both radial pulses it indicates supravalvular aortic stenosis,
aortic isthmus stenosis or pre-ductal CoA with the left
subclavian arising below the coarctation and the aortoarteritis
with obstruction to left subclavian artery. The right arm pulse
is usually better felt than the left arm pulse, because blood
pressure is slightly higher in right upper limb (the difference
is <10 mm Hg). If pulse in the right upper limb is much better
felt than the left upper limb, one should suspect supra-aortic
stenosis. The discrepancies occurs because the jet of blood flow
from supravalvular aortic stenosis (SVAS) has a preferential
trajectory into the brachiocephalic (innominate) artery. This is
called the Coanda effect. Also, the blood pressure is more in
the right upper limb than in the left upper limb (the difference
being >10 mm Hg).
The character of the pulse can give a clue to some of
the acyanotic CHDs. Collapsing pulse (also known as a
water-hammer pulse) is jerky, with a full expansion phase
followed by a sudden collapse upon raising the arm to the
level above the heart, as there is a rapid peripheral runoff
of blood in addition to a large stroke volume from the left
ventricle. It can occur in patent ductus arteriosus (PDA)
with normal pulmonary pressures, aortopulmonary window,
large arteriovenous fistula and bicuspid aortic valve with
severe aortic regurgitation. Pulsus parvus et tardus is a
pulse that is slow-rising with delayed upstroke, late-peaking,
low amplitude and is characteristic of severe valvular aortic
stenosis. It is best palpated on the carotid artery. A delayed
peak and slower upstroke of the carotid pulse suggests a
prolonged left ventricular ejection time. In patients with aortic
stenosis with incompetence, there may also be a palpable
vibration (thrill) on the ascending limb of the pulse (carotid
shudder). It is often difficult to palpate the carotid pulses of
such patients, because of lower pulse pressure and lack of a
rapid rise on the upstroke of the pulse.
facies indicates valvular pulmonic stenosis (PS). Musculoskeletal

abnormalities can be seen in Marfan syndrome (Figures 5A
to D). The common clinical syndromes in CHD are given in
Box 2.
The height, weight, head circumference and chest circum
ference should be plotted on appropriate growth charts. In the
absence of specific genetic conditions, head circumference
and length are generally spared in children with clinically
significant heart disease. The puffiness of the face, pitting
edema over the back of the hand and dorsum of the feet indicate
CHF. Poor physical development in the context of CHD is
very important. Weight at birth carries clinical significance.
Sometimes infants of large birth weight may also have cardiac
problems like cardiomyopathy (infants of diabetic mothers) or
cyanotic heart disease like transposition of the great arteries
(TGA). Infants with low birth weight particularly premature
infants (less than 1.5 kg of birth weight) have more chance
of CHD.
One should look for clubbing and any peripheral signs of
infective endocarditis (IE). They are less common overall
in children than in adults.The peripheral signs of IE are (a)
petechiae which are common but nonspecific; (b) subungual
(splinter) hemorrhages which are dark red linear lesions in
the nailbeds; (c) Osler nodes are tender subcutaneous nodules
usually found on the distal pads of the digits; (d) Janeway
lesions are nontender maculae on the palms and soles; (e)
Rarely, Roth spots which are retinal hemorrhages with small
and clear centers.
The vital signs like temperature, pulse, blood pressure,
heart rate and respiratory rate should be documented and
interpreted in the light of the childs general state at the time
of examination (e.g. quiet and cooperative, febrile or crying).
173
Basics
Blood Pressure
Jugular Venous Pressure
Recording blood pressure (BP) is essential, when assessing

the cardiovascular system. It is often difficult to measure exact
blood pressure in the upper and lower limbs in newborns and
infants, more so when the neonate is a premature one. Blood
pressure is taken by different methods at different ages. The
methods are: (i) Flush method, (ii) Doppler ultrasound
method and (iii) Oscillometric (Dinamap) method (these
are mainly for infants) besides conventional methods like
palpation.
Blood pressure cuff of the sphygmomanometer should be
of appropriate size according to the arm circumference. The
National Heart, Lung, and Blood Institute (NHLBI) has prepared
a range of blood pressure values based on the age, sex and height
of the children between the ages 3 to 17 years. These values are
based on percentiles. Hypertension is defined as either systolic
and/or diastolic blood pressure 95th percentile measured on
three or more separate occasions. The normal range of blood
pressure according to the age given in Table 7.
In all patients suspected of cardiac disease, one should
record accurately the BP in both arms and one leg. This helps
in diagnosis of conditions causing obstruction such as CoA,
recognition of conditions with aortic runoff, such as PDA,
aortopulmonary window and identification of conditions with
reduced cardiac output. The patient should be in a quiet, resting
state and appropriate sized BP cuff must be used. The ideal
cuff should have a bladder length that is 80 to 100 percent and
a width that is at least 40 percent of the arm circumference.
In infants, placing the cuff around the forearm and leg rather
than around the arm and thigh is easier. A 2-inch-wide cuff
can be used for almost all infants.
Upper extremity hypertension can be an important first sign
of CoA, but is often missed in children younger than 3 years
if BP is not obtained. The CoA is suspected, when the systolic
pressure is < 20 mm Hg in the legs than in the arms. Pulse
pressure (the difference between the systolic and diastolic
pressures) normally should be approximately one-third of
the systolic BP. A narrow pulse pressure is associated with
a low cardiac output or severe aortic stenosis. Pulse pressure
widens in conditions with an elevated cardiac output (anemia
and anxiety) or with abnormal runoff of blood from the aorta
during diastole (PDA or aortic insufficiency).
Jugular venous pressure (JVP) is raised, when the mean right

atrial (RA) pressure increases indicating right-sided heart
failure. The JVP is difficult to interpret in newborns and infants
(due to short neck and tachycardia). But in cases of younger
children and adolescence, JVP is easily studied. Prominent a
wave indicates a forceful atrial contraction present in cases
of tricuspid atresia, pulmonary stenosis with intact ventricular
septum, right atrial myxoma and Eisenmenger syndrome due
to ASD or PDA. In Lutembacher syndrome left atrial a wave
is reflected in the JVP. The schematic representation of various
waves of the normal JVP correlating with heart sounds and
electrocardiogram is illustrated in Figure 6.
Table 7
Normal range of blood pressure values
174
Age group
Systolic
(mm Hg)
Diastolic
(mm Hg)
1. Neonates
6070
2060
2. Infants
87105
5365
3. Toddler
95105
5366
4. Children
97112
5771
5. Adolescents
112128
6680
Oxygen Saturation
Documentation of systemic oxygen saturation with pulse
oximetry is generally reserved for patients with active
respiratory issues or known cyanotic heart disease.
Documentation of oxygen saturation of less than 94 percent
in the lower extremity would alert the practitioner, either to
cyanotic CHD or to any condition in which there is right-toleft shunting through the PDA into the descending aorta. This
differential cyanosis is seen in left heart obstructive lesions
such as CoA, interrupted aortic arch, hypoplastic left heart
syndrome, critical aortic stenosis or pulmonary hypertension
with PDA.
Precordial examination
Inspection
The precordium is the front of the chest overlying the
heart. One should look for abnormal chest shape, visible
pulsations, operation scars and an implanted pacemaker.
The left side of the thorax is prominent anteriorly or the
precordial bulge is seen due to the left atrial enlargement,
as in post-tricuspid shunts. The upper sternum may bulge
in children with a large left-to-right shunt and pulmonary
hypertension or with elevated pulmonary venous pressure.
As the left atrium is a posterior structure it has to enlarge
anteriorly and hence pushes the compliant sternum and
anterior ribs forward. This may not be evident in the first
month of life, but it certainly will be by 3 months of age.
In older patients with right ventricular (RV) hypertrophy
secondary to pulmonary hypertension there can be a
prominant precordium. Other types of chest deformities
are pectus carinatum, (Figure 7A) and pectus excavatum
(Figure 7B). Subcostal indrawing is abnormal and usually
indicates stiff lungs from either cardiac or pulmonary
causes. If the child has been symptomatic with respiratory
distress due to heart failure for more than 2 months, bilateral
Harrisons sulci may be seen. This is due to the increased
11
Palpation
Apex Beat
Figures 7A and B: A. Pectus carinatum and B. Pectus excavatum
diaphragmatic contractions during respiration, which

produces a sulcus in the lower thorax, with outward flaring
of the inferior ribs.
The abnormal location of the apical beat for age indicates
cardiomegaly. The visible pulsations over the precordium or
hyperdynamic precordium is mainly seen in volume overload
conditions like in post-tricuspid shunts. Left parasternal
pulsations and lift can be seen in large atrial septal defects
and in cases of RV hypertrophy. In patients with PDA,
aortopulmonary window, aortic insufficiency, aortic stenosis
and CoA, suprasternal pulsations can be visible.
Several findings may be discovered by palpation, the most

important being the localization of the cardiac apex, which
is an indicator of cardiac size. Obviously, if the apex is in
the right hemithorax, there is dextrocardia. The apex beat
is the point of maximal cardiac impulse. In infants and
children below 4 years, the apex beat is located in the fourth
intercostal space (ICS). Between 4 and 7 years it can be either
in the fourth or fifth ICS and thereafter in the fifth ICS. The
displacement of the apex beat laterally or inferiorly indicates
cardiac enlargement. A hyperdynamic apical impulse is seen
in volume overload conditions like post-tricuspid shunts and a
sustained heaving apical impulse is seen in pressure overload
conditions like in LVOTO.
Figure 6: Showing normal jugular venous pulse (JVP), carotid pulse tracing and electrocardiogram. The a wave of JVP occurs just prior
to the first heart sound (S1). The peak of v wave occurs just after the second heart sound (S2)
Thrill
A thrill is a palpable vibration caused by turbulent blood
flow and is always pathological. Thrills are best identified
by palpation of the precordium with the palmar surfaces
of the metacarpophalangeal and proximal interphalangeal
joints. Thrills are coarse, low-frequency vibrations occurring
with a loud murmur and are located in the same area, as the
maximal intensity of the murmur. Thrills at the lower sternal
border are more likely to be associated with VSDs than mitral
or tricuspid regurgitation. Thrills at the right upper sternal
border (RUSB) or suprasternal notch are most likely to be due
175
Basics
to severe aortic stenosis. Other less common cause of thrill

in the suprasternal notch is pulmonary stenosis. Diastolic
thrills are less common. Parasternal lift or heave is a forceful,
outward movement of the left lower parasternal region of the
precordium and it indicates RV hypertrophy.
Percussion
Percussion of the heart can substantiate estimation of cardiac
size in addition, to that obtained by inspection and palpation.
It is redundant now.
Auscultation
For the auscultation of heart sounds in infants and small
children pediatric-sized bell and diaphragm should be used.
High-pitched murmurs, first and second heart sounds are
better heard with the diaphragm; low-pitched murmurs, third
and fourth heart sounds are most evident with the bell. The
patient should be examined in a quiet area and in multiple
positions such as supine, left lateral decubitus, upright and
leaning forward, as well as during inspiration and expiration.
The examiner should auscultate over the listening areas; 2nd
RICS, 2nd LICS, 4th LICS and the apex. The carotids and
chest areas, both front and back, should also be included.The
auscultatory areas are shown in Figure 8.
Heart Sounds
The first and second heart sounds are produced by the valve
closure of the atrioventricular (AV) and semilunar valves
respectively. The normal heart sounds include S1, S2 and in
176
Figure 8: Standard auscultatory areas
the young individual S3. Normally, mitral (M1) and aortic

(A2) heart sounds are louder than and precede tricuspid (T1)
and pulmonary (P2) heart sounds. In children, the individual
mitral and tricuspid components are usually indistinguishable,
so the first heart sound is apparently single. Occasionally, two
components of this sound are heard. A loud S1 can occur with
increased flow across the AV valves from large left-to-right
shunts, such as ASD, VSD or PDA.
Potain in 1866 recognized splitting of the two components,
aortic (A2) and pulmonic (P2), of the second heart sound during
normal inspiration. Splitting of S2 is physiological and normal
on inspiration, when the degree of splitting increases, whereas
on expiration it decreases. Shaver et al in 1974 described this
Hangout interval as a time interval or gap between the arterial
pressure curve and the respective pumping chamber pressure
curve (right or left ventricle) at the level of incisura. Incisura is
the notch on the descending limb of the arterial pressure curve,
which coincides with the pulmonary or aortic valve closure.
In the highly compliant (low-resistance, high-capacitance)
pulmonary vascular bed, the hangout interval may vary from
30 to 120 msec contributing significantly to the duration of
RV ejection. In the left side of the heart, because impedance is
much greater, the hangout interval between the aorta and left
ventricular pressure curve is negligible (less than or equal to 5
msec). The hangout interval therefore correlates closely with
the impedance of the vascular bed into which blood is being
injected. Its duration appears to be inversely related to vascular
impedance. Leatham in 1964 described the second heart sound
as the key to the auscultation of the heart. The S2 is of great
diagnostic significance and also helps in assessing the severity
of the lesion.
Normal splitting: Some acyanotic CHDs with normal
splitting are small VSD, mild aortic or pulmonic stenosis.
The second heart sound can be split abnormally either as
wide (persistent splitting, with normal respiratory variation)
or fixed split (persistent splitting without respiratory variation)
or paradoxical (reversed) splitting.
Wide splitting: The wide splitting of S2 can occur either due
to conditions prolonging RV ejection and causing a delay in
the pulmonic valve closure with a wide hangout interval or
in conditions with short left ventricular systole causing an
early closure of the aortic valve. Acyanotic CHDs causing
a delay in P2 may occur either due to decreased impedance
of the pulmonary vascular bed (e.g. ASD, partial anomalous
pulmonary venous connection (PAPVC), idiopathic dilatation
of the pulmonary artery) or due to RV pressure overload
lesions (e.g. moderate to severe valvular pulmonic stenosis,
pulmonary hypertension with right heart failure and acute
massive pulmonary embolism). Wide splitting may occur
with an early A2 in patients with decreased resistance to left
ventricular outflow.
Fixed splitting: The fixed splitting of S2 denotes absence of
significant variation of the splitting interval with respiration,
such that the separation of A2 and P2 remains unchanged
during inspiration and expiration.
valve or deformity of the chest wall or lung. Loud A2 is due

to increased flow, increased pressure and dilatation of the
root of aorta. It can also be appreciated in acyanotic CHDs
like COA and in ascending aortic aneurysm. Soft A2 can be
appreciated in valvular, supra valvular aortic stenosis and in
aortic regurgitation.
The P2 is considered to be abnormally loud in a subject
over the age of 20, if it is greater than the aortic component
in the second left ICS or if it is audible at the cardiac apex.
The P2 is accentuated when PAH occurs, due to the elevation
of pulmonary vascular resistance (PVR) or due to increased
pulmonary arterial blood flow. As the level of pulmonary
arterial pressure increases, the P2 becomes louder and closer
to the aortic component and there is a narrow split of the
second sound. When the PVR is equal to or greater than
systemic vascular resistance, closure of A2 and P2 will be
nearly simultaneous, resulting in an audible single S2, as in
PAH and Eisenmenger syndrome. In cases of ASD, P2 may
be heard at the apex without PAH due to the RV dilatation.
However, if P2 is very loud and increases with mild exercise,
then PAH with ASD can be diagnosed. The P2 is soft or muffled
in acyanotic CHDs like pulmonary stenosis. Masking of P2
may be due to loud A2, early opening snap and holosystolic or
continuous murmurs.
Third and Fourth Heart Sound

The third heart sound (S3) and the fourth heart sound (S4)
occur in the ventricles and are low pitched and best heard
with the bell of stethoscope. They are heard loudest over the
ventricle in which they occur. The S3 is usually related to high
flow, whereas S4 reflects a poorly compliant ventricle. The S3
occurs due to rapid ventricular filling in early diastole. They
are normal in children with hyperdynamic circulation and thin
chest wall, but are usually abnormal in patients older than 30
years of age. It occurs at the peak of ventricular inflow into
the compliant ventricle. The S3 may originate from the left or
right ventricle and is best heard at the cardiac apex or the left
lower sternal border respectively. The S3 is prominent, when
there is increased volume of ventricular inflow (as is seen
in lesions with left to right shunts causing increased PBF),
valvular regurgitation and high cardiac output (as is seen with
anemia). A gallop rhythm heard in congestive cardiac failure,
often represents exaggeration of the third heart sound in the
presence of tachycardia.
The S4 is never considered normal and is due to atrial
contraction inducing ventricular filling late in diastole. They
occur with the P wave of the ECG and is synchronous to the
atrial a wave. They are found in conditions in which, either the
atrium forcefully contracts against a ventricle with decreased
compliance, as from fibrosis or marked hypertrophy, or when
the flow from the atrium to the ventricle is greatly increased.
The S4 may be audible as a presystolic gallop, particularly if
tachycardia is present.
11
In ASD the fixed nature of the split is due to approximately

equal inspiratory delay of the aortic and pulmonic components,
indicating that the two ventricles share a common venous
reservoir. In ASD the second heart sound is widely split
because the pulmonary hangout interval is wide and fixed, as
the RV stroke volume does not show the normal respiratory
changes. This is due to the dynamic phasic shunting across
the interatrial septum, which keeps the RV diastolic as well as
systolic volume relatively constant. The respiratory variation of
S2 splitting, immediately returns to normal following surgical
repair of an ASD, although the pulmonic closure sound may
remain delayed for weeks or months. Fixed splitting is also
seen in severe right heart failure due to the relatively constant
RV output as RV inotropism is not good enough to handle
the inspiratory augmentation of RV end diastolic volume.
The RV fails to respond to the increased volume produced
by inspiration and the impedance to forward flow from the
RV barely falls during inspiration due to the congested lungs.
In partial anomalous pulmonary venous return without ASD,
fixed splitting is not usually seen.
Paradoxical splitting or reversed splitting is heard maximal
during expiration and minimal or not in inspiration. Thus
P2 precedes A2. Paradoxical splitting always indicates
significant underlying cardiovascular disease and is
usually due to prolongation of left ventricular activation or
prolonged left ventricular emptying that may delay the aortic
component, causing it to follow the pulmonary component.
Left ventricular ejection is prolonged in conditions in which
the left ventricle ejects an increased volume of blood into
the aorta (e.g. PDA), in left ventricular outflow obstruction
(e.g. severe aortic stenosis) or in delayed depolarization of the
left ventricle (complete left bundle branch block). The most
common cause of paradoxical splitting of the second sound is
left bundle branch block. Thus, wide splitting and paradoxical
splitting of the second heart sound occur from similar cardiac
abnormalities, but on opposite sides of the heart. Paradoxical
splitting is associated with severe left-sided disorders.
When the A2-P2 interval is just more than 30 msec then
narrow splitting is appreciated. This is seen in shunt lesion
with severe pulmonary artery hypertension (PAH) without
RV failure. Patients with VSD, who develop PAH may no
longer have splitting of S2. Patients with ASD and associated
PAH maintain a wide and fixed split of S2. Splitting is narrow
(less than 30 msec), but remains physiologic, in patients with
PDA who develop PAH. In acyanotic CHD like severe aortic
stenosis, due to the delayed aortic closure one can appreciate
a single S2.
The loudness of each component of S2 is proportional
to the respective pressures in the aorta and pulmonary
artery at the onset of diastole. Dilatation of the aorta or
pulmonary artery may also cause accentuation of the aortic
and pulmonic components, respectively. Decreased intensity
of either component of the second sound may be due to stiff
semilunar valve, decreased pressure beyond the semilunar
177
Basics
Ejection Clicks
Clicks are classified as ejection or nonejection clicks. The
most common clicks occur in systole and are related to
abnormalities of the aortic, pulmonic and mitral valves.
Systolic ejection clicks are abnormal and they mark the
transition from the isovolumetric contraction period, to the
onset of the ventricular ejection. It can be heard shortly after
the opening of the semilunar valves and are sharp, high-pitched
sounds with a click-like or clicking quality. They are heard
loudest over their respective valves, except the aortic click
that is usually well heard at the apex. These sounds have been
classified as valvular, originating from deformed aortic and
pulmonic valves or as vascular, due to the forceful ejection
of blood into the great vessels. The vascular clicks indicate
dilatation of either ascending aorta or pulmonary trunk. The
dilatation may be due poststenotic dilation secondary to either
aortic or pulmonary valvular stenosis or from conditions with
dilated major arterial trunk, like in Marfans syndrome or
pulmonary hypertension. The mechanism of valvular click
is unknown. It occurs at the point of maximal opening of a
stenotic valve suggesting a valvular origin. It may also result
from tensing of the wall of a dilated great vessel in which
there are degenerated elastic fibers and the wall is supported
by collagen, which is indistensible.
Ejection clicks in patients with a stenotic semilunar valve
occurs more commonly in mild or moderate stenosis and is
absent with severe stenosis. The pulmonary ejection click is
unique in that it is loudest during expiration. It is heard best
with the diaphragm, in the pulmonary area with the patient
sitting. The aortic ejection clicks is widely transmitted and
heard best at the cardiac apex or over the left lower thorax
with the patient in a supine position. They do not vary with
respiration. The aortic valvular ejection sound is found
in non-stenotic congenital bicuspid valves. Clicks are not
associated with dysplastic pulmonary valves, which move
poorly if at all, or with fixed subvalvular stenosis.
Midsystolic click or non-ejection clicks with or without
a late systolic murmur is heard at the apex in mitral valve
prolapse. They are sharp, high-pitched and best heard at the
cardiac apex. They vary with maneuvers, which alter the left
ventricular volume. They are louder, when patient is standing
or sitting as LV volume is small and softer when patient
reclines or squats, which results in larger LV volume.
Murmurs
178
A cardiac murmur is defined as a relatively prolonged series of

audible vibrations of varying intensity (loudness), frequency
(pitch), quality, configuration and duration. Cardiac murmurs
are generated by turbulence in the normal laminar blood
flow through the heart. Leatham has attributed production of
murmurs to three main factors:
1. High flow rate through normal or abnormal orifices.
2. Forward flow through a constricted or irregular orifice or

into a dilated vessel or chamber.
3. Backward or regurgitant flow through an incompetent
valve, septal defect or patent ductus arteriosus.
A combination of these factors is frequent. Before laying
a stethoscope on the patients precordium, the physician must
have a clear concept of what to listen and where to auscultate.
The importance of listening with the child supine cannot
be over- stressed. Murmurs, which are frequently detected
in children, may either be innocent (Stills murmur) or
pathological and it is important for the clinician to decide the
category.
The murmurs are classified by their timing as systolic
(occurring between the first and second heart sounds), diastolic
(between the second sound and the first sound) or continuous
(present continuously throughout the cardiac cycle). Continuous
murmurs also includes the murmur that begins in systole,
marches over the second sound and ends in diastole. Other
characteristics of the murmur to be observed are the location,
shape (crescendo, decrescendo, diamond, plateau), character
or quality (e.g. harsh, soft, blowing, rumbling, vibratory),
radiation (the general rule of thumb is that the sound radiates in
the direction of the blood flow), intensity or grades, pitch (low,
medium or high) and variation with maneuvers (inspiration,
standing, squatting).
The most popular classification of murmur intensity is
described by Freeman and Levine. The systolic murmurs are
graded from 1 to 6 and the diastolic murmurs are graded from
1 to 4. The intensity of murmur varies with the velocity of
blood flow across the area, where murmur is produced. The
velocity, in turn, is directly related to the pressure that drives
the blood across the murmur producing area.
Grading of Murmurs
Grade 1so faint that it can be heard only with special
effort.
Grade 2faint, but can be heard easily.
Grade 3moderately loud, but no thrill.
Grade 4loud with palpable thrill.
Grade 5extremely loud and can be heard if only the edge of
stethoscope is in contact with skin.
Grade 6
exceptionally loud and can be heard with
stethoscope just removed from skin contact.
Age of Presentation of Murmur

If a murmur is audible in the first few hours of life it is often
due to structural heart disease particularly outflow obstruction
or valvular heart disease, as their flow characteristics is
independent of PVR changes. These murmurs are usually due
to tricuspid valve regurgitation, aortic or pulmonary valve
stenosis or else subvalvular aortic or pulmonary stenosis.
Frequently, the PDA murmur is not continuous in the first week
of life and may be loudest at the left sternal border in the third
and fourth interspaces. Occasionally, a long, high-pitched,
Systolic Murmurs
Systolic murmurs are heard between S1 and S2. They can
be classified according to the time of onset and termination
in systole: early systolic, midsystolic (ejection systolic),
late systolic and holosystolic (regurgitant) murmur (Figure
9). An ejection systolic murmur (midsystolic) begins after
the S1 and ends before A2 (left sided) or P2 (right sided).
An early systolic murmur starts with S1 and extends for a
variable length in systole, but does not extend up to S2. A late
systolic murmur starts after S1 and extends to A2 (left sided)
or P2 (right sided). A holosystolic murmur starts with S1 and
extends up to A2 (left sided) or P2 (right sided).
The ejection systolic murmur or midsystolic murmur
results from the turbulent blood flow across the semilunar
valves. Mid-systolic murmurs typically have a crescendodecrescendo character, that is, they start softly and become
loudest near midsystole, followed by a decrease in sound
amplitude. They are also called crescendo-decrescendo or
diamond-shaped murmurs. These murmurs are seen in fixed
or dynamic outflow tract obstruction, increased flow across
normal semilunar valves, dilatation of the aortic root or
pulmonary trunk and in anatomical changes in the semilunar
valves without obstruction.
A bicuspid aortic valve is a frequent cause of a ejection
systolic murmur; this diagnosis should be entertained if the
murmur is brief with an aortic ejection sound. The murmur
is best heard over the right second interspace with little or no
radiation. In valvular aortic stenosis, the maximum intensity
is appreciated over the right second interspace; the ejection
systolic murmur is harsh and rough and a thrill may be palpable
over the same area. The murmur radiates up into the neck and
over both carotid arteries. In patients with aortic stenosis, the
longer and later peaking murmur is usually associated with
hemodynamically significant obstruction; a brief and early
peaking murmur indicates mild stenosis. The intensity of the
murmur is variable and may not correlate with the severity of
stenosis. In the presence of heart failure and a reduced stroke
volume, the duration, configuration and intensity bear a poor
correlation to the degree of obstruction. The ejection sound
is usually absent in severe stenosis. The site of maximum
intensity and direction of radiation of the murmur are related
to the site of obstruction and the direction of the jet in the aortic
root.
In supravalvular aortic stenosis, the murmur may be loudest
at a slightly higher location than in valvular aortic stenosis. In
addition, the intensity of the radiated murmur over the right
carotid may be greater than over the left carotid artery. In
subvalvular left ventricular outflow obstruction (hypertrophic
cardiomyopathy), the maximum intensity of the murmur is
usually located along the lower left sternal border or over the
cardiac apex. It radiates poorly to the base and neck.
It is usually not difficult to distinguish between fixed
(aortic stenosis) and dynamic (obstructive hypertrophic
cardiomyopathy) LVOTO. The character of the carotid pulse
provides important clues. In aortic valve stenosis, the initial
upstroke and the peak of the carotid pulse are delayed and
the volume may be reduced. In obstructive hypertrophic
cardiomyopathy, the initial upstroke of the carotid pulse
is usually sharp and the volume is normal. The change in
intensity of the ejection systolic murmur in response to
different maneuvers is also useful diagnostically. Assuming
a standing position increases the intensity of the murmur
in hypertrophic cardiomyopathy; it decreases the murmur
of aortic valve stenosis. The murmur of hypertrophic
cardiomyopathy increases in intensity with the straining phase
of the Valsalva maneuver and the carotid pulse decreases or is
unchanged. Both the intensity of the murmur and the carotid
pulse volume decline with the Valsalva maneuver in aortic
stenosis; the heart rate increases and arterial blood pressure
falls.
The murmur of valvular pulmonary stenosis is harsh and
best heard over the left second interspace. When the murmur
is loud it radiates to the left side of the neck and is frequently
accompanied by a palpable thrill. A pulmonary ejection sound
at the onset of the murmur may be heard and S2 is widely
split with a decreased intensity of P2. The murmur duration
correlates reasonably well with the severity.
11
blowing, organic-sounding, systolic murmur is encountered,

heard maximally in the axillae. Common in prematures, it
also can be heard in full term babies with an increased stroke
volume. This murmur arises in the peripheral pulmonary
arteries and is usually innocent and should disappear by 2
months of age. The murmur of a VSD is often not present in
the first week of life. As PVR drops in the first few days in a
variable manner and continues to decrease during the first few
months of life, murmurs of shunt lesions, such as VSD, AV
canal (endocardial cushion) defect, PDA and ASD, become
audible.
Holosystolic Murmurs
Holosystolic (pansystolic) murmurs begin with the first heart
sound and extend through systole. The intensity of these
murmurs is high immediately after the onset of S1 and it
extends to just before the S2. Often the S1 and S2 sounds
are overwhelmed by the murmur and may be difficult to
hear. This type of murmur is typically heard in AV valve
regurgitation. Mitral and tricuspid regurgitation murmurs
are high pitched, with variable intensity and blowing quality.
The murmur of mitral regurgitation is accentuated when the
patient is in the left lateral decubitus position and it classically
radiates to the axilla and left infrascapular region; its intensity
does not change with respiration. The murmur of tricuspid
regurgitation increases in intensity with inspiration. It tends
to radiate to the xiphoid area or epigastrium and right sternal
border, but not to the axilla. Tricuspid regurgitation is often
179
Basics
Figure 9: Schematic diagram of various murmurs in different acyanotic congenital heart diseases. A2 = Aortic component of second heart sound;
AS = Aortic stenosis; ASD = Atrial septal defect; EC = Ejection click; MR = Mitral regurgitation; MS = Mitral stenosis; P2 = Pulmonary component
of second heart sound; PDA = Patent ductus arteriosus; PH = Pulmonary hypertension; PR = Pulmonary hypertension; PS = Pulmonary
stenosis; S1 = First heart sound; TR = Tricuspid regurgitation; VSD = Ventricular septal defect;
180
Diastolic Murmurs
Diastolic murmurs occur after S2 and are therefore associated
with ventricular relaxation and filling. Diastolic murmurs are
also classified according to the time of onset and termination
of the murmur in diastole. Diastolic murmurs are usually
abnormal and may be early, mid or late diastolic. They may be
caused by aortic or pulmonic valve regurgitation or by mitral or
tricuspid valve stenosis. Early diastolic murmurs, immediately
follow S2 and are seen in aortic and pulmonary regurgitation.
Mid-late diastolic murmurs occur due to stenosis or increased
flow across the mitral or the tricuspid valves. These murmurs
can occur in mitral stenosis, tricuspid stenosis, or as flow
murmurs of ASD, VSD and PDA. Late diastolic (presystolic)
murmurs occur due to pathological narrowing of the AV
valves. The pulmonary regurgitation murmur in patients with
normal pulmonary artery pressure, is low-pitched and early
diastolic because of the low-pressure gradient. In patients with
pulmonary hypertension, the murmur, known as the GrahamSteell murmur is heard, which is also early diastolic but is high
pitched and decrescendo, because of the high pressure gradient
between the pulmonary artery and the right ventricle in
diastole. The murmur of pulmonary regurgitation increases in
intensity during inspiration, unlike that of aortic regurgitation.
Continuous Murmurs
The continuous murmur is a murmur that begins in systole
and continues without interruption, encompassing the second
sound, throughout diastole or part of thereof. Continuous
murmurs result from blood flow from a higher pressure
chamber or vessel to a lower system associated with a
persistent pressure gradient between these areas during systole
and diastole. These murmurs may occur due to aortopulmonary
connections, arteriovenous communication and disturbances
in the flow patterns in the arteries or veins. The continuous
murmur from aortopulmonary communications is loudest
around the S2. The arterial continuous murmur is characterized
by a more pronounced systolic component while a venous
continuous murmur is characterized by a more pronounced
diastolic component. The differential diagnosis for continuous
murmurs is given in Box 3.
The systolic-diastolic murmur or the so-called to-andfro murmur, is not a continuous murmur. It being different
through a small silence separating the two murmurs. A toand-fro murmur, involves two components: a systolic one in
which the blood flows in one direction and a diastolic one in
which the blood flows in the opposite direction, while in those
with true continuous murmur, the blood flows in the same
direction in both systole and diastole.
Box 3: Classification of continuous murmurs

Continuous murmurs caused by high-to-low pressure
shunts:
Systemic artery to pulmonary artery (patent ductus arteriosus, aortopulmonary window, truncus arteriosus, pulmonary atresia with collaterals, anomalous left coronary artery,
bronchiectasis, sequestration of the lung)
Systemic artery to right heart (ruptured sinus of Valsalva,
coronary artery fistula)
Left-to-right atrial shunting (Lutembacher syndrome, mitral
atresia with restrictive atrial septal defect)
Venovenous shunts (anomalous pulmonary veins, portosystemic shunts)
Arteriovenous fistula (systemic or pulmonary)
Continuous murmurs secondary to localized severe
arterial stenosis:


Branch pulmonary artery stenosis
Carotid stenosis
Celiac mesenteric stenosis
Renal stenosis
Femoral stenosis
Coronary stenosis
Continuous murmurs caused by rapid blood flow:

Venous hum
Mammary souffl
Hemangioma
Hyperthyroidism
Acute alcoholic hepatitis
Hyperemia of neoplasm (hepatoma, renal cell carcinoma,
Paget disease)
11
associated with pulmonary hypertension and hence signs such

as a sternal heave (right ventricular hypertrophy) and a louder
P2 may provide additional clues.
Abdominal Examination
Normally liver is palpable (23 cm below costal margin) at
midclavicular line up to 4 to 5 years of the age, after that
it remains palpable up to 1 cm till late childhood. If liver
is palpable further downwards and the infant is irritable it
probably indicates presence of congestive heart failure. If the
liver is in midline and palpable symmetrically, it indicates
cardiac malpositions and underlying complex heart disease.
The site of the gastric fundus is detected by percussion, which
determines visceral situs. Spleen is not normally palpable; if
palpable it indicates possibility of infective endocarditis.
Respiratory System Examination

Apart from rate of respiration, it is important to auscultate both
lung fields. Bilateral crepitations is an important sign of left
heart failure. Unlike adults, where crepitations is commonly
basal, in neonates and infants it is more diffusely heard and
often associated with rhonchi. The clinical characteristics of
common types of CHD are summarized in Table 8.
181
Basics
Table 8
Characteristics of common types of lesions

Left-to-right shunts
Right-to-left shunts
No shunt lesions (obstruction to blood

at different levels)
Usually acyanotic
Cyanosis (may be associated clubbing)
No cyanosis
Frequent chest infections
U
sually no history of recurrent chest
infections
N
o recurrent chest infections
P
ulsatile precordium (active
precordium with or without precordial
prominence)
N
o precordial activity (silent
precordium)
S
ilent precordium, but forceful RV/LV
impulse
Cardiomegaly
N
o cardiomegaly
No cardiomegaly
Shunt murmurs and flow murmurs (if

shunt large)
No shunt murmurs
H
arsh ejection systolic murmurs (may
be with thrill)
Increased pulmonary vascularity

(plethoric lung fields)
D
ecreased pulmonary vascularity
(oligemic lung fields)
Normal pulmonary vascularity
T
endency for CHF to occur at early
phase mainly during infancy
C
HF occurs in late phase
C
HF occurs in very late phase; rarely it
occurs early in severe stenotic lesions
CHF = Congestive heart failure; LV = Left ventricle; RV = Right ventricle
conclusion
Clinical assessment is a solid foundation for diagnosis and
management strategy for cases of CHD. Meticulous history is
the cornerstone of the diagnosis of some CHDs.
Auscultation is an art. Never auscultate from the wrong side
of the bed. One should know, what to hear and where to hear.
One should find out the reason, if one does not hear what is
expected after analyzing the good history, thorough general and
systemic clinical examination. The clinician should not leave
the bedside until systematic analyses has been done of what
one has heard on auscultation. The clinician is the captain of the
ship (patient). If he fails to detect the disease in time by clinical
examination then he will not get the relevant investigations
done and the patient is denied the proper treatment.
Stages of Learning
1. Unconscious Incompetence: I do not know that I do
not know how to do this. This is the stage of blissful
ignorance before learning begins.
2. Conscious Incompetence: I know that I do not know
how to do this, yet. This is the most difficult stage,
182
where learning begins and where the most judgments

against self are formed. This is also the stage that most
people give up.
3. Conscious Competence: I know that I know how to
do this. This stage of learning is much easier than the
second stage, but it is still a bit uncomfortable and selfconscious.
4. Unconscious Competence: What, you say I did something well? The final stage of learning a skill is when it
has become a natural part of us; we do not have to think
about it.
Suggested Reading
1. Clinical Methods. In: Walker HK, Hall WD, Hurst JW (Eds).
The history, physical and laboratory examinations. 3rd edition.
Boston: Butterworths; 1990.
2. Libby. Braunwalds. In: Libby P, Bonow RO, Mann DL, Zipes
DP (Eds). A Textbook of Cardiovascular Medicine. 8th edition.
Elsevier Saunders; 2007.
3. Perloff JK, Marelli AJ. Clinical recognition of congenital heart
disease. 6th edition. Philadelphia: Saunders, an imprint of
Elsevier Inc; 2012.
C hapter
12
Clinical Approach to
Cyanotic Heart Diseases
Sudhayakumar N
Cyanotic congenital heart disease (CCHD) can be defined as an

anatomical congenital cardiovascular birth defect, which results
in systemic arterial desaturation due to right-to-left shunt. Review
of literature reveals a reported incidence of congenital heart
disease (CHD) varying between 1.2 and 17 per thousand live
births (probably on an average 8 per 1,000), of which cyanotic
congenital heart disease (CCHD) may contribute to about
one-fourth.1,2 With recent advances in diagnostic modalities
and improvement in interventional and surgical management,
the survival and quality of life of children with CCHD have
improved tremendously. Though technology has revolutionized
the diagnostic tools, a clear understanding of pathophysiology
along with meticulous clinical examination and analysis of
simple bedside investigations like 12-lead electrocardiogram
and chest skiagram can contribute heavily to proper diagnosis
and management of even very complex CCHDs.
Cyanotic congenital heart disease includes a wide spectrum
of anatomical and physiological aberrations ranging from a
relatively simple lesion like mild tetralogy of Fallot to very
complex problems like hypoplastic left heart syndrome
(HLHS). Though there are different approaches to classification,
an initial basic approach is based on the pulmonary blood
flow (PBF), as the systemic arterial saturation is primarily
determined by the volume of oxygenated blood that comes
to the systemic circulation from the pulmonary capillaries.3,4
Thus, CCHDs can be classified as those with,
1. Reduced pulmonary blood flow (Qp/Qs < 1).
2. Increased pulmonary blood flow (Qp/Qs > 1).
3. Near normal pulmonary blood flow.
Basic abnormality in this group is a very high resistance
to PBF either because of pulmonary stenosis or severe
pulmonary arterial hypertension (PAH), so that the ventricles
find it easier to empty to the systemic circulation. Hence,
these entities can be subdivided into those with pulmonary
stenosis (PS) and those with PAH. CCHDs with increased
PBF are usually complex lesions with bidirectional shunt

and hyperkinetic PAH; cyanosis in these situations is due
to intercirculatory mixing or because of a transposition like
physiology.
1. CCHD with low PBF and no PAH
i. Tetralogy of Fallot (TOF).
ii. TOF equivalents (pulmonary stenosis with ventricular
septal defect like pathology).
a. Double outlet right ventricle (DORV) + VSD + PS.
b. D-transposition of great arteries (d-TGA) + VSD +
PS.
c. L-transposition of great arteries (l TGA) + VSD
+ PS.
d. Tricuspid atresia + VSD + PS.
e. Single ventricle + PS.
f. Truncus arteriosus with small pulmonary arteries.
iii. Pulmonary atresia with intact interventricular septum.
iv. PS with atrial septal defect (ASD).
v. Ebstein anomaly of tricuspid valve.
2. CCHD with low PBF and PAH
Eisenmenger syndrome.
3. CCHD with high PBF
i. Intercirculatory mixing (admixture physiology)
a. Venous leveltotal anomalous pulmonary venous
drainage (TAPVD).
b. Atrial levelsingle atrium, tricuspid atresia, HLHS.
c. Ventricular levelsingle ventricle.
d. Arterial leveltruncus arteriosus.
ii. Transposition physiology
a. d-TGA.
b. Taussig-Bing anomaly.
4. CCHD with near normal PBF
i. Pulmonary arteriovenous fistula.
ii. Anomalous drainage of vena cava to left atrium (LA).
iii. Unroofing of coronary sinus into the LA.
basics
CCHD can also be classified in a different approach as

follows:
1. TOF physiology.
2. Transposition physiology.
3. Admixture physiology.
PretricuspidTAPVD, HLHS, tricuspid atresia, single
atrium
Post-tricuspidsingle ventricle, truncus arteriosus.
4. Eisenmenger physiology.
5. Ductus dependent physiology.
Ductus-dependent pulmonary circulation, e.g. pulmonary
atresia
Ductus-dependent systemic circulation, e.g. HLHS.
6. Near normal physiology, e.g. pulmonary arteriovenous
fistula.
7. Miscellaneous, e.g. Ebstein anomaly, PS + ASD.
Approach to clinical diagnosis of

Cyanotic congenital heart disease
Clinical approach to diagnosis of CCHD should aim at
delineating the anatomical and physiological abnormalities
and also the rhythm status of the child. Following aspects
have to be addressed.
Physiology
Pulmonary circulationflow, pressure, resistance
Systemic circulationoxygen saturation, cardiac output,
blood pressure, resistance
Ventricular function
Venous pressuressystemic/pulmonary
Any obstruction to circulation
Ductus dependent or not
Any compensatory mechanisms.
Anatomy
Visceral and cardiac situs
Visceroatrial/atrioventricular/ventriculoarterial connection
Right ventricular/left ventricular/biventricular pattern
Great artery relationnormal/transposed/malposed
Status of inflow tract and outflow tract of the ventricles
Venous connectionpulmonary and systemic
Coronary anatomy
Collaterals.
Symptomatology contributes to the assessment of physiology
and physical findings guide to anatomical status; radiology and
electrocardiogram add to this.
Symptoms
184
As outlined initially the main aim is to assess the pulmonary

blood flow. Reduced PBF group with TOF physiology has
characteristically varying degrees of cyanosis depending on

the severity of pulmonary stenosis and history of squatting.
Cyanotic spell is almost diagnostic for this entity. Those with
increased PBF will have features of heart failure (dyspnea,
interrupted feeding due to dyspnea, failure to thrive, etc.),
frequent respiratory tract infection and relatively lesser degrees
of cyanosis. Acute pulmonary edema like presentation in the
neonatal period in a cyanotic baby may indicate obstructed
TAPVD or HLHS with restrictive interatrial communication.5
Cyanosis in TOF typically appears a few weeks after birth;
however, as the severity of Fallot increases, the cyanosis can
appear earlier. Cyanosis on day 1 indicates either d-TGA or
other complex situations. In Ebstein anomaly, a characteristic
biphasic pattern is describedcyanosis at birth; disappears as
pulmonary resistance falls and reappears later as right heart
failure ensues.6
Maternal history is also important; d-TGA may have
a correlation with maternal diabetes though this has not
been supported by recent observations. History of maternal
ingestion of teratogens can also be contributory to diagnosis
maternal consumption of alcohol has been correlated with
occurrence of d-TGA, lithium with Ebstein anomaly and sex
hormones with d-TGA and TOF.
Physical Findings
Meticulous physical examination contributes greatly to arrive
at a reasonable clinical diagnosis of the entity. Presence of
dysmorphic or syndromic features gives us a clue to the
underlying condition based on the established associations.6,7
A few examples are given below:
Down syndromeatrioventricular canal defects (AVCDs)
DiGeorge syndrome8,9interrupted aortic arch, truncus
arteriosus, TOF
Laurence-Moon-Biedl syndromeTOF
Ellis Van CrevaldCommon atrium
Alagille syndromeTOF
Velocardiofacial syndromeconotruncal anomalies
CHARGE syndromeHLHS
Extracardiac anomalies are seen with a relatively higher
frequency in certain CCHDs48 percent in truncus arteriosus,
30 percent in TOF, 20 percent in tricuspid atresia, 15 to 30
percent in HLHS; but less frequent with d-TGA (< 10%).10
Differential cyanosis is diagnostic for Eisenmenger patent
ductus arteriosus, whereas reversed differential cyanosis occurs
in d-TGA with ductus and preductal coarctation or PAH.11
Pulse, Blood Pressure and Jugular

Venous pulse
Bradycardia suggestive of complete heart block occurs
more frequently with lTGA and atrioventricular (AV) canal
defects.12 High volume pulse with wide pulse pressure in a
cyanotic indicates aortic runoff as in aortic regurgitation in TOF,
Precordium
Cardiac and visceral situs has to be assessed straightaway
as cardiac malpositions and they have some specific
associations e.g. higher incidence of l-TGA in dextrocardia
with situs solitus, very complex lesions in levocardia with
situs inversus. A normal cardiac size with quiet precordium,
absent pulmonary artery pulsation and murmur of PS is quite
characteristic of a TOF like physiology, whereas cardiomegaly
with dynamic precordium and features of PAH indicate a high
pulmonary flow group. Assessment of ventricular dominance
is of importance as outlined below.
Right Ventricle Dominant

TOF, DORV + VSD + PS, d-TGA + VSD + PS, lTGA + VSD
+ PS, PS + ASD, HLHS.
Left Ventricle Dominant

Tricuspid atresia, double inlet left ventricle (DILV), pulmonary
atresia with intact ventricular system (IVS), Ebstein anomaly
with hypoplastic right ventricle and non-restrictive ASD.
BiventricularIndicates Increased Pulmonary Blood

Flow (no Pulmonary Stenosis)
Double outlet right ventricle + VSD, d-TGA + VSD, tricuspid
atresia with VSD, truncus arteriosus.
Normal
Pulmonary AV fistula, vena caval drainage to LA, unroofing
of coronary sinus.
Prominent pulsations in the second left intercostal space
occurs in high PBF group; however, in a case of high PBF, if
pulmonary artery pulsations are not felt it may be a clue for
transposition. In lTGA, the ascending aortic pulsation may
be strongly felt in second and third left space quite laterally.
Auscultation
A loud and split first heart sound is characteristic of Ebstein
anomaly of tricuspid valve. Second heart sound is single in
majority of the conditions and is often loud (loud A2 in TOF,
lTGA and truncus or loud P2 in high PBF physiology or

PAH).Wide split S2 in a cyanotic patient in the absence of
right ventricular failure indicates TAPVD or single atrium.
Left ventricular third heart sound indicates a high pulmonary
blood flow.
Pulmonary stenosis murmur is heard in TOF physiology
length of murmur being inversely related to the severity. In
TOF, this murmur is best heard in third left intercostals space;
in DORV, it may be relatively higher. As the pulmonary
artery is vertically oriented in d-TGA, the pulmonary stenosis
murmur may be heard well in the upper midsternal or upper
right sternal area. A loud VSD like murmur can be heard in
truncus arteriosus and tricuspid atresia. Mitral mid-diastolic
murmur indicates increased pulmonary flow; in a low PBF
group, it may indicate tricuspid atresia or pulmonary atresia
with intact IVS. Tricuspid mid-diastolic murmur in CCHD
points to TAPVD, single atrium, AV canal defects or Ebstein.
Early diastolic murmur could be of aortic regurgitation
in TOF, truncal regurgitation, pulmonary regurgitation in
Eisenmenger syndrome or the normotensive pulmonary
regurgitation of absent pulmonary valve in TOF; the latter can
be heard following intracardiac repair of TOF also. Continuous
murmur occurs in low PBF group (especially pulmonary
atresia)in second left space due to patent ductus arteriosus
and in lung fields due to aortopulmonary collaterals. Venous
hum persisting despite occlusion of right jugular vein is
characteristic of the classical supracardiac variety of TAPVD
due to the increased superior vena caval flow.
12
clinical approach to cyanotic heart diseases
truncal regurgitation or aortopulmonary runoff through a ductus

or aortopulmonary collaterals in conditions like pulmonary
atresia. It can also occur following a palliative aortopulmonary
shunt for pulmonary oligemic situations. Radiofemoral delay of
coarctation of aorta occurs with a higher frequency in Taussig
Bing anomaly (20%), tricuspid atresia (8%) and d-TGA (5%).
Prominent a wave in a cyanotic is a clue for tricuspid atresia
or Ebstein anomaly; it is unusual in TOF.
Electrocardiogram
In addition to assessment of cardiac rhythm status, ECG
contributes to evaluation of atrial situs, ventricular loop,
ventricular dominance and electrical axis, which aids in the
clinical diagnosis; or it may have a typical diagnostic pattern
(Figures 1 and 2) as in the case of Ebstein anomaly (very tall
or Himalayan P wave suggestive of right atrial abnormality,
polyphasic QRS in chest leads, delta wave of right-sided
accessory pathway) or tricuspid atresia (right atrial P wave,
left axis deviation and absent right ventricular forces).13
Atrial tachyarrhythmias occur in conditions with dilated
atrium as in Ebstein and AVCDs. In the case of Ebstein anomaly,
presence of a right-sided accessory atrioventricular pathway
also contributes to the higher incidence of tachyarrhythmias.
Atrioventricular blocks occur more frequently in lTGA and
AVCDs. Complete heart block in lTGA may be present at
birth or many times it will manifest only later. Prolongation
of PR interval is common in DORV also. Superior P axis may
indicate visceral heterotaxy.
Absence of Q waves in V5, V6 in presence of LV dominance
indicates a possibility of ventricular inversion as in lTGA or
DILV of inverted type. Left axis deviation of QRS occurs in
presence of AV canal type of defects, tricuspid atresia and DORV
without PS. Majority of cases of CCHD has right ventricular
185
basics
Figure 1: Electrocardiogram showing very tall or Himalayan P wave suggestive of right atrial enlargement,
polyphasic splintered QRS in chest leads. Suggestive of Ebstein anomaly
Figure 2: Electrocardiogram in a 5-years-old child with tricuspid atresia with normally related great arteries with left superior axis,
diminished right ventricular forces, left ventricular enlargement with T wave changes
186
Radiology
A properly taken skiagram of the chest provides a lot
of information in CCHDs, primarily contributing to
assessment of PBF and pulmonary pressures and resistance;
in addition the visceral and cardiac situs including the
position of aortic arch can also be determined (Figures 3 to

7). Many times, the radiology picture could be diagnostic
as in supracardiac TAPVC (snowman appearance), TOF
(boot-shaped/coeur en sabot), d-TGA (egg on side) or
Ebstein anomaly (box shaped). Increased pulmonary
vascularity without prominent main pulmonary artery
segment may indicate malposition of aorta; a prominent
Figure 3: Classical lifted up right ventricular (RV) apex (coeur en

sabot), concave pulmonary bay, pulmonary oligemia and right aortic
arch in tetralogy of Fallot
Figure 5: Cardiomegaly, huge right atrium and reduced pulmonary

vascularity of Ebstein anomaly (box-shaped heart)
Figure 4: Cardiomegaly, increased pulmonary vascularity and narrow

vascular pedicle (absent visible main pulmonary artery) in d-TGA (egg
on side appearance)
Figure 6: Classical figure of 8 appearance of total anomalous

pulmonary venous connection
12
hypertrophy or biventricular hypertrophy. Prominent left

ventricular forces and left atrial overload indicates enhanced
PBF. Paucity of right ventricular forces is a clue for tricuspid
atresia, pulmonary atresia with intact IVS or DILV.
187
basics
Figure 7: Dilated right atrium (RA) and central pulmonary arteries and increased pulmonary vascularity in a cyanotic child,
suggestive of common atrium. MPA = Main pulmonary artery; RPA = Right pulmonary artery
Flow chart 1: Clinical approach to cyanotic congenital heart disease
BV = Biventricular; DORV = Double outlet right ventricle; d-TGA = d-transposition of great arteries; HLHS = Hypoplastic left heart syndrome;
LVD = Left ventricular dominance; PAH = Pulmonary arterial hypertension; PA-IVS = Pulmonary atresia with intact ventricular septum; PAVF =
Pulmonary arteriovenous fistula; PBF = Pulmonary blood flow; RVD = Right ventricular dominance; SA = Single atrium; SV = Single ventricle;
TAPVD = Total anomalous pulmonary venous drainage; TA = Tricuspid atresia; VC to LA = Vena cava to left atrium
188
hump along the left upper border suggests L-posed aorta.

Right aortic arch is common with truncus arteriosus
(40%), pulmonary atresia with VSD (30%) and TOF
(2025%).14,15 A higher incidence of left superior vena
cava has been observed in AVCDs (19%), mitral atresia
(17%), TOF (10%) and truncus arteriosus (9%). Near
normal cardiac silhouette with pulmonary edema pattern
in a neonate suggest the possibility of obstructed TAPVC

(pulmonary edema in neonate occurs in HLHS with
restrictive interatrial communication also).
Clinically, normal heart with normal ECG and chest X-ray
occur with pulmonary arteriovenous fistula, anomalous vena
caval connection to left atrium and unroofed coronay sinus in
left atrium.
The overall flow chart for clinical approach to CCHD is

illustrated in Flow chart 1.
Systematic clinical evaluation of a cyanotic child with proper

history and meticulous physical examination supported
by a careful ECG and X-ray chest interpretation can give a
reasonable clue to the nature of the underlying heart disease
(as shown in the flow chart), making echocardiographic
confirmation easier.
A doctor who cannot take a good history and a patient who
cannot give one are in danger of giving and receiving bad
treatment.
Author Unknown
References
1. Freed MH. The patholohy, pathophysiology, recognition
and management of congenital heart diseases. In: Fuster V,
Alexander RW, ORourke RA (Eds). Hursts The Heart, 10th
edition. Mc Graw Hill. 2001. pp. 1837-1905.
disease: prevalence at birth. The Baltimore-Washington Infant
Study. Am J Epidemiol. 1985;121:31-36.
3. Edwards WD. Classification and terminology of cardiovascular
abnormalities. In: Allen HD, Shaddy RE, Driscoll DJ, Felters
TF (Eds). Moss and Adams Heart Disease in Infants, Children
and Adolescents, 7th edition. Philadelphia: Lippincott, William
and Wilkins. 2008. pp. 34-57.
4. Perloff KJ. Introduction and formulation of the problem. In:
Perloff KJ (Ed). Clinical Recognition of Congenital Heart
Disease, 4th edition. Philadelphia: WB Saunders Co. 1994.
pp. 1-8.
5. Sudhayakumar N, Rajesh G. Hypoplastic left heart syndrome.
In: Satpathy M (Ed). Clinical Diagnosis of Congenital Heart
Disease, 1st edition. Jaypee Brothers; 2008. pp. 312-16.
12
Conclusion
6. Schiebler GL, Adams P Jr, Anderson RC, et al. Clinical

study of 23 cases of Ebsteins anomaly of the tricuspid valve.
Circulation. 1959;19:165-87.
7. Morris CD, Outclal J, Menashe VD. Hypoplastic left heart syndrome: natural history in a geographically defined population.
Pediatrics. 1990;85:977-1000.
8. Van Mierop LH, Kutsche LM. Cardiovascular anomalies
in DiGeorge syndrome and importance of neural crest as a
possible pathogenetic factor. Am J Cardiol. 1986;58:133-37.
9. Goldmuntz E, Clark BJ, Mitchell LE, et al. Frequency of
22q11 deletions in patients with conotruncal defects. J Am Coll
Cardiol. 1998;32:492-98.
10. Glauser TA, Rorke LB, Weinberg PM, et al. Congenital brain
anomalies associated with hypoplastic left heart syndrome.
Pediatrics. 1990;85:984-90.
11. Wernovsky G. Transposition of great arteries. In: Allen
HD, Shaddy RE, Driscoll DJ, Felters TF (Eds). Moss and
Adams Heart Disease in Infants, Children and Adolescents,
7th edition. Philadelphia: Lippincott, William and Wilkins;
2008. pp. 1038-87.
12. Daliento L, Corrado D, Buja G, et al. Rhythm and conduction
disturbances in isolated, congenitally corrected transposition of
the great arteries. Am J Cardiol. 1986;58:314-18.
13. Davachi F, Lucas RV Jr, Moller JH. The electrocardiogram
and vectorcardiogram in tricuspid atresia. Correlation with
pathologic anatomy. Am J Cardiol. 1970;25:18-27.
14. Bharati S, Paul MH, Idriss FS, et al. The surgical anatomy of
pulmonary atresia with ventricular septal defect: pseudotruncus.
J Thorac Cardiovasc Surg. 1975;69:713-21.
15. Butto F, Lucas RV, Edwards JE. Persistent truncus arteriosus:
pathologic anatomy in 54 cases. Pediatr Cardiol. 1986;7:95-101.
Suggested Reading
1. Allen HD, Shaddy RE, Driscol DJ, Felters TF (Eds).
Moss and Adams Heart Disease in Infants, Children and
Adolescents, 7th edition. Philadelphia: Lippincott, William
and Wilkins; 2008.
2. Perloff KJ (Ed). Clinical Recognition of Congenital Heart
Diseases, 4th edition. Philadelphia; WB Saunders Co, 1994.
189
C hapter
13
Role of Radiography in
Madhav Hegde, Vijayalakshmi IB
IntRoDuCtIon
BasIC InteRRogatIons on CHest X-Ray
The role of radiography especially chest X-ray (roentgenogram) has decreased as a tool of cardiovascular thoracic
imaging, because of the widespread reach of antenatal
(fetal echocardiography) and postnatal transthoracic 2D
echocardiography (TTE). The early detection of congenital
heart disease (CHD) by TTE and its management, has in turn
led to lessened classical appearances on radiography. Still
it continues to play an important role in evaluation of both
pediatric and grown up congenital heart diseases (GUCH).
Today, chest X-ray (CXR) is not a main diagnostic tool
for detection of CHD, however it is complimentary to clinical
assessment and TTE. With its decreased importance over the
last two-three decades, the ability of interpreting X-ray has
also declined across the medical fraternity. Although diagnosis
of CHD on CXR can be attempted, it is unfortunately less
accurate. Intricate anatomical and physiological phenomena
make the interpretation of CXR a complex process compared to
echocardiography. Echocardiography allows direct visualization
of the cardiac structures and their functional profile, whereas
CXR provides mere summation of these complex anatomic and
pathophysiological processes. In most cases, cardiac pathology
is reflected in an abnormal CXR image. In few situations, it is
easier to get and store data in terms of roentgenogram rather
than echocardiography, e.g. calcification of the patent ductus
arteriosus (PDA) and aortic knuckle, pulmonary arteriovenous
(AV) malformation, situs, pulmonary vasculature and laterality
of the aortic arch.
Chest X-ray needs to be regarded as a necessary tool with
limitations, with a specific role in the diagnosis of CHD. The
gallery of images showing the few current clinical scenarios,
where CXR has a vital role is given in this chapter. Evaluation
of the quality of X-ray requires some understanding of the
technical factors involved in the production of an X-ray
image. Without such understanding, the risk of making an
interpretive error is increased.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
Cardiac position.
Situs.
Bony cage.
Rotation.
Cardiothoracic ratio.
Thymic shadow.
Underexposed or overexposed?
Degree of inspiration.
Pulmonary vascularity.
Cardiac silhouette.
Lung fields.
Cardiophrenic (CP) angles.
Cardiac Position
Normally the major portion of the heart (2/3rd) lies to the left
of the midline. Any position other than left is considered as
malposition. The left sided heart with left ventricular apex on
the left side is called levocardia. When most of the heart is
in the right hemithorax and the base to apex axis points to the
right, it is called dextrocardia. When the heart is in midline
it is termed as mesocardia.
situs
Situs is the site or position of the viscera. Situs solitus is
the normal position, in which the liver is to the right and
the fundal gas shadow is to the left. Dextrocardia with situs
solitus is called isolated dextrocardia (Figure 1). In mirror
image dextrocardia there is situs inversus (Figure 2).
Visceroatrial Situs
Visceroatrial situs means that the right atrium (RA), liver,
inferior vena cava (IVC) and trilobed right lung are on one
13
figure 1: CXR image shows isolated dextrocardia with liver shadow to

the right and fundal gas shadow to the left (situs solitus, dextrocardia)
Role of RadiogRaphy in Congenital heaRt diseases
figure 3: Schematic representation of bronchial morphology

LB = Left bronchus; RB = Right bronchus
figure 4: CXR image shows in oblique view shows normal tracheal

bifurcation. LB = Left bronchus; RB = Right bronchus; TR = Trachea
figure 2: CXR image shows mirror image dextrocardia with liver

shadow to the left and fundal gas shadow to the right (situs inversus
dextrocardia)
side and the left atrium (LA), stomach gas bubble, spleen and
bilobed left lung are on other side. The position of the stomach
gas bubble helps in identifying the visceroatrial situs.
Bronchial Pattern
The bronchial pattern is important in isomerism
(Figure 3). CXR image gives valuable clues to the diagnosis,
as shown in Figures 4 and 5.
i. Tracheal bifurcation is best seen in an oblique view.
ii. Right bronchus is short, wide and straight.
figure 5: CXR image in right lateral view shows how

to identify the normal structures
191
BasiCs
figure 6: CXR image shows scoliosis
iii. Left bronchus is long, thin and curved.

iv. Measure the bronchus from the bifurcation, the longer of
the two is the left bronchus.
v. If the ratio between the left and right bronchus is greater
than or equal to 2 then it is situs solitus (longer bronchus
is on left) or situs inversus (longer bronchus is on right).
If the ratio is less than 1.5, then it indicates isomerism.
figure 7: Chest X-ray in a 2 years old child of patent ductus arteriosis

(PDA) with meningocoele, shows spina bifida, hemivertebrae (arrow)
with splaying of left lower ribs and the PDA coil is in situ
Bony Cage
All the CXR should be carefully observed systematically
for skeletal abnormalities from the cervical spine, scapula,
clavicle, thoracic spine and ribs in both frontal and lateral
view (Figure 5). In the bony cage one should look for scoliosis
(Figures 6 and 7) in posteroanterior (PA) view and for kyphosis
in lateral film. The incidence of scoliosis in acyanotic CHD
is 20 percent and in cyanotic CHD it is 66 percent. As the
skeletal deformity can pose problems during surgery, chest
X-ray is extremely useful in detecting the problems in the
bony cage. Rare conditions like hemivertebrae can be easily
detected by simple X-ray. The children with Down syndrome
often have only 11 pairs of ribs. Premature fusion of sternal
segment is usual in cyanotic CHD. Bilateral rib notching is
seen in coarctation of aorta (COA) and unilateral rib notching
is seen in subclavian pulmonary artery anastomosis as in
Blalock-Taussig shunt.
Is there significant Rotation?
192
Rotation means that the baby was not positioned flat on the
X-ray film and one plane of the chest is rotated in comparison
to the plane of the film. The centering of the CXR has to
figure 8: CXR image with correct centering. There is equal distance

between the medical end of clavicle and midline
be checked before reading it. The centering is checked by

clavicular symmetry. There should be equal distance between
the medial end of the clavicle and midline (Figure 8). If the
distance between medial end of the clavicle and center line
is unequal then centering is not correct (Figure 9). If the
centering is not correct then the interpretation can go wrong
due to rotation. Rotation can make the lungs look asymmetrical
and it can change the orientation of the cardiac silhouette. If
there is significant rotation, the side, which has been lifted
13
figure 10: The correct method of measuring the

TCD (a + b)
cardiothoracic ratio (CTR) CTR =
TTD (c)
may appear narrower and more dense (white) and the cardiac
silhouette appears more in the opposite lung field.
figure 9: CXR image with incorrect centeringunequal distance

between the medial end of clavicle and central line
Cardiothoracic Ratio
Before commenting on cardiomegaly the cardiothoracic
ratio (CTR) must be measured meticulously (Figure 10).
The CTR is equal to the transverse cardiac diameter (TCD)
divided by the transthoracic diameter (TTD) measured at the
inner border of the 9th rib (CTR = TCD/TTD) as shown in
Figure 10. Irrespective of CTR an increase of > 2 cm of TCD
is significant if previous CXR is available. The normal values
of CTR ratio in an adult is 0.41 to 0.5. The upper limit of
normal CTR ratio in infants is 0.55 and 0.60 in neonates.
A TCD of greater than 15 cm is significant irrespective
of normal CTR. An expiratory roentgenogram can lead to
pseudocardiomegaly and a prominent aorta. Epicardial fat in
the cardiophrenic angle can mimic as cardiomegaly as shown
in Figure 11.
thymic shadow
The thymic shadow is usually prominent in the first few years
of life. Thymic shadow should not be mistaken for mediastinal
widening. The shadow of the thymus lies anteriorly in
relationship to the heart and great vessels. The relative size
of the thymus increases with expiration and decreases with
inspiration. The thymus decreases in size during periods
of stress, such as during sepsis. Because the thymus is a
soft organ, its lateral margin can have indentations caused
due to the overlying costal cartilages, causing a wave sign
figure 11: CXR image in a patient epicardial fat in cardiophrenic

angle mimicking cardiomegaly
(Figure 12A). The right lobe of the thymus can insinuate

into the minor fissure, causing a sail sign (Figure 12B). The
awareness of various apperances of thymus on CXR can bail
one out of a situation wherein thymus mimics a pericardial
mass on echocardiography.
Is the X-ray underexposed or overexposed?

A properly penetrated chest radiograph is one, in which the
intervertebral bodies can be seen. Normally only the first four
193
BasiCs
figures 12a and B: A. CXR image shows the ribs causing indentation on the soft thymus, causing wave
sign (arrows); B. Right lobe of the thymus can insinuate into the minor fissure, causing sail sign (arrow)
vertebral bodies are visible. In overpenetrated or overexposed

CXR, the vertebral bodies are visible clearly through the
cardiac shadow. In underpenetrated or underexposed film
the vertebral bodies are not visible at all. An underpenetrated
chest CXR does not differentiate the vertebral bodies from
the intervertebral spaces. An overpenetrated film shows the
intervertebral spaces very distinctly. An overpenetrated CXR
will be darker and the subtleties will be harder to see. An
underpenetrated CXR will emphasize normal lung and make
it appear as if there are infiltrates. Hence it is important to
know whether the CXR is overexposed or underexposed.
Overexposure causes the image to be dark. Under these
circumstances, the thoracic spine, mediastinal structures,
retrocardiac areas, nasogastric and endotracheal tubes are
well seen, but small nodules and the fine structures in the lung
cannot be seen. However, the widespread availabilty of digital
imaging (computed radiography, direct digital radiography)
has reduced the importance of optimal exposure as images
can be manipulted on viewing monitors.
Degree of Inspiration
Normally, the right hemidiaphragm should be at the level of
6th rib anteriorly and the 9th rib posteriorly. If diaphragm is
below this level, it is a hyperinflated film. Expiratory films
produce apparent cardiomegaly and pseudotracheal deviation.
The heart appears larger on anteroposterior (AP) than in PA
view. Expiratory film, simulates pulmonary edema and the
heart appears larger.
Pulmonary Vascularity
194
Pulmonary vascularity can be nicely made out on CXR and one

can know whether the patient has decreased pulmonary flow
(oligemia) or increased pulmonary flow (plethora). Abnormal
pulmonary vascularity can be generally divided into four types:
i. Oligemia.
ii. Plethora.
iii. Pulmonary venous hypertension (PVH) (ground glass

appearance).
iv. Pulmonary edema (bat-wing appearance).
Oligemia
In oligemia, vascular shadows are reduced. They are not seen
even in the intermediate lung zones. Main pulmonary artery
(MPA), left pulmonary artery (LPA) and right descending
pulmonary artery (RDPA) are of small size (normally RDPA
is of the same size as the right lower lobe bronchus). Oligemia
occurs in critical pulmonary stenosis (PS) and in tetralogy
of Fallot (TOF). In pulmonary valvular stenosis along with
oligemia there is poststenotic dilation of the MPA and the
right ventricle (RV) and RA are enlarged (Figure 13A). In
TOF pulmonary bay is empty (MPA is small) and severe RVH
is seen without RA enlargement (as RV pumps into the overriding aorta and the pressure is not transmitted to RA). Nearly
25 percent of TOF can have right sided aortic arch (Figure
13B). The left or right aortic arch can be made out by the
ipsilateral indentation of the trachea.
Plethora
In plethora (Figure 14) the vascular shadows are numerous and
vessels can be traced in the lateral one-third of the lung fields
also. The MPA, LPA and RDPA are large. End on vessels are
more in number ( 3 in one lung field or 5 in both lung fields).
The end on vessel diameter is more than that of accompanying
bronchus. Normally it is 1.2:1 and in plethora it is 1.5:1. The
size of the RDPA in nomally < 14 mm and if it increased
(> 16 mm in male and >14 mm in female), it indicates a shunt
lesion. In normal children diameter of RDPA is less than that
of trachea. If the ratio of RDPA to trachea is more than 1 it
indicates significant left to right shunt. Plethora occurs in left
to right shunts, admixture lesions and transposition of the
great arteries (d-TGA) without PS. To have plethora left to
right shunts should be at least 1.5:1.
13
figures 13a and B: X-ray showing oligemia: A. Fluoroscopic image in a 10 month infant with pulmonary stenosis, shows oligemia with
right atrium, right ventricle and main pulmonary artery dilatation; B. CXR image in a 4 months infant of tetralogy of Fallot with severe
oligemia, boot-shaped heart, empty pulmonary bay and right sided aortic arch
figure 14: CXR image of a 12-year-old boy with large ventricular septal
defect and atrial septal defect with pulmonary arterial hypertension,
shows right atrium, right ventricle, main pulmonary artery dilated with
plethora
figure 15: Fluroscopic image of 4 months infant tetralogy of Fallot

with absent left pulmonary artery, shows oligemia in right lung and
absent vascular markings in left lung
Occasionally there can be unilateral plethora as in BT

shunt and in unilateral major aortopulmonary collateral artery
(MAPCA). Asymmetry in lung vascularity can also occur
after Glenn surgery and in pulmonary artery branch stenosis
or absent right pulmonary artery (RPA) or LPA (Figure 15).
there is equalization of the vascularity. When there is severe

obstruction to the pulmonary veins, the CXR shows ground
glass appearance (Figure 16A). The ground glass appearance
due to pulmonary venous hypertension is an important feature
and should be distinguished from hyaline membrane disease.
The normal pulmonary capillary wedge pressure (PCWP) is
< 12 mm Hg. Larry Elliot has graded PVH into four stages.
In stage I PVH, the PCWP is between 13 to 17 mm Hg. The
pulmonary veins in the upper lobe are more prominent than
that in the lower lobe. This is cephalization of the veins and
Pulmonary Venous Hypertension

Normally the upper lobe veins are less prominent than the
lower lobe veins. In PVH or postcapillary hypertension,
195
BasiCs
figures 16a and B: A. CXR image of a 2-month-old infant with obstructed infradiaphragmatic total anomalous pulmonary venous connection;
B. CXR of a 50-year-old lady with large atrial septal defect with pulmonary hypertension shows bat-wing appearance
is also called as staghorn or inverted mustache appearance.

In stage II PVH, as PCWP increases to between 18-25 mm
Hg, interstitial edema occurs and causes perihilar haziness,
peribronchial cuffing (increased thickness of the bronchial
walls seen end-on, usually near the hilum), subpleural
effusion and the appearance of Kerley B lines (short, thin, 1
to 2 cm long parallel lines seen at right angles to the pleura,
laterally at the lung bases). These lines represent fluid in the
interlobular septa. In stage III PVH, the PCWP is > 25 mm
Hg. There is frank pulmonary edema reaching to the hilum
and a typical bat-wing appearance on CXR (Figure 16B).
PVH and pulmonary edema occur in mitral valve disease,
obstructed total anomalous pulmonary venous connection
(TAPVC), hypoplastic left heart syndrome (HLHS), dilated
cardiomyopathy (DCM). Stage IV PVH is seen in chronic
pulmonary hypertension and there is hemosiderosis and
ossification.
Pulmonary Artery Hypertension
196
The characteristic radiological features of pulmonary

arterial hypertension (PAH) or precapillary hypertension are
prominent central pulmonary arteries and with tortuosity,
deviation, diminution in the size of arteries in the middle and
lateral thirds of the lungs (Pruned-tree appearance). Pruning
is defined as > 50% loss of vessel diameter at any degree
branching and is suggestive of PAH. With onset of PAH there
RV and RA enlargement. The heart size tends to normalize
with the severe PAH, though in patients of ASD with PAH the
right sided chambers remain enlarged.
Cardiac silhouette
In the frontal projection, the right border of the cardiac
silhouette consists of the following structures from top to
bottom: superior vena cava (SVC), ascending aorta, right
atrial appendage RA and IVC. The left border of the cardiac
silhouette is formed from top to bottom by the aortic knuckle
(aortic knob), pulmonary trunk, left atrial appendage and the
LV. Any enlargement or hypoplasia of a particular component
of the heart will alter the normal shape of the cardiac silhouette.
An upturned apex without cardiac enlargement occurs in right
ventricular hypertrophy.
The features of LV enlargement (lateral (L) and frontal
(F) views) are:
Mild-obliteration of retrocardiac (prevertebral) space (L)
Moderate-cardiac shadow overlies vertebral column (L)
Marked-cardiac shadow overshoots vertebral column (L)
Left cardiac border elongated and more convex (Figure 17)
(F)
Left cardiac border dips below left dome of diaphragm (F)
Apex rounded off (F).
The features of RV enlargement are:
Obliteration of retrosternal space.
Clockwise rotation of heartapex moves posteriorly and
RV comes to form the left cardiac borderrounded and
elongated apex away from the left dome of diaphragm.
The features of RA enlargement are:
Right cardiac border becomes more convex and elongated
It forms greater than 50 percent of right cardiac border
Dilation of SVC
13
Distance from midline to maximum convexity of right cardiac

border greater than 5 cm in adults and > 4 cm in children
RA border exceeds greater than 3 intercostal spaces.
Increased height of the RA border occupying more than
half of the vertical distance between medial end of right
clavicle and dome of right hemidiaphragm.
The features of LA enlargement are:
The LA is the uppermost and posterior most chamber in
subcarinal angle. The first evidence of LA enlargement is
the presence of a bulge, on the left heart border below the
pulmonary artery, caused by the left atrial appendage, the third
mogul sign. The next evidence is a double density through
the central heart shadow, followed by widening of the carinal
angle with elevation or posterior displacement of the left main
bronchus. There is also posterior esophageal displacement in
the right anterior oblique view. The displacement ends well
above the diaphragm. The LA shadow does not touch whereas
the RA shadow touches the right dome of the diaphragm. The
LA enlargement can be graded as follows.
Grade 1double cardiac density (contour)
Grade 2LA enlargement in flush with right cardiac
border
Grade 3oveshoots RA and itself forms right cardiac
border (Figure 18)
The characteristic cardiac contour in some anomalies are:
1. Boot-shaped heart (couer en Sabot): Tetralogy of Fallot
(Figure 19A): This deformity is due to the uplifting of the
cardiac apex because of RV hypertrophy and concavity
of the MPA. But in cases of TOF with absent pulmonary
figure 18: CXR image illustrates giant left atrium (LA), the border of
LA is seen beyond the right atrium (RA) with a prominent left atrial
appendage (LAA)
valve instead of a empty pulmonary bay it is filled with

aneurysmally dilated MPA (Figure 19B) .
2. Egg on side or egg on string: Transposition of great
vessels (TGA). The malposition of great vessles, in
association with stress-induced thymic atrophy and
hyperinflated lungs, results in the apparent narrowing of
the superior mediastinum on radiographs, which is the
the most consistent sign of TGA. The cardiovascular
silhouette varies from normal in the first few days after
birth to enlarged and globular, with the classic appearance
described as an egg on a string (Figure 20).
3. Figure-of-eight sign or snowman in snow storm: It is
seen in supracardiac TAPVC (Figure 21). The pulmonary
veins converge behind the heart to form a common
pulmonary vein that connects to the dilated vertical vein
on the left, which joins the left innominate vein on the top.
This drains into the SVC on the right to form the head of
the snowman. The body of the snowman is formed by the
enlarged RA along with cardiac shadow. Plethoric lung
with ground glass appearance looks like snow storm.
4. Scimitar sign: Scimitar is a Turkish sword with the curved
blade traditionally used by Persian and Turkish warriors.
The shadow resembling the shape of scimitar is produced
by an anomalous pulmonary vein that drains any or all of the
lobes of the right lung (Figure 22). The so-called scimitar
vein curves outward along the right cardiac border, usually
from the middle of the lung to the cardiophrenic angle and
usually empties into the IVC but also may drain into the
portal vein, hepatic vein or right atrium.
figure 17: CXR image in a 12 year old patient with Shones syndrome
showing cardiomegaly with left ventricular enlargement with pulmonary
venous hypertension
197
BasiCs
B
figures 19a and B: A. CXR image of Tetralogy of Fallot (TOF) with boot shaped heart with a empty pulmonary bay
with reticular pattern due to collaterals; B. TOF with absent pulmonary valve with dilated pulmonary artery
figure 20: CXR image shows narrow pedicle with egg on string
appearance in a 8-year-old with transposition of great arteries
figure 22: Fluoroscopic image of a 10-year-old girl

with scimitar vein (arrow)
198
figure 21: CXR image of posteroanterior view shows snowman in snow
storm appearance in total anomalous pulmonary venous connection
5. Box-shaped heart: The box-shaped or money bag shaped

cardiac silhouette is seen in Ebstein anomaly. The RA is
huge and fills the entire right hemithorax. The left atrium
is normal in size, but the left cardiac contour has a shelved
appearance because of the dilated right ventricular outflow
tract. The aorta is small and the pulmonary trunk which
normally appears as a discrete convex bulge is absent.
This combination of features produces a cardiac silhouette
that has been described as box shaped (Figures 23A
and B).
6. 3 sign: It is seen in COA. The number 3 is formed by the
dilatation of the left subclavian artery and aorta proximal to
13
figures 23a and B: CXR image shows A. Huge right atrium almost filling the entire right hemithorax in a case of severe
Ebstein anomaly; B. Narrow pedicle with box shaped or money bag appearance in a case of Ebstein anomaly
figures 24a and B: CXR image showing 3 sign and rib notching: A. Chest X-ray in coarctation of aorta (COA) shows concentric left
ventricular hypertrophy with figure-of-3 sign; B. Rib notching is seen in the X-ray of 16-year-old boy of COA with collaterals
the site of coarctation, indentation of the site and dilatation

of the aorta distal to the site (Figure 24A).
7. Rib notching: It is seen in the lower margin of the third
to eighth ribs (Figure 24B) in aortic coarctation due to the
enlarged, tortuous intercostal arteries supplying blood to
the descending aorta. The notching is not usually seen in
children younger than 5 years.
Apart from specific signs in some condition there are other
conditions which have characteristic features on radiography,
which are diagnostic, e.g. in cases with congenital corrected

transposition of great arteries (CTGV), the malposed ascending
aorta produces a long convexity on the left upper mediastinal
contour and cardiomegaly with increased pulmonary vascular
markings secondary to a ventricular septal defect (Figure 25).
The right pulmonary artery appears to have a high take off
because of an absent aortic shadow and is also quite prominent
indicating ventricular inversion. Also in tricuspid atresia,
CXR shows a mildy enlarged LV with a gap between RA and
199
BasiCs
200
figure 25: CXR image of corrected transposition of great arteries.

The ascending aorta producing a long convexity on the left upper
mediastinal contour
figure 27: CXR image of 32-year-old patient with large patent ductus
arteriosus with severe pulmonary hypertension shows dilated right
pulmonary artery and left pulmonary artery with peripheral pruning
figure 26: CXR image of film of tricuspid atresia shows normal sized
heart with mildly enlarged left ventricular configuration with a gap
between right atrium and the diaphragm, indicating hypoplastic right
ventricle
figure 28: Fluroscopic image of 22-year-old patient with large

ventricular septal defect with severe pulmonary hypertension with
right to left shunt shows the classic jug-handle appearance due to
aneurysmally dilated main and right pulmonary artery. Note the normal
sized heart with peripheral pruning
the diaphragm, indicating hypoplastic RV (Figure 26). The

pulmonary artery can be enlarged as in shunt lesions with
PAH (Figure 27). In Eisenmengers, the classic jug-handle
appearance due to aneurysmally dilated MPA and RPA can be
seen on CXR (Figure 28). There is a normal sized heart with
peripheral pruning. The CXR can be diagnostic in idiopathic
dilatation of pulmonary artery where there is aneurysmally
dilated pulmonary artery with normal cardia and lung fields
(Figure 29).
Lung Fields
Apart from the vascularity, the lung fields can give important
clue for the diagnosis of pulmonary embolization of either
thrombus or large vegetation from RV or pulmonary valve.
The Fleischner lines are the linear shadows seen in the
region of an embolus. The knuckle signAbrupt tapering or
termination of a pulmonary vessel. The Westermark sign is
the focal hyperlucency (Figure 30A). The Hamptons Hump
Cardiophrenic angles
figure 29: CXR image shows aneurysmally dilated pulmonary artery

with normal cardia and lung field of 18-year-old girl with idiopathic
dilatation of pulmonary artery
The cardiophrenic (CP) angle is obliterated in pericardial

effusion (Figure 33). It is obtuse and helps to distinguish from
cardiomegaly, in which the CP angle remains acute, however
great the enlargement is. In patients of CHD with congestive
heart failure along with the cardiomegaly the pleural effusion
can be detected on CXR as the costophrenic angle is obliterated.
13
is the classical peripheral wedge-shaped area of opacification

with apex towards the hilum (Figure 30B). The melting ice
cube sign is the decrease in the size of opacity like melting ice
cube on serial CXR/CT taken during the course of treatment.
With the advent of non-surgical transcatheter interventions the radiographs are useful for documenting the
position of the device (Figures 31A and B, Figure 32A) and
also detect the embolization of the device (Figure 32B). The
other devices like pacemakers and position of pacing leads
can be detected on CXR.
figures 30a and B: A. CXR image of a patient with pulmonary embolism shows the abrupt tapering and termination of a pulmonary vessels
(horizontal arrow) and hyperlucency (vertical arrows); B. CXR image of a patient with pulmonary infarction with peripheral wedge-shaped area
of opacification with apex towards the hilum
figures 31a and B: A. Fluoroscopic image showing atrial septal occluder in situ; B. Fluoroscopic image illustrating in situ ASD device
and a VSD device, in an apical position, deployed simultaneously in 12 years old boy
201
BasiCs
figures 32a and B: A. Fluoroscopic image illustrates the patent ductus arteriosis (PDA) device in situ; B. Fluoroscopic image
of the abdomen shows the PDA device embolized in aorta
figure 33: X-ray film shows the cardiomegaly with obtuse cardiophrenic angle, indicating the presence of pericardial effusion
ConCLusIon
202
Along with clinical evaluation CXR serves as a screening

tool for the detection of congenital cardiovascular diseases.
It is also a useful tool in short-term and long-term followup of post-surgical and post-procedure cases especially
device closures. It is simple documentation tool for situs,
cardiovascular silhouette, radio-opaque surgical and
percutaneous interventional devices. All importantly CXR
is a stimulating teaching tool and helps understanding the
complexity of CHD. CXR is not any more a primary diagnostic
tool in CHD but appreciating it as poor mans CT will not be
overstating its utility in routine clinical practice.
Correct interpretation of pulmonary vasculature requires

considerable experience and cannot simply be learned
from a book.
Kurt Amplatz
BIBLIogRaPHy
1. Ahmed MZ, Gera R and Kailas L. Chest X-rays in pediatric
cardiology.
2. Chokkalingam A, Chokkalingam V. Cardiac X-rays. Elsevier.
3. Sharada K and Gouthami V. Radiological Diagnosis of
Congential Heart Diseases.
4. Sutton D. Text Book of Radiology and Imaging, 7th edition.
Churchill Livingstone.
C hapter
14
Role of Newer Cardiac Imaging in

Sunita Maheshwari, Arjun Kalyanpur, Jayadeepa
Introduction
Cardiac CT in current day scenario
With the current state of technological advancements, the

increasing number of patients surviving after therapeutic
intervention for congenital heart disease (CHD) has remarkably
increased over the couple of decades. Echocardiography,
either transthoracic or transesophageal, however, has been
the cardiologists eyes to the heart for this purpose, and will
probably uphold that status, at least in the diverse spectrum
of CHD. The accurate diagnosis and frequent follow-up of
morphologic and functional cardiovascular status is required
in CHD, preferably with a non-invasive imaging techniques
such as cardiac computed tomography (CT) and magnetic
resonance imaging (MRI) holds potential to replace many of
the invasive angiograms done annually.1
Role of Cardiac CT in Congenital Heart Disease
need for Cardiac CT and MRILimitations of

echocardiography and catheter angiography
Although echocardiography and catheter-directed cardiac
angiography are, by definition, regarded as the cornerstones
of primary imaging techniques for evaluation of CHD, CT and
MRI are rapidly emerging complementary diagnostic tools.
In addition to being operator dependent, echocardiography
may not be singularly sufficient for evaluating extracardiac
structures, such as the pulmonary arteries, pulmonary veins,
and the aortic arch and great vessels due to acoustic window
limitations. Catheter-directed cardiac angiography is limited
by technical difficulties in evaluation in some situations,
e.g. of the pulmonary arteries in pulmonary atresia. Cardiac
catheterization, in comparison to CT, also entails a higher
complication rate owing to its invasiveness, requirement
of a larger volume of intravascular contrast material, more
frequent requirement of general anesthesia and risk of much
higher radiation exposure as compared to CT when appropriate
pediatric CT protocols are used.
The role of CT in the evaluation of pediatric CHD is constantly

evolving, refined and redefined with advances in the field and
ever-expanding in its range of applications. There are many
generally accepted clinical indications for evaluation of
patients with CHDeither known or suspected on the basis of
echocardiographic findings where in further imaging is needed
to characterize cardiac or extracardiac anomalies before
intervention.2,3 Prime examples are described given below.
Use of CT in Various Congenital Heart Diseases

Intracardiac Anomalies
1. Tetralogy of Fallot (TOF) (Figure 1): The evaluation of
pulmonary arteries (PAs) is the cornerstone of surgical
decision making in TOF (Figure 1). CT can provide
excellent delineation of PAstheir confluence, size and
nature of the distal portion of branches. This information
may not be always evident on echocardiography. Other
valuable information that CT can provide in low pulmonary
blood flow situations like TOF is regarding the pulmonary
venous drainage. It is possible that partial anomalous
pulmonary venous drainage may be missed on echo, but
can definitely be detected on CT.
2. Pulmonary atresia with ventricular septal defect (VSD):
Detailed evaluation of PAs and feeding vessels to PAs
is important for precise surgical planning. The branch
PAs may not have anatomical continuity (non-confluent).
Pulmonary blood flow may be derived from a patent
arterial duct (PDA) or from aortopulmonary collaterals.
CT can provide vital information on the issues related
to pulmonary arteries and its feeders and some pediatric
Basics
204
Figure 1: Confluent pulmonary arteries in tetralogy of Fallot.

LPA = Left pulmonary artery; PA = Pulmonary artery;
RPA = Right pulmonary artery
Figure 2: Oblique coronal maximum intensity projection (MIP)

reformat demonstrating coarctation of aorta (CoA).
AAo = Ascending aorta; DAo = Descending aorta
cardiac surgeons consider it as the most useful investigation

for surgical planning.
3. Tetralogy of Fallot with absent pulmonary valve: CT also
plays an vital role in patients diagnosed as TOF with absent
pulmonary valve who are symptomatic not only because
of the cardiac problem, but also because of the inherent
abnormalities in the lung parenchyma. Determining the PA
anatomy and its contribution to symptoms is of immense
importance in deciding the surgical management. Apart
from defining the amount of bronchial compression, it also
localizes areas of atelectasis or emphysema.
4. Interrupted aortic arch (IAA): IAA represents a separation
between ascending and descending aorta. Evaluation of
the distance between the proximal and distal segments, the
size of the patent ductus arteriosus (PDA), the narrowest
dimension of the left ventricular outflow tract and other
cardiac structural abnormalities are important for surgical
planning. CT scan and digital 3D reconstruction of the CT
images can recreate the entire anatomy for the surgeon and
simplify the surgical planning.
5. Coarctation of aorta (CoA) (Figure 2): CT scan can give an
excellent delineation of the lesion to aid the management
planning.4
6. Aortopulmonary window (APW): Echocardiography may
fail to pick up this lesion due to artificial dropouts and rapid
development of pulmonary hypertension. A great degree
of clinical suspicion needs to be exercised for the proper
diagnosis. The role of helical CT has been well established
in the diagnosis of this condition.5
7. Pulmonary artery sling: In this lesion, an aberrant left
pulmonary artery arises from the proximal right pulmonary
artery, courses between the trachea and esophagus and
extends to the left hilum. This may be associated with
tracheal anomalies including tracheal bronchus, complete

tracheal ring and localized tracheomalacia. CT scan and
digital 3D reconstruction of the CT images can give an
excellent recreation of the precise anatomy of this complex
lesion and is the investigation of choice.6
8. Total anomalous pulmonary venous connection (TAPVC)
(Figure 3): Although echocardiography can confidently
diagnose the condition in the vast majority, CT evaluation
gives excellent anatomical data regarding the pulmonary
veins and should be considered in case of any doubt or
when the echocardiographic data does not correlate with
the clinical condition.7
9. Postoperative situations: An important and established
role of CT in the follow-up of managed CHD is evaluation
for successful surgical outcome and recognition of a
variety of complications. CT angiography (CTA) can
assess surgical conduits and intravascular stent patency,
wherein lack of central opacification in these structures
suggests the presence of thrombosis that can have serious
clinical implications. CTA can also evaluate right ventricle
to pulmonary artery and modified Blalock-Taussig shunt
patency and stenosis. Similarly, CT can also assess
patients previously treated with a surgical cavopulmonary
anastomosis, such as bidirectional Glenn shunt and Fontan
procedures, where CT can establish pathway patency and
exclude abnormal pathway narrowing. Filling defects
within the pathway suggest the presence of thrombus.
Disadvantages of Computed Tomography

CT has its inherent disadvantages, including the inevitable
radiation exposure and risks related to use of iodinated
contrast material. Also, CT lacks in its ability at demonstration
Magnetic Resonance Imaging Sequences

and Techniques
of functional information such as right ventricular function,

pulmonary regurgitation fraction, etc. Additionally, in
neonates and young infants, paucity of fat planes, tachycardia,
tachypnea and motion-related artifacts can significantly affect
the image quality.
Cardiac MRI in the Current Day Scenario

Magnetic resonance imaging (MRI) has been an established
high-resolution imaging modality for demonstration of
cardiovascular morphology. In contrast to CT, MRI allows
functional evaluation in addition to morphologic detail in
CHD patients. Thus, in addition to anatomy, which can be
demonstrated by both techniques, cardiac MRI has the ability
to calculate ventricular function and assess valve regurgitation.
Right ventricular dilation and function assessment are
especially important in situations such as postoperative,
TOF with pulmonary regurgitation, where worsening right
ventricular (RV) function can necessitate pulmonary valve
replacement.
MRI with its advances in hardware design, new pulse
sequences and faster image reconstruction techniques allows
rapid high-resolution imaging of complex cardiovascular
anatomy in 3D space, quantitative assessment of ventricular
volumes, mass, stroke volume and ejection fraction, assessment
of myocardial function using tagging technique, quantification
of blood flow rate and imaging of non-cardiac structures
such as the trachea and bronchi. A comprehensive cardiac
MRI examination effectively characterizing cardiovascular
anatomy and physiology can now be performed in as little as
60 minutes.
Role of Newer Cardiac Imaging in Congenital Heart Diseases
Figure 3: Curved MIP reformat delineating the venous anatomy

in total anomalous pulmonary venous connection. SVC = Superior
vena cava
In MRI, magnetic fields and radiofrequency energy are used

to stimulate hydrogen nuclei in selected regions of the body
to emit radio waves that are then used to construct MRI
images. The heart, blood and blood vessels are in relatively
rapid motion compared to other body structures. An image at
a particular point during the cardiac cycle is built up from data
acquired over multiple cardiac cycles.8
Consequently, synchronization with the cardiac cycle is
required in order to return to the same point in the cycle
and effectively freeze cardiac motion. Imaging may be
synchronized or gated with a pulse oximetry trace (so
called peripheral gating) or more efficiently with a highquality electrocardiogram (ECG) signal. Because images are
constructed over multiple cardiac cycles, respiratory motion
can degrade image quality. The best approach to minimize
respiratory artifacts is to have the patient hold their breath
during image acquisition, which may not be possible with
very young and sick patients. Respiratory motion can be
monitored using a bellows device around the body or by MRI
navigator echoes, which concurrently image the position of
the diaphragm or heart.
The pulse sequence specifies how the magnetic field
gradients and radiofrequency pulses are applied and read during
image acquisition. In general, there are two major categories
of pulse sequencesspin echo and gradient echo. A particular
pulse sequence can often be modified by adding preparatory
pulses that alter tissue contrast. In addition, there are numerous
user selectable imaging parameters that effect tissue contrast,
image quality and temporal and spatial resolution.9
14
Anatomic Imaging and Tissue Characteristics

Spin echo pulse sequences are usually used to produce images,
in which flowing blood has a low signal intensity and appears
dark (black blood imaging). Other tissues appear as varying
shades of gray. Though cardiac-gated spin echo sequences
produce only one image per location and thus provide only
static anatomic information, their advantages include high
spatial resolution, excellent blood-myocardial contrast and
decreased artifact from metallic biomedical implants (e.g.
sternal wires, stents, prosthetic valves). Spin echo sequences
are also easily modified to alter tissue contrast and characterize
abnormal structures. Their clinical uses include evaluation
for arrhythmogenic right ventricular cardiomyopathy,
cardiac tumors, constrictive pericardial disease, vessel wall
abnormalities and thoracic masses.
Cardiac-gated gradient echo sequences can be used to
produce multiple images over the cardiac cycle in each
anatomic location. These images can then be displayed in a
cine loop format to demonstrate the motion of the heart and
vasculature over the cardiac cycle. On such cine MR images,
205
2
Basics
specialized software, regions of interest around a vessel are

defined and the flow rate is automatically calculated.13
Clinically, VEC MRI can be used to quantify cardiac
output, the pulmonary to systemic flow ratio, valvular
regurgitation, differential lung perfusion and coronary
flow. When flow encoding is performed in three orthogonal
directions, multidimensional flow imaging and shear stress
calculation can be accomplished.
Magnetic Resonance Angiography
Figure 4: Bright blood MR imaging sequence demonstrating

a large ostium secundum type of atrial septal defect (ASD)
flowing blood produces a bright signal and the myocardium

and the vessel wall are relatively dark (bright-blood imaging)
(Figure 4).10
Cine MRI is used to delineate cardiovascular anatomy
and assess ventricular function, evaluating the systemic and
pulmonary veins, atrial and ventricular septum, intracardiac
baffles and pathways (e.g. following Fontan, Mustard,
Senning or Rastelli procedures), ventricular outflow tracts,
ventricular arterial conduits, pulmonary arteries and the aorta.
It also has a role in identifying stenotic and regurgitant jets,
which appear as dark signal voids (Figure 5).11
Myocardial tagging is a modification of cine MRI that
allows for a sophisticated analysis of regional myocardial
function. Using a preparatory radiofrequency pulse, saturation
bands or tags that appear as dark lines on the image are
applied to the myocardium at end diastole. By analyzing the
movement and deformation of these tags over the cardiac
cycle, regional myocardial strain can be quantified.12
Another approach for improving the contrast between vascular

and non-vascular structures is to administer an exogenous
intravenous contrast agent, typically a gadolinium-chelate,
thereby dramatically shortening the T1-relaxation of blood,
resulting in a bright signal on T1-weighted sequences. This
method of angiography is less prone to flow-related artifacts
than other MR techniques and has a short acquisition time.
Contrast-enhanced MR angiography (MRA) is usually
performed without cardiac gating using a 3D fast gradient
echo acquisition lasting 15 to 30 s, while the patient holds their
breath. The time delay between contrast administration and
image acquisition determines the vascular territory illustrated
and several acquisitions can be performed. The entire
procedure takes only a few minutes to perform and yields a
high-contrast and high resolution 3D data set depicting all or
part of the thorax (Figure 6).
MRA is ideally suited to illustrate the anatomy of the
aorta and its branches, PAs, pulmonary veins and systemic
veins. Although this technique is mostly used for imaging
of extracardiac anatomy, it is also useful in the evaluation of
intra-atrial systemic and pulmonary baffles (such as in Mustard
Blood Flow Analysis
206
An ECG-gated velocity-encoded cine MRI (VEC MRI) is a

gradient echo sequence used to measure blood flow velocity
and quantify the rate of blood flow. The VEC MRI technique
is based on the principle that the signal from hydrogen nuclei
(such as those in blood) flowing through specially designed
magnetic field gradients accumulates a predictable phase shift
that is proportional to its velocity.
Multiple phase images are constructed across the
cardiac cycle, in which the voxel intensity or brightness
is in proportion to blood velocity within that voxel. Using
Figure 5: Velocity encoded MRI sequence demonstrating

the bicuspid configuration of the aortic value
for planning of interventional catheterization or surgical

procedures (Figures 7A and B).14,15
Although traditionally, the diagnosis of myocardial ischemia

has not been a focus of imaging in CHD, it clearly has relevance
in patients who have congenital coronary abnormalities (e.g.
anomalous origin of the left coronary artery, pulmonary
atresia with intact ventricular septum) and in older adults.
Several MRI techniques for imaging the coronary arteries
with sufficient resolution are available. MRI techniques are
also available for assessment of regional left ventricular
myocardial perfusion.
Some Clinical Applications of MRI
Figure 6: Contrast enhanced MRA with excellent delineation of

coronary collaterals in a case of Bland-White-Garland syndrome
or Senning operations and after Fontan procedures), as well

as for imaging of the outflow tracts (such as in repaired TOF
and the arterial switch operation). In addition to volume
rendered CT angiogram, the MRA clearly delineates the spatial
relationships between vascular structures, the tracheobronchial
tree, chest wall, spine and other landmarks that may be useful
The indications for cardiac MRI are to evaluate the right

ventricle, valve regurgitation, surgical systemic and pulmonary
venous pathways, Fontan pathways and the great vessels.
MRI may be considered the primary imaging modality in
adolescents and adults with repaired TOF, atrial and arterial
switch operations for transposition of the great arteries, Fontan
operation, aortic arch anomalies and several other conditions.
Postoperative Tetralogy of Fallot

In patients with repaired TOF, MRI is assuming an increasing
role as the primary non-invasive modality. In the post-operative
Figures 7A and B: A. Contrast enhanced MRA demonstrating anomalous origin of left coronary artery from left pulmonary
artery (ALCAPA); B. Volume rendered image of CT angiogram in ALCAPA illustrates left main coronary (LMC) artery arising
from main pulmonary artery (MPA). LAD = Left anterior descending coronary artery; LCX = Left circumflex coronary artery
Myocardial Ischemia and Viability
14
207
2
Basics
detection of collateral vessels that bypass the coarctation site,

assessment of left ventricular mass, dimensions and function
and detection of any associated lesions.17
Fontan Circulation
follow-up of TOF, the patients often have residual anatomic

and hemodynamic abnormalities such as chronic pulmonary
regurgitation, residual ventricular septal defect, right
ventricular volume overload and dysfunction, right ventricular
outflow tract obstruction, branch pulmonary artery stenosis,
residual aortopulmonary collaterals and others.
The goals of the MRI examination after TOF repair
include quantitative assessment of left and right ventricular
volumes, mass, stroke volumes and ejection fraction, imaging
the anatomy of the right ventricular outflow tract (Figure 8),
PAs, aorta and aortopulmonary collaterals and to quantify
pulmonary regurgitation, tricuspid regurgitation, cardiac
output and pulmonary to systemic flow.16
Fontan circulation population subset is at risk for complications

such as systemic ventricular dysfunction, thromboembolism,
dilation of the systemic venous atrium, obstruction of the
Fontan pathways, pulmonary artery stenosis, compression
of the pulmonary veins, atrioventricular valve regurgitation
and arrhythmias. Prompt detection of these complications is
therefore an important element of managing these patients.
Several reports have utilized MRI as an investigational tool
to study blood flow dynamics within the Fontan pathways
and to delineate the distribution of inferior and superior
caval flow to each lung. Myocardial tagging has proved an
important investigational tool in the evaluation of myocardial
mechanics in patients with a functional single ventricle and
Fontan circulation, demonstrating asynchrony and impaired
regional wall motion.18,19
The clinical utility of MRI in patients with the Fontan
circulation increases as the acoustic windows become more
restricted with growing years. The MRI examination in patients
with the Fontan circulation can assess the pathways from the
systemic veins to the pulmonary arteries for obstruction and
for a thrombus detection of Fontan baffle fenestration or leaks,
evaluation of the pulmonary veins for compression, systemic
ventricular volumes, mass and pump function, imaging of the
systemic ventricular outflow tract for obstruction, quantitative
assessment of the atrioventricular and semilunar valve(s) for
regurgitation, the aorta for obstruction or an aneurysm and for
aortopulmonary, systemic venous or systemic to pulmonary
venous collateral vessels.19
Aortic Arch Anomalies
Subpulmonic Ventricular septal defect
The use of MRI to image anomalies of the aortic arch is best

suited for non-invasive evaluation of congenital, acquired and
postoperative anomalies of the aorta in adolescents and adults.
Certain diagnostic categories are known to have a higher
risk for aortic complications such as patients with Marfan
syndrome and other connective tissue disorders who are at
risk for aortic aneurysm, dissection and rupture. Patients with
a coarctation of the aorta comprise another high-risk group
for late development of aortic complications, including restenosis of the repair site, transverse aortic arch hypoplasia,
progressive dilatation of the ascending aorta and aneurysm
formation. The objectives of the MRI evaluation of suspected
or repaired aortic coarctation include imaging of the aortic wall
at the coarctation site and any other abnormal aortic segment,
dynamic imaging of blood flow throughout the thoracic
aorta to detect high-velocity flow jets suggestive of stenosis,
MRI also aids in the diagnosis and management of supracristal

VSD. Echocardiography, despite being the primary imaging
modality for the evaluation of cardiac shunts is less accurate
for defining supracristal ventricular septal defect and cardiac
angiography despite its accuracy in localizing the lesion,
involves catheterization and ionizing radiation with attendant
risks to the patient. ECG-gated spin-echo MR imaging is an
effective and non-invasive alternative, which can typically
depict a characteristic defect between the base of the aorta and
the right ventricular infundibulum and cine MR images can
demonstrate a systolic flow jet from the left ventricle into the
right ventricular outflow tract, indicating a left-to-right shunt.
Shunt severity can be quantified by calculating the ratio of
pulmonary flow to systemic flow, with flow values obtained
from velocity-encoded cine MR planimetry. Additionally,
MR imaging can diagnose complications of supracristal
Figure 8: Multiplanar true FISP axial image showing large aneurysm

of the right ventricular outflow tract (RVOT) in a patient with posttetralogy of Fallot repair
208
Disadvantages of Magnetic Resonance Imaging

MRI has its own inherent limitations ranging from poorer
spatial resolution; image-degrading artifacts from implanted
metal, such as intravascular stents and embolization coils;
higher cost; limited availability to contraindications for
imaging of patients with pacemakers and increased need for
general anesthesia in younger children. MRI also takes longer
than CT, possibly a relative contraindication for imaging the
critically ill, thermally unstable and uncooperative pediatric
patients and more often requires onsite physician monitoring
to assure diagnostic image quality and customized compatible
monitoring equipment for the imaging per se. Finally, MRI is
limited in the evaluation of the airways and lungs, structures
that CT smartly depicts well. The Box 1 compares the pros
and cons of CT versus MRI in heart disease evaluation.
summary
Both CT and MRI, in the context of congenital heart
disease have competed with each other in recent years to
attain the ultimate goal: a one stop shop for comprehensive
information on cardiac status. This has led to sophisticated
technical innovations on both sides that have channelized the
Box 1: Pros and cons of computed tomography
versus magnetic resonance imaging in heart disease
evaluation
CT pros
Short examination time
Fewer requirements of sedation
Simultaneous evaluation of lung parenchyma
High spatial resolution
CT cons
Radiation exposure
Use of iodinated contrast material
Lack of functional information (e.g. right ventricular
function, pulmonary regurgitation fraction)
MRI pros
Multiplanar capability
Wide field of view
Lack of dependence on a rapid bolus of IV contrast
No radiation
Can give valuable functional information
MRI cons
Long scanning time, needs breath hold
Difficult to scan intubated sick children
Close monitoring
Lower spatial resolution
specificity and range of indications for which each of them

can be customized. Patients clinical history is by far the most
important information and basis for choosing the appropriate
modality. As shown by many recent studies, cardiac CT
allows for a reliable morphologic evaluation in CHD and
enjoys constantly high negative predictive value, especially in
assessment of postoperative assessment. MR is the modality
of choice in any functional aspect of cardiac imaging, whether
focusing on cardiac and valvular function or perfusion.
Diagnosis is not the end, but the beginning of practice.
Martin H Fischer
REFERENCES
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and CT of vascular anomalies and connections in patients with
congenital heart disease:significance in surgical planning.
RadioGraphics. 2002;22:337-47; discussion, 348-49.
2. Goo HW, Park IS, Ko JK, et al. CT of congenital heart
disease: normal anatomy and typical pathologic conditions.
RadioGraphics. 2003;23(Spec Issue):S147-65.
3. Flohr T, Stierstorfer K, Raupach R, et al. Performance
evaluation of a 64-slice CT system with z-flying focal spot.
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4. Becker C, Soppa C, Fink U, et al. Spiral CT angiography
and 3D reconstruction in patients with aortic coarctation.
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5. Sridhar PG, Kalyanpur A, Suresh PV, et al. Helical CT
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6. Lee KH, Yoon CS, Choe KO, et al. Use of imaging for assessing
anatomical relationships of tracheobronchial anomalies
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7. Kim TH, Kim YM, Suh CH, et al. Helical CT angiography
and three-dimensional reconstruction of total anomalous
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Am J Roentgenol. 2000;175:1381-86.
8. Mulkern RV, Chung T. From signal to image: magnetic
resonance imaging physics for cardiac magnetic resonance.
Pediatr Cardiol. 2000;21:5-17.
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1996;199:49-57.
11. Carr JC, Simonetti O, Bundy J, et al. Cine MR angiography of
the heart with segmented true fast imaging with steady-state
precession. Radiology. 2001;219:828-34.
12. McVeigh ER, Atalar E. Cardiac tagging with breath-hold cine
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13. Powell AJ, Geva T. Blood flow measurement by magnetic
resonance imaging in congenital heart disease. Pediatr Cardiol.
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14. Neimatallah MA, Ho VB, Dong Q, et al. Gadolinium-enhanced
3D magnetic resonance angiography of the thoracic vessels. J
Magn Reson Imaging. 1999;10:758-70.
14
ventricular septal defect, including aortic valve prolapse with

resultant aortic regurgitation and secondary right ventricular
enlargement or hypertrophy.20
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15. Masui T, Katayama M, Kobayashi S, et al. Gadolinium

enhanced MR angiography in the evaluation of congenital
cardiovascular disease pre and postoperative states in
infants and children. J Magn Reson Imaging. 2000;12:
1034-42.
16. Helbing WA, de Roos A. Clinical applications of cardiac
magnetic resonance imaging after repair of tetralogy of Fallot.
17. Bogaert J, Kuzo R, Dymarkowski S, et al. Follow-up of patients
with previous treatment for coarctation of the thoracic aorta:
comparison between contrast-enhanced MR angiography and

fast spin-echo MRI. Eur Radiol. 2000;10:1847-54.
18. Mayer JE Jr. Late outcome after the Fontan procedure. Semin
Thorac Cardiovasc Surg; Pediatr Cardiol Surg Annu. 1998;1:
5-8.
19. Balling G, Vogt M, Kaemmerer H, et al. Intracardiac thrombus
formation after the Fontan operation.
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Sec t i on
Defects in Atriovenous and

Pulmonary Arteriovenous
Connections
C hapter
15
Anomalies of Systemic Veins

Jayashree Kharge, Vijayalakshmi IB
INTRODUCTION
The abnormalities of position and connection of the major
systemic venous channels draining to the heart are mostly
rare incidental findings with not much of hemodynamic
significance, when visceroatrial situs is lateralized. In contrast,
the incidence of systemic venous anomalies in patients with
heterotaxy syndrome exceeds 90 percent.1 However, even
when not hemodynamically significant, they may complicate
interventional procedures and cause arrhythmias. In some
cases it can cause cyanosis, polycythemia, paradoxical
embolism and even stroke. The relevant embryology
and anatomy with individual anomalies and their clinical
significance is discussed.
Classification of Systemic Venous Anomalies

1. Anomalies of the superior vena cava
2. Anomalies of the inferior vena cava
3. Anomalies of the ductus venosus
4. Total anomalous systemic venous connection.
posterior veins join before entering the sinus horn and form
the short common cardinal veins. During the fourth week,
the cardinal veins form a symmetrical system.
Formation of the vena caval system is characterized by the
appearance of anastomosis between the left and right sides in
such a manner that the blood from the left side is channeled
to the right side (Figure 2). The anastomosis between the
anterior cardinal veins develops into the left brachiocephalic
vein (Figures 2 and 3).
Most of the blood from the left side of the head and the left
upper extremity is then channeled to the right. The terminal
portion of the left anterior cardinal vein entering into the left
brachiocephalic vein is retained as a small vessel, the left
superior intercostal vein (Figure 4). This vessel receives blood
from the second and third intercostal spaces. The superior
vena cava is formed by the right common cardinal vein and
the proximal portion of the right anterior cardinal vein.
A left-sided superior vena cava is an abnormality caused
by the persistence of the left anterior cardinal vein and
obliteration of the common cardinal and proximal part of the
anterior cardinal veins on the right. In such a case, blood from
Anomalies of the Superior Vena Cava

The development of the superior vena cava (SVC).
In the human fetus, during the fifth week of intrauterine
life, three pairs of major veins can be distinguished:2
1. The vitelline, carrying blood from the yolk sac to the sinus
venosus.
2. The umbilical veins, originating in the chorionic villi and
carrying oxygenated blood to the embryo.
3. The cardinal veins, draining the body of the embryo proper
(Figure 1). Initially, the cardinal veins form the main venous
drainage system of the embryo. This system consists of the
anterior cardinal veins, which drain the cephalic part of the
embryo, and the posterior cardinal veins, which drain the
remaining part of the body of the embryo. The anterior and
Figure 1: Cardinal veins. SV = Sinus venosus;

UV = Umbilical vein; VV = Vitelline vein
Defects in Atriovenous and Pulmonary Arteriovenous Connections
Subcategory of SVC Anomalies

1. Bilateral superior vena cava with normal drainage to the
right atrium.
2. Bilateral superior vena cava with an unroofed coronary
sinus.
3. Absent right superior vena cava in visceroatrial situs
solitus.
4. Left atrial or biatrial drainage of right superior vena cava.
5. Retroaortic innominate vein.
Bilateral SVC with Normal Drainage to the Right Atrium

Figure 2: Changes in the left anterior cardinal vein.
SV = Sinus venosus
The persistence of left superior vena cava (LSVC) is thought

to result from failure of left anterior and left common cardinal
veins to involute.3 It was first described by McCotter in
1916.4 It can present as an isolated anomaly or as a part of
more complex cardiac anomalies. In 98 percent of the cases, it
drains into the right atrium through the coronary sinus.5 In the
remaining 2 to 3 percent it drains into the left atrium through
the unroofed coronary sinus.
The incidence of LSVC is 0.3 to 0.5 percent in the general
population6,7 and the prevalence is much higher in patients
with congenital heart disease at 10 percent.8
The following congenital heart diseases are associated with
increased frequency of persistent LSVC:9,10
1. Tetralogy of Fallot (11%)
2. Atrioventricular septal defects (19%)
3. Mitral atresia (17%)
4. Juxtaposition of right atrial appendage (34%).
Anatomy and Course of LSVC

Figure 3: Formation of the left brachiocephalic vein
Typically the LSVC descends vertically, anterior, and to the left

of the aortic arch and main pulmonary artery. It runs adjacent
to the left atrium (LA) before turning medially, piercing the
pericardium to run in the posterior atrioventricular groove.11
About 90 percent of cases drain into the CS; alternative sites
include the inferior vena cava, hepatic vein and LA (Figure
5). In rare instances, the LSVC may drain directly to the roof
of the LA, resulting in partial anomalous systemic venous
return.
Clinical Manifestations of Persistent LSVC

Figure 4: Formation of the superior vena cava
214
the right is channeled towards the left by way of the right

brachiocephalic vein. The left superior vena cava drains into
the right atrium by way of the left sinus horn, i.e. the coronary
sinus.
There are no clinical manifestations when the persistent

LSVC drains into the right atrium through the coronary
sinus, as it is well tolerated. But the drainage of the LSVC
to LA, produces a right to left shunt and cyanosis, and this
can facilitate development of systemic abscesses or emboli.
When associated with other cardiac malformations there may
be diagnostic and technical difficulties during catheterization
and cardiac surgery.
15
Figure 5: Course of a left superior vena cava (LSVC) in presence

of a brachiocephalic vein. Courtsey: Robert Anderson
Figure 6: Parasternal long axis view demonstrating marked dilation

of the coronary sinus (CS) with no other apparent echocardiographic
abnormalities. LV = Left ventricle; RV = Right ventricle; Ao = Aorta;
LA = Left atrium
Diagnosis
Suspicion of LSVC may arise on the posteroanterior chest
X-ray, where it may appear as widening of the aortic shadow,
paramediastinal bulging, paramedian stripe, or a low-density
line along the upper left margin of the heart.12-14 Transthoracic
echocardiogram (TTE) is the main tool for diagnosing
persistent LSVC (Figure 6).15-19 As demonstrated in the case,
Figure 7: Apical 4-chamber view by transthoracic echocardiogram with

intravenous agitated saline when injected through the left antecubital
vein is seen in the right atrium (RA) and right ventricle (RV) via the
dilated coronary sinus (CS). LV indicates left ventricle
TTE gives a readily available bedside confirmatory test that

is noninvasive and inexpensive. It also helps identify other
cardiac anomalies that might be associated. Echocardiography
is poor at delineating the insertion site of the persistent
LSVC. This site is usually an enlarged coronary sinus, which
is confirmed by an agitated saline bubble study via the left
brachial vein. The observation of bubbles appearing first in
the coronary sinus and then in the right atrium (Figure 7)
confirms the diagnosis.
The differential diagnosis of dilated coronary sinus
includes right ventricular dysfunction, right atrial
hypertension, and anomalous venous drainage into the
coronary sinus. These abnormalities include persistent
LSVC, total anomalous pulmonary venous return, coronary
atrioventricular fistula, and anomalous hepatic venous
drainage. Rarer causes of dilated coronary sinus include
postoperative obstruction, thrombosis or ventricularization,
and unroofing of the sinus. Extreme dilation of the coronary
sinus can cause substantial problems during septal puncture
in balloon mitral valvotomy.
Persistent LSVC can be diagnosed by magnetic resonance
imaging (MRI) either by spin echo or by gradient echo
sequences. Magnetic resonance angiography (MRA) is
particularly suitable for rapid noninvasive delineation of
systemic venous anatomy.
By cardiac catheterization, LSVC can be suspected by
the presence of higher than expected coronary sinus oxygen
saturation. Left innominate vein angiography with balloon
215
The highest incidence of bilateral SVCs with a completely

unroofed coronary sinus is seen in patients with visceral
heterotaxy with asplenia. The increased frequency of its
occurrence in this group probably represents a remnant of
the normal early embryonic symmetry of the systemic veins
which is characteristic of visceral heterotaxy.
Clinical Features
Figure 8: Right heart catheter through right atrium (RA), coronary

sinus (CS) into left superior vena cava (LSVC). Hand injection of
contrast shows LSVC draining to CS
Diagnosis
occlusion proximal to the injection site is diagnostic. The
LSVC can be approached either through the right SVC (when
the innominate vein is present) or through the coronary sinus
(Figure 8). The diagnosis of systemic venous anomalies can
be reliably established by echocardiography and MRI, making
cardiac catheterization unnecessary in most patients.
Treatment
No treatment is necessary when the LSVC is draining into an
intact coronary sinus.
Bilateral Superior Vena Cava with Unroofed

Coronary Sinus
216
The persistent LSVC with unroofed coronary sinus functions

as an interatrial communication. The hemodynamic conse
quences are cyanosis and right to left shunting. There is
systemic arterial desaturation due to mixing of LSVC blood
with pulmonary venous blood in the left atrium. The degree of
desaturation is related to the net right-to-left shunting, which
in turn depends on the proportion of systemic venous blood
that crosses the atrial septum and reaches the pulmonary
circulation. The complications associated with right-to-left
shunting are paradoxical emboli, brain abscess, strokes and
death.
Unroofed coronary sinus has been classified morphologically

into four types by Kirklin and Barratt-Boyes, which are as
follows:20
Type I: Completely unroofed, with LSVC
Type II: Completely unroofed, without LSVC
Type III: Partially unroofed mid portion
Type IV: Partially unroofed terminal portion.
Raghib et al21 described eight cases with the following
findings:
1. Left superior vena cava drains into the left atrium.
2. An atrial septal defect is present. The defect lies in the
posteroinferior angle of the atrial septum and above the
posteromedial commissure of the mitral valve. It is separated
from the mitral valve by a small amount of septal tissue.
3. Coronary sinus is absent.
On the chest radiogram the LSVC may appear as a shadow

along the left upper border of the mediastinum.
The electrocardiogram is similar to ostium secundum ASD.
However, in patients with visceral heterotaxy, the frontal axis
of the P waves may be abnormal reflecting a left sinoatrial
node or an ectopic atrial rhythm.
The echocardiogram is the definitive imaging modality
with the subcostal or suprasternal window showing the LSVC
draining into the LA (Figures 9A to C).
Flow mapping with color Doppler is useful in demons
trating the flow from LSVC into the LA. A contrast injection
in the left arm vein demonstrates the appearance of the micro
bubbles in the left atrium before they appear in the right
atrium. CT angiogram and magnetic resonance imaging
is useful when the echocardiogram does not delineate the
anatomy clearly (Figure 9D).
Cardiac catheterization is diagnostic (Figure 10) and
there is also step-down in the oxygen saturation between the
pulmonary veins and the left atrium. Also the LSVC can be
selectively cannulated.
Treatment
It is important to assess the size of the left innominate vein
before any attempts to close the defect. If the LSVC is of small
size and the innominate vein is of adequate size, the LSVC
can be ligated and the interatrial communication closed. But
in the absence of an adequate sized innominate vein, it is
prudent to reroof the coronary sinus22 which is achieved by
baffling the coronary sinus along the posterior wall of the left
15
Figures 9A to D: A and B. Suprasternal modified view with colour Doppler in a 3 months old with left isomerism. There is absent right superior
vena cava with left superior vena cava (LSVC) draining into the left atrium (LA); C. Pulse wave Doppler on LSVC, confirms the biphasic venous
flow; D. CT angiogram shows LSVC draining into LA
atrium into the right atrium. The LSVC or coronary sinus can
be closed percutaneously with an ASD device.
Absent Right Superior Vena Cava in Situs Solitus
Figure 10: Fluoroscopic picture in a 6 years old girl, in frontal view,

shows right heart catheter through atrial septal defect into left
superior vena cava (LSVC). Selective contrast injection opacifies left
innominate vein (LIV), LSVC, left atrial appendage (LAA), left atrium
(LA) and left ventricle (LV). The right superior vena cava (RSVC) and
right atrium (RA) are also faintly opacified
The absence of the right superior vena cava is a very rare

anomaly occurring in about 0.07 to 0.13 percent of patients
with cardiac abnormalities.23,24 This anomaly is seen in both
patients with structurally normal hearts (54%) and in patients
with congenital heart defects (46%).25
It is characterized by the persistence of LSVC draining into
the right atrium via the coronary sinus and by the left-sided
azygos vein draining into the LSVC. It is mostly an incidental
finding and is usually asymptomatic. However, Bartram et al25
have reported rhythm disturbances such as atrioventricular
block, sinoatrial node dysfunction, right and left bundle branch
blocks and supraventricular tachycardia. It is easily diagnosed
on echocardiography, CT, MRI and angiography.
It is clinically important to recognize this anomaly to
avoid difficulties during the interventional procedures such
as transvenous permanent pacemaker implantation, venous
cannulation for cardiopulmonary bypass or extracorporeal
membrane oxygenator, pulmonary artery monitoring line
through the subclavian or jugular veins. And also prior to
217
218
surgery that includes cavopulmonary anastamosis and ortho

topic heart transplantation. It is not required to treat these
patients when the physiology is normal.
Right Superior Vena Cava Draining into the Left Atrium

The left atrial drainage of the right superior vena cava is a
rare anomaly, manifesting as unexplained cyanosis and
clubbing.26
This malformation probably represents a sinus venosus
defect of the SVC type in association with atresia of the right
SVC orifice. There is unroofing of the right upper pulmonary
vein and its branches which drain into SVC and its left atrial
orifice becomes the inter atrial communication. The left atrial
blood can be shunted into the SVC-RA junction or the right
SVC blood can enter the left atrium depending on the pressure
and the compliance differences between the two atria.
Cyanosis is the dominant clinical feature when the
right SVC drains into the left atrium. The risks include
polycythemia, systemic emboli, brain abscess, and other
cerebrovascular complications typically increasing with age.
On the echocardiogram the common entrance site of right
SVC and the right upper pulmonary vein in the roof of the left
atrium can be demonstrated.27
Surgery is the treatment of choice where the right SVC
flow is diverted into the right atrium. The preferred surgical
approach involves transaction of right SVC above the right
upper pulmonary vein and anastamosis of the transacted caval
end to the right atrial appendage.26
As against this, reduced shortening of the aortic arch as

seen in right aortic arch and high aortic arch may compress
and prevent the further development of the superior transverse
venous plexus. Abnormal development of the pulmonary arte
ries, either pulmonary atresia or pulmonary stenosis, encou
rages the sparing of the inferior transverse plexus, possibly
leading to formation of an anomalous course of the innominate
vein. This would explain frequent association of the retroaortic
innominate vein with TOF and right aortic arch.29-31
Usually, the retroaortic innominate vein in isolation has no
clinical importance. The descending portion of the retroaortic
innominate vein may be mistaken for persistent LSVC or
an ascending vertical vein in a total anomalous pulmonary
venous connection on echocardiography.32 The retroaortic
segment may be misinterpreted as right pulmonary artery in
patients with hypoplastic or atretic central pulmonary arteries,
or an early branching of right upper lobe pulmonary artery on
echocardiography.33,34
In a retrospective analysis of echocardiograms the
incidence of retroaortic innominate vein was found to be 0.55
percent amongst children with congenital heart disease. It was
most commonly associated with tetralogy of Fallot and right
aortic arch.35
It is widely considered to be anatomical variant without
clinical ramifications. However, knowing the precise
preoperative information about the anomaly can be critical in
planning surgical procedure.
ANOMALIES OF THE INFERIOR VENA CAVA
Retroaortic Innominate Vein
Anatomy
The left innominate (or brachiocephalic) vein is formed by

the left internal jugular and the left subclavian vein. In the
situs solitus, its usual course is obliquely downward to the
right, passing superoanterior to the aortic arch. Anomalous
course of the innominate vein is rare, being first described by
Kershner more than 100 years ago.28
Embryologically, the primordia of the systemic veins
first appear as paired anterior and posterior cardinal veins
that unite on each side to form a common cardinal vein (or
Cuvierian duct) that opens into the primitive sinus venosus.
During subsequent development, most of the left anterior car
dinal vein disappears. The venous drainage from the left side
of the head and neck and the left arm is then directed into
the right anterior cardinal vein by the development of new
transverse anastomotic channels above and below the fourth
aortic arch (superior and inferior transverse capillary plexus)
by the eighth week. Normally, the aortic arch shortens during
the embryological development and occupies the space of the
inferior transverse capillary plexus, thus causing its regression,
while the rest of venous blood shunts into the superior
transverse capillary plexus. This facilitates the development
of the normal supra-aortic course of the left innominate vein.
The normal inferior vena cava (IVC) is composed of four

segments: hepatic, suprarenal, renal, and infrarenal. The
hepatic segment is derived from the vitelline vein. The right
subcardinal vein develops into the suprarenal segment by
formation of the subcardinal-hepatic anastomosis. The renal
segment develops from the right supra-subcardinal and postsubcardinal anastomosis. It is generally accepted that the
infrarenal segment derives from the right supracardinal vein,
although this idea is somewhat controversial.36 In the thoracic
region, the supracardinal veins give rise to the azygos and
hemiazygos veins. In the abdomen, the postcardinal veins are
progressively replaced by the subcardinal and supracardinal
veins but persist in the pelvis as the common iliac veins.
Interrupted Inferior Vena Cava

Moller et al in 1967 concluded that interrupted IVC represents
one of the characteristics of the polysplenia syndrome.37
However, interrupted IVC has also been reported in patients
with normal hearts38,39 and very rarely in asplenia.40
Interrupted IVC is defined as the absence of the hepatic
segment of the IVC with azygos continuation into the right
or left superior vena cava. Infrahepatic interruption of the

IVC with azygos continuation (Figure 11) is a rare congenital
anomaly seen in 0.62% of patients with congenital heart
disease and in less than 0.3% of otherwise normal individuals.41
Rarely, the infrahepatic segment of the IVC may continue to
both right and left SVC via bilateral azygos veins.
Although the interrupted IVC does not result in physiologic
abnormality, the clinical importance lies in its frequent
association with the heterotaxy syndrome and polysplenia.
Rarely, the IVC may be interrupted by a membrane causing
abdomonal distension and discomfort (Figure 12A). In
surgeries that require redirection of the systemic venous
return to the pulmonary arteries such as bidirectional Glenn
and modified Fontan, prior knowledge of the anatomical
abnormality helps in planning the surgery appropriately.
15
Figure 11: Fluoroscopic image illustrates the interrupted inferior vena

cava with continuation through the azygos vein into the superior vena
cava showing a candy cane apperance
Interrupted IVC with azygos continuation can complicate

cardiac catheterization and interventional procedures such as
device closure and radiofrequency ablation.
The diagnostic features of interrupted IVC on Echo: The
diagnosis is based on imaging the size, location, and course of
the IVC and the azygos vein from the subxiphoid window.42,43
Normally, the short axis view at the level of the diaphragm
shows the aorta and the IVC to be placed symmetrically
with respect to the spine, with aorta to the left and IVC to
the right, when the renal-to-hepatic segment is intact. The
aorta is recognized by its typical systemic arterial pulsation
pattern. The inferior vena cava is traced below the level of
the liver and superiorly receives hepatic venous connection
below or at the level of connection with the right atrium. To
the left of the spine, the aorta is imaged in long axis and is
identified further by its slightly thicker wall compared with
the inferior vena cava and the typical branching pattern of the
celiac and superior mesenteric arteries. When the renal-tohepatic segment of IVC is absent, no IVC is seen below the
liver, azygos vein is enlarged and it can be followed cranially
with a SVC, which can also be imaged from the parasternal
and suprasternal windows. The three-dimensional MRA is
accurate in delineating normal and abnormal systemic venous
anatomy.
Treatment
The IVC interruption by a congenital membrane causing
distention of abdomen can be treated by transcatheter
intervention (Figures 12B and C). However, if patient is
asymptomatic no specific treatment is required. Inadvertent
ligation of azygos vein can lead to death.38
Inferior Vena Caval Drainage to the Left Atrium

The inferior caval vein has been reported as connecting
directly to the LA both with an intact atrial septum and in
Figures 12A to C: A. 3-year-old girl with distension of abdomen; B. Simultaneous injection of contrast in inferior vena cava (IVC) from below
through femoral vein approach and from above through jugular vein approach shows a membrane in IVC with tortuous collaterals; C. Check
venogram from IVC after membrane was punctured by Brockenbrough needle and dilatation with Inoue balloon, illustrates opened up IVC
(arrow) and disappearance of large collateral. RA = Right atrium
219
Figures 14A and B: Left sided inferior vena cava (IVC): A. Draining
into hepatic IVC and into right atrium (RA); B. Draining through
hemiazygos vein into left superior vena cava (LSVC) into the coronary
sinus (CS)
Figure 13: The cartoon shows a persistent Eustachian valve directing

inferior venous caval flow into the left atrium. This should not be
mistaken for connection of the inferior caval vein to the left atrium.
Courtsey: Robert Andersons
association with an atrial septal defect. In this respect, it is

necessary to distinguish between direct connection to the LA
and the arrangement in which an inferior caval vein overrides
a low-lying interatrial communication and allows functional
drainage of inferior caval venous flow to the LA. The latter
situation can be exacerbated by persistence of an unduly
prominent Eustachian valve that directs the flow into the LA
(Figure 13).
Clinical Features
The partial or complete drainage of the IVC into the LA
results in cyanosis due to right-to-left shunting, including
polycythemia, brain abscess, and paradoxical emboli.
Treatment
Inferior vena cava (IVC) blood is surgically redirected into
the right atrium.44,45
Left sided Inferior Vena Cava
220
A left sided IVC results from regression of the right

supracardinal vein with persistence of the left supracardinal
vein. The prevalence is 0.20.5 percent.46 The left IVC
typically joins the left renal vein, which crosses anterior to
the aorta in the normal fashion, uniting with the right renal
vein to form a normal right-sided prerenal IVC (Figure 14 A).
This anomaly can be misdiagnosed as left-sided paraaortic
adenopathy.47 Transjugular access to the infrarenal IVC for

placement of an IVC filter may be difficult.
Hemiazygos continuation of a left-sided IVC has several
variations.48-51 There are three likely routes for blood in the
hemiazygos vein to reach the right atrium. In the first route,
the hemiazygos vein drains into the azygos vein at T8T9. The
distal azygos and hemiazygos vein are enlarged. The second
route involves a persistent LSVC (Figure 14B). The blood
flows from the hemiazygos vein into the accessory hemiazygos
vein to the LSVC and then into the coronary sinus, all of which
are dilated. In the third route, the hemiazygos vein drains to the
accessory hemiazygos vein, left superior intercostal vein, left
brachiocephalic vein and then into a normal right SVC.48,49
Bilateral Inferior Vena Cava

Bilateral suprahepatic IVCs, that is a normal IVC and a
contralateral hepatic vein, are frequently seen in cases of
visceral heterotaxy with asplenia. Bilateral infrarenal IVCs
have also been reported but they too are of no hemodynamic
significance.
TOTAL ANOMALOUS SYSTEMIC VENOUS DRAINAGE

INTO THE LEFT ATRIUM
Total anomalous systemic venous drainage (TASVC)
including the hepatic veins and the coronary sinus draining
into the LA is extremely rare. It is thought to occur either
because of failure of regression of the right valve of the
systemic venous sinus (sinus venosus) or the systemic venous
sinus being incorporated into the LA. It is usually associated
with other complex congenital heart diseases.
There have been very few case reports of TASVC. In a case
report, an 11-year-old girl with heterotaxy syndrome presented
with cyanosis.52 On echocardiography, and CT angiogram there
was an interrupted IVC with hepatic veins draining directly
Treatment
Surgical correction to redirect the venous blood into the right
atrium.
Anomalies of Ductus Venosus

Figure 15A: Echocardiographic apical four-chamber view showing
ostium secundum atrial septal defect L-R shunt; dilated left atrium and
left ventricle; noncompaction of left ventricle; dilated superior caval
vein in cross-section in a 11 year old girl of total anomalous systemic
venous drainage. ASD = Atrial septal defect; LA = Left atrium; LV = Left
ventricle; SVC = Superior vena cava
Absent Ductus Venosus
15
all four cardiac chambers. Also, the drainage of the hepatic

veins to the LA, if left unrepaired during surgery may lead
to cyanosis and pulmonary atriovenous fistula during late
follow-up.
The absence of ductus venosus and abnormal termination

of umbilical veins is a rare anomaly and do not produce any
symptoms. However, there are a few reports of intrauterine
obstruction of umbilical veins and also of postnatal intestinal
obstructions secondary to anomalous termination of umbilical
veins.53-57 It is important to recognize this anomaly during prenatal and postnatal diagnostic studies, during catheterization
and at the time of umbilical vein cannulation.
Persistent Ductus Venosus

Horiguchi et al58 reported a few cases of intrahepatic portalsystemic shunts due to abnormal persistence of elements of
omphalomesentric system, causing portal systemic encepha
lopathy. This anomaly is well delineated by ultrasound or
by computed tomography by demonstrating a large tortuous
vessel originating from the portal vein and connecting to the
hepatic vein or IVC.59,60 In the absence of encephalopathy,
no treatment is required. However, prior to the ligation it is
important to establish the intergrity of the portal system which
if not intact can cause mesenteric venous congestion leading
to bowel ischemia.
Figure 15B: Volume rendered (VR) CT image showing
interruption of hepatic segment of inferior vena cava and hepatic
veins draining into the left atrium through a common channel45.
Image Courtsey: Dr KS Ravindranath
into the LA (Figures 15A and B). There was an associated

ostium secundum atrial septal defect and non-compaction of
the left ventricle. Oximetry revealed equal saturation in all the
four cardiac chambers. CT angiography revealed polysplenia.
The patient was treated surgically by redirecting the SVC into
the right atrium.
Conclusion
The anomalies of systemic venous return are rare and
usually missed by routine interrogation. They are usually
asymptomatic but may pose problem during surgery. Hence,
detection of anomaly prior to surgery is pertinent. They can be
detected with gratifying results by segmental approach. These
segments are SVC, LSVC, IVC, coronary sinus, hepatic veins
and azygos veins.
Clinical Significance of TASVC

It is one of the rare causes of cyanosis in cyanotic heart
disease and yet another cause for equal oxygen saturations in
Surgeons must be very careful

When they take the knife!
Underneath their fine incisions
Stirs the Culprit - Life!
Emily Dickinson
221
222
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C hapter
16
Anomalies of Pulmonary Veins

Prasanna Nyayadhish, Sanjeev Kumar
IntroduCtIon
Anomalies of the pulmonary veins are a heterogeneous group
of heart diseases with varied clinical presentation, course and
outcome. Non-invasive imaging techniques have allowed for
quantum leaps in visualizing these anomalies and the overall
outcomes of patients have improved dramatically in recent
years.
There are normally four pulmonary veins, right upper and
lower, left upper and lower. Occasionally there is a variation
in this normal pattern. The most common variation, reported
in 25 percent of the individuals, is a single pulmonary vein
on one side and normal number on the other side. Patients
with heterotaxy and asplenia are known to have single
common pulmonary vein returning to the left atrium. In about
2 percent of the population right middle lobe may have a
separate vein.1
ClAssIfICAtIon
The pulmonary venous anomalies can be grouped as:
1. Anomalous connections.
2. Anomalous drainage with normal connections.
3. Stenotic connections.
4. Abnormal numbers of pulmonary veins.
Embryology
The knowledge of the pulmonary venous development is
essential to understand the anatomical abnormalities (Figures 1
A to D). Recent work has demonstrated that they develop from
the dorsal mesocardium within the posterior mediastinum.
They arise as a new channel and not as an outpouching from
the sinus venosus that is forming the systemic veins that join
the right atrium. In the early part of the development, lungs
get enmeshed by the vascular plexus from the foregut (i.e.
splanchnic). As the differentiation progresses these develop
into the pulmonary vascular bed. At 25 to 27 days gestation,
Figures 1A to D: Development of pulmonary veins: A. At 27 to 29 days

of gestation, the primordial lung buds are enmeshed by the vascular
plexus of the foregut (the splanchnic plexus). A small evagination
can be seen in the posterior wall of the left atrium to the left of the
developing septum secundum; B. By the end of the 1st month of
gestation, the common pulmonary vein establishes a connection
between the pulmonary venous plexus and the sinoatrial portion of
the heart; C. Next, the connections between the pulmonary venous
plexus and the splanchnic venous plexus involute; D. The common
pulmonary vein (CPV) incorporates into the left atrium so that the
individual pulmonary veins connect separately and directly to the left
atrium. LA = Left atrium; LCCV = Left common cardinal vein; LLB =
Left lung bud; RA = Right atrium; RCCV = Right common cardinal vein;
RLB = Right lung bud; UV = Umbilical vein
PArtIAl AnomAlous PulmonAry VEnous

ConnECtIon
In this anomaly, one or more of the pulmonary veins, but not
all of them, connect abnormally to systemic venous system.
Key features
Partial anomalous pulmonary venous connection (PAPVC)
results in atrial level left-to-right shunt and increased
pulmonary blood flow (Qp : Qs > 1).
The first description of this anomaly was made by Winslow
in 1739; however Brody in 1942, more clearly summarized
the condition.3 The advent of surgical correction of cardiac
defects necessitated a more critical approach to diagnosis and
resulted in the identification and description of hundreds of
cases. The reported incidence varies from 0.6-0.7 percent,
however most of them are autopsy studies and clinical
incidence could be still lower.3
16
AnomAlies oF PulmonAry Veins
the developing pulmonary venous plexus retains connections

to the right superior vena cava (SVC), left SVC and portal
system. No direct communication to the left atrium exists. At
the end of the first month of gestation, the common pulmonary
vein can be identified, draining the pulmonary venous plexus.
The origin (development) of the common pulmonary vein
is debated. Many believe that common pulmonary vein
originates as an evagination from the left atrium (sinoatrial
region). Some believe that the common pulmonary vein starts
from a confluence of vessels from the pulmonary plexus.
The intraparenchymal pulmonary veins connect with the
left atrium by establishing a connection with the common
pulmonary vein.3
Should the pulmonary venous channel fail to develop, these
anastomoses between pulmonary and systemic venous systems
persist and enlarge. An anastomosis with the anterior cardinal
systemic venous system then results in supracardiac anomalous
connection. Anastomosis with the systemic venous sinus or
the left sinus horn, produces cardiac anomalous connection,
while the infradiaphragmatic connection is the consequence of
anastomosis with the omphalomesenteric system.
Anomalous connection always denotes anomalous blood
return or flow; however, anomalous drainage or return can occur
without an anomalous connection. For example, in common
atrium, the right pulmonary vein may connect normally to the
left atrium, but functionally also enter the morphological right
atrium, mixing with the systemic venous return. Likewise, with
the malposition of the septum, the vein may connect normally
to the morphological left atrium, but malposition of the septum
may cause anomalous drainage of the pulmonary venous
return, allowing it to mix with systemic blood. Thus we cannot
interchange the terms return or drainage with connection. For
the purposes of this chapter we will use anomalous connections
to imply abnormal anatomic attachments.
Embryology
The developmental basis (Figures 2A and B) for PAPVC could
be that the developing pulmonary vein might have made a
connection only with part of the developing pulmonary venous
plexus. Anastomoses between the unconnected pulmonary
segments and systemic venous plexus persist and develop.
Anatomy
Anatomic variants of PAPVC (modification of Kirklin and
Barrett-Boyes classification) (Figures 3A to D) are:
1. Right pulmonary veins to the right SVC or azygos vein.
This is the most common type. The anomalous pulmonary
Figures 2A and B: A. By Day 40, the primitive connections from the pulmonary vascular bed to the cardinal veins should have regressed, but
in partial anomalous venous connections, the anomalous connections persist; B. At term, the anomalous connection will have developed into
anomalous pulmonary veins draining most commonly into the SVC on the right, or the brachiocephalic vein on the left. IVC = Inferior vena cava;
LA = Left atrium; RA = Right atrium; SVC = Superior vena cava
225
DeFeCts in AtrioVenous AnD PulmonAry ArterioVenous ConneCtions
Other connections such as to the coronary sinus are also

known, however they are rare. Right pulmonary veins are
more commonly involved than the left. Most of the time when
PAPVC involves the left pulmonary vein they do not connect
directly to right atrium. They often drain into persistent left
superior vena cava that connects to the left innominate vein.
Pathophysiology
A
Figures 3A to D: Common forms of partial anomalous pulmonary

venous connections (PAPVC): A. Anomalous connection of the right
pulmonary veins (RPV) to the SVC. A high or sinus venous defect is
usual in this anomaly; B. Anomalous connections of the RPV to the
IVC. The right lung commonly drains by 1 pulmonary vein without
its usual anatomic divisions. Parenchymal abnormalities of the right
lung are common, and the atrial septum is usually intact. This type
of PAPVC is found in Scimitar syndrome; C. Anomalous connection
of the left pulmonary veins (LPV) to the left innominate vein (LIV)
by way of a left vertical vein (LVV). An additional left-to-right shunt
may occur through the ASD; D. Anomalous connection of the LPVs
to the coronary sinus (CS). IVC = Inferior vena cava; LA = Left
atrium; LV = Left ventricle; RA = Right atrium; RV = Right ventricle;
SVC = Superior vena cava; VV = Vertical vein
2.
3.
4.
5.
226
veins attach to the lower side of the SVC or the SVCright

atrium junction.
Right pulmonary vein to the right atrium. The right
pulmonary veins connect directly to the right atrium.
Right pulmonary veins to the inferior vena cava (Scimitar
syndrome). The anomalous right pulmonary vein, generally
draining the entire right lung, descends in a cephalo-caudad
direction toward the diaphragm and then curves sharply to
the left to join the inferior vena cava (IVC) or IVCright
atrium junction, superior to the hepatic vein orifices.
Left pulmonary veins to the left innominate vein. The left
pulmonary veins may connect to the left innominate vein
by way of an anomalous vertical vein.
Bilateral PAPVC. A rare form of PAPVC. Most commonly,
the atrial septum is intact, the left superior pulmonary
vein attaches to the left innominate vein by way of an
anomalous vertical vein, and the right superior pulmonary
vein attaches to the SVCright atrium junction
The principal physiological hemodynamic abnormality is

due to the pre-tricuspid atrial level left to right shunt causing
increased pulmonary blood flow. This left-to-right shunt leads
to the dilatation of the right heart chambers and the main
pulmonary artery. The left heart chambers are not dilated and
have preserved function. The magnitude of the left-to-right
shunt is determined by:
1. Number of anomalously connecting veins.
2. Severity of obstruction.
3. Compliance of the chamber into which the anomalous
veins connect.
4. Relative resistances of the normal and abnormal pulmonary
veins.
A greater number of veins draining anomalously, results in
more blood returning to the right side of the heart. The defect
clinically becomes significant when more than 50 percent of
the veins return anomalously. The source of the returning blood
plays a role in determining the clinical effect of the defect.
In the upright posture, individual blood flow to the lungs is
directed primarily to the lower and middle lobes. Therefore,
one would expect more blood to return to the right side of the
heart in individuals in whom the anomalous connection drains
either the right middle and lower lobes or the left lower lobe.
Though the above mentioned factors influence the amount
of the blood returning to the right side of the heart, there is
no right to left shunt. The associated non-cardiac conditions
like pulmonary parenchymal disease exacerbate clinical
progression.
PAPVC is often associated with an atrial septal defect (ASD),
especially of the sinus venosus type. Sinus venosus defects
physiologically allow an atrial level communication, but are not
true ASDs as they do not involve septum. In 20 percent of the
patients, the atrial septum is intact. PAPVC may also occur in
patients with visceral heterotaxy and polysplenia.4
scimitar syndrome
Scimitar or pulmonary venolobar syndrome is a rare but
well known congenital cardiovascular defect that includes
a hypoplastic right pulmonary artery and right lung, which
leads to the displacement of the cardiac structures into the
right hemithorax, anomalous systemic arterial supply to the
right lung and a characteristically curved anomalous right
pulmonary vein that drains into the IVC. This resembles
the curved Middle Eastern Ottoman sword Scimitar5
(Figures 4A to C). The Scimitar syndrome was first described
16
Figures 4A to D: A. Schematic diagram of a Scimitar or curved Turkish sword from the age of the Ottoman Empire seen in; B. Chest X-ray
demonstrating a curvilinear density that represents a vessel draining the right lung; C. Angiogram; D. CT angio (arrow) showing the anomalously
draining Scimitar vein. Image Courtesy: Dr IB Vijayalakshmi
by Chassinat in 1836, accounting for 0.5-1 percent of

all the CHDs. Isolated partially anomalous pulmonary
venous return to the IVC without the other components
is known as Incomplete Scimitar syndrome. There are
two forms of Scimitar syndrome, the infantile form and
the adult form. Infantile form is associated with multiple
thoracic abnormalities and vascular malformations. Cardiac
malformations associated with this form include coarctation of
aorta, tetralogy of Fallot, patent ductus arteriosus, ventricular
septal defects and other conoseptal anomalies.6 Adult form is
associated with a smaller shunt, minimal symptoms and lack
of other associated malformations.
Clinical manifestations
The majority are asymptomatic in early life, regardless of
the presence of an associated ASD. Clinical symptoms are
similar to those of ASD. The most common manifestation
in symptomatic children is exercise intolerance. Depending
upon the shunt volume, children are either asymptomatic or
have increased frequency of respiratory tract infections. Like
ASDs, symptoms usually appear in the late 20s to early 40s
and consist of exertional dyspnoea and palpitations which
are almost always supra-ventricular in origin. Physical
examination is often normal in those with single anomalous
pulmonary venous return. Peripheral oedema can occur
in adults with cardiac failure. Even in older, symptomatic
patients, evidence of pulmonary artery hypertension with
right-to-left atrial shunting manifested by reduced oxygen
saturations or overt cyanosis is unusual. In those with more
than one anomalous pulmonary venous return, clinical
findings are similar to those of ASDs like a soft systolic
ejection murmur in the pulmonic area, wide fixed splitting
of the second heart sound and hyperactive right ventricular
impulse.
InVEstIgAtIons
Chest radiograph
The X-ray findings are similar to those of an ASD. A
snowman appearance would suggest return to the left vertical
vein; in older patients with return to the inferior caval
vein, the anomalous pulmonary vein is always visible. The
other associated lung findings (pulmonary sequestration,
hypoplasia) of Scimitar syndrome might be seen.
Electrocardiogram
The electrocardiogram (ECG) is identical to that of an ASD.
Specifically, V1 shows an rsr or rsR, or rarely a QR pattern
in V1. Partial return to the IVC with intact atrial septum is
characterized by a terminal s or S wave in V1 (Figure 5). Most
ECGs in PAPVC are essentially normal.
Echocardiography
Echocardiography is the mainstay of diagnosis. Both
transthoracic (TTE) and transesophageal echocardiography
(TEE) are commonly used in the diagnosis. Two dimensional
echocardiography with color Doppler is highly useful. The
subcostal and suprasternal view (so called crab view) allows
visualization of all the pulmonary veins, SVC, aorta, right
innominate vein and the right pulmonary artery. In the most
common form of PAPVC (right middle and upper pulmonary
vein to SVC) an abnormal color flow can be seen entering
the wall of the SVC. The spectral Doppler assessment of
color flow will confirm the systolic and diastolic flow pattern
typical of the pulmonary venous flow. The color flow mapping
allows rapid detection of small pulmonary veins and also the
possibility of stenosis in them.
227
Figure 5: Typical 12-lead electrocardiogram in a patient with PAPVC. There is an rsR pattern in lead V1 consistent
with mild right ventricular conduction delay or volume overload. The P waves are not peaked in this example
Figures 6A and B: A. Subcostal view showing the anomalous connection of the pulmonary vein into the right atrium; B. Crab view with
2-dimensional and color Doppler demonstrating the absence of the right upper and right lower pulmonary veins. Ao = Aorta; LA = Left atrium;
LV = Left ventricle; LLPV = Left lower pulmonary vein; LUPV = Left upper pulmonary vein; RA = Right atrium; RPA = Right pulmonary artery;
RMPV = Right middle pulmonary vein; RPV = Right pulmonary vein
Subcostal view is particularly useful in patients with

Scimitar syndrome. Majority of the patients with PAPVC
have enlargement of right atrium and right ventricle. It is
recommended that TEE be performed in any patient with right
ventricular enlargement in whom transthoracic examination is
inconclusive7 (Figures 6A and B).
ComPutEd tomogrAPhy
228
Computed tomography (CT) is being increasingly used for

visualization of the anomalous connections of the pulmonary
veins since 1990. A recent retrospective series of CT scans
found the prevalence of previously undiagnosed PAPVC to

be 0.2% in a general adult population. With advent of newer
multi-slice CT machines, scan can be performed in few
seconds without the need for breath holding. Also images can
be reconstructed in three dimensions with a better anatomical
description. This helps the surgeon in deciding the technique
and approach8 (Figure 7).
mAgnEtIC rEsonAnCE ImAgIng

Cardiovascular magnetic resonance imaging (CMR) is an
invaluable tool for the diagnosis of PAPVC in adult patients.
16
Figure 7: PAPVC to the azygos vein. Series of CT scans shows anomalous right upper lobe vein (arrows)
draining into the dilated azygos arch. AZ = Azygos
With refinements in technology, rapidly improving the

quality of images obtained, fewer children require invasive
angiography. CMR angiography with the use of a contrast
agent, such as gadolinium, may further enhance the images
diagnostic import by improving the delineation of the vessel
borders, which may be important for surgical planning and
may not be visible clearly in many patients using other
modalities, such as echocardiography. In individuals with
normal anatomy, a transverse magnetic resonance imaging
demonstrates a ring like structure derived from the mediastinal
fat surrounding the SVC. This ring is broken only at the point
of entry of the azygos vein into the SVC in normal individuals.
In some patients with PAPVC, the ring of fat also appears to
be breached (or broken) at the site of entry of the anomalous
vein. This is classically described as the broken ring sign
by Julsrud in 1985. A recent study of adult patients with
congenital defects found CMR to be 100 percent sensitive for
PAPVC and ASDs when catheterization or echocardiography
was incompletely diagnostic. CMR delineates better the soft
tissue spatial relationship which is of extreme help in surgical
planning. CMR has become an extremely valuable modality
for the diagnosis as well as the post-operative evaluation of
PAPVC9 (Figure 8).
Figure 8: Contrast-enhanced volume-rendered magnetic resonance

image shows that left superior pulmonary vein drains to the left
brachiocephalic vein (black arrowhead) via the vertical vein (VV).
Remaining pulmonary veins drain normally to the left atrium. Ao =
Ascending thoracic aorta; MPA = Main pulmonary artery; RBCV =
Right brachiocephalic vein; SVC = Superior vena cava
229
Cardiac Catheterization
Prognosis
As non-invasive diagnostic modalities have increased the

sensitivity and specificity of diagnosis of PAPVC, the need for
diagnostic catheterisation has decreased. The most definitive
technique for diagnosing PAPVC at cardiac catheterisation is
to enter the right pulmonary vein directly with the catheter and
perform a selective angiogram in it or selective left pulmonary
artery angiogram in levophase illustrates the left pulmonary
veins draining into vertical vein, then horizontal vein (left
innominate vein) and into right atrium (RA) at the superior
vena cava (SVC) and RA junction (Figure 9). This will
help to demonstrate the venous drainage pattern, associated
atrial level communication, measure pulmonary pressures
and calculate Qp: Qs. Oximetry is of little value when the
anomalous connection is to the IVC, as there is selective
streaming of the oxygenated blood from the renal vein.
Inability to pass the catheter from the right atrium to the left
atrium or a difference in right atrial pressure and pulmonary
wedge pressure is suggestive of PAPVC with intact septum.
The prognosis of PAPVC is similar to an isolated ASD with

a comparable left-to-right shunt. Patients with Scimitar
syndrome have a worse outcome than the other types of
PAPVC, especially those with early onset of symptoms. Of
those cases that require surgical repair, operative mortality
rates are low (under 1%). Systemic or pulmonary vein
obstruction as well as sinus node dysfunction has been rarely
reported.10
management
Surgery is the definitive treatment. Infants with Scimitar
syndrome may develop respiratory distress and need early
surgical treatment. Indications for surgery are Qp : Qs > 2,
recurrent respiratory tract infections, Scimitar syndrome
and when surgery is being considered for other indications.
Surgery is usually carried out between 2-5 years of age under
cardiopulmonary bypass. Surgical mortality is less than 1
percent. Postoperative complications include SVC obstruction
and atrial arrhythmias.
totAl AnomAlous PulmonAry VEnous

ConnECtIons
definition
In this condition, all the pulmonary veins have abnormal
connection to the systemic circulation. They do not connect
directly to the left atrium.
The term total anomalous pulmonary venous connection
(TAPVC) implies an absence of a direct connection between
the pulmonary veins and the left atrium. The pulmonary
veins connect via systemic veins to the right atrium and are
often obstructed. This results in mixing of deoxygenated
and oxygenated blood in the right atrium. The reported
incidence for TAPVC ranges from 0.4 to 2 percent from
prior autopsy studies.11 Males and females are equally
affected, however few studies have demonstrated higher
incidence in males especially in the infracardiac type.12
The non-cardiac conditions associated with TAPVC are
asplenia or polysplenia heterotaxy syndromes. There is no
known genetic inheritance pattern. Maternal lead exposure
is often considered as an etiology.13 Often TAPVC occurs
as an isolated lesion except for the associated inter-atrial
septal defect. However, it is known to be associated
with other cardiac malformations like transposition of
the great arteries, pulmonary atresia, truncus arteriosus,
atrioventricular septal defect and single ventricle
physiology.14
Anatomy
230
Figure 9: Cardiac catheterization: Pigtail angiogram in LPA demonstrating the anomalous drainage of the left pulmonary veins through
the vertical vein and horizontal vein (left innominate vein) into right
atrium (RA) at the superior vena cava (SVC) and RA junction
A number of classification schemes for describing the different

types of TAPVC have been proposed. The most widely
adopted system (Darling et al)15 classifies TAPVC according
to the anatomic location of the anomalous connection (Figures
10A to D).
Type 1 - Supracardiac type of total anomalous pulmonary
venous connection
Type 2 - Cardiac type of total anomalous pulmonary venous
connection
Type 3 - Infracardiac type of total anomalous pulmonary
venous connection
Type 4 - Mixed type of total anomalous pulmonary venous
connection
Type 2 (Cardiac) Total Anomalous Pulmonary

Venous Connection
As the name implies, the anomalous connection occurs at the

cardiac level. It is the second most common variant after the
supracardiac type, accounting for 15 to 20 percent of all cases.
Most of the time, the veins connect to the coronary sinus or
to the posterior midportion of the right atrium. Obstruction is
less frequent, however, it can occur at the common pulmonary
vein or the orifice of coronary sinus or in the individual
pulmonary vein.
16
course of the vein is between the left pulmonary artery and the
left bronchus, these two structures clasp the venous channel
producing the bronchopulmonary (hemodynamic) vice, which
may cause obstruction. In a rare variant of supracardiac
TAPVC pulmonary veins connect directly to SVC. This type
of supracardiac TAPVC is rarely associated with obstruction.
There will be ASD with obligatory right to left shunt for
survival.
Type 3 (Infracardiac) Total Anomalous Pulmonary

Venous Connection
Figures 10A to D: Types of TAPVC: A. TAPVC to the left innominate

vein (LIV) by way of a vertical vein (VV); B. TAPVC to the coronary
sinus (CS). The pulmonary veins join to form a confluence designated
the common pulmonary vein (CPV), which connects to the coronary
sinus; C. TAPVC to the right atrium. The left and right pulmonary veins
(LPV and RPV) usually enter the right atrium separately; D. TAPVC
to the portal vein (PV). The pulmonary veins form a confluence from
which an anomalous channel arises.This connects to the portal vein,
which communicates with the IVC by way of the ductus venosus (DV)
or the hepatic sinusoids. IVC = Inferior vena cava; LA = Left atrium;
LH = Left hepatic vein; LP = Left portal vein; LV = Left ventricle;
RA = Right atrium; RH = Right hepatic vein; RP = Right portal vein;
RV = Right ventricle; SMV = Superior mesenteric vein; SV = Splenic
vein; SVC = Superior vena cava
Type 1 (Supracardiac) Total Anomalous Pulmonary

Venous Connection
It is the most common subtype of TAPVC, representing
approximately 40 percent of all the cases. In this abnormality
the anomalous connection occurs at the supracardiac level.
Two pulmonary veins from each lung converge behind the
left atrium and form a pulmonary venous confluence. Then,
an anomalous vertical vein arises from the left portion of the
confluence and courses toward the left innominate vein . The
left innominate vein empties normally into the right SVC.
If the vein passes anterior to the left pulmonary artery, then
this course is not associated with obstruction. However, if the
The infracardiac or infradiaphragmatic type of TAPVC

represents 20 percent of all the cases. The anomalous
connection occurs at the infradiaphragmatic level and in 7080 percent cases they connect to the portal vein. This type
of TAPVC is almost always associated with obstruction.
Newborns have a stormy course with severe tachypnea and
cyanosis. The pulmonary veins form a common chamber,
inferior and posterior to the left atrium. A common vessel
arises from this confluence and descends anterior to the
esophagus. The anomalous descending vessel then joins
the portal vein at the confluence of the splenic and superior
mesenteric veins. In the majority of the cases, this common
pulmonary vein connects to the portal venous system, either
at the splenic vein or at the confluence of the splenic and
superior mesenteric veins. It could also join the IVC proper
or the left hepatic vein. Hence, the obstruction can occur at
various levels.
Type 4 (Mixed) Total Anomalous Pulmonary

Venous Connection
It is the rarest type, accounting for less than 5 percent of
all cases. It is associated with other non-cardiac defects.
Mixed variant is often associated with other major cardiac
structural defects and can have obstruction at several
levels. The most common type of mixed connections has
connection of the left pulmonary veins to a vertical vein
leading to the left innominate vein along with connection
of the right pulmonary veins to either the right atrium or
coronary sinus.
231
Pathophysiology
TAPVC results in complete mixing of the systemic and

pulmonary blood. There is an obligatory right-to-left shunt as
the pulmonary venous return is to the systemic veins. Most
of the times the right-to-left shunt occurs at the atrial level
and rarely it has been reported at ventricular level or at ductal
level with intact septum. Hence, the mixed venous blood may
enter the right ventricle and the pulmonary circuit or may
pass through the obligatory right-to-left atrial communication
and fill the left ventricle (LV) and the systemic circulation. A
non-restrictive ostium secundum ASD is seen in 20% of the
patients with simple TAPVC.16 Remaining 80 percent of the
infants have PFO with restricted right to left shunt. As the
neonates grow there is a decrease in the pulmonary vascular
resistance which further decreases the right to left shunt.
Most of the blood recirculates through the low resistance
pulmonary circulation resulting in increased pulmonary blood
flow and decreased systemic output. These neonates manifest
with respiratory distress and hypoxemia. They typically have
elevated right atrial pressures, pulmonary artery hypertension
and low cardiac output. When the shunt is at the level of the
atrium there is tendency for the fetal pattern of the circulation
to be maintained. In case of the infradiaphragmatic variant of
TAPVC, the oxygenated blood ascending the inferior caval
vein towards the right atrium is directed towards the left
atrium. Accordingly, the systemic arterial oxygen saturation
is relatively higher than the pulmonary arteries. Conversely
,in supracardiac TAPVC, oxygenated blood tends to be
directed down the SVC and through the tricuspid valve into
the pulmonary circulation. Hence, the pulmonary oxygen
saturation is likely to be more than systemic.
Obstruction to the pulmonary venous return results in the
rise of the pulmonary capillary wedge pressure and rapid
progression to pulmonary edema. With further rise of the
pulmonary capillary pressure, the RV compliance decreases
leading to increase in the right atrial pressure and right-to-left
atrial shunt. This ultimately leads to systemic hypoxemia and
metabolic acidosis. If the ductus is still open this will again lead
to increased right-to-left shunt and worsening of the systemic
hypoxemia and pulmonary oligemia. The progressive rise in the
metabolic acidosis leads to multiorgan failure. The outcome will
be fatal without the relief of the pulmonary venous obstruction.
232
Two factors determine the severity of the symptoms in TAPVC.

One is the severity of the pulmonary venous obstruction and
other is the restriction of the inter-atrial communication.
Neonates with infracardiac variant of TAPVC (commonly
associated with obstruction), present within 48 hours of birth,
with intense cyanosis and tachypnea. They are often treated as
respiratory distress syndrome (RDS) of the newborn.17 Unlike
RDS of the newborn, grunting respiration is very rarely seen
in obstructed venous return. Rare manifestations (especially

in infracardiac TAPVC) include sudden death, unconjugated
hyperbilirubinemia and hematemesis. The infants with
large inter-atrial communication present at later age. They
often present with failure to thrive, tachypnea and frequent
respiratory tract infections. On examination, neonates with
infracardiac TAPVC are sick, cyanosed with signs of poor
peripheral perfusion. Findings are similar to an ASD, with
a wide split second heart sound and mid systolic murmur.
Precordium is quiet. Sometimes there is a venous hum heard
below the left clavicle especially in supracardiac TAPVC to
the left innominate vein. It differs from other venous hums in
that it persists even with compression of the neck veins and is
not louder in diastole. P2 is loud. Hepatomegaly may be seen
when the anomalous drainage is to the portal vein.18 Infants
without pulmonary venous obstruction present with typical
features of an ASD. The precordium is hyperdynamic with
wide fixed splitting of the second heart sound.
Investigations
Chest Radiography
In newborns with severe pulmonary venous obstruction,
cardiac silhouette is normal or small with ground glass
appearance of the lung fields. Sometimes the findings may be
misinterpreted as RDS, which is more common in the newborn
period. However, unlike obstructive TAPVC, in RDS usually
homogeneous patchy infiltrates along with air-bronchograms
are noted.19,20
In patients without the obstructive physiology, the X-ray
findings are similar to those with right-sided volume overload.
In older patients the pulmonary trunk may be prominent;
sometimes the left vertical vein may be prominent when that is
the site of anomalous connection. This gives rise to snowman
appearance also called WC Fields heart (Figures 11A and B).
Electrocardiography
Right axis deviation with a clockwise frontal plane loop and
right ventricular hypertrophy is seen. V1 usually shows an
rsR pattern, though a qR is seen in four-fifths of the patients,
which indicates severe pulmonary hypertension. By the age of
3 to 4 months most of the patients have features of right atrial
enlargement on ECG.
Echocardiography
Echocardiography is the cornerstone investigation for
diagnosis of TAPVC. The accuracy of echocardiography in
diagnosing TAPVC is 100%.21, 22 The key to the diagnosis of
TAPVC is identifying the anatomic connections of all four
pulmonary veins.23,24 Correlative anatomical studies suggest
that the subcostal and apical approaches image the normal left
16
B
Figures 11A and B: A. Chest X-ray (PA view) showing a snowman in a snowstorm;
B. Obstructive infracardiac TAPVC (ground-glass appearance)
lower and right upper pulmonary veins, while the suprasternal

approach, given a good window, can demonstrate all four. A
universal finding in TAPVC is right-sided volume overload,
with enlargement of the right atrium, right ventricle, and
main pulmonary artery. The clue to diagnosis is the exclusive
right to left shunt at the atrial level. An essential element is
identifying the size and location of each vein and how and
where they enter the heart. This is especially important
because it has been shown that the sum of the individual
vein sizes is an independent risk factor for postoperative
mortality. Specifically, small veins before surgery lead to
higher postoperative mortality.25 In patients who are difficult
to image with TTE, TEE may provide better visualization of
the pulmonary veins and their site of drainage because of their
posterior location.26
Localizing the Confluence of Pulmonary Veins

The suprasternal view or parasternal short axis view better
demonstrates the venous confluence in TAPVC. Confluence
is seen as an echo free non-pulsatile structure posterior to the
left atrium. It has a separate venous egress connecting to the
systemic vein. Supracardiac TAPVC can generally be best
seen from the parasternal imaging and infracardiac TAPVC
is best visualized from subcostal views, however, multiple
views are often used. For obvious reasons, it is often difficult
to localize the pulmonary venous confluence in neonates with
RDS. Because of its size, shape and posterior location, the
pulmonary venous confluence can sometimes be difficult to
image directly, even by TEE.
Intracardiac TAPVC: The coronary sinus itself will be

dilated. It can be dilated because of a persistent left SVC
as well. Thus, delineating the connection of the confluence
into the coronary sinus is imperative. The pulmonary venous
confluence is directly posterior to the left atrium. It is thus
well visualized in the parasternal, apical four-chamber and
subcostal views (Figure 12).
Supracardiac TAPVC: The pulmonary venous confluence
is usually superior to the left atrium and is thus best visualized
in the parasternal views. It may also be seen from the subcostal
long-axis views. Drainage to the SVC is either direct or
through the left vertical vein. Left vertical vein connects to
the brachiocephalic vein which is better visualized in suprasternal view (Figures 13A and B). An easy way to identify and
trace the left vertical vein is to inject contrast bubbles into the
left arm.
Infracardiac TAPVC: The pulmonary veins usually converge
just above the diaphragm. Therefore, the pulmonary venous
confluence is often small and inferior to the left atrium or
may not exist as a distinct, separate chamber. The descending
vein is better demonstrated in the sub-costal long axis view
(Figures14A and B). It should be differentiated from the aorta
and the IVC. It is non-pulsatile and doesnt connect to either
atrium. Another easier way to differentiate it from the IVC is
to inject contrast micro-bubbles into the leg veins.
Mixed Form of TAPVC: This form of TAPVC is suspected
when only two pulmonary veins are seen to enter the venous
confluence in multiple views and planes. Special attention
should be paid to the coronary sinus and the innominate vein,
as potential sites of drainage. Echocardiography can be used
233
Figure 12: Cardiac total anomalous pulmonary venous connection (type II). Gray-scale and color Doppler echocardiographic images show
common pulmonary vein confluence (PVC) posterior to heart that empties into the right atrium (RA). LA = Left atrium; LV = Left ventricle
Figures 13A and B: Suprasternal: A. and apical B echocardiographic planes demonstrating a pulmonary venous confluence (PVC) posterior
to the left atrium (LA) that is being drained by a vertical vein (VV). The apical four-chamber view; B. More clearly shows the VV arising from the
PVC and heading cephalad. Ao = Aorta; LV = Left ventricle; RA = Right atrium
234
to trace the final common pathway of pulmonary venous

drainage into the systemic vein. Obstruction in the pathway
is recognized by the turbulent flow and pulse wave Doppler
offers an objective measure. The presence of a focal increase
in flow velocity (~2 m/sec) with a continuous, non-phasic
flow pattern distally is a characteristic finding. A sensitivity
of 100% and specificity of 85 percent have been claimed for
detection of obstruction by cross sectional imaging and color

Doppler (Figure 15).
Computed Tomography and Magnetic Resonance Imaging

These non-invasive modalities of imaging are of great help
in diagnosis and pre-operative work up. Considering the
16
Figures 14A and B: A. Infracardiac total anomalous pulmonary venous connection (type III). Common pulmonary vein confluence is seen
posterior to the heart; B. Right and left pulmonary veins form a confluence posterior to the left atrium. Descending common pulmonary vein
arising from the confluence joins the portal vein. CPV = Common pulmonary vein; DCPV = Descending common pulmonary vein; HV = Hepatic
vein; LA = Left atrium; LPVC = Left pulmonary venous channel; PVC = Pulmonary venous confluence; RA = Right atrium; RPVC = Right
pulmonary venous channel ; RV = Right ventricle
Figures 15: Doppler echocardiogram of a patient with mixed TAPVC

showing left upper pulmonary vein (LUPV) entering the left atrial
appendage (LAA). Ao = Aorta; LA = Left Atrium
complexity involved in understanding three dimensional

anatomical relationships between the pulmonary veins and
other thoracic structures computed tomography (CTA) and
magnetic resonance imaging (MRI), provide straight forward
information. Main advantages of CTA are that it is very rapid,
does not incur radiation exposure and is not contraindicated
in many implanted devices. As early as 1991, Masui and
colleagues found MRI to be superior to both echocardiography
and conventional angiography in patients with TAPVC.
Magnetic resonance imaging and angiography (MRA) also
provides superb multiplanar imaging of these abnormal
vascular structures (Figure 16). Additional advantages include
its ability to obtain functional data, such as flow velocities
Figure 16: MRI 3D reconstructed image showing mixed total anomalous pulmonary venous connection (type IV). AA = Aortic arch;
CS = Coronary sinus; LIPV = Left inferior pulmonary vein; LPA = Left
pulmonary artery; RIPV = Right inferior pulmonary vein; RPA = Right
pulmonary artery; RSPV = Right superior pulmonary vein; SVC =
Superior vena cava
within individual pulmonary veins and accurate chamber

volumes and function.27
Catheterization for the diagnosis of TAPVC is obsolete
these days. However, the diagnosis can be established by
entering the anomalous venous channel with the catheter and
235
performing the angiogram. The oximetry will demonstrate the

step-up of the saturation to > 90 percent in the right atrium.
Saturations in the right ventricle and pulmonary circulation
are usually identical; however, it should be noted that because
of the streaming and incomplete mixing there could be a small
difference in saturation. In TAPVC, the oxygen saturation in
the right atrium usually ranges between 80 percent and 95
percent, and saturations in the right atrium, right ventricle,
pulmonary artery, left atrium, left ventricle, and systemic
arteries are nearly identical. The right ventricular and
pulmonary arterial pressures are usually suprasystemic with
obstructed TAPVC, but right atrial pressures are normal or
nearly so. Pulmonary artery wedge pressure is elevated,
whereas left atrial pressure is low. The size of the atrial
communication is important for left heart preload and its size
can be determined at catheterization using an inflated balloon
catheter. An interatrial communication less than 5 mm in
diameter is definitely restrictive.28 Selective pulmonary
arteriography is usually diagnostic. Following injection and
passage of the opaque dye through the pulmonary fields, the
dye collects in the pulmonary venous channels and clearly
outlines the anomalous connection. Rarely after selective
left pulmonary artery angiogram in levophase we can see
the left pulmonary veins (LPVs) draining into azygos system
(Figure 17A). Sometimes the right heart catheter through the
azygos system can enter the right pulmonary veins (RPVs).
The hand injection of contrast can confirm the RPVs draining
into azygos system (Figure 17B). If selective injection of
the contrast material into the anomalous venous channel is
contemplated in the patient with TAPVC with obstruction,
the injection should be done by hand. In a newborn with
TAPVC to the portal venous system, blood obtained from the
A
236
umbilical vein is fully saturated, confirming the diagnosis.

The catheterization also gives the opportunity to perform the
interventions; however the catheter-based interventions are
proved to be ineffective and are not typically undertaken.
Balloon or blade atrial septostomies were previously
performed as a palliative measure, but they only delayed
definitive repair. The percutaneous stenting of the pulmonary
vein is largely ineffective and should not be undertaken.29,30
differential diagnosis
Pulmonary venous atresia also presents as TAPVC with
severe pulmonary venous obstruction. Clinically, these two
conditions are indistinguishable. However, the unobstructed
variant of TAPVC needs to be distinguished from other
conditions like transposition of great vessels with ventricular
septal defect. Atrioventricular septal defect with common
atrium can be distinguished from this condition on the basis
of ECG. Other conditions likely to cause mild cyanosis and
heart failure need to be distinguished.
management
Surgery is the only intervention with proven short and longterm success for TAPVC. As a matter of fact, TAPVC is the first
condition in which neonatal open heart surgery was performed.
TAPVC with severe pulmonary venous obstruction requires
urgent or emergent surgical intervention. Preoperatively
medical treatment needs to be started to stabilize the patient.
Neonatologists often start prostaglandin infusion in newborns
with respiratory distress and cyanosis considering the possibility
of ductus dependent circulation. It was considered dangerous
Figures 17A and B: A. Angiogram in LPA in levophase shows left pulmonary veins (LPVs) draining into azygos system; B. Right heart catheter
through the azygos system into right pulmonary vein (RPV) and hand injection of contrast shows RPV draining into azygos vein. LPA = Left
pulmonary artery; LPV = Left pulmonary vein; RPV= Right pulmonry vein. Image courtsey: Dr IB Vijayalakshmi
Prognosis
The prognosis in TAPVC is determined by the size of the
inter-atrial defect and by the presence of obstruction to the
anomalous venous pathways. Without surgery most of the
neonates do not see their first birthday. With improvements
in surgical techniques the operative mortality has decreased
significantly. Currently, the operative mortality in the neonatal
period is 05 percent.34,35 The anatomical type of TAPVC is
less well correlated with the surgical outcome, however the
supracardiac TAPVC has a better outcome compared to other
forms.36 Rather than the anatomical subtype, it is the size of
the pulmonary veins and their confluence that determines
the outcome. The long-term outcome of the neonates with
surgical repair is excellent. However 10 percent of these cases
are known to develop pulmonary stenosis. The exact reasons
for this are unknown. Re-operation carries a high mortality
and a strong chance of recurrence.
pulmonary tuberculosis or invasion by a tumor. Congenital pulmonary vein atresia is usually associated with other
cardiac malformations. It may occur in either lung, with no
right- or left-sided predominance.
Pathophysiology
Severity of the manifestations depends upon the number of
the pulmonary veins affected, severity of the obstruction
and other associated cardiac malformations. The pulmonary
venous pressure on the affected side is elevated. This results
in elevation of the pulmonary artery pressure.37 However, few
cases have been reported where pulmonary artery pressures
are normal.38 The pulmonary artery hypertension causes
elevation of the right ventricular end-diastolic pressure
which might cause right-to-left shunt through the foramen
ovale. It has been observed that the ipsilateral pulmonary
artery is hypoplastic, probably because of the preferential
pulmonary artery perfusion to the contralateral side, with
resultant impaired growth of the affected pulmonary artery.
This pulmonary artery hypoplasia probably accounts for the
arterial systemic-to-pulmonary collateral vessels.39
16
in case of TAPVC with obstructive pulmonary circulation, as

it can increase the pulmonary blood flow and hence worsening
the respiratory distress. However, Bullaboy et al argued that
the PGE1 could be of benefit by maintaining the patency of
the ductus venosus allowing for some decompression of the
obstructed infradiaphragmatic TAPVC. They do consider that
there may be right-to-left shunting through the patent ductus
arteriosus, which could decompress the pulmonary circulation
and increase the systemic blood flow. Hence, PGE may be a
reasonable medication during transport or until the diagnostic
evaluation has been completed.31
In most of the developing nations facilities for emergency
surgery are not available, hence an alternative approach of
initial balloon septostomy followed by definitive surgery is
undertaken. Septostomy no longer seems appropriate because
it delays the definitive procedure and is of little value when an
anomalous venous channel is also obstructed.32,33 Preoperative
inotropic agents, diffuse pulmonary vein stenosis, emergency
surgery and postoperative pulmonary hypertensive events are
considered to be predictors of in-hospital mortality. In one
of the studies, the cardiac form of TAPVC was associated
with higher mortality. The specific surgical technique used
is determined by the anatomy of the defect. Primary surgical
approach in many cases is creating an unrestrictive side-toside anastomosis between the pulmonary venous confluence
and the left atrium while resecting other means of egress from
the confluence. In the cardiac TAPVC, surgeons can unroof
the coronary sinus to the left atrium and close the coronary
sinus orifice with a patch. However, the specific surgical
technique and approaches are beyond the scope of this book.
Clinical features depend upon the number of the veins affected
and the severity of the obstruction. Most of the children
with single pulmonary vein affection can be asymptomatic.
However, most of the children present in early childhood with
recurrent episodes of chest infections, dyspnea, failure to thrive,
hemoptysis and occasionally cyanosis. On auscultation, second
heart sound is loud; however murmurs are usually absent.40
Investigations
Chest X-ray
Cardiothoracic ratio on chest X-ray remains normal.
Pulmonary trunk might appear prominent. The affected
lung may be hypoplastic with mediastinal shift (Figure 18).
Reticular opacities with septal lines are present in most of the
patients and are most marked in the lower lobes.41
Electrocardiogram
Right ventricular hypertrophy and right atrial enlargement,
without left-sided changes, is invariably found on the electrocardiography.42
Echocardiography
stEnosIs or AtrEsIA of IndIVIduAl

PulmonAry VEIns
Several acquired conditions can also be present with pulmonary vein stenosis like constrictive pericarditis, mediastinitis,
A diagnosis by standard echocardiography and Doppler

methods is made more difficult by the distance of the
pulmonary venous connection to the left atrium as measured
by the transducer of the surface echocardiographic acoustic
237
Figure 18: Posteroanterior chest radiograph shows small right

hemithorax and diminutive right pulmonary artery
windows.43 However, the pulmonary veins are in close

proximity to the transducer with TEE. Pulsed Doppler
echocardiography can be a useful tool for the evaluation of
patients with suspected congenital pulmonary vein stenosis.
Normal pulmonary venous flow is laminar and triphasic
with the first and highest inflow during ventricular systole,
the second inflow during the rapid filling phase of ventricular
diastole and flow reversal after atrial contraction. However,
stenotic pulmonary veins have a pattern of continuous flow
that is disturbed without the normal phasic variation as well as
the turbulent flow (Figures 19A and B). A definitive diagnosis
requires a cardiac catheterization.
Figures 19A and B: A. Normal pulsed Doppler pulmonary vein flow

pattern in a child. There are well-dened systolic and early diastolic
peaks of approximately 1 m/s and the flow reaches the baseline or
even reverses in late diastole; B. Typical pulsed Doppler flow pattern
of pulmonary vein stenosis. The flow pattern is turbulent, continuous
and has an abnormally high peak velocity
238
A pulmonary catheterization can be accomplished by the right

side venous or left side arterial approaches. Although, a transseptal puncture is needed to enter the pulmonary veins, in the
case of isolated pulmonary vein stenosis without interatrial
communication, Bahl VK et al described an alternative
retrograde non-trans-septal arterial approach for the pulmonary
vein using steerable left atrial catheter.44 The diagnostic
features include the difference between the left atrial pressure
and the pulmonary artery wedge pressure and the preferential
flow occurring in the contralateral lung when unilateral
pulmonary venous stenosis is associated with a left-to-right
shunt. Pulmonary angiography shows the constriction of the
affected pulmonary vein and the slow clearance of the contrast
medium from one lung in the case of unilateral pulmonary
venous stenosis. Pulmonary arterial wedge angiography
(Figure 20) may be a better technique to demonstrate the precise
anatomy of the pulmonary venous stenosis than pulmonary
Figure 20: Pulmonary artery wedge angiogram of a patient with

severe left superior pulmonary vein stenosis caused by radiofrequency
ablation for atrial brillation. Note the balloon catheter wedged in the
superior segment of the left lung, which allows excellent visualization
of the vein on levophase
arteries, suggesting that the hemodynamic effect of unilateral

pulmonary vein stenosis is reflected in the caliber change in
the branch pulmonary arteries. The computed tomography
is also equally effective in delineating the pulmonary vein
stenosis.
Computed Tomographic and Magnetic

Resonance Angiography
management
When pulmonary vein stenosis is suspected, MRA is performed

as the initial MRI sequence. In a study by Valsangiacomo et
al, MRA visualized the central two-thirds of the pulmonary
veins in 99 percent, while echocardiography was able to
identify the pulmonary veins in only 89 percent.45 Contrast
enhanced MRA (Figures 21A and B) visualizes not only
the stenotic lesion, but also the collateral venous channels
to the unobstructed pulmonary veins. The significance
of the stenosis can be evaluated by measuring flow in the
pulmonary veins and arteries in the affected and unaffected
lungs. On the other hand, vessel caliber and blood flow profile
of the stenosed pulmonary vein do not necessarily reflect the
real severity of the stenosis, because redistribution of blood
flow to the unaffected lung areas results in reduced blood
flow through the reduced caliber of the affected pulmonary
vein. Roman et al. demonstrated that unilateral pulmonary
vein stenosis was associated with reduced systolic forward
flow and diastolic flow reversal in the ipsilateral branch
pulmonary artery.46 Furthermore, the cross-sectional area
ratio of the right and left branch pulmonary arteries correlated
well with the ratio of net forward flow through the pulmonary
Surgery is the definitive treatment. Advances in the technique

of surgical repair of pulmonary vein stenosis have been based
on the concept of reducing trauma to the veins in the hope of
reducing any stimulus for regrowth of the obstructive tissue.
A technique by which the pericardium around the pulmonary
veins is attached to the left atrium avoids any stitches in the
cut edges of the pulmonary veins and is now considered the
best approach. Limited experience suggests that this sutureless
marsupialization may be superior to previous approaches that
used direct anastomosis after the resection of the stenotic
segments or patching of the stenotic vein. Overall, freedom
from reoperation or death at 5 years, however, is still only
~50 percent. Patients with milder degrees of stenosis and
stenosis of only one or two pulmonary veins clearly have
a better prognosis. Pneumonectomy may be necessary for
hemoptysis. In a small number of patients with unrelenting
progression and development of severe pulmonary
hypertension, lung transplantation has been successful. Singlecatheter interventions for treatment of pediatric pulmonary
vein stenosis have also met with limited success. Immediate
improvement is usually seen angiographically, but recurrent
stenosis occurs in a large majority of patients.47
16
arteriography, where selective pulmonary venous injection

is preferred especially in cases with isolated pulmonary vein
stenosis.45 Pulmonary arteriography is often disappointing
in demonstrating the precise anatomy of pulmonary venous
stenosis.
Figures 21A and B: Contrast-enhanced magnetic resonance angiograms, reformatted in slanted coronal planes, reveal
complete occlusion of the left upper (LUPV) and left lower (LLPV) pulmonary veins. A. The left middle pulmonary vein (LMPV)
has an unobstructed connection to the left atrium (LA); B. Collateral channels (arrows) are seen between the peripheral
branches of the unobstructed LMPV and the branches of the obstructed LUPVs and LLPVs. Ao = Aorta; LA = Left atrium;
RA = Right atrium; RLPV = Right lower pulmonary vein; RPA = Right pulmonary artery
239
Prognosis
Echocardiography
Most patients will die before reaching adulthood, and

frequently much sooner.37 The mode of demise is usually
a pulmonary hypertensive crisis, intercurrent pulmonary
infection, or hemoptysis. Breinholt et al found a mortality rate
of 83 percent in patients with 3 or 4 stenosed pulmonary veins
versus zero percent in patients with 1 or 2 stenosed pulmonary
veins.38 More cases of mild forms of pulmonary vein stenosis
are undoubtedly being diagnosed in relatively asymptomatic
patients as a result of increased awareness and improvements
in non-invasive imaging modalities. The precise natural
history of milder forms of pulmonary vein stenosis is therefore
not entirely clear.
It is very difficult to visualize the small pulmonary venous

confluence. The features that should raise the possibility of
presence of this condition include presence of right-to-left
shunt through the foramen ovale, pulmonary hypertension
and inability to visualize the pulmonary vein or its confluence
entering the left atrium. The pulmonary venous return would
not connect to right side structures.
AtrEsIA of thE Common PulmonAry VEIn

The common pulmonary vein is a transient structure normally
identifiable only during the early stages in the development of
the pulmonary venous system.
The term atresia of the common pulmonary vein refers to a
pattern of abnormal pulmonary venous development in which
the individual pulmonary veins are formed, but no connection
exists between these veins and the heart or major systemic
veins.49 Pulmonary veins converge behind left atrium and
form a confluence without draining into it.
Pathophysiology
The proposed route by which blood reaches the systemic
circulation include:
1. Bronchopulmonary venous anastomoses pleurohilar
bronchial veins azygos, hemiazygos and brachiocephalic
veins.
2. Pulmonary capillaries pulmonary arteries bronchopulmonary arterial into the systemic circuit.
The pulmonary capillary pressure increases leading to the
accumulation of fluid. However, there are reports of babies
surviving for a month.49
Clinical features
The clinical features in the atresia of the common pulmonary
vein resembles that in TAPVC. Respiratory distress and
cyanosis occurs in the first few hours after birth. The condition
is often misdiagnosed as RDS as there is no cardiomegaly
and pulmonary parenchyma shows reticular pattern (due
to pulmonary venous hypertension). It can manifest as
spontaneous pneumothorax.50
Investigation
240
Electrocardiography reveals right ventricular hypertrophy.
Cardiac catheterization might be required for accurate
definition of the condition. However, catheterization can
be a high-risk procedure. During catheterization injection
of contrast material into the right ventricle causes the
persistence of the contrast in the pulmonary artery and nonopacification of the left atrium. Also there will be severe
pulmonary hypertension with desaturation in all chambers and
vessels.51
management
Surgery is the definitive treatment of this condition.
Previously, surgery carried a high mortality. But with advent
of extracorporeal membrane oxygenation, its use in the
perioperative period has resulted in improved outcome.52
unIlAtErAl PulmonAry VEnous AtrEsIA

Unilateral pulmonary venous atresia is a rare condition carrying
high mortality. Till now 30 cases have been reported.53 There
is absence of the luminal continuity between the pulmonary
venous drainage between one lung and the left atrium. Most
are diagnosed in the preschool period. It is usually diagnosed
on lung perfusion studies. Often there is poor blood supply to
the affected lung. Pneumonectomy carries the better outcome
compared to other modalities of surgery.54
ConClusIon
The abnormal embryonic pulmonary vein development may
result in a wide spectrum of congenital anomalies of the
pulmonary veins. These conditions have traditionally been
evaluated with echocardiography and angiography and now
they can be more accurately diagnosed with mutlidetector CT
and MRI. The improved neonatal care and surgical techniques
have reduced the perioperative mortality in most centers.
Reading a technically poor echocardiogram is like looking
at a polar bear in a snow storm.
Lynn Y Zoiopoulos, DO
rEfErEnCEs
16
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C hapter
17
Congenital Pulmonary
Arteriovenous Fistula
Chandrakant B Patil, Kiron Varghese
Introduction
Pulmonary arteriovenous fistulas (PAVF) are rare pulmonary
vascular anomalies characterized by a direct communication
between the branches of the pulmonary artery and the
pulmonary veins, bypassing the capillary bed. They are also
named as pulmonary arteriovenous malformations (PAVM),
pulmonary arteriovenous aneurysms, pulmonary angiomatosis
and pulmonary hamartomas.1
While more than half of the patients are asymptomatic, they
can manifest with dyspnea, fatigue, cyanosis and paradoxical
embolization due to right to left shunting. Central nervous
system (CNS) complications include stroke and brain abscess.
There is a strong association between PAVF and hereditary
hemorrhagic telangiectasia (HHT). Chest radiography and
contrast enhanced computed tomography (CT) are essential
initial diagnostic tools, but pulmonary angiography is the gold
standard. Contrast echocardiography is useful for diagnosis
and monitoring after treatment. Most patients, if symptomatic
need treatment. Therapeutic options include angiographic
embolization with metal coils or balloon occlusion and if
needed be surgical excision.2
Historical Background
Churton in 1897 first described PAVF in a 12-year-old
boy, who had episodes of epistaxis, hemoptysis and a loud
pulmonary systolic bruit. At postmortem examination he was
found to have multiple bilateral PAVMs. In 1917, Wilkins
described the necropsy findings in a 23-year-old woman with
cyanosis, clubbing, telangiectasia and bilateral axillary bruits,
who died from hemothorax after rupture of a PAVF into the
pleural cavity. In 1938, Rhodes recognized the association
between telangiectasias and PAVF.3 Smith and Horton in
1939 made the first clinical diagnosis of PAVF in a 40-yearold man who had cyanosis, clubbing, bruit and polycythemia.
In 1942, Hepburn and Dauphinee reported the first case of
successful surgical removal of a pulmonary hemangioma with

disappearance of the patients polycythemia and clubbing after
pneumonectomy. Surgical techniques were further refined to
lobectomy in 1950 and to local excision in 1959. In 1978,
Taylor and coworkers reported the first case of successful
percutaneous catheterization and embolization of PAVM.2
After the initial description of telangiectasia and epistaxis
by Henry Joules Rendu in 1986, Sir William Osler reported a
family with HHT. In 1907, Frederick Weber described other
manifestations of this disorder. Since then HHT has been
known as Rendu-Osler-Weber syndrome. Approximately 70
percent of arteriovenous fistulas are associated with HHT and
about 15 to 30 percent of individuals with HHT have PAVF.4
Through refinements in interventional equipments and
techniques, results have progressively improved to avoid
device embolization. Transcatheter occlusion of the afferent
artery or fistula is usually, accomplished using a coil umbrella
or sack device rather than liquid adhesives or beads.5
PREVALENCE, GENETICS AND ETIOLOGY

The PAVF are a result of an embryonic fault in the vascular
complex that is responsible for the development of pulmonary
arteries and veins. It is a RASopathy. The fistulas can be solitary
or multiple, unilateral or bilateral or diffuse throughout both
the lungs.6 The PAVF may be single or multiple in occurrence
and the incidence of single fistula ranges from 42 to 74 percent.
Most solitary fistulas are seen in bilateral lower lobes, the left
lower lobe being the most common location followed by right
lower lobe, left upper lobe, right middle lobe and right upper
lobe. Majority of multiple PAVFs are also confined to bilateral
lower lobes, the incidence of which ranges from 8 to 20 percent.2
Approximately, 50 to 70 percent of these fistulas are situated in
the lower lobes. The size of the lesions vary from microscopic to
1 to 5 cm.7
Approximately, 75 percent of congenital PAVFs involve the
lower lobes or right middle lobe. They usually occur without
244
coexisting congenital heart disease (CHD). Isolated exceptions

have been reported with left isomerism and atrial septal defect
(ASD). Estimated minimal prevalence rate is 1 per 10,000
births.6 The incidence is 2 to 3/100,000 population. The male
to female ratio varies from 1: 1.5 to 1.8 in various series.2
The PAVFs are usually congenital in origin. However,
they may be acquired in a variety of conditions such as
hepatic cirrhosis, schistosomiasis, mitral stenosis, trauma,
actinomycosis and metastatic thyroid carcinoma and even
after cavopulmonary anastomosis.4,5
The HHT is an autosomal dominant disease with frequency
estimated at estimated as 1-2 per 100,000 persons. A wide
geographic variation in disease prevalence is reported. It is
genetically heterogeneous disease with at least 3 abnormal
chromosomal loci (9q, 12q, and a third locus). HHT gene
has been identified as endoglin, a transforming growth factor
(TGF) beta binding protein. Mutations in endoglin may alter
cellular ability to bind TGF beta 1 with significant potential
consequences in cell regulatory mechanisms. Presumably the
vascular abnormalities seen in patients with HHT may arise
from such aberrations in endothelial cell regulations and
functions.8
PATHOLOGY, PATHOPHYSIOLOGY AND

MORPHOLOGY
Pathology
Anatomically PAVFs are dilated and aneurysmal vessels
that directly connect pulmonary arteries to pulmonary veins
and thus bypass the normal capillary bed, which results in
two important physiological consequences. First, right to
left shunting occurs with the degree of shunt related to the
number of PAVFs and their size. Second, the pulmonary
capillary bed normally acts as a filter for venous blood, blood
flowing through the PAVM bypasses this filtering process
and acts as a conduit through which paradoxical systemic
embolism can occur. The abnormal vascular architecture
of PAVMs, their resultant right to left shunting and the
associated impairment of pulmonary filtering capacity leads
to recognized complications including pulmonary vascular
hemorrhage, hypoxemia and neurological sequelae.8 The
histopathology is structural heterogeneity in the arterial and
venous components. Degenerative changes and aneurysm
formation may be associated with vessel wall rupture.
Patients may have hemoptysis, hemothorax and pulmonary
hemosiderosis.5 In a case of a surgically resected PAVF, the
pathological findings were reported as lung tissue with focal
abnormal proliferation of vascular channels with thick walls,
along with diffuse congestion and alveolar hemorrhage of
surrounding lung tissue and diffuse interstitial angiomatosis.7
Mayor et al after review of 7 out of 15 pathologic specimens
described distended afferent and efferent arteries and veins
with either a direct connection through one or several large
vascular channels or a tangle of smaller vessels instead of

capillaries. They attributed the aneurysmal connection to
the transmission of arterial pressure directly through the
connection with the veins. It is suggested that all PAVFs begin
as plexus type connection for unknown reasons; aneurysms
arise by progressive dilatation of one or several limbs of a
small plexus.9
Morphology
Morphologically PAVFs are divided into two types:
1. Localized lesions commonly occurring in HHT or isolated
PAVF.
2. Diffuse lesions occurring in patients with CHD, liver
disease, portal vein thrombosis and Glenn shunts.
PAVFs range from small pinpoint lesions (1 mm) to huge
tubular or saccular, multilobulated structures occupying most
of a lobe or an entire lung. Lesions may be single or multiple,
unilateral or bilateral. Small lesions tend to be multiple,
diffuse and located deep within the parenchyma. Larger
malformations are usually isolated involving the subpleural
regions of the lower lobes (65%). The airways and lung
parenchyma surrounding the malformations are normal.5
Physiology
Pulmonary arteriovenous fistulas do not affect cardiac
hemodynamics.2 The PAVF creates a right to left shunt from
the pulmonary arteries to the pulmonary veins, resulting in
systemic arterial desaturation and secondary polycythemia. If
the channels are small there is no significant shunting, cardiac
output (CO) is not increased, plasma volume remains normal
and the pulmonary blood flow and pressure are unchanged.
The total pulmonary vascular resistance is normal, resistance
within the arteriovenous fistula is low, but resistance in the
other lung segments may be elevated two-fold. Since normal
pulmonary artery resistance is low, the arteriovenous fistula
shunt does not significantly reduce the overall pulmonary
vascular resistance. Because emboli and bacteria can pass
directly through the fistula in to the systemic circulation,
stroke and brain abscess are well-known complications.5
The degree of shunt determines the clinical effects on the
patient. If shunting is minimal the symptoms are subacute
or absent. If right to left shunt is greater than 20 percent of
systemic CO or there is reduced hemoglobin more than 50
g/L the patient will have obvious cyanosis, clubbing and
polycythemia. In some cases of HHT cyanosis may be hidden
by anemia caused by epistaxis or gastrointestinal bleed. The red
cell mass and blood volume are usually increased, while plasma
volume is normal. The peripheral oxygen saturation is low and
as expected does not normalize with 100 percent oxygen.2
A high percentage of patients with PAVFs demonstrate
orthodeoxia (greater hypoxemia, while in sitting or standing).
This is due to the basal location of most PAVFs, because of the
SIGNS and SympTOMS

Symptoms
Pulmonary arteriovenous fistulas may be asymptomatic in 13
to 55 percent of patients. The classic triad of dyspnea, cyanosis
and clubbing is found in 10 to 30 percent of patients.5 In
asymptomatic patients PAVM can be less than 2 cm size and
the amount of right to left shunting is low. In early adult life
cyanosis, clubbing and polycythemia appear. Cyanosis can be
present from infancy, but in HHT blood loss and the resulting
anemia may mask the cyanosis. In asymptomatic patients the
diagnosis is often made by chest X-ray or abnormal oximetry.5
PAVF affects both the sexes equally6, but the association with
HHT is more in women.8 Fistulas increase in size and number
as age advances. The mean age of presentation is 39 years (age
range 373 years).6 Symptoms include dyspnea (37%67%),
hemoptysis (13%) and hemothorax (9%). Hemoptysis is due
to the rupture of the thin-walled PAVF. Chest pain may be due
to the subpleural arteriovenous malformation rupture causing
hemothorax. Associated HHT can lead to nose bleeds, hematuria,
vaginal and gastrointestinal bleeds.5 Dyspnea and fatigue may
be due to anemia secondary to bleeding telangiectasia.
Neurological symptoms occur in 43 to 67 percent2 and
include migraine headache (43%), seizures, speech disorders,
ocular disturbances and numbness. Transient ischemic attacks
(TIA) occur in 37 percent and stroke in 18 percent due to
paradoxical embolism. The risk of stroke is 1.5 percent per
year. Occasionally, cerebral abscess (9%) and seizures (8%)
can occur.2 The causes are multifactorial and include systemic
hypoxia, polycythemia, small vessel thrombosis and recurrent
cerebral hemorrhage.5 Cerebral symptoms may be brief or
prolonged, isolated or recurrent and tend to have similar
pattern during subsequent attacks.6
Pregnancy can precipitate symptoms because of vasodilation
and they can resolve after delivery. Pregnancy can have favorable
effects by compressing lower lobe fistulas by elevation of
diaphragm.6 Pulmonary hemorrhage is common during the 3rd
trimester of pregnancy. Platypnea (dyspnea in upright position)
and orthodeoxia (oxygen desaturation in upright position) are
less common than exertional dyspnea and may be related to the
predominance of PAVF in basal portions of lungs.8
The severity of symptoms usually depends on the size of
the lesions. If the size is more than 2 cm, dyspnea, palpitations,
fatigue, epistaxis and hemoptysis can occur and cyanosis may
be present.7
Physical Signs
Abnormal physical findings occur in 75 percent of patients.
Superficial telangiectasia can be seen in associated HHT. Groups
of tiny ruby lesions on the nasal and oral mucous membranes,
face, tongue, skin, retina, nail beds occur and they blanch with
pressure and bleed with minor trauma. Examination of the
arterial pulse and precordium is unremarkable. Common signs
are cyanosis, clubbing and a pulmonary vascular bruit, which
is heard in 50 percent of patients, and is a faint systolic or
continuous murmur heard on the chest wall overlying a lesion.
The bruit increases on inspiration and the Mller maneuver
and decreases on expiration and with the Valsalva maneuver2.
The bruit may be absent if the lesion is deep inside or small
or diffuse.6 The accentuation of a bruit by deep inspiration is
due to the increased blood flow through the lesion.5 Standing
increases the murmur of fistulas situated in the lower lobes and
the lateral decubitus position decreases the murmur, because
of compression. Pregnancy also decreases the murmur by
compression of the lower lobe fistulas. Cyanosis will be
absent, when systemic arteries rather than pulmonary arteries
feed the fistulas.6
17
Congenital Pulmonary Arteriovenous Fistula
gravitational shifts of pulmonary blood flow to the base of the

lung, when assuming erect posture. The tendency for increased
shunting and cyanosis with age is not well-understood. Many
factors have been implicated including an increased number
of intravascular communications, opening of previously
unfilled channels, dilatation of existing communications or
progressive polycythemia.5
Investigations
Many major complications of PAVFs including stroke, brain
abscess and hemoptysis can be prevented if detected early.
All persons of HHT should undergo screening for PAVFs and
need monitoring and if the feeding vessel is more than 3 mm
in diameter, in a symptomatic person, treatment is indicated.
Because PAVFs tend to grow overtime, rescreening is reco
mmended every 10 years.8
Chest Radiography
Chest radiograph is an important diagnostic tool (Figures 1
and 2A). If PAVFs are small or microvascular, retrocardiac,
or at costophrenic angles, they may be missed on X-ray. It has
sensitivity of 83 percent and specificity of 92 percent and a
low negative predictive value.8 The lesion is often seen as a
lobulated, round or oval sharp mass of uniform density, 1 to 5
cm in diameter, connected to the hilum and often situated in
lower lobes.2 About 50 percent of patients have 2 to 8 lesions
and may appear like lung nodules.4
Higgins and Waxier have classified PAVFs radiographically as solitary, multiple of different sizes and diffuse (telangiectatic), which appears to be appropriate in both children
and adults.9
Pulse Oximetry
Pulse oximetry is non-invasive, inexpensive, safe and useful
to detect hypoxia and orthodeoxia. However, a normal result
does not rule out PAVF.8
245
246
5 percent by this method is considered abnormal. In a study of

32 patients the shunt fraction ranged from 3.5 to 35 percent and
higher shunt fraction was observed in patients with multiple
PAVFs.2 Quantification of shunt is useful in monitoring patients
after treatment also.8
Contrast Echocardiography (Bubble Study)

Contrast echocardiography is a widely available, reliable, highly
sensitive, safe and simple non-invasive test and can detect even
microscopic and clinically insignificant PAVFs. It is performed
by injecting agitated saline in a peripheral vein. Normally, the
bubbles that appear in right atrium and right ventricle are trapped
in the pulmonary capillary bed and do not appear in left atrium
(LA). If there is a right to left shunt in the heart (e.g. ASD), bubbles
appear in the LA within 1 to 3 cardiac cycles. In PAVF, bubbles
appear in LA after 3 to 5 cardiac cycles, on an average (Figures 2B
and C), but this test does not quantify the shunt fraction.
Figure 1: Chest X-ray showing pulmonary arteriovenous fistula (PAVF)
in left lower zone
Electrocardiography
Electrocardiography is usually normal because hemodynamic
burden is modest in PAVF.6
Arterial Blood Gas Analysis with Shunt Study

Normally, less than 5 percent of the cardiac output bypasses
the pulmonary circulation. In PAVFs the percentage of blood
shunted can be estimated using arterial blood gas (ABG)
measurement. In a sitting position patients are given 100 percent
oxygen for 20 minutes through a mouthpiece. Normal persons
have arterial oxygen content (PaO2) of 600 mm Hg at the end of
20 minutes. In PAVFs it decreases to less than 600 mm Hg. The
percentage of shunt can be calculated based on the measured
arterial oxygen level. A shunt fraction of equal to or greater than
Radionuclide Imaging
Radionuclide imaging is a useful adjunct in diagnosis
and quantification of PAVF. Right to left shunting can be
demonstrated by ventilation perfusion scan of lung. Ordinarily,
95 percent of technetium labeled macroaggregated albumin is
trapped in the pulmonary capillary bed. In right to left shunting
particles elude pulmonary microvasculature, with radio labeled
macroaggregates subsequently appearing in the brain and
kidneys. Quantification of shunt fraction may also be done, but
does not differentiate intrapulmonary from intracardiac shunts.8
A positive result is not specific, but a negative result excludes the
diagnosis. It is not employed routinely as it is expensive and has
limited availability, which prohibits its widespread use.2
High Resolution CT Scan

High resolution CT scan is a non-invasive imaging modality.
It is useful for the structural description of PAVFs like
Figures 2A to C:A. X-ray chest in posteroanterior view shows non-homogeneous opacity in the left upper lobe in 1 year old boy referred for
cyanosis, recurrent respiratory infection, SaO2-60 percent; B. Contrast echocardiography shows bubbles in right atrium and right ventricle with no
evidence of atrial septal defect/patent foramen ovale or ventricular septal defect. C. Bubbles of contrast echocardiography appear in left atrium
and left ventricle after 3 to 4 cardiac cycles. Courtesy: IB Vijayalakshmi
17
Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) has a limited role, because
most lesions in the lung have relatively long relaxation time
and produce medium to high intensity signals, whereas PAVFs
and aneurysms with rapid blood flow will result in signal
void or low signal intensity lesions. It has reduced sensitivity
and specificity and often yields conflicting results, which
are difficult to interpret. Other limitations include limited
availability, higher cost and the need for specialized staff to
interpret the results.2 To improve the sensitivity, rotating,
gated MRI technique and gradient-recalled echo MRI are
utilized. Phase contrast cine sequences are most accurate in
detecting PAVFs. MR Angiography may be used to define the
vascular anatomy of a PAVF.4
Angiography
Despite its lower sensitivity, angiography is the gold standard
for the diagnosis of PAVF and is necessary in most cases to
confirm the diagnosis. A detailed angiographic evaluation of
morphology of vascular lesions including the complexity and
size of feeding vessels is useful prior to embolization or surgery
Figure 3B: Contrast enhanced computed tomography showing

pulmonary arteriovenous fistula with its communication at the hilum
and it may reveal other unsuspected PAVFs and intrathoracic

and extrathoracic vascular communications. However, it is
an invasive procedure using contrast and should be done by
experienced hands. Super selective pulmonary angiography
should be performed to evaluate all segments of both lungs.
Angiography has high specificity, but lower sensitivity than
ultra fast CT or 3D CT and may miss smaller PAVF. However,
most of smaller fistulas may be clinically insignificant. Digital
subtraction angiography (DSA) has to some extent, replaced
conventional angiogram, but its sensitivity is lower than that
of contrast enhanced ultra fast CT scanning or 3D spiral CT
scanning.4
morphology, size and number of vascular lesions. It is

more sensitive than conventional CT and if 3D is added to
it, it gives angiographic architecture in 95 percent of cases.
Contrast enhanced tomography is used in lieu of pulmonary
angiography to define the location and anatomy of PAVFs8
and is significantly better than conventional angiography
in detecting PAVFs (98 vs 60 percent).2 Contrast enhanced
CT can nicely illustrates the PAVF with its communication
(Figures 3A and B).
Natural History
Most patients are asymptomatic in infancy and childhood.
Although rare, symptomatic infants are difficult to treat as their
age, size and the severe lung involvement are poor prognostic
factors. Beyond infancy the frequency of fatal complications
like rupture, massive hemorrhage, endoarteritis and cerebral
abscess is high. Hence elective treatment is recommended. In
one series, 27 percent of patients died in childhood or early
adult life, 12 percent were alive, but symptomatic, 37 percent
were alive and asymptomatic and 24 percent died due to
unrelated causes.5
Indications For Treatment
Figure 3A: Contrast enhanced computed tomography showing

pulmonary arteriovenous fistula
Although information regarding the natural history of PAVFs

is limited, definitive treatment is generally indicated in
patients who are symptomatic, have hypoxia or have one or
more fistula larger than 2 cms. Persons who have PAVFs and
who develop signs and symptoms of right to left shunting
like dyspnea, fatigue, exercise intolerance or cyanosis and
247
who anticipate pregnancy, need treatment. Asymptomatic

patients without hypoxia and with a feeding vessel diameter
less than 3 mm are usually monitored at least every 3 years.
Follow-up in this population is necessary as more than half of
PAVFs appear to increase in size over time. Pregnancy with
PAVF has high risk of maternal complications as the fistula
size increases, because of vasodilatation or other hormonal
influences and hence increases risk of complications including
worsening right to left shunt, pulmonary hemorrhage and
stroke. Morbidity associated with untreated PAVF is up to 50
percent compared to about 3 percent in treated patients.10-12
Mortality figures range from 0 to 55 percent in various
studies. The purpose of treatment is to reduce neurological
complications, prevent progressive hypoxia and high output
cardiac failure. Development of new symptoms at any time
should prompt a re-evaluation.8
TREATMENT
Goals of therapy include relief of symptoms of dyspnea
and fatigue, prevention of complications like hemoptysis
and hemothorax and prevention of sequelae of paradoxical
embolization including stroke and brain abscess. An attempt
to raise the PaO2 to 60 mm Hg or higher, which represents
SaO2 of 90 percent.
Most patients with one or more PAVFs are candidates
for resection of the lesion. Asymptomatic patients or those
with small lesions (1015 mm) or who have a small shunt
are not treated, though their condition is followed regularly.7
An intervention is necessary in all symptomatic patients
even with mild symptoms, whose lesions are visible in chest
X-ray or CT scans. Excision is a highly successful procedure
A
248
in isolated fistula, which is recommended in patients with

permanent bleeding secondary to intrapleural rupture or
hemoptysis despite embolization. Morbidity, mortality and
recurrences are low. Since most fistulas are subpleural, they
are curable by resection.7
Transcatheter coil/vascular plugs/and device embolization
has become the treatment of choice in multiple and bilateral
arteriovenous fistulas, which are not suitable for surgery
(Figures 4A and B). This can also be done in patients as also in
patients in whom thoracotomy and general anesthesia would
carry a high risk due to massive shunting. In 1977, Portsman
used home made metal coils, followed soon after by stainless
steel coils and detachable balloons for embolotherapy.
Through refinements in interventional equipment and techni
ques, embolization results have progressively improved. To
avoid device embolization (through the PAVF into systemic
circulation) transcatheter occlusion of the afferent artery or
fistula is done using an umbrella, coils or plugs rather than
liquid adhesives or beads. The Amplatzer vascular plug is a selfexpandable, cylindrical device made from a nitinol wire mesh.
The device is secured on both ends with platinum marker bands,
especially designed for arterial and venous embolizations in
the peripheral vasculature. Various sizes of vascular plugs are
available measuring from 4 to 16 mm (Figures 5A and B).
Excellent results have been achieved with embolotherapy and
the goal is to occlude all afferent arteries more than 3 mm in
diameter and to raise the systemic arterial oxygen saturation.
The advantages of embolotherapy over surgery are that it avoids
thoracotomy and general anesthesia and multiple lesions can
be embolized without significant loss of lung tissue. It appears
to be a durable form of treatment. In a series of 46 patients with
82 PAVFs followed for 2 to 4 years after embolotherapy, only
Figures 4A and B: A. Right pulmonary artery angiogram in frontal view in a 1 year old boy with SaO2-60 percent shows multiple pulmonary
arteriovenous fistulas in the upper branch; B. Check angio after multiple coils, Amplatzer duct Occluder and vascular plug. Post procedure the
SaO2 improved to 94 percent. Courtesy: Dr IB Vijayalakshmi
17
Figures 5A and B: A. Vasular Plug; B. Vasular Plug II; C. Vascular Plug IV; D. Diagrammatic representation of vascular plug in the vessel
2 PAVFs showed evidence of reperfusion. Even large PAVFs

can be treated successfully with embolotherapy. In a series of
45 patients with 52 PAVFs with feeding arteries 8 mm or larger
in diameter, all were successfully treated with embolization.
However, 15 percent required repeat embolotherapy for
persistence of PAVF or recanalization after treatment.8 In 76
adult patients, 276 PAVFs were occluded providing persistent
relief of hypoxemia, resolution of orthodeoxia and minimal
growth of small remaining PAVFs. Some patients required
multiple catheterizations.5 In another study done by White et
al,9 patients with 91 PAVFs were evaluated by super selective
angiography and balloon embolotherapy was effective in
permanently obliterating the malformations in 14 patients
with rise in arterial PaO2 from 49 mm Hg to 65 mm Hg and
in 3 patients it was not effective. Complex PAVFs required
occlusion of all feeding arteries.9
Embolotherapy is successful in initially blocking the PAVF
more than 95 percent of the time and has a low complication
rate. Depending on the size of the original PAVF, 5 to 15
percent of the PAVFs may reopen over time and a new PAVF
may grow. Therefore, it is very important to follow-up within 6
months and then at least every 3 to 5 years to check the success
of the procedure.13 With the exception of diffuse PAVMs,
embolotherapy results in improvement of oxygenation and
reduction in shunt fraction. Follow-up with chest X-ray/
CT scan, usually shows that lesions have disappeared in
1 year following embolotherapy. While a residual scar may
be seen in some patients, lack of radiological resolution
suggests recanalization of PAVM or inadequate embolization.
Complications of embolotherapy are:
1. Thrombosis, air embolism, arrhythmias.
2. Pleurisy: It occurs in approximately 14 percent of patients.
A delayed pleurisy 4 to 6 weeks later can also occur.
Paradoxical embolization occurs in less than 1 percent of
patients.8
In summary embolization has minimal morbidity and no
mortality and hence radiological intervention is the first choice
of treatment in PAVF. Embolotherapy is a suitable alternative
to surgical interventions in the elderly, who are poor surgical
candidates, in patients with multiple lesions and patients, who
decline surgery.2
Surgical Treatment
The surgical treatment for PAVFs is lobectomy, pneumon
ectomy, subsegmental resection or ligation of the vascular
pedicle feeding the PAVF. The first successful pneumonectomy
was performed in 1940 and the first segmental resection was
performed by Blalock in 1947. Current surgical treatment
is segmental resection or lobectomy, removing the smallest
amount of lung, while completely excising the PAVF. The
operative mortality is 5 percent and the cure rate is 75 percent. In
infants or children surgical lobectomy may result in chest wall
deformities, causing alterations in pulmonary mechanics. There
is a long-term risk of developing arteriovenous malformation in
contralateral lung.5
Until 1978, surgical excision of solitary PAVF or the largest
PAVFs in patients with multiple fistulas was considered the
therapy of choice. Unfortunately in patients with multiple
PAVFs recurrences of symptoms occurred over 10 to 20
years as small PAVFs grew. In 1978, Tailor et al reported
successful embolotherapy using wool coils in a patient with
multiple PAVFs. Despite complicating pulmonary infarction,
the patient recovered uneventfully with excellent results. In
1980 additional PAVFs were treated by coil embolotherapy
and balloon embolotherapy.9
Surgery is necessary in patients who fail to respond to
embolotherapy, develop serious bleeding complications
despite embolotherapy, have intrapleural rupture of the PAVF
or have untreatable contrast allergy and lesions not amenable
to embolotherapy. Lung conservation resection, local resection
or segmentectomy is the procedure of choice, whenever
possible. Staged bilateral thoracotomies were performed
in a case of an extensive bilateral PAVFs. Recently, videoassisted thoracoscopy was employed in the resection of a
small PAVF. Reported mortality is 0 percent after 1960.2 As
with embolization it is important to follow-up these patients
every 3 to 5 years to check for growth of new PAVFs.13
CONCLUSION
Pulmonary arteriovenous fistula is an unusual clinical
problem, which should be considered, when a suspected
case of cyanotic CHD is normal on clinical examination or
249
250
in symptomatic patients with the triad of exertional dyspnea,

cyanosis and clubbing with normal cardiac examination.
In such cases when cardiac findings are normal one should
suspect PAVF. A diagnosis of HHT has to be kept in mind
in all PAVFs with mucocutaneous telangiectasia. These
patients should be monitored and treated promptly to prevent
potential complications of paradoxical embolism, hemoptysis,
endocarditis and cerebral abscess. Once diagnosed, the lesion
morphology and the degree of the shunt should be assessed by
appropriate imaging methods and treated with embolotherapy
or surgery wherever indicated. All patients with PAVFs who
are symptomatic need intervention, the nature of which
may depend on the morphological features of the lesions.
Embolotherapy if available is a relatively safe and an effective
procedure and preferred treatment for PAVF. Lung conserving
resection is an optimal treatment for symptomatic patients,
when embolotherapy is not feasible. Regular follow-up is
needed to detect recurrences of the lesions.
Heart one of the most wonderous features of animate
nature is surely the most perfect harmony existing between
structure and function.
John Hunter
Acknowledgment
We wish to thank Dr IB Vijayalakshmi, Professor of Pediatric
Cardiology, for sharing some of her images.
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fistula. Diagnosis and prognosis in noncomplaint patients. Am
Rev Respir Dis. 1969;100:177-88.
12. Puskas JD, Allen MS, Moncure AC, et al. Pulmonary
arteriovenous malformations: therapeutic options. Ann Thorac
Surg. 1993;56(2):253-7; discussion 257-58.
13. Gossage J. Overview Pulmonary (Lung) Arteriovenous Mal
forma tions. 2012: Georgia Health sciences University. http://
www.georgiahealth.edu/medicine/medicine/pulmonary/pvd/
hht/pavm.html.
Sec t i on
4
Shunt Defects
c hapter
18
interatrial Defects
Shada J Al-anani, Ziyad M Hijazi
introDuction
Interatrial defects are amongst the most common congenital
heart disease encountered at all ages. These defects are defined
as any opening between the two atria other than a competent
foramen ovale.1 The true incidence of interatrial defects is
underestimated due to high rate of early spontaneous closure
and the delay in presentation into adulthood due to subtle signs
and symptoms.2 Isolated secundum atrial septal defects (ASD)
constitute 6 to 10 percent of all congenital heart defects, with
a female preponderance of 2 : 1 ratio.3 There have been major
advances in the approach and management of such lesions in
the last decade.
In this chapter, we will discuss pathology, natural history
and clinical presentation of such defects. In addition, relevant
investigation and management both surgical and catheter
based interventions.
PAtHoLoGY
Anatomically the atrial septum not only separates the two
atria ASD but in part separates the right atrium from the left
ventricle.
Embryologically interatrial communication is vital for
survival during fetal life. Septum primum initially separates
both atria anteroinferiorly, lined by endocardial cushion cells.
In order to maintain this mandatory interatrial communication,
cribriform perforations in the septum primum are later formed
joining together into ostium secundum (fossa ovalis).
Septum secundum, on the other hand, develops through
enfolding of the roof of the atrium to the right of septum
primum, the leading margins of septum secundum constitutes
what is called the superior limbus of fossa ovalis.4
This embryological evolution of the atrial septum leads
to a better understanding of the current classification of the
interatrial communications. Patent foramen ovale (PFO) is
the persistence of this fetal communication due to failure of
the functional and anatomic apposition of the septum primum
flap to the crescent shaped septum secundum. Probe PFO is

known to occur in 25 percent of normal subjects beyond the
1st year of life.5
Secundum ASD occurs secondary to deficiency of the
septum primum (the valve of fossa ovalis) in the majority
of cases and rarely due to deficient septum secundum
counterintuitively. From this we can differentiate between
the PFO and secundum ASD with the latter being larger
and unguarded by the valve effect of the septum primum
apposition to the septum secundum. Secundum defects
comprise 70 percent of ASD and are seen at fossa ovalis
position (Figure 1).
Septum primum is lined by endocardial cushion cells early
in fetal life and so primum ASD are acquired due to abnormal
formation of the endocardial cushions. These are considered
to be part of the atrioventricular (AV) canal defects and are
associated with cleft mitral valve.6 They are usually located in
anteroinferior location relative to the fossa ovalis (Figure 1).
Other less frequent types of ASD are sinus venosus
defects which include superior vena cava (SVC) and rarely
inferior vena cava (IVC) type and coronary sinus defects.
These defects are not true ASDs, but rather a consequence of
abnormal development of the embryologic venous tributaries;
the right venous horn (sinus venosus defects) or the left sinus
venous horn (coronary sinus defects).
Sinus venosus defects (411%) SVC type is a result of
straddling of the right upper/middle pulmonary vein opening
to the right atrium leading to a form of partial anomalous
venous return ASD.7 This type of ASDs lack superior
boundaries and relates directly to the ostia of the SVC
and the pulmonary veins. They are seen superior and posterior
to fossa ovalis. The IVC type of this defect is rarely seen
(Figure 1).
Coronary sinus defects are infrequent (< 1%) and they are
due to defect in the wall that separates the coronary sinus from
the left atrium and ultimately leads to inter atrial mixing, this
is usually seen as dilated coronary sinus opening into the right
atrium and is often associated with persistent left SVC.7
Shunt DefectS
figure 1: Different types of atrial septal defects from the right atrial
view. Note: The position of each defect to fossa ovalis. AO = Aorta;
CS = Coronary sinus; IVC = Inferior vena cava; PA = Pulmonary artery;
RA = Right atrium; RPV = Right upper pulmonary vein; RV = Right
ventricle; SVC = Superior vena cava; SVD = Sinus venosus defect
GEnEticS
The genetic basis of the ASD is not completely understood.
In the majority of cases this is a sporadic lesion, yet some
homebox gene defects have been found to explain some of
the well-known familial cases with ASDs, such as NKX2chromosome 5, which has an autosomal dominant inheritance
and AV conduction defect.8
Identification of ASD or other congenital heart defects
in more than one family member should prompt clinical
evaluation of all relatives.9
Other genetic syndromes with skeletal abnormality such
as Holt-Oram syndrome, which is caused by mutations in the
transcription factor TBX5, essential in the development of
both the heart and upper limbs.10
Atrial septal defects can be part of many other syndromes
and more complex congenital heart diseases. Down syndrome
is associated with both primum and secundum ASD, while
Noonan syndrome most commonly is associated with
secundum ASD and pulmonary valve stenosis.
nAturAL HiStorY
254
Secundum ASDs have been clinically described as early as

1900.11 Several studies were conducted to find the outcome of
such common defects looking for the criteria that could predict
spontaneous closure and the incidence of complications later
in life.
One of the early studies carried out in 1983 by

Cockerham et al12 who followed 87 children for which
cardiac catheterization was done at less than 4 years of age
for a clinically significant secundum ASD. They found that
spontaneous closure occurred in 22 percent in patients who
had their cardiac catheterization before the first year of life.
This decreased to 3 percent in patients who were between
2 to 4 years at the time of their 1st cardiac catheterization.
Their recommendation was to wait until after age 4 years for
elective closure.
Later, studies based on 2D Echocardiography were
conducted by Radzik et al13 in 1993 showing that ASDs
smaller than 5 mm including PFO closed spontaneously in 87
percent of the cases. No spontaneous closure was found in
defects more than 8 mm.
Recent studies have also confirmed previous findings, a
retrospective study in Austria in 2006 in which 200 children
with ASD more than 4 mm were followed for a period more
than 6 months found that using a multivariate analysis smaller
ASD and younger age at diagnosis were both independent
predictors of spontaneous closure. ASDs 4 to 5 mm in diameter
at diagnosis showed spontaneous closure or regression to
a diameter less or equal to 3 mm in 86 percent of the cases
and none required surgical closure, of ASDs with a diameter
of greater than 10 mm at diagnosis (21% of the cases), none
closed spontaneously, whereas 77 percent required surgical or
device closure.14
Another question that was answered by a study by
McMahon et al15 whether ASD can with time enlarge in
size or not. 104 children older than 4 years with ASD were
followed up for 3 years. In 65 percent of patients the defects
enlarged, some to the extent that they could not be closed by
transcatheter techniques at that time.
In summary, defects larger than 8 to 10 mm are less likely
to close spontaneously and most likely will require surgical
or transcatheter closure, regardless of the age at diagnosis.
On the other hand, ASDs diagnosed after the first 4 years of
life are less likely to spontaneously close and they can present
later in life with several complications.
We will discuss below possible the complications that can
ensue from interatrial communications.
complications
Symptoms of Exercise Intolerance and Fatigue/
Congestive Heart Failure
Although congestive heart failure is an uncommon presentation
in childhood, these symptoms are common among older
patients. Craig and Selzer in an early series of adult patients
with ASD found that incidence of symptoms increases from
14 percent at 20 to 40 years to more than 24 percent between
40 to 60 year. Exertional dyspnea can reach up to 75 percent
in patients in their 6th decade.16,17
Atrial Arrhythmias
Fixed Pulmonary Hypertension

Pulmonary vascular disease is one of the most serious
complications of ASDs, rendering the disease to be inoperable.
Fortunately, this is not common at young age (14 to 18%
between 2040 year of age)16 and occurs more frequently
in female patients. It is still debatable whether this is caused
by the presence of large shunts or due to other predisposing
conditions such as thromboembolic phenomena.20 Severe form
of pulmonary hypertension leading to cyanosis as a result of
reversal of the shunt (Eisenmenger syndrome) is infrequent and
usually present late in life. Konstantinides et al reported a mean
age of 56 years.17 Sinus venosus defects patients are more prone
to develop pulmonary hypertension at an earlier age, therefore,
close follow-up and early repair is warranted in this subset of
patients.21
Systemic Embolization
The existence of a potential right-to-left shunt through
interatrial communication carries the risk of paradoxical
embolization. This was confirmed by comparative studies
that found existing risk even in patients who do not have
atrial arrhythmias.17 The hazard of cardiogenic event such as
cryptogenic stroke increases dramatically in situations where
the right atrial pressure increases such as in pregnancy and
scuba diving.
Reduced Life Expectancy

Secondary to pulmonary arterial thrombosis, congestive
heart failure, paradoxical embolism and recurrent respiratory
infections. It is difficult nowadays to estimate age of survival
in patients with unrepaired ASDs in the modern era of surgical
and catheter interventions. One study estimated the mortality
rate to be 0.6 to 0.7 percent per annum in the 1st decade of life
and more than 7.5 percent in the 6th decade.22
18
InteratrIal DefectS
Right atrial dilation secondary to chronic stretching and volume

overload predispose older patients to atrial arrhythmias such
as atrial fibrillation and less commonly atrial flutter, this can
exacerbate sign and symptoms of heart failure. They are one
of the common presenting symptoms in the 4th to 5th decade
of life. Incidence can reach up to 52 percent in patients older
than 60 years of age.18,19
dependent on not only the size of the defect, but also on the
relative difference in the gradient between the two atria, which
is a mere reflection of the end-diastolic pressure difference
between the two ventricles when both AV valves open in
diastole.
This explains the timing of presentation for large shunts in
infancy, which usually occurs between 6 to 8 weeks. At that
point, the pulmonary vascular resistance drops to its normal
levels and the right ventricle becomes more compliant,
leading to increase pressure gradient between the two atria
and subsequently a larger shunting volume. On the other
hand, later in life the left ventricle becomes more stiff perhaps
secondary to aging and ischemic changes and so the size of the
shunt also increases, which might explain that most patients
with ASDs present in their 4th to 5th decade.16,17 Symptoms in
this age group include fatigue, dyspnea on exertion, peripheral
edema and other symptoms of heart failure. This is rarely the
case in children, where congestive heart failure or failure to
thrive are very uncommon.
Cyanosis as a result of right-to-left shunting can be due
to high pulmonary vascular resistance (pulmonary vascular
obstructive disease) at an old age, but it also might be
secondary to direction of deoxygenated blood from the
IVC through prominent eustachian valve or thebesian valve
through the defect to the left atrium. Differentiation between
these two phenomena is crucial for future management.
Most of the time physical examination is unremarkable, typical physical findings include normal oxygen saturation, apart
from aforementioned conditions. Other findings include wide
fixed splitting of the second heart sound, which is an exaggeration of a normal phenomena that leads to delay in closure of the
pulmonary valve as a reflection of the dilation of the pulmonary
artery that warrants longer time to achieve adequate pressure to
close the pulmonary valve, other factors that explain this, is the
prolonged emptying of the right ventricle.
Auscultatory findings also include soft crescendodecrescendo ejection systolic murmur on the left upper sternal
border as a result of pulmonary blood overflow across that
valve and a mid-diastolic murmur at the lower left sternal
border related to increased blood flow across the tricuspid
valve in larger shunts.
Once pulmonary hypertension develops these findings
completely change to a cyanotic patient with prominent
second heart sound, short systolic murmur and absent fixed
splitting or diastolic murmur.
rELEvAnt invEStiGAtionS
cLinicAL PrESEntAtion
chest X-ray
Patients with ASDs are usually asymptomatic early in life.

In fact, most children present with a murmur on incidental
cardiac examination or when they are referred for cardiology
consultation for other purposes. Clinical characteristics
depend mainly on the magnitude of the shunt. Findings are
Prominent pulmonary artery, hilar vessels and increased

pulmonary vascular markings point out to a large left-toright shunt. Enlarged cardiac silhouette can also be seen as a
consequence of prolonged volume overload to the right atrium
and ventricle.
255
Shunt DefectS
This indeed is not seen in case of pulmonary obstructive

disease; on the contrary, the lung fields at that point would be
oligemic.
Electrocardiogram
Three points has to be kept in mind, while looking at an
electrocardiogram in patients with ASDs: rhythm, AV
conduction and signs of right-sided volume overload.
In most instances the rhythm is normal sinus, but sometimes
and especially at an older age there might be evidence of atrial
fibrillation or atrial flutter. Low atrial rhythm (negative P
wave) might point to a sinus venosus defect.
First degree AV block can be seen at older age secondary
mostly to interatrial delay. Occasionally complete heart block
can be found in familial ASD.
Peaked tall P wave as can be seen in right atrial dilation,
while right ventricular volume overload may manifest as
rSR pattern (incomplete right bundle branch block) in leads
V1 to V3. This is usually seen with right axis deviation
between 95 to 170. If left axis deviation is found then primum
ASD should be highly suspected (Figure 2).
Exercise stress test are not required as part of a regular
assessment of ASDs, unless there is inconsistency between
the symptoms and the clinical findings. Maximal exercise
testing is contraindicated in severe pulmonary hypertension.23
Echocardiography
Transthoracic 2D Echocardiography
Transthoracic 2D echocardiography (TTE) is the principal
tool in the diagnosis and follow-up of patients with interatrial
communication especially in children and thin adults where
the acoustic windows are clear. Confirmation of location and
the size of the ASD from several views is necessary. Anatomic
256
landmarks and other associated lesions should be also sought.

In addition, looking for hemodynamic consequences of large
shunts, mainly right atrial and ventricular dilation, flattening
of the ventricular septum (Figures 3A to F).
It is prudent to avoid false drop out that may be confused
with a true ASD. This is achieved by finding the best view
where the echo beam is perpendicular to the defect.
The subcostal view is perfect for PFO and secundum atrial
defects using color Doppler for confirmation. Identification of
the rims is very important for catheter-based interventions. For
that, sagittal view provides good assessment for superior and
inferior rims. In this view also, close attention should be paid
to the insertion of the right upper pulmonary vein and SVC.
Absence of the wall between these two structures constitutes
the major diagnostic finding in sinus venosus defectsuperior
type (Figures 4A to C).
Apical 4-chamber view, on the other hand, has a high rate
of false drop out and is therefore inappropriate for diagnosis
of ASDs. However, it is appropriate for evaluation of right
ventricular dilation and estimation of right ventricular systolic
pressure using tricuspid regurgitation jet.
Parasternal short-axis view might offer an alternative
for the subcostal view in the adult population, high right
parasternal view in right decubitus position is particularly
useful. PFO, sinus venosus defect can be readily identified in
this position. In addition, parasternal short-axis view is the
proper view for evaluation of anterior (aortic) and posterior
rims of the of secundum ASD.
Coronary sinus defects should be suspected when a dilated
coronary sinus is seen with dilated right atrium and right
ventricle. Looking for the defect posteroinferiorly in the
subcostal view shows the defect just above the right atrium and
IVC junction with intact foramen ovale. Sometimes mistaken
as septum primum defect, evidence of left SVC and absence
of cleft mitral valve should prompt the diagnosis (Figures 5A
and B).
figure 2: An electrocardiogram of 25-year-old female patient with large atrial septal defect showing normal sinus rhythm, right axis deviation and
rsR pattern in V1 consistent with right ventricle volume overload. aVR = Augmented vector right; aVL = Augmented vector left; aVF = Augmented
vector foot
18
InteratrIal DefectS
figures 3a to f: A 2D transthoracic echocardiogram of secundum atrial septal defect. A. Four-chamber apical view: this demonstrates the atrial
septal defect (arrow) and dilated right atrium and right ventricle; B. Left-to-right shunt seen on color Doppler; C and D. Parasternal short-axis
view showing the defect (arrow) and the deficient anterior (aortic rim) and the posterior rim confirmed shunt on color Doppler; E and F. Subcostal
sagittal view of showing the defect (arrow) and superior inferior margins with left-to-right shunt. RA = Right atrium; LA = Left atrium; LV = Left
ventricle; RV = Right ventricle; Ao = Aorta
figures 4a to c: Transthoracic 2D echocardiogram: A. Four-chamber view showing dilated right atrium and right ventricle with no ASD seen
in this view. This should raise the suspicion of the presence of a shunt; B. Looking carefully in subcostal sagittal view a sinus venosus defect is
appreciated. Notice the anomalous drainage of the right upper pulmonary vein; C. Finally, this is clearly identified in high esophageal TEE in the
biatrial long-axis view where the ASD (arrow) is seen with superior vena cava overriding the defect. RA = Right atrium; LA = Left atrium; LV = Left
ventricle; RV = Right ventricle; SVC = Superior vena cava; IVC = Inferior vena cava; RUPV = Right upper pulmonary vein
257
Shunt DefectS
figures 5a and B: Transthoracic 2D echocardiogram of a coronary sinus defect: A. Frontal subcostal view showing a posteroinferior defect;
B. Suprasternal view showing persistent left SVC draining into the left atrium. In this particular case, the coronary sinus is completely unroofed
in what is called Raghib syndrome. RA = Right atrium; LA = Left atrium; LV = Left ventricle; RV = Right ventricle; LSVC = Left superior vena cava
Color and spectral Doppler confer a valuable method

for accurate evaluation of the hemodynamics too determine
the direction of flow of the shunt, mean gradient across the
septum between the left and right atrium, estimation of the
right ventricular systolic pressure using tricuspid velocity jet
and the acceleration of pulmonary blood flow.
Contrast Echocardiography
Verification of the presence of interatrial communication can
sometimes be challenging, particularly if the defect is small
or the acoustic windows are not optimal in older adults.
Peripheral intravenous line can be used to inject agitated
saline using a three-way stopcock, while imaging the atria in
4-apical view. Air bubbles should opacify the right atrium,
negative wash out will be seen in the case of left-to-right shunt.
This technique is used more frequently to look for presence of
right-to-left shunt at rest or during Valsalva maneuver. It is
confirmed by the passage of the micro-air bubbles into the left
atrium through a PFO.
Transesophageal 2D Echocardiography
Transesophageal echocardiogram, is used in adult patients
whom the transthoracic acoustic windows are not optimal. It is
valuable in determining the ASD size, rims and the pulmonary
venous drainage. It is also used to guide transcatheter device
closure (Figures 6A to F).
Intracardiac Echocardiography
258
Another valuable guiding tool for transcatheter device closure

of ASD using a small disposable imaging catheters in the
interventional suite. It obviates the need for general anesthesia
required for TEE and provides high-resolution intracardiac

images for the defect, its rims and adjacent structures.
3D Echocardiography
3D transesophageal echocardiography has an outstanding clear
image with spatial relationship to surrounding landmarks. It is
useful especially when attempting to close multiple defects
percutaneously (Figures 7A and B).
cardiac ct scan and cardiac Mri

The use of cardiac computed tomography (CT) and cardiac
magnetic resonance imaging (MRI) is not routine in evaluating
ASDs. These non-invasive techniques are reserved for complex
atrial defect anatomy. They provide wide field view with
detailed resolution of the defect and the adjacent structures,
specifically the pulmonary veins without the limitation of poor
acoustic windows sometimes encountered in echocardiography.
Cardiac MRI has the advantage of accurately estimating
right ventricle volume and even the shunt size (Qp : Qs ratio)
thus offering better physiological understanding of the defect.
On the other hand, MRI cannot be performed in patients who
have pacemakers or coils and it also requires sedation in
young patients.
cardiac catheterization
The role of cardiac catheterization in ASD has changed
considerably over the past years from a diagnostic tool to
more of an interventional function.
Nevertheless the indications for diagnostic cardiac
catheterization are to calculate pulmonary vascular resistance
and to assess the reactivity of the pulmonary vascular bed
18
InteratrIal DefectS
figures 6a to f: 2D Transesophageal echocardiogram of secundum atrial septal defect: A and B. Mid-esophageal 4-chamber view (020) for
mitral valve and tricuspid valve rims and with clockwise rotation of the probe, the right upper pulmonary vein (RUPV) should be readily visualized.
Color Doppler also confirms presence of left-to-right shunt as seen by the blue jet; C and D. High esophageal short-axis view (3040) showing
the atrial septal defect (arrow) and the aortic rim is appreciated clearly in this view. Color Doppler is seen in D showing left- to-right shunt across
the defect; E and F. High esophageal biatrial long-axis view (90100): this evaluates SVC and IVC rims accurately. RA = Right atrium; LA =
Left atrium; LV = Left ventricle; RV = Right ventricle; SVC = Superior vena cava; IVC = Inferior vena cava
in patients with pulmonary hypertension. Other indications

include partial anomalous pulmonary venous return where
non-invasive data are nonconclusive for the course of these
veins and their drainage.23
Rarely, hemodynamic significance of atrial defects cannot
be determined by echocardiography. Otherwise, hemodynamic
study is performed as part of an interventional procedure
during device closure of these defects.
Hemodynamic Changes
Management questions arise when an ASD is found:

factors that should guide the decision to close such defects,
appropriate timing and the options for closure.
As it is the case in most congenital heart diseases, presence
of symptoms is certainly an indication for closure. This should,
however, be carefully understood in ASDs. Delaying closure
until complications develops is not advisable. Thus, absence
of symptoms should not preclude closure, if other criteria are
met.
Understanding the natural history of ASDs allows us to
infer that size and age play major role in the management.
More than 5 percent (serial measurements) to 7-10 percent

(one measurement) step up in the oxygen saturation is
expected from the SVC to the right atrium.
Differential Diagnosis
Partial anomalous pulmonary venous return, left ventricle
to right atrial shunt (Gerbode defect), AV septal defects or
ventricular septal defects (VSD) with tricuspid insufficiency.
Equal pressure in both atria in large shunts

Normal to mild elevation of right ventricular pressure
Normal to mild elevation of pulmonary artery pressure
Pulmonary vascular resistance should not exceed 4 Woods
units
Unless there is pulmonary hypertension (Figure 8).
trEAtMEnt
259
Shunt DefectS
figures 7a and B: This is a 3D transesophageal echocardiography view from the right atrium showing the outstanding 3D image
of secundum atrial septal defect and relationship to surrounding structures. This figure also shows the spatial orientation of each
of the 2D-TTE and TEE images: Long-axis view (LAX) is a superior inferoposterior cut into the defect: showing the SVC and IVC
relation to the defect. Short-axis view (SAX) is a anterior posterior cut into the defect showing the anterior (aortic rim) and posterior
rim of the defect. The 4 chamber view is a superoposterior and inferoanterior cut into the defect and this shows the relationship to the
atrioventricular valves. Ao = Aorta; CS = Coronary sinus; IVC = Inferior vena cava; LA = Left atrium; LV = Left ventricle; RA = Right atrium;
RV = Right ventricle; SVC = Superior vena cava; TV = Tricuspid valve
260
figure 8: A diagrammatic view for oxygen saturation and pressure

data of a 38-year-old patient found to have 27 29 mm ASD secundum
defect. Qp : Qs ratio is 3.1 and pulmonary vascular resistance is 3.61
Woods units
During the 1st year of life, small atrial level communications

less than 3 to 5 mm usually close spontaneously. Right
ventricular volume overload is not expected as a hemodynamic
consequence of such defects. Thus, closure of PFO and small
ASD is only justified in particular circumstances where the
risk of paradoxical embolism is high. This includes pregnancy,
scuba diving or history of previous stroke/transient ischemic
attack confirmed by specific findings on MRI of the brain.23
Migraine headaches remain controversial as an indication
for closure of PFO. Passage of certain vasoreactive substances
(serotonin) without inactivation by lung tissue has been
claimed to cause increased incidence of migraine among PFO
patients. This, however, has not been proven in randomized
clinical trials.
Follow-up of such patients who do not meet the criteria for
closure includes an echocardiogram every 2 to 3 years looking
for development of any criteria warranting closure.
Patients with larger defects will suffer ultimately from
complications later in their lives. For that reason, patients
who present with large defects (> 8 mm), large shunts (Qp : Qs
explaining this phenomenon: one of which is right-to-left

shunt secondary to redirection of the blood by the Eustachian
valve and the thebesian valve into the left atrium through
PFO. This, however, should be confirmed with diagnostic
cardiac catheterization.
SurGErY
History
Dennis et al25 in 1951 reported the first surgical attempt to
close an ASD; although this was not a success story, dramatic
improvement in cardiopulmonary bypass technique later in
1950s led to a safe surgical closure of ASDs in the current era.
18
InteratrIal DefectS
more than 1.52 : 1) or right ventricle volume overload with or

without symptoms should be considered for surgical or device
closure.
Clinical and laboratory findings of right ventricular volume
overload can manifest with physical findings of diastolic
flow rumble due to tricuspid regurgitation, cardiomegaly and
increase pulmonary vascular markings on chest X-ray, signsof right ventricular hypertrophy on electrocardiograms and
ultimately echocardiographic findings of right ventricular
hypertrophy with possible paradoxical wall motion of the
ventricular septum.23,24
Unless the infant cannot be managed medically for signs
of congestive heart failure (which is quite unusual in this
condition), closure is recommended after the 2nd year of life
in anticipation of spontaneous closure or decrease in size.
Development of inevitable sequelae of large shunts later in
life further complicates the management of older patients. Atrial
arrhythmias should not preclude the closure of large defects.
This, however, should be preceded by successful cardioversion
or ablation before the access to left atrium is closed.23
A major complication, mainly encountered in adulthood is
pulmonary hypertension. Incidence of such complication is
variable among studies. Careful evaluation of these patients
should include cardiac catheterization to determine the
operability and risk of closure. It allows direct measurement of
the pulmonary arterial pressure and pulmonary vasoreactivity
test with oxygen or nitric oxide.
Balloon occlusion testing temporarily in the cardiac
catheterization laboratory can provide insight to the risk of
closure in patients with reversible pulmonary hypertension or
bidirectional shunt or in patients whose response to medical
therapy for pulmonary hypertension is evaluated prior to
closure of the defect.
Several studies tried to identify patients at high risk of
mortality and morbidity for shunt closure. Pulmonary vascular
resistance (PVR) of more than 15 Woods unit was found to be
a strong mortality predictor by Steele and colleagues. Patients
with less severe hypertension (PVR of 79 Woods units)
improved after surgery. General consensus is to avoid closure
in patients with PVR more than 8 Woods units or if pulmonary
arterial pressure exceeds 2/3 systemic pressure, net right-toleft shunt, no response to pulmonary vasodilator therapy and
failed test occlusion.20,23
Two points should be mentioned here. First: elderly patients
who develop left ventricular diastolic dysfunction as a result
of ischemic heart disease, hypertension or acquired valvular
disease are considered a high risk for closure. Elevated left
ventricular end-diastolic pressure reflected by high pulmonary
wedge pressures should be anticipated. Adequate medical
treatment prior to closure of the defect and balloon test
occlusion before closing the defect are advised.
Second: a rare condition is called orthodeoxia-platypnea.
In this condition, despite the finding of cyanosis, closure of the
defect is considered curative. There are different hypotheses
technique
This is achieved by direct closure of the ASD using pericardial
or Dacron patches and sometimes stitch closure for PFO.
Associated anomalies should be identified prior to surgery:
cleft in the mitral valve in septum primum defects should
be repaired at the same time, while in sinus venosus defects,
identification of right upper/middle pulmonary venous
drainage should be taken into consideration during surgery.
Transesophageal echocardiography in the operating room
is mandatory to identify any residual shunt after closure and
to rule out any AV regurgitation prior to closure of the chest.
Minimally invasive surgeries nowadays avoid midsternotomy approach using different less extensive incisions for
cosmetic purposes.
Follow-up and outcome

Over the past decades several studies looked at the outcome
of patients with ASDs following surgical repair.One of the
major findings was the excellent outcome and low operative
mortality especially at a younger age ranging between 0 to 1
percent. Older patients (> 60 years) have, however, a higher
risk.26
Operative morbidities include residual shunt due to
incomplete closure of the defect. Postpericardiotomy
syndrome resulting in pericardial and pleural effusion.27 New
onset arrhythmia after surgical closure, stroke and acute left
heart failure in earlier series especially at old age.26,27 Sinus
venosus defect repair can be complicated by pulmonary
venous or SVC obstruction. Sinus node dysfunction and AV
conduction delay requiring permanent pacemaker have been
seen more in patients following sinus venosus repair (6%).28,29
Childhood long-term outcome studies demonstrated no
cardiovascular mortality, heart failure, stroke or pulmonary
hypertension in any patient for more than 25 years of followup. Risk of development of atrial arrhythmias was only 8
percent. Long-term survival after surgical closure in childhood
showed that no change from the general population.30
261
Shunt DefectS
This has not been the case in adult outcome series that
showed higher incidences of adverse outcomes and decreased
life expectancy. Murphy et al31 in a follow-up study of
patients operated between 1956 to 1960 showed that survival
among patients younger than 24 years were no different from
rates among controls. Patients over 41 years of age, on the
other hand, survival rates were significantly less. Independent
predictors of long-term survival according to multivariate
analysis were age at operation and systolic pressure in the
main pulmonary artery before operation. Late heart failure,
stroke and atrial fibrillation were significantly more frequent
in older patients thus requiring close follow-up.31
Comparison between medical and surgical treatment in
older individuals showed repeatedly better outcome in the
surgical arm of these studies improving survival, decreasing
morbidity (recurrent pulmonary infection), increasing exercise
tolerance in this group of patients.17,32
This however has not been proven in preventing atrial
arrhythmias. In fact, Berger et al19 showed atrial arrhythmias
persisted in more than 48 percent after surgery in patients older
than 60 years which did not show significant improvement
from incidence prior to surgery. They concluded that in this
group of high-risk patients (with atrial fibrillation) surgical
atrial closure should be combined with Cox-maze procedure.
Pulmonary vascular disease had been proven to be a strong
predictor of poor outcome after surgery. PVR higher than 15
Wood units was shown to be associated with high mortality rate.
Defects in patients with high PVR but less than 15 Wood units
were partially closed, leaving a small residual shunt that allows
decompression of the left atrium. Regression in symptoms and
262
lower mortality rate were noticed postoperatively in this group

although they usually have an expected difficult immediate
postoperative course.20
trAnScAtHEtEr cLoSurE oF AtriAL

SEPtAL DEFEctS
History
It has been more than 35 years since King and Mills33 first
described their double umbrella device closure of an ASD
in 1976. Since then, major advancements in techniques,
devices and outcomes were achieved. Currently, there are two
devices approved for use by the United States Food and Drug
Administration (FDA) are the Amplatzer Septal Occluder
device (St, Jude Medical, Plymouth, MN) (Figures 9A and
B) and the Gore Helex Septal Occluder device (WL Gore and
Associates, Flagstaff, AZ), (Figures 10A and B).
It was not until 2002 when the non-randomized multicenter
study that compared percutaneous approach using Amplatzer
device in more than 400 patients to surgical approach
was reported. It demonstrated similar success rates, lower
complication rate and shorter hospital stay in the device
closure group versus the surgical repair group.34
Nowadays, transcatheter closure of septum secundum atrial
defects and PFO is the mainstay of treatment for patients with
suitable defects. Nevertheless, there are defects that are nonamenable to this approach in which surgery should be the
appropriate option for closure. This includes, primum septal
defects, sinus venosus and coronary sinus defects and defects
figures 9a and B: Amplatzer septal occluder device (AGA Medical Corporation, Plymouth, MN). The waist of the device (that correlates
with the defect size) can be seen B. The device is made of Nitinol, an alloy of nickel and titanium
B
figures 10a and B: Helex septal occluder device (WL Gore and
Associates, Flagstaff, AZ). The device can be seen mounted on the
preassembled delivery system. It is made of ePTFE patch material
supported by a single nitinol wire frame
with associated anomalous pulmonary venous drainage.

Secundum atrial defects that are larger than 38 mm in diameter
or defects that have insufficient rims (< 5 mm) are also not
suitable for transcatheter device closure.
Choice of the ASD that is amenable to transcatheter device
closure is a crucial step as is careful patient selection. High-risk
patients include extremes of age: infants due to the need of large
sheath size and risk of vessel injury and elderly patients with
left ventricular dysfunction. Other relative contraindications
include active infection, pregnancy, uncontrolled arrhythmias
or conditions where antiplatelet therapy is not tolerated.
18
InteratrIal DefectS
Device Experience (MAUDE)/FDA have shown that mortality

with the Amplatzer device of less than 0.1 percent and rescue
operation was needed in 0.83 percent.35
The more recently approved Helex septal occluder device is
used for percutaneous closure of smaller ASDs and PFO showed
similar success in a multicenter study in 2007 demonstrating low
complication rate mainly device embolization requiring catheter
retrieval (1.7%).36
Other complications of catheter-based interventions
include arrhythmias, which are usually transient in the first
3 months. A recent long-term follow-up study showed an
incidence of 7 percent of documented arrhythmias in patients
who received the Amplatzer septal occluder between 1998
to 2002. Such arrhythmias included mainly supraventricular
tachycardia, atrial fibrillation and premature ventricular beats.
Rare reports of AV block have been described.37,38
Thrombus of the left atrial disc with risk of systemic
embolism has been reported. Although current devices are
less thrombogenic, antiplatelet therapy with clopidogrel and
Aspirin are used for 2 to 12 months. Post-procedure atrial
fibrillation and persistent atrial septal aneurysm had been
found as significant predictors for thrombus formation.39
Other serious complications such as occluder malposition
with impingement on surrounding structures, migration
after release, erosion to neighboring structures or cardiac
perforation are all rare incidents for which the patients are
observed for at least 24 to 48 hours after device closure.
The safe and effective nonsurgical option to close interatrial defects should be assured by proper patient selection,
continuous assessment during device closure and close
monitoring after deployment of the appropriate device.
concLuSion
Atrial septal defect is a common non-cyanotic congenital heart
disease. Although usually carries benign course in childhood,
it has significant morbidity with advancing age. Closure of
an ASD has certain indications. Safe non-surgical option via
transcatheter closure is available for certain types of defects.
Genius is one percent inspiration and ninety-nine percent
perspiration.
Aphorism
technique
Technique of percutaneous approach includes hemodynamic
and echocardiographic assessment of the defect followed by
balloon sizing of the defect. Deployment of the device under
continuous echocardiographic guidance after selecting the
appropriate type and size of the device.
Follow-up and outcome
AcknowLEDGMEntS
The authors acknowledge Dr Qi-Ling Cao and John Bokowski,
PhD, for their help in the echocardiography images in this
chapter.
rEFErEncES
Due to the relative short period, widespread use of

percutaneous approach of ASD closure follow-up data is
limited. Nevertheless, the Manufacturer and User Facility
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defect with pulmonary vascular obstructive disease: Long-term
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21. Vogel M, Berger F, Kramer A, et al. Incidence of secondary

pulmonary hypertension in adults with atrial septal or sinus
venosus defects. Heart. 1999; 82:30-33.
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HM, Dearani JA, del Nido P, Fasules JW, Graham TP, Hijazi
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SM, Halperin JL, Hunt SA, Krumholz HM, Kushner FG, Lytle
BW, Nishimura RA, Page RL, Riegel B, Tarkington LG, Yancy
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30. Roos-Hesselink JW, Meijboom FJ, Spitaels SEC. Excellent
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31. Murphy JG, Gersh BJ, McGoon MD, et al. Long-term outcome
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265
C hapter
19
Ventricular Septal Defects

Vijayalakshmi IB, Chitra Narasimhan, Prasanna Simha Mohan Rao
IntroDuCtIon
Ventricular septal defect (VSD) is a developmental defect of
the interventricular septum (IVS) wherein a communication
exists between the cavities of the two ventricles.1,2 VSD is
a common congenital cardiac anomaly, occurring in both
children and adults. It can occur in isolation or as part of more
complex defects. Isolated VSDs are the second most common
congenital cardiac defect encountered after bicuspid aortic
valves and this is also so in India.3, 4 The isolated VSDs can be
repaired surgically with an acceptable mortality rate. Recently
nonsurgical transcatheter device closure of VSD is in vogue.
Understanding the nature of the anomaly, clinical picture, the
physiologic data and the natural history of VSD is important
for planning the management strategy.
About 20 percent of VSDs are associated with almost
all forms of congenital heart disease (CHD).5,6 They occur
frequently as an integral part of other anomalies like tetralogy
of Fallot (TOF), truncus arteriosus, atrioventricular septal
defects, double-outlet right ventricle (DORV) and transposition
of great arteries (TGA) or in association with coarctation of
the aorta (COA), patent ductus arteriosus (PDA), atrial septal
defect (ASD), pulmonary stenosis (PS), etc. This chapter will
discuss only isolated VSDs.
HIStorICal reVIew
The first clinical description of VSD was made by Henri
Roger, a French pediatrician, at the age of 70 years, in 1879.1
He described the clinical and auscultatory findings of six
acyanotic patients and autopsy finding of a child with VSD.7
He described it asThere is a malformation of the heart
unaccompanied by cyanosis, in spite of the communication
between the ventricles and in spite of the free admixture
of venous and arterial blood; this malformation, which is
compatible with life and even with prolonged existence,
is simple and is not accompanied by pulmonary stenosis; it

consists in patency of the septum between the ventricles in its
upper portion. It is revealed only by auscultation and shows
itself by a physical sign with quite distinctive characteristics:
this is a loud, prolonged whirring sound; it is a single murmur,
beginning with systole and continuing in such a way as to
entirely mask the normal rhythm; its maximum intensity is not
at the apex or at the right or left side of the base, but over the
upper third of the precordial region; it is central like the septum
itself and diminishes gradually from this central point the
farther from it one listens; it is not transmitted; it corresponds
to no other sign of organic disease except the purring thrill.
An abnormal murmur, which combines these characteristics
is the pathognomonic sign of patency of the ventricular
septum. His name is remembered by two eponymous terms:
Maladie de Roger (Rogers disease), which is a congenital
asymptomatic VSD and Bruit de Roger (Rogers murmur),
which is a loud pansystolic murmur of VSD.
In 1898, Eisenmenger described a patient with VSD,
cyanosis and pulmonary hypertension (PH). This combination
of VSD, pulmonary vascular disease and cyanosis has been
termed as Eisenmenger complex. Pulmonary vascular
disease and cyanosis in combination with any other systemicto-pulmonary connection has been called Eisenmenger
syndrome.8 In 1958, Heath and Edwards described the
morphologic changes associated with pulmonary vascular
disease and their 6 categories of vascular changes have
remained the standard of comparison to the present.9 The
earliest surgical treatment of VSD was pulmonary banding10
and subsequently Lillehei et al described the first successful
surgical closure.11 The anatomic assessment of VSD has
dramatically improved after the advent of 2D echocardiography
in 1979. Since the first successful percutaneous VSD device
closure in 1987 by Lock et al with the Rashkind double
umbrella,12 there have been several reports of transcatheter
closure of the VSD using different devices.13,14 Amplatzer

table 1
Aneuploid syndromes associated with ventricular septal defect
Syndrome
Del 4q, 21, 32
Del 5p
Ventricular septal defects occur either as an isolated defect

or as a component of a more complex lesion. It occurs in 50
percent of all children with CHD and in 20 to 30 percent as
an isolated lesion.22,23 The incidence rates, however, are not
related significantly to race, sex, maternal age, birth order or
socioeconomic status. They are more common in premature
infants and those born with low weight.24 The advent of
transthoracic 2D echocardiography (TTE) has demonstrated
the higher incidence of VSDs, especially the small muscular
type in newborns to be 5 to 50 cases per every 1,000 live
births.25 The lower prevalence in adults is due to spontaneous
closure of many defects. VSDs are slightly more common in
females (56%).26 The doubly committed subarterial or juxtaarterial defect is more common, about 30 percent in Asian
populations, whereas muscular and multiple defects are less
common in the same population.27
60
3060
Type of CCVM
VSD, ASD
VSD
Trisomy 13
80
ASD, VSD, TOF
Trisomy 18
(Edwards syndrome)
100
VSD, TOF,
DORV
4050
VSD, AVCD
Trisomy 21
(Down syndrome)
Del 22q 11
(DiGeorge syndrome)
epIDemIology
CCVM
(%)
50
Truncus
arteriosus, TOF,
VSD, interrupted
aortic arch
19
ventricular septal defects
muscular VSD device was employed by Thonopoulos et al

and Tofeig et al to close muscular VSDs.15,16 Catheter closure
of perimembranous VSD using Amplatzer membranous VSD
occluder was initially reported by Hijazi et al.17 CardioSEAL/
STARFlex devices were used by Marshall and Perry18 and
Lee et al19 used the Nit-occlud device to close the VSDs.
There are case reports of the use of Amplatzer duct occluder
II for closure of VSDs.20 The Amplatzer perimembranous
ventricular septal occluder device (pmVSO2 device) is under
trial.21 In recent years, with the advent of new devices and
refinement of techniques, a number of reports on percutaneous
closure of VSD have been published with encouraging results.
CCVM = Congenital cardiovascular malformation; AVCD = Atrioventricular

canal defect; ASD = Atrial septal defect; DORV = Double-outlet right
ventricle; TOF = Tetralogy of Fallot; VSD = Ventricular septal defect
InHerItanCe
Siblings of patients with VSD have three times the incidence
of VSD, as compared to the general population.32 VSDs are
found in 3.3 percent of the first degree relatives33 and in nearly
30 to 60 percent of siblings of the index case.34 Maternal
VSDs have a recurrence risk of 6 to 10 percent, whereas
with paternal VSDs, the recurrence risk in the offspring is 2
percent.35 VSDs have been reported in identical twins, but the
frequency of discordance is high.32
embryology
etIology
Congenital heart defects are believed to be multifactorial, in
which the interaction between hereditary predisposition and
environmental influences result in the defect.3 The definitive
cause of any individual CHD is rarely determined. Genetic
risk factors include the presence of certain chromosomal
syndromes like Trisomy 13, Trisomy 18, Trisomy 21,
Del 22q 11, Del 4q, 21, 32 and Del 5p.28 Further studies
have shown an interaction between TBX5, GATA4 and
NKX2.5, suggesting that transcriptional activation may
be responsible for septal defects.29 Aneuploid syndromes
associated with VSD are shown in Table 1.3 In the majority
of the patients (95%) with an isolated VSD, the defect is
not associated with a chromosomal abnormality and the
cause is unknown.
The VSDs may be associated with exposure to certain
environmental factors during pregnancy, especially within the
first 8 weeks of gestation. Some of the environmental factors
are maternal phenylketonuria, diabetes or exposure to febrile
illness, especially rubella, influenza or teratogens like alcohol,
cocaine, marijuana, ibuprofen, anticonvulsants (hydantoin,
carbamazepine) or organic solvents.30,31
The normal development of the IVS is a complex process and

depends upon the endocardial cushions, conotruncal ridges,
growth of tissues at the crest of the IVS and the muscular
septum. The VSDs result from a deficiency of growth or a
failure of alignment or fusion of the component parts of the
IVS beyond the first 7 weeks of intrauterine life. The reason
for this delayed or incomplete closure is still unknown. The
membranous VSD occurs as a result of failure of fusion of the
endocardial cushions, the conotruncal ridges and the muscular
septum. The outlet VSD may occur because of failure of
fusion of the conal septum. The inlet VSD may occur due to
the incomplete fusion of the right endocardial cushion with
the muscular septum. Muscular defects may occur because
of lack of merging of the walls of the trabecular septum or
excessive resorption of muscular tissue during ventricular
growth and remodeling.36 The fetal circulation is not altered
significantly in uncomplicated VSDs.37
anatomy
The IVS is a complex curvilinear, non-planar intracardiac
partition. Soto et al divided IVS into four regions by its
267
shunt defects
landmarks on its right ventricular aspect.38 The normal

ventricular septum is mostly muscular with a small fibrous
portion, the membranous septum.
The four regions are the inlet septum, trabecular septum,
outlet or infundibular septum (together making up the
muscular septum), and the membranous septum.
The inlet septum is smooth walled and extends from the
septal attachment of the tricuspid valve (TV) to the distal
attachments of the tricuspid tensor apparatus. The inlet septum
separates the septal cusps of the mitral and tricuspid valves.
The apical trabecular zone separates the coarse trabeculations
of the right ventricular from the fine ones seen in the left
ventricular apical septum. The trabecular portion separates
the body and apices of the two ventricles. It extends from the
attachments of the tricuspid leaflets outward to the apex and
upwards to the crista supraventricularis. The smooth-walled
outlet or infundibular septum, extends from the crista to the
pulmonary valve. The outlet septum separates the outlets
of the ventricles. The supraventricular crest is an extensive
ledge in the muscular zone in the normal heart that separates
the tricuspid from the pulmonary valves and the pulmonary
from the aortic valves. The three muscular components of
the ventricular septum fan out from the small membranous
septum, which lies under the commissure of the anterior
and the septal tricuspid leaflets and below the right and the
noncoronary cusps of the aortic valve. The membranous
septum is further divided by the septal leaflet of the TV into
atrioventricular and interventricular components.38 Schematic
diagram of the location of various types of VSD is given in
Figure 1.
The four main anatomic components that make up the
normal IVS as described by Van Praagh et al39 are as follows:
1. Atrioventricular canal septum (inlet septum).
2. Muscular septum or ventricular sinus septum (trabecular or
muscular).
3. Parietal band or distal conal septum (outlet septum).

4. Septal band or proximal conal septum (conoventricular
septum).
The atrioventricular node located in the triangle of Koch
(formed by the tendon of Todaro, the coronary sinus ostium
and the septal leaflet of the TV) gives rise to the atrioventricular
bundle (Bundle of His).40 The atrioventricular septum is itself
pierced by the atrioventricular bundle as it passes from the
apex of the triangle of Koch to reach the crest of the muscular
septum.41 At this point, the bundle is on the posteroinferior
margin of the membranous septum, which lies just posterior
to the commissure of the septal and anterior leaflets of the
TV. The right bundle branch traverses along the anteroinferior
border of the membranous septum to then enter the right
ventricle (RV). Sometimes in inlet defects, the bundle of His
passes anterosuperiorly to the defect.
ClaSSIfICatIon
Many classifications of VSDs have been proposed. Soto et al
classified VSDs depending on their location in the IVS as seen
from the right ventricular side.38 They are divided into four
types of defects: 1. Perimembranous, 2. Muscular, 3. Outlet
and 4. Inlet.
Anderson et al42 classified the VSDs according to the
relation of the defect to the atrioventricular conduction axis,
i.e.
i. The membranous septum.
ii. The relation of the defect to the atrioventricular valves.
iii. The relation of the defect to the arterial valves.
iv. The position of the defect within the ventricular septum,
i.e. the inlet, trabecular or outlet part of the septum.
They have classified VSDs into four types: perimembranous, muscular defects, doubly committed juxta-arterial and
juxtatricuspid (non-perimembranous) defects.
anatomical Classification
268
figure 1: Schematic diagram of the anatomical position of various

types of ventricular septal defects. Source: The Lancet, 377 (9771),
Penny DJ, Vick GW 3rd; Ventricular Septal defect 1103-12 Copyright
(2011), with permission from Elsevier
I. Perimembranous defects (infracristal, subaortic, membranous, conoventricular): They are the most common
and account for 80 percent of all VSDs. These defects
involve the membranous septum with extension into the
adjacent inlet, outlet or muscular septum. They lie in
the outflow tract of the left ventricle (LV), immediately
beneath the aortic valve. There is fibrous continuity between the aortic and tricuspid valves. The conduction
bundle is always found in the posteroinferior margin of
the defect. In perimembranous VSD, rarely LV to right
atrium (RA) shunt (Gerbode defect) may be seen. Van
Praaghs classification considers that perimembranous
is a misnomer for this VSD as peri is the Greek prefix meaning around. They suggest that the appropriate
terminology should be paramembranous VSD as the
defect lies beside the membranous septum.39
Kirklins Classification47
Type I:
VSDs are termed as supracristal, infundibular,

juxtaarterial or conal. This defect lies caudal to the
pulmonary valve in the infundibular portion of the
right ventricular outflow tract.
Type II: VSDs are termed as perimembranous or paramembranous and are located adjacent to the membranous
portion of the ventricular septum and the septal leaflet of the TV.
Type III: VSDs are termed as inlet or atrioventricular canal
VSDs and are located posteriorly at the inlet portion
of the right ventricular septum (corresponding to the
outlet portion of the left ventricular septum).
Type IV: VSDs are muscular defects and include a variety
of single and multiple defects in the muscular
septum.
19
In paramembranous defect, there can be a variable degree of anterior malalignment between the infundibular septum and the anterior ventricular septum such
that the aortic valve appears to override the defect.38
Posterior or leftward malalignment also occurs, producing subaortic stenosis. Anterior malalignment of the
conal septum is seen in TOF and posterior malalignment
is seen in interrupted aortic arch (IAA).
II. Muscular defects (trabecular): They account for 5 to 20
percent of all the VSDs. They are entirely bounded by the
muscular septum and are often multiple, when viewed
from the right side.
Kirklin et al43 further subclassified them depending on
their location in the muscular septum as: (a) anterior, (b)
midmuscular, (c) apical, (d) posterior. An anterior or
marginal muscular defect is anterior to the septal band.
A central midmuscular defect is posterior to the septal
band. Apical defects are inferior to the moderator band
and the posterior defects are beneath the septal leaflet of
the TV.
When multiple muscular defects are seen, it is often referred to as Swiss cheese type of VSDs. Some believe
that a Swiss cheese septum is actually an entity distinct
from multiple VSDs. The morphology of the Swiss
cheese septum is believed to originate from septal noncompaction during embryologic development. Thus,
unlike a group of muscular VSDs, Swiss cheese defects
cannot close spontaneously.42,44,45
III. Subarterial or Outlet defects (supracristal, conal,
infundibular, subpulmonary, doubly committed
subarterial, doubly committed juxta-arterial): They
occur in 5 to 7 percent of VSDs. They are situated just
beneath the pulmonary valve and communicate with the
right ventricular outflow tract above the supraventricular
crest. The incidence is as high as 30 percent in Asian
populations.27 This defect frequently leads to prolapse
of the right coronary cusp or less likely the noncoronary
cusp of the aortic valve causing aortic regurgitation
(AR). In the perimembranous outlet defects there may be
considerable degree of malalignment of the ventricular
with the infundibular septum.46 The conduction system
is remote to the outlet defects.
IV. Inlet defects (canal type, endocardial cushion type,
atrioventricular septum type, juxtatricuspid): These
VSDs account for about 8 percent of all the VSDs.
They are located posteriorly and inferior to the
membranous septum. A muscular inlet defect can be
remote or have the conduction system bordering the
defect superiorly. In the perimembranous inlet defects
there may be some degree of malalignment of the
ventricular and the atrial septum.46 There can then
be overriding or straddling of the tricuspid or mitral
valve.
HemoDynamICS
The most important variables that determine the hemodynamics in a patient with VSD are the size of the VSD,
pulmonary vascular resistance (PVR), systemic vascular
resistance (SVR) and the presence of associated defects such as
ASD, PDA, right and left ventricular outflow tract obstruction
and arch obstruction. The location of the VSD is irrelevant.
The pathophysiologic effects of VSD are secondary to the left
to right shunt and changes in the pulmonary vasculature. A left
to right shunt at the ventricular level has three hemodynamic
consequences:
1. Increased LV volume load.
2. Excessive pulmonary blood flow (PBF).
3. Reduced systemic cardiac output.48
As cardiac output decreases, compensatory mechanisms
are stimulated to maintain adequate organ perfusion. These
mechanisms include increased catecholamine secretion and salt
and water retention by means of the renin-angiotensin system.
The ventricular level shunts occur primarily during
ventricular systole, in contrast to atrial level shunts, which
occur primarily during ventricular diastole and the arterial
level shunts which typically occur both during systole and
diastole. The left to right shunting across the VSD occurs
mainly during systole, and is determined by the relative
pulmonary and systemic vascular resistances. The shunting
is increased during the early phase of contraction, as LV is
activated before RV and the LV pressure rises faster than the
RV pressure. Shunting continues from this early phase of
systole till the semilunar valves open. During the early stages
of diastole (isovolumic relaxation), the LV relaxes more
quickly than RV, resulting in a transient pressure gradient
favouring a right to left shunt across a moderate or a large
VSD. The right to left shunt across the VSD is significant with
marked elevation of PVR.
269
shunt defects
VSDs may be classified into small, moderate and large

based on the size of the defect and also based on the
hemodynamics.2,48,49
Small or restrictive Defects (maladie de roger)

The small VSD is less than one-third of the size of the aortic root
or the orifical area is <0.5 cm2/m2. It is also called restrictive
as the size of the defect limits the left to right shunt and there
is a significant pressure gradient between the LV and RV. The
pulmonary/aortic systolic pressure ratio is <0.3 with a small
shunt (Qp/Qs < 1.4:1).The degree of LV volume overload is
minimal. There is no tendency to develop increased PVR. But
they can develop AR or bacterial endocarditis.
moderate or moderately restrictive Defects

The VSD size is said to be moderately restrictive, when it is 1/3
2/3 of the size of the aortic root or the orifical area is > 0.5 to 1
cm2/m2. They are large enough to permit a moderate shunt, yet
small enough to offer some resistance to flow. The pulmonary/
aortic systolic pressure ratio is < 0.66 with a moderate shunt
(Qp/Qs > 1.42.2:1). The peak systolic pressure difference
is 20 mm Hg between the two ventricles. They develop
moderate left to right shunt leading to volume overload of the
left sided cardiac chambers causing LV and left atrium (LA)
dilatation and hypertrophy. The RV is not dilated and RV and
pulmonary artery pressures may remain low or be moderately
elevated. The PVR is low, but variable and rarely progresses
to PH.
large or nonrestrictive
270
The VSD is large, when it measures more than 2/3 of the size
of the aortic root or the orifical area is 1 cm2/m2. It is also
called nonrestrictive VSD as there is no resistance to flow
across the defect. The pressures in the ventricles are equal
and they function as a common pumping chamber with two
outlets. The degree of left to right shunt is dependent on the
relationship between the pulmonary and systemic vascular
resistance. The pulmonary/aortic systolic pressure ratio is
>0.66 with a large shunt (Qp/Qs > 2.2:1).
In infants with moderate or large VSDs the decline in
the PVR may be delayed for several months. At about 4 to
6 weeks of life, the large left to right shunt causes increased
PBF and subsequently increases pulmonary venous return
into the LA and ultimately into the LV. This leads to dilatation
of LA and LV and increased LV end-diastolic pressure.
This is reflected in increased LA pressure and consequently
in increased pulmonary venous pressure. The pulmonary
overcirculation leads to increase in the pulmonary interstitial
fluid and in severe forms may manifest as pulmonary edema.
The RV pressure increases and this causes RV dilatation and
hypertrophy. The increased pulmonary blood flow raises
the pulmonary capillary pressure and there is elevated, but

subsystemic PVR, which is variable. Therefore, in a large VSD
both pulmonary arterial and venous pressures are elevated.
During the second year of life, the manifestations of
congestive heart failure (CHF) decreases as the pulmonary
artery pressure increases. As PVR increases and exceeds
SVR, right to left shunt occurs. Initially it is mainly during
exercise, due to the fall in SVR. Later, the right to left shunt
occurs at rest with persistent cyanosis. There is marked
fall in PBF with persistent hypoxemia. RV failure finally
supervenes.
eisenmenger VSD
A large VSD, if left untreated, can result in irreversible
damage to the pulmonary arterial tree with development
of pulmonary vascular obstructive disease (PVOD) and
Eisenmengers syndrome. The systolic pressure ratio is 1 and
Qp/Qs is less than 1 : 1, with a net right to left shunt. There
is identical RV and LV systolic pressures and suprasystemic
PVR.
ClInICal featureS
History
The clinical manifestations of isolated VSDs have a wide
spectrum, which varies depending upon the size of the defect
and the magnitude of the shunt. It may range from being
asymptomatic to severe heart failure. The signs and symptoms
begin to develop, when the fetal PH starts declining sufficiently
to permit left to right shunting.
The infants with large VSDs present with symptoms due to
CHF by 4 to 6 weeks, as the PVR decreases. The symptoms are
increased respiratory rate (tachypnea), chest retractions, feeding
difficulties with suck-rest-suck cycle, excessive sweating of
forehead, repeated respiratory infections and failure to thrive.
In infants with moderate VSD, the parents may observe
pulsations over the precordium or feel a thrill. Child may have
mild tachypnea, cough during feeding and fatigue. Sweating
especially during feeding is frequent in infants below 6
months. They may also present with lack of adequate growth
and with one or more episodes of pneumonia. Older children
may present with effort intolerance and fatigue.
The children with small VSDs are asymptomatic and may
be detected, because of the murmur on a routine health checkup. Older asymptomatic children may be detected during
routine school health check-up.
The older children seen for the first time may be referred
by pediatricians for bacterial endocarditis, CHF, and rarely
arrhythmia. Patients with large VSD with high PVR may
not have much symptoms at rest, but with exercise may have
symptoms, which include exertional dyspnea, cyanosis, chest
pain, syncope and hemoptysis.50
physical examination
Arterial Pulse
Pulse is normal in small VSDs. In moderate VSDs, the pulse is
brisk due to the vigorous LV ejection. In nonrestrictive defects
with large left to right shunts and CHF there may be low
volume pulse. The pulse is normal in Eisenmenger syndrome,
as the systemic stroke volume is maintained.
Jugular Venous Pulse

The jugular venous pulse (JVP) is not raised in VSD. So much
so if JVP is raised it indicates intact IVS and clinically rules
out VSD. In Eisenmengers syndrome it is usually normal or
with a small dominant a wave.
natural History
In moderate to large VSDs, precordial pulsations are visible

due to LV volume overload. The apical impulse is LV type,
hyperdynamic, displaced downward and outwards. In small
and moderate VSDs a precordial thrill is best felt in the third
and fourth intercostal space (ICS) at the left sternal border
(LSB). In cases with subarterial VSD the thrill maybe palpated
in the second or first ICS and may radiate upwards to the left
into the suprasternal notch and into left side of neck.51 In large
VSDs with high PVR a left parasternal lift may be present. In
patients with severe PH, there is a left parasternal heave with
a palpable P2 in the left second ICS.
The natural history of the patient with VSD has a wide spectrum,
ranging from spontaneous closure to CHF to death in early
infancy. The natural history is influenced by its position, size,
number of defects and association of other malformations.
Small defects remain asymptomatic but are predisposed to
endocarditis and AR. Large defects often develop LV failure,
PH (Eisenmenger syndrome) and eventually RV failure. Thus,
in the natural history of VSDs there may be:
1. Spontaneous diminution in size or closure.
2. Development of right ventricular outflow tract obstruction
(Gasuls effect).
3. Development of AR.
4. Development of left ventricular outflow tract obstruction.
5. Development of pulmonary vascular obstructive disease.
6. Infective endocarditis.
With the advent of surgical closure and nonsurgical device
closure, the natural history of VSD has altered dramatically.
Auscultation
SpontaneouS CloSure of VSD
The first heart sound is normal. The second heart sound (S2)
is normal with normal split. Sometimes A2 may be obscured
by the long murmur in small VSDs. Pulmonary component is
normal or mildly increased in moderate VSDs. In large VSDs,
the pulmonary component of the second sound is usually loud
with a narrow split. LV S3 can be prominent in large shunts or
RV S3 may be present in large VSD with severe PH.
The murmur in small VSDs is grade 4/6, harsh long systolic,
crescendo-decrescendo best heard along the lower LSB. In very
small apical or muscular defects the murmur is soft, grade 2/6 or
Henri Roger did not anticipate spontaneous closure of

VSD. But in 1918, in the reports the possibility of a loud
congenital heart murmur disappearing when a child grows
up52 and can the clinical manifestation of congenital heart
disease disappear with the general growth and development
of the patient?53 speculated spontaneous closure of VSD.
The impact of these two reports are so dramatic and
vociferous that even after decades many clinicians advice
the parents Do not worry, the hole will close. As a
result many children grow up and develop Eisenmengers
Precordial Movement and Palpation
19
The infants with large shunts with CHF are malnourished with
poor growth and development. These infants are tachypneic
with chest retractions and there is precordial bulge with
bilateral Harrison sulcus. If CHF is severe or if there is added
pneumonia, there may be retractions and grunting. Infants
with nonrestrictive VSDs with balanced shunts may become
cyanotic on crying or exercise. Cyanosis and clubbing are
seen in adolescent and adults with large VSD with high
PVR/Eisenmenger syndrome. Peripheral edema is unusual in
infants. The VSDs can be associated with various syndromes
like Trisomy 18, 13, 21, Del 22q 11, Del 4q, 21, 32 and Del 5p.
less, as the defect practically closes during systole. The murmur

in moderately large defects are long, low pitched decrescendo
murmur best heard in LSB. The systolic mumurs in outlet
defects are heard in the second ICS and may radiate upwards
to the left into the suprasternal notch and into the left side of
neck. In outlet defects, the holosystolic murmur is crescendo or
cresendo-decresendo. When the shunt is large (Qp/Qs > 2:1),
a short mid-diastolic murmur is heard at the apex due to the
increased flow across the mitral valve. The soft blowing early
diastolic decrescendo murmur in the left second and third ICS
could be due to associated AR and peripheral signs are present
if the AR is significant.
In patients with large VSDs with high PVR, the LV
precordial impulse is replaced by the RV impulse. There is a
very short soft decrescendo murmur or rarely no murmur in
balanced shunts. The ejection click may be heard due to the
flow in the dilated hypertensive pulmonary trunk. Second
sound is quite loud, palpable with narrow splitting. The third
sound of RV origin may be present along the LSB. There is no
diastolic rumble at apex, but a short early diastolic murmur of
pulmonary regurgitation (Graham Steell murmur) may be heard
in the left upper parasternal area.
271
shunt defects
syndrome. Hence it is very important to know, when and

how the VSDs close spontaneously.
Spontaneous closure occurs frequently in children and
the process continues through adolescence and adulthood.54
The incidence of spontaneous closure in perimembranous
and muscular VSDs is high, while it is low in outlet defects
and inlet defects do not close. Swiss cheese muscular defects
do not close spontaneously. Studies have documented that
the spontaneous closure within the first year is significantly
higher for muscular than for perimembranous defects.55,56
In patients with restrictive VSDs followed up from birth,
there is a higher incidence of spontaneous closure (50-75
percent).2 The incidence of spontaneous closure in moderate
and large VSDs is only 5 to 10 percent. Thus, most defects
which close do so in the first year of life and approximately
60 percent close before 3 years and 90 percent by 8 years of
age.24,57,58 Therefore, blanket advice by the pediatrician that
VSD will close should be avoided, unless the size and site
of VSD is assessed properly. Small perimembranous VSD
can close by various methods:
1. The adherence of the septal leaflet of TV to the IVS causing
an aneurysm-like pouch. This can partially or completely
close the defect, but this is at the cost of causing tricuspid
regurgitation (TR).
2. The ingrowth of fibrous tissue with endocardial proliferation
causing septal aneurysm (Figure 2).
3. Prolapse of the aortic cusp especially the noncoronary or
the right coronary cusp, through the defect can close the
VSD at the cost of causing AR (Figure 3).
4. Growth and hypertrophy of the muscular portion of the
septum around the defect.
5. The vegetation caused by bacterial endocarditis on the RV
side of the VSD, but this is at the cost of infection (Figure 4).
rIgHt VentrICular outflow obStruCtIon

Right ventricular outflow obstruction occurs secondary to VSD
in 3 to 7 percent.59,60 Gasul et al61 were the first to suggest that
large VSD can over a variable period develop hypertrophy of
the crista supraventricularis leading to significant infundibular
obstruction. This is seen particularly with perimembranous
trabecular defects. There may be no clinical evidence of the
infundibular stenosis in many infants, but it can be documented
on catheterization and on echocardiography. The left to right
shunt may decrease with increasing stenosis and in severe
stenosis may become right to left. Cyanosis is initially seen
with exercise and is intermittent and later becomes persistent.
The development of infundibular hypertrophy is one of the
factors that may account for decrease in the symptoms of
cardiac failure in an infant with a large VSD.
figure 2: Transthoracic echocardiography in apical fourchamber view shows large subaortic VSD (12 mm) with septal
aneurysm with a 6 mm opening and a small subaortic membrane.
LA = Left atrium; LV = Left ventricle; RA = Right atrium; RV = Right
ventricle
figure 3: Transthoracic echocardiography in parasternal long axis

view shows small ventricular septal defect with cusp prolapse and
severe aortic regurgitation. Ao = Aorta; LA = Left atrium; LV = Left
ventricle
aortIC regurgItatIon
272
The incidence of aortic cuspal prolapse in outlet VSDs has

been shown to be as high as 73%. They can progress to AR
figure 4: Transthoracic echocardiography in parasternal long axis

view shows large vegetation on the right ventricular (RV) side literally
closing the small VSD. Ao = Aorta; LA = Left atrium; LV = Left ventricle.
19
figures 5a to c: Schematic representation of the movement of the aortic cusp during systole and diastole with prolapse and noncoaptation of
the cusp causing aortic regurgitation (AR). CC = Coronary cusp; IVS = Interventricular septum; LV = Left ventricle; PA = Pulmonary artery; RV =
Right ventricle; VSD = Ventricular septal defect;
in 5278% of the patients. In perimembranous VSDs, aortic

cuspal prolapse has been shown to be 14% with progression
to AR in 6%.62 In infancy and early childhood only aortic cusp
prolapse without AR may be present, but progressive AR may
develop. The cause of the aortic cusp prolapse and AR in the
doubly committed subarterial VSD is due to the unsupported
right coronary cusp with the combined Venturi effect produced
by the VSD jet. In early systole, blood is ejected from the
LV and is also shunted through the VSD. The anatomically
unsupported coronary cusp and aortic sinus are driven into the
RV due to the Venturi effect. The Venturi effect is caused by
the high velocity jet passing through the small VSD causing
negative pressure. In diastole the intra-aortic pressure forces
the aortic valve leaflet to close, but the unsupported cusp
(right or noncoronary) is pushed down into the left ventricular
outflow tract away from the opposed coronary cusp, resulting
in AR (Figures 5A to C).63 In perimembranous defects, the
AR is more due to the prolapse of the noncoronary cusp. The
AR is mainly as a result of the structural abnormality due to
the maldevelopment of the aortic commissure (between noncoronary and right cusp) and is aggravated by the Venturi
effect of the VSD jet.64,65 Occasionally, the deformity of the
aortic cusps themselves can cause the AR, this is mostly seen
with perimembranous defects.
Subaortic Stenosis
Patients with membranous VSDs can occasionally develop
discrete fibrous or fibromuscular subaortic stenosis, which is
generally progressive and there is potential for damage to the
aortic valve resulting in AR.
postnatal fall, but there is a small risk of increase, usually

beyond 20 years of age. In patients with pulmonary artery
systolic pressure >50 percent of the systemic arterial systolic
pressure, there is significant risk for the development of
pulmonary vascular changes.23 Measured PVR falls to high
normal levels in infancy and gradually rises in the ensuing years
if the defect does not become smaller. The risk of development
of permanent pulmonary vascular disease is very rare before
the first year of life.66,67 Hence, prompt diagnosis and closure
of these defects at least prior to 18 months of age is likely to
reduce the incidence of development of pulmonary vascular
disease. If untreated these large or non-restrictive VSDs will
have a progressive rise in pulmonary artery pressure and a fall
in left to right shunting. In turn, eventually this leads to higher
PVR and to Eisenmenger syndrome.
InfeCtIVe enDoCarDItIS
Infective endocarditis (IE) is an uncommon risk occurring in
<1 to 3 percent of patients with VSD.67,68 A small perimembranous VSD that does not close spontaneously is
generally associated with a good prognosis, but is at risk for
development of IE. The vegetation is usually located on the
septal tricuspid leaflet at the site of impact of the jet. In muscular
VSDs the incidence of IE is low, as the jet is dispersed in the
RV cavity. The site of the vegetation can occasionally be on
the aneurysm of the ventricular septum. Rarely, an acquired
left ventricular to right atrial shunt, Gerbode defect, can occur
due to the perforation of the septal tricuspid leaflet secondary
to endocarditis.
gerboDe DefeCt
pulmonary Vascular obstructive Disease

Pulmonary vascular obstructive disease may develop in 10
percent of the large VSDs. In patients with pulmonary artery
and RV systolic pressure < 50 percent of the systemic arterial
systolic pressure there is moderate left to right shunt with
possible CHF. The PVR does not increase after the initial
A Gerbode defect is a rare type of VSD communicating

between the LV and RA. The LVRA communications were
first described in the 19th century by Thurman.69 It was not
until 1958, however, that interest in this lesion was renewed
following the publication by Gerbode et al. of a series of
five patients who underwent successful surgical repair.70
273
shunt defects
274
The defect is usually congenital, but rarely is acquired. They

account for approximately 0.08% of all congenital cardiac
anomalies.71 Associated abnormalities occur in about 1/3
of cases, of which ASD is the most common.72 An acquired
Gerbode defect has been described following ventricular
septal perforation in the setting of bacterial endocarditis,73
trauma,74 myocardial infarction,75 valve replacement76 and
following surgical closure of VSD.77
The Gerbode defects result from a defect in the
membranous septum. The TV is normally more apically
displaced than the mitral valve. Riemenschneider and Moss72
classified LVRA communications into supravalvular
and infravalvular types (Figure 6). It was based on the
insertion of the septal leaflet of the TV, which divides the
membranous septum into atrioventricular (supravalvular)
and interventricular (infravalvular) portions. Sakakibara
and Konno have classified the LA-RA communications as
Types I, II and III.78 The types of Gerbode defects are:
1. The supravalvular defect, which accounts for 1/3, occurs
in the atrioventricular septum. The shunt occurs between
the LV and RA above the septal leaflet of the TV, which
remains intact. It is also called as direct type or Type I. It is
the less common form and is usually acquired, more often
due to IE.
2. The more common infravalvular defect, which accounts
for the remaining 2/3, occurs in the interventricular
membranous septum. This shunt produces a communication
between the two ventricles and the shunted blood entering
the RV is in turn diverted to the RA through associated
defects in the TV. There may be a variety of forms of
which septal leaflet perforation(s) are the most common.
This defect is found inferior to the insertion of the TV and
is also called as indirect type or Type II.
figure 6: Schematic diagram showing the anatomic position of

the Gerbode defects. A. Direct or supravalvular type B. Indirect or
infravalvular type. The combined type is a combination of A and B.
3. The third is the combined supravalvular and infravalvular

defect or also called as Type III.
The physiological consequences of the Gerbode defects
depends upon the magnitude of the shunt which is dependent
on the size of the defect and PVR.79 The shunting from the
LV to RA is predominantly systolic due to the large systolic
gradient between these chambers. The small gradient which
exists during diastole produces negligible shunting. Smaller
defects result in small size shunts and they can remain
clinically silent. In the presence of large defect, the entire shunt
flow is returned to both ventricles during diastole, causing
biventricular volume overload and enlargement of all four
chambers. This is contrary to VSDs, where only LV volume
overload and in ASDs where RV volume overload occurs.73
Significant PH can occur, but is not common.
The clinical picture of Gerbode defect varies with mixed
symptoms related either to the LV to RA shunt or the underlying
etiology. In small defects, the shunt is well tolerated and there
may be no characteristic symptoms or clinical signs. These
defects can remain clinically silent. In larger defects there
may be significant symptoms like failure to thrive, or exercise
intolerance and CHF. Physical findings are similar to VSD
with a loud harsh holosystolic murmur often associated with a
thrill at the left sternal margin in the fourth or fifth intercostal
space.73
InVeStIgatIonS
electrocardiogram
Electrocardiogram (ECG) is a useful mirror of the physiologic
changes and not the anatomical location of the VSD. The
size of the VSD, degree of volume overload and PVR can
be predicted by ECG. Small VSDs have normal ECG. The
permembranous VSDs with septal aneurysm have increased
incidence of rhythm and conduction disturbances like atrial
fibrillation, flutter, paroxysmal atrial tachycardia, junctional
rhythm and complete heart block.80
Moderate VSDs have sinus rhythm, PR interval is normal
or slightly prolonged. The axis is usually normal. In about
8 percent of patients, the QRS axis is leftward, superior
and counter clockwise, as in endocardial cushion defects,
regardless of size.81 Inlet VSDs have left axis deviation (LAD),
when there is a component of atrioventricular septal defect.2
In multiple VSDs, 40 percent can have LAD. There can be
broad notched left atrial P waves in L1 and L2 with broad P
terminal force in V1. There is varying degrees of LVH. The tall
R waves may be associated with tall, peaked T waves in L2, L3
and aVF. The leads V5 to V6 show prominent Q waves, tall R
waves and tall, peaked T waves.
In large nonrestrictive VSDs evidence of combined
ventricular hypertrophy is common. This is seen in the mid
precordial leads as large equiphasic RS complexes (> 50 mm),
the Katz-Wachtel phenomenon (Figure 7). There is usually
19
figure 7: 12 lead ECG ( standardization) shows large equiphasic RS complexes (> 50 mm),
the Katz-Wachtel phenomenon in the midprecordial leads as seen in large ventricular septal defects
figure 8: 12 lead ECG shows large equidiphasic RS complex in the midprecordial leads with tall R >18 mm
in V1 in a 12-year-old child with large ventricular septal defect and pulmonary hypertension
right axis deviation. The biventricular hypertrophy is seen as

tall R wave in lead V1, deep Q waves, tall R and peaked, tall
T waves in V5 to V6 (Figure 8). In Eisenmenger complex,
the P waves are peaked with right sided axis. There is a tall
monophasic R preceded by small q or followed by small s
wave in V1.
In Gerbode defects there is both biatrial and biventricular
enlargement. The tall peaked right atrial P wave in Lead II may
be present from infancy. There is rSr in V1, and prominent left
precordial q waves, tall R waves, upright T waves indicating
biventricular volume overload. The hallmark in the ECG is
the combination of right atrial P waves with left ventricular

hypertrophy.70,72
Chest X-ray
In 1913, Vaquez and Bordet described the radiological features
of VSD.82 Chest X-ray is practically normal in small VSDs.
Moderate VSDs show cardiac enlargement of varying severity
and increased pulmonary vascular markings (PVM) or plethora
(Figure 9A). The downward and leftward displacement of
the cardiac silhouette is due to LV enlargement. The PVMs
275
shunt defects
figures 9a to c: Chest X-ray in posteroanterior view A. shows cardiomegaly with pulmonary plethora in moderate sized ventricular septal
defect (VSD); B.shows huge cardiomegaly with dilatation of the cardiac chambers with plethora in a case of very large VSD with mild pulmonary
hypertension (PH) ; C. shows peripheral pruning with no vascularity seen in lateral 1/3 of the lung fields (multiple arrows) in a case of large VSD
with severe PH, with dilated right atrium and no cardiomegaly
are increased in both central and peripheral portions of the

lung fields. The main pulmonary artery (MPA) is prominent.
LA enlargement is better seen on lateral films. More severe
degrees of LA enlargement shows widening of the tracheal
bifurcation.
In large VSDs, there is generalized cardiac enlargement
with increased PVM (Figure 9B). There is prominence of the
MPA with RV enlargement. LV apex is displaced posteriorly
due to RVH.
In large VSDs with PH, the heart size is normal. There is
RV enlargement with the cardiac apex rotated slightly upward
and to left and posteriorly. There is marked prominence of
the MPA and its adjacent vessels with decreased pulmonary
vascularity in the outer third of the lung fields or peripheral
pruning (Figure 9 C).
The radiological finding in Gerbode defect is the
disproprionate RA enlargement. This huge RA enlargement
on the right with RV infundibulum and LV enlargement on
the left side, gives a ball shaped appearance to the cardiac
silhouette.2,72
figure 10: Transthoracic echocardiography in apical four chamber

view with color Doppler shows midmuscular ventricular septal defect
with septoparietal bands in right ventricle
echocardiography
276
Echocardiography with color Doppler flow evaluation is

widely used to diagnose and provide physiologic information
about the VSD. The color Doppler allows for as small as
2 mm VSDs, not seen on two-dimensional echocardiography,
to be identified. To assess VSD completely, one must not only
localize it, but also define its shape and dimensions (Figure 10),
which is accomplished by viewing the defect from multiple
imaging planes (Figure 11). The standard echocardiographic
views like apical four chamber view, parasternal long axis view,
parasternal short axis view, subcostal sagittal views provide
accurate information about the specific anatomical location of
the VSDs. Apical four chamber view is helpful in diagnosing
figure 11: Transthoracic echocardiography in inverted apical four

chamber view shows large perimembranous ventricular septal defect
trans VSD jet velocity is high with restrictive defects, reflecting

normal pulmonary and RV systolic pressure. The trans VSD
gradient of >64 mm of Hg indicates a restrictive VSD with
a normal pulmonary artery pressure. The RV pressure can be
also assessed from the velocity of the regurgitant tricuspid jet.
Serial echocardiograms are performed to monitor defect size
and development of PH. Also one needs to assess for potential
complications such as aortic cusp prolapse or AR.
In Gerbode defects, Dzwonczyk et al. suggested that color
flow imaging in the parasternal short-axis, apical short-axis,
and subcostal projections is useful to confirm the diagnosis
and eliminate the other possibilities like rupture of a sinus of
Valsalva aneurysm, endocardial cushion defect and tricuspid
regurgitation.83 They also indicated that a disturbed color
signal in the RA not originating from the TV and with a velocity
of 4.0 m/sec or more should suggest a LV-RA communication.
19
inlet VSDs, mid muscular and apical muscular defects.

Parasternal long axis view demonstrates the perimembranous
defects with or without formation of septal aneurysms.
Parasternal short axis view at the semilunar valve level images
defects in the outlet septum at the 1 oclock position, defects in
the subaortic septum at the 11 oclock to 12 oclock positions,
and perimembranous defects at the 10 oclock to 11 oclock
positions. In the parasternal short axis view at the level of the
mitral valve, the anterior defects of the trabecular septum are
imaged between 12 and 1 oclock position, mid muscular defects
between 9 and 12 oclock position and the inlet defects between
7 and 9 oclock position. Multiple defects and any associated
cardiovascular anomalies can be recognized (Figure 12). The
rare Gerbode defects are suspected on echocardiography when
there is an unusually dilated RA and a high Doppler gradient
between LV and RA. The TTE with color Doppler can make
out the type of defect and the presence of TR (Figure 13). The
physiologic consequences can be assessed by the amount of
LV and LA dilatation, as well as RV hypertrophy. The Doppler
method of recording the maximal velocity of the shunt allows
estimation of the systolic pressure gradient across the defect.
If this value is subtracted from the measured arterial systolic
blood pressure, it is possible to obtain an estimate of the right
ventricular pressure. This reflects the pulmonary artery systolic
pressure if there is no right ventricular outflow obstruction. The
Transesophageal and 3D Echocardiography

Transesophageal echocardiography (TEE) is occasionally
used. In the pediatric age group, it is used most often
intraoperatively to assess the completeness of the repair.
Three-dimensional echocardiography has proved accurate for
quantifying shunt and can provide accurate visualization of
defects that otherwise are difficult to evaluate by TTE.20,84,85
magnetIC reSonanCe ImagIng
figure 12: Modified two chamber view with color Doppler in postsurgical residual shunt shows hyperechogenic surgical patch with residual and Swiss cheese ventricular septal defects
figure 13: Transthoracic echocardiography in apical four chamber

view with color Doppler shows type II Gerbode defect (arrow)
Magnetic resonance imaging (MRI) is a useful adjunct tool

infrequently required for the diagnosis of VSDs. MRI is
usually used only when echocardiography is not feasible
or its findings are not diagnostic. However, because MRI
data about systemic and pulmonary flows have been wellvalidated and well-correlated with catheterization data, one
of the indications for its use is in a VSD that is judged to
be borderline during echocardiography, in terms of the level
of the left to right shunt. Phase-contrast velocity mapping
is an accurate tool for the assessment of the Qp : Qs. It also
gives an accurate account of the hearts volumes and of the
associated anomalies that are sometimes difficult to diagnose
by echocardiography.42
Cardiac Catheterization and Cineangiography

Many of the issues that required definition by catheterization
in the past can be resolved by good quality TTE studies
and catheterization is not routinely required. Some of the
indications are:86
1. If there is uncertainty regarding either defect number, size,
location and hemodynamic burden or additional lesions.
The anatomy of multiple apical VSDs is delineated
on angiogram even those defects which MRI and
echocardiography sometimes cannot identify.87
2. Interventional device closure of one or more defects.
277
shunt defects
3. To assess PVR and to study reactivity of the elevated PVR

to different pulmonary vasodilators (100% O2 and inhaled
nitric oxide), especially in older patients.
The step-up in oxygen saturation in VSD is observed in
the RV and may vary between 5 and 20 percent. Qp : Qs that
can be estimated by (aortic O2 sat - mixed venous O2 sat)/
(pulmonary venous O2 sat - pulmonary arterial O2 sat). The
calculated Qp : Qs greater than 2 : 1 is generally considered
an indication for intervention. The PVR may be calculated in
Wood units (mm Hg/L/min) as:
PVR =
Mean PA pressure Mean LA pressure

Pulmonary blood flow (Qp)
The calculated PVR is normally 1 to 2 Wood units. The

PVR is elevated if it is >3.0 Wood units. PVR/SVR (ratio
of pulmonary to systemic vascular resistance) of <0.25 is
considered operable, whereas a ratio of >0.5 is usually beyond
the operable range. Marked elevation of the PVR (>8.0 Wood
units) with a Qp : Qs <1.5 are not suitable candidates for
surgery.54
Angiography can provide information regarding the
location of VSD, number and the degree of AR. The left
ventricular angiography documents the location, size and
number of VSDs. The perimembranous, midmuscular and
apical VSDs are best seen in the left anterior oblique (LAO)
view. The subpulmonary and anterior muscular VSDs are best
seen in the right anterior oblique (RAO) view. The inlet and
posterior muscular VSDs are best seen in the hepatoclavicular
(40 LAO and 40 cranial angulation) view.
The perimembranous VSDs have been classified on
ventriculography into four types88 (Figures 14A to D).
1. Tubular type: The shunt jet is long and the diameter in the
left and right sides of the septum is the same.
2. Window-like type: The shunt jet is scattered immediately
after crossing the septum.
3. Aneurysmal type: The shunt jet has an aneurysmal shape.
4. Conical type: The shunt jet is wide on the left side of the
septum and narrow on the right side.
meDICal management
278
The children with small VSDs are asymptomatic and have

excellent long-term prognosis. The parents need to be given
reassurance, advise on subacute bacterial endocarditis prophylaxis and periodic clinical follow-up. Medical therapy is required
for patients with moderate to large VSDs till any intervention
is done to close the defect. Patients will also require nutritional
support with increased caloric density of feeds to ensure adequate weight gain.The drugs are usually a combination of
diuretics (i.e. furosemide), afterload-reducing agents angiotensin-converting enzyme (ACE) inhibitors and digoxin.89,90
Many studies have shown that the contractile function of the
LV is normal or increased, casting doubts on the usefulness of
digoxin.91,92 However, symptomatic relief has been document-
figures 14a to d: Left ventricular angiogram in the left anterior

oblique view shows the various types of perimembranous ventricular
septal defect
ed, and some experimental protocols have demonstrated acute

benefit of digoxin on hemodynamic measurements.93
1. Diuretics (e.g. furosemide) may be used to relieve
pulmonary congestion. Furosemide is usually given in a
dosage of 1 to 3 mg/kg/day in 2 or 3 divided doses.
2. Captopril is the most frequently used ACE inhibitor in
children, especially in neonates and infants where usage
of enalapril may induce renal dysfunction. The intitial
starting dose is 0.1 mg/kg/dose; it is gradually increased
to 0.5-1 mg/kg/dose three times a day. Maximum dose is
2 mg/kg/dose. Blood pressure and renal parameters should
be monitored when up titrating the dose. Enalapril is
commonly prescribed in older children. The initial dosage
is 0.1 mg/kg/24 hours divided twice daily, gradually
increasing to 0.5 mg/kg/24 hours divided into twice daily
dose.
3. Digoxin in a dose of 5 to 10 mcg/kg/day may be indicated
if diuresis and afterload reduction do not relieve symptoms
adequately.
19
approaCHeS to VentrICular
Septal DefeCt CloSure
1. Surgical closure.
2. Transcatheter techniques.
3. Hybrid approach.
Surgery for Ventricular Septal Defect

The indications for surgical closure of VSD in general are:
1. Refractory heart failure and/or failure to thrive.
2. Large defects that are unlikely to close, with or without
symptoms.
3. Development of AR or aortic cusp prolapse especially in
subpulmonic or outlet VSDs.
4. Asymptomatic older children with QP/QS greater than 2:1.
The inlet and outlet VSDs which do not close spontaneously
are indications for closure of VSDs.94 We deprecate the term
spontaneous closure of VSDs and champion the nomenclature
monitored natural closure of VSDs. The indication for
surgery at various age groups are given in Table 2.
table 2
The indications for surgery at various age groups
S. No. Age
Indication for surgery
1. < 6 months
Uncontrolled congestive heart failure,

failure to thrive
2. 624 months
Pulmonary hypertension, symptomatic
3. 25 years
Qp/Qs > 1.5 : 1, aortic regurgitation
4. > 5 years
Aortic regurgitation
Surgery for VSDs are done through median sternotomy

using conventional hypothermic cardiopulmonary bypass
with bicaval cannulation. Rarely in small infants, deep
hypothermia with circulatory arrest may be used. The aim
of closure is to have a secure and complete closure without
damaging adjacent structures, depending on the anatomy.
The conduction tissue and the aortic valve are particularly in
danger in perimembranous VSDs. The conduction system is
related to the posteroinferior margin and the region adjacent
to the septal leaflet and upto the papillary muscle of Lancisi,
represents the danger zone, where the conduction system
may be damaged. Muscular VSDs have adequate muscle
protecting the conduction system and do not pose a danger to
the conduction system.
Closure of VSDs are based on the type of the VSDs
and ease of access. The current trend is to try to avoid a
ventriculotomy as far as possible. Perimembranous and inlet
VSDs are exposed through the RA and everting the TV leaflets
by appropriately placed traction sutures. Closure may be done
by using interrupted or continuous sutures taking care to avoid
the conduction system (Figure 15). Sutures are placed on the
base of the septal leaflet in the area adjacent to the triangle of
figure 15: Subaortic VSD being closed with interrupted sutures

through the tricuspid valve
conduction system. Outlet VSDs can be approached through

the pulmonary artery. Subarterial VSDs can be approached
through the aorta or pulmonary artery. An RV approach can
be used as an alternate approach for VSDs depending on the
site. Apical VSDs can be done through the RA or at times
through a limited left ventriculotomy, though this can lead to
left ventricular dysfunction.
Patients with high PVR pose a considerable problem as they
can have pulmonary hypertensive crises postoperatively. This
can be managed by using pulmonary vasodilators like nitric
oxide and at times extracorporeal membrane oxygenation
(ECMO). Another option is flap valved VSDs closure,
which allows temporary right to left shunting preventing
suprasystemic RV pressures. This is at the cost of systemic
desaturation, but it allows the patients left sided cadiac output
to be maintained.95
Postoperative problems include residual VSDs, conduction
disturbances (varying degrees of heart block), which may
need pacemaker insertion, TR and persistant PH.
The mortality for elective VSDs closure is ever diminishing
(less than 1%). Incremental risk factors include multiple VSDs,
severe PH and associated cardiac anomalies. Late presentation
with PH and severe cardiac cachexia are particular problems
in developing countries.
Devices for percutaneous Closure of Ventricular

Septal Defect
Transcatheter closure of VSDs in animal models was described
for the first time by Rashkind in 1975.96 He used hooked
single-disc and double-disc devices. Subsequently Lock et
al12 and Goldstein et al97 performed transcatheter closure
of VSDs using Rashkind double-umbrella and Clamshell
devices. The transcatheter device closure of muscular VSDs
279
shunt defects
have been in vogue for the past 15 years. Although relatively

common, perimembranous VSDs can be difficult to close
percutaneously. Previous devices (e.g. Rashkind or button
devices) have been unsuccessful in attempts to close these
VSDs, because of the proximity of the defects to the aortic
valve and the potential for aortic valve damage.
Now many varieties of new devices like muscular septal
occluder for muscular VSDs, asymmetrical and symmetrical
perimembranous septal occluder and Amplatzer duct
occluder II (ADO II) are available to close perimembranous
VSDs and rarely Gerbode shunts. The Amplatzer devices
(St. Jude Medical, Plymouth, MN) are made up of Nitinol,
an alloy of 55 percent nickel and 45 percent titanium and
this has superelastic properties.98 It also has been proven
to have excellent biocompatability. The muscular VSD
occluder (AVSDO) is a double-disc device. The thickness
of the nitinol wire is 0.004 for devices 10 mm and smaller
and 0.005 for larger devices. The leading retention disc
280
is 4 mm larger and the proximal disc is 3 mm larger than

the diameter of the waist. To achieve immediate complete
closure, three Dacron polyester patches are sewn securely
with polyester thread into the two discs and the waist of the
device. The device size corresponds to the diameter of the
waist. The mechanism of closure involves stenting of the VSD
by the device and subsequent thrombus formation within
the device with eventual complete neoendothelialization.
The device is available in sizes from 6 to 24 mm and these
are delivered through 6 to 9 French sheaths. The delivery
system is prepackaged with a long Mullins type sheath,
loader, diaphragm with side arm flush, delivery cable and
pin vise. The Amplatzer membranous VSD occluder, is an
asymmetric, self-expandable, double-disc device, unlike the
muscular septal occluder. Current recommendations are to
use this device in older patients, who weigh > 8 kg and who
have a subaortic rim >2 mm. The various types of devices
with their characteristics are shown in Figures 16A to E.
figures 16a to e: A. Midmuscular

ventricular septal occluder; B. Asymmetric
perimembranous VSD occluder with only
0.5 mm retention disc towards the aortic
valve. C. Symmetric perimembranous
VSD occluder; D and E. Amplatzer
membranous VSD occluder 2, has a dual
layer waist to minimize radial pressure
against the rims of the defect, and the
waist length is increased to 3 mm to
decrease the clamping effect on the
ventricular septum
reCommenDatIonS for DeVICe CloSure

of muSCular VSDs99
Class IIA is reasonable for infants who weigh 5 kg, children

and adolescents with hemodynamically significant (left
ventricular or left atrial volume overload or pulmonary to
systemic blood flow ratio 2:1) muscular ventricular septal
defect (MVSD) to undergo percutaneous VSD device closure
(level of evidence: B).
Class IIb
Neonates, infants who weigh < 5 kg and children with
hemodynamically significant (left ventricular or left atrial
volume overload or pulmonary to systemic blood flow ratio
> 2 : 1) MVSD and associated cardiac defects requiring
cardiopulmonary bypass may be considered for performance of
hybrid perventricular closure of the VSD off bypass, followed
by surgical repair of the remaining defects or device placement
during cardiopulmonary bypass (level of evidence: B).
Class III
1. Neonates, infants and children with hemodynamically
significant (left ventricular or left atrial volume overload
or pulmonary to systemic blood flow ratio >2 : 1) inlet
MVSDs with inadequate space between the defect and
the atrioventricular or semilunar valves should not
undergo device closure (hybrid or percutaneous) (Level of
Evidence: B).
2. Neonates, infants and children with a small to moderatesized MVSD (without symptoms or evidence of pulmonary
hypertension) in whom there is a reasonable expectation
that the defect will become smaller over time should be
followed up expectantly and do not need closure of the
VSD (Level of Evidence: B).
patient Selection
Patients are selected for transcatheter occlusion based on the
presence of a hemodynamically significant VSD with left to
right shunt. The patients are evaluated with history, physical
examination, ECG and TTE.
Exclusion criteria include: Weight less than 3.0 kg (unless
the hybrid perventricular approach is used); distance of less
than 4 mm between the VSD and the aortic, pulmonic, mitral
or tricuspid valves; PVR greater than 7 indexed Wood units;
sepsis and patients with conditions that would be expected to
be exacerbated by the use of aspirin unless other antiplatelet
agents could be used for 6 months.99
Prior to the transcatheter closure procedure, a
comprehensive TTE study is of critical importance. Accurate
Procedure
Most procedures are performed with the patient under general
anesthesia and with either TEE guidance. The complications
encountered in transcatheter closure of muscular VSD using
an AVSDO are arrhythmias occurred during or soon after
the procedure. Fortunately all the reported arrhythmias were
transient. Reported complications have included aortic and
tricuspid regurgitation, device embolization, complete heart
block, transient left bundle-branch block, hemolysis and small
residual shunts.
In our experience perimembranous VSDs can be closed with
asymmetrical or symmetrical perimembranous VSD occluders
depending on the length of the septal tissue below the aortic
valve, (Figure 17A) so that there is no impingement of the
aortic valve leading to AR (Figure 17B). If perimembranous
VSDs are small (<6 mm) with adequate aortic rim one can use
ADO II with excellent results (Figures 18A and B). The ADO
II is also useful in closing fenestrated septal aneurysm (Figures
19A and B).
Spontaneous closure of Gerbode defects is very rare and
closure of essentially all Gerbode defects is recommended to
avoid progression of TR and occurrence of IE. Surgical closure
remains the mainstay of treatment, yet transcatheter device
closure is shown to be an effective alternative. There are a few
reports of successful transcatheter closure of congenital and
acquired Gerbode defect.100 The ADO II meant for closing long
ducts in infants is very handy in closing these rare Gerbode
VSDs (Figures 20 A and B).The major concerns during device
closure of these defects include alignment of the device,
conduction disturbances, and worsening TR. Transcatheter
device closure of Gerbode defect is safe and effective. The TTE
can demonstrate the well-positioned device between the LV and
RA space (retention disc below the TV) with disappearance of
TR (Figures 21A and B).
Unlike the regular ventricular septal occluder, the
deployment of ADO II is done from the aortic end without
making an arteriovenous loop. Hence, the fluoroscopic and
procedure time is shorter. As the cost of ADO II is lesser
compared to regular ventricular septal occluders, it is also
very useful in the closure of multiple VSDs, especially post
surgical residual shunts (Figures 22A and B).
In a case with ASD and VSD, simultaneously VSD and
then ASD can be closed in the same setting (Figure 23). The
alternative routes are either jugular or rarely through an ASD
19
Class IIa
delineation of anatomic details of the number and location of

defects, their origin and exit on the left and right ventricular
aspects and their relationships with neighboring muscle
bundles and valvular apparatus are important for effective
transcatheter therapy. For apical muscular VSD, the anatomy
in the apical region is also important for the choice of device
and implantation route.
281
shunt defects
figures 17a and B: A. Left ventricular (LV) angiogram in left anterior oblique view shows 8 mm perimembranous ventricular septal defect; B:
Aortic root angiogram in left lateral view shows 10 mm symmetrical, perimembranous VSD device in situ with no aortic regurgitation
a
282
figures 18a and B: A. Left ventricular (LV) angiogram in left anterior oblique (LAO) view shows a conical shaped ventricular septal defect,
well away from the aortic valve; B. LV angiogram in LAO view shows ADO II in situ with no residual shunt
19
figures 19a and B: A. Left ventricular (LV) angiogram in left anterior oblique (LAO) view shows a large septal aneurysm with two jets
opacifying RV; B. LV check angiogram in LAO view shows 6 x 6 ADO II in situ closing both the defects
figures 20a and B: A. Left ventricular angiogram in anteroposterior view shows the ventricular septal defect jet opacifying right atrium (RA) in
a 10-year-old patient with Gerbode defect; B. Hand injection of contrast given from the side arm of Y connecter shows the proper positioning of
ADO II device. Ao = Aorta; LV = Left ventricle; RV = Right ventricle
283
shunt defects
figures 21: Post procedure transthoracic echocardiogram in apical four chamber view with color Doppler shows Amplatzer duct occluder (ADO
II) with two retention skirts (arrow) one in left ventricle (LV) and another in right atrium (RA) with no tricuspid regurgitation or residual shunt in the
infant with Type II Gerbode defect. Note the dilatation of LV and RA due to the Gerbode defect.
figures 22a and B: A. Left ventricular angiogram in postsurgical ventricular septal defect (VSD)
closure patient (sternal suture wires are seen) with residual VSDs, non-compaction of left ventricle with
Swiss cheese VSDs; B. Fluoroscopy in left anterior oblique view shows two ADO II devices (arrows)
in situ
284
There is not much literature on device closure of large

midmuscular VSDs with severe PH. The surgery carries highrisk in such patients. However in selected cases, akin to flap
surgery, the fenestrations can be done with large dilator prior
to deploying the device. A 12-year-old girl had previously
undergone PDA ligation 4 years years back. Her aortic pressure
was 110/70 m 83 and pulmonary artery pressure was 92/60 m 71
mm Hg (PCW pressure was 22), which dropped to 76/46 m 56
mm Hg and PVRI decreased from 13.8 to 7.7 after 100 percent

O2 inhalation. The QP: QS increased from 1.2 to 2:1 after O2
inhalation and the right to left shunt disappeared, SaO2 increased
from 90 to 98 percent. This patient underwent device closure
with 24 mm VSD muscular septal occluder after 2 fenestrations
were iatrogenically created with 7F dilator (Figures 25A
and B). After deploying the fenestrated device, one can
check with either RV or LV angiogram (Figures 26A and B).
Hybrid Surgery
Hybrid surgery is a combined surgical and nonsurgical
approach to close MVSDs, especially in infants with low
weight. The transcatheter approach for large MVSDs requires
large introducing sheath. Hence device closure is not feasible
in small infants. Under general anesthesia, hemisternotomy is
done with systemic heparinisation. The pericardium is opened.
Purse string is taken over the anterior surface of the RV. The RV
figure 23: Fluoroscopy shows atrial and ventricular

septal devices in situ
19
The position of the device and residual shunt can be assessed

by either TTE or TEE with color Doppler. On one year followup, the pulmonary artery pressure has dropped to 40 mg Hg on
TTE assessment. Apart from using the fenestrated device, one
can open the patent foramen ovale with balloon dilatation, in
case the pulmonary artery pressure mounts despite pulmonary
vasodilators.
The transcatheter device closure has come as a boon to
the children with VSD. Except the subpulmonic and inlet
VSDs, most of the other VSDs can be closed without surgery.
Surgical closure of VSD in dextrocardia can be tedious. The
device closure can be done easily and safely in dextrocardia
figures 24a and B: A. Left ventricular angiogram in left anterior oblique view in a 14-year-old boy shows large apical ventricular septal defect
(VSD) with hypertrophied bands in right ventricle (RV), which makes it difficult for closure from the jugular approach; B. As the patient had atrial
septal defect (ASD), the Mullin sheath is passed through ASD into left ventricle and then through the VSD into RV directly. But still the device is
seen in the RV bands
285
shunt defects
figures 25a and B: A. Method of creating fenestration in the 24 mm Lifetech muscular septal occluder;
B. Two iatrogenically created fenestrations with 7F dilator seen
figures 26a and B: A. Left ventricular (LV) angiogram in left anterior oblique (LAO) view shows large
midmuscular ventricular septal defect (VSD); B. LV angiogram in LAO view shows 24 mm VSD muscular
device in situ with jet of contrast through the holes. Post-procedure pulmonary artery pressure dropped
from 92/60 m 71 to 76/46 mm 56 mm Hg, oxygen saturation increased from 90 to 98 percent
286
puncture is done with a 18 gauge needle (modified Seldinger)

under TEE guidance. 0.038 95 cm diagnostic guide wire is
introduced through the needle and through the VSD into LV.
A 10 F sheath is passed over guidewire into LV (Figure 28A).
Through the sheath, the Amplatzer VSD occluder is passed
and the LV disc deployed in LV and the device is deployed by
releasing the proximal disc in the RV (Figure 28B). The major
advantage of this procedure is avoidance of cardiopulmonary
bypass, less blood loss and speedy postoperative recovery,
since it is accomplished on the beating heart. The position of

the device can be checked by both LV angiogram and TEE
future Direction
The interventional treatment of VSD is much more
complicated than closure of secundum ASD or PDA. There
are mitral and tricuspid valve apparatus in both ventricular
19
figures 27a and B: A. Left ventricular angiogram in right anterior oblique view shows non-compaction of left ventricle; B. Fluoroscopic image
in posteroanterior view shows situs inversus with dextrocardia with 5 4 ADO II in situ
figures 28a and B: A. 14 mm ventricular septal defect (VSD) muscular septal occluder being introduced in a 9 kg girl; B. Hybrid closure of
VSD. Note: The sternal spreader, the deployed device, the sheath placed through the RV free wall under fluoroscopic and transesophageal
echocardiographic guidance
cavities. There are also moderator and other muscle bands

in the right ventricular cavity. The chordae tendinae and
papillary muscle of septal leaflet of TV sits on the septum
and come in the way of making an arteriovenous loop.
Perimembranous VSD is usually located in an area quite
near the aortic and tricuspid valves. Encroaching any of these
structures would cause severe complications. In addition, the
position and orientation make the defect, difficult to be passed
by catheters or guide wires. Therefore, most of the defects

targeted for closure are muscular defects, which are at least
4 mm away from any cardiac valve. The closure results and
safety depends on the device used and also on the location
of the defects. With AVSDO, the complete closure rate is as
high as 100 percent. Besides, ADO and ADO II are also used
in selected cases. ADO II has simple and smaller delivery
system and can be effectively repositioned or retrieved
287
shunt defects
figures 29a and B: A 2-year-old girl with 8 mm, midmuscular ventricular septal defect (VSD) closed
with 14 mm Amplatzer muscular VSD through hybrid surgery. The pulmonary artery pressure dropped
from 80/40 to 50/12 mm Hg after hybrid device closure: A. Left ventricular angiogram in left anterior
oblique view; B. Transthoracic echocardiogram in apical four chamber shows device in situ with no
residual shunt
until it is released in an optimal position from the aortic

end, without making an arteriovenous loop. Thus, with the
newly designed devices like AVSDO II, transcatheter closure
of perimembranous VSD in selected patients can be done
as an alternative to surgical closure. Hybrid device closure
has further brought down the lower limit of age and weight
criteria for the device closure.
ConCluSIon
Ventricular septal defect is one of the most common CHDs.
It may be small, medium or large. The defect may be located
in the membranous or muscular portion of the ventricular
septum. The good clinical, echocardiographic assessment is
important for timely management. The transcatheter closure
of VSDs in selected patients has been very encouraging with
the specially designed Amplatzer VSDO. Many common
types of muscular VSDs can be effectively occluded with the
device. The spectacular results with device closure makes
the various devices important in the armamentarium of the
interventional cardiologist caring for patients with VSD.
Device closure of VSD could be an attractive alternative to
traditional surgery. The surgery is the age old time tested
method of management offered for large VSDs, not suitable
for device closure and for subpulmonic VSDs. In this modern
era no patient of VSD should be allowed to develop IE or
Eisenmengers complex.
288
The patient does not care about your science; what he

wants to know is, can you cure him?
Martin H Fischer
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C hapter
20
Atrioventricular Septal Defects

Atrioventricular septal defect (AVSD) is characterized by

the anatomical hallmark of a common atrioventricular (AV)
junction coexisting with deficient AV septation. AV septum in
normal hearts separates left ventricular outflow tract (LVOT)
from the facing right atrium. AVSD is characterized by the
absence of muscular and membranous components of this AV
septum. The components of AVSD includes a common AV
valve ring with five leaflet valve that guards a common orifice,
unwedged LVOT, an aortic orifice that is anterosuperior to the
common AV junction and disproportion of the left ventricular
(LV) mass characterized by longer distance from apex to
aortic valve than apex to left AV valve (Figures 1 to 4). The
Figure 2: Parasternal long-axis view

atrioventricular septal defect showing
inflow (line-a) and outflow (line-b)
DA = descending aorta; LA = Left
RV = Right ventricle.
from an infant with complete

discrepancy in left ventricular
measurements. Ao = Aorta;
atrium; LV = Left ventricle;
terms AV canal defect and endocardial cushion defect are used

in reference to this group of defects; however, AVSD is now
the preferred terminology.
InCIDenCe
Figure 1: Subcostal short-axis view at the level of the common AV

valve showing the components of the common AV valve. Ao = Aorta;
IBL = Inferior bridging leaflet; LV = Left ventricle; PA = Pulmonary
artery; RV = Right ventricle; SBL = Superior bridging leaflet.
Incidence of AVSD varies from 1.4 to 10.8 percent (45%)

in some studies of congenital heart disease (CHD). These
constitute 0.19 per 1,000 live birth (New England Regional
Infant Cardiac Program). Prevalence of 0.362 was seen in the
Baltimore Washington Infant Cardiac study. Prevalence of
0.203 using invasive method for diagnosis and 0.242 using
non-invasive method (Alberta heritage study). The incidence
of CHD in offspring of female with AVSD is 9.6 to 14.3
percent.
20
AtrioventriculAr SeptAl DeFectS
Figure 3: 2D echocardiography in apical four-chamber view showing

loss of offsetting with inlet ventricular septal defect in a case of
common. AV valve LA = Left atrium; LV = Left ventricle; RA = Right
Figure 4: Subcostal coronal view with anterior tilt (modified view) in

diastole showing gooseneck deformity of left ventricular outflow tract,
i.e. left ventricular outflow tract in elongated with anterior unwedged
position of aorta. Inferior bridging leaflet is seen (arrow). Ao = Aorta;
LV = Left ventricle; RA = Right atrium; RV = Right ventricle.
Figures 5A to D: Schematic diagram showing the various types of atrioventricular septal defects. LA = Left atrium; LPV = Left pulmonary vein;
LV = Left ventricle; RA = Right atrium; RPV = Right pulmonary Vein: RV = Right ventricle.
ClASSIfICAtIon
Classification I
Patients with AVSD are classified into the following groups
(Figures 5A to D):
1. Partial AVSD: When the two bridging leaflets are joined
to each other, by a tongue of tissue dividing the AV valve
into two separate orifices. Thus, partial AVSD has primum
defect, two distinct mitral and tricuspid AV valve annuli
and cleft mitral valve is present invarably.
2. Complete AVSD is when the bridging leaflets are free,
guarding the opening of both the atria to the respective
ventricle as a common opening. Thus in complete AVSD

primum atrial septal defect (ASD) is contiguous with an
inlet ventricular septal defect (VSD) and the common AV
valve has a single annulus.
3. Transitional AVSD: Subtype of partial AVSD. Additional
finding is a small inlet VSD that is partially occluded by
dense chordal attachment to the septum.
4. Intermediate AVSD: Subtype of complete AVSD that has
distinct right and left AV valve orifices despite having only
one common annulus.
Cleft anterior mitral leaflet (AML): Cleft is actually the
meeting point of left halves of anterior and posterior
bridging leaflets. It is a type of commissure. The cleft
293
Shunt DeFectS
Figures 6A to c: Schematic diagram of atrioventricular septal defects showing the level of shunting;
A. Both atrial and ventricular shunting; B. Atrial shunting only; C. Ventricular shunting only. LA = Left atrium; LV = Left ventricle;
RA = Right atrium; RV = Right ventricle. Reproduced from Atrioventricular septal defect: from fetus to adult. Craig B.Heart.
2006;92:1879-85, with permission from BMJ Publishing Group Ltd.
Figures 7A and B: Apical four-chamber with color flow mapping in a child with partial atrioventricular septal defect showing, common
atrioventricular junction and small inlet ventricular septal defect with left-to-right shunt. Ventricular septal defect is small due to the attachment
of superior bridging leaflet to crest of ventricular septum (arrow). LA = Left atrium; LV = Left ventricle; RA = Right atrium; RV = Right ventricle.
of AVSD is directed towards midportion of ventricular

septum. The isolated cleft in the AML is directed towards
aortic valve annulus.
Classification II
294
Rarely AVSD is classified depending on level of shunting of the

blood in the cardiac chambers (Figures 6A to C):
Interatrial and interventricular shunts
Interatrial shunt only (primum ASD)

Interventricular shunt only (AV canal VSD) (Figures 7A
and B)
AVSD with intact interatrial and interventricular septum.
Rarely with complete AVSD, there will be absence of any
interatrial shunt when the superior bridging leaflet is attached to
the lower end of atrial septum and absence of VSD when it is
firmly attached to the ventricular septum as described with partial
AVSD.
20
Figures 8A and B: Apical four-chamber view with A. Schematic diagram;

B. Echocardiography showing unbalanced atrioventricular septal defect with right
ventricular dominance. IVC = Inferior vena cava; LA = Left atrium; LV = Left ventricle;
RA = Right atrium; RV = Right ventricle; SVC = Superior vena cava
Figures 9A and B: Apical four-chamber view with A. Schematic diagram; B. Echocardiography

showing unbalanced atrioventricular septal defect with left ventricular dominance. LA = Left atrium;
Classification III
This type of classification depending upon the size of the
ventricular chambers has practical importance as it helps in
deciding the modality of treatment for AVSD (univentricular
versus biventricular pathway).
Balanced type
Unbalanced AVSD: Unbalance in AVSD refers to two
distinct but related anatomical features:
1. Ventricular hypoplasia.
2. Malalignment of the AV valve junction. Latter may
affect ventricular size developmentally.
Unbalanced with right dominant type (Figures 8A and
B): This is the common type, usually associated with arch
hypoplasia, coarctation of aorta.
Unbalanced with left dominant type (Figures 9A and B): It

is usually associated with pulmonary stenosis/pulmonary
atresia.
The decision between balanced and unbalanced ventricles
in borderline cases is best done using AV valve index (AVVI).
Method
Tracing the circumference of the common AV valve orifice
during end-diastole, averaged over three cardiac cycles using
a subcostal view on 2D echocardiography. This circumference
is then divided by a line drawn over the place of intact
ventricular septum (IVS) from the tip of the infundibuluar
septum to the crest of the muscular septum, thus dividing AV
295
Shunt DeFectS
Figures 10A and B: Assessment of balanced AV septal defect using the image in Figure 1. Tracing circumference of the common AV valve
orifice during end-diastole, averaged over three cardiac cycles using a subcostal view on 2D echocardiography. This circumference is then
divided by a line drawn over the place of IVS from the tip of the infundibuluar septum to the crest of the muscular septum, thus dividing AV valve
into left and right components. The AVVI is expressed as the smaller AV valve area over the larger AV valve area. For a balanced AVSD (Area I
and Area II in Figure) should be between 0.4 and 0.6
Figures 11A to c: Subcostal short-axis view at the level of AV valves showing the Rastelli classification:
A. Type A; B. Type B; C. Type C patterns of AV valves
296
valve into left and right components. For a balanced AVVI

should be between 0.4 and 0.6 (Figures 10A and B).
When the right-sided component is small, the right ventricle
is hypoplastic, the tricuspid valve overrides a malaligned inlet
ventricular septum and the right AV valve has attachments that
straddle the VSD. When the left-sided component is small,
the morphological left ventricle is hypoplastic, but straddling
does not occur despite AV malalignment because straddling is
reserved for conoventricular malalignment.
Classification IV/Rastelli Classification

It is more of historical importance. Complete AVSD is divided
into type A, B, C based on extent of straddling of anterior
bridging leaflet into right ventricle (RV) (Figures 11A to C).
Type A: It is seen in 50 to 70 percent of patients. Anterior
bridging leaflet (ABL) is completely committed to left
ventricle and there is minimal bridging of leaflet into
RV. Chordae are attached to the crest of the ventricle.
SpeCIAl foRmS of AVSD

malaligned Atrial Septum or Double-outlet Right Atrium
The atrial septum is deviated to the left of the AV junction.
Both right and left AV valves are visualized from right atrium,
which is connected to both ventricles through primum ASD.
Pulmonary veins may be isolated and obstructed if deviation
to the left is extreme.
of the superior and inferior endocardial cushions. Complete

AVSD: Lack of fusion between the superior and inferior
cushions resulting in the formation of separate anterior and
posterior bridging leaflets.
Failure of the endocardial cushions to fuse results in defect
in the AV septum. Recent work has shown that the lesion should
be considered as defect of dorsal mesenchymal protrusion
and inadequate development of vestibular spine rather than
endocardial cushion defect. Additional experimental work has
shown that the ingrowth through this vestibular spine/dorsal
mesenchymal protrusion is derived from the second heart
stage being regulated by islet-1 gene.
Large primum ASD results in downward displacement of
AML to the level of the septal tricuspid leaflet. The distance
from cardiac crux to LV apex is foreshortened and the distance
from apex to aortic valve is increased. LVOT and aorta are
unwedged from their normal positionsprung aorta giving
the appearance of gooseneck deformity.
AVSD may be associated with conotruncal anomalies like
TOF and DORV. Dextrodorsal conus cushions contribute to
the development of right AV valve and the outflow tracts lie
adjacent to their inflow tracts. Shift of the AV valve orifice to
either side results in disproportionate or unbalanced ventricle.
20
This type is the most common type associated with

Downs syndrome.
Type B: More bridging of ABL into RV and chordae are
attached into the papillary muscle of RV. It is least common
type seen in 3 percent of patients of AVSD. It is almost
always associated with unbalanced AVSD with right
dominance.
Type C: It is seen in 30 percent of patients of AVSD.
Maximal bridging of ABL into RV with chordal attachment
into RV free wall. It is commonly associated with complex
anomalies like tetralogy of Fallot (TOF), double outlet
right ventricle (DORV), transposition of the great arteries
(TGA) and in hetrotaxy syndromes.
nAtuRAl HIStoRy
AVSD with Intact Ventricular Septum

This rare condition was first described by Anderson RH in
1984 in two cases diagnosed on postmortem examination.
JP Kaski has described five cases of complete AVSD with intact
septum diagnosed by echocardiography. They were diagnosed
as AVSD because they had the essential morphologic features
which include:
1. Disproportion between inlet and outlet portions of
interventricular septum.
2. Malorientation of the aortic valve relative to the AV valve.
3. Common AV junction guarded by common AV valve.
Such an entity is being described also in relation to the
spontaneous closure of AVSD.
Common Atrium
Common atrium is characterized by the near absence of
the atrial septum and in the presence of two ventricles, it
is always associated with an AVSD. In these cases TGA,
DORV, univentricular AV connection and anomalous venous
connections, asplenia syndrome are frequently encountered.
The radiological and electrocardiographic characteristics of
the patients are indistinguishable from AVSD.
embRyology
It is characterized by the faulty development of the endocardial
cushions and AV septum. Partial AVSD: Incomplete fusion
With improved diagnostic modalities and surgical advances,

more and more cases of AVSD are being diagnosed antenatally
(Figures 12A to D) and are successfully living normal adult
lives. Factors on which fetal outcome depends are:
1. Morphology of the defect
2. Size of VSD
3. Degree of ventricular hypoplasia
4. Degree of AV valve regurgitation (most important for
intrauterine survival)
5. Associated LVOT obstruction
6. Associated coarctation and syndromes.
Outcome of the non-surgical patients of complete AVSD
may be extrapolated from the 1979 study of Bollinger et al.
They had 54 percent survival at 6 months, 35 percent at 12
months, 15 percent at 24 months, 4 percent at 5 years. Most
patients die by 2 to 3 years of age without surgery. Patients
of partial AVSD and minimal AV regurgitation do well.
Atrial fibrillation is an important cause of late morbidity and
mortality.
The risk of infective endocarditis coincides with the
regurgitation and not with the abnormal structure of a
functionally competent valve. Paradoxical emboli are rare
with ostium primum ASD in contrast to ostium secundum
ASD, because emboli that originate in the lower extremities
are carried by inferior vena caval blood towards the midportion
of the atrial septum. Superior vena caval streaming targets the
lower atrial septum, but emboli rarely originate in the upper
extremity.
297
Shunt DeFectS
Figures 12A to D: Fetal echocardiogram demonstrating cases of AVSD: A. Balanced AVSD diagnosed in a 19 weeks fetal echocardiogram;
B. Fetal echocardiogram showing four-chamber view with moderate AV regurgitation; C. Fetal echocardiogram in a 18 weeks old showed
unbalanced AVSD; D. Four-chamber view demonstrates shunting across the ASD and VSD components of a case of AVSD. LA = Left atrium;
eVAluAtIon AnD InVeStIgAtIVe

moDAlItIeS foR AVSD
298
These are related to degree of the shunt and AV valve

regurgitation. In complete AVSD, tachypnea and failure to
thrive occurs in view of congestive heart failure virtually in
all patients by 1 year of age as a result of the large shunt and
AV valve regurgitation further compounds this problem. If
these patients do not develop symptoms one should suspect
early development of pulmonary vascular obstructive disease.
Patients of partial form have a presentation similar to large
ASD. The phenotypic features of associated syndromes
particularly Downs syndrome should be looked for.
physical examination
In the setting of pulmonary vascular obstructive disease, there
may be baseline systemic desaturation. A small water hammer
pulse is due to the rapid ejection of the large left ventricular
stroke volume of severe left AV valve regurgitation. The v
wave is dominant in the jugular venous pulse especially in the
presence of left AV valve regurgitation being transmitted across
the ASD. The presence of congestive heart failure elevates
both a and v waves. The physical examination shows
hyperactive precordium, an accentuated first heart sound and
wide split second heart sound with P2 increased in intensity.
A loud holosystolic murmur of AV valve regurgitation may be
heard at the apex. Findings of AV valve regurgitation in the
presence of a pretricuspid shunt strongly favors the clinical
electrocardiography and electrophysiology

Atrioventricular node is displaced posteriorly near the orifice
of the coronary sinus and the His bundle is displaced inferiorly.
In conjunction with the ventricular septal myocardium, the
His bundle is shorter than normal and is posteriorly placed,
the left bundle branch is displaced posteriorly and arises from
the common bundle immediately after it enters the ventricular
septum. The left anterior division of the left bundle branch
has fewer fibers than normal and is increased in length, the
left posterior division is shorter than normal and provides
small branches to the posterobasal wall of the left ventricle.
The right bundle branch is abnormally long and this results in
characteristic features of AVSD on electrocardiogram (ECG).
Sinus rhythm is seen in most patients of primum ASD.
Prolongation of PR interval in relation to the patients age
and heart rate is seen in 18 to 70 percent of the patients, due
to increased intra-atrial conduction time. P wave changes
indicating right or left or biatrial enlargement are seen in 54
percent of the patients. Superiorly directed p wave axis may be
seen in cases of left isomerism.
The mean QRS axis ranges from 30 to 120 degrees,
most commonly between 30 and 90 in partial form and
between 90 and 120 in complete form, due to specific
anomaly of the conduction system. Extreme left axis deviation
is a feature seen commonly in Downs syndrome. The
superiorly oriented frontal QRS axis is manifested by dominant
S waves in leads III and aVF and prominent R wave in aVR.
Further the frontal axis is deviated upwards and to the right, the
deeper the scooping of the ventricular septum and more likely
that there will be a common valve orifice. Counterclockwise

depolarization results in q waves in leads I and aVL (Figure
13). The S waves in leads II, III and aVF are characteristically
notched on their upstrokes because of a change in the direction
of the terminal force of QRS (better seen on vector loop). In
few of the patients, the initial portion of the QRS is directed
downward and to the right.
Chest X-ray
The X-ray in isolated primum ASD is similar to any other
pretricuspid shunt or secundum ASD. When left AV valve
regurgitation is present, the right atrium is especially enlarged
because regurgitation flow is directed into the right atrium.
The left cardiac border is straightened by a prominent right
ventricular outflow tract. In Downs syndrome, the lateral
chest X-ray may show a double manubrial ossification
center and the posterioanterior projection may show absent
or rudimentary 12th rib. Hyperinflation of the lung may be
present because of upper airway obstruction in patients with
Downs syndrome.
20
diagnosis of AVSD. The mid-diastolic flow murmurs occurs

across the AV valves. They can heard at the left lower
parasternal border and may be also heard at the apex.
echocardiography
The assessment of the AV junction is readily achieved by
two-dimensional echocardiography and since AVSD are
primarily an abnormality of this region, reliable delineation
of their detailed morphology is possible. Color flow Doppler
interrogation compliments the anatomical investigation by
demonstrating the sites of intracardiac shunting and AV
regurgitation, as well as defining any obstruction in the LVOT
if present. Pulsed and continuous wave Doppler is used for
quantitative measurements to assess pulmonary artery pressure,
severity of left ventricular outflow tract obstruction (LVOTO).
Figure 13: 12-lead ECG of a 3-year-old patient of AVSD showing qRS axis of 30 degrees (left-axis deviation). Normal P
axis. Right ventricular hypertrophy. Note: The superiorly oriented frontal qRS axis is manifested by dominant S waves in
leads III and aVF and prominent R wave in aVR and counter clockwise depolarization results in q waves in I and aVL
299
Shunt DeFectS
Various views may be used for defining various

echocardiographic features common to AVSD (Box 1).
Subcostal coronal view shows common AV junction, loss of
offsetting of AV valves, scooped out inlet septum and inferior
bridging leaflet of AV valve (Figures 1 to 4). Subcostal sagittal
view shows common AV junction and in addition to that both
superior and inferior bridging leaflets and anterior unwedged
position of aorta can be very well profiled. Parasternal shortaxis view shows trileaflet left AV valve, presence of cleft
mitral valve (Figure 14), presence of common AV junction
and abnormal position of the papillary muscles in the left
ventricle. Parasternal long-axis view shows discrepancy in
left ventricle inflow and outflow measurements (Figure 2)
and presence of LVOTO obstruction. Subcostal long-axis
view LVOT shows gooseneck deformity (long left ventricle
outflow with anterior position of aorta) (Figure 4). While
evaluating a patient with AV septal defect, the things that need
to be addressed are tabulated in Box 2.
Straddling of AV valve is also an issue, which needs
to be defined. Straddling of left AV valve is defined in the
parasternal long-axis view, while for right AV valve the fourchamber view and subcostal enface view are required to
profile the chordal attachment (Figure 1).
Color flow mapping is required to define presence and
direction of shunting across interatrial or interventricular septum
(Figure 15), presence of AV valve regurgitation (Figure 16)
or stenosis, presence of left or right ventricular outflow tract
obstruction. Direction of shunt across ASD or VSD can be
profiled from views used to define the defects. Subcostal, apical
four chamber and parasternal short axis views are required to
look for presence of AV valve regurgitation, presence of left
Box 1: Two-dimensional echocardiographic findings

common to AvSD patients
1.
2.
3.
4.
5.
6.
Loss of offsetting of atrioventricular valves.

Deficiency of inlet portion of ventricular septum.
Presence of common atrioventricular valve fibrous orifice.
Abnormal morphology of atrioventricular valve cusps.
Abnormal position of papillary muscles.
Longer left ventricular outflow and anterior unwedged
position of aorta.
Box 2: checklist for echocardiographic

evaluation of AvSD
1. Type of defect, partial or complete atrioventricular septal
defect.
2. Extent of atrial shunting.
3. Extent of ventricular shunting.
4. Presence and degree of atrioventricular valve regurgitation.
5. Commitment of atrioventricular valves to respective
ventricles, is there balanced atrioventricular connection or
unbalanced atrioventricular connection, degree of ventricular
hypoplasia if present.
6. Presence of straddling.
7. Potential for left or right ventricular outflow obstruction.
8. Pulmonary artery pressures.
9. Associated lesions.
ventricle-right atrial shunt or right ventricle-left atrial shunt.

Right ventricle-left atrial shunt could be a cause of cyanosis in a
child with partial AV canal defect with normal pulmonary artery
pressure. The quantitative assessment of valvar stenosis is not
accurate by Doppler echocardiography when there is large ASD.
So, it is important to evaluate valve anatomy by two-dimensional
echocardiography and look especially for dysplasia, tethering
of leaflets and valve orifice. In such cases valve stenosis may
manifest after closure of the ASD.
The outflow tract of both left and right ventricle should be
assessed, as subvavular obstruction of both semilunar valves
is common.
left Ventricular outflow tract obstruction
300
Figure 14: Echocardiography from a 4 years old child with partial

atrioventricular septal defect showing trileaflet left atrioventricular
valve, and presence of cleft (arrow). LV = Left ventricle; RV = Right
ventricle.
In AVSD, the LVOT is longer and narrower than normal

though in most cases there is no overt stenosis. Any factor
which causes further narrowing of LVOT causes LVOTO.
LVOTO is usually progressive and common in postoperative
patients who were operated for partial AVSD. Causes of
LVOTO are highlighted in Box 3.
Obstruction in LVOT can be profiled on echocardiography
from subcostal coronal view with anterior tilt, subcostal
sagittal view and parasternal long-axis view. Color flow
mapping shows turbulence starting in the subaortic area.
Careful Doppler interrogation shows the site of the obstruction
and severity of LVOTO.
Box 3: Causes of left ventricular outflow tract

obstruction in AvSD
CompleX AtRIoVentRICulAR SeptAl DefeCt
Figure 15: Apical four-chamber with color flow mapping in a child with
partial atrioventricular septal defect showing intact interatrial septum,
common atrioventricular junction, and small inlet ventricular septal
defect with left-to-right shunt. Ventricular septal defect is small due to
attachment of superior bridging leaflet to crest of ventricular septum
(arrow). LA = Left atrium; LV = Left ventricle; RA = Right atrium; RV =
Right ventricle.
Complex AVSD can be defined as AVSD morphology, which

precludes two-ventricle correction. The following conditions
can be the cause of such a situation.
1. The most frequent is the association of AVSD with hetrotaxy/
isomerism. Anomalous systemic/pulmonary venous
connection, hypoplasia of ventricles and abnormalities
of ventricular arterial connection frequently precludes
biventricular connection.
2. Abnormalities of ventricular arterial connections
AVSD can be associated with DORV making it difficult
or impossible to route the VSD (which is remote from the
aorta) to the aorta thus precluding a two ventricle repair.
3. Right/Left ventricular dominant AVSDBecause of
extreme straddling/overriding of the common AV valves
across the VSD one of the ventricle may be hypoplastic.
This will prevent two-ventricle repair. In most cases
quantification of hypoplasia is subjective and is based on
echocardiography.
1. Tight adherence of the superior bridging leaflet to the septal

crest causing left ventricular outflow tract (LVOT) to be longer
and narrower. LVOT obstruction is more common in partial
atrioventricular septal defect and common atrioventricular
septal; defect with small ventricular septal defect (with
Rastelli type A).
2. Abnormal chordal attachment of the superior bridging leaflet.
3. Discrete subaortic membrane.
4. Tissue from an aneurysm of the membranous septum bowing
into the LVOT.
5. Septal hypertrophy.
6. Prominent anterolateral muscle bundle.
20
ASSoCIAtIon
Figure 16: Subcostal sagittal view with color flow mapping from a child
with partial atrioventricular septal defect showing left atrioventricular
valve regurgitation through cleft (arrow). LV = Left ventricle; RV = Right
ventricle;
Right Ventricular outflow tract obstruction

Pulmonary stenosis can occur at subvalvular (malalignment
of outlet septum, infundibular hypertrophy), valvar or supravalvular levels and can also be well profiled on echocardiography.
There is a strong association of AVSD with trisomy 21. Nearly

30-50 percent of patients with AVSD have trisomy 21. 40 to
45 percent of patients with Downs syndrome have CHD and
amongst these 40 percent have a AVSD (40% rule). Complete
AVSD also occur in patients with hetrotaxy syndrome (more
common in patients with asplenia than polysplenia). Common
atrium has been associated with Ellis Van Creveld syndrome.
The presentation of the defect ranges from fetal life to those
with partial forms presenting even in later age group.
TOF (occurring in 6% of patients), DORV (occurring in
6% of patients), malposed great vessels (occurring in 3%
of patients) are frequently associated with complete AVSD
especially in setting of isomerism. With unbalanced AV
connection leading to hypoplastic left ventricle, aortic arch
should be well profiled in suprasternal long axis view to rule
out arch anomalies like coarctation of aorta and aortic arch
interruption. With hypoplastic RV, pulmonary stenosis and
pulmonary atresia may be the associations.
301
Shunt DeFectS
CARDIAC CAtHeteRIzAtIon AnD AngIogRApHy

As discussed, preoperative assessment can now generally
be achieved by echocardiography alone. Catheterization is
indicated only when there is strong echo-based evidence of
severe pulmonary hypertension. Catheter usually courses low
in the septum, has a typical curve on fluoroscopy and may enter
the left ventricle through the cleft unlike in other ASDs where
it tends to enter left atrial appendage. It may also be difficult to
manipulate a stiff catheter to the RV and would preferentially
go through the VSD. A tip deflector or a balloon catheter may
come handy in this setting. The best known angiographic
feature is the gooseneck malformation (Figure 17). The body
of the goose is produced by the abnormal parietal attachment
of the left component of the common AV junction.
ASSeSSment of opeRAbIlIty
Conventional clinical examination continues to be an important
tool. A patient of complete AVSD with normal venous
drainage and with cyanosis and clubbing in the absence of
right ventricular outflow tract obstruction is clearly inoperable.
What is required is the assessment of patients with borderline
operability. This is further analyzed by echocardiography and
cardiac catheterization.
Echocardiographic features of inoperability are hugely
dilated pulmonary arteries, a dominant RV, a compressed
appearing LV (not a small LV of unbalanced AVSD) and chest
X-ray showing absence of plethora.
Cardiac catheterization is useful in borderline cases. A raised
and fixed pulmonary vascular resistance (> 8 Wood units/m2)
with little or no fall after 100 percent oxygen administration,
indicates inoperability. An important precaution in these
patients is that the venous sample should be obtained high up
in superior vena cava because of the atrial level of shunt.
In a hypothetical situation of a complete AVSD with a large
ventricular component, on room air the response to oxygen to
help to decide operability should have a large quantam of rise
in Qp : Qs (beyond 5 : 1) than just a smaller rise (2 : 1).
LV angiogram in left anterior oblique (LAO) position gives
an important guide to the relation of the pulmonary to aortic
blood flow. If the dye appears earlier in pulmonary artery and
the density is more than aorta, it indicates a significant left-toright shunt and points to operability.
HemoDynAmIC ASSeSSment of AtRIoVentRICulAR

SeptAl DefeCt
302
Hemodynamics of AVSD essentially depend upon the potential

for shunting and AV valve regurgitation. The degree of the former
depends upon the relationship of the bridging leaflets and of the
connecting tongue if present, to the lower edge of atrial septum
and to the crest of the scooped out ventricular septum.
Figure 17: Left ventricular angiogram in left anterior oblique view

shows the typical gooseneck deformity. Courtsey: Dr IB Vijayalakshmi
1. If the leaflets are not attached to atrial and ventricular

level then potential for shunting is there at both atrial
and ventricular level. The extent of ventricular shunting
depends upon the proximity of the bridging leaflets to
the septal crest. If there is free-floating leaflets then there
will be large ASD and VSD. When cords from septal crest
tether to one or both of the bridging leaflet than ventricular
shunting can be limited.
2. When both the superior and inferior bridging leaflets are
attached to septal crest then shunting occurs only at atrial
level.
3. Sometimes, the bridging leaflets and a tongue, if present
attached to the under surface of the atrial septum, this
arrangement permits shunting to occur only at the
ventricular level.
4. The degree of LV outflow obstruction augments left-toright shunt and also augments AV valve regurgitation.
5. Paradoxical embolization seen with ASD secundum is rare
with ostium primum defects.
Without pulmonary Stenosis

Partial Atrioventricular Septal Defect
Partial atrioventricular septal defects behave like ASD. In
the absence of significant AV valve regurgitation and normal
pulmonary artery pressure, the lesion is well tolerated and
patients may present late like fossa ovalis ASD. Significant
AV valve regurgitation, however may cause early congestive
heart failure. Accurate assessment of pulmonary artery
pressure and AV valve regurgitation is critical in decision
making in timing of surgery. Doppler assessment of
pulmonary artery pressure is usually performed by assessing
Mechanism of Atrioventricular Valve Regurgitation

In the majority of cases, the AV valve regurgitation occurs
through the cleft in the left AV valve (Figures 15A and B).
Atrioventricular valve regurgitation can also occur through
the commissures of the left AV valve or through the right AV
valve also.
Complete Atrioventricular Valve Septal Defect

Complete AVSD is associated with large VSD and pulmonary
arterial hypertension. Thus, congestive heart failure develops
in the first few months of life. Also rapid progression of
pulmonary vascular disease, within 6 months of life, occurs
in this condition. Thus, there is an urgent need to correct these
lesions early in life.
With pulmonary Stenosis

Patients with pulmonary stenosis present physiologically as
TOF. However, the morphology is much more complicated.
The VSD, which is predominantly of the inlet type, also
extends into the outlet. Anterior malalignment of the outlet
septum causes right ventricular outflow obstruction and other
morphological abnormality associated with tetralogy.
mAnAgement of AVSD
With the exception of those rare patients with small septal
defects and competent AV valves, the treatment for all patients
with an AVSD will be surgical correction. Medical therapy
with digoxin and diuretics serves to stabilize the patients with
a large shunt and cardiac failure during early infancy. Feeding
by gastric tube is sometimes necessary to provide adequate
caloric intake. The only aim of medical therapy is to postpone
surgery in symptomatic infants, preferably until the age of 6
months. In young infants with a very high pulmonary vascular
resistance, oxygen is occasionally given continuously during
the last weeks prior to surgery in an attempt to reduce the
incidence of postoperative pulmonary hypertensive crises.
Normally, in the absence of congenital cardiac disease,
pulmonary vascular resistance drops and remains fairly
constant after 1 month of age. In the presence of AVSD with
interventricular shunting, resistance may increase following
the initial drop. In some infants, resistance may even never
show the anticipated initial drop. This rise in pulmonary
vascular resistance has served as a strong incentive to operate
earlier in life. It is generally observed that repair below a body
weight of 5 kg or an age of 6 months, is only possible at the

cost of more complications and a higher rate of reoperation.
Severely symptomatic patients may benefit from earlier
operative repair because of failure to thrive and to prevent
secondary changes accompanying a large shunt and/or severe
AV valvar regurgitation. In these patients, the AV valve
annulus may dilate as a result of the large shunt and valvular
tissue may fibrose at the site of regurgitation, factors that may
complicate a repair if postponed for too long.
Factors that increase surgical risk are:
a. Young age.
b. Severe AV valve regurgitation.
c. Hypoplasia of LV.
d. Increased/fixed pulmonary vascular resistance
e. Severe preoperative regurgitation.
f. Associated defects viz double orifice mitral valve, single
left papillary muscle, additional VSD.
20
tricuspid regurgitation velocity. Care should be taken in not

confusing left ventricle-right atrial shunt (LV-RA shunt) for
tricuspid regurgitation as the former invariably produce highvelocity signals and will wrongly overestimate pulmonary
artery pressure.
objectives of Surgical Correction

Repair of complete AVSD must be done prior to the
development of irreversible pulmonary vascular obstructive
disease, preferably before 6 months of age. Surgical correction
aims at closure of all septal defects, maintenance of competent
AV valves and repair of associated defects.
Closure of the Septal Defect

Methods of repair can be categorized classically as use of
one or two patches for closure of the entire defect, presuming
there are atrial and ventricular components to close. A further
categorization is whether or not bridging valvar leaflets are
cut in order to expose the AV valvar annulus at the ventricular
septal junction. The cutting of bridging leaflets can be applied
to both the superior and inferior bridging leaflet, depending on
their extent of bridging. A further variable is provided by the
possibility of attaching one or both bridging leaflets directly
to the septal crest. The various surgical strategies used in the
surgical repair of AVSD are enumerated in Box 4.
Repair of the left Atrioventricular Valve

Two schools of approach has evolved in the past decade for
repair of the left AV valve depending upon whether to leave
the left AV valve bifoliate or trifoliate.
Surgery for Dual orifices in the left

Atrioventricular Valve
Dual orifices in the left or right ventricular components of
the AV valve occur in about one-twentieth of patients, more
often in the setting of separate left and right valvar orifices. It
is an abnormal and incomplete connection between two of the
leaflets that forms the anatomical basis for the extra orifice,
303
Shunt DeFectS
Box 4: permutation of these strategies results in at

least eight possible combination of techniques
1. Using one patch and cutting the bridging leaflets.
2. Using one patch, but leaving the bridging leaflets intact,this
is only possible with minimal bridging of both bridging
leaflets and constitutes a numerically minor subset.
3. Using one patch in which a cut is made to accommodate
one of the bridging leaflets, this is applicable when one of
the bridging leaflets bridge minimally, as in the Rastelli A
malformation.
4. Using one patch, having sutured the bridging leaflets
directly to the ventricular septal crest.
5. Using two patches and attaching the inferior bridging
leaflet to the ventricular septal crest, while inserting a patch
between the septal crest and the superior bridging leaflet,
which is left intact.
6. Using two patches, attaching the inferior bridging leaflet
to the ventricular septal crest, while cutting the superior
bridging leaflet.
7. Using two patches and cutting the bridging leaflets.
8. Using two patches, leaving the bridging leaflets intact.
which in the setting of the left valve is usually committed

to a inferomural or superomural papillary muscle and most
significantly, is usually not regurgitant. Any annuloplasty will
reduce even further the effective area of the valvar orifice. If
possible, these extra orifices are best left alone.
Intraoperative Assessment
Because of the complexity of the repair, echocardiographic
assessment in the immediate postoperative period and in long
term is mandatory to detect any important imperfections in the
repair. Following lesions should be sought for in the patients
following AVSD repair.
Residual Atrial or Ventricular Septal Defects

Doppler color flow mapping is particularly useful as a rapid
screening technique for residual septal defects and to look for
their location, size and hemodynamic impact.
Inadequate Repair of Common Atrioventricular Valve
304
Inadequate repair of common atrioventricular valve is by far

the most common postoperative problem. This will result in
left/right AV valve regurgitation or left/right AV valve stenosis.
Left atrioventricular valve regurgitation: This is more
common in patients with complete form of AVSD than partial.
Most commonly it occurs at the commissure between anterior
and posterior bridging leafletscleft mitral valve. Large
mural leaflet is also more common in patients with significant
residual left AV valve regurgitation. Echocardiography helps
in assessment of severity of regurgitation and its hemodynamic
significance.
Left atrioventricular valve stenosis: It can result from

excessive suture closure of cleft, congenital anomaly of
AV valve or inappropriate surgical division of common
atrioventricular valve between the two ventricles. Doppler
echocardiography helps in assessment of severity and need
for reintervention.
Right atrioventricular valve stenosis or regurgitation: It is
less common and has less serious hemodynamic consequences
than left AV valve regurgitation. It can be accurately diagnosed
by careful Doppler evaluation.
Left Ventricular Outflow Tract Obstruction

Subaortic stenosis occurs more frequently after repair of the
partial AVSD. Underlying mechanisms producing stenosis
include, adherence of anterior bridging leaflet to the crest of
ventricular septum, membranes or chordae crossing LVOT or
redundant atrioventricular valve tissue protruding into LVOT.
Echocardiography helps in identifying the cause and severity
of obstruction.
postoperative management
After the operation, the patient is kept intubated and ventilated
until the hemodynamic situation is stable. Because of the
known tendency of these postoperative patients to develop
pulmonary hypertensive crises, it is wise to prevent acidosis
and to avoid other precipitating factors, such as overly vigorous
intratracheal suction. Monitoring of pulmonary arterial
pressure is advantageous in patients known to have pulmonary
hypertension. The presence of a conspicuous left atrial v
wave on left atrial pressure tracing, both before and after the
procedure, is a good indication for regurgitation. The absence
of a v wave, unfortunately, is not a fool proof indicator that
the valve will be competent immediately after repair, possibly
because of the altered hemodynamics due to anesthesia or
through the damping effect of a large atrium. Presence of
substantial v waves, nonetheless, is an indication for further
investigation and usually, further attempts at repair of the valve.
ReSultS of SuRgICAl RepAIR

The function of the left AV valve, ventricular imbalance and
pulmonary hypertension are the sole incremental surgical risk
factors for death. Results of surgical repair have improved
steadily over the decades, concomitant with developments
in medical therapy, more appropriate criteria for selection
and improvements in myocardial preservation, surgical skill
and postoperative care. The function of the left AV valve has
determined the operative result, in both the short and the long
term. Late reoperations for left AV valvar dysfunction have been
a source of considerable morbidity and indeed also mortality.
At least 25 percent of patients require reoperation, most
commonly because of progressive left AV valve regurgitation
DoWnS SynDRome
Discussion of surgical treatment of AVSD cannot be concluded
without consideration of the problems created by coexisting
Downs syndrome. Children with Downs syndrome are more
likely to have AVSD than children without Downs syndrome.
Rastelli type A are more common in Down and are more likely
to have associated TOF. Sidedness and splenic anomalies are
less common. LVOTO, left ventricular hypoplasia, coarctation
of aorta and additional muscular VSD are less common.
Three principle issues are at stake. First, it is often claimed
that children with Downs syndrome have a higher incidence of
pulmonary hypertension. Second, the anatomical spectrum is
different in children with Downs syndrome, when compared
with their chromosomally normal peers. Third, there has been
some controversy on the perceived benefit of surgical repair.
Pulmonary hypertension is about 10 times more prevalent
in patients with Downs syndrome and has an earlier onset.
Those patients with Downs syndrome, therefore, must
undergo surgery at a very young age, preferably before 6
months, while some argue for even earlier repair. Pulmonary
hypertension has been reported to be more prevalent in those
having the Rastelli A configuration.
Obstruction to the left ventricular inflow and outflow, in
contrast, is said to be far less frequent in the setting of Downs
syndrome. This probably reflects the more frequent existence of
common valvar orifice in association with trisomy 21. Extensive
bridging of both inferior and superior leaflets, rather than one or

both leaflets being committed primarily to the LV, is more usual
in children with trisomy 21. Accordingly, the angle of the zone
of apposition between the inferior and superior leaflets is usually
perpendicular to the ventricular septum in children with Downs
syndrome, while this angle is often crooked and deviated from
perpendicular, in those with normal chromosomes. Recently
published series show that Downs syndrome is not a risk factor
for surgical repair. If anything, anatomy is more favorable in
those with trisomy 21. It is pulmonary vascular resistance, itself
related to age and other associated problems, that determine the
risk for these patients.
ConCluSIon
AVSD is characterized by the anatomical hallmark of a
common AV junction coexisting with deficient AV septation.
The components of AVSD includes a common AV valve ring
with five leaflet valve that guards a common orifice, unwedged
LVOT, an aortic orifice that is anterosuperior to the common
AV junction, disproportion of the left ventricular mass. There
are a number of classifications based upon the morphological
characteristics and hemodynamic features of the lesion.
Clinical features and presentation of AVSD depend on degree
of AV valve regurgitation and magnitude of left to right shunt.
An associated pretricuspid shunt in combination with a post
tricuspid shunt has a presentation of exaggerated pretricuspid
shunt lesion. Jugular venous pulse exhibits a dominant V
wave (not only with the presence of tricuspid regurgitation)
also as right atrium receives the regurgitate jet also from the
left ventricle. Precordial examination and palpitations are
similar to ostium secundum defect with the addition of the
apical systolic murmur that radiates towards the sternum as
far as the right sterna border. A fixed splitting of the second
heart sound (as for the pre-tricuspid shunt) may be associated
with mid-diastolic flow murmur because of the flow across
the right sided AV valve associated with systolic flow
murmur across the pulmonary valve. The electrocardiogram
typically shows a left axis deviation with counterclockwise
depolarization. The chest X-ray shows increased pulmonary
vascularity with dilated right atrium and right ventricle. The
features are altered with the of degree of pulmonary artery
hypertension and AV valve regurgitation. Echocardiography
is the investigative modality of choice and would even
decide the type of surgical intervention and modification of
the surgical intervention if required. Long term outcomes
are generally good and depend on the residual defects, left
ventricular outflow tract obstruction and degree of AV valve
regurgitation.
Medicine is the only profession that labours incessantly to
destroy the reason for its own existence.
James Bryce, 1914
20
or for relief of LVOTO. The results published to date include

the follow-up over a period of 43 years of surgical corrections
between 1958 and 2000 of 133 patients with shunting
exclusively at atrial level. Actuarial survival was 78 percent.
Mortality at 30 days was about 7 percent, which currently
could be expected to be no more than 1 percent. Extrapolating
from this premise would make predicted actuarial survival for
current patients about 84 percent. Survival of an age- and eramatched population without any congenital cardiac anomaly
was about 90 percent. Subtraction of these two figures leads us
to predict an excess mortality of just 6 percent, 43 years after
the surgical correction. Similar results have been reported
elsewhere, but it is impossible to predict with total accuracy
the outcomes for correction at the present time, albeit that
results are anticipated to be excellent for those with shunting
exclusively at atrial level, presuming it is possible to create a
competent left AV valve. Long-term results for repair of those
having a common AV valve are well-documented in analysis
of 801 children in Sweden born alive between 1973 and 1997.
Mortality at 30 days for the 502 patients undergoing surgical
correction over the last 5 years of the study was 1 percent.
The actuarial survival curve flattens off after 1 or 2 years, and
shows a loss of lives of about 10 percent in 30 years. How
this compares to an age- and era-matched population is not
known. Although similar results have been published, there
are not many papers on results over the long term.
305
Shunt DeFectS
306
SuggeSteD ReADIngS
1. Anderson RH, Ho SY, Falcao S, et al. The diagnostic features
of atrioventricular septal defect with common atrioventricular
junction. Cardiol Young. 1998;8:33-49.
2. Allwork SP. Anatomical-embryological correlates in
atrioventricular septal defects. Br Heart J. 1982;47:419-29.
3. Cetta F, Minich L, Edwards W, et al. Arioventricular septal
defect. In: Allen HD, Shaddy RE, Driscoll DJ, Feltes TF
(Eds). Heart Diseases in Infants, Children and Adolescents, 7th
edition. Lippincort Williams and Wilkins; 2008. pp. 647-67.
4. Chan KY, Redington AN, Rigby ML. Color flow mapping in
atrioventricular septal defects: Does it have an important role in
diagnosis and management? Cardiol Young. 1991;1:315-23.
5. Defects in cardiac septation. Snider AR, Serwer AG, Ritter
SB (Eds). Echocardiography in Pediatric Heart Disease. 2nd
addition. Mosby. 1997. pp. 235-97.
6. Ebels T, Anderson RH. Atrioventricular septal defect. In:
Anderson RH, Macartney RF, Shinebourne EA, Baker EJ,
Rigby ML, Tynan M (Eds). Paediatric, Cardiology. 2nd edition.
Churchill Livingstone: Har Court Publishers Limited. 2002.pp.
939-81.
7. Kaski JP, Wolfenden J, Josen M, et al. Can atrioventricular
septal defects exist with intact septal structures? Heart.
2006;92:832-35.
8. Mehta S, Hirschfeld S, Riggs T, et al. Echocardiographic
estimation of ventricular hypoplasia in complete atrioventricular
canal. Circulation. 1979;59:888-93.
9. Minich LA, Snider AR, Bove EL, et al. Echocardiographic
evaluation of atrioventricular orifice anatomy in children with
atrioventricular septal defect. J Am Coll Cardiol. 1992;19:149-53.
10. Rastelli GC, Kirklin JW, Titus JL. Anatomic observations on
complete form of persistent common atrioventricular canal
with special reference to atrioventricular valves. Mayo Clin
Proc. 1966;41:296-308.
11. Reeder GS, Danielson GK, Seward JB, et al. Fixed subaortic
stenosis in atrioventricular canal defect: a Doppler
echocardiographic study. J Am Coll Cardiol. 1992;20:
386-94.
12. Shrivastava S, Radhakrishnan S, Tomar M. Atrioventricular
septal defects in Echocardiography in congenital heart diseases,
A practical approach. 1st edition. 2008. pp. 42-51.
13. Silverman NH, Zuberbuhler JR, Anderson RH. Atrioventricular
septal defects: cross sectional echocardiographic and
morphologic comparison. Int J Cardiol. 1986;13:309-31.
14. Sigfsson G, Ettedgui JA, Silverman NH, et al. Is a cleft in
the anterior leaflet of an otherwise normal mitral valve an
atrioventricular canal malformationt? J Am Coll Cardiol.
1995;26:508-15.
15. Smallhorn JF, Tommasini G, Anderson RH, et al. Assessment
of atrioventricular septal defects by two dimensional
echocardiography. Br Heart J. 1982;47:109-21.
16. Wenink AC, Ottenkamp J, Guit GL, et al. Correlation of
morphology of the left ventricular outflow tract with twodimensional Doppler echocardiography and magnetic
resonance imaging in atrioventricular septal defect. Am J
Cardiol. 1989;63:1137-40.
17. Welke KF, Morris CD, King E, Komanapalli C, Reller MD,
Ungerleider RM. Population-based perspective of long-term
outcomes after surgical repair of partial atrioventricular septal
defect. Ann Thorac Surg. 2007;84:624-8.
18. Frid C, Bjrkhem G, Jonzon A, Sunnegrdh J, Annern G,
Lundell B. Long-term survival in children with atrioventricular
septal defect and common atrioventricular valvar orifice in
Sweden. Cardiol Young. 2004;14:24-31.
19. Talwar S, Singh V, Chandra N, Marwah A, Sharma R.
Challenges in Delayed Repair of Atrioventricular Septal
Defects. World Journal for Pediatric and Congenital Heart
Surgery. 2010;1:87-90.
C hapter
21
Patent Ductus Arteriosus

Ramesh Arora, Vijayalakshmi IB
IntroDuCtIon
Patent ductus arteriosus (PDA) is a common congenital heart
disease (CHD), in which there is a persistent communication
between the descending aorta and the pulmonary artery that
results from the failure of the normal physiologic closure of
the fetal ductus arteriosus. PDA closes spontaneously in the
vast majority of infants and persists into later life in some.
PDA is defined as persistent patency in term infants even after
three months.1 PDA may be isolated or may be an essential
component of a complex lesion or may also coexist with other
cardiac anomalies. PDA is critical for survival in neonates
with severe obstructive lesions to either the right or left side
of the heart and this has been dealt in the chapter on Duct
Dependant Circulation (Chapter 5).
HIStorICAL rEVIEW
The ductus arteriosus and the foramen ovale has been described
as early as in 181 AD by the Greek physician and philosopher
Galen in his original descriptions of the fetal circulation.2
Karl von Rokitansky, a professor of pathology from Vienna,
recognized PDA as a congenital malformation and illustrated
it in his monograph in 1852.3 William Harvey, proposed the
concept of active circulation of the blood. He stressed on the
large size of the arterial ductus and the fact that during fetal
life blood flowed from right to left through it.4 Highmore,
a friend of Harvey, described closure of the oval foramen
and arterial ductus to occur with the onset of respiration.5
He rightly believed that the arterial ductus collapsed as a
consequence of blood being diverted to the lungs. Virchow6
was the first to suggest that closure of the arterial ductus
results from contraction of its mural smooth muscle, while
Gerard7 introduced the concept of two-stage closure, in which
functional constriction is followed by anatomic obliteration.
In 1898, George Alexander Gibson described the
classic continuous murmur and other features of this
lesion.8 In 1907, John Munro first suggested the surgical

ligation of the PDA.9 In 1938, Robert Edward Gross from
Boston performed the first successful closure of PDA
in a 7-year-old girl with intractable heart failure.10 This
surgery introduced an amazing era of progress in the field
of surgery of congenital malformations of the heart. In
1991, the next surgical modification was introduced when
PDA closure was done by video-assisted thoracoscopic
surgery.11
Porstmann et al in 1967 reported the first successful
attempt of non-surgical closure of PDA using an Ivalon
plug.12 In 1979, Rashkind reported the use of a foam covered
wire hook device for closure of PDA, but the results were
less encouraging in the initial human studies.13 Subsequently
his group in 1987 described the successful deployment of a
percutaneously delivered double umbrella device in an 3.5
kg infant.14 Lock-Clamshell device was used for occlusion
of large ducts.15 Sideris introduced a self-adjustable PDA
device and this was followed by its modification into a
buttoned device in 1991.16 In 1992, Cambier et al reported
the use of Gianturco coils to occlude small PDA.17 In
1998 worldwide, the Amplatzer duct occluder (ADO)
was introduced and later its subsequent modifications
like Amplatzer duct occluder II (ADO II).18-20 The recent
Amplatzer duct occluder II additional size (ADO II AS) are
currently being used for infants below 6 kg and premature
neonates.21
Closure of PDA in preterm babies, with drugs like
indomethacin, a non-selective prostaglandins (PG)
inhibitor, was first reported in 1976.22 The first large and
comprehensive randomized controlled trial evaluating
the role of indomethacin and establishing its role in the
management of PDA was published in 1983.23 In 2000,
it was proved that ibuprofen therapy is as efficacious as
indomethacin for the treatment of PDA in preterm babies
with respiratory distress syndrome and is significantly less
likely to induce oliguria.24
Shunt DefectS
EMBrYoLoGY
The ductus arteriosus is derived from the sixth aortic arch. In
human beings, it develops by about the 6th week of embryonic
development from the distal portion of one of the sixth paired
aortic arches.25 The left, right or both ductus can sometimes
persist.26,27 The proximal portion of the sixth pair of embryonic
aortic arches usually persist as the proximal branch pulmonary
arteries and the distal portion of the left sixth arch persists as
the ductus arteriosus. In the typical left aortic arch, the aortic
end of the ductus arteriosus arises distal to the origin of the
left subclavian artery and inserts at the junction of the main
and left pulmonary arteries. The distal right sixth aortic arch
loses its connection to the dorsal aorta and degenerates. This
transformation is complete by 8 weeks of fetal life.28 In the
fetus, the ductus is about the same diameter as the descending
aorta and at term this is about 10 mm.29 The ductus arteriosus
usually is functionally closed within 48 hours of birth in fullterm neonates and is considered abnormal if it is patent in
full-term infants older than 3 months.1,30 The major factors
influencing its closure after birth are the increased production
of local vasoconstrictors (like endothelin) in response to higher
arterial oxygen tension. Also the levels of the vasodilators,
PGE2 and PGI2 (prostacyclin), fall due to the metabolism in
the now functioning lungs and elimination of the placental
source.28
InCIDEnCE
Isolated PDA accounts for 9 to 12 percent of all CHDs with
a higher incidence in females, with a female to male ratio of
2 : 1.31,32 The estimated incidence of isolated PDA is 1 in
2,500 to 1 in 5,000 live births.33-35 If all children with PDA
including those with silent PDA (only echocardiographic
Doppler evidence) are included, then the incidence has been
estimated to be as high as 1 in 500 or 0.1 to 0.2 percent of the
population.36
EtIoLoGY
308
In premature infants, the PDA is due to immaturity rather

than a developmental anomaly. In the premature neonate,
the occurrence of PDA is inversely related to the gestational
age and maturity. The incidence is 8 per 1,000 live births
and ranges from 20 to 42 percent.37,38 In preterm neonates,
weighing less than 1,000 g, the incidence can be as high as
80 percent.39 The patency of the ductus after birth in preterm
babies is due to the fact that the immature ductal tissue is
less sensitive to oxygen-mediated constriction and more
sensitive to PG-mediated vasodilation.40 The incidence
of PDA is higher in neonates with persistent low oxygen
tension in the blood like respiratory distress syndrome,
acute intrapartum stress, asphyxia and in those born at high
altitudes.41
A decreased incidence of PDA is seen in those neonates

whose mothers received prenatal steroids at least 24 hours
before delivery or who had prolonged rupture of membranes
of more than 72 hours duration. Decreased incidence is
also seen in neonates with intrauterine growth restriction.42
Antenatal steroids inhibit PG production and increase the
responsiveness of the ductus to the constricting effect of
oxygen and decrease its sensitivity to the dilating effects of
prostaglandins.42
Most cases of PDA are sporadic and many are believed to
be due to multifactorial inheritance.43 The recurrence rates
are between 1 to 5 percent among siblings of individuals with
isolated PDA.44-48 The mechanism of the genetic inheritance
is not yet known. It occurs with increased frequency in
several genetic syndromes with chromosomal abnormalities
such as trisomy 21 and 18, deletion syndromes 4q, 16p13.3
(Rubinstein-Taybi) and 9p (CHARGE), single-gene mutations
(such as Carpenters syndrome and Holt-Oram syndrome)
and X-linked mutations (such as incontinentia pigmenti).28,49
Familial patent arterial ductus can be either isolated or part
of a syndrome like Char syndrome, familial thoracic aortic
aneurysm/dissection and with bicuspid aortic valve with hand
anomalies.49
A number of teratogens are known to influence the development of the ductus, including rubella, alcohol, amphetamines,
anticonvulsants like hydantoin and valproate. The ductus is
most sensitive from 18 to 60 days of gestation.50,51 Rubella infection, especially in the first 4 weeks of gestation, has a high
occurrence of PDA. The incidence in these rubella affected infants is as high as 85 percent, when associated with other cardiac defects and is about 50 percent when it occurs as an isolated
lesion.52,53
AnAtoMY
In a patient with a normal left-sided aortic arch, the PDA
connects the main pulmonary artery near the origin of the left
pulmonary artery (LPA) with the descending aorta, 5 to 10 mm
distal to the origin of the left subclavian artery. The anatomy
is more varied in the presence of a right-sided aortic arch. In
the neonatal period, the size and shape varies greatly from
case to case. The PDA is most commonly left sided and is less
frequently right sided and arises distal to the right subclavian
artery and inserts near the proximal right pulmonary artery. In
rare instances, there is a bilateral PDA.54 The right-sided PDA
is especially associated with aortic arch anomalies.55-57
The proper knowledge of anatomy is needed for the cardiac
surgeon doing the surgical ligation. The PDA passes from the
anterior aspect of the pulmonary artery to the posterior aspect
of the aorta (Figure 1). The anatomic marker of the ductus is
the recurrent laryngeal nerve, which typically arises from the
vagus nerve just anterior and caudal to the ductus and loops
posteriorly around the ductus to ascend behind the aorta en
route to the larynx. It is the most commonly injured anatomic
21
Patent DuctuS arterioSuS
figure 1: Patent ductus arteriosus (PDA) passes from the anterior

aspect of the pulmonary artery to the posterior aspect of the aorta with
the recurrent laryngeal nerve just anterior and caudal to the ductus. Ao
= Aorta; LPA = Left pulmonary artery; MPA = Main pulmonary artery;
SVC = Superior vena cava.
structure in ductal ligation. Other less commonly injured

structures include the phrenic nerve and the thoracic duct.
Structures that have been mistaken for the PDA in surgical
procedures include the aorta, the pulmonary artery and the
carotid artery.
The PDA may persist in a wide variety of shapes and
sizes. The total length of the PDA and the size of the ampulla
can vary from few millimeters to several centimeters. It is
generally 5 to 10 mm in length.58 The ductus may enlarge with
age. In an infant the PDA seldom exceeds the diameter of the
aorta, which is 8 to 10 mm. In an adult, the ductus may be 15
to 25 mm in diameter, more consistent with the adult aortic
diameter.28,59,60 The PDA can be classified according to the
size of the internal ductal diameter in the lateral angiographic
view. PDA is silent if it is less than 1 mm, very small if less
than or equal to 1.5 mm, small if it is 1.5 to 3 mm, moderate if
it is 3 to 5 mm and large if it is more than 5 mm.61
Most often PDA is conical or funnel shaped with a large
aortic end (ampulla) tapering into the small pulmonary end.
This conical shape is mainly due to the ductal smooth muscle
constriction at the pulmonary artery insertion. It can vary from
being short and tubular to long and tortuous, have multiple
constrictions or have bizarre shapes. The angiographic
appearance of isolated PDA and its variations into five
types (Figure 2) has been described by Krichenko in 1989.62
The type A or conical type of PDA has a narrow end at the
pulmonary insertion with a well-defined ampulla at the aortic
end. The type B or window type of PDA is short and wide. It
figure 2: Illustrates the schematic and angiographic types of the

configuration of the ductus based on Krichenko et al classification.62
Ao= Aorta; MPA = Main pulmonary artery; PA = pulmonary artery;
PDA = Patent ductus arteriosus
309
Shunt DefectS
may be narrow at the aortic insertion. The type C or tubular

type of PDA is tubular without any constriction. The type D or
complex type of PDA has multiple constrictions. The type E or
elongated type of PDA has a bizarre shape with an elongated
conical appearance and the constriction being remote from
the anterior border of the trachea. Within the types A and
B, it is further classified into three subgroups depending on
the relationship of the site of insertion of the PDA at the
pulmonary end to the tracheal shadow.62
Abnormal Anatomy
In the presence of complex CHD, the usual anatomy of the
ductus may not be present. In the duct dependant cyanotic
CHDs, the ductus is markedly varied with regards to its
origin from the aorta, size and shape, length, tortuosity and its
insertion onto the pulmonary artery.63 There are four groups
seen.64 In the first group A, the PDA arises from the proximal
descending aorta and resembles Krichenko type A PDA. It
is seen in pulmonary atresia with intact ventricular septum
(PAIVS), critical pulmonary stenosis (PS) and tricuspid
atresia. In the second group B, the PDA arises from the
proximal or middle part of the aortic arch (vertical ductus
arteriosus). These ducts are most commonly seen in tetralogy
of Fallot-pulmonary atresia (TOF-PA), transposition of great
vessels, ventricular septal defect (VSD) with pulmonary
atresia and in single-ventricle physiology. In the third group
C, there is intermediate origin of the PDA. The PDA arises
more proximally than those in group A, but not as extreme
as seen in group B. PDA arises from the opposite side of
the origin of the left subclavian artery (LSCA). In the fourth
group D, the PDA arises from the subclavian artery. It is the
least common type, comprising less than 5 percent and this
PDA has the peculiar appearance of a Blalock-Taussig (BT)
shunt. The long tubular ductus arises from the LSCA (or from
the right subclavian artery in a right aortic arch) and joins the
pulmonary artery in a roughly perpendicular fashion.64
MECHAnISM of DuCtAL CLoSurE
310
As soon as the baby is born and starts crying and taking breath,
the collapsed lungs expand and the pulmonary circulation
starts functioning. The ductus arteriosus, which was essential
for fetal circulation, starts closing. The postnatal closure
of the ductus occurs in two stages. In the first stage within
12 to 15 hours after birth (in full-term infants), there is
contraction of the medial smooth muscle in the wall of the
ductus, which leads to shortening and increased wall thickness.
There is also protrusion of the intimal cushions into the lumen
and all this results in functional closure.65,66 In the second stage,
2 to 3 weeks after birth, there is infolding of the endothelium
with necrosis and proliferation of subintimal layers which leads
to fibrosis and permanent sealing of the lumen to produce the
ligamentum arteriosum.67 Closure begins at the pulmonary
end of the ductus; it may remain incomplete and dilated at the

aortic end and is known as ductus ampulla or ductus bump.
The histopathology of a normal ductus, not yet closed and
a persistently patent ductus is different, thus suggesting a
primary anomaly and not a secondary effect.68,69 The ductus
is a muscular artery with a thicker intima, less elastic tissue,
spirally arranged smooth muscle fibers and more hyaluronic
acid than the adjacent pulmonary trunk and aorta. The media
of the other arteries is composed mainly of circumferentially
arranged elastic fibers.68-70
The mechanism of ductal closure involves a complex
interaction of the level of arterial oxygen, circulating PGs,
genetic predetermination and unknown factors.71 The rise in
systemic oxygen saturation with the onset of ventilation, after
birth, causes active constriction in the ductus. Simultaneously,
there is a decrease in the level of circulating PGs due to
both factors, i.e. reduced production following removal of
the placenta and increased metabolism in the pulmonary
circulation resulting from the increase in pulmonary flow.
Removal of the strong vasodilatory effect of the PGs promotes
further constriction of the ductus.72,73 Other vasoactive
substances (such as acetylcholine, bradykinin and endogenous
catecholamines or variations in pH) may be involved in this
dynamic process of ductus closure.72-75 Response to PGs and
oxygen varies with ductal maturity: in the full-term infant the
ductus is sensitive to oxygen, while in the premature infant
the PGs have a dominant effect. Consequently, in premature
infants failure of ductal closure results from incomplete ductal
development, whereas in full-term infants, PDA results from
structural abnormalities of ductal tissue.
HEMoDYnAMICS
The persistent patency of the ductus causes left-to-right
shunting of the high aortic pressure blood into the lowpressure pulmonary artery, in both systole and diastole.
The magnitude of the left-to-right shunt in the PDA
depends on:76,77
1. The size and length of the PDA (directly proportional to the
diameter, inversely proportional to the length).This governs
the resistance offered to flow. In a small or restrictive PDA,
the magnitude of the left-to-right shunt is determined by
the resistance offered by the ductus.
2. The ratio between the systemic vascular resistance (SVR)
and the pulmonary vascular resistance (PVR). The pressure
difference between the aorta and the pulmonary artery
is dynamic and is dependent on the SVR, PVR and the
cardiac output. In a large PDA, the magnitude of shunting
is determined by the relationship of the SVR and PVR.
Hence, the left-to-right shunting through PDA has been
defined as dependent shunting.77
In the early weeks of life in term infants, significant
shunting is unusual because a high PVR limits the
development of a large aorto-pulmonary pressure gradient.78
activity and circulating catecholamines.28 These mechanisms

are responsible for the rapid heart rate and sweating often seen
in infants with heart failure. The diastolic runoff through
the PDA decreases the diastolic blood pressure in the aorta.
Along with this the shorter diastolic time due to tachycardia,
increased intramyocardial tension from left ventricular
dilatation and increased myocardial oxygen demand may
result in subendocardial ischemia.84
The physiological consequences of significant PDA in
preterm babies may include pulmonary overcirculation and/
or systemic hypoperfusion. Both the increased pulmonary
blood flow and the increased lung interstitial fluid contributes
to decreased lung compliance and pulmonary hemorrhage.85
The increased capillary penetration of serum proteins to the
lung tissue leads to the inactivation of surfactant and this
increases the risk of respiratory distress syndrome in the
newborn.86 Systemic hypoperfusion can occur with large
ductal shunts, where over 50 percent of the flow can go
backwards, up into the aorta. This may result in significant
hypoperfusion to the brain, kidneys and gastrointestinal tract
even before a hemodynamically significant ductus is clinically
suspected. This organ hypoperfusion can result in renal
dysfunction, necrotizing enterocolitis, feeding intolerance and
intraventricular hemorrhage in the brain.87-89
The premature infants develop left ventricular failure on the
second or third postnatal day itself, even with a small ductus.
This is because the compensatory mechanisms are not well
developed. This may lead to low cardiac output syndrome and/
or alveolar edema.90 The immature myocardium contains fewer
contractile elements, sympathetic innervation is not adequate
and the left ventricle is less compliant in preterm than in term
babies.91,92 Preterm babies with a symptomatic PDA may
frequently have ST-segment depression on an electrocardiogram
(ECG), suggestive of subendocardial ischemia that normalizes
after the surgical closure of PDA.93 The subendocardial
ischemia is as a result of aortic run off to the low resistance
pulmonary circulation, which reduces the diastolic pressure and
flow particularly to the coronary circulation.
21
After a few weeks, volume overload of the left heart develops

with chamber enlargement as seen in VSD. Therefore, the
onset of congestive heart failure (CHF) with PDA is similar
to that in a VSD. The pulmonary vascular bed, left heart and
ascending aorta dilate proportionately to the net shunt.79 The
chambers that enlarge are the same as those in VSD, except
for an enlarged aorta, at the level of the PDA (i.e. enlarged
ascending aorta and transverse arch), which also handles an
increased amount of blood flow.
Isolated PDAs are classified80 hemodynamically according
to the degree of left-to-right shunting into:
1. Silent: Tiny PDA detected only by non-clinical means
(usually echocardiography).
2. Small: Continuous murmur common; Qp/Qs < 1.5/1.
3. Moderate: Continuous murmur common; Qp/Qs = 1.5 to
2.2/1.
4. Large: Continuous murmur present; Qp/Qs > 2.2/1.
5. Eisenmenger: Continuous murmur absent; substantial pulmonary hypertension (PH), differential hypoxemia and
differential cyanosis (pink fingers, blue toes).
The physiologic features of PDA depends on the magnitude
of the left-to-right shunt and the ability of the infant to handle
the extra volume load.81 The shunting results in increased
pulmonary flow and left heart volume overload.
In patients with moderate or large shunts, the left ventricular
dilatation increases the left ventricular end-diastolic pressure
and in turn the left atrial pressure leading to left atrial
dilatation. The increased pulmonary fluid causes decreased
lung compliance, which results in increased work of breathing.
Later there is overt left heart failure and rarely pulmonary
edema. A stretched, incompetent foramen ovale secondary to
left atrial dilation is a fairly common association.81 If the PDA
is large with PH, right heart failure can occur.
In a large PDA, due to the long-standing left-to-right
shunting, the pulmonary vascular bed is exposed to highpressure and increased pulmonary blood flow. This leads
to progressive morphological changes in the pulmonary
vasculature. These changes, including arteriolar medial
hypertrophy, intimal proliferation, fibrosis and eventual
obliteration of the pulmonary arterioles and capillaries. These
changes results in progressive increase in PVR. When PVR
approaches and exceeds SVR, there is reversal in the ductal
shunting and it becomes right to left.28 The pathophysiological
mechanisms for this are not completely understood, but there
is evidence that microvascular injury stimulates production of
growth factors and enzymes that result in intimal proliferation
and medial hypertrophy.82 Endothelial dysfunction and
platelet activation may also play a role in the obliteration of
pulmonary arterioles.83
Several compensatory physiologic mechanisms help to
improve myocardial performance and thereby maintain a
normal systemic output. The left ventricle compensates by
increasing stroke volume and eventually may hypertrophy. The
neuroendocrine adaptation causes increase in the sympathetic
CLInICAL fEAturES
The clinical history of patients with PDA varies from those
who present with CHF in infancy to those who are completely
asymptomatic upto adulthood. The clinical status is dictated
largely by the size of the left-to-right shunt, which depends on
the size of ductus and age of the patient. Infants with moderate
to large PDA may present with symptoms of CHF, including
poor feeding with failure to thrive, tachypnea and diaphoresis,
within the first few weeks of life as the left-to-right shunt
increases with the falling PVR. More commonly, many PDAs
are detected during evaluation of an asymptomatic heart
murmur.94 Others are detected incidentally by echocardiograms
performed for unrelated reasons in patients without symptoms
or clinical manifestations. Some older children may be
311
Shunt DefectS
healthy, but report exercise intolerance or carry the diagnosis

of asthma. The clinical course of prematures is different from
that in full-term born babies.
Physical Examination
On examination, the patient may have stunted growth,
precordial bulge (pigeon chest), bilateral Harrison sulcus.
Differential cyanosis and clubbing are important to detect
severe PH, as desaturated blood from the pulmonary artery is
shunted to the descending aorta.
Arterial Pulse
The radial pulse is typically bounding (collapsing or high
volume, waterhammer). The carotid, brachial, femoral
and even the dorsalis pedis pulses are bounding. The blood
pressure typically shows wide pulse pressure.
Inspection and Palpitation

On inspection jugular venous pulse is normal, but hopping
carotid pulsations are seen. The precordium is hyperdynamic
with hyperdynamic left ventricular apex on palpation. There
is a systolic or continuous thrill in the left second intercostal
space on palpation in small to moderate-sized PDA.
Auscultation
312
The characteristic physical finding is a continuous murmur

heard at the upper left sternal border or the left infraclavicular
area, often referred to as a machinery murmur.95 This murmur
is also called as Gibson murmur and is the hallmark of PDA.
This murmur typically accentuates in late systole and marches
over the second sound without change in the character of the
murmur. The loudness of the murmur depends largely on
the magnitude of shunting. The left-to-right shunt occurs in
both phases of the cardiac cycle, producing the characteristic
continuous murmur. In patients with high PVR (newborns) a
murmur may not be present. In the early weeks of life, only
systolic murmur may be present and the diastolic component
becomes apparent as the PVR falls and the diastolic shunting
increases. The murmur is often heard in the back, particularly
on the left.94 If the shunt is large, a thrill may be present and a
diastolic rumble may be audible at the cardiac apex, due to the
increased flow across the mitral valve. In patients with high
PVR, there may be no murmur during systole or diastole, as
shunting may be minimal. The Eddy sounds may be heard.
These sounds are produced due to the turbulent flow inside
the ductus, which is caused by the head on collision of the
diagonally opposite flows from the aorta and pulmonary artery.
The intensity of the pulmonic component of the second heart
sound may be increased in large PDA and paradoxical splitting
of the second heart sound can occur. Patients with tiny,
incidentally discovered silent PDAs have normal cardiac

examination.
An untreated large PDA can also produce pulmonary
vascular obstructive disease, with a resulting bidirectional
shunt at the ductus level. The bidirectional shunt may produce
cyanosis only in the lower half of the body (i.e. differential
cyanosis). Auscultation no longer reveals the continuous
murmur or the apical rumble as a result of the shunt reduction.
The S2 is usually narrowly split with loud P2 due to PH.
Clinical findings in Preterms

Premature infants can have a unique presentation. Clinical
signs of hemodynamically significant PDA (hsPDA) usually
appear between days 3 and 4 of life and may include a general
deterioration in the status with multiple episodes of apnea,
increasing oxygen requirements with ventilator dependence
and poor perfusion with cardiopulmonary deterioration.80
They can also present with necrotizing enterocolitis. CHF
often occurs earlier as compared to term infants. This is
because they have a significant left-to-right shunt due to the
immature pulmonary arteries and decreased PVR. Persistent
tachycardia and tachypnea are frequently seen. There may be
increase in the precordial activity with bounding pulses and a
wide pulse pressure (> 25 mm Hg). Palmar pulses, which are
palpable pulses in the palms of the hands, may be present. A
gallop rhythm may be heard. A systolic murmur at the left mid
to upper sternal border is more common than a continuous
murmur, which is less frequent. An enlarged liver can often
be appreciated.
Clinical diagnosis of hsPDA needs at least two of the
following findings like heart murmur, persistent tachycardia
(heart rate > 160/min), active precordium, bounding pulse
or pulse pressure > 25 mm Hg, hepatomegaly, pulmonary
hemorrhage (defined as blood or blood-stained fluid aspirated
from the endotracheal tube in association with a respiratory
deterioration and radiographic evidence of pulmonary
hemorrhage), increasing respiratory support by 20 percent
increase in oxygen supplementation or in pressure support and
chest radiographic evidence of cardiomegaly or pulmonary
congestion.96 The physical examination may not rule out PDA
in the very low birth weight preterm on mechanical ventilation
and an echocardiography is necessary to confirm the presence
of PDA.
InVEStIGAtIonS
Chest X-ray
The findings on chest X-ray are proportionate to the degree
of shunting. The chest radiograph may be completely normal
in a small PDA. The chambers enlarged in moderate to large
PDAs are the left atrium (LA), left ventricle (LV), pulmonary
artery (PA) and the ascending aorta with plethoric lung fields
21
figures 4a and B: A. Transthoracic echocardiography in ductal view

shows large patent ductus arteriosus (PDA) with its ampulla; B. Color
Doppler shows mosaic jet entering the pulmonary artery. The width of
the jet indicates the size of PDA. AO= Aorta; MPA = Main pulmonary
artery;
figure 3: Chest x-ray in posteroanterior view in a case with large patent

ductus arteriosus shows cardiomegaly, prominent main pulmonary
artery with plethoric lung fields
(Figure 3). Main pulmonary artery (MPA) dilatation is the

earliest radiological sign and is known as Cap of Zinn. The
chest X-ray films of PDA are indistinguishable from those
of VSD. As in VSD with Eisenmenger syndrome, in patients
with PDA with Eisenmenger syndrome, the heart size returns
to normal because of the reduced magnitude of the shunt. The
peripheral pulmonary vascularity decreases, but the central
hilar vessels and the MPA are greatly dilated owing to severe
PH. Calcified ductus arteriosus calcifications (railroad track
sign) can be seen in adults.
Electrocardiogram
Electrocardiogram findings are proportionate to the degree
of shunting. In patients with small PDA, the ECG is often
completely normal. In patients with moderate sized PDA,
ECG may show volume overload of LV and LA, Those with
larger shunts may demonstrate sinus tachycardia, LVH and
LAH. The free transmission of the aortic pressure to the
PA produces PH, resulting in right ventricular hypertrophy
(RVH). Therefore, the ECG shows biventricular hypertrophy
and LAH in a large PDA with elevated PA pressure. The
ECG in a patient with large PDA and irreversible PH shows
pure RVH because the LV is no longer volume overloaded.
Echocardiography
The diagnosis of PDA is usually made on clinical grounds
and confirmed by transthoracic echocardiography (TTE).
figure 5: PDA measurements to be made on echocardiography.

A = Minimal diameter; B = Ampulla length; C = Ampulla diameter
(Reprinted: from Ramaciotti C, Lemler MS, Moake L, Zellers
TM. Comprehensive assessment of patent ductus arteriosus by
echocardiography before transcatheter closure. J Am Soc Echocardiogr.
2002;15:1155 with permission from Elsevier)
It is classified as silent, small, moderate or large. TTE done in

high parasternal short-axis view (ductal view) can delineate
further, the PDA characteristics that can be used to select
candidates for coil or device closure in the catheterization
laboratory (Figures 4A and B). Therefore, measurement of
the minimal diameter and the ampulla size are of extreme
importance. The minimal diameter of the PDA is the
narrowest inner echocardiographic dimension measured.
The ductal ampulla is the vascular structure between the
narrowest diameter and the ductal aortic end. The ductal
ampulla length is the distance between the mid-position of
the narrowest diameter and the mid position of the ductal
aortic end. The ampulla diameter, which is the diameter of
the ductal end at the descending aorta, is visualized from the
long-axis suprasternal or high parasternal views (Figure 5).97
313
Shunt DefectS
The greatest value of TTE and Doppler evaluation in the

diagnosis of PDA is to exclude other significant intracardiac
lesions.
In a patient with moderate to large PDA, the LA and LV
are enlarged, while in a small PDA chamber sizes are usually
normal. The ratio of the LA size to the aortic root size (both
measured in systole) can be used to estimate the degree of
ductal shunting. If this ratio is greater than 1.2 (normal is 0.8
1.0), it suggests a significant shunt.94
Doppler echocardiography reveals continuous flow from
the aorta into the MPA. If the magnitude of the left-to-right
shunt is large, continuous flow around the aortic arch into
the ductus arteriosus in diastole and flow reversal in the
descending aorta are evident.98 There may be also variable
levels of continuous flow in the branch pulmonary arteries
related to the magnitude of shunt. As the shunt magnitude
increases, increased flow in the pulmonary veins is evident.
Color Doppler is a very sensitive modality in detecting the
presence of PDA and is used to estimate the degree of ductal
shunting. Color flow signal can detect an extremely tiny
patent ductus entering the PA near the origin of the LPA. In a
patient with large PDA with PH, with low velocity or right-toleft flow, it may be difficult to demonstrate even a large PDA.
Associated findings such as septal flattening, unexplained
RVH and high-velocity pulmonary regurgitation should make
one investigate for a PDA.28 Contrast echocardiography may
be helpful and the microbubbles are seen in the descending
aorta (from ductal right-to-left shunting) and not in the
ascending aorta. The RV pressure can be estimated from the
peak velocity of the tricuspid regurgitation jet. The Doppler
velocity of the pulmonary regurgitation flow, if present, can
be used to estimate the pulmonary artery diastolic pressure.
(approximately Qp : Qs > 2) and this had more than 90 percent

specificity and sensitivity.101
Magnetic resonance Imaging and

Computed tomography
Computed tomography (CT) can assess the degree of
calcification in adults.102 Volume rendered (VR) CT image
can define the anatomy of the PDA well (Figure 6). Magnetic
resonance imaging and computed tomography is used to
define anatomy in a PDA with unusual geometry and with
associated abnormalities of the aortic arch.103 Cardiac
magnetic resonance imaging may be useful to evaluate the
anatomy, if a ductus arteriosus aneurysm is suspected.104
nAturAL HIStorY
The functional closure of the PDA occurs in 20 percent of the
term infants at 24 hours after birth, 82 percent at 48 hours and
100 percent by 96 hours of life.105 The term winking ductus
was coined in a study that showed that in healthy newborns
up to day 5, there could be intermittent shunting even when
the PDA seems to have closed.106 Even after functional
ductal closure, the potential to reopen exists for the next 7 or
Echocardiography in Preterm Neonates
314
Echocardiography is not recommended routinely for all preterm

neonates. A clinical diagnosis of PDA should preferably be
confirmed by echocardiography prior to starting medical
therapy. A hsPDA is diagnosed in the presence of a ductus
diameter more than 1.5 mm and absent/retrograde diastolic
flow in the postductal aorta.99 PDA has also been classified as
small, moderate or large on the basis of the ratio of the smallest
ductal diameter to the ostium of the LPA (PDA: LPA ratio). A
ratio greater than or equal to 1 defines a large PDA, greater than
or equal to 0.5 but less than 1, a moderate PDA and less than 0.5
a small PDA.100 The pattern of diastolic flow in the descending
aorta has been compared with pulmonary to systemic blood
flow (Qp : Qs). This also showed a significant relationship:
antegrade diastolic flow, absent diastolic flow and retrograde
diastolic flow showing mean Qp : Qs of 1.01 : 1, 1.3 : 1 and
1.7 : 1, respectively. El Hajjar et al found that ductal diameter
more than 1.4 mm/kg, LA : Ao more than 1.4 : 1, LPA mean
velocity more than 0.42 m/s or LPA diastolic velocity more
than 0.2 m/s, all predicted an LV output: SVC ratio more than 4
figure 6: Volume rendered (VR) computed tomography image

illustrates a large window type of patent ductus arteriosus (PDA). Ao =
Aorta; MPA = Main pulmonary artery;
been reported in adults.112,113 The true incidence of aneurysm

of the PDA is unclear, although it has been reported to be as
high as 8 percent.114 It is incidentally discovered and can
resolve spontaneously without sequelae. The etiology may
be genetic or it may develop after IE, surgical closure or
transcatheter coil occlusion.115-117 Arterial duct aneurysms
are classified into:
a. The spontaneous infantile type that is present at birth
and grows rapidly.
b. The adult type that grows during childhood or
adulthood.58
Falcon et al118 classified this disorder into three types: (1)
aneurysms that are patent on both the aorta side and pulmonary
artery side of the arterial ductus, (2) those that are patent on
the pulmonary artery side, and (3) those after operation for
PDA. Type 1 is frequently observed in children/infants and
type 2 in adults.
The ductus arteriosus aneurysm may present with
symptoms due to compression of the adjacent nerves or
pulmonary structures.119,120 They usually have a benign
course; but surgical resection is indicated if there is functional
compromise of the adjacent structures, persistent patency of
the ductus beyond the neonatal period, thrombus extending
into adjacent vessels, evidence of thromboembolic events,
or underlying connective tissue disease.121 The role of
transcatheter occlusion with aneurysm obliteration has not
been established for ductus arteriosus aneurysm, but one
promising technique is placement of a covered stent in the
aorta to simultaneously exclude the aneurysm and occlude the
PDA.122
CoMPLICAtIonS
DIffErEntIAL DIAGnoSIS
Patients with PDA have increased morbidity and mortality,

primarily due to the development of CHF and infective
endocarditis (IE).40 Pulmonary hypertension is a less common
problem.
1. Congestive heart failureCHF occurs in the preterms, young
infants and in adults with large PDA. In the adult, atrial
arrhythmias (fibrillation or flutter) frequently accompany the
heart failure.110
2. Infective endocarditisroutine treatment of PDA with transcatheter or surgical closure and antibiotics has decreased the
IE. The vegetations usually accumulate at the pulmonary end
of the PDA. The IE associated with PDA remains a significant
health problem in underdeveloped countries with limited
health resources and access to health care.111
3. Pulmonary vascular diseasean isolated large PDA, as
with any large left-to-right shunt, can result in PH and
eventual irreversible vascular disease. It is now extremely
rare to encounter a patient with pulmonary vascular
obstructive disease due to the early diagnosis and timely
intervention.
4. Aneurysm of PDAthe PDA aneurysm is a rare complication and commonly presents in infancy, but has also
The differential diagnosis for PDA are aortopulmonary window

(APW), VSD with aortic regurgitation, rupture of sinus of
Valsalva, coronary arteriovenous fistula, systemic arteriovenous
fistula, branch pulmonary artery stenosis, coarctation of aorta
(COA) with collaterals and rarely venous hum.
21
8 days especially in preterms.107 In preterm babies, patency

of ductus arteriosus is common, as due to immaturity they
lack the normal mechanisms for postnatal ductal closure.
Delayed spontaneous closure of the ductus may be anticipated
if the preterm baby does not succumb to other problems.80
Premature babies who had a significant PDA are more likely
to develop bronchopulmonary dysplasia.
The natural history of PDA is determined by the size
and magnitude of the shunt and the status of the pulmonary
vasculature. Patients with small PDA will have a normal
prognosis with only the risk of infective endarteritis. Patients
with small to moderate PDA are asymptomatic during
infancy and childhood. Infants with large PDA presenting
with CHF may not survive without intervention, succumbing
to poor nutrition and respiratory failure. In many infants,
the PVR remains modestly elevated but in rare instances it
never falls significantly after birth and the child may remain
asymptomatic or minimally symptomatic despite the presence
of a large PDA. In theses patients even with the timely
intervention of closure of PDA, pulmonary vascular disease
may progress and eventually prove fatal, suggesting that the
PH may be primary rather than secondary to the PDA.108,109
At present, with widespread use of echocardiography, the
diagnosis is being made at a younger age and virtually all cases
are being closed either with devices or surgically. It is now
extremely rare to encounter a patient with pulmonary vascular
obstructive disease. This can occur by age of 2 years in an
untreated large PDA. Rarely irreversible pulmonary vascular
disease or Eisenmenger syndrome may occur gradually over
time in patients with untreated, large, non-restrictive PDA.94
MAnAGEMEnt
Medical Management
Medical therapy for CHF due to large PDA should be short term,
until definitive surgical or transcatheter closure is performed.
Acute medical treatment for PDA before definitive closure
is usually not necessary as most term babies and children
are asymptomatic. Symptomatic patients usually improve
with a standard regimen of diuretics and afterload reduction.
Patients who are considered unacceptable candidates for
definitive closure of PDA, due to pulmonary vascular disease
may be managed with pulmonary vasodilating agents, such as
chronic oxygen therapy, prostacyclin, nifedipine, bosentan or
sildenafil.94 Recent guidelines do not recommend endocarditis
prophylaxis for patients with isolated PDA.
315
Shunt DefectS
Preterm Infants
Treatment of PDA in preterms varies with the magnitude of
shunting and the severity of hyaline membrane disease. The
PDA may contribute to the mortality in these preterms with
respiratory distress syndrome. Intervention is required in
preterm babies, who demonstrate signs of a significant left-toright shunt and who are unresponsive to the medical measures
to control the CHF. Medical management in premature
babies consists of pharmacologic closure using inhibitors of
the arachidonic acid metabolism pathways. The commonly
used drugs to constrict and close the PDA are indomethacin
or ibuprofen. Both these drugs inhibit PG synthesis. Fluid
restriction and diuretic therapy are also required in these
preterms to treat CHF. Surgical ligation is required in
about 10 percent of these babies who are unresponsive to
indomethacin.80
Indomethacin has been used for many years to successfully
close PDA. The medication is contraindicated in patients
with active bleeding, low platelet count, intracranial hemorrhage, renal insufficiency or necrotizing enterocolitis.23
Ibuprofen has been studied extensively as an alternative to
indomethacin. It has less side effects on organ blood flow than
indomethacin.123,124 The parenteral preparations of ibuprofen
are more expensive than indomethacin and not available in
many places. A study with oral ibuprofen administration has
suggested that the oral route of administration can achieve
PDA closure with similar efficacy as compared to the
intravenous indomethacin.125
The dosage of indomethacin is an initial dose of 0.2 mg/kg
stat followed by two additional age adjusted doses given at 12
to 24 hours intervals. It is given as an infusion over 30 minutes,
with a usual maximum of two courses (Box 1).99 Some studies
have shown that 0.1 mg/kg daily of indomethacin for 6 days
achieved similar closure rates with fewer side effects.126,127
Ibuprofen is usually given at 10 mg/kg stat followed by 2
doses of 5 mg/kg/dose 2 doses at 24 hour intervals.24
There have been several approaches to the timing of
treatment of PDA in preterms. The unresolved issues are
whether to treat these infants when they become clinically
Box 1: Dosage of indomethacin and ibuprofen for
closure of patent ductus arteriosus
indomethacin
Initial dose
0.2 mg/kg stat followed by age adjusted doses
Subsequent dose
< 2 day-0.1 mg/kg/dose 12 hourly for 2 doses
2-7 day-0.2 mg/kg/dose 12 hourly for 2 doses
> 7 day-0.25 mg/kg/dose 12 hourly for 2 doses
ibuprofen
316
10 mg/kg stat followed by

5 mg/kg/dose 24 hourly for 2 doses
symptomatic or give targeted presymptomatic or prophylactic

treatment. None of these approaches has shown unequivocal
benefits in terms of outcomes.128
Interventions
Technical advancements in device design coupled with
improvements in quality of catheters, delivery sheaths, wires,
retrieval equipments and superior non-invasive imaging
modalities for identifying anatomical variations in ductus
anatomy have resulted in evolution of device closure of PDA
as a preferred modality of management in most interventional
cardiology centers.129,130 Currently the benefits of transcatheter
closure of PDA compared to surgical closure seem obvious in
terms of short hospital stay, no thoracotomy scar, comparable
success rate and very minimal morbidity.129-132
InDICAtIonS for PDA CLoSurE

Premature Infants
PDA closure is indicated in all patients less than 10 days of age
with symptomatic PDA, who had no response to indomethacin
and for those who are more than 10 days old. Symptomatic
PDA is defined as respiratory rate of more than 70 per minute,
heart rate more than 160 per minute, liver enlargement more
than 3 cm below costal margin and cardiomegaly more than
60 percent on chest X-ray.133
Children and Adults

Symptomatic and even asymptomatic PDA should be closed
to avoid CHF, pulmonary vascular disease, IE and aneurysm
formation.112,133,134
Silent Patent Ductus Arteriosus

With the widespread use of echocardiography and Doppler
color flow imaging, silent PDA has been shown to be
present in 0.5 to 1.0 percent of the patients undergoing
echocardiography for unrelated reason. The term silent
PDA was first used to describe patent, but not audible arterial
ductus in preterm babies with respiratory distress syndrome.
Management of these silent ducts is controversial. Balzer
et al135 published a case report of silent PDA presenting
as endarteritis and recommended ductal closure, whereas
others clearly opposed it because of the potential mortality,
morbidity and expense.36,133 Bennhagon and Benson in
their analysis of hemodynamics and angiographic study
found that the PDA murmur becomes silent probably due
to the direction of the jet across the ductus arteriosus not
reaching the anterior wall of the main pulmonary artery.136
Considering the findings with no difference in ductal size
and consequently no difference in clinical importance
between silent and audible PDA, these authors drew the
Class III
Sideris Buttoned Device
1. Transcatheter PDA occlusion should not be attempted in

a patient with a PDA with severe pulmonary hypertension
associated with bidirectional or right-to-left shunting that
is unresponsive to pulmonary vasodilator therapy (Level
of Evidence: C).
Regular buttoned device introduced in 1990 was used

for occluding PDA of all types and sizes upto 15 mm by
transvenous route through 7-8 F long sheath during a 6
year period ending in August 1996 in 284 patients with 98
percent success rate. But, residual shunt was high (40%) at
implantation, which decreased with time to 0 percent at the
end of 5 years, yet the risk of IE continued.145 For that reason,
modified devices-folding plug, infant buttoned device and for
adults wireless devices particularly the transcatheter patch for
large PDA 12 to 22 mm have undergone clinical trials.146,147
recommendations for transcatheter PDA occlusion137

Class I
1. Transcatheter PDA occlusion is indicated for the treatment
of a moderate-sized or large PDA with left-to-right shunt
that results in any of the following: Congestive heart
failure, failure to thrive, pulmonary overcirculation (with
or without pulmonary hypertension), or an enlarged
left atrium or left ventricle, provided the anatomy and
patient size are suitable (Level of Evidence: B).
Class IIa
1. Transcatheter PDA occlusion is reasonable in the presence
of a small left-to-right shunt with normal-sized heart
chambers when the PDA is audible by standard
auscultation techniques (Level of Evidence: C).
Class IIb
Catheter Interventions
Transcatheter closure of small PDA using coils (single or
multiple) has become an accepted alternative to surgical
closure in most cardiac centers specially in developing
countries.138-140 Gianturco coils are small coiled spring wires
with fabric strands woven into springs (Figure 7A). They are
available as standard 0.035, 0.038 and 0.052 with 3 to 15
mm helical diameter. The size of the ideal coil for a given
ductus is not clear. The minimum PDA diameter, configuration
of the entire ductus, size of the ampulla and the age/weight
of the patient determines the coil size and combination.138
21
1. In rare instances, transcatheter PDA occlusion may be

considered in the presence of a bidirectional PDA shunt
due to pulmonary hypertension and obstructive pulmonary
vascular disease but reversible to pure left-to-right shunting
with pulmonary vasodilator therapy (Level of Evidence:
C).
2. Transcatheter PDA occlusion may be considered in a PDA
associated with a small left-to-right shunt with normal
heart size and an inaudible murmur (Level of Evidence: C).
In almost all patients echocardiographic assessment of the

ductus can be obtained by using high parasternal duct and
suprasternal views, which can be confirmed by angiography
during the procedure. The coil diameter should be at least
two times the minimum PDA diameter and yet fit within the
ampulla of the ductus.138,139 For small to moderate size PDA
0.038 coils are usually selected, but for large PDA 0.052 are
more advantageous. There are no specific guidelines available
for coil sizes (thickness, diameter and length).
Several techniques have evolved following the first
successful use of standard coil by the antegrade route for
occlusion of small PDA (< 2.5 mm). The retrograde approach
was described for closure of small PDA (< 3.3 mm)141 and
encouraged by these results, with antegrade technique
delivery of multiple coils to close the larger size PDA was
attempted.142 The immediate success rate using single or
multiple coils ranges from 67 to 95 percent, almost invariably
related to ductus size.139,140,143 Although ducts as large as
7 mm have been closed with coils, a larger ductus diameter is
an unfavorable factor.140 In addition, the success and occlusion
rate are also related to type and number of coils used (Figures
7B to D). The accurate placement of coils in a PDA, specially
if large, can be technically challenging.
The most common complication is embolization to the
distal pulmonary arteries (620%).140 Embolization is another
inherent complication even with the use of bioptomeassisted
technique.139 Retrieval of coil mass is at times difficult,
requires placement of larger sheath and adds to the expense of
the procedure. There is very little margin for error in infants
less than 5 kg with large ductus, where use of multiple coils
and a coil turn left in the LPA may lead to progression of
stenosis in the LPA.138 Lastly, the occlusion rates are still
lower than other occlusive devices and surgery.129,139,144
conclusion that silent PDA, when diagnosed should be

recommended for surgical or transcatheter closure.
Gianturco-Grifka Vascular Occlusion Device

Gianturco-Grifka vascular occlusion device is a fabric sac into
which a long coil is extruded, which confirms to the size and
shape of the large PDA with controlled delivery system.148
It is ideal for long tubular PDA and should not be attempted
in window type PDA, as there is not enough vessel length
317
Shunt DefectS
figures 7a to D: A. Patent ductus arteriosus (PDA) coil; B. Post procedure echocardiogram showing PDA coil in situ; C. Lateral angiogram
showing type D PDA; D. Post procedure angiogram showing coil in situ with no residual shunt. Ao = Aorta; MPA = Main pulmonary artery.
against which sac contact can maintain its position.62 The

device is not technically suitable for PDA more than 6 mm in
size and for infants less than 3 kg as the delivery sheath is 8
F. Using strict criterias for its use, only one-third of the cases
were found suitable by Ebeid et al.149 The prospective larger
clincial trials have not been done.
Duct-occlud and Nit-occlud Device

318
The duct-occlud device was developed to have a proper match

with the size and shape of the PDA with a high stability during
and after closure, as well as for achieving higher complete
closure rates.150 A modification of the duct-occlud device is the

reinforced device that has a cone-shaped appearance instead
of hourglass and achieves denser coil looping in the PDA
facilitating total occlusion. Nit-occlud device is a modification
of the reinforced device and has same clinical configuration
but is made of nitinol-titanium alloy, which has higher shape
memory than steel coils and is suited for Type A conical
PDAs (Figures 8A to C). The European registry and United
States Food and Drug Administration (US-FDA) trial reported
successful implants in 90 percent and 77 percent respectively. In
the former trial, there was a report of rupture of PDA that needed
surgical intervention and pulmonary artery embolization in 3.4
21
figures 8a to c: A. Picture of Nit occlud; B. Fluoroscopy in right anterior oblique (RAO) view illustrates Nit occlud attached
to the delivery cable;C. Check aortic angiogram in RAO shows Nit occlud in position with no residual shunt
percent cases. The standard device is recommended for PDA

less than 2 mm and Nit-occlud for PDA less than 6 mm.150
Amplatzer Devices
There are various types of Amplatzer duct occluders and
devices to close the PDA (Figures 9 A to D).
1. Amplatzer duct occluder (ADO): It was designed to
overcome the drawbacks of the other devices used in the
recent past. This occluder has gained popularity owing to its
user friendly delivery system, needing low fluoroscopic time,
easy repositioning and adaptation to all anatomical variations
of PDA (Figure 9A). It is the only FDA approved device and
is available in various sizes from 5/4 to 16/14 mm, can be
delivered through 5 to 8 F sheath; closes the ductus by stenting
the communication with its tubular part and by thrombosis.129
Calibrated angiography is done to select the specific occluder
for a given PDA. In general, a device is chosen so that the
diameter of the pulmonary arterial end of the device is 2 to 3
mm larger than the narrowest diameter of the ductus (usually
the pulmonary end of the ductus) (Figures 10A and B).
Although for the selection of the long delivery sheath there
are recommendations by the manufacturer, usually one size
higher is preferred by the operators. There are multiple studies
suggesting high level of safety and efficacy of ADO.129,151 Pass
et al in their multicenter USA trial performed to obtain FDA
approval, included 439 patients with exclusion criteria of those
less than 5 kg, PVR more than 8 Wood units, inferior vena
cava thrombosis and sepsis.129 The procedure was successful
in 435 (99%) with PDA size of 0.9 to 11.2 mm. The efficacy
rate (echocardiographic complete occlusion of PDA) was
99.7 percent at one year. Additionally, virtually every shape
of the ductus was closed using the ADO. The complication
rate was 2.3 percent with a single death that was unrelated
figures 9a to D: A. Amplatzer duct occluder with the retention disc

on aortic end; B. Amplatzer muscular ventricular septal occluder with
retention disc on both the sides; C. Amplatzer duct occluder II with
two retention discs of 3 mm on either side with central cylinder with no
polyester material; D. Amplatzer duct occluder II AS is additional size
with a bigger central cylinder
to device implantation. The most concerning morbidity was

aortic obstruction in 1 and LPA stenosis in 2 (gradient > 20
mm Hg) at 1 year. Device embolization occurred in one case
requiring surgery, as retrieval is not always possible. Amongst
the devices currently available, ADO has the highest efficacy
and safety in closing PDA more than 5 mm.130
Occasionally, large PDA may be encountered, which are
not amenable to closure even with the largest available ADO.
Such ductus have been closed with Amplatzer ventricular
septal occluder and no pulmonary or aortic obstruction was
observed on follow-up.130,152 Angiographic ventricular
319
Shunt DefectS
figures 10a and B: Descending aortic angiogram in left lateral view shows a large patent ductus arteriosus (PDA)
opacifying main pulmonary artery (MPA); B. 10 x 8 Amplatzer duct occluder (device) in situ. Check angiogram shows no residual shunt.
320
assessment in adults with large PDA may be potentially

imprecise due to the overlap between large aorta and
pulmonary artery. A compliant balloon may be used to assess
the minimum diameter, configuration and distensibility of the
PDA or intravascular ultrasound imaging can be done.153
Kinking of the delivery sheath commonly occurs and it
mandates selection of kink resistant sheath with optimal shape
and length.154 Fischer et al evaluated the role of ADO in eleven
infants with PDA measuring angiographically 1.5 to 5 mm.155
The procedure was successful in 82 percent and residual
flow was seen in one patient at 24 hours, which subsequently
disappeared at 45 days follow-up. But technical problems
in advancing the device through sheath at right ventricular
outflow tract (RVOT) occurred in 75 percent. The closure of
large PDA in very small infants was considered challenging in
the past and not recommended by the device manufacturers.
But a recent study shows device closure of large PDA, in
infants weighing 6 kgs was successful in 60/61 infants
(98.4%). The age, ranged from 9 days12 months (mean 8.9
months), weight ranged from 2.2 to 6 kg (mean 5.3 kg), and
PDA measured 3.2 to 8.7 mm (mean 4.8 mm). The largest
device used was 12 10 mm. Mild aortic obstruction occurred
in 2 cases (3.3%), as the device got displaced towards the small
aorta after release. The device embolized in 2 cases (3.3%).
In one it was retrieved by a novel method like fastening the
screw in the aorta and was subsequently closed with a 4 6
Amplatzer duct occluder II. Left pulmonary artery obstruction
occurred in one case (1.6%). Four cases (6.6%) had minor
vascular complications.156
2. Angled Amplatzer duct occluder: Regular ADO however
was not found very suitable for infants and small children due
to the possibility of encroachment into LPA or aorta causing
significant hemodynamic obstruction as a result of protrusion
of the occluding device. Since PDA is a remnant of the sixth

aortic arch, it results in an acute angle with the descending
aorta of 31.6 to 34.4 degree. For this, ADO with a 32 degree
angled retention disc was specially designed and its initial
human experience confirms it to be safe and efficacious for
infants having small PDA ampulla/window type ductus
(Figures 11A and B).19,157
3. Amplatzer plug device: Amplatzer vascular plug without
retention disc can be deployed in very small children to avoid
obstruction in aorta and pulmonary artery. Thanopoulous
et al attempted it in nine children, aged 0.5 to 3 years, PDA size
1.5 to 10.5 mm.158 Success rate was 100 percent but one patient
with large PDA had residual shunt with hemolysis and required
two coils for complete occlusion. This experience is however
limited and larger clinical trials are needed.
4. Amplatzer duct occluder II (ADO II): Recently,
ADO II is a specially designed for long ducts in infants
has become available for transcatheter closure of PDA.
This newer generation device, ADO II, is a self expanding
device with 2 retention discs (at both aortic and pulmonary
ends) that articulate with a central plug, which is sized to
the diameter of the midpoint of the PDA and is composed
of fine Nitinol wire mesh with no polyester fabric (Figure
9 C). The advantage of the ADO II is that it has a very low
profile and can be easily delivered through a 4 or 5 F sheath
in infants. As it has a retention skirt on either side, it can
be delivered either from the pulmonary or the aortic end,
which is especially useful in infants with severe pulmonary
hypertension. The ADO II with its thin delivery cable and
more flexible kink-resistant sheath makes the crossing of
the RVOT very easy in infants. The ADO II is delivered
through a TorqVue low profile catheter (St. Jude Medical,
Plymouth, MN), which comes in 4 and 5 French sizes.
21
figures 11a and B: A. Angled Amplatzer duct occluder (ADO) with concave retention disc with no polyester material;
B. Check angio with 12 X 10 angled ADO in situ shows no aortic obstruction and no residual shunt
It has a 90 degree curve to accommodate transvenous or

transarterial delivery. Because the ADO II is much more
flexible, it can be implanted in small infants.20 In our series,
the youngest neonate was 9 days old, weighing 2.2 kg,
with a large PDA, PH with biventricular dysfunction. As
the optimal medical management failed and patient was not
fit for surgery, as a bailout procedure the PDA was closed
with 3 4 ADO II through 4 F sheath from the aortic end
(Figures 12A and B). Loss of pulse in right lower limb was
treated with 2,000 IU of streptokinase. The left ventricular
ejection fraction improved from 35 to 48 percent and the
PA pressure dropped from 52/20 to 28/16 mm Hg. This is
probably the first reported case of PDA device closure in an
neonate with ADO II.156 The ADO II has two retention discs
on either side and the disc diameter is 6 mm more than the
central waist diameter. (Figures 12C and D).
5. ADO II AS: It is additional sizes of ADO II in which
the width of central disc is bigger and the retention disc is
not wide (Figure 9 D). The ADO II AS adds to the current
devices for PDAs in infants and premature babies.21 It is a
step further than the ADO II as it has smaller diameter discs,
stiffer, wider range, can close ducts up to 4 mm, best if tubular
and in small or premature babies. All sizes can go through 4
French TorqVue low profile catheter. Also the flexible Nitinol
cable minimizes the tension. The ADO II AS has small rims
to prevent the obstruction of LPA and the aorta. Arterial
approach may be preferable in some cases. Echocardiographic
guided intervention is a new concept and may be appealing,
logistically easier but more precise assessment is needed.
6. Lifetech duct occluder: It is the replica of Amplatzer duct
occluder with ceramic coating to prevent nickel toxicity.The
devices are available up to 26 24 mm to close very large PDA.
The custom made devices can be obtained up to 30 28 mm.
figures 12a to D: A. Aortic angiogram in right anterior oblique view

illustrates 3 x 4 Amplatzer duct occluder (device) II in situ, deployed
from the aortic end in a nine day old neonate with biventricular
dysfunction; B. Check angiogram after release of the device shows no
residual shunt; C. Aortic angiogram in left lateral view shows a type A
conical PDA (3.4 mm) in a 18 months child; D. Illustrates the central
cylinder in the ductus and the two retention discs of 5 x 4 ADO II on
either end of the ductus (pulmonary and the aortic end)
321
Shunt DefectS
Special Situations
Pulmonary Artery Hypertension
The feasibility of temporary balloon occlusion of PDA in
the catheterization laboratory allows assessment of the size
and hemodynamic parameters in patients with systemic
or near systemic pulmonary artery pressures (Figures 13A
to C). Although fall in systolic pressure of 20 percent
after O2 inhalation and tolazoline was being considered
as an indication for ductus closure, follow-up results of

Francis et al have shown that decline in PA pressure to
half of the systemic pressure is predictive of favorable
outcome and long-term results after PDA closure.159
Thanopoulus et al evaluated the use of ADO in seven
patients. Device delivery was successful in all without
complications with a fall in mean PA systolic pressure from
106 13 to 61 6 mm Hg.160 To prevent embolization into
aorta, the Amplatzer muscular VSD occluder also seems to
be more ideal in severe PH patients (Figures 14A and B).
figures 13a to c: A. Aortic angiogram in a 14 years old girl in right anterior oblique view shows large tubular duct measuring 13 mm and ampulla
21 mm; B. Balloon cocclusion of ductus was done and simultaneously pressure was monitored by another catheter through additional venous
access (arrow). Pulmonary artery pressure -115/80 mean 92 mm Hg, Aortic pressure-120/80 mean 93 mm of Hg; C. Aortic angiogram in left
lateral view illustrates Lifetech 18 x 16 duct occluder in situ, with no residual shunt. Post procedure, the pulmonary artery pressure dropped to
86/39 mean 55 and aortic pressure increased to 130/85 mean 100 mm of Hg
322
figures 14a and B: a. Aortic angio in left lateral view in a 10 years old girl showed 20 mm window type B patent ductus arteriosus (PDA); B. 20
mm muscular ventricular septal defect (MVSD) device in situ. The pulmonary artery pressure decreased from 120/80 mean 93 to 78/57 mean 60
mm Hg. The oxygen saturation (SaO2) preprocedure in upper limb92%, lower limb84% and this improved to 98% after device closure. After
3 months on follow-up pulmonary artery pressure had come down to 50 mm Hg and after 1 year the pulmonary arterial systolic pressure was 30
mm Hg and SaO2-98%. Ao = Aorta; MPA = Main pulmonary artery.
Adult Patients
With advancing age, the morphologic characteristics of
the ductus changes, altering the success of any procedure
for their closure. In the surgical series, the incidence of
calcification or aneurysmal changes ranges from 6 to 33
percent.161 Conventional methods of division and ligation
can be difficult, incomplete or even hazardous. In particular,
severe calcification makes the ductus too fragile for standard
clamping thereby mandating the use of more invasive total
cardiopulmonary bypass (CPB) with transaortic patch closure
or may require the use of hypotensive anesthesia for easier and
more effective surgical manipulation.161,162 Thus, morphologic
changes necessitate the need for a more complex procedure
and its associated morbidity and mortality. Not only that onefifth of the patients with severe pulmonary artery hypertension
are predisposed to the risk of intraoperative hemorrhage. On
the other hand in adults, the technical success and complete
occlusion with Amplatzer devices was observed in nearly
100 percent of the patients.163 None had any complication
such as intravascular hemolysis, IE, device embolization or
arrhythmias on follow-up. However, PDA associated with
large aneurysms should be handled carefully. Placement of
device may apply localized forces to the aneurysm leading
to dissection and rupture. Exclusion of the aneurysm using a
stent graft or covered stent is a novel approach.164
21
Retrieval of embolized device could be tricky and

challenging. At times the embolised device caught by
the regular snare, if not coaxial with the sheath, wrinkles
making it impossible to retrieve the device (Figure 15A).
The basket snare cannot catch the device sometimes (Figure
15B). Hence all types and sizes of retrieval basket, goose
neck snares and large sheaths must be available in the
catheterisation laboratory. The ADO was retrieved in two
patients by a very novel and unique method by fastening
the screw to the device inside the aorta in one and in the
left common iliac artery in another case. Then device was
pulled into the 7 F sheath like loading the device (Figures
16A and B).
Associated Coarctation of Aorta

a
figures 16a and B: A. 8 x 6 Amplatzer duct occluder (device) embolised

into the aorta; B. The screw is fastened in aorta and the device is being
pulled into the sheath
Associated COA is a challenging situation and strategy

depends on the age of the patient, size of PDA and aorta. If
the patient is suitable for stent, a device (ADO) may initially
be placed in the ductus and subsequently the coarctation can
B
figures 15a and B: A. The device caught by regular 10 mm goose neck snare is not coaxial with the sheath (arrow)
and sheath is wrinkled (arrow); B. The basket type of snare used to catch the device
323
Shunt DefectS
figures 17a to D: Patent ductus arteriosus (PDA) closure in a one year old with 4 mm ductus and severe
coarctation of aorta. A. Aortogram showing a conical PDA with coarctation of aorta; B. Deployment of 8 x
6 Amplatzer duct occluder (Device); C. Balloon dilatation of the coarcted segment; D. Aortogram showing
complete occlusion of PDA and opened up coarcted segment (white arrow)
be stented.165 Alternatively, a covered stent may be deployed

both to close the PDA and to repair the coarctation.166 PDA
can be closed by using ADO with concomitant dilatation of
the coarcted segment (Figures 17A to D).
Sick Ventilated Small Infants
324
Large PDA in full-term/premature babies is known to cause

CHF early in life.167 Superadded respiratory infections are not
uncommon and can result in respiratory insufficiency requiring
ventilatory support. When medical therapy with indomethacin
(for preterms), fluid restriction and diuretics fails, closure of the
PDA becomes a necessity. Surgical ligation by open thoracotomy
is the standard treatment.144 This can be done even on site in the
neonatal intensive care units, avoiding the risk of transferring
unstable neonates.168 Moreover, video-assisted thoracic surgery
has been proved to be effective and minimally traumatic in
premature infants with very low birth weight.169 This facility
is not however uniformly available. Surgery related morbidities
(pleural effusion, chylothorax, bleeding, pneumothorax, etc)

can result in prolonged mechanical ventilation and intensive
care stay.131 Encouraged by the successful coil closure of
large ducts especially with the availability of 0.052 coils,138
the procedure has been attempted for five small sick ventilated
infants, weighing 0.960 to 4.0 kg.170 Bioptome-assisted coil
delivery was done and PDA closure was achieved in all. There
were two instances of embolization of coils with successful
retrieval and redeployment. All infants could be weaned
off mechanical ventilation over the next 24 to 72 hours and
remained asymptomatic at 3 months follow-up. But only ducts
with adequate ampulla are suitable and the procedure needs
certain degree of expertise.
Marfan Syndrome
Younger patients with connective tissue abnormalities may also
be at risk for development, progression and rupture of ductal
or aortic aneurysms after device closure. Marasini et al171
reported the development of giant aneurysm in a patient with

Marfan syndrome after coil occlusion of PDA, the explanation
for which remained speculative, as trauma from catheter or
wire manipulation increased radial forces of the coils inside
the ductus or caused spontaneous dissection. In such cases, a
careful manipulation of catheters/wires inside the ductus, and
regular follow-up with radiography plus echocardiography is
recommended.
Infective Endarteritis
Patients presenting with IE need to be hospitalized and
treated with appropriate antibiotics in adequate dosages for a
period of 4 to 6 weeks. Echocardiographic evaluation usually
reveals vegetations on the pulmonary artery and rarely on the
pulmonary valve or PDA (Figure 18). In hemodynamically
stable patients, after 8 weeks of stopping the antibiotics,172
if blood culture is negative and there is no other evidence
of infection, elective closure of the PDA can be considered.
Sadiq et al attempted device occlusion in 8 and surgical
ligation in 5 children, without CPB.111 But, great caution
should be taken in adults with degenerative changes, as
the ductus may be fragile, due to the superadded infection
(although treated). Even in the absence of mycotic aneurysm,
where device closure is not possible, surgical ligation appears
to be a better choice on/standby CPB.131,161
Residual Shunts
Residual shunts have been observed after transcatheter
closure and surgical ligation and rarely after recanalization
21
figure 18: Transthoracic echocardiography in parasternal short axis

view shows large mobile vegetation (VEG) in the main pulmonary
artery (MPA) in a 9-year-old boy with patent ductus arteriosus (PDA)
with coil occlusion.131,138,139,173 Residual shunts129 are

classified as:
a. Smoke like with no jet.
b. Small shunt with a jet less than 2 mm in diameter.
c. Large shunt with the jet more than 2 mm.
Assessment is usually done by angiography 10 minutes
after the release of the device and by echocardiography with
Doppler color flow imaging on follow-up. The incidence is
variable depending upon the type of device used:
1. Amplatzer duct occluder: With this occluder, residual
shunts immediately after the procedure are seen in 24 to 30
percent,129,174 but on follow-up after 1 to 3 months there is
complete closure in 99.8 to 100 percent. Non-requirement
of the second device in the majority is an advantage over
the use of coils. However, hemolysis due to residual
shunt is a difficult therapeutic problem. In one patient the
appropriately sized, correctly deployed ADO completely
occupied the lumen of the ductus and the leak was through
the device and not between the device and ductal wall.175
The cause of the residual shunt was incomplete coverage
of the polyester patch on the pulmonary end in a large, but
short and wide PDA. The hemolysis was controlled by
placing a coil inside the device.
2. Coils: Residual flow and hemolysis are the inherent
limitations of using coils. If after implanting the coils,
immediate angiogram displays a residual jet of flow
through the PDA, a second coil should be deployed. If not,
the persistent PDA keeps the patient at risk for endocarditis
and hemolysis due to high velocity flow. Proper hydration
and observation should be done as hemolysis resolves
spontaneously, but if it persists for more than 24 hours,
immediate closure is needed by another coil or referral
for surgery.176 On follow-up if the leak does not close
spontaneously after 1 year or there is recanalization, repeat
catheterization should be performed to implant another coil
to achieve complete closure.177
Surgery
Since the initial report by Gross et al10 in 1939, surgical
repair has become a routine and relatively safe procedure,
but it carries the potential risk of morbidity and rarely
mortality associated with thoracotomy specially in infants
and adults.131,144,161 Degenerative changes like calcification,
friability and aneurysm formation with advancing age make
the conventional procedure of division and ligation difficult
and may mandate the use of more invasive approach including
total CPB and transaortic patch closure.131,161 Significant
advances in technology over the past decade have allowed the
development of minimally invasive video-assisted thoracic
surgery, which has been found to be safe and effective not
only in older children, but even in premature infants with
very low birth weight, when medical treatment fails.9 But this
has limitations in patients with calcified ducts, severe pleural
scarring and short, wide window like ducts. Also, robotically
325
Shunt DefectS
assisted closure of PDA has been attempted and found

comparable with closure by means of videoscopic technique.
However, it appears more complicated, demanding and time
consuming having no particular advantage over the regular
technique.178
Indications for Surgery

Surgical closure is contemplated in all patients in whom
medical and interventional treatment fails or is not possible.
1. Failure of catheter based closure or anatomy of ductus not
suitable (Type C).
2. Preterm infants with contraindications or failure of
pharmacotherapy.
3. Calcific PDA, aneurysmal ductus, hypertensive ductus,
inflamed ductus.
4. Recurrent ductus, giant ductus.
5. PDA with complex CHD.
Contraindications
1. Severely elevated PVR (> 8 Wood units).
2. Failure of PVR to fall (< 8 Wood units) with isoproterenol
during cath study at 0.14 mg/kg/min.
3. Qp:Qs of 1.5 to 1.8 at rest that becomes < 1 during exercise.
4. Ductal dependent lesions.
Procedure
326
The PDA has to be controlled in all patients undergoing

surgery under CPB as the presence of an open PDA during
CPB can cause flooding of the lungs and distention of the LV
in the arrested heart on CPB. The PDA is ligated or divided.
Cardiopulmonary bypass is required in special circumstances
like a calcified ductus, ductal aneurysm or a friable ductus with
endarteritis. The usual approach is through the fourth intercostal
space through a posterolateral thoracotomy. A video-assisted
thoracoscopic approach can also be used. Some surgeons ligate
the ductus through a minithoracotomy incision. The lung is gently
retracted and the ductus and the posterior pleura is incised. The
superior intercostal vein is divided and stay sutures are placed. It
is ensured that there is adequate blood present in the operating
room, suction apparatus is functioning and the ductus clamps
are checked. Under hypotensive anesthesia, sharp and blunt
dissection of the ductus arteriosus is done and the aorta above
and below the ductus are defined. The pericardial lappet needs
to be dissected and lifted off to allow definition of the ductus
(Figure 19). The ligatures are passed around the ductus and under
controlled hypotension the ductus arteriosus is ligated. In case
of a hypertensive ductus, a trial clamping may be done initially
and if there is any bradycardia and hypotension after clamping
the ductus, the clamps may be released. If division is planned,
ductus clamps are placed and the ductus is divided and running
sutures are placed over both ends and clamps are removed. In
neonates, a large hemoclip can be placed after defining the upper
figure 19: Operative image shows the exposed patent ductus

arteriosus (PDA), just before ligation
and lower borders of the ductus. Hemostasis is checked, pleura is

covered and the chest is closed. In small children an extra pleural
approach can also be attempted.
Closure from the midline sternotomy approach is done in
cases where ligation is being done along with concomitant
repair of the cardiac lesions, difficult ductus arteriosus and
residual ductus. It is also required to be done after device
embolization.The procedure is done by applying traction to
the MPA and the PDA appears like a continuity of the MPA.
The right and left pulmonary arteries are noted and ligation
of the ductus is done before CPB or at the initiation of CPB.
In case of a complicated ductus, the ductus is temporarily
interrupted by invaginating the MPA with a finger to occlude
the ductal orifice, while CPB is established. A balloon
catheter may be placed to occlude the PDA after opening the
MPA during a period of temporary low flow. After cooling
the patient to the required temperature, head low position
is given and under low flows, the orifice of the PDA is
closed with a patch or directly depending on the size of the
ductus.
Complications
Bleeding is a major complication and can occur during
looping the ductus and also during division of the ductus.
Recanalization can occur both after ligation and even rarely
after division. Device closure of a residual ductus can be
done. Chylothorax due to division of lymphatics or thoracic
duct, hematomas and recurrent laryngeal nerve injury can also
occur after ductal ligation through a thoracotomy.
In premature infants, the operative mortality is related more
due to the associated comorbid conditions and associated medical
problems and can be as high as 10 to 15 percent. Uncomplicated
ductal ligation is associated with minimal mortality. The
recanalization can occur in upto 0.5 percent of cases.
ConCLuSIon
The best physician is the one who is able to distinguish

between the possible and the impossible.
Herophilus
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159. Francis E, Anil SR, Sivakumar K, et al. Trial balloon occlusion
for large patent ductus arteriosus with elevated pulmonary
vascular resistance. Indian Heart J. 2002;54,E-57:499.
160. Thanopoulos BD, Tsaousis GS, Djukic M, et al. Transcatheter
closure of high pulmonary artery pressure persistent ductus
arteriosus with the Amplatzer muscular ventricular septal
occluder. Heart. 2002;87:260-3.
161. Wright JS, Newman DC. Ligation of the patent ductus.
Technical consideration at different ages. J Thorac Cardiovasc
Surg. 1978;75,695-8.
162. John S, Muralidharan S, Jairaj PS, et al. The adult ductus:
review of surgical experience with 131 patients. J Thorac
Cardiovasc Surg. 1981;82:314-9.
163. Arora R, Singh S, Dalra GS. Patent ductus arteriosus:
catheter closure in the adult patient. J Interv Cardiol.
2001;14:155-9.
164. Rogues F, Hennequin JL, Sanchez B, et al. Aortic stent-graft
for patent ductus arteriosus in adults: the aortic exclusion
technique. Ann Thorac Surg. 2001;71:1708-09.
165. Hakim F, Hawelleh AA, Goussous Y, et al. Simultaneous stent
implantation for coarctation of the aorta and closure of patent
ductus arteriosus using the Amplatzer duct occluder. Catheter
166. Sadiq M, Malick NH, Qureshi SA. Simultaneous treatment of
native coarctation of the aorta combined with patent ductus
331
C hapter
22
Aortopulmonary Window
Vijayalakshmi IB, Praveen Jayan, Satish Govindaiah
INTRODUCTION
CLASSIFICATION
Aortopulmonary window (APW) or aortopulmonary septal

defect is a rare congenital heart disease occurring in 0.2 to
0.6 percent of all patients with congenital heart disease.1
APW was first described by John Elliotson in 1830.1 APW
represents a communication between ascending aorta and
pulmonary trunk. It is characterized by the presence of welldefined and separate aortic and pulmonary valves, unlike in
truncus arteriosus, where only an isolated truncal valve is
noted.2 Half of the patients with APW are associated with
other cardiac defects. The most common associated defect is
the type A interrupted aortic arch (IAA). The other associated
cardiac defects includes aortic origin of right pulmonary
artery, anomalous origin of right coronary or left coronary
artery from pulmonary artery, tetralogy of Fallot, patent ductus
arteriosus (PDA) and right aortic arch. It is rarely associated
with ventricular septal defect (VSD).3-5
Aortopulmonary window, a defect in the aortopulmonary

septum, is classified into various types by different authors.
Mori et al classified the APW into three types3:
Type I or proximal defect is the most common (7096% of
cases) and occurs in the proximal part of the aortopulmonary
septum. They are located just above the semilunar valves.
Type II or distal defect (1425%) occurs in the distal part of
aortopulmonary septum adjacent to the right pulmonary artery
(RPA). They involve the pulmonary bifurcation at the level of
the RPA. This form may be associated with type A IAA.8
Type III or total defect (5%) is a large confluent defect
where there is total absence of the aortopulmonary septum.
Later Ho et al9 modified the above classification of APW
into four types according to its morphologic features:
1. Proximal defect is between the ascending aorta and the
main pulmonary artery, having little inferior rim separating
the APW from the semilunar valves.
2. Distal defect is between origin of the RPA and ascending
aorta having a well-formed inferior rim, but little superior
rim. This defect is associated with aortic origin of the RPA.
3. Confluent defect, is a combination of the first and second
types with little superior and inferior rims.
4. Intermediate type is characterized by adequate superior and
inferior rims. It is the intermediate type of defect, which is
best suited for device closure (Figure 1).
Kutsche and Van Mierop described three types of aortopulmonary defect:
1. A defect with a circular border located between the
semilunar valves and pulmonary bifurcation.
2. A similarly located fenestration in which the border
represents a helix.
Synonyms
The synonyms like aortopulmonary septal defect, aortopulmonary fenestration or aortopulmonary fistula are not commonly used.
EMBRyOLOGY
The aortopulmonary septum is formed during early embryogenesis by the opposing truncal cushions which fuse
to divide the truncus arteriosus into aortic and pulmonary
channels.6 Maldevelopment of this aortopulmonary septum leads to the development of APW. Unlike truncus
arterious, APW is not associated with DiGeorge syndrome.7
22
Figure 1: Diagrammatic representation of types of aortopulmonary window (APW). (Reprinted from Barnes ME, Mitchell ME, Tweddell JS.
Aortopulmonary window. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2011;14:67-74, with permission from Elsevier)
3. A large defect with no posterior or distal border. According

to the author the first type may reflect non-fusion of
aortopulmonary septum and truncal septum. The second
type suggests malalignment of the aortopulmonary septum
and truncal septum, while the third type result from total
absence of embryonic aortopulmonary septum.1,6
Natural History and Hemodynamics

There is neither the tendency for APWs to close spontaneously
nor does the defect size decrease with time and growth
of the patient. The defect is variable in size, but all defects
result in a large and generally continuous left-to-right shunt,
when the pulmonary vascular resistance falls, similar to
other interarterial communications such as PDA or truncus
arteriosus.7 After the immediate perinatal period there is
enlargement of left atrium and left ventricle. The pulmonary
arteries are dilated due to the increased pulmonary blood flow.
The ascending aorta can be small in patients with APW with
proximal defects or with associated arch anomalies.10 Without
corrective surgery, irreversible obstructive changes in the
pulmonary vascular bed develop early, followed by death in
the second decade, although patients surviving into the 4th
decade have been reported.5,11 There is an interesting report
of a patient with Eisenmenger syndrome secondary to a large
unrepaired APW who gave birth to three children in her 30s,
survived into her 50s with relatively preserved quality of life,
and died at age 60 years.12 The defect is small in about 10
percent of patients and they usually present late in childhood
like any other moderate sized left-to-right shunt.
resistance, and the presence of associated defects. Clinical

features of APW are those of a large left-right shunt. Clinically
APW is indistinguishable from PDA. Signs of congestive heart
failure (tachypnea, diaphoresis, failure to thrive and recurrent
respiratory infections) develops during first week of life. If
associated with aortic arch anomalies, the patient can present
in the neonatal period with metabolic acidosis and cardiogenic
shock following the closure of PDA.
Clinical examination reveals tachypnea and intercostal
retraction, a bounding arterial pulse and wide pulse
pressure similar to nonrestrictive PDA with low pulmonary
vascular resistance. On auscultation second heart sound
is accentuated and narrowly split indicating pulmonary
hypertension.3,12 Large nonrestrictive APW generates a
loud systolic ejection murmur at the third left intercostal
space along with eddy sounds. Apical mid-diastolic murmur
is heard which represents increased flow across the mitral
valve.
Moderately, restrictive APW generates a continuous
murmur in the upper left sternal border. Large APW associated
with severe pulmonary arterial hypertension (PAH) and
reversed shunt presents with Graham Steell murmur due to
the marked dilatation of hypertensive pulmonary trunk.
The signs and symptoms mimics large PDA and truncus
arteriosus (Type I). In APW associated VSD and right-sided
aortic arch are extremely rare.
ELECTROCARDIOGRAPHY
CLINICAL FEATURES
The clinical presentation is determined by the size of the defect,
the relationship between systemic and pulmonary vascular
There is no characteristic electrocardiography (ECG) finding

in patients with APW. Large APW is characterized by
biventricular hypertrophy (Figure 2).
333
Shunt Defects
Figure 2: ECG in APW shows volume overload of LV with RVH due to PAH. ECG = Electrocardiography; LV = Left ventricle;
APW = Aortopulmonary window; RVH = Right ventricular hypertrophy; PAH = Pulmonary arterial hypertension
aortopulmonary area and color Doppler shows left to right

shunt from aorta to pulmonary artery (Figures 4A and B). T
artefact at the edges of the defect helps to distinguish it from
normal dropouts.13
Color Doppler study reveals continuous forward flow in
the pulmonary arteries with significant diastolic flow reversal
in the proximal aortic arch and abdominal aorta. Fetal
echocardiography also picks up the APW in utero.
Figure 3: X-ray chest posteroanterior (PA) view shows cardiomegaly

with biventricular hypertrophy with prominent MPA with plethora
Radiological Features
The chest X-ray shows cardiomegaly with left ventricular
contour, LA enlargement and plethoric lung fields are seen
in patients with large APW (Figure 3). The aortic knuckle
is not prominent in contrast to PDA. Peripheral pruning of
pulmonary vessels with prominent main pulmonary artery
indicates severe pulmonary artery hypertension.
Echocardiography
334
Two-dimensional echocardiography reveals dilatation

of the left atrium and left ventricle. The right ventricle
may be hypertrophied with significant dilatation of
pulmonary arteries. APW is usually seen as a dropout in the
In the current era of good resolution echocardiography,

cardiac catheterization is rarely indicated for the diagnosis of
APW. The right ventricular and pulmonary artery pressures
are systemic. In the presence of large defects, aortic diastolic
pressure is low with wide pulse pressure. The catheter can be
manipulated into ascending aorta from the pulmonary artery.
An ascending aortogram in shallow right arterior oblique
projection reveals the defect with opacification of the main
pulmonary artery (Figures 5A and B) and demonstrates arch
anomalies.3 Main pulmonary artery angiogram shows filling
of the ascending aorta and when present the anomalous orgin
of the coronary artery from the pulmonary artery can be
demonstrated.
TREATMENT
World literature on transcatheter closure of APWs is limited
to closure of restrictive defects, that too in adults or older
children. Different operators have used different types of
devices for percutaneous closure of APWs including umbrella
device, Amplatzer septal occluder and duct occluders.
Intermediate type defect, which has adequate superior and
inferior rims is best suited for device closure. There are few
case reports of device closure of non-restrictive APW in
infants.14-16 Depending on the PA pressure either Amplatzer
duct occluder or Amplatzer septal muscular occluder is
22
Figures 4A and B: A. Parasternal short axis view shows drop out in the aortopulmonary area; B. Color Doppler shows left to right shunt.
AO = Aorta; APW = Aortopulmonary window; LPA = Left pulmonary artery; MPA = Main pulmonary artery; RA = Right atrium; RPA = Right
pulmonary artery; RV = Right ventricle.
Figures 5A and B: Ascending aortogram in right anterior oblique shows opacification of dilated pulmonary artery (PA) through aortopulmonary
window (APW) type III large confluent defect involving the entire aortopulmonary septum; B. Aortic root angiogram in anterioposterior view shows
opacification of PA through APW type II (arrow).
used. If the APW is not delineated clearly with angiography,

then balloon sizing can be done. The standard arteriovenous
loop is made and then selected device is introduced from
the venous end. The successful closure can be checked with
angiogram and also transthoracic echocardiogram (Figures
6A to C).
Surgery
Gross first successfully ligated an APW in 1948.17 This
technique was associated with distortion of the semilunar
valves and distortion of the left coronary artery. Several surgical
techniques and modifications have been described, with or
without extracorporeal circulation, through a transaortic or

transpulmonary approach, and with or without the use of a
patch. Transaortic approach allows close inspection of the
coronary ostia, correction of arch anomalies and coronary
anomalies.8 Recent revisions have used a pulmonary artery
flap to close the defect and this technique avoids the use of
prosthetic material.
Conclusion
The survival of an infant with large APW, presenting with
congestive heart failure is poor. Approximately 20 to 30
percent of large APW, patients die within 1 year. Early
335
Shunt Defects
Figures 6A to C: A. Aortic root angiogram shows Type IV aortopulmonary window (APW);; B. Shows 10 x
8 Amplatzer duct occluder (device) in situ; C. Transthoracic echocardiography in parasternal short axis view
with color Doppler shows device in situ with no residual shunt AO = Aorta; PA = Pulmonary artery
surgical closure with Dacron patch is the accepted modality

of treatment. It has to be done before the child develop
severe PAH. Early detection of APW is very important as
they develops severe PAH very early in life. Transthoracic
echocardiogram and and magnetic resonance imaging are
useful for diagnosis. Transcatheter non-surgical device
closure is useful in small restrictive APW.
A smart mother makes often a better diagnosis than a poor
doctor.
August Bier
REFERENCES
1. Kutsche LM, Van Mierop LH. Anatomy and pathogenesis of
aorticopulmonary septal defect. Am J Cardiol. 1987;59:443-7.
2. Mert M, Paker T, Akcevin A, et al. Diagnosis, management,
and results of treatment for aortopulmonary window. Cardiol
Young. 2004;14:506-11.
3. Mori K, Ando M, Takao A, et al . Distal type Aortopulmonary
window. Report of 4 cases. Br Heart J. 1978;40:681-9.
4. Redington AN, Rigby ML, Ho SY, Gunthard J, Anderson RH.
Aortic atresia with aortopulmonary window and interruption of
the aortic arch. Pediatr Cardiol. 1991;12:49-51.
5. Meisner H, Schmidt-Habelmann P, Sebenning F, Klinner
W. Surgical correction of aorto-pulmonary septal defects. A
review of the literature and report of eight cases. Dis Chest.
1968;53:750-8.
6. Van Mierop LH S, Kutsche LM. Embrology of the Heart. In:
Hurst JW, (Ed). The Heart. (6th edn) New York: McGraw-Hill,
1986.
336
7. Marmon LM, Balsara RK, Chen R, et al. Congenital cardiac

anomalies associated with the DiGeorge syndrome: A neonatal
experience. Ann Thorac Surg. 1984;38:881-4.
8. Pillekamp F, Hannes T, Koch D, Brockmeier K, Sreeram N.
Transcatheter closure of symptomatic aortopulmonary window
in an infant. Images Pediatr Cardiol. 2008;35:11-7.
9. Ho SY, Gerlis LM, Anderson C, Devine WA, Smith A. The
morphology of aortopulmonary window with regard to their
classification and morphogenesis. Cardiol Young. 1994;4:146-55.
10. Moguillansky D, Munoz R, Morell VO. Aortopulmonary Window.
In Critical Care of Children with Heart Disease: Basic Medical
and Surgical Concepts. Munoz R, Morrell V, da Cruz E, Vetterly
C (eds). Springer-Verlag London Limited; 2010: 191-197.
11. LC Blieden and Moller JH. Aorticopulmonary septal defect.
An experience with 17 patients. Br Heart J. 1974;36:630-5.
12. Su-Mei AK, Ju-Le T. Large unrepaired aortopulmonary
windowsurvival into the seventh decade. Echocardiography.
2007;24:71-3.
13. Balaji S, Burch M, Sullivan ID. Accuracy of cross-sectional
echocardiography in diagnosis of aortopulmonary window.
Am J Cardiol. 1991;67:650-3.
14. Atiq M, Rashid N, Kazmi KA, Qureshi SA. Closure of
aortopulmonary window with Amplatzer duct occluder device.
15. Rohit M, Nandakumar S, Bahl A, Kubba S, Talwar KK.
Transcatheter closure of aortopulmonary window. Indian Heart
J. 2005;57:161-3.
16. Sivakumar K, Francis E. Transcatheter closure of distal
aortopulmonary window using Amplatzer Device. Congenit
Heart Dis. 2006;1:321-3.
17. Gross RE. Surgical closure of an aortic septal defect.
Circulation. 1952;5:858-63.
C hapter
23
Aorticocameral Tunnels
Vijayalakshmi IB, Chitra Narasimhan
Aorticocameral tunnels are extremely rare congenital extra

cardiac vascular channels or communications, which connect
the ascending aorta above the sinotubular junction to any of
the chambers of the heart. The ascending aorta is reported to
be the most common site of origin for aorticocameral tunnels
but rarely tunnel arising from the descending thoracic aorta
has also been reported.1,2
More than 90 percent of the aorticocameral tunnels
communicate with the left ventricle, occasionally with the
right ventricle, rarely with the atria.3 The most common of
these infrequent conditions is the aorto-left ventricular tunnel
(ALVT), followed in frequency by the aorto-right atrial tunnel,
aorto-right ventricular tunnel (ARVT) and the aorto-left atrial
tunnel. All of these conditions produce the physiology of
congenital aortic insufficiency, but when the tunnel connects
to a right heart chamber, an important left-to-right shunt is
also produced.4
Aortoventricular Tunnel
Introduction
Aortoventricular tunnel is a congenital extracardiac channel
that connects the ascending aorta above the sinotubular
junction to the cavity of left ventricle or (less commonly) right
ventricle. The aortoventricular tunnel differs from ruptured
sinus of Valsalva aneurysm in having its vascular orifice in the
tubular aorta, rather than in the sinus of the aortic valve and
in passing outside the heart into the tissue plane between the
muscular subpulmonary infundibulum and the aortic valvar
sinuses.5 The tunnel bypasses the normal ventriculoarterial
junction but does not penetrate the septal musculature. The
aortoventricular tunnel is the most common cause of abnormal
blood flow from the aorta to a ventricle in infancy.
Historical Review
The ALVT was originally described by Edwards and
Burchell6 who considered the malformation as a separation
between the aorta and the heart or a type of aneurysm, which
lay against the outflow tract of the right ventricle and origin
of the pulmonary trunk. The aortico-left ventricular tunnel
was described by Levy and colleagues in 19637 and the term
aorto-left ventricular tunnel was introduced about 10 years
later by Ross and colleagues.8 The more general designation
'aorto-ventricular tunnels' has recently been applied to this
group of malformations, as they may extend to either the left
or the right ventricular cavity.9
Incidence and Etiology

The incidence of ALVT varies between 0.05 to 0.46 percent
as reported in a clinicopathological series.5 Although, more
than 130 cases of ALVT have been reported, ARVT is a rare
entity and only 17 cases have been reported.5,10-26 It is twice
more common in males than in females, and is seldom seen
in patients of Asian, Oriental or African descent. The etiology
of aortoventricular tunnel is uncertain. It appears to result
from the abnormal development, which involves failure of the
outflow cushions to properly seperate from the arterial sinuses,
the valvular leaflets and the fibrous interleaflet triangles.
The cushions, which form the facing aortic and pulmonary
sinuses with their respective valvar leaflets normally become
separated by an extracardiac tissue plane due to the regression
of the surrounding muscle. The coronary arteries, which are
initially encased by this cuff of myocardium, grow through it
to connect with the aortic sinuses. If this tissue plane fails to
develop normally it may then result in a tunnel above one of the
facing aortic sinuses and also is the reason for the associated
Shunt Defects
involvement of the proximal coronary arteries and valve

leaflets. Thus, this is one of the few congenital malformations
which may simultaneously involve both the pulmonary and
aortic valves.7,27 Nearly half of the aorticocameral tunnel
patients suffer from other cardiac defects particularly aortic
valve and/or coronary artery anomalies.28,29
Pathological Anatomy
The aortoventricular tunnel is an abnormal channel that
connects the lumen of the ascending aorta to the cavity of
either the left or right ventricle. The aortic opening of most
tunnels lies above the right coronary sinus of Valsalva. The
tunnel courses in the tissue plane between the free-standing
muscular subpulmonary infundibulum and the aortic sinus
and communicates with the left ventricle in the fibrous
interleaflet triangle between the right and left coronary aortic
leaflets or the right ventricle immediately above or below
the subpulmonary infundibulum.30 Tunnels lying above
the left sinus of Valsalva or the intercoronary commissure
have less uniform morphology and they virtually never
enter this fibrous triangle.9 The tunnel itself may be dilated
aneurysmally through part or the entirety of its course.
The origin of the tunnel from the tubular aorta is above the
sinotubular junction, which differentiates it from the rupture
of an aneurysm of sinus Valsalva. The ruptured sinus of
Valsalva aneurysm originates below the sinotubular junction
and remains completely within the heart. The differentiation
of the tunnel from the coronary-cameral fistula is less clear
as a coronary arterial orifice may arise above the sinotubular
junction and the coronary arteries have been found to arise
from within the aortoventricular tunnel.9 But the coronarycameral fistula passes through the myocardium to enter the
cardiac chamber and does not involve the hingepoint of an
aortic valvular leaflet. Histologically, the arterial end of the
tunnel resembles the aorta with fibrous tissue, elastic fibers
and smooth muscle cells, while the ventricular end contains
hyalinized collagen and muscle. This reflects that the walls
of the tunnels incorporate the structures through which they
pass.5
Types of Aorto-left Ventricular Tunnel
338
Hovaguimian et al31 have proposed an anatomic classification

of ALVT based on morphology. They classified them as
Type I A simple tunnel with a slitlike opening at the aortic
end and no aortic valve distortion
Type II A large extracardiac aortic wall aneurysm of the
tunnel with an oval opening at the aortic end, with or
without ventricular distortion
Type III
Intracardiac aneurysm of the septal portion of the
tunnel, with or without right ventricular outflow tract
obstruction
Type IV Combination of type II and III
Schematic representation of the most common type of ALVT

is shown in Figure 1.
Anomalies of the aortic root are present in about half of
these patients with tunnels.7,9,32,33 Aortic regurgitation is the
most common association, probably due to the weakness of
the aortic sinus wall, especially the unsupported right coronary
cusp with resultant aortic root ectasia.33,34 Aortic valve stenosis
has been reported with bicuspid or unicuspid aortic valves.27,32
Severe aortic dysplasia or atresia can also occur.35,36
Valvular pulmonary stenosis37,38 occurs less frequently
(around 5%), while compression of the right ventricular out
flow tract by the tunnel may produce subpulmonary obstruc
tion.27,39 Rarely, both semilunar valves are stenotic.7,27 An as
sociated ventricular septal defect is rare,28,40 but there can be
an associated sinus of Valsalva aneurysm.33,41
Aortoventricular tunnels have important relationships to
the proximal portions of the coronary arteries.42 The ostium
of a coronary artery may lie within an aortoventricular tunnel.
Atresia of the left11,43 or right8,15,28,31,32,44,45 have both been
observed with this anomaly.
Pathophysiology
The pathophysiological effect depends on the size of the
tunnel and the amount of regurgitation. Interference with
coronary blood flow may be a contributing factor. Fetal
hydrops or death has occurred when the tunnel has been large,
antenatally.46 The large tunnels cause severe congestive heart
failure and most patients are symptomatic in infancy and most
often under a month of age.32,33,40,44,47,48 Patients with smaller
tunnels are asymptomatic and present between 1 and 15 years
of age. But almost all have aortic valve regurgitation or signs
of left ventricular dilatation and hypertrophy. The oldest
patient presented at 63 years of age with multiple tunnels.3
In one patient the tunnel closed spontaneously.28 Infective
endocarditis has been reported in one case.49
The onset, severity and progression of symptoms are variable.
While many patients may have no symptoms, others may pre
sent with rapid progression or sudden death. Death in utero
may also occur. The symptoms are dependant on the size of
tunnel, its hemodynamic influence and the associated cardiac
defects.3 Congestive heart failure may occur at any age due to
severe AR.50,51
The signs may include bounding pulses, a wide pulse pressure
and a loud 'to-and-fro' systolic and diastolic murmur. It is usually
accompanied by systolic and diastolic thrills felt on a wide area on
the precordium. In patients with ALVT with pulmonary stenosis,
the onset of heart failure is delayed. In those with a tunnel, with
associated severe aortic valve obstruction, heart failure occurs
early, with or without low cardiac output and nearly one third of
reported cases having died before birth or on the first day of life.19
23
Figure 1: Schematic representation of the most common type of aorto-left ventricular tunnel. The middle figure shows a cross-sectional view at
the approximate level of the aortic sinotubular junction. The tunnel passes from the ascending aorta into the tissue plane between the aortic and
pulmonary roots. (a) is a longitudinal section across the left ventricular outflow, through the left and right coronary sinuses of Valsalva (plane a
of the central figure). In this example, the aortic end of the tunnel lies above the ostium of the right coronary artery, while the ventricular end is
found within the intercoronary, interleaflet triangle. The position of the aortic opening is variable and may be found anywhere above the left or
right coronary sinus, or the intervening commissure. (b) depicts a longitudinal section crossing the noncoronary and right coronary aortic sinuses
(line b in the central figure). Because the pulmonary valve lies distal to the aortic valve, the tunnel may displace the free-standing, muscular,
sub-pulmonary infundibulum enroute to the left ventricular cavity. It does not, however, pass through any ventricular myocardium. Reprinted with
permission from McKay R. Aorto-ventricular tunnel. Orphanet J Rare Dis. 2007;2:41
Diagnostic Methods
Chest X-ray shows cardiac enlargement with uniform
dilatation of the ascending aorta. The dilated aorta is not
infrequently mistaken for the thymus gland. In some patients,
the tunnel itself can be seen as a leftward prominence of the
aortic root in the area of the pulmonary trunk.8 The tunnel
itself can be seen as a right border on chest X-ray in ARVT
(Figure 2). The electrocardiogram typically shows left or
biventricular hypertrophy with a strain pattern of inverted T
waves seen in the precordial leads. The electrocardiogram can
be occasionally normal.52
The two-dimensional transthoracic echocardiography
(TTE) with cross-sectional and color Doppler imaging is
the diagnostic investigation of choice.40,53-55 The apical five

chamber view provides the clear anatomic picture of the tun
nel arising from the aorta (Figures 3A and B). Apical four
chamber view with color Doppler shows the dilated tunnel
entering the RV (Figures 4A and B).
The subcostal or apical four chamber view can demonstrate
the device in situ after the transcatheter closure of the tunnel
(Figures 5A and B). The aortic origin of the tunnel as well as its
course and opening into the left ventricle can be demonstrated
in a parasternal long-axis view with color Doppler (Figures 6A
and B) sometimes with clockwise rotation of the probe.28,56
The device in situ can be nicely demonstrated in the same
view (Figure 6C). Tunnels which open into the right ventricle
339
Shunt Defects
Figures 4A and B: Echocardiogram in apical four-chamber view with

color Doppler shows the dilated tunnel entering the right ventricle and
the arrow indicates the extracardiac portion of the tunnel. LA = Left
atrium; LV = Left ventricle; RA = Right atrium; RV = Right ventricle.
Figure 2: Chest X-ray shows the aorto-right ventricular tunnel

as the right border of the heart with the device in situ
Figures 5A and B: Echocardiogram with color Doppler in the subcostal

view shows no flow in the extracardiac tunnel, with the Amplatzer duct
occluder (device) at the end of the tunnel in the right ventricle with no
residual shunt. LV = Left ventricle; RV = Right ventricle.
Figures 3A and B: Echocardiogram with color Doppler in an 11

month infant with aorto-right ventricular tunnel: A. Apical five-chamber
view shows the dilated tunnel arising from the right aortic sinus;
B. Parasternal short-axis view shows normal sized left and right
coronary arteries arising from left coronary sinus. Ao = Aorta; LA = Left
atrium; LCA = Left coronary artery; LV = Left ventricle; RCA = Right
coronary artery; RV = Right ventricle.
340
are visualized in the apical four-chamber view. The parasternal

short-axis view helps to distinguish the coronary AV fistula
from the tunnel by delineating normal sized coronaries
separately from the tunnel.
On color Doppler studies, diastolic flow is seen passing
from the aorta to the left ventricle and systolic from the
ventricle to the aorta. In ALVT, the ventricular function, which
may be variably impaired with hypertrophy and dilatation, is
assessed in short-axis views.5 The fetal diagnosis can also be
reliably done with both two-dimensional and real-time threedimensional echocardiography.48,57,58
In the occasional patient in whom the diagnosis is difficult,

magnetic resonance imaging (MRI) or computed tomographic
(CT) angiography can be done, especially to delineate the
coronaries (Figures 7A and B) or cardiac catheterization
may be helpful to know the anatomy for device closure.
Magnetic resonance angiography (MRA) also has been used
to demonstrate tunnels to the left55 and right19 ventricles,
but is not widely available in clinical practice. Cardiac
catheterization with angiography is now indicated only
when associated lesions or coronary arterial origins cannot
be evaluated with certainty on non-invasive studies or when
percutaneous intervention is planned.
Of all these features, extensive and uniform dilation of
the ascending aorta may be the best non-invasive clue to
the diagnosis of aortoventricular tunnel, for this is hardly
ever present early in life with other cardiac malformations.
Extremely rarely enlargement of the aorta is not present,
specifically when there is critical obstruction of both the aortic
valve and within the tunnel.59
The most common diagnostic errors from echocardiography
have been to confuse the ventricular end of the tunnel with
23
Figures 6A to C: A. Echocardiogram in parasternal long-axis shows tunnel arising from aorta entering into the left ventricle; B. Color Doppler
shows the course of aorto-left ventricular tunnel; C. Shows the 16 X 14 Amplazter duct occulder (device) in situ in a 4-year-old boy. AO = Aorta;
LA = Left atrium; LV = Left ventricle;
Figures 7A and B: A. Computed tomography angiogram shows the

dilated tunnel arising from right sinus with right coronary artery and left
coronary artery (branching into left anterior descending and circumflex
arteries) arising from left coronary sinus (three white arrows) B. Shows
tunnel encircling the right atrium and opening into the right ventricle.
Ao = Aorta; LV = Left ventricle; RV = Right ventricle.
a ventricular septal defect7,27 or to mistake displacement of

the subpulmonary infundibulum for Fallots tetralogy.29 Flow
of blood through the tunnel has also been misinterpreted as
valvular aortic regurgitation29 or a ruptured aneurysm of the
sinus of Valsalva.46
The differential diagnosis include lesions, which cause rapid
aortic run-off and produce cardiac failure. These include rupture
of sinus of Valsalva aneurysm, truncus arteriosus with valvular
regurgitation, aortopulmonary window, ventricular septal defect
with aortic regurgitation, patent ductus arteriosus, coronarycameral fistula, valvar aortic stenosis and regurgitation, tetralogy
of Fallot with absent pulmonary valve and cerebral arteriovenous malformation.9
Antenatal Diagnosis
The most consistent echocardiographic feature on antenatal
examination between 18 and 33 weeks gestation is dilatation
and hypertrophy of the left ventricle, with severe and

progressively reduced shortening fraction.
Apparent aortic regurgitation which is extremely
uncommon during fetal life and enlargement of the aortic root,
further supports a diagnosis of aortoventricular tunnel. The
flow while flow of blood around the hinge of the valve can also
be imaged with color flow Doppler echocardiography.46 It is
possible to diagnose the tunnel on fetal echocardiography after
18 weeks gestation. The key to diagnosis in fetal life is aortic
regurgitation, sometimes with left ventricular dysfunction and
hydrops.46 There are no known molecular markers for aortoventricular tunnel at present and it is not associated with any
recognized genetic syndrome.5
Natural History
The anomaly can be detected in utero and if the tunnel is large,
it causes left ventricular dysfunction.9,48 One intrauterine
death has been attributed to the tunnel but several fetuses
had congestive heart failure.46 Nearly 60 to 70 percent of
these patients present in infancy. If they present in infancy in
congestive heart failure, medical management results in almost
100 percent mortality, usually soon after presentation.33 A 63
years old patient has been reported with multiple aortic cameral
tunnels.3
Management
Surgical correction of tunnel carrying significant blood flow
should be undertaken without delay, even in asymptomatic
patients, as only those repaired in the first 6 months of life
have been shown to have subsequent normalization of
ventricular size and function.44 Moreover, lack of support for
the right or left coronary aortic leaflet invariably results in
progressive aortic regurgitation,60 often necessitating repair
or replacement of the valve. Observation may be appropriate
for the occasional asymptomatic patient with a very small (2
millimeter) ALVT.28
341
Shunt Defects
Surgery
Repair consists of closing the tunnel such that the
aortic valve is supported, the coronary circulation is
not compromised and left or right ventricular outflow
obstruction is prevented or relieved. In most cases of ALVT,
this has been accomplished by transaortic patch closure of
the aortic end and placement of a second patch through the
tunnel itself to close the ventricular orifice and support the
aortic valve.5 The tunnel wall itself can be used alternatively
to achieve an equivalent anatomical result.61 The aortic
orifice can be closed by direct suture,28,41,62 but more
often, the tunnel recurs or progressive aortic regurgitation
through an unsupported or distorted right coronary leaflet
leads to subsequent valve replacement. The residual high
pressure in the blind-ending pouch may compress the right
ventricular outflow, if the ventricular end of an ALVT is
not closed.39 In ARVT, it is less certain that the ventricular
orifice needs to be closed but in most reported cases this has
been done, either with a patch or direct suture, through a
right ventricular incision.5 Associated lesions like aortic or
pulmonary stenosis are treated as indicated either separately
or at the time of tunnel repair.
Non-Surgical
Transcatheter closure of an ALVT with an Amplatzer duct
occluder has been reported in two patients (Figures 8A
and B).63,64 Transcatheter closure of ARVT has been done in
two patients, one with a duct occluder22 and another at our
institution using Amplatzer duct occluder II in an eleven month
infant26 (Figures 9A and B). Due to the benefit of providing
support for the aortic valvar leaflets, as well as the spectrum
of associated coronary arterial anomalies, it seems likely that
repair of the aortoventricular tunnels should remain largely, if
not exclusively, within the surgical domain as it is questionable
Figures 8A and B: A. Aortic root angiogram shows dilated aortic

root with moderate aortic regurgitation and aneurysmally dilated
extracardiac portion of tunnel entering the left ventricle; B. Check
angiogram shows the 16 X 14 Amplatzer duct occulder (device) device
with residual shunt
342
Figures 9A and B: A. Aortic root angio in left anterior oblique (LAO)

view shows the aorto-right ventricular tunnel with aneurysmally dilated
proximal portion before opening into the right ventricular outflow
tract. Both the left and right coronaries are seen arising from the left
coronary sinus; B. Check angiogram in LAO shows complete closure
of the tunnel with no residual shunt. Amplazter duct occulder II (device)
is seen as two hyperechogenic points in the retention discs.
if percutaneous interventions can achieve long-term outcomes

equivalent to those of current surgical techniques, for which
operative mortality approaches zero.28,44
Aortoatrial tunnels
Aortoatrial tunnel is a very rare congenital anomaly. There is
an abnormal tunnel-like vascular extracardiac communication
arising from the aortic root and terminating in either the right
(Figures 10A and B) or left atrium. The tunnels between the
aorta and the left atrium is extremely rare and is more often
associated with complications of infective endocarditis65 and
paravalvular abscess, aortic dissection66 and after surgery
affecting the valve or aortic root.
Aorta-Right Atrial Tunnel

The aorta-right atrial tunnel was first described in 1980.67
It is a vascular channel that originates from any of the three
sinuses of Valsalva and terminates in the right atrium.67-71
The tunnel is classified as anterior or posterior, according
to their origin and course in relation to the ascending
aorta. The tunnel originating in the left sinus of Valsalva
usually has a posterior course whereas, the tunnel from
right sinus of Valsalva, has an anterior course before
joining the right atrium.72 The origin of the tunnel above
the sinotubular ridge differentiates it from an aneurysm
of the sinus of Valsalva and the absence of myocardial
branches differentiates it from a coronary-cameral fistula.
Associated conditions with this anomaly are secundum
type of atrial septal defect and persistence of the left
superior vena cava.72
The embryologic background and pathogenesis of this
anomaly are not clear. These are attributable either to an
aneurysmal dilation of the sinus nodal artery or to a congenital
weakness of the elastic lamina in the aortic media.68,72 Due to
23
Figures 10A to D: A. Transthoracic echocardiography in apical four-chamber view shows aorto-right atrial tunnel in 5 years old boy, draining
into right atrium (RA) with extracardiac portion of the tunnel seen with color Doppler; B. Aortic root angio done in right anterior oblique shows the
aortic tunnel arising from left sinus and draining into RA with extracardiac aneurysmally dilated portion; C. Tortuous extracardiac portion of the
tunnel; D. The guidewire through the tortuous tunnel. AO = Aorta; LA = Left atrium; LV = Left ventricle; RV = Right ventricle.
the high aortic pressure the defective area in the aortic wall
forms an extracardiac tunnel, leading to gradual enlargement
and rupture into the RA because of its anatomic proximity and
low filling pressure.
Symptoms and Signs

This aorto-right atrial communication behaves like a
left-to-right shunt at the atrial level. Most patients may
be asymptomatic or they may present with exertional
breathlessness, palpitations or recurrent respiratory tract
infections.72 On physical examination, a continuous murmur
at the right parasternal border is present.
10B). Rupture of sinus of Valsalva can be differentiated

by demonstrating a tunnel with an extracardiac course.68
Aortography also helps to differentiate it from coronary
cameral fistula and to delineate the tunnel and to assess the
tortuosity and suitability for transcatheter interventions
(Figures 10C and D).
Electron beam tomography or MRA might might
be additional non-invasive tools for diagnosis. The CT
angiography is an additional non-invasive diagnostic tool.
Electron beam tomography can be a good diagnostic tool,
showing the tunnel taking its origin from the aortic root and
entering the right atrium through a tortuous communication.71
Management
Diagnosis
The tunnel can be readily identified by TTE. The apical
four chamber view shows the tunnel opening into the right
atrium and the color Doppler also delineates the extracardiac
portion of the tunnel (Figure 10A). Retrograde aortography
combined with selective coronary angiography is essential for
the demonstration of its course and the coronary ostia (Figure
Closure of an aorta-right atrial tunnel is recommended even

in asymptomatic patients69 as there is only a low rate of
procedural complications. Moreover, the continued patency
of the tunnel leads to risk for biventricular volume overload,
bacterial endocarditis, pulmonary vascular disease, aneurysm
formation, calcification of the wall, aortic regurgitation and
spontaneous rupture.67-69,72
343
Shunt Defects
Treatment options are available according to the type of

tunnel/fistula, its caliber, tortuosity, calcification, course and
relation of the coronary ostia to the aortic orifice of the tun
nel/fistula. They include transcatheter closure, ligation under
controlled hypotension or repair with the patient under under
cardio pulmonary bypass.72,73
Surgical options include plication of the tunnel or patch
closure of aortic origin with direct closure of the atrial
opening. The ligation for anteriorly located aorta-right atrial
tunnel includes ligation near the aortic end, and for posteriorly
located tunnels, ligation should be done between between
superior vena cava and aorta as close to the aorta as possible.72
External ligation of the tunnel close to the aorta should be
performed only after accurate evaluation of the external
anatomy and of the relationship between the coronary ostia
and the orifice of the tunnel at the aortic end.74 If the coronary
artery arises from the tunnel, an alternative is to re-implant the
artery as a button into the aortic sinus.71
Transcatheter treatment is an option in selected cases,
where the opening of the right atrial end is small or there is a
constriction in the course of the fistula.72 The appropriate sizes
of coils or device can be used. There are a few case reports of
transcatheter closure.75,76 However, persistence of the dilated
sinus of Valsalva with transcatheter device closure constitutes
a concern and demands further follow-up and evaluation for
a determination of its evolution.75 Sometimes, if the tunnel is
very tortuous the device closure may not be possible.
Conclusion
Aorticocameral tunnels are extremely rare congenital cardiac
anomalies. Imaging by TTE and MRI are of great help in
diagnosis. Surgical closure of tunnel along with repair of the
associated cardiac defects has been achieved with satisfactory
results in the past. Recently, transcatheter closure of tunnels
with Amplatzer duct occluder, Amplatzer duct occluder II
and coil closures have become a better and more attractive
alternative to surgery in selected cases without associated
cardiac defects.
By medicine life may be prolonged, yet death will seize the
doctor too.
William Shakespeare
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C hapter
24
Aneurysm of Sinus of Valsalva

Biswajit Bandyopadhyay, Debasree Ganguly, Kumsi Sridhar
Introduction
The sinuses of Valsalva are three small outpouchings in the
wall of the aorta immediately above the attachments of each
aortic cusp. First report of ruptured sinus of Valsalva was
published in 1839 by Hope.1 Thurnam named the sinuses
according to their relationship to the coronary arteries as
the right coronary sinus, the left coronary sinus and the noncoronary sinus.2
Aneurysm of sinus of Valsalva (ASV) accounts for 1
percent of congenital anomalies of the heart and circulation.3
The aneurysms tend to be single although exceptionally more
than one sinus is involved.4-7
The incidence varies from 0.14 to 0.35 percent.4 The
prevalence is more in Asian population compared to Western
world.7 The developmental fault is at the junction of the aortic
media and the annulus fibrosis and sets the stage for avulsion
and aneurysm formation.8 Rupture is rare in infancy and
childhood, being more commonly seen in adults.
PATHOLOGY
Mural weakness of aortic sinuses causes congenital aneurysm
of the sinuses, which produces downward prolapse of the
leaflets. The dilated sinus may bulge into an atrium or ventricle
and may rupture.
Aneurysms can be congenital or acquired after bacterial
endocarditis (BE). The BE can also occur on congenital
aneurysms. Sometimes, it becomes difficult to identify
whether BE is the effect or cause of the aneurysm rupture.
Rupture has been reported in Behet disease and may also
occur long time after repair of aortic dissection.
In 30 to 50 percent cases, congenital aneurysms are
associated with ventricular septal defect (VSD) especially
defects of the outlet septum. Proportion of VSD is higher
with aneurysms of right aortic sinus. Subpulmonic VSDs
are often associated with prolapse of aortic cusps and aortic

incompetence. Coarctation of the aorta, atrial septal defect,
tetralogy of Fallot and patent ductus arteriosus also may be
associated with these aneurysms.5
Most aneurysms are single and most commonly affect
the right coronary aortic sinus. Two-thirds of the aneurysms
are located in the right aortic sinus, one-fourth in the noncoronary sinus and the rest in the left aortic sinus.9
Aneurysms of the right coronary aortic sinus usually
prolapse into the right ventricle or right atrium and those from
the non-coronary sinus into the right atrium. Aneurysms of the
left coronary aortic sinus prolapse into the left ventricle.10,11
Rupture can also occur through the septal leaflet of the
tricuspid valve, producing an acquired atrioventricular septal
defect.10 There is an increased incidence of rupture when
an aneurysm occurs in the presence of a doubly committed
subarterial ventricular septal defect. Rupture in these cases
occur into the right ventricular outflow tract. Rarely, rupture is
into the pulmonary artery,12-14 left ventricle,15-17 left atrium17
or pericardial cavity.18,19 Also rarely, a sinus aneurysm dissects
into the interventricular septum and either remains unruptured
or perforates into the left or right ventricle.15,20 Box 1 depicts
the working classification of ASV.17
A large unruptured aneurysm may compress the superior
vena cava, right atrium, right ventricle21,22 or a coronary
artery23,24 or may cause aortic regurgitation by interfering
with coaptation of aortic leaflets.25,26 A rare case of unruptured
aneurysm of both right and left sinuses causing right ventricular
ouflow tract (RVOT) and left ventricular outflow tract (LVOT)
obstruction and burrowing into interventricular septum, which
does not fit into any classification is reported (Figures 1
and 2).27 The congenital etiology of an aortic sinus aneurysm is
debatable if it originates in the left coronary sinus and ruptures
into the left side of heart.17,28 At surgery most fistulas resemble
windsocks projecting from the sinus into the chamber of entry,
with one or more openings near the end of the windsock.
Shunt Defects
Box 1: Sakakibara and Konnos

classification of ASV17
Type I: The aneurysm originates in the left portion of the right
sinus, protrudes forward and ruptures into the right ventricle
near the pulmonary valve. The concurrent presence of VSD
under the pulmonary valve is frequent.
Type II: The aneurysm originates in the mid portion of the
right sinus, protrudes and ruptures in the right ventricle. A
concurrent VSD is uncommon.
Type III: The aneurysm originates in the mid portion of the
right coronary sinus and protrudes towards the tricuspid
valve. It often ruptures into the right atrium and sometimes
into the right ventricle, just below the septal leaflet of the
tricuspid valve. VSD is rarely encountered.
Type IV: The aneurysm originates in the right portion of the
non-coronary sinus and ruptures into the right atrium. The
presence of an associated VSD is uncommon.
ASV = Aneurysm of the sinus of Valsalva; VSD = Ventricular septal
defect.
Figures 2A and B: A. The apical four-chamber view shows dilation of

the left ventricle and left atrium, with the aneurysm of the right sinus
of Valsalva burrowing into the ventricular septum. Note the moderately
severe mitral regurgitation. B. The apical five chamber view shows
the aneurysmally dilated left sinus of Valsalva prolapsing into left
ventricle, producing saccular protrusions and aortic regurgitation.
ASV = Aneurysm of sinus of Valsalva; AR = Aortic regurgitation; IVS =
Intraventricular septum; LV = Left ventricle; MR = Mitral regurgitation;
RA = Right atrium; RV = Right ventricle
1. The amount of blood flowing through the rupture.

2. The rapidity with which the rupture develops.
3. The chamber that receives the rupture.
Depending on the chamber, which receives the ruptured
blood, both right and left side of the heart is under volume
overload, which if large and sudden can lead to congestive
heart failure. Aneurysm rupturing into right atrium causes
volume overloading of all four chambers.30
SIGNS AND SYMPTOMS

A
Figures 1A and B: A. Transthoracic echocardiographic parasternal

long axis view shows aneurysms of both aortic coronary sinuses of
Valsalva obstructing the left ventricular outflow tract. B. Parasternal
short-axis view shows the aneurysm of the right sinus protruding
into the right ventricular outflow tract. Ao = Aorta; ASOV = Aneurysm
of sinus of Valsalva; LA = Left atrium; LV = Left ventricle; LVOT =
Left ventricular outflow tract; PA = Pulmonary artery; RVOT = Right
ventricular outflow tract.
PHYSIOLOGY
348
About 75 percent of the patients are male. Ruptured aortic

sinus aneurysms typically express themselves in young men
after puberty, but before the age of 30 years.29 Congenital sinus
of Valsalva aneurysms come to attention because of the acute
development of a large perforation, gradual development of a
small perforation or because of an asymptomatic or symptomatic
unruptured aneurysm. The physiologic consequences of rupture
depend on three factors:
Unruptured aneurysms are usually asymptomatic and are

discovered during investigation for some other reasons such
as a VSD. Occasionally, unruptured aneurysms can produce
symptoms of intractable angina because of distortion of the
origin of the coronary arteries.30
Natural history of unruptured aneurysms is not known.
Although rupture has been reported in the neonatal period,31
it occurs more frequently in the third or fourth decade of
life. Rupture often, but not necessarily develop after physical
exertion.
Rupture may be accompanied by a tearing pain in the chest
or upper abdomen. The sudden onset of dyspnea rather than
pain or mild chest pain may occur for weeks before the onset
of dyspnea and tightness in the upper abdomen.32-34 If a huge
shunt develops rapidly, the symptoms of congestive heart
failure appear almost immediately, but with smaller fistulas
it may take several months for heart failure to develop.9
Pain is presumably related to the rupture itself. Occasionally,
the aneurysm compresses a coronary artery so symptoms of
myocardial ischemia or infarction coexist.33
Figure 3: Schematic diagram showing the location of the murmur

depending on the site of rupture of the sinus of Valsalva. RA = Right
atrium; RV = Right ventricle
Occasionally, there is only a diastolic murmur in fistulas

entering the left ventricle9 or the high-pressure right ventricle
in a neonate. Myocardial infarction may be the consequence
of compression of the coronary arteries and may occasionally
be fatal.40 Other possible complications include transient
ischemic attacks and cerebral embolism.25,32
Death from congestive heart failure usually occurs within
a year after rupture.34,37 Sudden death follows perforation into
the pericardium and syncope or sudden death is an occasional
sequel of complete heart block caused by a ruptured or
unruptured43 aneurysm that dissects into the base of the
ventricular septum. Conversely, long survival sometimes
follows small slow perforations.41
Unruptured aneurysms announce themselves by a to-andfro murmur due to flow in and out of the intact aneurysmal
pouch, a murmur of tricuspid regurgitation or a midsystolic
murmur caused by obstruction to right ventricular outflow,
myocardial ischemia due to coronary artery compression, aortic
regurgitation caused by lack of apposition of aortic cusps,45
superior vena caval obstruction, a paracardiac mass in the chest
X-ray, systemic emboli, complete heart block or syncope or
sudden death.43,44
24
aneurysm of sinus of valsalva
When chest pain, dyspnea and a continuous murmur suddenly

develops in a patient with a ventricular septal defect, the reason
is likely to be rupture of a coexisting aortic sinus aneurysm.34-36
The acute symptoms last for hours or days, sometimes
subsiding gradually and leaving patient temporarily improved,
but congestive heart failure reappears and relentlessly
progresses.37,38 About 20 percent of patients are asymptomatic.
Small insidious perforations progress gradually and initially
go unnoticed.39,40 Mild dyspnea without pain sometimes
precedes congestive heart failure by months or years.41-43
Patients who present during a relatively asymptomatic
interval have a continuous murmur, collapsing radial pulse,
raised jugular venous pressure with tall a wave, prominent
parasternal heave and thrill. Unlike the patent ductus arteriosus
(PDA) murmur, in ruptured sinus of Valsalva (RSOV) the
continuous murmur does not peak around S2, infact the
intensity of murmur decreases at S2. The diastolic accentuation
of murmur at a atypical site is characteristic of RSOV. The
diastolic murmur may be further accentuated if associated
aortic regurgitation is present and that can be mistaken for a
PDA.35
Small perforations come to attention because of an
asymptomatic continuous murmur44 or a systolic murmur
caused by subpulmonary obstruction or a diastolic murmur
caused by aortic regurgitation or because of infective
endocarditis or because of diagnostic investigation or
operation for VSD.
There may be only a continuous murmur like that of a
PDA, but with its maximal intensity in the third or fourth
intercostal space near the sternal edge; if the fistula enters the
right atrium, the murmur may be maximum to the right of
the sternum (Figure 3).35 With larger fistulas, there will be a
wide pulse pressure, a collapsing pulse and left ventricular
hyperactivity. If the fistula enters the right side, there will be
right ventricular hyperactivity as well. A large fistula entering
the left ventricle may give rise to a to-and-fro murmur.
INVESTIGATIONS
Small and slowly developing aortic sinus ruptures are
accompanied by normal electrocardiograms. The rhythm is
normal sinus even when a large rupture is into the right atrium.
The PR interval tends to be prolonged. Atrioventricular
conduction defects including complete heart block and
right or left bundle branch block or bifascicular block5,43
result when a ruptured or unruptured aneurysm penetrates
the base of the ventricular septum. Varying degree of ST-T
abnormalities are present depending on the presence of
ischemia or infarction.
Rupture into the right atrium or right ventricle results in
volume overload of both ventricles, but the electrocardiogram
usually shows left ventricular hypertrophy by voltage criteria
and ST segment and T wave abnormalities.46 Right ventricular
hypertrophy may coexist, but does not occur alone46,47 and is
usually associated with aneurysms that cause right ventricular
outflow obstruction.
Volume overload of both ventricles with congestive heart
failure accounts for the radiologic picture when an aortic sinus
aneurysm ruptures into the right side of the heart.46
Small or insidious rupture usually does not cause prominent
radiologic changes. Large rupture causes pulmonary venous
congestion because of sudden rise in end diastolic pressure of
an unprepared left ventricle, and also prominence of pulmonary
trunk because of increased pulmonary blood flow.39,46
Moderate left atrial enlargement is seen in the lateral
projection, a right atrial convexity appears at the right lower
cardiac border and a moderately dilated left ventricle occupies
the apex.39,48 Rupture into the left ventricle causes pulmonary
349
Shunt Defects
venous congestion without increased pulmonary arterial

blood flow and with a selective increase in left ventricular
size. Rarely, calcium is deposited in the aortic sinus aneurysm.
Occasionally right or left aortic sinus aneurysm may project
out as dense convex paracardiac shadow.49
Transthoracic echocardiography (TTE) can detect the ASV
(Figure 4). 2D echocardiography with color flow imaging and
Doppler identifies the ruptured or unruptured aneurysm, the
chamber receiving the shunted blood, volume overloading of
the heart, associated defects and degree of aortic regurgitation
(Figures 5A and B). Unruptured defects are characterized
by phasic expansion and relaxation and to-and-fro pulsed
Doppler signals at the site of origin from the aorta, but no
color flow evidence of rupture. Echocardiographic diagnostic
criteria50 include:
1. Root of the aneurysm above the aortic annulus.

2. Saccular-shaped aneurysm.
3. Normal size of aorta above the aneurysm.
4. Continuous systolic and diastolic turbulence detected by the
pulsed wave Doppler just distal to the area of perforation at
high velocities.
5. Color flow mapping with mosaic turbulence across the
perforated aneurysm in real time.
Ischemic left ventricular regional wall motion abnormalities
caused by compression of the coronary artery origins by the
aneurysm are evident on real time screening.
Non-invasive imaging with computed tomography or
magnetic resonance scans have been shown to provide
excellent definition of the aneurysm and the tissue planes
involved.51
MANAGEMENT
Figure 4: Transthoracic echocardiography (TTE) in parasternal

short-axis shows aneurysm of the sinus of Valsalva
350
Figures 5A and B: A. Transthoracic echocardiogram (TTE) in

parasternal long-axis view shows non-compaction of of left ventricle
with subaortic ventricular septal defect. B. TTE in parasternal long-axis
view with color Doppler shows rupture of aneurysm of sinus of Valsalva
into right ventricle and aortic regurgitation jet into left ventricle.
The conventional treatment of these aneurysms has

been surgical repair with patch closure at both ends
under cardiopulmonary bypass. A simple and functional
classifcation system by Vural et al52 can be used as a guideline
for the therapeutic approach to ASVs, based on the clinical
picture and the echocardiographic findings (Figure 6). The
indication for surgery is for both ruptured ASV (Type A) and
for symptomatic unruptured ASV (Type B-II). The size of the
aneurysm detemines the indication for surgical intervention
in unruptured asymptomatic ASV (Type B-I). Surgical
treatment is necessary, if the size of the aneurysm is larger
than 50% of the average size of the other two normal Valsalva
sinuses or is increasing in consecutive echocardiographic
examinations. In addition, patients should be operated on if
there is compression or malformation of the adjacent tissues.
Surgery is indicated for the extracardiac type of ASV (Type C).
Although, the mortality is low (< 2%), the potential morbidity
from cardiopulmonary bypass and thoracotomy including the
scar are the underlying hazards. Although the long-term result
of the successful repair is usually good, residual shunt may
require reoperation, which carries a high mortality.53
The first percutaneous intervention for a shunt of this
kind was attempted by Hourihan et al in 1992 for acquired
arteriovenous fistula after aortic valve replacement.54 In 1994,
Cullen described closure of recurrent left-to-right shunt after
surgical repair of perforated congenital sinus of Valsalva
aneurysm, with Rashkind umbrella device.55
In the present era, ruptured aortic sinus aneurysm can
be closed percutaneously with device after careful patient
selection. Patient with left-to-right shunt with pulmonary to
systemic flow ratio of greater than 1.5:1 with right ventricle
volume overload greater than 1.5 cm/m2 and the margin of the
defect at least 5 mm from the right coronary ostia are suitable
for device closure.56 Device closure of the defect has been
shown to be a safe and effective alternative to surgery on shortterm follow-up of a small series of patients.57
24
Figure 6: The algorithm for therapeutic approach to aneurysm of the sinus of Valsalva (ASV) by Vural et al52* Normal size of a sinus
can be estimated by the average of the other uninvolved sinuses on echocardiographic or angiographic examination
Figures 7A and B: A. Aortic root angiogram shows opacification of right ventricle (RV) through rupture of sinus of Valsalva (RSOV);
B. Aortic root angiogram after device closure shows 8 x 6 duct occluder (device) in situ with no residual flow
Defects are usually closed with Amplatzer duct occluder

(ADO). The selected size of ADO should be 1 to 2 mm greater
than the measured defect size (Figures 7A and B).
The procedure is performed under local anesthesia with
fluoroscopic and transthoracic/transesophageal echocardiographic guidance. Some centers prefer general anesthesia for
the procedure.
After establishing femoral artery and venous access, intra

venous antibiotics and heparin is given at 100 mg/kg, right
and left heart catheterization is done, and direct pulmonary
artery pressure is measured. Coronary angiography is
performed to document coronary arteries anatomy and their
distance from the defect before closure is attempted. Aortic
root cine-angiogram is performed in at least two orthogonal
351
Shunt Defects
views to define the opening of the wind sock defect and its
size.
The defect is then crossed with a multipurpose or a right
coronary catheter from the left ventricle to the right ventricular
side. As the defect is crossed with the catheter, an exchange
length Terumo wire is advanced through the catheter across
the defect and is kept into the superior vena cava or the
pulmonary artery and snared from there and taken out from
the femoral vein forming an arteriovenous circuit.
Subsequently, an appropriate sized device is advanced
via a Mullins sheath from the femoral venous side and is
advanced into the ascending aorta. With the distal device end
open the whole assembly is then withdrawn to the opening
of the defect on the aortic side. An aortography is then
performed to check the position of the device and residual
shunt. Simultaneously the device position is checked by
transesophageal echocardiography and once satisfied with
the position, the device is then deployed within the defect.
Selective coronary angiography may also be performed to rule
out any encroachment of the device.56
Gianturco-Grifka vascular occlusion device is another
alternative from the venous route. Patients should receive anti
coagulant prophylaxis and infective endocarditis prophylaxis
for 6 months after the procedure.
Device closure should not be attempted in patients with
an aneurysm which has ruptured into the pulmonary artery
and left ventricle, presence of associated lesions such as as
VSD and aortic regurgitation, aneurysmal opening within 5
mm of coronary ostia, right-to-left shunting across the defect
with systemic saturation less than 94 percent, patients with
pulmonary vascular resistance greater than 7 Wood units and
significant right ventricle/left ventricle dysfunction with left
ventricular ejection fraction less than 30 percent.58
Surgical Management of Rupture of Sinus of Valsalva
352
A diagnosis of RSOV requires surgical intervention to

prevent progression of the disease resulting in death from
right heart failure. There are many variants of RSOV,
which may require a specific technique to repair the defect.
However, the basic technique remains the same. Excision
of windsock, patch closure of RSOV, VSD closure if
present and an aortic valve repair or replacement for aortic
regurgitation.
Initial preparation (CPB) is as for any open-heart
procedure. After midsternotomy, pericardium is opened and
an external evaluation is done. There are no external evidence
of aneurysm. The sac of aneurysm may be palpated through
the freewall of the right ventricle.
Cardiopulmonary bypass is established after cannulation
of ascending aorta and direct caval cannulation.With mild-tomoderate hypothermia, aorta is cross clamped, right atrium
opened and a vent suction introduced through foramen
ovale.Aorta is opened transversly, cardiac arrest achieved by
infusing antegrade cold cardioplegia through the coronary

ostia directly. The orifice of the RSOV is visualized and
the VSD if present is visualized by lifting the aortic cusp.
Redundancy or cusp prolapse is noted.
Repair of RSOV can be attempted through right atrium
or right ventriculotomy. The thin windsock, which is the
aneurysmal sac with a single opening or multiple perforations
is excised, creating a large defect in the right sinus, which is
down stream or cephalad to the VSD, separated by a hinge
line of the aortic cusp. Dacron or polytetrafluoroethylene
(PTFE) patch is sewen to close the VSD and the defect in the
sinus of Valsalva, taking care to suture the aortic cusp hinge
to the patch at appropriate level. The ventriculotomy or atrial
opening is closed with continuous polypropylene suture.
The aortic valve cusps are inspected and any cuspal
redundancy or prolapse is addressed by performing a Trusler
repair. If valve cusps are not suitable for repair, aortic valve
may have to be replaced.
The RSOV can be repaired through aorta or pulmonary
artery or right atrium. The approach could be through aorta or
right atrium alone if there is no associated VSD.
CONCLUSION
Aneurysm of the sinus of Valsalva is an uncommon disorder,
most commonly presenting subsequent to rupture into a
cardiac chamber. The ruptured sinus of Valsalva is usually
acquired later in life, usually with no history of heart disease.
It can occur spontaneously, following chest wall trauma or an
episode of bacterial endocarditis. The onset is usually sudden
or acute with a loud continuous murmur and often associated
with significant congestive heart failure. The timely surgical
closure or transcatheter device closure can reduce the
morbidity and mortality.
People pay the doctor for his trouble; for his kindness they
still remain in his debt.
Seneca
acknowledgment
We express our thanks to Dr IB Vijayalakshmi, Professor of
Pediatric Cardiology, for providing all the illustrative images
for this chapter.
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short term follow up. Ann Pediatr Cardiol. 2009;2:79-82.
58. Arora R, Trehan V, Rangashetty UM, Mukhopadhyay S,
Thakur AK, Kalra GS. Transcatheter closure of ruptured sinus
of valsalva. J Interv Cardiol. 2004;17:53-8.
Sec t i on
Right and Left Ventricular

Obstructive Lesions
C hapter
25
Right Ventricular Outflow

Tract Obstructions
Suresh Kumar R
The right ventricular outflow tract (RVOT) may be deemed to

commence at the infundibulum and to comprise the pulmonary
valve and the pulmonary arterial tree. The obstruction of this
region are discussed under the following headings:
1. Pulmonary valve stenosis.
2. Infundibular stenosis.
3. Double-chambered right ventricle.
4. Peripheral pulmonary artery stenosis.
VALVAR PULMONARY STENOSIS

Isolated pulmonary valvar stenosis is an acyanotic malforma
tion with normal or diminished pulmonary blood flow. The
ventricular septum is intact in 80 percent of cases. The first
description of this malformation was given by Morgagni in
1761.1
Incidence
Stenosis of the pulmonary valve represents 8 to 12 percent
of all congenital heart defects in children2,3 and 15 percent
of all congenital heart defects in adults.4-6 Isolated valvar
pulmonary stenosis with an intact ventricular septum is the
second most common congenital cardiac defect in children of
the United States. It occurs with equal incidence in both the
sexes.6
Clinical Features
Valvar pulmonary stenosis has distinctive clinical features
based on the age of presentation. Hence, clinical features may
be described as for the neonate, child and adult.
Valvar Pulmonary Stenosis in the Neonate

Critical valvar pulmonary stenosis in the neonate presents
dramatically with profound hypoxia. The term critical
pulmonary stenosis with intact ventricular septum is applied
to severe pulmonary valvar stenosis resulting in systemic/
suprasystemic right ventricular pressures and right to left
shunt across the atrial septum, often with significant tricuspid
regurgitation. The pulmonary flow may be completely duct
dependentfunctional pulmonary atresia. The affected
neonate has cyanosis, congestive heart failure, hypotension,
feeding difficulty and tachypnea. On clinical examination,
there is no impressive murmur quite often. The pulmonary
component of the second sound is delayed, soft or absent.
There may be a pansystolic murmur of tricuspid regurgitation.
Milder stenosis is asymptomatic and is characterized by the
phasic ejection click and ejection systolic murmur, once the
pulmonary vascular resistance has fallen. Two-dimensional
(2D) echocardiography is diagnostic for this condition.
Valvar Pulmonary Stenosis in Children
Genetics
Non-syndromic pulmonary valve stenosis is an isolated
lesion, even though autosomal dominant inheritance has
been reported in some families.7 Syndromes associated with
valvar pulmonary stenosis include Noonans syndrome,
Williams syndrome, rubella syndrome, Leopard syndrome
and cardiofacial syndrome. Seven percent of children
with pulmonary stenosis have Noonans syndrome.8 The
critical region for Noonans syndrome type-1 is located on
chromosome 12 q24.
Valvar pulmonary stenosis is generally well tolerated and even

severe stenosis is often asymptomatic. General examination is
unremarkable, though atypical moon-like facies and chubby
cheeks have been described.6 Jugular venous pressure (JVP)
shows prominent a waves in severe stenosis. Apex beat is
normal. A left parasternal heave represents severe stenosis.
The second heart sound is often widely split with P2 well
preserved in milder stenosis. The auscultatory hallmark of
valvar pulmonary stenosis is the phasic ejection click. This
click is characteristically louder in expiration, representing
Right and Left Ventricular Obstructive Lesions
the greater range of mobility the valve has in this phase of

respiration. The click moves closer to the first sound as the
stenosis progresses and eventually appears to merge with it. In
severe pulmonary stenosis, the S1 appears to be accentuated
in expiration in the pulmonary area, due to the fused click. A
harsh ejection systolic murmur, often associated with a thrill
in the left upper sternal border is characteristic of pulmonary
stenosis. A long murmur with delayed peak characterizes
severe pulmonary stenosis.
Valvar Pulmonary Stenosis in Adults

Survival into adulthood may occur in many uncorrected patients
with pulmonary stenosis. Fibrous thickening and occasionally
calcification of the valve occurs with age. Clinical features
vary from mild exertional dyspnea to signs of right heart
failure. Moderate to severe obstruction leads to inability to
augment pulmonary blood flow during exercise, resulting in
fatigue, syncope or chest pain. Adults with mild or moderate
pulmonary stenosis have findings similar to those described in
children. Severe pulmonary stenosis may present with features
of right heart failure. JVP is elevated with prominent a waves.
Cardiomegaly is common. Second heart sound is widely split,
the pulmonary component is often inaudible. Right ventricular
third and fourth heart sounds are heard. The murmur has
the characteristics already described. However, the tricuspid
regurgitation murmur may overshadow the clinical presentation.
Investigation
Electrocardiogram
Baseline electrocardiogram (ECG) is usually normal in mild
to moderate pulmonic stenosis.9 In more severe cases, right
atrial enlargement, right ventricular hypertrophy and right
axis deviation are observed. Incomplete right bundle branch
block (RBBB) may be seen. Left bundle branch block (LBBB)
and left axis deviation point to Noonans syndrome.10 The T
wave may be upright or inverted with occasional ST segment
changes suggestive of ischemia.11 For patients between 2
and 20 years, the resting right ventricular pressure can be
calculated from the ECG using the following formula.12
Right ventricular (RV) pressure in mm Hg = R wave length
(mm) in V1 5.
Chest Radiogram
358
In mild to moderate pulmonary stenosis, the heart size

and pulmonary vascular markings are normal. The most
distinctive feature is a prominent main pulmonary artery
segment secondary to poststenotic dilatation of the pulmonary
trunk and the proximal part of the left pulmonary arteryseen
in 90 percent of patients. Poststenotic dilatation may be absent
in infants, small children and in patients with dysplastic
pulmonary valve as in Noonans syndrome.13,14
Echocardiogram
Two-dimensional echocardiography is the best diagnostic

modality for assessment of pulmonary valve anatomy,
localization of stenosis and evaluation of right ventricular size
and function. Typical valvar stenosis is characterized by mildly
thickened leaflets that dome in systole.15 Presystolic doming
of the valve may be seen during atrial contraction in patients
with severe stenosis and a non-compliant right ventricle.15
Truly dysplastic valves are characterized by markedly
thickened and seemingly immobile leaflets, small valve
annulus and often supravalvular narrowing.16 It is important
to identify dysplastic valves, as balloon valvuloplasty in these
patients may achieve only suboptimal results. Continuous
wave Doppler measurement of peak systolic velocities
estimates the transpulmonic gradient, which is comparable
to values obtained at cardiac catheterization.17,18 The severity
is typically defined by the peak systolic gradient across the
pulmonic valve.19 Values less than or equal to 40 mm Hg
denote mild stenosis, while values more than equal to 80
mm Hg denote severe stenosis. However, in the outpatient
setting, values above 64 mm Hg may be considered to indicate
moderate stenosis warranting intervention.
Color Doppler is particularly useful to identify the jet
width of severe pulmonary stenosis and to identify ductal
flow. However, pulmonary regurgitation can also be detected
and quantitated.20
Management
Children with mild pulmonary stenosis do not need intervention
in childhood.21 They should be clinically followed yearly.
Limitations in exercise or activity levels are not needed.
Infective endocarditis prophylaxis is indicated during surgery
or any procedure likely to produce bacteremia.
Patients with moderate to severe pulmonary stenosis
(Doppler gradient 64 mm Hg) should undergo intervention.
After the obstruction is relieved, routine care and endocarditis
prophylaxis are recommended as in the case of mild
stenosis.
Patients with signs of right ventricular failure should be
treated with decongestive measures followed by intervention
to relieve the obstruction. The right ventricular function may
not recover completely in adults.
Balloon Pulmonary Valvuloplasty

Currently, balloon valvuloplasty is the treatment of choice for
managing isolated pulmonary valve stenosis.22,23 Jean S Kan
reported the first case of balloon pulmonary valvuloplasty in
1982.24
Indications
1. Neonates with critical pulmonary stenosis (severe
pulmonary stenosis with systemic desaturation).
Technique
The procedure is done under intravenous sedation. The
neonate/young infant with suprasystemic right ventricular
pressures may be electively ventilated. After appropriate
venous access, a right ventricular angiogram is done, usually
in the lateral view (Figure 1). This helps in demonstrating
the valve anatomy and in providing a measurement of the
valve annulus. Unsuspected infundibular or supravalvular
pathology can be recognized. Further, the angiogram provides
the road map for crossing the valve. In the neonate, often a
hand injection is performed in the RVOT, while the older
infant/child could have a regular pressure injection.
The key to crossing the valve in a severe stenosis is an
appropriate catheter. 4 Judkins right coronary catheter, 4F
multipurpose catheter or a Swan-Ganz catheter serve the
purpose. Using a hydrophilic wire, the valve is crossed. An
appropriate size superstiff wire (e.g. Amplatz super-stiff wire)
is placed well buckled in the left pulmonary artery. A balloon
(e.g. Tyshak II) of appropriate length and diameter (balloon/
annulus ratio = 1 : 1.25)26,27 is placed across the valve and
inflated to recommended pressure. Disappearance of the waist
is the radiological proof of abolition of stenosis. When the
pulmonary valve annulus is too large to be dilated with a
single balloon, simultaneous inflation of two balloons across
the pulmonary valve may be performed.28,29 Right ventricular
pressure can be measured with a multitrack catheter without
disturbing the wire position. Right ventricular pressure

less than half-systemic levels denote good result. If the
right ventricular pressure is more than the desired level, it
is important to look for infundibular spasm, a hypoplastic
annulus or a supravalvar stenosis before upsizing the balloon
for a repeat attempt. When the residual infundibular gradient is
more than 50 mm Hg, beta-blocker therapy is recommended.
This infundibular reaction greatly regresses at follow-up.30-32
Follow-up Evaluation
Clinical evaluation, ECG and Doppler echo evaluation may be
done at 1-month, 6-month and 1-year after the procedure.33 ECG
is a useful adjunct in the evaluation of follow-up results34 as it
shows regression of right ventricular hypertrophy. This change
is usually seen 6 months after the procedure.34 Doppler gradient
generally reflects residual obstruction and is a useful and reliable
monitoring tool.35 Restenosis (gradient > 50 mm Hg on Doppler
echo) is observed in nearly 10 percent of cases.36 Predictors
of restenosis include a balloon-to-annulus ratio of less than
1.2 and a gradient of more than 30 mm Hg immediately after
valvuloplasty. In addition, small valve annulus, postsurgical or
complex pulmonary stenosis are also predictive of restenosis.37
Data on long-term follow-up results is scarce. Some studies
have shown 1 to 2 percent recurrence of pulmonary stenosis.38
In one study, surgical intervention was needed in 5 percent of
the patients for subvalvar or supravalvar stenosis;38 freedom
from intervention was 88 percent and 84 percent at 5 and 10
years respectively. Pulmonary insufficiency was noted in 80 to
90 percent of the patients, but was usually mild.
25
Right Ventricular Outflow Tract Obstructions
2. Infants or older children a peak-to-peak catheter gradient

or echocardiographic peak instantaneous gradient of >
40 mm Hg or clinically significant pulmonary valvar
obstruction in the presence of RV dysfunction (Class I
indication).25
Other Catheter Interventions

Other catheter interventions may become necessary in patients
with pulmonary stenosis:
1. Transcatheter closure of a significant size patent ductus
arteriosus with a coil or device.
2. Occlusion of an atrial septal defect with a septal occluder.
3. Balloon atrial septostomy in neonates39 with a severely
hypoplastic right ventricle.
4. Coronary artery angiography/angioplasty in adults during
catheterization for balloon pulmonary valvuloplasty.
Surgical Technique
The currently preferred technique for valvar pulmonary
stenosis is transpulmonary arterial valvotomy under cardio
pulmonary bypass.40
Indications
Figure 1: Valvar pulmonary stenosis. Right ventricular angiogram in
lateral view. Note the doming pulmonary valve
1. Dysplastic pulmonary valve with valve ring hypoplasia.

2. Fixed infundibular and supravalvar stenosis with pulmonary
valvar stenosis.
359
Isolated Infundibular Stenosis

Infundibular stenosis commonly occurs in association with a
malaligned ventricular septal defect (VSD) in the setting of
tetralogy of Fallot (TOF). Isolated infundibular stenosis with
intact ventricular septum is a very uncommon defect, initially
described by Elliotson in 1830. It accounts for 5 percent of all
cases of RVOT obstruction. It is of two types41
1. A fibrous band at the junction of the infundibulum and cavity
of the right ventricle (Figure 2). This is the more common
type resembling double-chambered right ventricle.
2. Fibromuscular obstruction directly below the pulmonary
valve.
The proposed embryologic abnormality is an arrest of
bulbus cordis involution during the development of the
outflow tract.
The physical findings consist of a loud, systolic ejection
murmur with a widely split second sound and soft pulmonary
component. Two findings that help to distinguish infundibular
from pulmonary valve stenosis are the relatively lower
location of the murmur at the lower sternal border and the
absence of an ejection click. The ECG features are similar
to those of pulmonary valve stenosis. The X-ray findings are
not distinctive. Echo-Doppler studies help in distinguishing
infundibular from valvar stenosis. Systolic fluttering of
the pulmonary valve, as against doming, is the hallmark of
subvalvular obstruction. The severity of the obstruction can
be estimated by continuous wave Doppler. Selective right
ventriculogram in right anterior oblique (RAO) cranial
and lateral projections demonstrate the site of infundibular

obstruction well. The narrowing is more during systole, with
normal pulmonary valve and no poststenotic dilatation of the
main pulmonary artery. The treatment of significant primary
infundibular stenosis is surgical resection of the fibrotic area
or hypertrophic muscle.
Double-Chambered Right Ventricle

Double-chambered right ventricle (DCRV) is a distinctive
anatomic entity, wherein there is a muscular obstruction
below the infundibulum dividing the right ventricle into a low
pressure infundibulum and a high pressure apical portion.
Anderson has provided an elegant description of the
pathologic anatomy of this entity.42 The septal band of the
septomarginal trabeculation is a prominent muscular shelf on
the septal surface of the right ventricle, from where a series
of muscle bundles extend to the free wall as septoparietal
trabeculationsthe most prominent one going to the anterior
papillary muscle as the moderator band. The obstructive
muscle bundles of DCRV are abnormally hypertrophied septoparietal trabeculations extending towards right ventricular
apex. Two characteristic locations of obstruction include:
a. Low oblique one close to the apex.
b. Higher horizontal one close to the infundibulum.
The right ventricular inlet continuous with the apical
trabecular portion has a higher pressure and the infundibular
chamber has a lower pressure.
Prevalence
Double-chambered right venticle cardiac defect typically
presents in infancy and childhood. Ten percent of children
undergoing correction of VSD and TOF may have associated
DCRV.43 There are isolated reports in adults.44
The DCRV is seldom seen as an isolated anomaly. Most
commonly it is associated with a perimembranous VSD. Other
lesions include subaortic stenosis, pulmonary valve stenosis,
double outlet right ventricle,45 TOF, anomalous pulmonary
venous drainage, complete or corrected transposition of
the great arteries, pulmonary atresia with intact ventricular
septum and Ebstein anomaly.
Clinical Features
360
Figure 2: Right ventricular (RV) angiogram in AP with 10 right anterior

oblique view illustrates highly trabeculated RV with hypertrophied
bands causing isolated infundibular stenosis (arrows) in 8 years old girl.
INF = infundibulum; MPA = Main pulmonary artery; RV = Right ventricle
Image Courtesy: Dr IB Vijayalakshmi
Patients with isolated DCRV and mild to moderate

right ventricular outflow tract obstruction (RVOTO) are
asymptomatic. When RVOTO is severe, exertional fatigue,
dyspnea, light headedness, or chest discomfort (right
ventricular angina), may be experienced.45 The variability
of presentation is in part attributable to the multiplicity of
severe forms, the obstruction is seen as a pyramidal filling

defect, with its base broadly attached to the anterior ventricular
wall and with the apex protruding superiorly47 (Figure 3A). In
the lateral view, the filling defect is seen in the anterior wall
between the inflow and outflow portions of the right ventricle
(Figure 3B).
Management
Patients with significant right ventricular cavity gradient
require surgical resection of the obstruction.
Investigation
Electrocardiogram
The ECG usually shows RV hypertrophy and right axis
deviation, but may have atypical features like dominant
R in lead V4R, with only an rS complex in V1. These
electrocardiographic abnormalities are attributed to the
absence of hypertrophy of the distal right ventricular chamber.
Chest X-ray
Radiologic findings may vary from a small heart with decreased
vascularity to cardiomegaly with increased vascularity of the
lungs, depending on the presence of a large left to right shunt
or RV dysfunction.
25
associated lesions. If there is an interatrial communication

or if the VSD is proximal to the obstruction cyanosis may
occur. Severe RVOTO results in RV heave. The ejection
systolic murmur, which is characteristically loud and long, is
of maximal intensity in the third or even fourth left interspace.
The site of the thrill, if present, is also low.
A diminished right ventricular stroke output caused by the
small proximal chamber and the relatively low immediate
subvalvular pressure allows the pulmonary valve to close
earlier. Hence P2 is not too soft or too delayed.
2D Echo
The best view for diagnosing DCRV is the subcostal shortaxis view in infants and young children.43,46 In older patients,
the parasternal short-axis view at the level of the aortic valve
is useful.4 An anomalous bundle is identified, just below the
ostium of right ventricular infundibulum in the short-axis
view.5 The distal portion of the infundibulum located under the
pulmonary valve is wide open and free of obstruction. The exact
site of obstruction could be identified on color flow Doppler.2
Associated lesions like VSD may be recognized. Care is needed
not to mistake the systolic jet of a VSD from that resulting due
to the obstruction within the ventricular cavity.6
Transesophageal echo would allow better definition of the
lesion in adults.
The pressure data characteristically shows a low pressure
tracing in the pulmonary artery, as well as the infundibular
chamber, while the pressure is high (often suprasystemic)
in the RV apex. Angiocardiography in RAO/AP and lateral
views is the ideal diagnostic technique in cases of DCRV.7
The anomalous muscle bundles in anteroposterior projection
take the form of one or more filling defects that cross the right
ventricular cavity either diagonally or horizontally. In most
B
Figures 3A and B: A. Double-chambered right ventricle. Right
ventricle (RV) angiogram in anteroposterior view showing severe
sub-infundibular stenosis and the pyramidal filling defect with its base
towards anterior RV wall; B. Double-chambered right ventricle. Same
findings in lateral view
361
Pulmonary Artery Stenosis

The word pulmonary artery stenosis refers to obstruction
anywhere in the area from the main pulmonary artery and
its branches to the distal intrapulmonary arteries. The term
peripheral pulmonary artery stenosis has generally been used
synonymously. The word supravalvar pulmonary stenosis has
been used to describe main pulmonary artery (MPA) stenosis.
Gay and Smith have classified peripheral pulmonary artery
stenosis into four types (Figure 4):
1. Proximal main pulmonary artery stenosis.
2. Bifurcation stenosis.
3. Distal pulmonary artery stenosis.
4. Combination of multiple levels of stenosis.
Causes
1. Congenital
Ductal constriction
tof
Pulmonary atresia/VSD/major aortopulmonary collateral
arteries (MAPCAs)
Alagille syndrome
William-Beuren syndrome
Noonans syndrome
Congenital rubella syndrome
Cutis laxa
Ehlers-Danlos syndrome
Silver syndrome.
2. Acquired
Postoperative:
TOF repair
Arterial switch operation for transposition of great
vessels
Central or Blalock-Taussig shunt
Pulmonary artery banding
Reimplantation of pulmonary artery

arteriosus, aortopulmonary collaterals)
Pulmonary arterioplasty
Fibrosing mediastinitis
Mediastinal tumor
Takayasus arteritis.
(truncus
Clinical Features
The diverse etiology of pulmonary artery stenosis makes
difficult the prediction of an incidence figure. The disease
may manifest itself at any age from neonatal period to late
adulthood. Diffuse peripheral pulmonary artery stenosis
can present with life threatening central pulmonary artery
hypertension in the neonatal period. Postoperative pulmonary
artery stenosis may manifest at any age from immediate
post operative period to late adulthood. Discrete pulmonary
artery branch stenosis is usually asymptomatic, but may
worsen pulmonary regurgitation in a repaired TOF and cause
congestive heart failure. Central pulmonary artery stenosis,
bilateral pulmonary artery stenosis or diffuse peripheral
pulmonary artery stenosis may elevate central pulmonary
artery and right ventricular pressure.
Clinical examination reveals characteristic dysmorphic
features in situations like Noonans syndrome or Williams
syndrome. Cyanosis may occur if right ventricular pressure
is high and a PFO is shunting right-to-left. JVP may
show prominent a waves. Left parasternal heave may be
prominent. First heart sound is normal, while 2nd heart
sound may be variably split. Depending upon the degree of
central pulmonary artery hypertension, RV S3 or S4 may
occur.
Investigation
Chest X-ray
May show RA enlargement. MPA may be enlarged if stenosis
is of both branches or diffuse. Decreased vascularity on one
side is characteristic of unilateral obstruction.
2D Echo
May show dilatation of RA/RV and right ventricular
hypertrophy (RVH). The nature and site of stenosis are
demonstrated by echo. One can also estimate RV pressure
from tricuspid regurgitation (TR) Doppler signal.
CT Angiography or MR Angiography
362
Figure 4: Classification of peripheral pulmonary artery stenosis
These demonstrate the site and degree of stenosis best. Today,

these are the best guides for intervention.
Perfusion lung scan shows ventilation-perfusion mismatch
in affected areas.
Indications for Intervention48
Management
Transcatheter Intervention
The procedure has been applied to both central pulmonary
artery and its branches. While the basic technique is similar
to pulmonary balloon valvotomy, the following guidelines are
important:
1. Choose a balloon three to four times the waist, but not
exceeding twice the diameter of normal segment.
2. The waist in the inflated balloon should be more than or
equal to 50 percent of inflated balloon diameter (too small
a waist has a high risk of vessel rupture).
3. Use a balloon with a burst pressure of at least 6 atm (often
higher) for 5 to 30 seconds.
Balloon angioplasty has success rate of 30 to 60 percent in
large series. Postoperative stenosis responds better than native
stenosis. Distal intralobar stenosis usually does not respond to
balloon dilation.
25
1. RV pressure more than 50 percent systemic pressure.

2. Perfusion scan showing decreased perfusion by >20 percent.
3. RV dysfunction/cyanosis.
4. Symptomatic patient.
across the RVOT and across the lesion. The sheath should be
across the lesion by a few mm. Now the stent balloon assembly
is negotiated across the lesion. Once the stent-mounted balloon
is across the lesion, repeat hand injection of contrast from
the side arm of the sheath confirms the placement. Initial
gentle predilation with a small balloon at 4 to 6 atm, tests
the compliance and makes the passage of the larger balloon/
stent assembly easier. After suitable placement, balloon is
inflated to recommended pressure, deploying the stent. Further
angiograms from the sheath confirm accurate placement and
stent expansion. The deflated balloon is withdrawn over the
wire into the PA proximal to the stent and then removed. Now
an end hole catheter is gently advanced over the wire and the
wire withdrawn into the catheter (Figures 5A to C). Catheter is
then gently withdrawn without displacing the stent.
Complications include stent displacement, hemoptysis,
vessel rupture, hypotension. Long-term complications include
stent fracture and restenosis (2 to 15%).48
Pulmonary Artery Stenting

The PA stenting overcomes the problem of immediate recoil
following balloon pulmonary arterioplasty. The stents are
generally improvisations of peripheral arterial stents, but
having a fair range of options minimizes the problems of
imperfection. Some of the commonly used stents include
Genesis (Cordis, Florida, USA).
As the stents can be expanded over a range, it is the size of
the balloon that needs to be chosen. Higher pressure balloons
like Opta Pro, Maxi LD (Cordis, Florida, USA) or Atlas are
useful. The stent is hand mounted and crimped over the balloon.
The venous sheath should be atleast 2F size bigger than that
recommended for the balloon to accommodate the stent. Using
a short sheath across the valve of the introducer sheath will
prevent slippage of the stent. The lesion is crossed with an end
hole catheter and hydrophilic wire. An extra-support wire (e.g.
Amplatzer Super Stiff) usually 0.035 with 200 to 300 mm
length is placed well buckled into the distal pulmonary artery. It
is the author`s practice, having initially performed a computed
tomography (CT) angio to use a multitrack catheter to perform
an angiogram in an appropriate oblique view. From the image,
the lesion diameter and length (to reach normal artery on each
side) are measured. The balloon chosen should be of the size
of a distal normal vessel. At this stage, the stent is mounted on
the balloon. The femoral sheath is changed to a long braided
sheath with dilator, size being chosen on +2F size principle. It
requires perseverance and skill to maneuver the sheath-dilator
B
Figures 5A and B: Pulmonary artery stenting: A. Post-extracardiac
Fontan (LPA) stenosis; B. Post-Fontan LPA stenosisstent positioning
363
5
2.
3.
4.
5.
6.
7.
8.
Figure 5C: Post-Fontan LPA stenosis: post stent angiogram
9.
10.
Some of the currently available stents allow redilation at

a later date. Drug eluting stent may decrease restenosis rate
and self-dissolving stents may address the issue of future
expansion limitation.
Cutting balloon angioplasty: In peripheral pulmonary
stenosis, involving very distal branches, especially in
unifocalized systemic arteries, cutting balloon angioplasty has
been found to be more useful.
11.
12.
13.
14.
Conclusion
Right ventricular outflow tract may be obstructed anywhere
from the infundibulum to the distal pulmonary arteries.
Whereas valvar or arterial lesions are generally amenable
to catheter interventions, infundibular/sub-infundibular
obstruction require surgical repair. Regular follow up of mildmoderate lesions and a high index of suspicion can avoid silent
progression of obstruction to right heart failure.
15.
16.
17.
Medicine heals doubts as well as diseases.

Karl Marx
ACKNOWLEDGMENT
The work done by Dr Bhushan Chavan, Fellow in Pediatric
Cardiology, Institute of Cardiovascular Diseases, The Madras
Medical Mission, in the preparation of this manuscript is
sincerely acknowledged.
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Takao S, Miyatake K, Izumi S, et al. Clinical implications of
pulmonary regurgitation in healthy individuals: detection by
cross sectional pulse Doppler echocardiography: Br Heart J.
1988;59:542-50.
35. Rao PS. Value of echo-Doppler studies in the evaluation of

the results of balloon pulmonary valvuloplasty. J Cardiovasc
Ultrasonography.1986;309-12.
36. Rao PS, Thapar MK, Kutayli F. Causes of restenosis after
balloon valvuloplasty for valvular pulmonary stenosis.Am J
Cardiol.1988;62:979-82.
37. McCrindle BW. Independent predictors of long-term results
after balloon pulmonary valvuloplasty. Valvuloplasty and
Angioplasty of Congenital Anomalies (VACA) Registry
Investigators.Circulation.1994;89:1751-9.
38. Rao PS, Galal O, Patnana M, et al. Results of three to
10 year follow-up of balloon dilatation of the pulmonary
valve.Heart.1998;80:591-5.
39. Rao PS. Role of interventional cardiology in neonates:
Part I. Non-surgical atrial septostomy. Congenital Cardiol
Today.2007;5:1-12.
40. Castaneda AR, Jonas RA, Mayer JE.Surgery for infants with
congenital heart defects. Cardiac Surgery of the Neonate and
Infant,1st edition.1993. pp. 1013-35.
41. Cheatham JP. Pulmonary stenosis. In: Arthur Garson, J Timothy
Bricker, Dan G Mcnamara (Eds). The Science and Practice in
Pediatric Cardiology, vol. 2.pp.1406-7.
42. Restivo A, Cameron AH, Anderson RH, et al. Divided right
ventricle: a review of its anatomical varieties. Pediatr Cardiol.
1984;5:197-204.
43. Hoffman P, Wojcik AW, Rozanski J, et al. The role of
echocardiography in diagnosing double-chambered right
ventricle in adults. Heart. 2004;90:789-93.
44. Kobayashi S, Terumi Hayashi, Shiroh Nakahara, et al. A
case of double chambered right ventricle associated with an
interventricular septal aneurysm in an elderly patient. J Med
Ultrasonics. 2002;29:55-61.
45. Galal O, Al-Halees Z, Solymar L, et al. Double-chambered
right ventricle in 73 patients: spectrum of the disease
and surgical results of transatrial repair. Can J Cardiol.
2000;16:167-73.
46. Matina D, van Doesburg NH, Fouron JC, et al. Subxiphoid
two-dimensional echocardiographic diagnosis of doublechambered right ventricle. Circulation. 1983;67:885-8.
47. Alva C,Ho SY,Lincoln CR,et al. The nature of the obstructive
muscular bundles in double-chambered right ventricle. J
48. Kyong-Jin Lee. Transcatheter interventions on the central and
pulmonary arteriescurrent techniques and outcomes. In:
Andrew N Redington, Glen S Van Arsdell, Robert H Anderson
(Eds). Congenital Diseases in the Right Heart. Springer; 2009.
pp.73, 9.
25
21. Drossner DM, Mahle WT. A management strategy for mild

valvar pulmonary stenosis.Pediatr Cardiol. 2008;29:649-52.
22. Rao PS.Balloon pulmonary valvuloplasty for isolated pulmonic
stenosis.Transcatheter Therapy in Pediatric Cardiology.WileyLiss;1993.pp.59-104.
23. Rao PS. Transcatheter treatment of pulmonary outflow tract
obstruction: a review.Prog Cardiovasc Dis.1992;35:119-58.
24. Kan JS, White RI, Mitchell SE, et al. Percutaneous balloon
valvuloplasty: a new method for treating congenital pulmonaryvalve stenosis.N Engl J Med. 1982;307:540-2.
Association. Circulation. 2011;123:2607-52.
26. Berman W, Fripp RR, Raisher BD, et al.Significant pulmonary
valve incompetence following oversize balloon pulmonary
valveplasty in small infants: A long-term follow-up study.Catheter
Cardiovasc Interv.1999;48:61-5; discussion 66.
27. Rao PS. Late pulmonary insufficiency after balloon dilatation of the pulmonary valve. Catheter Cardiovasc Intervent.2000;49:118-9.
28. Rao PS. How big a balloon and how many balloons for
pulmonary valvuloplasty? Am Heart J.1988;116:577-80.
29. Rao PS, Fawzy ME.Double balloon technique for percutaneous
balloon pulmonary valvuloplasty: comparison with single
balloon technique.J Interven Cardiol.1988;1:257-62.
30. Engle MA, Holswade GR, Goldberg HP, et al. Regression
after open valvotomy of infundibular stenosis accompanying
severe valvular pulmonic stenosis. Circulation. 1958;17:
862-73.
31. Johnson AM.Hypertonic infundibular stenosis complicating
simple pulmonary valve stenosis. Br Heart J. 1959;21:
429-39.
32. Gilbert JW, Morrow AG, Talbert JL.The surgical significance
of hypertrophic infundibular obstruction accompanying
valvular pulmonic stenosis. J Thorac Cardiovasc
Surg.1963;46:457-67.
33. Rao PS.Long-term follow-up results after balloon dilatation
of pulmonic stenosis, aortic stenosis, and coarctation of the
aorta: a review.Prog Cardiovasc Dis. 1999;42:59-74.
34. Rao PS, Solymar L. Electrocardiographic changes following
balloon dilatation of valvar pulmonic stenosis. J Intervent
Cardiol.1988;1:189-97.
365
C hapter
26
Left Ventricular
Outflow Tract Obstructions
Vijayalakshmi IB, Vimala J
INTROdUCTION
Left ventricular outflow tract obstructions (LVOTO) include a
series of stenotic lesions starting in the anatomic left ventricular
outflow tract (LVOT) and stretching to the descending portion
of the aortic arch.1 The obstruction can be at the subvalvar,
valvar or supravalvar region. These obstructions to the LVOT
may be alone or frequently in association with other cardiac
defects. The patients with LVOTO comprise a diverse group
of neonates, infants, children and young adults. The patients
may be critically ill or asymptomatic.2 The LVOTO increases
the afterload on the left ventricle (LV) and if the obstruction is
severe and untreated, it results in hypertrophy and eventually
dilatation and failure of the LV in some patients. In the vast
majority, the LVOTOs are congenital, with the exception of
some variants of subaortic stenosis (SAS). All these patients
with LVOTO are at high-risk for developing infective
endocarditis. The incidence of LVOTO is 6/10,000 live births.
The classification of LVOTO is given in Box 1.3 In
this chapter, the presentation, diagnosis, management and
outcomes are discussed in patients with SAS, supraaortic
stenosis and Shones anomaly. The valvar aortic stenosis (AS)
Box 1: Classification of left ventricular outflow obstruction
Subvalvular
Discrete membranous stenosis
Fibromuscular tunnel
Hypertrophic obstructive cardiomyopathy (HOCM)
Valvular
Unicuspid
Bicuspid
Dysplastic
Supravalvular
Discrete (membranous or hourglass)
Aortic hypoplasia or atresia
Interrupted aortic arch
Coarctation of aorta.
is dealt in Chapter 33. Coarctation of the aorta and hypoplastic

left heart syndrome are discussed in Chapter 34 and 47
respectively.
SUBAORTIC STENOSIS
The SAS is the LVOT obstruction just below the aortic valve.
In 1842, Cheevers4 recorded the first description of subaortic/
subvalvular AS. It is classified by the nature of the obstructing
lesion as either fixed or dynamic. The dynamic form, idiopathic
hypertrophic obstructive cardiomyopathy (HOCM), in which
the obstruction is caused by a generalized hypertrophy of the
LVOT and interventricular septum, is discussed in Chapter 51.
The fixed SAS is the second most common form of
LVOTO. Rarely, abnormal accessory mitral valve tissue or
chords may cause SAS. It has been found that the distance
between the mitral and aortic valves in patients with SAS is
consistently increased.5 The fixed SAS accounts for 15 to 20
percent of all types of LVOTO.6 The subaortic obstruction is
almost always progressive and is not static.
Anatomy and Embryology

There is some debate about whether this lesion is indeed
congenital, since it is rarely observed in newborns. There is
clinical and experimental evidence that fixed SAS is an acquired
lesion with an underlying ill-defined congenital disorder. It
is therefore often regarded as an acquired lesion. It has been
hypothesized that the alteration in direction of blood flow near
the crest of the interventricular septum leads to differentiation
of embryonic cells into a fibrotic tissue variant.5 It is usually
associated with other congenital anomalies in 50 to 65
percent of the cases, e.g. perimembranous type of ventricular
septal defect (VSD) (Figure 1), bicuspid aortic valve (BAV),
coarctation of aorta (COA), patent ductus arteriosus and left
superior vena cava.7 Subvalvar obstruction has also been
reported after surgical patch closure of malaligned VSDs and
26
is thought to be secondary to fibrous tissue proliferation at

the sites of turbulent ouflow.8 Persistent endocardial cushion
tissue that retains proliferative capacity has been suspected
for SAS. Familial occurrence of SAS in humans has been
reported.9 SAS may also be present as part of a complex of
obstructive lesions, as in Shones complex, which frequently
includes parachute mitral valve, mitral stenosis, BAV and
COA.10
Pathophysiology
The physiology of isolated SAS is identical to that of valvar
AS. The left ventricular hypertrophy occurs in response to high
systolic pressure. Poststenotic dilatation is not a feature of SAS
and even if dilatation occurs it is mild. The aortic leaflets are
frequently malformed, resulting in aortic regurgitation (AR) in
about 50 percent of cases. The aortic cusp abnormalities result
either from close proximity of the membrane or fibromuscular
collar to the leaflets or from injury caused by the impact of
the eccentric jet when the obstruction is more distal to the
valve.11 The high-velocity systolic jet collides with the aortic
valve (AV) leaflets and results in damage, scarring, leaflet
redundancy and prolapse. This distortion of AV increases its
susceptibility to infective endocarditis.12,13
The subaortic obstruction is divided into three types:
1. Discrete membranous diaphragmatic.
2. Fibromuscular ridge.
3. Tunnel-like obstruction.
Discrete Subaortic Membrane

The obstruction is caused by either a thin, fibrous membrane
(75 to 85 percent) or a thick, fibromuscular band and is found
more with left-sided obstructive lesions.7 The lesion is thought
to result from abnormal motion, growth or hypertrophy of the
left ventricle and is usually progressive in nature.14 The lesion
is often associated with aortic insufficiency, VSD and COA.
Figure 2: Parasternal long-axis view in a 12-year-old boy shows

subaortic membrane (M with arrows) just below the aortic valve. AO =
Aorta; LV = Left ventricle;
These patients are more prone for infective endocarditis. The

SAS is almost always progressive and is not static. Subaortic
obstruction may have a diaphragm just beneath the AV, which
may be crescentric or form a complete circle. Clinically it is
difficult to distinguish subaortic membrane from valvar AS.
For example, a 12-year-old boy diagnosed as AS in fact had
subaortic membrane just below the aortic valve (Figure 2).
Left VentricuLar outfLow tract oBstructions
Figure 1: Apical four-chamber view shows large subaortic ventricular

septal defect (VSD) with bidirectional shunt with subaortic membrane
without obstruction. LA = Left atrium; LV = Left ventricle; RA = Right
atrium; RV = Right ventricle;
Fibromuscular Subaortic Ridge

It is associated with fibrous ring and muscular hypertrophy
and located just below the aortic valve to 1 cm or more
into the body of the ventricle causing more diffuse area of
LVOTO.7 It also frequently encroaches on the anterior mitral
leaflet (Figure 3).15
Subvalvular Fibromuscular Collar or Tunnel

It is a severe form of SAS and is seen in 10 to 15 percent of the
SAS patients.7 It produces a more extensive area of obstruction,
which is characterized by an inward bowing of the echoes
from the anterior and posterior margins of the outflow tract
immediately beneath the aortic valve. There is more diffuse
obstruction extending well into the ventricle associated with
left ventricular hypertrophy (LVH). In this type there is a
dense fibroelastic endocardial tissue involving the entire LVOT
(Figure 4) with annular hypoplasia and fibrous cusps. These
patients are a major surgical challenge.
Clinical Features
The primary hemodynamic effect on the left ventricle is of
increased afterload, resulting in increased intracavitary pressure
367
right and Left VentricuLar oBstructiVe Lesions
The early diastolic murmur (EDM) may be heard at left sternal

border (LSB) in patients with associated AR. The clinical
features in severe SAS are slow rising, low volume pulse, LV
impulse is laterally displaced and sustained with a 3/6 latepeaking MSM at LUSB/RUSB. S4 gallop is common. An
ejection click is uncommon and is heard in less than 5 percent
of patients with SAS.16
diagnosis
Electrocardiogram and Chest Radiograph
Figure 3: Apical five-chamber view shows fibrous ring associated

with muscular hypertrophy and located approximately 1 cm below
the aortic valve and extending downwards causing more diffuse area
of left ventricular outflow obstruction like a tunnel. The concentric
hypertrophy of left ventricle is seen. AML = Anterior mitral leaflet; Ao =
Aorta; LA = Left atrium; LVH = Left ventricular hypertrophy
Figure 4: Parasternal long-axis view in a 8-year-old boy shows

Tunnel (T) like subaortic stenosis caused by dense fibromuscular
collar, attached to interventricular septum (IVS) and extends onto the
anterior mitral leaflet (AML) with narrow orifice with severe obstruction
(gradient 114 mm Hg). Ao = Aorta; LA = Left atrium; LV = Left ventricle
368
and wall stress. In accordance with Laplaces law, the ventricle

hypertrophies in an attempt to reduce the wall stress. Patients
may present with one of the triad of symptoms associated with
severe valvar AS: angina, heart failure or syncope.1 Diminished
and delayed arterial pulses is felt in severe SAS. In mild SAS
apical impulse is normal or non-sustained and non-displaced
with grade 2/6 midsystolic murmur (MSM) at left upper
sternal border (LUSB) and right upper sternal border (RUSB).
The electrocardiogram (ECG) is usually abnormal and shows

LVH (Figure 5) in 65 to 85 percent of patients.17,18 About 25
percent of cases show strain pattern. The chest radiography
is similar to that in valvar AS. There is no cardiomegaly,
but prominent LV contour is seen. Poststenotic aortic root
dilatation is uncommon and is seen in only 25 percent of
patients.17,19
Transthoracic Echocardiography
Transthoracic echocardiography (TTE) is crucial in the
diagnosis and management of SAS. TTE is said to be
superior to angiography in diagnosis of SAS. Sometimes
echocardiographically can miss the membrane because of its
close proximity to the aortic valve (Figure 2). One has to look
carefully for the fibroelastic membrane just below the aortic
valve. Otherwise one ends up reporting it wrongly as just LVH.
The classical M-mode feature is the abnormal fluttering and early
closure of aortic valve (Figure 6). This is due to the turbulence
of blood distal to the SAS. Though on TTE it looks like small
ridges, on necropsy they are much more extensive. Therefore,
careful interrogation in multiple views like parasternal long axis,
apical four-chamber and five-chamber views may delineate the
defect better. Apical five-chamber view may be a useful adjunct,
because it places the membrane or ridge perpendicular to the
path of the scan plane, thereby enhancing the visualization.
Sometimes transesophageal echocardiography (TEE) may be
necessary. As treatment consists of complete resection of the
membrane along with a limited myomectomy, it is important for
an echocardiographer to evaluate the extent of the membrane or
the ridge. Color Doppler demonstrates associated AR and VSD
(Figure 7). Doppler study to obtain the peak velocity is very
important and this must be distinguished from the signal of
VSD and mitral regurgitation (MR).
Often subaortic membrane may be attached to anterior mitral
leaflet (AML) and this crucial information should be reported
so that the surgeon can take precautions during excision of
the membrane and avoid damage to the AML. Because of the
likelihood of progressive damage to the aortic valve leading to
thickening, regurgitation and sometimes severe LV dysfunction,
there is some consensus that the membrane should be removed
early to prevent progressive aortic valve damage. It has been
26
proposed that a LV outflow malformation characterized by a

wider mitral aortic separation, an exaggerated aortic override
and a steeper aortoseptal angle is present in children with
VSD or COA, who subsequently develop SAS.20 Therefore,
careful imaging in the parasternal long-axis and short-axis
is important to delineate the true dimensions of the LVOTO.
Congenital subaortic obstruction is a challenge for the clinician
and the murmur caused by subaortic membrane does not fit into
ejection systolic murmur of AS or pansystolic murmur of MR
or long systolic murmur of VSD. Hence, echocardiography
is the best diagnostic tool, which can delineate the type of
subaortic obstruction and give information about the gradient
across LVOT, LV function, LVH, AR and associated anomalies.
Echocardiography not only helps in accurate diagnosis, but also
assists in management strategy.
Figure 5: Electrocardiogram in half standardization shows severe left ventricular hypertrophy with strain pattern
in an 8-year-old boy with severe subaortic stenosis
Figure 6: M-mode shows fluttering of aortic valve and early systolic
closure of the aortic valve
Figure 7: Subaortic membrane (M) seen just below the aortic valve
in parasternal long-axis view. Color Doppler shows turbulence in the
left ventricular outflow tract beyond the membrane and in the right
ventricle due to the ventricular septal defect. Ao = Aorta; LA = Left
atrium; LV = Left ventricle; RV = Right ventricle.
As SAS is usually associated with other cardiac anomalies both

right and left heart catheterization is recommended. The LV
is entered with an end hole catheter on a Terumo guidewire
from aortic end. The pullback tracing is taken from LV apex to
LVOT and then aorta across the AV. However, when subaortic
membrane is very close to AV getting the separate gradient across
the membrane becomes difficult. In patients with associated
VSD there may be little or no gradient across the membrane.
The end-hole catheter is exchanged with pigtail catheter and
LV angiogram is done to demonstrate the SAS (Figure 8). The
aortic root angiogram invariably shows thickened AV without
doming with various degree of aortic regurgitation. The LVH
is obvious in severe SAS. Although percutaneous balloon
dilatation of subaortic membrane was tried in the past this
procedure has not gained popularity because of progressive AR
and progression of SAS itself, despite the good initial results. 21
It is important to differentiate valvar, subvalvar and supralvar
stenosis (Table 1).
369
Table 1
Differential diagnosis of valvar, subvalvar and supravalvar aortic stenosis

Features
Valvar
Subvalvar
Supravalvar
Face
Normal
Normal
Typical elfin face
Pulse
Normal to anacrotic (parvus et

tardus), depending on the severity
Normal to anacrotic
Unequal-right radial, brachial better felt

than left (Coanda effect)
Apical impulse
Heaving
Heaving
Heaving
Ejection click
Present in BAV
Uncommon
Absent
ESM
Right first ICS conducted to carotids
Left second, third ICS
Right first, second ICS and conducted

to right carotid (shudder)
EDM
Rare
Common
Uncommon
TTE
Aortic valve thickened, doming with

gradient
Subaortic membrane or
tunnel with gradient and AR
Hourglass appearance or membrane in

aorta with gradient
Angiogram
Prussian helmet appearance
Gradient and AR
Membrane in LAO/RAO
view
Narrowing in ascending aorta
AR = Aortic regurgitation; BAV = Bicuspid aortic valve; EDM = Early diastolic murmur; ESM = Ejection systolic murmur; ICS = Intercostal space; LAO/RAO = Left/
right anterior oblique; TTE = Transthoracic echocardiography.
Surgery
Figure 8: Left ventricular (LV) angio in a 8-year-old boy shows severe

subaortic obstruction. LV pressure was 190 mm Hg and pressure
above and below the aortic valve was 114/84 mm Hg (Gradient is 76)
Management
370
Once the Doppler-derived LVOT gradient reaches 50 mm Hg,

there is an increased risk of moderate to severe AR.22 Some
degree of AR occurs in 50 percent of patients with SAS and
moderate or severe AR occurs in 12 percent of patients.23
The degree of SAS may be underestimated by the pressure
gradient in the presence of depressed LV function or a nonrestrictive VSD, that allows left-to-right shunting to the
pulmonary arterial circulation.
Surgical resection is the intervention of choice for treatment of

SAS. The excision of membrane is usually done under direct
vision via a transaortic approach using cardiopulmonary
bypass. It is important to resect as much of membrane as
possible without damaging the mitral leaflet or causing
VSD.24 Surgical mortality is low (0-6%) and complications
are generally minimal.17,24 Patients with a resting catheterdetermined or Doppler-derived estimated peak instantaneous
pressure gradient of greater than or equal to 50 mm Hg
have severe SAS and should undergo operative resection of
SAS.25 Surgical intervention should be considered in patients
with lower gradients (peak instantaneous pressure gradient
< 50 mm Hg) if there is LV systolic dysfunction, moderate/
severe AR or a VSD. Development of symptoms attributable
to SAS (angina, dyspnea or syncope/presyncope) with or
immediately after exertion should prompt surgical intervention. Asymptomatic patients planning to become pregnant
or wishing to participate in competitive sports should be
considered for SAS resection if the gradient is greater than or
equal to 30 mm Hg.1
Surgical management consists of discrete membrane
excision and/or blunt dissection in focal SAS with focal
septal myomectomy. Tunnel-type SAS is more surgically
challenging and often necessitates concomitant myomectomy
or application of the Konno-Rastan procedure to reconstruct
the LVOT.23,26,27 Concomitant repair of the AV is performed if
AR severity is more than mild. SAS recurs in up to 37 percent
of cases after surgical resection.23 In this series, tunnel-type
SAS recurred in 71 percent of patients versus a 14.7 percent
recurrence rate for discrete SAS over 6 years of follow-up.
Even discrete SAS was far more likely to recur, however,
to get the echocardiography done to detect the SAS in time

when it can be treated with simple surgical excision and
correction of associated lesions.
SUPRAVALVAR AORTIC STENOSIS

definition
Supravalvar aortic stenosis (SVAS) denotes obstructive
constriction of the ascending aorta above the AV. This anomaly
is commonly associated with elfin facies like in Williams
syndrome36 and other vascular lesions such as peripheral
pulmonary stenosis and coarctation and coronary artery or renal
artery stenosis. There are three additional features of SVAS:
1. Anatomy of the extramural coronary arteries,
2. Condition of the aortic leaflets and aortic sinuses,
3. The association with Williams syndrome.
Historical Review
Supravalvar aortic stenosis was first described by Chevers
in 1842.4 Later Deniel et al in 1958 described SVAS during
cardiac catheterization.37 In 1961, Williams, Barratt-Boyes
and Lowe described association of SVAS with characteristic
facies consisting of protruding lips, low-set ears, epicanthic
folds and strabismus along with mental retardation. In 1964,
Beuren et al described the full syndrome of SVAS, consisting
of characteristic facies associated with peripheral pulmonary
arterial stenoses, a metallic timber of the voice, dental
hypoplasia and peripheral systemic arterial stenosis.36,38
26
if the resting preoperative gradient was greater than 40 mm

Hg. The presence of an immediate postoperative gradient of
greater than 10 mm Hg led to progressive recurrent SAS in
75 percent of patients; therefore, considerable attention must
be paid by a qualified surgeon to the excision of all abnormal
tissue to include myomectomy of the base of the membrane
and removal of the membrane from the AML. Time to
recurrence depends on SAS type; the tunnel-type lesions recur
earlier than the discrete lesions.
Progressive AR may develop despite relief of SAS.
Persistently turbulent flow patterns in the LVOT after SAS
resection may continue to cause valve damage. In the
surgical series by Brauner et al,23 a higher preoperative
LVOT gradient predicted late progression of AR. Other
investigators have reported less postoperative AR in patients
who underwent SAS resection at a younger age or had a low
LVOT gradient.28-30 It is reasonable to consider surgery at the
time of diagnosis even in patients with low gradients if late
outcome can be safely improved by this strategy. However,
this early aggressive approach should be weighed against the
significant incidence of recurrent obstructive lesions even
in patients with low LVOT gradients.31-33 One should not
allow it to progress to type II or III, as extensive myomectomy
could lead to complete heart block in type II or extensive
resection, aortic valve and/or root replacement is needed in type
III. Therefore, although surgical resection is the treatment of
choice for this disease, the optimal timing for surgery can be
elusive. Percutaneous balloon dilation of a fixed focal stenosis
causes short-term improvement in the gradient and may be
considered for palliation of SAS.32,34 The long-term effects of
percutaneous balloon intervention for SAS are uncertain.
Incidence
Natural History
The natural history of SAS is not clear, because until the
widespread use of TTE for the precise diagnosis all the
patients were grouped as AS. Many a times the natural history
depends on associated lesions rather than SAS. In congestive
heart failure sudden death can occur in some children, but
this could be secondary to the associated lesions. SAS is a
progressive disease in which the gradient is said to increase
in more than 75 percent of patients by about 25 mm Hg in
5 years.35 The progression of gradient is more rapid than in
valvar AS especially in patients with fibromuscular tunnel.
The incidence of bacterial endocarditis is as high as 13 to
25 percent.24 The sudden deaths are reported but the exact
incidence is not certain.17
The incidence of SVAS is found in about 7.7 percent of patients

with LVOTO.39 The peripheral pulmonary artery stenosis
occurs frequently in patients with Williams syndrome. The
renal abnormalities occur in nearly half of afflicted patients
and are represented by renal artery stenosis, segmental
scarring, cystic dysplasia, nephrocalcinosis, asymmetry of
kidneys, single kidney or pelvic kidney.15 Williams-Beuren
syndrome (WBS) is generally sporadic with an incidence of
1/13,700 to 1/25,000 live births with no sex preference.40 In
the familial form of the disease, children have normal facies
and mental development and there is a strong family history
of SVAS.41 The prevalence of associated cardiovascular
anomalies is reported to be as high as 85 percent.42
Genetics
SummarySubaortic Stenosis
The hypothesis that discrete SAS is a progressive disorder
and may develop into tunnel-like SAS is documented by
serial hemodynamic and angiographic investigations. Early
detection is very important. Hence, the onus lies on clinicians
Supravalvar aortic stenosis is an inherited obstructive vascular

disease that affects the aorta, carotid, coronary and pulmonary
arteries. Previous molecular genetic data have led to the
hypothesis that SVAS results from mutations in the elastin
gene (ELN).
371
Williams-Beuren syndrome results from the hemizygous

contiguous gene microdeletion of a region of chromosome
7q11.23 containing 28 genes. It is thought to be caused by
haploinsufficiency of certain dosage-sensitive genes within
the deleted region and the feature of SVAS has been attributed
to reduced elastin caused by deletion of ELN.43 Fluorescence
in situ hybridization is widely used for diagnostic confirmation
and microsatellite deoxyribonucleic acid markers are
considered highly informative.40
Pathology
Defective elastin production results in deficient arterial
elasticity causing excessive shear stress and secondary smooth
muscle proliferation and collagen deposition. There is severe
compensatory medial thickening in the large elastic systemic
arteries. The resultant obstruction to the lumen of the vessels
ranges from localized stenosis of the proximal ascending aorta
to diffuse narrowing extending into the arch and may affect the
entire aorta, renal arteries and other major aortic branches.44-46
The origins of the coronary arteries may be involved. Other
large elastic arteries like pulmonary arteries may also be
involved.44 The edge of the obstructing tissue may impinge
on a sinus of Valsalva, compromising flow to the coronary
ostia. Occasionally, the coronary occlusion is complete, a
leaflet of the distorted AV adhering to the obstructing collar
of tissue. When the aortic lumen is compromised, there is
proportionate left ventricular hypertension and hypertrophy.
The obstruction is commonly localized, but in about 20
percent, it extends diffusely into the ascending aorta (Figure
9). The aortic cusps are often thickened and distorted,
sometimes adherent to the aortic wall, but although AR is
common, it is rarely severe. Williams-Beuren syndrome is a
neurodevelopmental disorder with characteristic facies, SVAS
and mental retardation. Children with this condition have
distinctive elfin facial features, a hoarse voice associated with
growth retardation, mental retardation and an overfriendly
personality; hyperacusis, infantile hypercalcemia and prematurely wrinkled skin are other associated features.40
Classification
The SVAS is classified as three morphologic subtypes as
shown in Figures 10A to C:7,45,46
1. Hourglass type/deformity (5075%).
2. Diffuse type (25%).
3. Rarely there may be a third subtype, a discrete membrane
above the valve. This may be a localized variety of the
hourglass deformity.
Associations
372
The commonest associated anomaly is hypoplasia of the

right ventricular outflow tract and branch pulmonary arteries,
which is reported in 64 percent. Coronary artery abnormalities
Figure 9: Transthoracic echocardiography in parasternal long axis

shows diffuse narrowing of aorta (type II). Ao = Aorta; LA = Left atrium;
LV = Left ventricle.
are present in 7 percent.44 The origin of the coronary arteries

is usually proximal to the obstruction and they are subjected
to high systolic pressure and limited diastolic flow. There
may be partial or complete ostial obstruction of the coronary
arteries, ectasia or aneurysm of the coronary arteries. Proximal
coronary artery involvement may be caused either by coronary
artery medial hypertrophy or by adherence of aortic cusps to
the ostial walls. Coronary artery involvement is a cause for
increased risk of sudden cardiac death in these children as
compared to the normal population.44
Clinical Features
Most children with SVAS are asymptomatic at the time of
diagnosis.44 Patients with significant LVOTO may present
with angina, dyspnea or syncope. On examination, children
may have dysmorphic features. The right radial, brachial
pulses are better felt than the left as the jet of blood flow
from the SVAS has a preferential trajectory into the right
brachiocephalic (innominate) artery. This is called the
Coanda effect in which the blood pressure is more in the
right upper limb than in the left upper limb (the difference
being > 10 mm Hg). The rest of the clinical findings are that
of LVOTO similar to aortic valvar stenosis except for the
absence of an aortic valve click.
diagnosis
Electrocardiogram
Electrocardiogram may show LVH with or without ST
changes.
26
Figures 10A to C: A. Hourglass type; B. Diffuse narrowing of ascending aorta; C. Discrete membrane above the aortic valve
Chest X-ray
On chest X-ray the only finding that may suggest the diagnosis
of SVAS is the absence of poststenotic dilatation of the aorta.47
Echocardiography
Supravalvar aortic stenosis was first identified by cardiac
catheterization and later echocardiography (Figures 11A and
B) has been shown to have good correlation with the ratios
calculated from angiography. Good correlation was also
shown between the ratio of the surface areas calculated from
the echocardiogram and the corresponding measured pressure
differences.48,49 Echocardiographically and angiographically
it is diagnosed as congenital stenosis of the ascending aorta
distal to the aortic annulus.44 The characteristic finding is the
narrowing of the diameter of the aortic lumen at the stenotic
area just distal to the AV. As the transducer sweeps further
cephalad, the aortic lumen widens to a normal diameter.50
It has been shown that TEE images are far superior to TTE
and TEE can define the mechanism of coronary artery ostial
obstruction associated with SVAS.51 In adults, TTE and TEE
are done to demonstrate the diameter and anatomy of the aortic
sinus, sinotubular ridge and the proximal ascending aorta.
Also origins of the coronary arteries, the systolic gradient
across the SVAS and the degree of LVH can be demonstrated.
Catheterization
As there may be long-segment obstruction, assessment of
the gradient may require cardiac catheterization for complete
assessment of hemodynamic severity of the stenosis. The
morphology of the stenotic lesion may be classified as either
B
Figures 11A and B: A. Transthoracic echocardiography in apical five
chamber view shows type III discrete membrane causing SVAS in a 6
year old boy; B. CW Doppler shows 107 gradient. AV = Aortic valve;
LV = Left ventricle; SVAS = Supravalvar aortic stenosis
373
loacalized (Figure 12) or diffuse. The localized phenotype is

limited to the sinotubular junction and proximal ascending
aorta. This is described as the hourglass appearance
angiographically. In the diffuse phenotype, changes are
not limited to the supravalvar region and luminal hypoplasia
may extend into the distal ascending aorta, arch or beyond.
The transverse arch, coarctation shelf and descending thoracic
aorta may also display areas of narrowing. According to
various studies about 18 to 30 percent are of the diffuse type.
A smaller indexed transverse aortic arch diameter has been
shown to be associated with Williams-Beuren syndrome.44
Computed Tomography/Magnetic Resonance Imaging

The ECG-gated multidetector computed tomography (CT)
and magnetic resonance imaging (MRI) are also useful in the
diagnosis of SVAS owing to their high sensitivity in diagnosing
anomalies of the mediastinal vessels.52,53 It is recommended
that MRI or CT can be performed in adult patients to assess
the anatomy of the LVOT, the ascending aorta, coronary artery
anatomy and flow. Also one can assess the main and main and
branch pulmonary artery anatomy and flow.
Management
A large proportion of children with congenital SVAS may
not need surgical intervention because the lesion gradually
regresses overtime. The indexed LVOT dimensions have
been observed to increase overtime in patients who did not
undergo an operation. The natural history of pulmonary
arterial involvement in Williams-Beuren syndrome has also
been seen to gradually improve with time. Therefore, most

of the children with SVAS are managed expectantly and a
large proportion of the children managed non-surgically,
demonstrate stable peak LVOT gradients and gradual
improvement in ascending aortic dimensions. The overall
mortality in SVAS is low.44 Operation has been recommended
for patients with SVAS of either the discrete or diffuse types
with symptoms such as angina, dyspnea or syncope and for
patients with mean gradient greater than 50 mm Hg or peak
instantaneous gradient by Doppler echocardiography greater
than 70 mm Hg. Surgical repair may also be recommended
for adults with lesser degrees of supravalvar LVOTO when
associated with symptoms or LVH or LV systolic dysfunction
or if pregnancy is planned.54
SummarySupravalvar Aortic Stenosis

The severity of SVAS is variable and it often requires surgical
intervention. A lack of treatment may result in progressive
heart failure and can be fatal.
SHONES ANOMALY
Multiple levels of left heart obstruction are found in patients
with Shones anomaly, which was first described in 1963 by
Shone et al.10 In their abstract they described this anomaly
as followsA developmental complex is described in which
four obstructive anomalies of the left side of the heart and
aorta coexist. These anomalies are:
1. Parachute mitral valve
2. Supravalvar ring of left atrium
3. Subaortic stenosis of either the muscular or membranous
type
4. Coarctation of the aorta.
Eight cases form the basis of this report. In two cases, each
of the four anomalies was present; all of the other six cases
represent partial forms of the complex or formes frustes, in that
only two or three of the anomalies were present. The clinical
picture is compounded due to the effects of several anomalies
of the complex and of the frequent association with still other
anomalies, including VSD. In practice, in Shones anomaly,
the lesions of valvar mitral, AS and SVAS have been included.
In patients with Shones anomaly, a wide spectrum of severity
exists in each of the obstructive components. This creates a
non-uniform group of patients with varied presentations and
long-term outcomes. 55
Clinical Features
374
Figure 12: Aortic root angiogram shows type I hourglass supravalvar

stenosis (arrows) with both right and left coronaries arising from single
left coronary ostia
The clinical presentation of patients with Shones anomaly

depends on the dominant level of obstruction to flow within
the left heart. With obstruction at the level of the mitral
valve secondary to a supravalvar mitral ring (Figure 13)
or a parachute mitral valve as the dominant lesion, these
Investigations
Figure 13: Transthoracic echocardiography in modified two chamber

view shows supramitral ring (SMR with arrow) with deformed parachute
mitral valve. LA = Left atrium; LV = Left ventricle.
patients present with congestive heart failure (CHF), with

an enlarged left atrium and passive pulmonary congestion
noted on chest X-ray. These patients are at risk for pulmonary
artery hypertension (PAH) and may have palpable pulmonary
component of the second heart sound (P2). When the dominant
lesion is at the level of the aortic valve (i.e. subvalvar, or
supravalvar), these patients present with heaving apical
impulse due to LVH and a harsh ejection systolic murmur.
LVH with strain pattern is possibly seen on ECG. If the
dominant lesion is coarctation of the aorta, the patient may
present with hypertension in upper limbs and decreased
pressure in lower limbs with radiofemoral delay in pulse. Age
of presentation may vary from the newborn period in severely
affected infants to early school age in less-affected children.
In the past, the complete diagnosis of Shones complex

diagnosis was done by autopsy but today the modern tool
like two-dimensional transthoracic echocardiography and
Doppler evaluation is excellent for assessing the severity
of various lesions. One of our patients, a 12 years old girl
of Shones complex had parachute mitral valve (Figures
14A and B), interruption of aorta diagnosed on TTE and
confirmed on CT angio (Figures 15A and B). She also had
bicuspid aortic valve (Figure 16). Cardiac catheterization is
performed to further evaluate the pressure gradients across
the LVOT (i.e. subvalvar, valvar, supravalvar and COA) and
to obtain the pulmonary artery pressure, noting the presence
and severity of PAH. The angiogram is done to delineate the
various obstructions (Figures 17A to D). Serial evaluations
are required because the obstructive nature of the lesions is
usually progressive.
Of the patients in the study by Brauner et al,56 the anatomic
lesions found were as follows: mitral valve abnormalities
in 100 percent (supravalvar mitral ring 47%, parachute
mitral valve 63%), SAS in 79 percent (discrete membrane
67%, long segment fibromuscular tunnel 33%), BAV in
26
Brauner et al56 described the presentation of 19 consecutive

patients with Shones anomaly. Two patients presented with
asymptomatic murmurs; the remaining presented with varying
degrees of CHF in the neonatal period. Five patients presented
in cardiogenic shock secondary to critical coarctation of the
aorta or critical valvar aortic stenosis; two presented with
severe CHF; five presented with moderate CHF and five
patients presented with mild CHF. Initial chest radiographs
were normal in six of the 19 patients; cardiomegaly was mild
in three, moderate in six, and severe in two; five had passive
pulmonary congestion and four had frank pulmonary edema.
Figures 14A and B: A. Transthoracic echocardiography in a in 12-year-old girl shows parachute mitral valve (PMV) with single papillary muscle
(SPM) in apical 2 chamber view; B. Parasternal short axis view at papillary muscle level. LA = Left atrium; LV = Left ventricle.
375
Figures 15A and B: A. Transthoracic echocardiography in

suprasternal view shows Type A interruption of aortic arch
i.e interruption after the left subclavian artery (SCA); B.
CT angiogram in the patient confirms Type A interruption
of aortic arch. ASC Ao = Ascending Aorta; Desc
Ao = Descending aorta; MPA = Main pulmonary artery;
PDA = Patent ductus arteriosus
B
79 percent, SVAS in 10 percent and coarctation of the aorta
in 68 percent.
Management
376
Figure 16: Parasternal short axis in the same patient with Shone's
complex shows bicuspid aortic valve
The management of patients with Shones anomaly depends

on the age of the patient and the dominant lesion. Neonates
who present with severe coarctation of the aorta are started on
prostaglandin (PGE1) and the metabolic acidosis corrected.
They are treated either by percutaneous balloon aortoplasty
or surgical repair of the COA is performed. If these neonates
present with the dominant lesion of critical aortic stenosis,
they are started on PGE1 metabolic acidosis corrected and AS
is treated either by percutaneous balloon valvuloplasty or by
surgical valvotomy. The transcatheter balloon valvuloplasty
and balloon aortoplasty is done as a safe bridge to future
intracardiac repair. In neonates with the dominant lesion of
left ventricular inflow obstruction (i.e. mitral stenosis and
supravalvar mitral ring), the resultant CHF is treated medically
until surgical resection of the supravalvar mitral ring, mitral
26
Figures 17A to D: A. Left ventricular angiogram

in the frontal view shows subaortic stenosis;
(arrows) B. Aortic root angio in left anterior
oblique in a 12-year-old boy illustrates hourglass
appearance of supravalvar stenosis (arrows)
with aortic regurgitation, contrast not visualized
in descending aorta due to coarctation of aorta
(COA); C. Angiogram in the arch of aorta confirms
the COA in this boy in whom the LV pressure
was 300 mm Hg, ascending aorta pressure was
144/90 mm Hg, pressure in descending aorta was
80/60 mm Hg; D. Successful balloon aortoplasty
was done before sending for intracardiac repair.
AO = Aorta; LV = Left ventricle.
valvuloplasty or mitral replacement is performed. When the

dominant lesion is LVOTO then surgical resection of the SAS
with or without ventricular septal myomectomy, aortic valve
repair or left ventricle to ascending aorta homograft placement
is performed.55 The median age at first operation in the 19
patients described by Brauner et al was 4.2 months (range, 2
day4.5 year). Specifically, the median age at intervention for
coarctation of the aorta was 1.5 months (2 day2 year); for LV
inflow obstruction, the median age was 2.1 years (1 month7
year); and for LVOT obstruction, the median age was 2.5
1.5 years. These 19 patients underwent 46 major operations,
including 94 distinct surgical procedures.56
Prognosis
The surgical outcomes of patients with Shones anomaly as
noted by Brauner et al56 seemed to vary with the age at initial
intracardiac repair, severity of PAH and severity of the mitral
valve lesion. The operative mortality rate was as high as 16
percent, the total mortality rate was 26 percent. The actuarial
survival rate was 79 percent at 1 year and 73 percent at 7
years. Of the 14 survivors, 10 had significant hemodynamic

abnormalities, including AS, left ventricular dysfunction,
mitral stenosis or regurgitation, pulmonary hypertension, or
recoarctation of the aorta.
SummaryShone's Anomaly
Patients with Shones anomaly require lifelong follow-up
even after transcatheter procedure or surgical correction,
because the obstruction at various levels may progress or
recur. Several procedures are usually required, either by
surgery or by interventional cardiac catheterization, to repair
or palliate the obstructive lesion. The treatment of these
patients continues to evolve and, despite the complexity of
these patient's lesions, the morbidity and mortality rates have
decreased and are expected to decrease further in the future.
Formerly, when religion was strong and science weak, men
mistook magic for medicine; now, when science is strong
and religion weak, men mistake medicine for magic.
Thomas Szasz, The Second Sin, 1973
377
378
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379
C hapter
27
Left Ventricular Inflow Obstructions

Left ventricular inflow obstructions are an extremely rare form

of congenital heart disease (CHD). It includes a number of
malformations, either single or in combination, that orginate
proximal or at the mitral valve. These malformations are
acyanotic heart diseases with no shunt lesion, but they can
cause pulmonary venous and pulmonary arterial hypertension,
with very similar clinical manifestations. Although their
existence in isolation is described, most of the left ventricular
inflow anomalies exist in conjunction with anomalies of left
sided structures. The anomalies can be described as per the
anatomical site at the supramital , mitral valve annulus, mitral
leaflets and submitral apparatus levels.
They left ventricular inflow obstructions are broadly
divided into:
1. Obstruction above the mitral valve
a. Cor triatriatum
b. Supravalvular stenosing ring
c. Pulmonary vein stenosis
d. Hypoplastic pulmonary veins
2. Obstruction at the level of the mitral valve
a. Congenital mitral stenosis

Parachute mitral valve
Anomalous mitral arcade
Double orifice mitral valve
Accessory mitral valve tissue/orifice
b. Hypoplastic mitral valve.
OBSTRUCTIONS ABOVE THE MITRAL VALVE

Cor Triatriatum Sinister
Cor triatriatum is a heart with three atria (triatrial heart). It is
rare and has been reported in 0.10.5% of all congenital heart
diseases. In Cor triatriatum sinister (also known as divided
left atrium) a partition divides the left atrium into a proximal
portion (the pulmonary sinus), into which the pulmonary
veins drain and a distal portion (the left atrium) that empties
into the left ventricle through the mitral valve and to which
the appendage is attached (Figures 1A to C). Cor triatriatum
dexter is the persistence of right valve of the sinus venosus.
Figures 1A to C: A. Schematic image of Cor triatriatum; B. Apical four chamber zoomed up view on two-dimensional echocardiography showing
shelf in left atrium, stretching from atrial septum on right side to left atrium lateral wall on left side; C. Zoomed up view of the left atrium with color
flow mapping showing turbulence (mosaic jet) starting in mid atrial cavity. DC = Distal chamber; LV = Left ventricle; PC = Proximal chamber; RA
= Right atrium; RV = Right ventricle.
Pathological Anatomy
Box 1: Anatomic classification of Cor triatriatum
(incidence of each lesion is mentioned in the brackets)

I. Accessory atrial chamber receives all pulmonary veins and
communicates with left atrium
1. No other connectionsclassic Cor triatriatum (67%)
2. Other anomalous connections:
a. To right atrium directly (17%)
b. With total anomalous pulmonary venous connection
(3.6%)
II. Accessory atrial chamber receives all pulmonary veins and
does not communicate with left atrium
Embryology
Embryologically the anomaly represents failure of the common
pulmonary vein to fuse completely with the evaginating left
atrium. There are frequently associated abnormalities of
pulmonary venous connection, atrial septum. and sometimes
systemic veins. Another theory states that abnormal growth of
the septum primum accounts for Cor triatriatum. The second
theory is difficult to reconcile with the observations of most
workers in this field.
Classification
Available classifications include Herlong and Lucas
classification. Herlong starts with letters, then numerical
followed by alphabetic subdivisions (e.g. A2a) and Lucas
classification starts with Roman numerals and then alphabetic
followed by numerical subdivisions (e.g. IB1). The two
classifications are otherwise almost identical (shown in
Box 1). There are slight differences in the anatomical
classification. It divides the Cor triatriatum into: (a)
Diaphragmatic type: most common form with proximal
accessory chamber and distal true left atrial chamber separated
by fibrous or fibromuscular ridge. (b) Tubular Cor triatriatum:
it is a primitive form where the proximal chamber retains the
shape of the common pulmonary vein, the distal end joins the
left atrium directly without any membrane. (c) The hourglass
type: the constriction projects inward as an obstructing shelf
which is seen externally as an hourglass deformity at the
junction of the accessory chamber and the true left atrium
(Figures 2A to H). Herlong has another subtype not listed by
Lucas, namely C2b in which the remaining pulmonary veins
have a different anomalous connection (mixed connection).
Pathophysiology and Clinical Presentation

The hemodynamics of Cor triatriatum depends on the extent of
left ventricular inflow obstruction. If the holes in the membrane
are restrictive (some studies put it as observed value of less
than 6 mm in diameter, roughly equivalent to 1 cm2), there is
pulmonary venous hypertension. Frequently mean pulmonary
arterial wedge pressures are over 20 mm Hg. Patients with
an obstructive orifice usually have severe pulmonary arterial
1. Anomalous connection to right atrium directly (3.6%)

2. With total anomalous pulmonary venous connection
(0.3%)
III. Subtotal Cor triatriatum
1. Accessory atrial chamber receives part of pulmonary
veins and connects to left atrium
The partition in left atrium was first recognized by Andral in

1829. Borst (1905) named the lesion as Cor triatrium and Church
published the first detailed pathological description in 1971.
Cor triatriatum is an obliquely oriented fibro-muscular
partition between the two portions in the left atrium and has a
lenticular shape opening. This opening connects two portions.
It may be non-obstructive or small. Sometimes there may be
multiple openings or it may be imperforate.
27
i. Remaining pulmonary veins connect normally (2.6%)

ii. Remaining pulmonary veins connect anomalously
(4.3%)
2. Accessory atrial chamber receives part of pulmonary
veins and connects to right atrium (1.3%)
i. Remaining pulmonary veins connect normally
ii. Part of Lucas classification. Remaining pulmonary veins
connect abnormally.
hypertension (PAH). The pulmonary arterial pressure is

usually raised more than the increment in pulmonary venous
pressure. This is because of increased pulmonary vascular
resistance due to pulmonary vasoconstriction, pulmonary
edema or anatomic changes in the small pulmonary arteries.
Some pulmonary vascular disease is common, with increased
pulmonary arterial smooth muscle and even grade 3 intimal
lesions. Severe PAH has been associated with hemoptysis,
wheezing and pulmonary hemosiderosis. Patients may
have chest pain, almost always associated with pulmonary
hypertension due to right ventricular ischemia. It is however
possible to have a tiny communication between the upper
and lower chambers without pulmonary hypertension, if
the upper chamber is decompressed by an atrial defect
or partial anomalous pulmonary venous connection or if
pulmonary venous return is very low, because of a cyanotic
congenital heart lesion. Under these circumstances, repair of
the associated lesion without removing the membrane can
be disastrous. Occasionally, thrombi form proximal to the
membrane and systemic embolism has been reported. Some
patients present with symptoms due to an atrial arrhythmia,
usually atrial fibrillation.
The membrane moves towards the mitral valve during
diastole, reflecting diastolic gradient and moves away from
381
right and left ventricular obstructive lesions
Figures 2A to H: Variants of Cor triatriatum: A. Classic Cor triatriatum. The pulmonary venous chamber (PVC) receives the right and left
pulmonary veins (RPV and LPV respectively) and the only egress for pulmonary venous return is through the opening in the Cor triatriatum
(arrow); B. Cor triatriatum with a communication between the PVC and the right atrium (RA). This communication allows decompression of
the PVC; C. Cor triatriatum with an anomalous connection between the PVC and the left innominate vein (LIV). This anomalous connection
(levoatriocardinal vein) decompresses the PVC. The PVC does not communicate directly with the left atrium (LA); D. Pulmonary venous
return reaches the right atrium through a communication between the PVC and the right atrium. Blood then reaches the LA via the foramen
ovale; E. The PVC decompresses via a vertical vein to the portal vein. Subtotal Cor triatriatum; F. The confluence of the RPV communicates
with the LA via a stenotic orifice. The LPV connect normally to the LA; G. Subtotal Cor triatriatum of the right pulmonary veins associated
with partially anomalous pulmonary venous connection of the veins LPV to the LIV; H. Subtotal Cor triatriatum of the RPVs to the RA via a
stenotic orifice. The (LPV) connect normally. IVC = Inferior vena cava; LV = Left ventricle; RV = Right ventricle; SVC = Superior vena cava;
VV = Vertical vein. (Adapted from: Krabill KA, Lucas RV Jr. Abnormal pulmonary venous connections. In: Emmanouilides GC, Reimenschneider
TA, Allen HD, et al, (Eds). Heart Disease in Infants, Children, and Adolescents. 5th edition Baltimore: Williams and Wilkins, 1995;839-874).
382
the mitral valve during systole, reflecting the reversal of

gradient as the left ventricular contraction exerts pressure on
the membrane through the closed mitral valve.
Associations: As is evident with the hemodynamics of
the lesion, about two-thirds of the patients have associated
congenital cardiac lesions. Atrial septal defect, either a patent
foramen ovale or a true fossa ovalis defect, occurs in about
half of the patients. If the defect connects the right atrium to
the true left atrium (lower chamber), then it is not a part of
the classification. A sinus venosus defect has been reported.
Atrioventricular septal defects are quite common, ranging
from ostium primum defects (often intermediate) to a common
atrium and less frequently, a complete atrioventricular canal.
Abnormalities of the pulmonary veins (partial or total
anomalous pulmonary venous connection) are common, as is
a persistent left superior vena cava, often associated with an

unroofed coronary sinus. Other abnormalities of the left atrium
or mitral valve can also occur, possibly more frequently than
can be accounted for by coincidence. Mitral regurgitation often
occurs and can be severe and a supramitral stenosing ring has
been seen. Apart from these atrial and venous anomalies, there
are occasional associations with most other forms of congenital
heart disease: patent ductus arteriosus, ventricular septal defect
(VSD), coarctation of the aorta, pulmonary stenosis, valvar
aortic stenosis (including bicuspid aortic valve) or subvalvar
aortic stenosis, tetralogy of Fallot, Ebstein anomaly, doubleoutlet right ventricle, hypoplastic left heart syndrome and
occasionally other anomalies. Abnormalities of situs and
heterotaxies are uncommon. The right-sided chambers are
hypertrophied if there is significant pulmonary hypertension.
Coronary Sinus Obstruction
Supravalvular Stenosing Ring

Supravalvular stenosing ring is a fibrous ring just proximal to
the mitral valve. The ring is often partly adherent to the mitral
Figures 3A to D: A. Apical four chamber view with color flow mapping in a case of supramitral ring causing left ventricular inflow obstruction; B.
Turbulent flow starts above the level of mitral annulus; C and D. Apical four chamber view with color flow mapping in a case of annular type of
supramitral ring causing left ventricular inflow obstruction. Turbulent flow starts at the level of mitral annulus. LA = Left atrium; LV = Left ventricle;
RA = Right atrium; RV = Right ventricle.
27
Persistent left superior vena cava may lead to coronary sinus

dilation and left ventricular inlet obstruction. The mitral
leaflets are normal; however, the thickened posterior atrial
wall produces a funnel-like obstruction within the left atrium
requiring resection of the roof of the dilated coronary sinus.
leaflet and may or may not be obstructive (Figures 3A and

B). The tissue may form an obstructing fibrous ring or shelf
involving the atrial wall and extending to the leaflet. The tissue
may be several millimeters above the valve or may be closely
adherent to the valve, impairing diastolic annular and leaflet
mobility (annular type Figures 3C and D). Isolated stenosing
supramitral ring is a rare condition. Underlying mitral valve
apparatus is usually abnormal, as this condition is frequently
associated with other mitral and ventricular anomalies such
as commissural fusion or parachute mitral valve. Unlike Cor
triatriatum, the foramen ovale and left atrial appendage
lie above the plane of the membrane. Obstruction is often
383
severe. One should maintain a high index of suspicion for

this condition in patients with signs and symptoms of leftsided heart obstruction, particularly in the face of other mitral
and left ventricular malformations. Failure to diagnose it
preoperatively can lead to a fatal outcome. In one report, the
posterior circumflex coronary artery ran in the ridge.
Pulmonary Vein Stenosis

Congenital pulmonary vein stenosis is a rare condition. This
disorder usually coexists with a number of other congenital
malformations. One or more of the pulmonary veins may be
involved. This anomaly has been described in the chapter on
anomalies of pulmonary veins (Chapter 16).
investigations
Electrocardiogram: Broad notched left atrial P waves have
been ascribed to the prolonged conduction in the proximal
accessory chamber. Rest of the electocardiogram (ECG)
finding are essentially similar to that of mitral stenosis as
described later in the chapter.
X-ray: The radiological appearance of pulmonary venous
congestion without left atrial enlargement is a radiological
feature of Cor triatriatum. Rest of the features of pulmonary
congestion and pulmonary hypertension as seen in mitral
stenosis may be observed.
Figure 4: The various components of the mitral valve with chordae

tendinae and two papillary muscles. AML = Anterior mitral leaflet;
PML = Posterior mitral leaflet
OBSTRUCTIONS AT THE MITRAL VALVE

Anatomy
384
Mitral valve consists of the annulus, two leaflets, two

papillary muscles and two sets of chordae tendineae (Figure
4). The atrioventricular orifice is reinforced by the annulus
fibrosis of the cardiac skeleton in the posterior and lateral
two thirds of the annulus. The remaining medial third is
supported by attachment to the left atrium and by fibrous
support to the aortic semilunar valve. The bicuspid mitral
valve has two leafletsanterior (medial or aortic) and
posterior (inferior or mural, wall) resembling the cardinals
hat or mitre, hence the term mitral valve (Figure 5). The
anterior leaflet is trapezoidal shaped and its attachment on
the annulus to its free edge is longer (twice that of posterior
leaflet) than the length of attachment across the annulus.
The posterior leaflet is relatively narrow, with a very long
attachment distance across the annulus with its free edge
subdivided into the anterior, central and posterior crescent
shapes (Figures 6).
Papillary muscles in conjunction with chordae tendineae,
attach to the leaflets in order to secure them in place to
prevent the prolapse of the leaflets up into the atrium. There
is considerable overlap of the leaflets, when the valves are in
the closed position and they remain relatively close together
Figure 5: The mitral valve orientation within the heart and its resembelance to the cardinals hat mitre and hence the name mitral valve
even when the atrium is contracting and the ventricle is filling.

The junctions of the two leaflets are called anterolateral and
the posteromedial commissures. The line of apposition of
the leaflets during valvular closure is indicated by a fibrous
ridge. There are two papillary muscles that extend from the
ventricular free wall. The anterior papillary muscle is slightly
larger than the posterior and each papillary muscle consists
of a major trunk that often has multiple chordae tendineae.
The chordae tendineae of each papillary muscle extends to
the two valvular commissures and to the multiple crescent
shapes of the posterior cusp. In addition, the posterior leaflet
occasionally has chordae that extend from the ventricular
myocardium without a papillary muscle.
the free edges of the dysplastic valve leaflets are thickened

and rolled, the valve may be incompetent as well as stenotic.
Figure 6: Apical four chamber view from an infant with congenital

mitral stenosis due to dysplastic mitral valve showing thickened and
domed mitral leaflets. This child also had single papillary muscle (not
shown in this picture). LA = Left atrium; LV = Left ventricle; RA = Right
The hypoplastic mitral valve (Figures 7A and B) is nearly

always associated with hypoplastic left heart syndrome or
its variant. Left atrium may be small in size. Mitral valve is
often dysplastic with a small annulus, thickened leaflets, short
chordae, attaching directly into the left ventricular wall. The
papillary muscles are poorly developed or rudimentary, with a
very small left ventricular cavity. The left ventricular outflow
tract including aortic arch is very small or atretic. An atrial
septal defect is mostly present. With restrictive atrial septal
defect, left atrial pressure remains very high leading to severe
pulmonary venous hypertension. LV inlet obstruction is
greater, when associated with mitral supravalvar ring. Severe
left ventricular hypoplasia is observed in 80 percent and left
ventricular outflow tract obstruction is usually present. Such
infants present with symptoms and signs of acute left heart
obstruction during the 1st day of life.
Hypoplasia of the Mitral Valve and Mitral Valve Atresia
27
Anomalies of the Leaflets

Mitral Valvar Dysplasia
(Typical Congenital Mitral Stenosis)
Imperforate Valve
Mitral valvar dysplasia (Figure 6) is the most common lesion

underscoring congenital mitral stenosis, found in 49 percent
cases of congenital mitral stenosis. It can be isolated, but
most frequently is seen in the setting of hypoplasia of the
left heart. All components of the complex are malformed,
when the valve is dysplastic and hypoplastic. The leaflets
are thickened, the intercordal spaces often obliterated and
the papillary muscles are deformed, the last frequently
extending as muscular strands directly into the leaflets. When
Imperforate valve or mitral atresia (Figure 8) is an extreme

anomaly involving the leaflets, seen most frequently in
combination with aortic atresia, when they form an integral
part of the hypoplastic left ventricle syndrome. In this
setting, from the stance of anatomy, the imperforate valve
is distinguished from absence of the left atrioventricular
connection, since both produce atrioventricular valvar atresia.
Approximately, 12 percent of patients may have a relatively
normal left ventricle, although often associated with a large
Figures 7A and B: A. Two-dimensional echocardiography from apical four-chamber view showing hypoplastic mitral valve annulus (arrows),
hypoplastic left ventricle cavity with dilated right ventricle; B. Echocardiography of a neonate with hypoplastic left heart syndrome apical fourchamber view showing dilated right ventricle and hypoplastic left ventricle. la = Left atrium; LV = Left ventricle; ra = Right atrium; RV = Right
ventricle
385
Figure 8: Apical four chamber view from a child with atretic left
atrioventricular valve. The left atrioventricular valve is also overriding
the interventricular septum with malalignment of interatrial and
interventricular septum (arrows). LA = Left atrium; RA = Right atrium;
Rud LV = rudimentary left ventricle; RV = Right ventricle.
VSD or straddling tricuspid valve. In hypoplasia of the left

heart, when the left atrioventricular connection is absent, the
right atrium is connected to a dominant right ventricle. The
left atrioventricular connection can also be absent, when the
right atrium is connected to a dominant left ventricle. This
lesion is best considered in the setting of the functionally
univentricular heart.
Ebstein Malformation of the Mitral Valve

Ebstein malformation can rarely affect the morphological
mitral valve. When this is the case, the mural leaflet is plastered down onto the ventricular wall, with its hinge below the
atrioventricular junction. In this setting, there is no thinning
of the atrialized inlet portion, as is usually seen when it is
the morphological tricuspid valve that is deformed in the setting of concordant atrioventricular connections. Such lack of
morphologic atrialization is also a feature of Ebstein
malformation of the left-sided atrioventricular valve in the setting of congenitally corrected transposition (Ebsteinoid valve).
Funnel-Shaped Valve
Another isolated anomaly of the valvular leaflets is the so called
funnel-shaped valve. This entity is characterized by thickening
and retraction of the leaflets, with fused tendinous cords, but in
the presence of normal papillary muscles. The funnel produces
mitral stenosis. It is rare in postmortem collections.
Dual Orifices of Mitral Valve

386
Dual orifices of mitral valve (DOMV) are produced by a tongue

of valvular tissue that extends between the mural and aortic
leaflets, dividing the valvular orifice into two components,

with each orifice then supported by one of the papillary
muscles. Isolated DOMV is unusual and may be an incidental
echocardiographic finding, detected in association with other
congenital heart disease. Atrioventricular septal defect is
present in approximately 50 percent and left heart anomalies
including coarctation and VSD in 40 percent. Dual orifices
are more common within the left half of the atrioventricular
valve of patients having atrioventricular septal defects with
common atrioventricular junction. Mitral insufficiency is
most commonly present (4550%), followed by a normal
flow pattern (35%). Severe valvular stenosis may be present
in approximately 13 percent. The medial and lateral orifices
are balanced in size with a central fibrous subdivision in only
15 percent of cases (Figures 9A and B). More commonly,
they are unequal, with the smaller orifice directed toward
the anterolateral commissure (41%) or the posteromedial
commissure (44%). In the latter, atrioventricular septal defects
are common (90%) and mitral regurgitation is often present.
The incidence of functional mitral stenosis is more common if
the atrioventricular septum is intact.
Surgical intervention is not necessary except in those with
severe stenosis. In the eccentric, small hole-type DOMV, the
tissue between the orifices is usually normal valve tissue and
should not be excised, as it may result in iatrogenic mitral
valve insufficiency.
Hypoplasia of Mural Leaflets

A rarer abnormality that can result in congenital mitral valvar
regurgitation is hypoplasia of the mural leaflet, such that the
valve leaflets cannot coapt normally during systole.
Overriding of Valvar Leaflets

More frequent is straddling and overriding of the valvar leaflets.
These anomalies can affect either the tricuspid or the mitral
valve. Bridging of leaflets is also a common feature of the
common atrioventricular valve, albeit that a common valve can
be exclusively connected to one or other of the ventricles. It
is the spectrum between the commitment of straddling valves
to one or other ventricle, underscoring the difference between
functionally univentricular and biventricular arrangements.
When the morphological mitral valve straddles and overrides,
the valve always straddles through an anterosuperior inter
ventricular communication and is found with either discordant
or double outlet ventriculoarterial connections.
Fibrous Ridge that Anchors Together the

Aortic and Mural Components
While discussing malformations of the leaflets, we should
also pay attention to a fibrous ridge that anchors together the
aortic and mural components, narrowing the valvular orifice.
27
Figures 9A and B: Apical four chamber view showing a case of double orifice mitral valve (DOMV) with separate subvalvular apparatus of each
orifice. Parasternal short axis view of the same patient at the level of mitral valve showing two distinct orifices of equal sizes. This patient had
associated ventricular septal defect (VSD) and underwent VSD closure with no intervention for DOMV
Although usually described as a supravalvular structure, the

abnormal fibrous shelf is an integral part of the atrial surface
of the leaflets and can readily be removed at surgery. Shelves
can exist within the left atrium and produce true supravalvular
rings, but these are much rarer than the variant attached to the
atrial aspect of the leaflets.
Mitral Valve Prolapse

The commonest lesion afflicting the leaflets of the mitral valve is
prolapse. The problems concerning the pathology of prolapse of
the mitral valve, however, are as numerous as those concerning
its clinical features. There is no unanimity concerning
nomenclature or etiology and perhaps more important, no
standard definition of what precisely constitutes prolapse of the
leaflets. More commonly the lesion is associated with mitral
regurgitation than mitral stenosis and hence being discussed in
in the chapter on mitral valve diseases (Chapter 31).
one can see either direct insertion of the leaflets into the
papillary muscles or insertion through short, thick chordae.
Also seen is the bridge of fibrous tissue adherant to the
inferior aspect of anterior mitral leaflet (Figure 10). This
abnormality usually results in both mitral stenosis and mitral
regurgitation. Abnormal mitral arcade may be association
with atrial septal defect, patent ductus arteriosus, valvular
and subvalvular aortic stenosis and coarctation of aorta.
Anomalies of the Papillary Muscles

Parachute Mitral Valve
Parachute mitral valve is characterized by unbalanced chordal
attachments to a single papillary muscle. Two variants include:
Anomalies of the Tension Apparatus: Mitral Arcade or

Hammock Valve
In hammock valve, papillary muscles extend directly to the
edges of the leaflets. In the most severe form, the muscles
fuse on the leading edge of the aortic leaflet, forming the
muscular arcade. When viewed from the atrial aspect
(surgeons view), with the valve intact, the intermixing of
cords attached to the enlarged papillary muscle gives the
appearance of a hammock. The valve has the shape of a
funnel without commissures with a central orifice of variable
size. Thickened papillary muscles of left ventricle may
also result in partial obstruction to left ventricular inflow.
When examined from the left ventricular side in apical or
subcostal four chamber view or apical two-chamber view,
Figure 10: Apical four chamber view in a case of Hammock mitral valve
showing the attachments of the papillary muscles to the mitral valve
387
388
1. Two papillary muscles, but focalized chordal attachments

(commoner).
2. A classic type with a single papillary muscle (Figures 11A
and B).
Generally, the chordae are shortened and thickened. Single
papillary muscle has variable anatomy. The anterolateral or,
rarely, both papillary muscles may be completely absent or
two identifiable, but partially fused papillary muscles may
be present and interpapillary muscle distance reduced. In
those with single papillary muscle or true parachute mitral
valve, the commissures are variably fused or absent and the
valve tissue is funnel-like with its orifice centrally located
above the solitary papillary muscle. This classic form is
relatively rare. In most cases, a parachute-like mitral valve
is present. Two papillary muscles are present; however, the
chordae are predominately committed to a single papillary
muscle, generally the posteromedial, which is normal in
size and location. The anterolateral papillary muscle is
displaced superiorly toward the mitral leaflet and may be
fused along its length to the posterior ventricular wall,
appearing absent and simulating a true parachute mitral
valve with single papillary muscle. The free margin of the
leaflet occasionally attaches directly to the lateral papillary
muscle. The remaining cords to the posteromedial muscle
are progressively shortened and fused, constraining the
leaflets. The annulus may be normal and the commissure
present, but the orifice is eccentrically directed between the
leaflets over the dominant papillary muscle. This condition
has been termed a parachute-like asymmetric mitral valve.
The degree of stenosis is progressive, according to the
tethering of the leaflets and reduction of the distal orifice.
However, the degree of stenosis is generally milder than
that of cases of typical congenital mitral stenosis with
symmetric or balanced cord attachments to the papillary
muscles and milder than those with supravalvular mitral

ring.
Commonly associated conditions include isolated or
combined supramitral ring, coarctation of the aorta, atrial
septal defect and VSD, aortic subvalvular or valvular
stenosis or the complete Shone complex of anomalies.
In those with mild to moderate stenosis, a good longterm prognosis has been described. The severity of mitral
stenosis remains relatively non-progressive and most will
not require valvotomy. There is no progression in mean
valvular pressure gradient over time. Higher pressure
gradients are associated with vsd and supravalvular stenotic
ring. Survival without mitral valve surgery approaches 95
percent at 6 months and 80 percent at 10 years of age. Left
ventricular endocardial sclerosis is often present, when
associated with significant left ventricular outflow tract
obstruction, but left ventricular size is usually normal to
mildly reduced (within 70% of normal) in most patients.
Long-term survival correlates best with left ventricular size
and with risk factors including coarctation and subvalvular
aortic stenosis, but not with mitral valve orifice size. When
required, surgical valvotomy seems preferable to balloon
valvuloplasty, particularly when the dominant obstructive
component is tethering of the leaflets by asymmetric chordal
attachments.
Excessive Mitral Valvular or Chordal Tissue

In the most severe form the interchordal spaces are obliterated
by excessive valvular tissue. Histopathology of such
accessory valve leaflets shows fibrous tissue and myxoid
dysplasia. There may be the presence of left ventricular
outflow tract obstruction, because of redundant mitral leaflet
tissue prolapsing in the left ventricular outflow tract, causing
Figures 11 A and B: A. Transthoracic echocardiography (TTE) zoomed up echocardiographic image illustrates chordal attachment to a single
papillary muscle in a 12-year-old case of parachute mitral valve; B. TTE in short axis shows mitral valve orifice with single papillary muscle
(SPM). Image Courtesy: Dr IB Vijayalakshmi
Pathophysiology
Flow across a mitral orifice is between the leaflets (interleaflet)
and between the chordae tendinae (interchordal). In mitral
inflow obstructive lesions either of the flow gets compromised,
e.g. in parachute mitral valve the interchordal flow is
compromised because of reduced or obliterated interchordal
spaces. In case the chordae are elongated the same will result
in mitral regurgitation. The functional consequences and
symptomatology of the congenital mitral stenosis is anologus
to acquired mitral stenosis as described below.
Mitral inflow obstruction results in a diastolic pressure
difference between the left atrium and left ventricle with a
consequent elevation of left atrial pressure. Patients in sinus
rhythm, have tall a wave in the left atrial trace. Coexistence
of an interatrial communication results in decompression of
the left atrium. This may be so profound, as to obscure or
eliminate the transmitral pressure difference, even when
the mitral valve is imperforate. By contrast, excessive
flow through the mitral valve, as may result from an
associated VSD, will exaggerate the transmitral diastolic
pressure difference. Functional obstruction of the mitral
valve apparatus impairs pulmonary venous flow from the
left atrium into the left ventricle. Consequently, left atrial,
pulmonary venous and capillary pressures rise (Figures
12A and B). In accordance with Starlings concept of
transvascular fluid exchange, the net exchange of capillary
water into the interstitial and alveolar spaces occurs, when
the hydrostatic pressure gradient exceeds that of plasma
oncotic pressure.
Simultaneously, pulmonary lymphangiectasia secondary
to increased venous and lymphatic hydrostatic pressure leads
to decreased reabsorption of interstitial fluid and pleural
effusion. Eventually, hypoxic and hypercapnic pulmonary
vasoconstriction may supervene. Congested bronchial
veins encroach on the small bronchiolar airways, causing
an increase in airway resistance. These factors adversely
affect mechanical and gas exchanging properties of the
lung and lead to increased effort of breathing, hypoxemia
and hypercapnia, particularly in small infants. An acute
increase in left atrial pressure leads to greater intraluminal
pressures, which distend the vasculature and lead to a
compensatory lowering of pulmonary vascular resistance.
However, chronic mitral valve obstruction may lead to
pulmonary venous and arterial hypertension and secondary
right ventricular dysfunction. The associated increase of
pulmonary arterial pressure and resistance is complex and
has important clinical implications.
In children with mitral stenosis, isolated pulmonary venous

obstruction is associated with arterial and pulmonary venous
medial muscular hypertrophy, as early as 12 months of age.
Subsequently, there may be arterial and venous intimal
thickening. However, advanced and irreversible changes
such as intimal cellular proliferation and plexiform lesions,
common in patients with left-to-right shunts such as VSD,
were not seen in children with pulmonary venous obstruction
even when pulmonary pressures were similar in magnitude and
duration. Thus, the nature of pulmonary vascular pathology
differs in patients with pulmonary venous obstruction. The
origins of these differences are not entirely understood,
but are likely related to the higher flow and greater intimal
shear forces and vessel wall stresses encountered with vsd.
These differences account for the relatively good expectation
for postintervention reversal of pulmonary hypertension
during the first 2 to 3 years in patients with congenital mitral
27
variable degrees of subaortic obstruction and also because

of anomalous mitral valve leaflet or chordal attachments to
the left ventricular septum. Associated forms of congenital
heart disease include partial atrioventricular septal defects
particularly, when associated with Down syndrome.
B
Figures 12A and B: Hemodynamic changes in severe mitral stenosis.
A. Shows skiagram showing normal connections; B. Shows the effect
of mitral stenosis. Enlargement and hypertrophy of the left atrium
(LA), pulmonary venous hypertension and possibly pulmonary edema
result. Reflex vasoconstriction of the pulmonary arterioles leads to
pulmonary arterial hypertension and right ventricular hypertrophy.
LV = Left ventricle; PAH = Pulmonary artery hypertension; RV = Right
ventricle; RVOT = Right ventricular outflow tract;
389
obstruction. The rise in pulmonary vascular resistance and

consequent fall in pulmonary blood flow, means that, on
sequential cardiac catheterizations in individuals with mitral
stenosis, the gradient is frequently found to fall.
Although the natural history of pulmonary hypertension
in children with acquired mitral valve stenosis suggests that
pulmonary hypertension, generally resolves postoperatively,
this is not necessarily the case with longer-standing congenital
mitral valvular disease and severe or chronic pulmonary
hypertension. Consequently, the substrate for pulmonary
hypertension remains a significant acute postoperative risk
factor and underscores the importance of pulmonary vasodilator
management in the initial postoperative period. In patients
with severe mitral stenosis, the reduction of left ventricular
volume or mass, ischemia, fibrosis and left ventricular
dysfunction may also compromise cardiac output. Critical
reduction of cardiac output and vital organ dysfunction leads
to metabolic insufficiency and cachexia. Chronic low cardiac
output is associated with peripheral circulatory maladaptation
including excessive stimulation of the sympathoadrenal axis
and systemic vasoconstriction.
Finally, renal insufficiency, fluid and electrolyte imbalance
are caused by abnormal intake, renal hypoperfusion and
hormonal factors. While associated distal obstructive lesions
may exaggerate the mitral insufficieny, by contrast, severe
pulmonary stenosis in the setting of a VSD may mask entirely
the effects of the valvar obstruction by reducing the flow of
blood to the lungs. Left atrial pressure is bound to be lower than
pulmonary arterial pressure, irrespective of the severity of the
mitral obstruction and hence the hemodynamic data observed.
INCIDENCE AND ETIOLOGY

Congenital deformities of the mitral valve are rare and constitute
0.6 percent of postmortems and 0.21 to 0.42 percent of clinical
series (those excluding associated AVSD). Development of one
abnormality upstream, during morphogenesis, may result in a
series of more distal abnormalities owing to disturbance in the
patterns of flow. Annular hypoplasia of the mitral valve is almost
always associated with hypoplasia of the left ventricle and aortic
stenosis or atresia. VSD is quite common in this setting and
double outlet right ventricle and tetralogy of Fallot occasionally
occur. When the mitral valve is imperforate, left ventricular
hypoplasia is inevitable unless there is an associated VSD.
There is male predilection (in contrast to aquired
rheumatic mitral stenosis) in congenital mitral stenosis.
Familial recurrence has not been reported in congeital mitral
stenosis.
CLINICAL PRESENTATION AND SYMPTOMATOLOGY

History and Physical Examination
390
Manifestations of symptoms of mitral valve stenosis depend

upon the degree of obstruction to left ventricular inflow, the
presence and type of associated lesions and the growth rate

of the infant. Mitral inflow obstructive lesions are generally
symptomatic in fetal and early neonatal life. Infants with less
severe mitral valve obstruction or less significant associated
lesions, generally present beyond the neonatal period with
a history of antecedent pulmonary infections and failure to
gain weight appropriately. Other features include irritability,
exhaustion at feeding, diaphoresis, tachypnea and chronic
cough. Congenital mitral stenosis is associated with syncope,
but seldom with hemoptysis. Aphonia may occur because of
compression of recurrent laryngeal nerve by hypertensive
pulmonary trunk. Clinical features associated with a
particularly poor outcome are presentation early in infancy,
signs of low systemic cardiac output and right-sided heart
failure. On examination severe mitral valve obstruction is
associated with diminished peripheral perfusion and pulses.
Normal sinus rhythum is generally a rule in congenital
mitral stenosis. Jugular venous pulse shows increased a
wave secondary to pulmonary hypertension. Palpation of the
heart will reveal either a normal impulse or right ventricular
hypertrophy and there may be an apical diastolic thrill.
Pulmonary valvar closure will be palpable if pulmonary
hypertension is severe. The first heart sound in contrast to
acquired rheumatic mitral stenosis, is relatively soft and mitral
valve opening sound (snap) is usually absent, because the
mitral valve leaflets are relatively inflexible and immobile. The
second heart sound varies from widely split to narrowly split
with an accentuated pulmonary component, when pulmonary
hypertension is present. Although, left ventricular inflow tract
obstruction should preclude auscultation of ventricular filling
sounds, right ventricular third or fourth heart sounds may be
present. A low-frequency, low-intensity mid-diastolic murmur,
often with presystolic accentuation, is heard at the apex.
Because of the rapid heart rates and displacement of the apex
by the dilated hypertensive right ventricle, apical mid-diastolic
murmur with presystolic accentuation is rarely observed in
congenital mitral stenosis. In some cases, however, a loud,
high-frequency diastolic murmur may be present and its timing
is confirmed only by palpation of the peripheral pulses. The
murmur may diminish in intensity or may be completely absent
when cardiac output is markedly reduced. The murmur of
mitral insufficiency, pulmonary valve insufficiency secondary
to pulmonary hypertension (Graham Steell murmur) and
findings characteristic of associated cardiac malformations
may be present.
INVESTIGATIONS
Electrocardiography
Sinus rhythm is the rule in children, in contrast to theumatic
where atrial fibrillation is observed though first-degree heart
block is common, particularly when the left atrium is greatly
enlarged. Left atrial hypertrophy occurs in about nine-tenths
of patients and right atrial hypertrophy is the rule in patients
27
Chest Radiography
Whatever the nature of the mitral abnormality, cardiac en
largement tends to be considerable. Splaying of the bronchi
by the enlarged left atrium is particularly prominent.
Infants with imperforate mitral valve or severe mitral
stenosis particularly in the absence of decompression (i.e
without ASD), very occasionally show the ground-glass
appearance of pulmonary edema. More commonly, left atrial
hypertension is manifested in older children by Kerley B lines
and diversion of blood to the upper lobes (cephalization). In
infants, the pulmonary trunk and left atrial appendage do not
form discrete bulges on the upper left cardiac border, which
is consequently straighter than normal. In older children,
prominence of the left atrial appendage is the rule and, in
patients with pulmonary hypertension, the pulmonary trunk
is prominent (Figure 13).
Straigtening of the left heart border by an enlarged left
atrial appendage is much less common than in rheumatic
mitral stenosis. Calcification of the mitral valve is also
generally absent. These appearances may be profoundly
modified by associated abnormalities. If the ascending aorta
is seen on the left upper cardiac border (l-malposed aorta) and
the patient has clinical features of mitral incompetence, then
congenitally corrected transposition with tricuspid rather than
mitral incompetence is the most likely diagnosis.
Echocardiography
M-mode Echocardiography
M-Mode echocardiography provides non-specific evidence
as to enlargement of the left ventricle, left atrium and right
ventricle. Features suggestive of mitral stenosis, include
anterior movement of the mural leaflet in diastole, a
prolonged time to reach one-fifth of the peak rate in change
of left ventricular dimensions and a reduced peak rate of these
changes in dimension. Flattening of the E-F slope is suggestive,
but difficult to recognize in infants with tachycardia. The
time from closure of the aortic valve to opening of the mitral
valve and from left ventricular minimum dimension to mitral
opening, have proved unhelpful as indicators of congenital
mitral stenosis, unlike their use in assessment of acquired
mitral valvar disease.
Figure 13: Chest X-ray in posterioranterior view view in a 12-yearold girl of Shones complex with parachute mitral valve with stenosis
and regurgitation, shows dilated left atrial appendage (LAA), double
shadow due to right atrial (RA) and grade 2 left atrial (LA) enlargement
(courtesy: Dr I B Vijayalakshmi)
with pulmonary hypertension. In mitral stenosis, the mean

frontal QRS axis is usually normal or to the right and inferior,
whereas it is generally normal in mitral incompetence. The
pattern of ventricular hypertrophy reflects the underlying
hemodynamics.
Consequently, patients with mitral stenosis tend to
have right ventricular hypertrophy, while those with mitral
incompetence have left ventricular hypertrophy. All of these
findings are modified by associated abnormalities.
Cross-sectional Echocardiography
Mitral valve is best visualized in parasternal long-axis,
apical four chamber and two chamber views. Also, it can be
interrogated from the atrial aspect in parasternal short-axis
view. Addition of color Doppler further helps to diagnose the
abnormalities. Echocardiography and Doppler is also very
helpful in providing assessment of the mitral valve apparatus.
Parasternal long-axis view shows the motion of mitral valve
leaftlets for any evidence of doming or prolapse. The chordal
length, chordal thickening and chordal insertion, etc. are
also well seen in this view. Additional abnormalities of left
ventricular outflow tract like subaortic membrane, tubular
narrowing etc. can be assessed. Apical four chamber view
shows ventricular inflow region for any obstructive membrane
or ring in the atrium, like supramitral ring. The valve annuli
can be measured. The valve prolapse is also seen well in this
view. Apical four chamber view is good for showing dilatation
of atria, which may occur secondary to atrioventricular valve
stenosis and/or regurgitation. Parasternal short-axis view with
sweep from base to apex, shows orientation of commissures,
chordae and papillary muscles including the number of
papillary muscles. Cleft mitral valve and double orifice mitral
valve (Figure 9A and B) are also best diagnosed in this view.
Addition of color flow mapping is necessary for quantifying
the regurgitation and in cases with stenosis, to see the level
of stenosis (Figure 3). The effective orifice size cannot
be determined by 2D echocardiography when the flow is
interchordal and the valve closure is eccentric. Doppler is also
useful in estimating gradients and valve area. Gradients by
391
392
Doppler may be underestimated due to associated interatrial

defect or due to poor alignment secondary to multiple levels
of obstruction to left ventricular inflow. Pressure half time
method is often not reliable in this setting. Planimetry of
the mitral valve orifice in parasternal short-axis view may
be the best method for assessment of mitral valve area. The
normal mitral valve area is 2.4 to 3.6 cm2/m2. In mild mitral
stenosis the valve area is reduced to 1.2 to 2.4 cm2/m2; in
moderate mitral stenosis, mitral valve area is 0.6 to 1.2 cm2/
m2 and in severe mitral stenosis, the valve area is < 0.6 cm2/
m2. Echocardiography is useful for evaluation of associated
cardiac defects seen in 90 percent of cases with congenital
mitral valve abnormality.
Pulsed and Continuous Wave Doppler Echocardiography

Doppler echocardiography is a useful modality for assessment
of mitral stenosis. With mitral valvar stenosis, a turbulent
inflow jet is seen, on color Doppler. Both pulse and continuous
wave Doppler (Figure 14) can be used to calculate the gradient
across the valve. In adults and older patients, the pressure halftime provides an accurate assessment of area, independent
of cardiac output. This same technique can be applied to
children, although absolute areas calculated in this way are
of little value, because of the wide variation in body surface
area. Mean gradients across the valve, as assessed using color
flow images, have traditionally been used in assessment of
congenitally malformed hearts, despite the limitation of their
dependency on cardiac output. Color flow Doppler of mitral
valve excludes or establishes associated regurgitation and,
pinpoints the site of obstruction and the pattern of flow across
the valve. This technique also provides valuable clues about
the site of exit of the blood. In a parachute valve there appears
to be a conical jet of blood, whereas in those with two papillary
muscles, the jet is more dispersed.
Figure 14: Continuous wave Doppler shows both mitral

stenosis and regurgitation

Use of Magnetic resonance imaging (MRI) for functional
assessment in congenital heart disease including assessment
of mitral regurgitation is an evolving concept. Using this
technique, a very good correlation has been found between
measured and calculated regurgitant volumes, with a
correlation coefficient of 0.99. MRI provides more reliable
data with regards to mitral annular diameter, when compared
to cross-sectional echocardiography. Three-dimensional
echocardiography has shown good correlation to MRI
assessment of mitral valve lesions.
Two-dimensional and Doppler echocardiographic assessment
of mitral valve stenosis, usually replaces the necessity for
cardiac catheterization, unless surgical or interventional
catheterization management seems indicated. The important
characteristic of mitral obstruction is difference in diastolic
pressures between the left atrium and ventricle. The high left
atrial pressure seems to seal the valvar mechanism of the oval
foramen, thus may require transseptal puncture for the same. A
satisfactory pulmonary capillary wedge pressure simultaneous
with the left ventricular pressure may also be used for the same
(Figure 15). The presence of a diastolic pressure gradient
between pulmonary artery pressure and mean pulmonary
capillary wedge pressure suggests the presence of associated
pulmonary vasoconstriction or pulmonary vaso-occlusive
disease. Administration of oxygen or pulmonary vasodilators
such as nitric oxide and occasional open lung biopsy, may
be necessary to define the underlying pulmonary vascular
pathology and prognosis. Finally, comparison of pulmonary
capillary wedge and left atrial pressure is required if pulmonary
vein obstruction is suspected. Routine measurement of wedge
Figure 15: Showing simultaneous left atrial and left ventricular trace
from a patient with mitral stenosis. Shaded area shows the area
calculation for the mitral valve mean gradient. Note the diastolic
pressure difference between the left atrium and left ventricle
pressures during cardiac catheterization goes a long way

towards detecting otherwise masked mitral stenosis.
Angiography is largely replaced nowadays with echo

cardiography. It should be performed with the greatest caution
in patients with congestive failure or severe pulmonary
hypertension. Injections into the pulmonary artery or
left ventricle in the right anterior oblique projection may
demonstrate thickening and restricted mitral valve leaflets in
patients with isolated mitral valve stenosis or an hourglassshaped diastolic left ventricular filling defect characteristic of
parachute mitral valve malformation. Mitral insufficiency may
be present. Associated congenital cardiac malformations should
be actively considered. In rare instances of severe stenosis or
mitral atresia with VSD and normally developed left ventricle,
balloon or blade atrial septostomy or stenting of the foramen
ovale should be performed to decompress the obstructed
left atrium. However, this must be balanced with the need to
maintain high pulmonary vascular resistance in neonates with
ductus arteriosus dependent systemic blood flow.
MANAGEMENT
Medical Management and Timing of Intervention
Medical management is frequently dictated by the nature and
severity of the associated lesions. Treatment with diuretics
may buy some time, while the definitive repair is awaited.
Although surgical repair is possible, the long-term results
are disappointing. Unfortunately, pulmonary hypertension is
frequently encountered in these patients, thus forcing the hand
of the cardiologist and surgeon. There is little data for balloon
angioplasty performed in the setting of congenital mitral valvar
stenosis, albeit that encouraging results have now been reported.
Surgical Management
Patients with severe mitral valvar stenosis, who present in
the neonatal period and frequently have some degree of left
ventricular hypoplasia and aortic valvar stenosis, now tend to
be managed by Norwood sequence of operations followed by
univentricular pathway repair.
Mitral Valve Repair

Beyond the neonatal period mitral valve repair is the best
option, as valvar replacement in children is still fraught with
problems. The presence of intractable heart failure, severe
pulmonary hypertension or pulmonary edema, means that
the need for operation in infancy or early childhood is forced
upon the management team. In contrast, in congenital mitral
incompetence, the generally good prognosis with medical
management means that operation can usually be postponed
27
Angiocardiography
for as long as is possible. The exception to this conservative

approach is that for the isolated cleft of the anterior mitral
leaflet, where the results of repair are so good as to justify
surgery at any age if there is significant cardiomegaly.
Reconstructive surgery currently has acceptable results
with regards to mortality and morbidity over the medium term.
A younger age at presentation and association with additional
intracardiac lesions are poor prognostic features. In general,
survival over the medium term is close to 90 percent, with
a freedom from reoperation of approximately 76 percent
over the variously reported periods of follow-up. There are
multiple surgical techniques that are tailored to the specific
pathology at the levels of the annulus, leaflets and supporting
tension apparatus. Frequently, due to the complex nature of
the valvar pathology, one or more of these has to be applied
to an individual patient. For regurgitant valves, it is possible
to perform annuloplasty or insert mitral rings, with the latter
currently being designed, so as to fit the normal saddleshape of the mitral valvar annulus. For those with dysplastic
leaflets, augmentation has been employed with some success.
Occasionally, it is necessary to place a stitch between the
leaflets, so as to create double orifices within the valve. For
stenotic lesions, it is possible to resect supramitral ring, split
the papillary muscles in those with the parachute malformation,
enlarge the zone of apposition between the leaflets or resect
accessory valvar tissue. It is also possible to shorten or transfer
the tendinous cords, as well as insert synthetic cords.
Prosthetic Valve
Mitral valve replacement is considered only after all other
surgical options have been exhausted. The results of valvar
replacement are somewhat disappointing, particularly in the
very young child. The initial experience gained with insertion
of homograft valves was disappointing, with reoperation
needed in two-fifths at 5 years and three fifths by 7 years.
Mechanical valves are the treatment of choice, with the valves
inserted usually being bileaflet and having a low profile. From
several series that followed patients for 10 to 15 years, overall
survival was in the mid-1960s, with freedom from the need
to insert a second valve varying between 54 percent and 66
percent.With improved management of anticoagulation, the
incidences of thrombosis and infection are low, occurring in
less than one-tenth. It is the need for valvar replacement and
the size of the initial prosthesis, that stratifies the patients. In
many younger patients, where stenosis is the predominant
lesion, there is associated annular hypoplasia that limits the
size of the prosthesis, which can be inserted during the initial
operation. Indeed, in some cases the annulus is deemed too
small and the prosthesis has to be positioned in the supraannular position. To overcome this problem, some groups have
used a pulmonary autograft in the so-called Ross-2 procedure.
The pulmonary valve removed from the patient is sewn into
a Dacron tube, which is then inserted into the mitral annulus.
Although experience is limited with this technique, the initial
393
results seem encouraging, with a low mortality, albeit that as

yet there is no data over the long-term.
CONCLUSION
Congenital obstruction to left ventricular inflow can originate
at various levels. The anomalies may be associated with other
left sided anomalies (e.g Shones Complex). The presentation
of the patient depends on the degree of left ventricular
inflow obstruction and patients with severe obstruction
present in infancy. Echocardiography is helpful not only in
understanding the pathophysiology, hemodynamics and
anatomical basis to decide for the anatomical subtype of the
obstruction. Echocardiography may also be helpful to look
for associated anomalies and also to guide the surgeon for
appropriate surgical management. The outcome of the lesion
depends on the underlying anatomical lesion and its severity
at the time of presentation.
It is easy to get a thousand prescriptions but hard to get one
single remedy.
Chinese Proverb
Suggested Readings
1. Asante-Korang A, OLeary PO, Anderson RH. Anatomy and
echo of the normal and abnormal mitral valve. Cardiol Young.
2006;16:27-34.
2. Baylen BG,Atkinson DE. Mitral Inflow Obstruction. Iin
Heart Disease in infants, children and Adolescents including
the fetus and young adult. Allen HD, Driscoll DJ, Shaddy
RE, Feltes TF, 7th edition, Lippincort Williams and Wilkins
Publishers;2008:922-37.
3. Chauvaud SM, Milhaileanu SA, Gaer JAR, et al. Surgical
treatment of congenital mitral valvar stenosis: The Hospital
Broussais experience. Cardiol Young. 1997;7:15-21.
394
4. De Lange FJ, Moorman AFM, Anderson RH, et al. Lineage

and morphogenetic analysis of the cardiac valves. Circ Res.
2004;95:645-54.
5. Julien IE Hoffman. Cor Triatriatum Sinister in the Natural and
Unnatural History of Congenital Heart Disease, 1st edition,
Wiley Blackwell. 2009. pp. 329-34.
6. Kanani M, Moorman AFM, Cook AC, et al. Development of
the atrioventricular valves: Clinicomorphologic correlations.
Ann Thorac Surg. 2005;79: 1797-804.
7. McElhinney DB, Sherwood MC, Keane JF, et al. Current
management of severe congenital mitral stenosis, outcomes of
transcatheter and surgical therapy in 108 infants and children.
Circulation. 2005;112:707-14.
8. Nath RK, Saxena A.Congenital Atrioventricular valve aomalies
in Echocardiography in congenital heart diseases, A practical
approach. 1st edition. 2008. pp. 58-68.
9. Rorie M, Xie GY, Miles H, et al. Diagnosis and surgical
correction of cor triatriatum in an adult: combined use of
transesophageal echocardiography and catheterization. Catheter Cardiovasc Interv. 2000;51:83-6.
10. Shone JD, Sellers RD, Anderson RC, et al. The developmental
complex of parachute mitral valve, supravalvular ring of left
atrium, subaortic stenosis, and coarctation of aorta. Am J Cardiol. 1963;11:714-25.
11. Smallhorn J, Tommasini G, Deanfield J, et al. Congenital mitral
stenosis: Anatomical and functional assessment by echocardiography. Br Heart J. 1981;45:527-34.
12. Smallhorn JF, Anderson RH. Abnormalities of the morphologically mitral valve In: Paediatric Cardiology. Anderson RH,
Macartney RF, Shinebourne EA, Baker EJ, Rigby ML, Tynan
M. 3rd edition. Churchill Livingstone, Harcourt Publishers limited; 2010. pp. 730-2.
13. Van der Bel Kahn J, Duren DR, Becker AE. Isolated mitral
valve prolapse: Chordal architecture as an anatomic basis in
older patients. J Am Coll Cardiol. 1985;5:1335-40.
14. Wood AE, Healy DG, Nolke L, et al. Mitral valve reconstruction
in a pediatric population: Late clinical results and predictors
of long-term outcome.J Thorac Cardiovasc Surg. 2005;130:
66-73.
Sec t i on
Congenital Valvar Lesions
C hapter
28
Tricuspid Atresia
P Syamasundar Rao
INTRODUCTION
Tricuspid atresia is a cyanotic, congenital cardiac anomaly
and is defined as congenital absence or agenesis of the
morphologic tricuspid valve.1,2 It is the third most common
cyanotic congenital heart defect and is the most common cause
of cyanosis with left ventricular hypertrophy. Whereas, there
is a controversy with regard to terminology (tricuspid atresia,
univentricular heart or univentricular connection), the author
is of the opinion that the term tricuspid atresia is the correct
and logical term to describe this well-characterized pathologic
and clinical entity; the reasons are detailed elsewhere.2-4
A methodical and thorough review by Rashkind5 suggests
that the first documented case of tricuspid atresia was that of
Kreyszig in 1817,6 although the 1812 report by the editors
of London Medical Review7 appears to fit the description of
tricuspid atresia.
The true prevalence of tricuspid atresia is not known.
Extensive review of the literature revealed an autopsy
prevalence rate of 2.9 percent and a clinical prevalence rate
of 1.4 percent among subjects with congenital heart disease.8
With the known prevalence of congenital heart defects of 0.8
percent of live births, it is estimated that tricuspid atresia occurs
approximately 1 in 10,000 live births.8 There is no gender
preponderance for tricuspid atresia, but male preponderance
appears to be present in the subgroup of tricuspid atresia
patients with associated transposition of the great arteries
male to female ratio was 2 : 1.8,9
In this chapter, classification, anatomic, physiologic and
clinical features, non-invasive and invasive evaluation,
management and prognosis of tricuspid atresia are discussed.
CLASSIFICATION
Tricuspid atresia is classified on the basis of valve
morphology,10 roentgenographic appearance of pulmonary
vascular markings11 and associated cardiac defects.1,12-15 Based
on morphology of the atretic tricuspid valve, it is classified

into muscular, membranous, valvar, Ebstein, unguarded with
muscular shelf and atrioventricular canal types.10,15-17 The
muscular type, constituting 89 percent of cases,15,17 is the most
common type, the remaining types account for 11 percent of
cases. A classification based solely on the X-ray appearance
of pulmonary vascular markings was put forward by Astley:11
Group A-Decreased pulmonary vascular markings and
Group B-Increased pulmonary vascular markings. Dick and
his associates9 added another group to Astleys classification:
Group C-Transition from increased to decreased pulmonary
vascular markings in serial chest films. The above two
classifications have clinical value, but a classification based
on associated cardiac defects appears to be more useful
clinically.1,15 A classification based on great artery interrelationship was first proposed by Khne in 1906.12 This was
later refined by Edwards and Burchell13 and by Keith, Rowe
and Vlad.14,18,19 Because of some apparent inconsistencies in
subgrouping and the need for inclusion of all variations in great
artery anatomy, we proposed an unified classification,1,20 and
this is listed in Box 1. First, the tricuspid atresia is classified
into four major types based on the great artery relationship.
Each type is identified with a Roman number:
Type I: Normally related great arteries
Type II: D-transposition of the great arteries
Type III: Malpositions of the great arteries other than
d-transposition
Type IV: Truncus arteriosus.
The type III is again subdivided into several subtypes (see
Box 1) and is identified with an Arabic number (1 to 5).
Each type and subtype are further divided into subgroups
on the basis of pulmonary arteries; each subgroup is indicated
by a lower case letter: Subgroup a Pulmonary atresia, b
Pulmonary stenosis or hypoplasia, and c Normal pulmonary
arteries (no pulmonary stenosis).1,15,17,20 Once a patient
with tricuspid atresia is thus classified, the status of the
interventricular septum, i.e. intact, small or large ventricular
Box 1: A unified classification of tricuspid atresia

Type I
Type II
Type III
Normally related great arteries

D-transposition of the great arteries
Malpositions of the great arteries other than
D-transposition

Subtype 1: L-transposition of the great arteries

Subtype 2: Double outlet right ventricle

Subtype 3: Double outlet left ventricle

Subtype 4: D-malposition of the great
arteries (anatomically corrected
malposition)

Subtype 5: L-malposition of the great arteries
(anatomically corrected malposition)
Type IV Persistent truncus arteriosus
Each type and subtype are divided into:

Subgroup a: Pulmonary atresia

Subgroup b: Pulmonary stenosis or hypoplasia

Subgroup c: Normal pulmonary arteries (no
pulmonary stenosis).
Courtesy: Reproduced from Rao1 with permission
septal defect (VSD), or multiple VSDs and other associated

malformations should be described. If one wants to follow
the terminology of congenital heart disease proposed and reemphasized by Van Praagh,21 one could include the remaining
segmental subsets, namely visceroatrial situs and ventricular
loop. Each case could be described by notations SDS, SDD,
SDL and so on as the case may be.21,22
PATHOLOGIC ANATOMY
398
The most common type of tricuspid atresia, muscular variety,

is characterized by a dimple or a localized fibrous thickening
in the floor of the right atrium (Figure 1) at the expected
site of the tricuspid valve14 and constitutes 89 percent of the
cases.16,17 No valvar material can be identified either by gross
or microscopic examination.14
Other anatomic types, namely, membranous type (6.6%)
with the atrioventricular portion of the membranous septum
forming the floor of the right atrium,24,25 valvar type (1%)
with minute valve cusps which are fused,15,26,27 Ebsteins
type (2.6%) with Ebstein deformity of the tricuspid valve
leaflets with fusion of the valve leaflets,10,24,28 common
atrioventricular canal type (0.2%) in which a leaflet of the
common atrioventricular canal completely seals off the only
entry into the right ventricle,16,29 and unguarded (0.6%) with
muscular shelf30 have been described. For further details the
reader is referred to our previous reviews.15,17
The right atrium is usually enlarged and its wall thickened
and hypertrophied. The interatrial communication, which is
necessary for survival, is usually a stretched patent foramen
ovale, sometimes an ostium secundum atrial septal defect and
rarely an ostium primum atrial septal defect. Occasionally
Figure 1: Heart specimen of a patient with muscular type of tricuspid

atresia; the right atrium is opened by cutting through the right atrial
appendage (RAA). Note dimple (arrow) in the floor of the right atrium
with muscle fibers radiating around it. An atrial septal defect (ASD) is
also shown. The impression that one gets from the literature is that this
dimple is present in most cases of tricuspid atresia. Careful inspection
of the heart specimen by several investigators suggests that this dimple
is seen in only 29 to 83% of muscular type of tricuspid atresia cases.
Courtesy: Rao PS, et al.23 Am Heart J 1991;122:829
the interatrial communication is obstructive and may form an

aneurysm of the fossa ovalis causing obstruction to the mitral
flow. The left atrium is enlarged and may be more so if the
pulmonary blood flow is increased.
The mitral valve is morphologically a mitral valve, usually
bicuspid, but its orifice is large and rarely incompetent. The
left ventricle is clearly a morphologic left ventricle with
only occasional abnormalities;25 however, it is enlarged and
hypertrophied.
The VSD may be large, small or non-existent (intact
ventricular septum), or multiple VSDs may be present. When
present, it may be:
a. Conoventricular or perimembranous (located inferior to
the septal band)
b. Conal septal malalignment VSD (located in between the
anterosuperior and posteroinferior limbs of septal band)
c. Muscular (located inferiorly when compared to a and b)
d. Atrioventricular canal type.22
In the authors experience, muscular VSDs are most
common.31-34 Also, most of these VSDs are restrictive and
produce subpulmonary stenosis in the type I patients and
subaortic stenosis in the type II patients.31-39
The right ventricle is small and hypoplastic; even the largest
of the right ventricles that are present in patients with large
VSDs and/or transposition of the great arteries are smaller
than those in normal. Its size, by and large, is determined
PATHOPHYSIOLOGY
In type I (normally related great arteries) patients with

intact ventricular septum and/or pulmonary atresia (type Ia)
and type II (transposition of the great arteries) patients with
pulmonary atresia (type IIa), the pulmonary blood flow must
be derived entirely through the ductus. Since, the ductus is
carrying only the pulmonary blood flow, representing 8 to 10
percent of combined ventricular output in contradistinction
to 66 percent in the normal fetus,43,44 the ductus arteriosus
is smaller than normal. This and the acute angulation of the
ductus at its aortic origin because of reversal of direction of
ductal flow may render the ductus less responsive to the usual
postnatal stimuli.43
In type I patients with moderate to large VSD, there is likely
to be anterograde blood flow from the left ventricle through
the VSD into the right ventricle, the pulmonary artery, and
ductus arteriosus, whereas there may be retrograde blood flow
from the aorta to the ductus arteriosus in the fetus with small
VSD. The larger the VSD, the greater is the probability of
normal anterograde ductal flow.
In type I patients with a small or no VSD, most of the left
ventricular blood is ejected into the aorta, which is then carried
to the entire body including the placenta and lower part of
the body. Thus, the aortic isthmus carries a larger proportion
of ventricular output than normal; presumably this is the
reason for the rarity of aortic coarctation in these subgroups
of tricuspid atresia patients. In type II (transposition) patients
without significant pulmonary stenosis, because the VSD
is usually smaller than the pulmonary valve ring,45 a larger
proportion of blood traverses the pulmonary artery and ductus
arteriosus and therefore the isthmic flow decreases, thus
accounting for higher incidence of aortic coarctation and aortic
arch anomalies seen with these types of tricuspid atresia.
28
Tricuspid Atresia
by anatomic type. It may be extremely small so that it may

escape detection on gross examination of the specimen as in
type Ia cases. It can be identified at the right upper aspect of
the ventricular mass. On occasion, it can be identified only
on microscopic examination.13,14 However, in most cases the
ventricle is a true right ventricle24,40 consisting of:
a. A sharply demarcated infundibulum with septal and
parietal bands
b. A sinus with trabeculae, which communicates with the left
ventricle via a VSD. The inflow region of the right ventricle,
by definition, is absent although papillary muscles may be
present occasionally.19
The relative position of the great vessels is quite variable
and has been the basis for classification of this anomaly,
which has been described in the preceding section. The
ascending aorta may be normal in size or large. Pulmonary
outflow obstruction may be either subvalvar or valvar in
patients with transposition of the great arteries, while in
patients with normally related great arteries the pulmonary
obstruction is often at the VSD level although, in a few cases,
subvalvar pulmonary stenosis, narrow tract of the hypoplastic
right ventricle and rarely, valvar pulmonary stenosis may
also be responsible for pulmonary outflow tract obstruction.
With pulmonary atresia, either a patent ductus arteriosus or
aortopulmonary collateral vessels may be present.
A large number of additional abnormalities may be present
in 30 percent of tricuspid atresia patients.41,42 Significant
among these are persistent left superior vena cava and
coarctation of the aorta; the latter is much more common
in type II (transposition) patients. The possible physiologic
reason for the latter is discussed in the next section.
Postnatal Circulation
Prenatal Circulation
Tricuspid atresia is not detrimental to normal fetal development.
In a normally formed fetus, the highly saturated inferior vena
caval blood is preferentially shunted into the left atrium via the
patent foramen ovale and from there into the left ventricle and
aorta. The superior vena caval blood containing desaturated
blood is directed towards the tricuspid valve and right ventricle
and from there into the pulmonary arteries, ductus arteriosus
and descending aorta. Thus, in a normal fetus, the head, heart
and upper extremities are supplied with blood at higher PO2
and the lungs, the lower part of the body and placenta with
lower PO2. In tricuspid atresia, both vena caval streams have
to be shunted across the foramen ovale into the left atrium and
left ventricle. Therefore, the PO2 differential to various parts of
the body that is normally present does not exist. Whether this
higher PO2 to lungs influences the pulmonary arteriolar smooth
muscle development or not, is not known.43 Lower than normal
PO2 to the brain and upper part of the body does not seem to
impair their development, at least as observed clinically.
An obligatory right-to-left shunt occurs at the atrial level in

most types and subtypes of tricuspid atresia. Usually, this
shunting is through a patent foramen ovale, but on occasion,
secundum or primum atrial septal defects may be present.
Thus, the systemic and coronary venous blood mixes with
pulmonary venous return in the left atrium. This mixed
pulmonary, coronary and systemic venous blood enters the
left ventricle.
In type I (normally related great arteries) patients with a
VSD, left-to-right ventricular shunt occurs, thus perfusing the
lungs. In the absence of a VSD, the pulmonary circulation
is derived either via a patent ductus arteriosus or through
bronchopulmonary or persistent embryonic aortopulmonary
collateral vessels. The presence of either a VSD or other
means of blood supply to the lungs is crucial for the patients
survival. The aortic blood flow is derived directly from the left
ventricle.
In type II (d-transposition of the great arteries) patients,
the pulmonary blood flow is directly derived from the left
399
ventricle. The systemic blood flow is via the VSD and the
right ventricle. In type III, subtype 1 with l-transposition of the
great arteries, the atretic morphologic tricuspid valve is a leftsided atrioventricular valve and therefore, in a physiological
sense, it behaves as mitral (left or pulmonary venous atrial)
obstruction. In other type III and type IV patients, the systemic
and pulmonary blood flows are determined by the size of the
VSD and other associated defects.
Other Physiologic Principles

Arterial Desaturation
Because of complete admixture of the systemic, coronary and
pulmonary venous returns in the left atrium and left ventricle,
systemic arterial desaturation is always present. The oxygen
saturation is proportional to the magnitude of the pulmonary
blood flow.43,46 The data from our study patients are plotted in
Figure 2; the pulmonary to systemic blood flow ratio (Qp : Qs)
which represents the pulmonary blood flow has a curvilinear
relationship with the arterial oxygen saturation. A Qp : Qs of
1.5 to 2.5 appears to result in an adequate oxygen saturation.46
Further increase in Qp : Qs does not result in better oxygen
saturation, but may subject the left ventricle to larger volume
overloading and, therefore is not advisable.46
Pulmonary Blood Flow

The magnitude of pulmonary blood flow is the major
determinant of clinical features in tricuspid atresia. An infant
with markedly decreased pulmonary blood flow will present
early in the neonatal period with severe cyanosis, hypoxemia
and acidosis. An infant with markedly increased pulmonary
flow does not have significant cyanosis, but usually presents
with signs of heart failure. Although there is some overlap,
patients with decreased pulmonary flow usually belong to type
I (normally related great arteries) and those with increased
pulmonary blood flow are usually type II (transposition of the
great arteries) and occasionally type Ic.
The magnitude of pulmonary blood flow in an unoperated
patient is dependent upon the degree of obstruction of
the pulmonary outflow tract and patency of the ductus
arteriosus. The pulmonary outflow obstruction is valvar or
subvalvar in type II patients and valvar, subvalvar or at VSD
level in type I patients. In our own experience with several
series of tricuspid atresia, we found the obstruction to be
located most commonly at the VSD level.31-34,37,38 When
the VSD is large and non-restrictive and the pulmonary
valve not stenotic, the pulmonary flow is proportional to
the pulmonary to systemic vascular resistance ratio. When
a systemic to pulmonary artery shunt has been performed,
the pulmonary blood flow is proportional to the size of the
anastomosis.
Left Ventricular Volume Overloading

Because the entire systemic, coronary and pulmonary venous
returns are pumped by the left ventricle, the left ventricle has a
greater volume overload than that in the normal. This volume
overloading is further increased if the Qp : Qs is high either
because of mild or no obstruction to pulmonary blood flow or
because of large surgical shunts, either of which may result
in heart failure. Normal left ventricular function is critical for
successful Fontan type of procedure and should be maintained
within normal range. Several studies have shown that the left
ventricular function tended to decrease with increasing age,
Qp : Qs and arterial desaturation.47-49
Size of the Interatrial Communication
400
Figure 2: The systemic arterial saturations, left ventricular (LV) or

aortic (Ao), are plotted against the pulmonary to systemic blood flow
ratio (Qp : Qs). Both type I and type II anatomy are included. Note
curvilinear relationship between two parameters. At low Qp : Qs levels,
a slight increase in Qp : Qs produces large increases in systemic
O2 saturation, whereas at higher Qp : Qs further increase does not
produce significant increase in O2 saturation. Ideal Qp : Qs appears
to be between 1.5 and 2.5, giving O2 saturations in low 80s. Aortic
saturations are marked as solid circles and LV saturations as open
circles. Courtesy: Rao PS: Tricuspid Atresia, p 196. Mount Kisco, NY,
Futura Publishing Co, 198246
The interatrial communication is usually a patent foramen

ovale. Because of the obligatory shunting, this fetal pathway
persists in the postnatal period; this is in part related to low
left atrial pressure. But, the entire systemic venous return must
pass through the patent foramen ovale. Therefore, interatrial
obstruction is anticipated, but very few patients with tricuspid
atresia have clinically significant obstruction.9 The right-toleft shunt occurs in late atrial diastole with augmentation
during atrial systole (a wave).46,50 A mean interatrial
pressure difference greater than 5 mm Hg is usually indicative
of interatrial obstruction. A tall a wave in the right atrium is
also suggestive interatrial obstruction.
Changing Hemodynamics
CLINICAL FEATURES
Approximately one-half of the patients with tricuspid atresia
manifest symptoms on the 1st day of life and 80 percent would
be symptomatic by the end of the 1st month of life.9,51 As
previously mentioned, the magnitude of pulmonary blood flow
determines the clinical features. Two modes of presentation
are recognizedthose with decreased pulmonary blood flow
and those with increased pulmonary blood flow.
28
Tricuspid Atresia
With growth and development, several changes may take

place in patients with tricuspid atresia. Closure of the ductus
arteriosus occurring in early neonatal period may result in
severe hypoxemia. The size of the interatrial communication
may diminish either in absolute terms or relative to the volume
of the systemic venous return and cause systemic venous
congestion and may require atrial septostomy. The ventricular
septal defect may close spontaneously,31-39 causing pulmonary
oligemia and hypoxemia in type I patients or subaortic
obstruction in type II patients. Such VSD closures occur over
a period of months and years. The reader is referred to other
publications17,38 for further discussion.
an occasional infant may present within the 1st week of life.9

They are only minimally cyanotic, but manifest symptoms of
dyspnea, fatigue, difficulty to feed and marked perspiration.
Recurrent respiratory tract infection and failure to thrive is
another mode of presentation. The majority of these patients
belong to type IIc, although a small number of patients may
be of type Ic. The association of aortic coarctation with type
II patients has already been mentioned and coarctation, when
present, makes them vulnerable to early cardiac failure.
Examination reveals tachypnea, tachycardia, decreased
femoral pulses (when associated with aortic coarctation, but
without significant-sized patent ductus arteriosus), minimal
cyanosis, prominent neck vein pulsations and hepatomegaly.
Prominent a waves in jugular veins and/or presystolic
hepatic pulsations may be observed with associated interatrial obstruction. The precordial impulses are increased and
hyperdynamic. The second heart sound may be single or split.
A holosystolic murmur of VSD is usually heard at the left
lower sternal border. An apical mid-diastolic murmur may be
heard. Clear-cut signs of congestive cardiac failure are usually
present.
NON-INVASIVE EVALUATION
Chest Roentgenogram
Decreased Pulmonary Blood Flow

Infants with pulmonary oligemia present with symptoms of
cyanosis within the first few days of life; more severe the
pulmonary oligemia, the earlier is the clinical presentation.
These hypoxemic infants may have hyperpnea and acidosis
if the pulmonary blood flow is markedly decreased. The
majority of these infants belong to type Ib. Patients with
pulmonary atresia (Subgroup a) irrespective of the type will
also present with early cyanosis, especially when the ductus
begins to close. Hypoxic spells are not common in the neonate
although the spells can occur later in infancy.
Physical examination reveals central cyanosis, tachypnea
or hyperpnea, normal pulses, prominent a wave in the jugular
venous pulse (if there is significant interatrial obstruction),
and no hepatic enlargement (presystolic hepatic pulsations
may be felt if there is severe interatrial obstruction). Quiet
precordium and absence of thrills is usual. The second heart
sound is usually single. A holosystolic murmur, suggestive of
VSD may be heard at the left lower or left midsternal borders.
No diastolic murmurs are heard. In patients with associated
pulmonary atresia, no murmurs are usually heard, although in
an occasional patient, a continuous murmur of patent ductus
arteriosus may be heard. Clinical signs of congestive heart
failure are notably absent.
Increased Pulmonary Blood Flow

Infants with pulmonary plethora usually present with signs
of heart failure within the first few weeks of life, although
Roentgenographic picture is, by and large, dependent upon

the total pulmonary blood flow. In patients with diminished
pulmonary flow (the majority of infants will fall into this
category), the heart size is either normal or minimally
enlarged, whereas in those with increased pulmonary blood
flow, the heart size is moderately to severely enlarged. Several
patterns of cardiac configuration, namely characteristic
tricuspid atresia appearance,52 coeur en sabot configuration,53
egg-shaped,19 bell-shaped,54 and square11 heart have been
described, but in the authors experience and that of others,19
there is no consistent pattern that would be diagnostic of
tricuspid atresia. There may be concavity in the region
of pulmonary artery segment in patients with pulmonary
oligemia and small pulmonary artery. The right atrial shadow
may be prominent.
Right aortic arch may be present in approximately 8
percent of patients with tricuspid atresia19 and is less common
than that observed in patients with tetralogy of Fallot (25%)
and truncus arteriosus (40%). An unusual contour of the left
border of the heart suggestive of 1-transposition may be
seen in association with type III, subtypes 1 and 5 tricuspid
atresia.55
The greatest use of the chest roentgenogram is its ability
to categorize babies into those with decreased pulmonary
vascular markings and into those with increased pulmonary
vascular markings. Often, this is all that is necessary to make
a correct diagnosis once a history, physical examination
and electrocardiogram (see the next section) have been
obtained.55
401
402
Electrocardiogram
The electrocardiogram (ECG) can be virtually diagnostic
of tricuspid atresia in a patient suspected to have a cyanotic
congenital heart defect. Right atrial hypertrophy, an abnormal,
superiorly oriented major QRS vector (so called left axis
deviation) in the frontal plane, left ventricular hypertrophy
and diminished right ventricular forces (Figure 3) are
characteristic findings.
The right atrial hypertrophy, manifested by tall, peaked
P waves in excess of 2.5 mm, is present in the majority of
the patients with tricuspid atresia.56 Although it has been
suggested that the amplitude of P wave in lead II is directly
proportional to the interatrial pressure difference and inversely
proportional to the size of the interatrial communication,
detailed analysis of these parameters did not suggest a
consistent relationship.9,57 A double peak, spike and dome
configuration of the P wave, referred to as P-tricuspidale56
may be present. The first taller peak is contributed by the right
atrial depolarization and the second smaller peak is presumed
to be due to left atrial depoloarization.56,58
Abnormal, superiorly oriented major QRS vector (ASV),
more popularly called left axis deviation, between 0 to 90 in
the frontal plane is present in the majority of the patients with
tricuspid atresia. ASV is present in excess of 80 percent of
patients with type I anatomy (normally related great arteries)
while only less than 50 percent of patients with type II and
type III anatomy show such a typical electrocardiographic
pattern.58 Normal (0-+90) or right axis deviation is present

in a minority of patients and most of these patients belong to
type II or III anatomy. It has been suggested that the ASV may
be related to destructive lesions in the left anterior bundle,56
fibrosis of left bundle branch,59 abnormal distribution of the
conduction system (unusually long right bundle branch and
origin of left bundle branch very close to the nodal-His bundle
junction),60-62 a small right ventricle or a large left ventricle.57
Ventricular activation data from our group58,63 suggested that
this characteristic QRS pattern in tricuspid atresia is produced
by interaction of several factors, the most important being
the right-to-left ventricular disproportion and asymmetric
distribution of the left ventricular mass favoring the superior
wall.
Regardless of the frontal plane mean QRS vector
orientation, electrocardiographic criteria for left ventricular
hypertrophy are present in the vast majority of patients. This
may be manifested by increased (above 95th percentile) S
waves in right chest leads and R waves in left chest leads or by
adult progression of the QRS in the chest leads in the neonates
and infants. ST-T wave changes suggestive of left ventricular
strain is present in 50 percent of patients.58 The reason for left
ventricular hypertrophy is the anatomic nature of the lesion
with the resultant hemodynamics as well as lack of opposition
of the forces of left ventricular activation by the hypoplastic
right ventricle. Occasionally, biventricular hypertrophy may
be present and majority of these patients belong to type II or
III anatomy with good-sized right ventricle.
Figure 3: Twelve electrocardiogram showing an abnormal, superiorly oriented mean QRS vector in frontal plane (45, left axis deviation), left
ventricular hypertrophy and diminished anterior (R waves in leads V1 and V2) and rightward (S waves in leads V5 and V6) forces. Tall P waves
are also seen in several leads, indicative of right atrial enlargement. This electrocardiogram is highly suggestive of tricuspid atresia
Echocardiogram
M-mode echocardiographic features include a large left
atrium (usually proportional to the magnitude of pulmonary
blood flow), dilated left ventricle with normal to decreased
left ventricular shortening fraction, a large posterior
atrioventricular valve in continuity with posterior semilunar
valve and a small right ventricle.55,64 The pulmonary valve may
or may not be recorded. The tricuspid valve is conspicuously
absent.55 Tricuspid valve-like echoes of low amplitude may
be recorded occasionally and this should not exclude the
diagnosis of tricuspid atresia.65
Two-dimensional echocardiography, apart from showing
enlarged right atrium, left atrium and left ventricle and a small
right ventricle demonstrates the atretic tricuspid valve directly.
In the most common muscular type, a dense band of echoes
is seen at the site, where tricuspid valve should be55,66 and
the anterior leaflet of the detectable atrioventricular valve is
attached to the left side of interatrial septum (Figure 4). Apical
and subcostal four-chambered views are best to demonstrate
the anatomy.
Atrial and ventricular septal defects can also be
demonstrated by 2D echocardiography. Semilunar valves can
be identified as pulmonary or aortic by following the great

vessel until the bifurcation of the pulmonary artery or arch
of the aorta is seen; this will help to decide, whether there
is associated transposition of the great arteries. Suprasternal
notch imaging will be of use in demonstrating coarctation of
the aorta, which is often seen in type II patients.
Contrast echocardiography with two-dimensional imaging
will clearly demonstrate sequential opacification of the right
atrium, left atrium, left ventricle and then the right ventricle.
However, contrast study is neither necessary nor recommended
for making the diagnosis.
Doppler examination is also useful in the evaluation of
tricuspid atresia patients. The obligatory right-to-left shunt
across the atrial septal defect can be demonstrated by placing
pulsed Doppler sample volume on either side of the atrial
septum and by color flow Doppler. Left-to-right shunting
across the VSD may also be demonstrated by Doppler. In
type I (normally related great arteries) patients, the VSD
peak Doppler velocity is helpful in estimating the size of the
VSD; the higher the velocity, the smaller is the VSD. Right
ventricular and pulmonary arterial pressure may also be
estimated using modified Bernoulli equation:
RV/PA systolic pressure = systolic BP 4V2
where, RV is right ventricle, PA is pulmonary artery, BP is arm
systolic blood pressure and V is VSD peak Doppler velocity.
In the presence of pulmonary hypertension or severe
infundibular or valvar pulmonary stenosis, the above VSD
Doppler velocities are not indicative of the size of the VSD. In
type II (d-transposition) patients, high velocity is suggestive
of subaortic obstruction.
Interrogation of right ventricular outflow tract in type
I patients and pulmonary artery region in type II patients
may reveal pulmonary or subpulmonary stenosis; higher the
velocity, more severe is the obstruction.
Doppler evaluation of descending aortic flow is helpful in
demonstrating aortic coarctation.
In summary, delineation of the majority of anatomic and
physiologic issues related to tricuspid atresia is feasible by
M-mode, two-dimensional and Doppler (pulsed, continuous
wave and color) echocardiography.
28
Tricuspid Atresia
Diminished R waves in right chest leads and S waves in

left chest are related to right ventricular hypoplasia.
Vectorcardiographic features closely resemble the scalar
electrocardiogram, but vectorcardiography is no longer
available for routine use.
Other Laboratory Studies
Figure 4: Apical four-chambered two-dimensional echocardiographic

view of a baby with tricuspid atresia showing enlarged left ventricle
(LV). Small right ventricle (RV) and a dense band of echoes at the
site, where the tricuspid valve (TV) echo should be. LA = Left atrium;
MV = Mitral valve; RA = Right atrium
Pulse oximeter and blood gas values are useful in quantitating

the degree of hypoxemia, thereby indicating the severity of
pulmonary oligemia. Hemoglobin and hematocrit values are
useful in children; the degree of polycythemia is useful in
estimating the severity of hypoxemia.67
Magnetic resonance imaging (MRI) and computed
tomography (CT) scan studies are not usually necessary
because the echo is good enough to define most of the issues
related to tricuspid atresia. Occasionally, these studies may
be indicated to define the pulmonary artery or aortic arch
anatomy, especially in older patients with poor echo windows.
403
The diagnosis of tricuspid atresia based on clinical,

electrocardiographic and echocardiographic features is
relatively simple and cardiac catheterization and selective
cineangiography, rarely, if ever, are essential for establishing
the diagnosis.46 Even neonates with significant arterial
desaturation need not undergo cardiac catheterization and
selective cineangiography; the diagnosis of tricuspid atresia
is usually made on the basis of clinical and non-invasive
evaluation, particularly echo-Doppler studies. Catheterization
may be indicated prior to bidirectional Glenn or Fontan
operations. If catheterization is performed, the following
features may be found.
Catheter Course
Because of atretic tricuspid valve, the right ventricle cannot
be directly catheterized from the right atrium. The catheter
can easily be maneuvered into the left atrium across the patent
foramen ovale. The catheter may follow a similar course in
patients with pulmonary atresia (or severe stenosis) with
intact ventricular septum and hypoplastic right ventricle or
severe tricuspid stenosis. Inability to enter the right ventricle
from the right atrium is not necessarily diagnostic of tricuspid
atresia, but in experienced hands, it is highly suggestive of
tricuspid atresia.
From the left atrium, the catheter can easily be manipulated
into the left ventricle. With the previous conventional
catheters, the left ventricle is the farthest structure that could
be catheterized in tricuspid atresia. However, with the use of
balloon-tipped catheters and other maneuvers using guide
wires, the aorta, the right ventricle and the pulmonary artery
can be catheterized, particularly in older infants and children.
But in neonates, once an adequate left ventricular angiogram
is performed, we will terminate the procedure because
further manipulation of the catheter may precipitate spells or
arrhythmia and the additional information obtained may not
be of much value.
In infants with clinical and/or blood pressure evidence
for aortic arch obstruction, retrograde arterial catheterization
(using percutaneous Seldinger technique or transumbilical
route) may be necessary especially, if the aortic arch anatomy
is not clearly demonstrated by left ventricular angiography.
by an increase of 6 percent or more in O2 saturation from the

superior vena cava to the right atrium in two or more sets of
saturations in 29 of 50 (58%) catheterizations in which the data
were adequate.50 However, in the shunt group, the left atrial v
waves were equal to or higher than the right atrial v waves
accounting for the left-to-right atrial shunting. Simultaneous
pressure recordings from the left atrium and the right atrium
with isosensitized miniature pressure transducers mounted 5
cm apart, revealed a higher pressure in the left atrium than
in the right atrium during atrial diastole (Figure 5). Based on
findings of that study,50 it was concluded that:
1. left-to-right shunt across the atrial septal defect occurs
frequently in tricuspid atresia
2. The left-to-right shunt is a result of instantaneous pressure
difference between atria and such shunts are physiologic.
The pulmonary venous saturations are usually in the normal
range. A significant decrease in left atrial saturation is expected
because of obligatory right-to-left shunting across the patent
foramen ovale. Falsely high or falsely low saturations may
be measured in the left atrium because of streaming. The left
ventricular saturations are usually well mixed and are more
reliable. The saturations in the left atrium and left ventricle as
well as those in the right ventricle, the pulmonary artery and
the aorta are identical. Systemic arterial desaturation is always
present and the extent of desaturation is proportional to the
Qp : Qs (Figure 2).46
The vena caval, left atrial, left ventricular and aortic
oxygen saturations are usually lower in type I patients than
those in type II patients.46 This is presumably related to greater
preponderance of pulmonary oligemia in type I patients.
Oxygen Saturations
404
Systemic venous oxygen saturations are usually diminished

and the extent of decrease is related to systemic arterial
desaturation and the severity of congestive heart failure.
Because of the obligatory right-to-left shunting across
the patent foramen ovale, it is generally believed that the
right atrial saturations are similar to vena caval saturations.
However, we found left-to-right atrial shunting, represented
Figure 5: Simultaneous pressures from the left atrium (LA) and right
atrium (RA) are recorded by means of high fidelity miniature pressure
transducers mounted on a catheter 5 cm apart. Note higher RA
pressure during atrial systole and higher LA pressure during atrial
diastole; the later finding may help explain the physiologic left-toright shunting at atrial level in tricuspid atresia patients. Courtesy: Rao
PS: Br Heart J 1983;49:345.50 a = a wave; ECG = Electrocardiogram;
v = v wave
28
Pressures
Calculated Variables
Systemic and pulmonary blood flows and resistances and
shunts can be calculated by the Fick principle either by
measuring oxygen consumption or by assuming it from tables
of normal values.46 The principles and methods of calculation
have been detailed elsewhere46 and will not be discussed here.
Although most of the calculations can be performed, Qp : Qs is
the most useful calculated value. The Qp : Qs is diminished in
type I hypoxemic infants with small or no VSD. It is markedly
increased in type I patients with moderate to large VSDs and
in most patients with type II anatomy.
Other calculated variables such as pulmonary vascular
resistance,46 preoperative catheterization index68 and transpulmonary gradient (pulmonary artery mean pressureleft
atrial mean pressure) are useful measures in the pre-Fontan
evaluation.
Cineangiography
Since the initial description by Campbell and Hills69 and
Cooley et al,70 two signs, namely, typical sequence of
tricuspid atresia and right ventricular window, on right
atrial angiography have been very helpful in the diagnosis of
tricuspid atresia. Selective right atrial or superior vena caval
angiogram reveals successive opacification of the left atrium
and left ventricle without immediate opacification of the right
ventricle (Figure 6). The negative shadow, so called right
Tricuspid Atresia
The right atrial mean pressure is minimally elevated. In the

absence of interatrial obstruction, it is dependent upon the left
ventricular end-diastolic and left atrial pressure. The right atrial
a waves are usually prominent. A mean pressure gradient of 5
mm Hg or more across the foramen ovale in favor of the right
atrium and giant a waves in the right atrium are indicative of
an obstructive foramen ovale. However, when there is marked
elevation of the left ventricular end-diastolic pressure and left
atrial pressure, lack of pressure gradient across the interatrial
communication does not exclude inter-atrial obstruction.46
The left ventricular end-diastolic pressure is usually
normal and increases with increasing Qp : Qs and decreasing
left ventricular function.
The right ventricular pressure is proportional to the size
of the ventricular septal defect in type I patients, while it is at
systemic level in type II patients. Systolic pressure gradient
across the VSD may be seen if it is restrictive. Pulmonary
artery pressure may be normal or increased depending upon
the size of the VSD in type I patients or upon the presence
or absence of subvalvar or valvar stenosis in type II patients.
Aortic pressures are usually normal. If coarctation of the aorta
is present, systolic hypertension and pressure gradient across
the coarctation may be present.
Figure 6: Selected frame from a posteroanterior view of a right atrial

(RA) angiogram in a child with tricuspid atresia showing successive
opacification of the left atrium (LA) and left ventricle (LV). There was no
direct and immediate opacification of the right ventricle; the negative
shadow, so called right ventricular window is shown with an arrow
ventricular window (Figure 6) seen in earlier frames of right

atrial angiography is due to failure of direct right ventricular
filling, but the right ventricle is seen subsequent to left
ventricular opacification. Although this area can be profiled
well in the elongated right anterior oblique and the fourchamber views,71 posteroanterior view is most commonly
used to demonstrate these signs and is perhaps far superior.19
The above described signs were initially thought to
be pathagnomonic of tricuspid atresia, but it is now wellrecognized that such appearance can be seen in patients with
pulmonary atresia or severe stenosis with intact ventricular
septum and large right-to-left shunting at atrial level, tetralogy
of Fallot with atrial septal defects (the so called pentology of
Fallot) and total anomalous pulmonary venous return to the
coronary sinus.19,71
Although the right atrial angiography is helpful in the
diagnosis, selective left ventricular angiography (Figure 7)
should also be performed in order to delineate the anatomy
and size of the left and right ventricles, size and type of
ventricular septal defects(s), relationship of great arteries and
the source of pulmonary blood flow. Frontal and lateral views
of the ventriculogram are most commonly used although left
anterior oblique view, long axial oblique view or a fourchambered view may help delineate desired anatomic detail.
In most neonates, selective right atrial and left ventricular
angiograms are all that will be necessary. Selective
antegrade or retrograde aortography to demonstrate either
the pulmonary arterial anatomy or aortic coarctation may
occasionally be needed. For additional discussion on
angiography in tricuspid atresia, the reader is referred to
other publications.18,71
405
Figure 7: Selective left ventricular (LV) cineangiogram in left anterior

oblique view demonstrating the relative position of the aorta (Ao) and
pulmonary artery (PA). The ventricular septal defect (VSD) is also
clearly seen. RV = Right ventricle
MANAGEMENT
Physiologically corrective surgery for tricuspid atresia72,73
and their modifications74-76 have improved the prognosis of
patients with tricuspid atresia. Such physiologic correction
is usually performed in patients older than 2 years. As stated
previously, most tricuspid atresia patients manifest symptoms
in the neonatal period and should be effectively palliated to
enable them to reach the age at which surgical correction could
be undertaken. The objective of any management plan, apart
from providing symptomatic relief and increased survival rate,
should be to preserve, protect and restore anatomy (good-sized
and undistorted pulmonary arteries) and physiology (normal
pulmonary artery pressure and preserved left ventricular
function) to normal such that a corrective procedure could be
performed at an appropriate age. Keeping the above objective
in mind the management plan may be discussed under the
following headings:
1. Medical management at the time of initial presentation
2. Palliative treatment of specific physiologic abnormalities
3. Medical management following palliative surgery
4. Historical aspects of physiologically corrective surgery
5. Physiologically corrective surgery
6. Follow-up after corrective operation.
Medical Management at the Time of Initial Presentation
406
The need for prompt identification and rapid transfer of a

cyanotic/distressed neonate with suspected serious heart disease
to a regional pediatric cardiology center is well-recognized.
During the process of identification, transfer to a pediatric

cardiology center, initial work-up and palliative surgery as
well as following surgery, neutral thermal environment, normal
acid-base status, normoglycemia, and normocalcemia should
be maintained by appropriate monitoring and correction, if
needed.77 No more than 0.4 FiO2 is necessary unless pulmonary
parenchymal disease is present.
Infants with low arterial PO2 and decreased oxygen
saturation may be ductal dependent and therefore, the
ductus should be kept open by intravenous administration of
prostaglandin E1(PGE1).78 The ductal dilating effect of this
drug results in an increase in pulmonary blood flow, thereby
improving oxygenation and reversing the metabolic acidosis
so that further diagnostic studies and surgical intervention can
be performed with relative safety. Current recommendations
are for intravenous infusion of PGE1 at a dose of 0.05 to
0.1 g per kilogram of body weight per minute. I usually
begin with a dose of 0.05 g/kg/min and reduce the rate of
infusion, provided the desired oxygen saturation levels are
achieved; this has been most helpful in reducing the incidence
and severity of some of the drugs bothersome side effects,
namely, apnea and hyperpyrexia. PGE1 infusion rate may be
increased, if there is no increase in PO2.
The occasional infant that presents with signs of congestive
heart failure (more common in type II patients) should be
treated with routine anticongestive measures.79 Patients with
associated severe coarctation of the aorta may also be helped
with PGE1 infusion; this time the ductal dilation improves
systemic perfusion. This should be followed by surgical relief
of coarctation. Alternatively, balloon angioplasty may be
utilized to relieve the aortic obstruction.80-82
Palliative Treatment of Specific Physiologic

Abnormalities
The palliation of patients with tricuspid atresia would largely
depend upon the hemodynamic abnormality produced by the
basic lesion and associated cardiac defects. These may be
broadly grouped42,79 into:
1. Decreased pulmonary blood flow
2. Increased pulmonary blood flow
3. Intracardiac obstruction.

Since, the description of subclavian artery-to-ipsilateral
pulmonary artery anastomosis in 1945 by Blalock and
Taussig,83 several other types of operations have been devised
to improve the pulmonary aorta flow. These include other
types of systemic-pulmonary artery shunts; namely, the
Potts anastomosis (descending aorta-to-left pulmonary artery
shunt), Waterston-Cooley shunt (ascending aorta-to-right
pulmonary artery anastomosis) and aorta-to-pulmonary artery
Gore-Tex shunt; superior vena cava-to-right pulmonary artery
Increased Pulmonary Blood Flow

Infants with a modest increase in pulmonary blood flow do
not have any significant symptomatology and indeed are less
cyanotic than the pulmonary oligemic patients. Markedly
increased pulmonary blood flow, however, can produce
congestive heart failure. Only type Ic and Type IIc patients,
i.e. without associated pulmonary stenosis, will fall into the
category of pulmonary plethora. A majority of these patients
will have type II anatomy and will usually manifest during
early infancy.
In type I patients, aggressive anticongestive measures
should be promptly instituted. The natural history of the
VSD has been well documented in this group;31-38 the VSD
becomes smaller and patients with pulmonary plethora will, in
due course, develop pulmonary oligemia, requiring palliative
surgical shunts. These patients can also develop right
ventricular outflow tract obstruction with resultant decrease
in pulmonary blood flow. Therefore, it is recommended that

pulmonary artery banding not be performed in this group of
patients. Among our 40 consecutive patients with tricuspid
atresia,38,42 only two with type I anatomy required pulmonary
artery banding and there are only a few cases reported in the
literature that required pulmonary artery banding. If optimal
anticongestive therapy with some time delay does not produce
adequate relief of symptoms,42 pulmonary artery banding
should be considered in type I patients; perhaps a serious
consideration for using absorbable band material should be
given.89-91 In those that did not have pulmonary artery banding
performed, careful follow-up studies with measurement
of pulmonary artery pressure and appropriate treatment are
necessary to prevent pulmonary vascular obstructive disease.
In type II patients, banding of the pulmonary artery should
be performed once the infant is stabilized with anticongestive
therapy. If there is associated coarctation of the aorta or aortic
arch interruption or hypoplasia, adequate relief of the aortic
obstruction should be provided concurrent with pulmonary
artery banding and the patent ductus arteriosus should be
ligated, if present. The importance of PGE1 administration
in temporarily relieving aortic obstruction and thereby
controling congestive heart failure has already been alluded.
The role of balloon dilation angioplasty of the coarctation80-82
in these complicated lesions has not yet been completely
delineated. Because of higher risk for poor outcome in patients
with transposition and those requiring pulmonary artery
banding and/or aortic arch repair, early, adequate appropriate
intervention is desirable.
28
Tricuspid Atresia
anastomosis (Glenn Procedure); formalin infiltration of the

ductal wall; stenting the ductus arteriosus and enlarging the
VSD. Systemic-pulmonary artery shunts are most commonly
used in the palliation of pulmonary oligemia. Because of the
problems associated with central shunts, Blalock-Taussig
type of shunt is preferred. At present, a modified BlalockTaussig shunt with a Gore-Tex graft interposed between
the subclavian artery and the ipsilateral pulmonary artery,
described by deLeval84 appears to be the preferred choice in
most institutions for palliation of the neonate and young infant
with pulmonary oligemia.
Enlargement of VSD and/or resection of right
ventricular outflow tract obstruction has been performed,
and recommended by Annecchino and his colleagues85 as
a palliative procedure to augment the pulmonary blood
flow. This is an ingenious approach and attacks the site of
obstruction rather than bypassing it. However, it is an open
heart procedure and may not be feasible or necessary in the
neonatal period.42 Placement of a stent in the ductus, to keep
it open to provide pulmonary flow is an attractive option,86,87
but, because of limited experience and technically demanding
nature of the procedure, it currently is not a therapeutic
procedure of choice. If the predominant obstruction is at the
pulmonary valve level, balloon pulmonary valvuloplasty88
may be considered.
In conclusion, despite the availability of many types of
palliative procedures to increase pulmonary blood flow, most
of them are either not advisable or effective and if effective,
may produce serious complications to deter from performing a
successful Fontan-Kreutzer procedure subsequently. Modified
Blalock-Taussig anastomosis84 has the least number of longterm complications, but at the same time, preserves suitable
anatomy for subsequent corrective procedures. Therefore, it
is recommended as the procedure of choice for palliation of
tricuspid atresia patients with decreased pulmonary blood flow.
Intracardiac Obstruction
Intracardiac obstruction can occur at two different levels,
namely, patent foramen ovale and VSD.
Interatrial obstruction: Since the entire systemic venous
return must egress through the patent foramen ovale, it should
be of adequate size to accommodate it. A mean atrial pressure
difference of 5 mm Hg or more with very prominent a waves
(15 to 20 mm Hg) in the right atrium is generally considered
to represent obstructed interatrial septum.9,46 Balloon atrial
septostomy,92,93 if unsuccessful blade atrial septostomy,93-95
and rarely surgical atrial septostomy may be necessary to
relieve the obstruction. Significant interatrial obstruction
requiring atrial septostomy in the neonate is rare and unusual
although this can be a significant problem later in infancy.42,92
Interventricular obstruction: Spontaneous closure of the
VSD causing severe pulmonary oligemia in type I patients
and subaortic obstruction in type II patients can occur;31-39
this usually takes months to years to develop. Management
of spontaneous closure of the VSD causing severe pulmonary
oligemia in type I patients is as alluded to in the preceding
section on pulmonary oligemia. Partial spontaneous closure of
the VSD in type II patients causes subaortic obstruction,33,34,38
which should be relieved or bypassed lest the resultant left
407
ventricular hypertrophy pose increased risk at the time of

the Fontan procedure.96 The obstruction must be tackled at
the time of either a bidirectional Glenn or a modified Fontan
operation. Resection of the conal muscular septum,97,98 thus
enlarging the VSD, is a direct approach, although concern
for development of heart block and spontaneous closure of
the surgically produced VSD remains.38 Alternatively, the
VSD, right ventricle and aortic valve may be bypassed by
anastomosis of the proximal stump of the divided pulmonary
artery to the ascending aorta (Damus-Kaye-Stansel) at the
time of bidirectional Glenn (or Fontan) operation. For further
discussion of this subject, the reader is referred elsewhere.33,34,38
Medical Management Following Palliative Surgery

Problems encountered with tricuspid atresia patients are similar
to those found in other types of cyanotic cardiac malformations.
Appropriate monitoring for and treatment of relative anemia,
polycythemia, coagulopathy and hyperuricemia should be
undertaken. The risks for development of a cerebrovascular
accident or brain abscess are similar to those seen with
other cyanotic anomalies. Antibiotic prophylaxis before any
bacteremia producing procedures or surgery is indicated, as
is routine immunization plus consideration for Palivizumab
(for prevention of RSV infection in infancy), polyvalent
pneumococcal vaccine or influenza vaccine.
Historical Aspects of Corrective Surgery

for Tricuspid Atresia
408
Fontan72 and Kreutzer73 concurrently described physiologi

cally corrective operations for tricuspid atresia in 1971.
Fontan operation, as described by Fontan consisted of
superior vena cavaright pulmonary artery shunt (classical
Glenn), anastomosis of the proximal end of the divided right
pulmonary artery to the right atrium directly or by means of
an aortic homograft, closure of the atrial defect, insertion of a
pulmonary valve homograft into the inferior vena caval orifice
and ligation of the main pulmonary artery, thus bypassing
the right ventricle completely;72 it would appear that Fontan
concept was to use the right atrium as a pump. Kreutzers
operation consisted of direct anastomosis of the right atrial
appendage with the pulmonary artery or through a pulmonary
homograft and closure of the atrial septal defect.73 He did not
perform a Glenn procedure nor insert a prosthetic valve into
the inferior vena cava. It appears that Kreutzers concept was
that the right atrium may not function as a pump and that the
left ventricle is the only suction pump in the system. Many
modifications of these procedures have been suggested, as
reviewed elsewhere by us.75,76 Based on these reviews it
would appear that direct atriopulmonary anastomosis (without
a valved conduit) became the standard procedure for most
tricuspid atresia patients. Over a period of time, a number
of other concepts/procedures evolved and these include total
cavopulmonary diversion,74 bidirectional Glenn,99 intra-atrial

tunnel74 and extracardiac conduit100 to divert the inferior vena
caval blood into the pulmonary artery, staged Fontan101,102
and fenestrated Fontan.103-105
Physiologically Corrective Surgery

Operations that divide the pulmonary and systemic venous
returns (Fontan-Kreutzer) are feasible for most patients
with tricuspid atresia. Hydrodynamic studies by de Leval
and colleagues74 concluded that the right atrium has no
efficient pump function; pulsations in non-valved circulation
generate turbulence with consequent decrease in net flow and
energy losses occur in the non-pulsatile chambers, corners
and obstructions. To address this issue, they proposed total
cavopulmonary anastomosis. The advantages of this procedure
are technical simplicity, maintenance of low right atrial and
coronary sinus pressure and reduction in risk of formation of
atrial thrombi and perhaps reduction in arrhythmias.
In the bidirectional Glenn procedure, the upper end of the
divided superior vena cava is anastomosed end to side to the
superior aspect of the undivided right pulmonary artery, thus
diverting the superior vena caval blood into both right and
left pulmonary arteries. Hemodynamic advantages associated
with the bidirectional Glenn include, improved effective
pulmonary flow, reduced total pulmonary flow and less left
ventricular volume overloading.
Staging the Fontan appears to decrease overall mortality,
presumably related to improving the ventricular function
by correcting afterload mismatch associated with one stage
Fontan. At the present time, staged Fontan with bidirectional
Glenn initially followed later by extracardiac conduit
diversion of the inferior vena caval blood into the pulmonary
artery appears to be the preferred approach.
As mentioned, currently preferred corrective procedure
is staged total cavopulmonary anastomosis. A bidirectional
Glenn procedure (superior vena cava to pulmonary artery
anastomosis) may be performed around the age of 6 months.
Preoperative catheter evaluation to define the pulmonary
artery pressure and anatomy and to exclude a persistent left
superior vena cava (because it may divert blood away from
the pulmonary arteries) prior to bidirectional Glenn surgery
should be undertaken. At the time of bidirectional Glenn
procedure, stenoses, if any of the pulmonary artery should
be repaired. Issues related to subaortic obstruction and mitral
valve regurgitation should also be addressed.
When the patient reaches the age and size (approximately
15 kg) suitable for Fontan-Kreutzer operation, diversion of
inferior vena caval blood into the pulmonary artery either
by a lateral tunnel or extracardiac conduit is recommended.
At the present time extracardiac conduit diversion of inferior
vena caval blood into the pulmonary artery is preferred by
most surgeons. Immediately prior to Fontan conversion,
cardiac catheterization should be undertaken to ensure normal
Follow-up after Corrective Operation

Close follow-up after correction is indicated. Some patients
may need inotropic and diuretic therapy. Afterload reduction
with an angiotensin-converting enzyme inhibitor is used by
some cardiologists to improve left ventricular output. Because
of the potential for development of thrombi in the right atrium,
anticoagulants are routinely used by most cardiologists.
I recommend platelet-inhibiting doses of Aspirin, others
advocate Warfarin anticoagulation.
Most patients do well after operation.107 However, some
problems have been seen after corrective surgery namely,
arrhythmia, obstructed pulmonary outflow pathways,
persistent shunts and systemic venous congestion including
protein-losing enteropathy.
Supraventricular arrhythmias (atrial flutter or fibrillation,
paroxysmal supraventricular tachycardia) may be seen,
particularly with older types of Fontan operation. They may
be treated with appropriate pharmacologic therapy. In a

patient without adequate control, electrophysiologic study and
surgical or transcatheter ablation may be needed.108 Revision
of the Fontan pathway to a cavopulmonary connection with
elimination of the enlarged right atrium has been considered
an alternative solution. Sick sinus node syndrome and
atrioventricular block occur in some children and may require
pacemaker therapy. Ventricular arrhythmia is less frequent.
Symptoms and signs indicative of obstruction to Fontan
pathways should be promptly investigated. Poor echo windows
make non-invasive evaluation difficult and cineangiography
or imaging studies (CT or MRI) may become necessary.
Obstructive lesions should be treated with balloon angioplasty,
stenting or even surgery, as necessary.
A persistent shunt may be due to intentional fenestration
created at the time of Fontan or a residual atrial septal
defect. If significant hypoxemia is present, the residual shunt
should be closed, preferably by a transcatheter device.109,110
Test occlusion109 of the defect to ensure that adequate
cardiac output will be maintained after defect occlusion is
recommended. Closing the defect has beneficial effect in
preventing paradoxical embolism and stroke.
Recurrent pleural effusion, liver dysfunction and proteinlosing enteropathy have occurred in a small number of
patients. Protein-losing enteropathy carries a high (75%)
mortality.110,111 The cause of protein-losing enteropathy is not
well-understood, but appears to be related to loss of protein
in the bowel by lymphatic distention secondary to increased
systemic venous pressure, although this can occur in patients
with reasonably normal pressures for the Fontan procedure.
Symptoms usually appear 6 months following the FontanKreutzer procedure or later. They manifest diarrhea, edema,
ascites and pleural effusion. Serum hypoalbuminemia and
increased 1-antitrypsin in the stool are present. One should
carefully scrutinize for evidence of obstruction in the FontanKreutzer pathway. If such is found it should be relieved.112
Supportive therapy with medium-chain triglyceride diet
and parenteral albumin supplementation may be instituted.
A number of treatment regimens including prednisone,
regular high-molecular-weight heparin, low-molecular-weight
heparin, elementary diet, calcium replacement, somatostatin,
high-dose spironolactone, sildenafil and resection of localized
intestinal lymphangectasia (if demonstrated) have been
attempted, all with variable success.112 Since protein-losing
enteropathy appears to be a fatal complication of the Fontan
procedure, aggressive management is suggested. Apart from
excluding and addressing obstructions and residual shunts in
the Fontan circuit plus other conventional treatment options,
consideration for:
1. Reduction of right atrial pressure by creation of an atrial
septal defect (Brockenbrough puncture plus static dilation
of the atrial septum)
2. Right atrial and left ventricular (atrioventricular sequential)
pacing,113,114
28
Tricuspid Atresia
anatomy and pressure of the pulmonary artery as well as

normal left ventricular end-diastolic pressure. At the same
time, aortopulmonary collaterals should be evaluated by
means of selective subclavian artery and descending thoracic
aortic angiography. If collateral vessels are present, they
should be occluded with coils or devices, as appropriate.
The criteria outlined by Choussat and associates106 have
been modified or exceeded by many groups of workers.
These factors, when present, would make the Fontan-Kreutzer
operation a high-risk procedure and should be identified at
the time of preoperative evaluation. They include elevated
pulmonary artery pressure (mean pressure >18 mm Hg) or
resistance (> 4 Wood units/m2), distorted or small (McGoon
ratio of 1.8 or less) pulmonary arteries, poor left ventricular
function (end-diastolic pressure above 12 mm Hg), significant
mitral regurgitation, subaortic obstruction and severe left
ventricular hypertrophy. With one or more of these risk factors,
physiologically corrective procedures of the Fontan type may
carry significant risk. In such high-risk Fontan-Kreutzer patients,
leaving open a small atrial septal defect to allow decompression
of the right atrium in the immediate postoperative period with a
plan to close the defect later has been proposed.103-105 The atrial
defect is closed by a preplaced suture103,104 or by transcatheter
techniques.105 Significant improvement in postoperative pleural
effusions, systemic venous congestion and higher cardiac index
and possibly shorter hospitalization have been the beneficial
effects of the fenestration, but at the expense of systemic arterial
hypoxemia. However, some surgeons prefer fenestration for all
patients. Six to twelve months later, transcatheter closure of
the fenestration may be undertaken if the fenestration did not
spontaneously close.
In patients with transposition of the great arteries, early
pulmonary artery banding, treatment of aortic coarctation,
and relieving or bypassing subaortic obstruction should also
be incorporated into the treatment plan.
409
3. Conversion of atrioventricular Fontan to total

cavopulmonary anastomosis,115,116 and/or
4. Cardiac transplantation117,118 should be given. However,
most patients do well after the Fontan-Kreutzer procedure.
PROGNOSIS
Untreated the prognosis of live born infants with tricuspid
atresia is poor; only 10 to 20 percent may survive their first
birthday.9,119 Palliative surgery to normalize the pulmonary
blood flow has markedly improved the survival rate. But, as
one can see from survival data from several large studies,51,120
there is still considerable early mortality. Because of recent
improvement in surgical mortality for the palliative surgery and
advances in neonatal care, the initial mortality should decrease.
Introduction of physiologically corrective surgery in the
early 1970s has, to some degree, improved the second bout of
mortality seen in children beyond 15 years of age. Because of
this improved prognosis, each neonate with tricuspid atresia
should be offered aggressive medical and surgical therapy.121
CONCLUSION
Tricuspid atresia is the third most common cyanotic
congenital heart defect. There are significant variations in
the morphology of the atretic tricuspid valve, the associated
cardiac defects and physiology, resulting in different clinical
presentations. The diagnosis is relatively simple and can often
be made on clinical features and simple laboratory studies
(chest roentgenogram and electrocardiogram), which can be
confirmed by echocardiography and if necessary by cardiac
catheterization and selective cineangiography. Aggressive
management to normalize the pulmonary blood flow and
correct physiologically important associated defects (e.g.
coarctation of the aorta) should be undertaken at the time of
presentation. Follow-up and treatment plans should strive
to maintain or normalize cardiac structures and function
(pulmonary artery anatomy and pressure and left ventricular
function). Finally, performing staged Fontan-Kreutzer surgery
prior to deterioration of the left ventricular function should
markedly improve the prognosis for tricuspid atresia patients.
He is the best physician who is the most ingenious inspirer
of hope.
Samuel Taylor Coleridge
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28
Tricuspid Atresia
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413
C hapter
29
Diseases of the Tricuspid Valve

INTRODUCTION
In this chapter, abnormalities of the morphologic tricuspid
valve, namely Ebstein malformation of the tricuspid valve,
Ebstein anomaly of the left-sided atrioventricular valve
in corrected transposition, tricuspid stenosis and tricuspid
regurgitation will be discussed; tricuspid atresia was discussed
in Chapter 28.
EbsTEIN MALFORMATION OF THE TRICUsPID VALVE

Ebstein anomaly of the tricuspid valve is a congenital
malformation, in which there is downward (apical)
displacement of insertion of septal and posterior leaflets.
Anterior leaflet is not usually affected. In addition, the
tricuspid valve leaflets are dysplastic. As a result of the
displacement, there is poor coaptation of the valve leaflets
leading to tricuspid regurgitation, which in turn causes right
atrial enlargement of a variable degree depending upon the
degree of tricuspid regurgitation.
No single gene defect has been consistently identified

with Ebstein anomaly. Ebstein anomaly appears to be
genetically heterogeneous and several candidate genes have
been suggested including GATA4, NKX2.5 and hypothetical
genes in 1p36.11 Mutations of sarcomere protein gene MYH7
has been proposed in a small group of patients with Ebstein
anomaly and left ventricular non-compaction.12 There is a
single case report suggesting association of Ebstein anomaly
with Williams syndrome.13
There is a higher incidence for recurrence in the offspring
of women (6%) than that seen the offspring of men (0.6%).14
Pathology
This anomaly, now called Ebstein, was first described by

Wilhelm Ebstein in 1866 in an autopsy of a 19-year-old laborer
who had cyanosis and dyspnea since early childhood.1 The very
first reported case in a live patient was in 1949 by Tourniaire
et al.2 Advent of two-dimensional echocardiography has led to
increasing recognition of this anomaly, including milder cases.
There are several anatomic components of Ebstein anomaly,15

namely:
1. Displacement of the septal and posterior leaflets towards
apex of the right ventricle (RV).
2. Anterior leaflet is usually attached at the annular level
and is large and sail-like with multiple attachments to
ventricular wall.
3. The portion of RV that is proximal to the level of the
displaced septal and posterior leaflets is called the
atrialized RV and is usually thin and dysplastic.
4. RV cavity beyond the attachment of the septal and posterior
leaflets is the functional RV and is smaller, lacks inlet
portion and has a small trabecular portion.
5. Infundibular portion of RV is sometimes obstructed by
redundant anterior leaflet or its chordal attachments.
Epidemiology
Valve Leaflets and Valve Orifice
Ebstein anomaly accounts for 0.3 to 0.6 percent of all congenital

heart defects.3,4 No gender predominance is noted. The majority
of cases are sporadic. Exposure to lithium during pregnancy
has been reported as an etiologic factor.5-7 However, some
recent studies have challenged Lithium as etiologic factor.8-10
Septal and posterior leaflets are adherent to RV and septal

myocardium and become free from myocardium at a lower
level than the annulus of the tricuspid valve. Extent of this
displacement varies among patients leading to variation in the
severity of clinical manifestations.
Historical Aspects
Right Atrium
The right atrium (RA) is dilated and hypertrophied. Severity
of hypertrophy and enlargement of RA is proportional to the
degree of displacement of the tricuspid valve leaflets and
resultant tricuspid regurgitation. Massive enlargement of right
atrium is common.
Right Ventricle
In mild and moderate cases, the RV cavity size is normal
with some degree of RV hypertrophy. However, in more
severe cases, the right ventricular myocardium may be quite
abnormal with variable thickness ranging from near-normal
thickness to very thin and dysplastic, similar to that seen with
Uhls anomaly.21,22
Conduction System
Supraventricular tachycardia is seen in association with
Ebsteins anomaly and may be related to accessory conduction
pathways simulating Wolf-Parkinson-White (WPW) syndrome.
Anomalies of the right bundle branch have been reported,
which may explain right bundle branch block pattern seen in
the electrocardiogram (ECG). The area of triangle of Koch is
much smaller in Ebstein anomaly hearts than in normal hearts.
While AV node and its extensions are normal in size, they are
displaced towards the base of Koch triangle and his bundle
penetrates well short of the apex of Koch triangle than normal.
Practical implication of this anatomy is that during treatment of
supraventricular arrhythmias with ablation at the base of Koch
triangle may result in higher incidence of AV block in patients
with Ebstein anomaly than in normal hearts.23,24
Associated Lesions
In most cases, either a patent foramen ovale (PFO) or an atrial
septal defect (ASD) is present. Other associated anomalies are
rare and include pulmonary stenosis (PS), pulmonary atresia,

ventricular septal defect (VSD), patent ductus arteriosus
(PDA), tetralogy of Fallot (TOF), double out let right ventricle
(DORV), right aortic arch, coarctation of aorta, transposition
of the great arteries (TGA) and mitral valve prolapse or
stenosis, non-compaction of left ventricle (LV) or RV25 and
absent pulmonary valve syndrome among others. A VSD may
be present either between LV and atrialized portion of RV
(Gerbode defect) 26 or between LV and functional RV.
Classification
Some authors27 classify Ebsteins anomaly as simple and
complex. Ebstein anomaly may be called simple when it is
not associated with other anomalies and complex when other
significant defects coexist.
However, surgical classification15 of Ebstein anomaly
categorizes it into four types (Carpentier types):
Type A: Mild displacement of proximal attachments of
septal and posterior leaflets. The volume of functional RV is
adequate.
Type B: Atrialized portion of RV is large, but anterior leaflet
is freely mobile
Type C: Anterior leaflet mobility is limited, right ventricular
out-flow tract (RVOT) is severely obstructed.
Type D: Almost complete atrialization of RV except for a
small infundibular portion. A fenestration in the commissure
between anterior and septal leaflets is the only communication
between atrialized RV and the infundibulum.
29
Diseases of the tricuspiD ValVe
There is redundancy and dysplasia of the leaflets as well.

Nodular appearance of the free edge of the leaflets is present.
Anterior leaflet of the tricuspid valve is usually large and saillike. This leaflet may have one or more holes in it leading to
additional tricuspid regurgitation.
Due to the displacement of the septal and posterior leaflets,
a portion of the right ventricular myocardium and ventricular
septum are atrialized. This portion is between the true
annulus and the false insertion point of septal and posterior
leaflets.
Tricuspid valve orifice is usually adequate. Rarely, there
may be concomitant tricuspid stenosis16 or even atresia.17
There may also be multiple orifices in tricuspid valve.
Redundancy of tricuspid valve tissue may encroach RV
outflow tract and cause sub pulmonary stenosis.18-20
Pathophysiology
Hemodynamic abnormalities are dictated by severity of the
lesion;28 main determinants are the degree of displacement of
the tricuspid valve and the degree of tricuspid regurgitation.
In patients with mild Ebstein tricuspid valve function is
close to normal. In moderate to severe forms, with each atrial
contraction, the blood is propelled into the atrialized RV.
With ventricular contraction that follows, the blood is forced
back into the right atrium. This is even more pronounced in
children with significant tricuspid regurgitation. With the next
atrial contraction, this blood is forced back into the atrialized
RV. This back and forth blood flow, the so called ping-pong
effect,29 causes right atrial dilatation and increases right atrial
pressure; the latter results in right to left shunt across ASD/
PFO. This shunt results in arterial desaturation and pulmonary
oligemia.
Newborn babies with severe Ebstein anomaly are cyanotic
secondary to right to left shunt across the atrial septum as
detailed above. This is further accentuated by the usual high
pulmonary vascular resistance that exists at this age.
Significant tricuspid regurgitation causes severe right atrial
enlargement in utero as well as after birth. Since significant
portion of RV may be atrialized in severe cases, there may be
415
congenital ValVular lesions
inadequate RV myocardium to generate high enough pressure

to achieve forward flow via the pulmonary valve. This is
compounded by high pulmonary vascular resistance and PDA
leading to inability of the pulmonary valve leaflets to open.
This leads to functional pulmonary atresia. In such patients,
pulmonary valve may open after the pulmonary vascular
resistance decreases either as natural course or by medical
treatment.
Right to left shunting at atrial septal level, leading to
cyanosis in the newborn, may resolve as the pulmonary
vascular resistance (PVR) decreases along with establishment
of forward flow via the pulmonary valve. Degree to which
such resolution occurs depends on the severity of the defect.
Cyanosis may return in later childhood or adolescence when
tricuspid valve function deteriorates (causing regurgitation).
This clinical course is described in the old literature as
transient or intermittent cyanosis.
Wide spectrum of pathophysiology, as noted above, allows for
differing presentations, which are dependent upon severity of
each component of lesion and associated lesions. Mild cases
may not be detected until adulthood. Mildest cases are detected
serendipitously during an echocardiogram performed for an
unrelated reason. Most severe forms present during neonatal
period.
Fetus
In fetus, Ebstein anomaly may present as cardiomegaly,
tricuspid regurgitation, with right atrial enlargement on fetal
echocardiography, arrhythmia or heart failure with hydrops.
Fetal presentation is associated with high incidence of fetal
loss.30
Neonates and Infants
416
Infants with milder forms are largely asymptomatic. However,

infants with severe forms become symptomatic and have
severe cardiomegaly and may have associated lung hypoplasia.
There is no forward flow due to ineffective RV and inability to
overcome the high PVR that exists in the early neonatal period.
There will be a functional/physiological pulmonary atresia. It
may be difficult to differentiate it from anatomic pulmonary
atresia that may also coexist with Ebstein anomaly. Therefore,
pulmonary blood flow is dependent on ductal patency.
Systemic venous return from the right atrium needs PFO
or ASD for egress. This causes significant cyanosis in the
newborn. If the PFO is restrictive, right atrial hypertension
and systemic venous congestion occur. If ductus arteriosus is
inadequate, there will be poor oxygenation from diminished
blood flow and inadequate cardiac output due to poor
pulmonary venous return coupled with small shunt via the
PFO. This leads to severe cyanosis and severe metabolic

acidosis in the newborn.
Cyanosis is noted in approximately 50 percent of the
newborn.3,31 In infants beyond the neonatal period, cyanosis is
also a common presentation. Murmur and heart failure features
are less common presenting features. Incidental finding of
cardiomegaly in a chest X-ray performed for another purpose
is another mode of presentation. Supraventricular tachycardia
may also be a presenting feature.
Children, Adolescents and Adults

They are largely asymptomatic and may be detected by a
cardiac murmur or by echocardiogram performed for an
unrelated problem. Infants with moderate to severe forms,
who improved after normalization of pulmonary pressures,
may become symptomatic as the tricuspid valve and right
ventricular function deteriorates. Easy fatigability, cyanosis
or arrhythmia may be presenting symptoms.
Celermajer et al32 reviewed 220 cases with Ebstein anomaly
and found that most common presenting symptom varied with
ageprenatal scans for fetuses is 86 percent, cyanosis for
neonates is 74 percent, heart failure for infants is 43 percent,
incidental murmur for children is 63 percent and arrhythmia
for adolescents and adults is 42 percent. Early presentations
were associated with RV outflow tract obstruction.
Flores Arizmendi and associates33 followed 52 patients
from the time of diagnosis (ranging from fetal life to
adulthood) to a mean of 16.7 years. 24 patients presented
during newborn period and eleven (46%) of these patients
died. Actuarial survival for the entire group at 30 years was
65 percent. Twenty-seven (66%) of the 41 survivors had
arrhythmias and 25 of the 27 were receiving medications for
arrhythmia. Nine patients have had surgery. Celermajer index
of three or four (See under Fetal and Neonatal Diagnosis
section) and CT ratio more than 65 percent were found to be
predictive of death.33
Arrhythmia
Supraventricular tachycardia (SVT) is common; this may
be secondary to accessory pathways or atrioventricular reentry. Atrial arrhythmias such as atrial flutter or fibrillation
may also be present. Accessory atrioventricular pathways are
present in 20 percent of patients with Ebstein anomaly; nearly
all of them are right-sided pathways. About half of these
patients have multiple accessory pathways.34 The accessory
pathways are usually located in the inferior portion of the
tricuspid valve annulusmost commonly posteroseptal and
posterolateral pathways.35 Due to slow conduction properties
of the accessory pathways that are located in the atrialized
portion of the RV, the conduction goes through AV node more
often and therefore, most of these accessory pathways do
manifest in sinus rhythm.
Investigations
Chest X-ray
In a newborn with mild form of Ebstein anomaly, there may
be no cyanosis, but may have multiple cardiac sounds (third,
fourth and or both), described as triple or quadruple rhythm.29
No significant murmur is heard. In moderate Ebstein anomaly,
there may be cyanosis with no significant respiratory distress.
The vital signs and peripheral pulses are normal. The
precordium is quiet and no other significant abnormality.
In severe cases, hyperdynamic precordium and a thrill at
the left lower sternal border may be present. Distension of
neck veins with a prominent V wave may be seen. Liver
enlargement may be present. The first heart sound is usually
normal. The second heart sound may be widely split or normal.
Third, fourth and/or both are common leading to appreciation
of multiple heart sounds. A holosystolic murmur of tricuspid

regurgitation is present especially when pulmonary artery
pressures are high. Careful auscultation may reveal a lowfrequency mid-diastolic murmur signifying either increased
forward flow through an adequate sized tricuspid orifice or
through tricuspid stenosis.
In children with milder forms the only abnormality is
multiple cardiac sounds. Precyanotic rubra may be present. In
moderate to severe Ebstein, cyanosis, multiple cardiac sounds
and holosystolic murmur of tricuspid regurgitation at the left
lower sternal border may be present.
29
In a multicenter study of pediatric patients with Ebstein

anomaly in Netherlands,36 there was 17 percent incidence
of arrhythmias (16 of 93 patients). Nine of them developed
arrhythmias in the newborn period. One neonate died at 6
days of age from intractable SVT associated with heart failure
and cyanosis. Another neonate is suspected to have had
arrhythmic death at 4 weeks of age. All 14 survivors exhibited
pre-excitation in the electrocardiogram (EKG), although four
of them exhibited pre-excitation only intermittently. The
incidence of arrhythmia in pediatric patients with Ebstein
anomaly is much lower than that in adults. In adults, additional
atrial arrhythmias due to long-standing tricuspid regurgitation
and right atrial dilatation adds atrial flutter or fibrillation to the
complement of arrhythmias.
Severe cardiomegaly is the rule in Ebstein anomaly

(Figures 1A and B). Increase in cardio-thoracic ratio is mostly
due to right atrial enlargement. Lung fields are either normal
or oligemic. Cardiomegaly in milder cases is commensurate
with the severity of tricuspid regurgitation.
Electrocardiogram
Right atrial enlargement, low QRS voltages and right bundle
branch block (RBBB) are typical findings in Ebstein anomaly
(Figure 2). Right axis deviation is usual. Rarely, left axis
deviation may be noted.31,37,38 Prolongation of PR interval
is noted in two-third of the nenonates.31,39 Features of WPW
syndrome with short PR interval are reported with higher
figures 1a and B: Panel A. Chest X-ray of a newborn with severe Ebstein anomaly of the tricuspid valve showing severe cardiomegaly, typical
for this lesion with right atrial enlargement, representing most of the enlargement of cardiac silhouette; Panel B. Chest X-ray of a 4-year-old child
with milder form of Ebstein anomaly
417
figure 2: Electrocardiogram of a newborn with Ebstein anomaly. Note the tall P waves representing right atrial enlargement
frequency (30%) in Ebstein anomaly while a few (12%) have

evidence of pre-excitation with normal PR interval.40
Echocardiography
The diagnosis is established by echocardiographic studies
and they provide necessary information for assessment of
severity and prognosis. Technological advances have made
echocardiography the main modality of diagnosis for Ebstein
anomaly. Morphologic correlates of Ebstein anomaly have
been well described in literature41-44 and well-reviewed in
textbooks.45
Objectives of echocardiography are to evaluate the degree
of dysplasia and displacement of tricuspid valve leaflets
from the true annulus (which in turn influence the degree of
tricuspid valve regurgitation), RV size and RV function.
Evaluation of Tricuspid Valve and its Attachments
418
1. Degree of inferior displacement of the tricuspid valve

(TV) leaflets. The hinge points of the septal and posterior
leaflets are usually displaced downward towards the
apex. Anterior leaflet usually is not displaced. Apical four
chamber view (Figures 3A and B) is the best to estimate the
displacement. Mitral valve annulus serves as a reference
to quantitate the degree of displacement. Severity of
Ebstein anomaly varies with the degree of displacement
of the septal leaflet. Moderate to severe displacements
are easy to detect. However, diagnosis of mild Ebstein

anomaly may be debatable since normal TV is displaced
slightly when compared with crux of the heart or mitral
valve annulus. In a study of 41 patients seen at Mayo clinic
(Minnesota) with mean age of 18 years, a displacement of
greater than or equal to 8 mm/m2 of body surface area
was established as a criterion to judge the displacement.41
However, in the opinion of the authors of this chapter,
this criterion alone will over-diagnose Ebstein anomaly
in the newborn whose usual body surface area is around
0.20 m2. TV displacement of 1.52 mm below the mitral
valve annulus or crux of the heart is not unusual in a
normal newborn. Presence of other features should also
be taken into account in this diagnosis rather than isolated
displacement of septal leaflets.
2. Dysplasia or absence of septal leaflet. Septal leaflet may
be dysplastic and/or fibrotic or absent. When the leaflet is
absent, it may be represented by remnants of tissue seen at
the mid-portion of the ventricular septum.
3. Subvalvar apparatus. Short chordae may attach the septal
leaflet to the ventricular septum. Sometimes, the chordae
may be absent with insertion of the leaflet directly to the
ventricular septum in apical four chamber view.
4. Anterior leaflet can be visualized in either apical four
chamber view or parasternal long axis view aimed towards
the right ventricular inflow. Anterior leaflet is usually
very large with sail-like mobility consisting of bulging
into RVOT during diastole and folding during systole.46
29
figures 3a and B: Apical four-chamber views of an echocardiogram of a newborn with mild to moderate form of Ebstein anomaly. Panel A shows
two-dimensional image demonstrating the insertion of septal leaflet of the tricuspid valve (arrow), which is displaced apically in comparison to the
insertion of mitral valve and atrialized right ventricle (aRV). Panel B shows color Doppler image showing moderate tricuspid valve regurgitation
(TR). LA = Left atrium; LV = Left ventricle; RA = Right atrium; RV = Right ventricle
Attachment of anterior leaflet is usually normal at the

level of TV annulus. There may be recesses in the anterior
leaflet adding to regurgitation via the commissure. There
may be attachments to the ventricular septumto the area
where remnant of septal leaflet are noted in the ventricular
septum; the attachments may lead to restriction of the
anterior leaflet mobility.
5. Attachment of posterior leaflet is best seen in subcostal
views and is assessed by using the crux of the heart for
comparison.
6. Distal attachments of valve leaflets, specifically of the
anterior leaflet, affects choice of surgical procedure and
therefore, need definition. This is best viewed in subcostal
view (Figure 4). The distal attachment is either a focal
attachment or tethering. Focal attachment is a normal
pattern, attaching to a papillary muscle. Tethering is said
to be present when there are three or more attachments of
the leaflets or leaflet is attached along a linear area at the
junction of inlet and trabecular portion of the right ventricle.
Tethering restricts mobility of the anterior leaflet and may
lead to obstruction of RV outflow. Degree of encroachment
of RVOT by anterior leaflets distal attachments can be
seen in subcostal views.
7. Occasionally, a tissue bridge forms connecting the leading
edges of septal and anterior leaflets turning the commissure
between septal and anterior leaflets into a key hole. In such
situation, if the anterior leaflet has a linear distal attachment
along the junction of inlet and trabecular portions of the
RV, the key hole become the only opening for forward flow
through tricuspid valve. This may lead to tricuspid stenosis
or even an imperforate TV if this closes completely.
figure 4: Subcostal coronal view of the chordal attachment of tricuspid

valve leaflets (unmarked arrow) in Ebstein anomaly. In this example
with Ebsteins anomaly, chordal attachment is normal. Valve true
annulus is shown with an arrow. The right atrium (RA), atrialized right
ventricle (aRV) are also shown. RV = Right ventricle; RVOT = Right
ventricular outflow tract
Evaluation of RA, RV and RVOT

1. Severe RA enlargement is usually seen in Ebstein
anomaly, especially in the presence of significant tricuspid
regurgitation. However, this may be minor in patients with
mild Ebstein anomaly with mild tricuspid regurgitation.
419
RV volume overload with paradoxical septal movement

is also seen. Apical four chamber view helps to measure
the sizes of the RA, atrialized RV and the functional distal
chamber of RV. Ratio of area of RA plus atrialized RV to
the combined area of functional, distal portion of RV, LV
and LA (Figure 5) has been used as a prognostic factor to
predict survival in newborn with Ebstein anomaly.47 (See
under Fetal and Neonatal Diagnosis section below).
figure 5: Apical four-chamber view showing all chambers of the heart

in end-diastole. Tracing on the image shows the two areas used to
obtain the ratio (Celermajer index) for prediction of outcome in fetal and
neonatal echocardiograms (see text for further details). Abbreviations
are same as those used in Figure 3
420
2. Certain degree of RV dysplasia may be present. This is

considered to exist if RV wall thickness is less than two
standard deviation (SD), size of RV is more than two SD or
there is dyskinesia of atrialized or the functional portion of
RV.43 Even though, the atrialized portion of RV bulges into
the LV outflow tract (Figures 6A and B), obstruction to LV
outflow tract rarely occurs to a clinically significant degree.
3. RV outflow tract obstruction may occur secondary to:
i. Attachment of anterior leaflet.
ii. Functional pulmonary valve atresia.
iii. True anatomic pulmonary valve atresia.
In a newborn, it may be extremely difficult to differentiate
functional from true pulmonary valve atresia. Functional
pulmonary atresia is said to exist if the pulmonary valve
leaflets are normally formed (not fused), but are unable
to open due to inability of the functional RV to generate
enough systolic pressure against the relatively elevated
pulmonary artery pressure. Pulmonary artery pressure in
a newborn may be elevated due to the normally elevated
neonatal pulmonary vascular resistance or due to presence
of a large PDA either naturally or from of prostaglandin
infusion (see Medical management section below).
Presence of any pulmonary regurgitation by color Doppler
imaging favors a functional pulmonary atresia. Ability to
pass a catheter across pulmonary valve should the baby
undergo a cardiac catheterization as newborn may help to
differentiate. However, inability to pass a catheter does not
always mean an anatomic pulmonary atresia. Occasionally,
only way to differentiate may be to wait until pulmonary
vascular resistance drops as the newborn transitions from
fetal circulation to postnatal circulation. There are reports
of inhaled nitric oxide therapy helping to differentiate this
as well.48
figures 6a and B: Apical five-chamber view of echocardiogram showing two-dimensional frame. A. With color Doppler; B. Showing the bulging
of the right ventricle (RV) into left ventricular outflow tract (LVOT). In this example, there is no significant obstruction; note laminar flow in the
LVOT and aorta (Ao). LA = Left atrium; LV = Left ventricle; RA = Right atrium
Three-dimensional Echocardiography
Cardiac CT or MRI
Computed tomography (CT) or magnetic resonance imaging
(MRI) are not usually necessary to define and evaluate
Ebsteins anomaly in newborn or children. In adults with poor
acoustic windows, transesophageal echocardiography (TEE)
and/or cardiac CT or MRI may be helpful in establishing and
completing the evaluation of Ebstein anomaly. RV function
and severity of Ebstein anomaly may also be evaluated.52,53
Cardiac catheterization is not usually necessary, but is
indicated for therapeutic purposes, when there is associated,
significant pulmonary stenosis. When catheterization is
29
Newer technology with three-dimensional imaging (transthoracic and/or transesophageal echocardiography) now enables
reconstruction of tricuspid valve and ability to visualize all
three leaflets of the tricuspid valve at the same time. Such
visualization helps with surgical planning.49,50
Three-dimensional echocardiography also has enhanced
the understanding and evaluation of tricuspid valve anatomy
prior to surgery. Using multiplanar three-dimensional
echocardiography, investigators in Southampton, United
Kingdom (UK)51 have shown that the valve orifice faces RV
outflow tract in Ebstein anomaly, while in tricuspid valve
dysplasia the valve orifice faces RV apex. Three-dimensional
echo also provides definition of degree of delamination of the
leaflets, subvalvar apparatus and dynamic morphology and
functional characteristics of tricuspid valve.51
performed, right to left shunting at atrial level may be present

by oximetry. Left to right shunting is unusual unless there
is VSD or PDA. Pressure traces have some characteristic
featuresRA pressure (mean) is usually elevated; a waves
are more prominent than v waves because of dissipation
of tricuspid regurgitation in a large, compliant right atrium.
Right ventricular pressure is low or normal. Low RV systolic
pressure is a poor prognostic sign-indicative of inability of
the RV to mount enough pressure to enable adequate forward
flow via pulmonary valve. High RV systolic pressure is
noted in the presence of VSD, PS or high PVR. RV enddiastolic pressure is usually elevated. Left sided pressures
(left atrium, left ventricle and aorta) are normal and have no
characteristic features in Ebstein anomaly.
Electrode catheter studies performed in the past29 for
diagnosis are no longer routinely performed because the
diagnosis can be made easily with echocardiography.
Selective right ventricular angiography (Figures 7A and
B) demonstrates displaced TV leaflets, degree of tricuspid
insufficiency and size and function of the RV as well as
pulmonary valve and pulmonary artery anatomy. Tricuspid
insufficiency during selective right ventricular angiography
and right atrial angiography (not necessary) produces a
trilobed heart representing, RA, atrialized portion of RV
and RV (Figure 8). The notch separating right atrium and
the atrialized portion of RV represents location of the true
tricuspid valve annulus and the second notch represents origin
of displaced tricuspid valve leaflets.29
Fetal and Neonatal Diagnosis and Prediction of Outcome

Features of Ebstein anomaly are likely to appear late in fetal life
(Figure 9), i.e. a fetus who had a normal fetal ultra sonogram
figures 7a and B: A. Right ventricular angiogram in posteroanterior view from an adolescent with Ebstein anomaly. Contrast was injected via
the venous catheter (C) in right ventricle (RV). Tricuspid valve regurgitation leads to opacification of an enlarged right atrium (RA). The true
tricuspid valve annulus (arrow) and attachment of the displaced tricuspid valve leaflets (arrows) are shown; B. In a subsequent cine frame,
atrialized RV (a RV) is shown. MPA = Main pulmonary artery
421
figure 8: Right ventricular (RV) angiogram in postero-anterior view

from a newborn with Ebstein anomaly. Severe tricuspid valve regurgitation lead to opacification of markedly enlarged right atrium (RA). In
this example, pulmonary arteries are not opacified indicating presence
of anatomic or functional pulmonary atresia. Trilobed appearance with
two notches, the first (arrow 1) separating the RA and the atrialized
portion of right ventricle (aRV) represents location of the true tricuspid
valve annulus and the second notch (arrow 2) represents origin of displaced tricuspid valve leaflets (see text for details). RHC = Right heart
catheter; UVC = Umbilical venous catheter
422
at 15 weeks may develop features of Ebstein anomaly at a

later gestational age, for example, 24 weeks.54
Celermajer et al44,47 devised a simple scoring/grading
system (now called Celermajer index) to predict outcome
based on fetal or neonatal echocardiogram. Apical fourchamber views (Figure 5) are used for measurement. Ratio
of area of RA plus atrialized portion of RV to the combined
area of functional, distal portion of RV, LV and LA is used for
grading; higher the grade greater is the mortalityGrade 1
(ratio < 0.5) had a mortality of 0 percent, Grade 2 (ratio 0.5
0.99) had a mortality of 10 percent, Grade 3 (ratio 1.0 1.49)
had a mortality of 44 percent and Grade 4 (ratio > 1.5) had 100
percent mortality (Figure 10).44,47
Simpson-Andrews-Sharland (SAS) Score (Table 1)SAS
score is based on observations from 44 fetal studies at the first
prenatal echocardiogram and includes:
i. Cardiothoracic ratiobased on circumferences in
fetal echocardiogram.
ii. Celermajer index.
iii. RV-LV ratio.
iv. Reduced/absent pulmonary valve flow.
v. Retrograde ductus arteriosus flow.
This score predicts survivors vs non-survivors and is useful
in counseling during pregnancy.55
figure 9: Fetal echocardiogram at 24 weeks gestation showing

four-chamber view of the heart with mild form of Ebstein anomaly.
Arrow denotes atrialized right ventricle (aRV). No hydrops was noted.
LA = Left atrium; LV = Left ventricle; RA = Right atrium
figure 10: Mortality rate based on the Celermajer index

from their study47
Outcome based on SAS scoreScores of 0 to 10 are

possible. There were no survivors when the score was greater
than or equal to 5. Conversely, when the scores were less
than or equal to 3, survival was 91 percent. In this study,
there was no one with score of 4. In addition, SAS score did
not change in most fetuses during follow-up in the rest of
pregnancy. However, there was one non-survivor whose score
increased in successive fetal echocardiograms from zero at
approximately 22 weeks five at approximately 27 weeks and
reached 10 at approximately 32 weeks.
Prognostic factorsWhen fetal diagnosis of Ebstein
anomaly or TV dysplasia is made, it is associated with
high mortality. In a study from France, 37 cases of Ebstein

table 1
Simpson-Andrews-Sharland (SAS) Score used to predict fetal outcome from fetal echocardiogram during pregnancy
0
Cardiothoracic ratio (based on

circumferences in the first fetal
echocardiogram)
< 0.65
0.65 0.75
> 0.75
Celermajer index
< 1.0
1.0 1.5
> 1.5
Pulmonary valve flow
Normal
Reduced
Absent
Ductus arteriosus flow
Antegrade
Both
Retrograde
RV:LV Ratio
<1.5
1.5 2.0
> 2.0
LV = Left ventricle; RV = Right ventricle
anomaly or TV dysplasia diagnosed between 19842010

were reviewed.56 Twenty-six had Ebstein anomaly and eleven
had TV dysplasia. There were pregnancy terminations in
ten, intrauterine deaths in five and neonatal deaths in eight.
Fourteen fetuses survived. Presence of retrograde flow across
the pulmonary valve in the first fetal echocardiogram was
a strong predictor of fetal or neonatal death. Presence of
antegrade flow through pulmonary valve was associated with
good prognosis. Celermajer index did not predict outcome in
this cohort adequately while the more extensive SAS predicted
outcome adequately.56
A recent single-center study from Boston Childrens
Hospital reviewed 66 patients diagnosed between 1984 and
2004.57 Sixty-one of them were Ebstein anomaly and five were
TV dysplasia. Thirty-three were diagnosed prenatally, while
33 were diagnosed after birth. Median follow-up duration
was 6.3 years. Of the 33 fetal diagnoses, 8 (24%) underwent
medical termination, 9 (27%) died in utero and 16 were born
alive. Nine of these 16 (56%) died in neonatal period. Overall,
7 of 33 fetal diagnosis patients survived beyond 1 month of
age. Factors associated with poor outcome were moderate or
severe tricuspid regurgitation, Celermajer index more than
1.0 and absence of forward flow through pulmonary valve. Of
the 49 newborn babies, 29 percent died in the hospital and 35
were discharged home. Even though mortality was lower for
the cohort diagnosed after 1997 (29% vs 54%), mortality still
remains high for the most severe group. Therefore, strategies
different from what are being used currently will be needed
such as steroids in the third trimester to help lung maturity,
delivery in middle of third trimester, early institution of
ventilation and management of metabolic derangement after
birth to help avoid burden from poorly expanded/poorly
formed lungs, etc.57 When the presentation is in the neonatal
period, severe RV outflow tract obstruction is also a risk factor
for mortality.43,57
In summary, when the presentation is in fetal and
newborn periods, the following are associated with death
by 3 months of agesevere RV outflow tract obstruction,
tethered distal attachment of anterior leaflet, RV dysplasia,
LV compression by RV dilatation and Celermajer index

exceeding one.43, 57
Variable
29
Severe cardiomegaly with pulmonary oligemia in a cyanotic
newborn is highly suggestive of Ebstein anomaly; however,
the following conditions should also be considered in
such situationsCritical PS or pulmonary atresia with
intact ventricular septum and functional pulmonary
atresia. Tricuspid atresia, TGA and TOF may rarely mimic
Ebstein anomaly. But, their clinical features are distinctive.
Echocardiography will differentiate these conditions from
Ebstein anomaly.
It is of considerable concern when these patients are
referred for surgery in that there is a potential for error in
the diagnosis of Ebstein anomaly when one is faced with a
tricuspid valve disease with significant tricuspid regurgitation.
In a study of cases referred, diagnosed as Ebstein anomaly
for surgical repair between 1982 and 1995, 22 patients
were identified in whom the diagnosis was changed. All 22
patients had prominent RA and RV enlargement. However,
Ebstein anomaly was ruled out in these patients prior to
surgery using two important echocardiographic parameters
namely:
i. Significant apical displacement of septal leaflet of
tricuspid valve ( 8 mm/m2).
ii. Redundant, elongated anterior leaflet of the tricuspid
valve.
Fifteen of these 22 patients underwent surgery and
Ebstein anomaly was ruled out by surgical anatomy
as well. Alternative diagnoses established in these
patients included TV dysplasia (n = 9), TV prolapse (n
= 4), trauma (n = 4), RV dysplasia (n = 3), endocarditis
(n = 1) and annular dilatation secondary to free pulmonary
regurgitation (n = 1). Absence of the two characteristic
echocardiographic signs of Ebstein anomaly, mentioned
above should raise possibilities of other types of tricuspid
valve diseases. 58
423
Natural History
Several studies38,59-62 examining natural history will be
reviewed in order to get a sense of how the patients do
over time. An early study from Boston Childrens Hospital
reviewed the outcome of Ebstein anomaly;38 isolated Ebstein
anomaly70 percent survived up to 2 yrs and 50 percent
survived up to 13 yrs. Ebstein anomaly patients with associated
anomalies, however had a 15 percent survival at 2 years.59 In
another study of 505 patients,59 minimal disability was present
in 73 percent of 1 to 15 year-old, 69 percent of 16 to 25 year
age group and 59 percent of subjects above 25 years of age.
Therefore, early diagnosis alone should not be an indication
for surgery.60 Carpentier type A and B14 babies are likely to
recover with medical management in the neonatal period.61
A recent study from Belgium62 documents outcome in a
cohort of 49 patients who were more than 16 years old. Mean
follow-up period was 11.4 years (132 year). Half of them
(51%) has undergone tricuspid valve surgery; surgical repair
of the valve (valvuloplasty) in 16 and valve replacements in
nine. Eight patients required reoperation to repeat tricuspid
valve repair. Twenty-six (51%) patients had SVT. Typical
WPW syndrome was noted in 15 (31%) and ablation was
performed in 17 (34%). Pacemaker was implanted in 5
(10%).62
Management
Medical Management
424
The management depends on severity and age at presentation.

Asymptomatic cyanotic newborn do not need any active
treatment unless cyanosis is severe. Treatment consists of
temporarily keeping the PDA open using prostaglandin
(PG) E1 infusion (0.050.1 mcg/kg/min) until PVR drops.
Occasionally, use of inhaled nitric oxide to reduce PVR
has helped to improve pulmonary blood flow and hence
the systemic oxygenation. Such therapy is usually needed
for a few days only, after which they can be safely weaned.
Intubation and positive pressure ventilation may help to
manage pulmonary hypertension more effectively. Deep
sedation and muscle relaxant may be necessary for few days
to manage pulmonary hypertension. Correction of metabolic
acidosis with bicarbonate infusions and inotropic infusions
for low cardiac output will be needed.28 Few neonates may
require surgical systemic-pulmonary shunt to maintain
adequate pulmonary blood flow and thus, maintain adequate
systemic oxygen saturation.
Features of heart failure from tricuspid regurgitation may
be treated with anti-failure medications such as Furosemide
and Digoxin.
Supraventricular tachycardia from accessory pathway or
atrial flutter from enlarged atrium should be controlled using
appropriate anti-arrhythmic medications.
Restrictive PFO/ASD may require balloon atrial septostomy
in order to stabilize the baby for further management. While this
may relieve systemic venous congestion, one should be aware

of the increase in cyanosis that may occur due to increased
right to left shunting at the atrial level after septostomy.
Right ventricular outflow tract obstruction is commonly
secondary to anterior leaflet attachments. Therefore, balloon
pulmonary valvuloplasty is unlikely to help unless valvar
stenosis is a significant part of RV outflow tract obstruction.
Surgical Management
Multiple surgical approaches have been described for
treatment of Ebstein anomaly and will be reviewed briefly.
Simple closure of ASD: Surgical closure of PFO/ASD
may provide symptomatic improvement by controlling a
significant left to right shunting and mild cyanosis (secondary
to right to left shunting) at baseline or with exercise. This may
be useful in a small number of individuals. In such patients,
transcatheter closure of ASD63 may be considered after a testocclusion to prove that the cardiac output does not decrease
and right atrial pressure does not unduly increase. For most of
the other patients, tricuspid valve (Ebstein anomaly) should
be addressed surgically.
Repair or replacement of tricuspid valve: Danielson et
al64 performed repair of tricuspid valve and closed the ASD
(Figures 11A and B). Repair of TV consisted of plication
of atrialized portion of RV, narrowing the size of tricuspid
valve and creating a monoleaflet tricuspid valve that is
competent.64,65 Supravalvar positioning of the prosthetic
tricuspid valve decreased the incidence of AV block following
surgery. In this method, the coronary sinus is left below the
prosthetic tricuspid valve.66,67
Carpentiers repair15 consists of placating the atrialized
portion of RV and narrowing the tricuspid valve annulus
but, in a direction at right angles from that performed by
Danielson. This results in a more normal-sized and shaped RV
than in Danielsons repair. Carpentier also used annuloplasty
ring.15 Quaegebeur et al68 performed repair similar to that of
Carpentier repair, but without using annuloplasty ring.
Some surgeons argue that a simple closure of ASD with
replacement of TV without plication of atrialized portion of
RV may be adequate. This argument is based on a consideration
that plication of atrialized portion of RV does not seem to
add any functional advantage to the RV. But, the widely-held
view69,70 is that plication of the atrialized portion of the RV
should be performed especially when the displacement of the
tricuspid valve is moderate or severe.69,70
Cone procedure: Da Silva et al71 described a repair that
consisted of mobilizing the anterior and posterior leaflets from
their anomalous attachments, rotating the detached edges
of these leaflets clockwise and suturing them to the septal
edge of the anterior leaflet at the level of true tricuspid valve
annulus. This creates a cone with its apex at the RV apex and
the base at the true tricuspid annulus. Septal leaflets, when
present are incorporated into this cone. ASD is closed as in the
other techniques. This procedure was performed with minimal
29
figures 11a and B: Schematic diagram showing the components of repair of Ebstein anomaly as described by Danielson and colleagues.65,66
A. 1 Plication of tricuspid valve annulus, 2 Mattress-sutures holding the pliacation of atrialized portion of right ventricle (RV) to the anatomic
tricuspid annulus level, 3 Patch closure of atrial septal defect; B. The schematic of plication of atrialized portion of RV to the anatomic tricuspid
valve annulus level. MPA = Main pulmonary artery
mortality of 2.5 percent in a cohort of 40 patients with a mean

age of 16 years and reasonably good TV function.71
Starnes procedure: This surgery (Figure 12) is performed
in neonates who are in extremis. Objectives of the surgery
are to exclude right ventricle and establish a reliable source
of pulmonary blood flow. RV exclusion is performed by
closing the tricuspid annular orifice using a pericardial
patch, removing the entire septum primum and placing either
a central aorto-pulmonary shunt (4 mm Gore-Tex graft)
or Blalock-Taussig shunt (3.5 or 4.0 mm Gore-Tex graft)
from innominate artery to right or left pulmonary artery.72
These neonates will subsequently need bidirectional Glenn
procedure and eventually Fontan operation.
One and a half ventricle repair: Small number of patients
with Ebstein anomaly may undergo the so-called one and
a half ventricle repair.73 Indications include presence of a
severely enlarged right atrium, severe tricuspid regurgitation,
bidirectional shunt across the PFO/ASD, very hypoplastic right
ventricle with minimal functional right ventricle, depressed
LV systolic function or a combination thereof. This surgery
consists of patch closure of ASD, repair of tricuspid valve
with reduction of the atrialized portion of right ventricle and
a bidirectional Glenn operation (i.e. end to side anastomosis
of the superior vena cava to the right pulmonary artery).
This surgery accomplishes the followingunloads the right
atrial and right ventricular volume by approximately onethird and still, right ventricle can contribute to the pulmonary
circulation maintaining pulsatile flow and allowing for
flexibility to cope with transient increases in pulmonary
vascular resistance and allows for more aggressive repair of
figure 12: Schematic showing the principle behind Starnes Procedure.

Patch Patch closure of the tricuspid valve orifice. Fenestration is
created to allow for escape of blood that returns through thebesian
veins to the right ventricle. ASD Atrial septal defect is enlarged.
A systemic to pulmonary arterial shunt (central shunt) is shown in
the figure. Alternatively Blalock-Taussig shunt may be performed.
CS = Coronary sinus
the tricuspid valve without concern for tricuspid stenosis due

to overcorrection.73-75
Fontan operation: This may be an optimal option for a rare
patient with tricuspid stenosis and hypoplastic right ventricle.
425
426
Fontan operation, of course, is usually preceded by either an

aortopulmonary shunt in the newborn period and followed by
a bidirectional Glenn operation, as a staged procedure.76
Neonates and young children: Indications for surgery in
newborns and infants with cyanosis and congestive heart
failure (CHF) are not clear and the decision to perform surgery
should be individualized. General principle of management
of a newborn with symptomatic Ebstein anomaly is to allow
sufficient time for medical management to work so that surgery
may be postponed or avoided early in life. In relatively milder
cases, reduction in pulmonary vascular resistance may allow
discontinuation of PG infusion resulting in closure of PDA
and weaning inhaled nitric oxide, if used in early treatment.
The babies that do not stabilize following withdrawal of above
management may need surgical repair as newborn.
Neonates who require surgical repair present a great
challenge. Management objectives in a neonate, as emphasized
above, are initially focused on avoiding surgical intervention.
However, if the baby has significant cyanosis and heart failure,
with or without RV outflow tract obstruction, anatomic or
functional, surgical treatment will become unavoidable.
One recent study from a single center reported 40
consecutive neonates seen over a 20 year period between
1988 and 2008.77 No intervention was necessary in 16 babies.
Surgical intervention was performed in 24 babies at a mean
age of 6 days and a mean weight 3.2 kg. Surgery consisted of
tricuspid valve closure (Starnes procedure) in 11 (3 of these
babies died early), TV repair in four (3 of these died early) or
only an aortopulmonary shunt in nine (all of them survived).
Of the nine shunt patients, two needed closure of TV later.
Overall, six of 24 babies died early. Of the 18 early survivors,
four died late during a 7 year follow-up period. Overall,
survival for surgical patients was 66 percent at 1 year, 62
percent at five and 10 years and 52 percent at 15 years of age.77
Better survival in shuntonly group of 89 percent at 1 year
and 76 percent at five and 10 years was also observed. Worst
results were for the TV repair group in whom three of the four
babies had early mortality. This is a single center experience;
the results will inevitably vary from one institution to the
other. These data would suggest aorto-pulmonary shunt or
Starnes procedure are good options to consider in the newborn
babies.
Postoperative management is largely dependent upon
the preoperative state of the child and quality of repair. In
a newborn, control PVR and initially support RV and LV
function with intubation, ventilation, sedation and inotropic
support. Low cardiac output state is the most common issue
that needs to be dealt with in this group of patientsprobably
secondary to large RA and atrialized RV and RV-LV interaction
leading to poor LV function. Postoperative arrhythmias may
occur specifically supraventricular tachycardia or atrial
arrhythmias and should be addressed aggressively.
Older children and adults: Indication for surgery in older
children and adults include the following:78
1. New York Heart Association (NYHA) III or IV.

2. NYHA I and II, but with CT ratio of 0.65 or more.
3. Significant cyanosis (80% or less; Hemoglobin 16 gm% or
more).
4. Paradoxical embolism.
5. Intractable arrhythmia (even though arrhythmia may not be
altered by surgery, but it is better tolerated after surgery).
A retrospective, single-center study from Munich,
Germany79 reviewed outcome from older age group of patients.
One hundred and thirty patients with Ebstein anomaly who
underwent valve repair or replacement between 1976 and 2007
at a mean age of 24 years were studied; 90 percent patients
underwent primary valve repair, while 10 percent underwent
valve replacement. Hospital mortality was 1.5 percent. Overall
survival was 87, 85 and 81 percent at 10, 20 and 25 years
respectively. Risk factors for mortality were NYHA functional
class more than II and CT ratio more than 0.6. The investigators
suggest that surgery should be performed, before functional
status deteriorates and significant cardiomegaly occurs.79
Adults with Ebstein Anomaly

Patients with mild Ebstein anomaly may be asymptomatic
in adulthood. Patients with moderate Ebstein anomaly
become symptomatic during adolescence or early adulthood.
Commonest symptoms are exercise intolerance and palpitation
from supraventricular tachycardia. When ASD is present,
cyanosis, stroke or transient ischemic attacks (TIA) may
occur. Sudden death from arrhythmias may also occur. Apart
from transthoracic echocardiogram and ECG, diagnostic
work-up may involve TEE, exercise testing with oximetry,
Holter monitoring and/or electrophysiology (EP) study and
MRI. Active management is indicated for NYHA class III
or IV, Cardiothoracic ratio more than 65 percent, significant
cyanosis, severe tricuspid regurgitation with symptoms and
stroke. As far as surgical repair is concerned, if the anterior
leaflet is mobile and there is adequate sized, functional RV,
valve repair or replacement should be attempted. Closure of
ASD only may help some patients with exercise limitation.
This can be performed using transcatheter technique if test
occlusion does not drop the cardiac output and RA pressure
does not increase. Some patients are candidates for one and a
half ventricle repair described above or for Fontan operation.
Atrial arrhythmias and supraventricular tachycardia are treated
either at surgery or by transcatheter techniques. Pregnancy is
well tolerated if the patient does not have cyanosis, right heart
failure or arrhythmias. Slightly higher incidence of premature
delivery has been reported.76
Arrhythmia Management
Supraventricular tachycardia (SVT) is common with Ebstein
as alluded to earlier. Types of arrhythmia noted in patients with
Ebsteins anomaly are SVT secondary to accessory pathways
CONCLUsION
Ebstein anomaly is a rare congenital heart disease. Clinical
manifestations vary depending upon the severity of the
lesion. Mild forms may be asymptomatic and may not
need any treatment. Moderate forms may be managed with
relative ease. Severe forms of the disease are a challenge to
manage. Prognosis depends on severity of the lesion, age at

presentation and type of surgical repair. Surgical outcomes
have improved over time but, early presentation as fetus and
newborn is associated with poor prognosis.
EbsTEINOID MALFORMATION OF LEFT AV VALVE (WITH

L-TRANsPOsITION OF GREAT ARTERIEs)
L-transposition of great arteries (L-TGA) was originally
described by von Rokitansky in 1875.82 L-TGA is a congenital
heart defect characterized by atrial situs solitus, atrioventricular discordance and ventriculo-arterial discordance,
i.e. right atrium empties systemic venous blood into a rightsided, morphologic LV and then into the pulmonary artery
(Figure 13A) and the left atrium empties pulmonary venous
blood into a left-sided, morphologic RV and then into the aorta
(Figure 13B).29,83 Since the pulmonary artery comes of the left
ventricle and the aorta from the right ventricle, transposition of
great arteries is deemed to exist. However, normal blood flow
pattern is preserved, hence, the term, congenitally corrected
transposition of the great arteries or corrected transposition in
short. In this condition the ventricles are essentially inverted
(Figure 13). Normally the aorta is located to the right of
pulmonary artery; however, in this condition, the aorta is
positioned to the left of pulmonary artery (Figure 13); hence
the term L-TGA.
While patients without any associated cardiac defects are
reported, the majority of the L-TGA patients have significant
associated defects, namely, VSD, PS, atrioventricular (AV)
block (spontaneous or after catheter or surgical intervention)
and Ebstein like malformation of the left-sided, morphologic
atrio-ventricular valve.
As discussed above, the morphologic RV is located on
the left side and morphologic LV is located on the right
side. The AV valves correspond to morphologic ventricular
chambers.84-87 Consequently, the tricuspid valve is on the left
side of the heart, associated with the morphologic RV. Ebstein
malformation of such left-sided AV valve is sometimes called
Ebsteinoid or Ebstein a like malformation to differentiate it
from classic Ebstein anomaly discussed in the preceding
section. L-TGA is more extensively discussed elsewhere
in this book. A brief description relevant to tricuspid valve
abnormalities is provided here.
29
(manifest WPW syndrome or concealed pathway) or atrioventricular re-entry tachycardia (AVNRT), atrial flutter or
fibrillation. Rarely, junctional tachycardia and ventricular
tachycardia have been noted.36 If a patient with Ebstein
shows WPW syndrome in the ECG, management depends
on presence of arrhythmia, its severity and frequency. No
consensus exists regarding the treatment of an asymptomatic
patient with Ebstein anomaly and WPW syndrome.34 Some
investigators advise a risk-stratification EP studyeither
transesophageal or intracardiac. If the refractory period of
the anomalous pathway is below a certain value (effective
refractory period less than 280 ms), radiofrequency ablation
is advised.80 Beta-blocker therapy remains the first-line of
medical therapy for SVT in patients with Ebstein anomaly,
similar to children without Ebstein anomaly.
Ablation is recommended if the arrhythmia is recurrent or
surgery is contemplated. Radiofrequency catheter ablation
specifically may be technically challenging due to anatomic
peculiarities of the tricuspid valve annulus, fragmented nature
of the ventricular electrograms from the atrialized portion
of the right ventricle and relative instability of the ablation
catheters. Use of appropriately pre-shaped catheters, use of
right coronary angiograms or use of 2-French catheter in right
coronary artery to mark the location of tricuspid valve annulus
and use of cryoablation have helped to ease the technical
difficulties in Ebstein anomaly.34 Smaller area of triangle of
Koch in Ebstein anomaly hearts may result in higher incidence
of AV block with ablation in patients with Ebsteins anomaly
than in otherwise normal hearts.23,24
Surgical therapy of arrhythmia is preferred by some
workers and is usually performed at the time of surgical repair
of Ebstein anomaly. In a study of adult patients from Mayo
clinic (median age of 25 years) with Ebstein anomaly and
arrhythmia, 83 of the 109 study patients underwent surgical
therapy for arrhythmia at the time of surgery for Ebstein
anomaly; these procedures consisted of at least one of:
a. Surgical ablation of an accessory pathway for SVT.
b. Surgical perinodal cryoablation for AVNRT.
c. Right-sided maze procedure and/or cryoablation of the
atrial isthmus for atrial flutter-fibrillation.81
Freedom from arrhythmia recurrence was 100 percent for
SVT at a mean follow-up of 48 months, 100 percent for atrioventricular nodal reentry tachycardia at a mean follow up of
57 months and 75 percent for atrial flutter or fibrillation at
a mean follow up of 34 months.81 Whether recent advances
in transcatheter ablation techniques change this approach
remains to be seen.
Symptoms in these patients occur in first month of life, more
from associated lesions such as VSD causing left to right
shunting or VSD and pulmonary outflow tract obstruction
together causing pulmonary oligemia rather than from
Ebsteinoid malformation. Sometimes, the regurgitation of
the Ebsteinoid valve may be the sole reason for symptoms
of heart failure in early life.87 The symptoms (dyspnea on
exertion) occur more often latter in life as seen in the patient
shown in Figures 13A and B.
427
figures 13a and B: Selected cineangiographic frames in postero-anterior view from an adolescent with L-transposition of the great arteries
and Ebstein anomaly of left atrioventricular valve. A. Right-sided morphologic left ventricular (MLV) angiogram demonstrating smooth walled
ventricular chamber giving rise to the main pulmonary artery (PA); B. Left-sided morphologic right ventricular (MRV) cineangiogram showing
trebeculated ventricular chamber giving rise to the aorta (Ao). Radio-opaque ring of the St. Jude valve (SJV) is seen (which was inserted to
replace severely regurgitant Ebstinoid left atrioventricular valve at the age of 5 years). Pacemaker wires placed at the time of surgery, marker
pigtail (MPG) catheter and sternal wires are seen
Loud single second heart sound may be heard because
of antero-posterior orientation of great arteries leading to
muffling of the posteriorly placed pulmonary valve sound.
Left sided AV valve regurgitation produces a holosystolic
murmur at apex and left lower sternal border. This may be
similar to VSD murmur but may be differentiated based on
radiation to anterior and mid-axillary lines.
Investigations
Chest X-ray
428
Echocardiogram
Echocardiogram is diagnostic, but may be challenging to
perform and interpret to a novice. Absence of continuity
between left AV valve and aortic valve due to presence of
conus on the left-side is one of the echocardiographic features.
Degree of downward displacement of the left-sided tricuspid
valve may be assessed in a four chamber view. Left AV valve
regurgitation may be semi-quantified. Associated lesions may
also be defined.
Other Studies
Chest X-ray findings include left atrial enlargement and peculiar

contour (straightening) of the left superior mediastinum due to
superior extension of left border of the cardiac silhouette. This
appearance is created by the ascending aorta arising from the
anterior and leftward aortic valve.
Simultaneous recording of pressures and intracavitary ECG

may help firm up the diagnosis,87 a manner similar to normally
located Ebstein anomaly of the tricuspid valve.29 But, such
studies may not be necessary given the diagnostic accuracy
of echocardiographic studies. Similarly, angiography is no
longer needed to confirm this diagnosis.
Electrocardiogram
Management
Electrocardiogram is characteristic with absence of Q wave in

left precordial leads and presence of Q wave in V1 indicating
reversal of septal depolarization.86 Left atrial enlargement
and right ventricular dominance are other features. Atrioventricular conduction block (prolonged PR interval through
3rd degree heart block) may be present.
Patients with mild AV valve insufficiency may need

periodic follow-up. Treatment of congestive heart failure
including afterload reducing agents may be needed in
moderate to severe AV valve insufficiency. Some of these
infants may require surgical repair or replacement of
left AV valve later in life. Discussion of considerations
for double switch operation is beyond the scope of this

chapter.
Congenital tricuspid valve stenosis is very rare as an isolated

lesion. Tricuspid valve stenosis may occur in association with
other defects such as pulmonary atresia or stenosis, double
outlet right ventricle, single ventricle, tetralogy of Fallot,
transposition of great arteries, ventricular septal defect or
Uhls anomaly.29 Isolated lesions are more common in female.
Familial cases have also been reported.29 Tricuspid valve
stenosis may also be acquired secondary to rheumatic fever,
though rare.
Pathology
Pathology of tricuspid valve stenosis includes either hypoplasia
of the valve including valve annulus, leaflets and chordae,
two-leaflet (mitralized) tricuspid valve with abnormal chordal
attachments or conversion of a sheet of valve structure attached
to short chordae and small or markedly abbreviated papillary
muscles.88 Parachute tricuspid valve has been reported in
association with tetralogy of Fallot and double-outlet right
ventricle. There is usually corresponding hypoplasia of the
right ventricle.89
Clinical Manifestation
Chief clinical manifestation is cyanosis from right to left
shunting across the patent foramen ovale or atrial septal defect.
Associated lesions will dictate rest of the clinical features.
Features of elevated right atrial pressure may be evident if the
atrial level shunt has restriction to flow. As right atrial pressure
increases, venous congestion with distension of jugular veins,
noticeable in older children and adults, liver enlargement,
ascites, pleural effusion and peripheral edema may become
evident. Chronic fatigue and exercise intolerance will be the
presentation in chronic patients who have mildly low cardiac
output or low reserve. Atrial arrhythmias may occur due to right
atrial enlargement. Since the atrium may hypertrophy and dilate
to accommodate the venous congestion, right atrial pressure
may remain low when measured by cardiac catheterization.
Chest X-ray
Chest X-ray demonstrates significant right atrial enlargement
and diminished pulmonary vascular markings.
Electrocardiogram
Electrocardiogram demonstrates right atrial enlargement, left
axis deviation of the QRS in the frontal plane, because it, along
with tricuspid atresia belong to a spectrum of morphologic
abnormalities of the tricuspid valve.90
Echocardiogram will help to distinguish this lesion from

tricuspid atresia and elucidate associated lesions. By cardiac
catheterization, diastolic gradient may vary depending upon
right atrial dilatation, severity of stenosis and chronicity of the
stenosis at the time of evaluation.
Management
Management is similar to tricuspid atresia. Associated lesions
will dictate management. Restrictive atrial level shunt may
warrant an emergency atrial septostomy in neonates. However,
in some marginal patients with adequate size right ventricle
and adequate tricuspid valve annulus, commissurotomy or
valve excision or replacement have been attempted. Rare
descriptions of balloon valvuloplasty of isolated tricuspid
valve stenosis have been reported, mostly in adult patients.91-93
29
TRICUsPID VALVE sTENOsIs
Echocardiogram
TRICUsPID REGURGITATION
Tricuspid regurgitation occurs in various clinical settings,
frequently in association with other pathologies. In these
clinical settings, tricuspid regurgitation may be considered
secondary, with largely a normal valve anatomy. However,
isolated tricuspid regurgitation, while rarely encountered, is
well-documented in association with anatomic abnormality
of the tricuspid valve94-98 such as tricuspid valve dysplasia
characterized by thickened, elongated or partially absent
leaflets, shortened and abnormally-inserted chordae tendinae
and underdeveloped papillary muscle.97
Transient tricuspid regurgitation in newborn is very
common in association with persistent pulmonary hypertension of newborn or transient myocardial ischemia
secondary asphyxia.99-102
Tricuspid regurgitation associated with other congenital
heart lesions such as pulmonary atresia or critical pulmonary
stenosis are secondary to extremely high right ventricular
pressure and lack of egress from right ventricle. Generally,
tricuspid valve is likely to be normally formed, though the
annulus may be hypoplastic to a variable extent depending
upon the right ventricular size.
Tricuspid regurgitation associated with Ebstein anomaly,
Uhls anomaly and atrioventricular septal defect (endocardial
cushion defects) are associated with abnormal valve
development and have been discussed elsewhere in this book.
Straddling and/or overriding tricuspid valve may also be
regurgitant.
Finally, a category of patients who constitute a large group
in pediatric cardiology practice include tricuspid regurgitation
that occurs after surgical repair of atrioventricular septal
defects. Rarely such tricuspid regurgitation may occur also
after repair of cardiac defects such as tetralogy of Fallot,
double outlet right ventricle and many other conditions
associated with placement of RV-PA conduit. Tricuspid valve
429
is usually normal in these lesions. Tricuspid regurgitation

may also occur secondary to chronic volume overload of
the right ventricle from free pulmonary regurgitationwith
or without associated pressure overload secondary to right
ventricular outflow obstruction. These patients become
symptomatic over several years during long-term follow-up
after surgical repair.
Neonates present with cyanosis at birth. If the cause
of tricuspid regurgitation is transient such as persistent
pulmonary hypertension of newborn or myocardial depression
from birth asphyxia, this will resolve as the primary cause
resolves and patent foramen ovale starts to close. Transient
heart failure features may occur, but uncommon. In older
children, presentation usually is chronic fatigue and exercise
intolerance. Clinical examination may include features of
heart failure, single S2, holosystolic murmur with thrill at
the left lower sternal border and sometimes a mid-diastolic
murmur may be heard at the left lower sternal border.29
Investigations
Chest X-ray
Chest X-ray shows severe cardiomegaly usually secondary
to right atrial enlargement and right ventricular enlargement.
Decreased pulmonary vascular markings are usually expected
in a newborn. In older children, this may not be present.
Electrocardiogram
Electrocardiogram shows right axis deviation, right atrial
enlargement and sometimes, right bundle branch block. This
may vary depending upon associated cardiac lesions and prior
heart surgery.
Echocardiography
430
Echocardiography is diagnostic and provides good

evaluation of severity and may help elucidate the mechanism
of regurgitation. Objectives of echocardiography include
assessing the severity of tricuspid regurgitation using a
combination of chamber size and pulse, continuous wave
Doppler and color Doppler imaging. Reversal of flow in vena
cavae and hepatic veins are helpful in assessing severity.
Mechanism of tricuspid regurgitation including assessment
valve anatomy, subvalvar apparatus and coaptation of
leaflets should be assessed. In older children and adults, TEE
may help when transthoracic acoustic windows are poor and
the image quality is inadequate. Assessment of severity of
other co-existing cardiac lesions should be performed as
well.103,104
Cardiac catheterization may be indicated for a variety of
reasons depending upon the etiology in a given patient. Right
atrial mean pressure may be elevated. However, in chronic
tricuspid regurgitation, right atrial enlargement and venous
compliance may accommodate the regurgitant volume
leading to relatively lower right atrial mean pressure than
expected. Prominent v wave in right atrial trace is indicative
of tricuspid insufficiency. Systemic desaturation occurs
if there is right to left shunting at atrial level. RV systolic
pressure may be elevated depending upon associated cardiac
lesions. Right ventricular end-diastolic pressure is elevated as
well. Right ventriculogram demonstrates the enlarged right
ventricle, reveals the severity of tricuspid regurgitation and
outlines the right atrium that is usually enlarged.
Management
In newborn with tricuspid regurgitation secondary to persistent
pulmonary hypertension or myocardial depression, treatment
should be directed at the primary cause such as nitric oxide for
pulmonary hypertension. In newborn with isolated tricuspid
regurgitation, prostaglandin infusion may help decrease
systemic hypoxia until pulmonary vascular resistance decreases
enough to decrease right ventricular pressure. Heart failure
may need diuretics and Digoxin. Other supportive therapy
depending upon the severity of the clinical manifestations will
be required such as monitoring arterial blood gases, correction
of any acidosis, electrolyte abnormalities, providing assisted
ventilation, etc. Every attempt is made to avoid neonatal surgery
for tricuspid regurgitation which may include annuloplasty
alone, valve repair or valve replacement. DeVega tricuspid
annuloplasty procedure was originally described in 1973 and is
performed either by itself or along with another cardiac repair
and provides excellent relief from tricuspid regurgitation.105,106
In older children, results of tricuspid valve surgery are better.
Although echocardiographic tricuspid regurgitation may
increase with time following repair, reintervention is rarely
necessary.107
sUMMARY AND CONCLUsION

In this chapter, Ebsteins malformation of the tricuspid valve,
Ebsteins anomaly of the left-sided atrioventricular valve
in corrected transposition, tricuspid stenosis and tricuspid
regurgitation were discussed.
In Ebsteins anomaly of the tricuspid valve, there is
downward (apical) displacement of insertion of septal
and posterior leaflets along with valve dysplasia leading to
tricuspid regurgitation, right atrial enlargement and varying
degrees of atrialization of the right ventricle. It is a rare
anomaly accounting for 0.3 0.6% of all congenital heart
defects. Differing presentations are seen which depend upon
Despite all our toil and progress, the art of medicine still
falls somewhere between trout casting and spook writing.
Ben Hecht, Miracle of the Fifteen Murderers
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29
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Ebsteins anomaly. Mayo Clin Proc. 1979;54:185.
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treatment of Ebsteins anomaly. J Thorac Cardiovasc Surg.
1992;104:1195.
66. Barnard CN, Schrire V. Surgical correction of Ebsteins
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67. Kirklin JK. Christian Barnards contribution to the surgical
treatment of Ebsteins malformation. Ann Thorac Surg.
1991;51:147.
68. Quaegebeur JM, Sreeram N, Fraser AG, et al. Surgery for
Ebsteins anomaly: The clinical and echocardiographic
evaluation of a new technique. J Am Coll Cardiol.
1991;14:1300.
69. Timmis HH, Hardy JD, Watson DG. The surgical management
of Ebsteins anomaly. The combined use of tricuspid valve
replacement, atrioventricular plication and atrioplasty. J Thorac
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Rao PS. Is the Term Tricuspid Atresia appropriate? (Editorial).
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Bourdillon PDV, Hookman LD, Morris SN, et al. Percutaneous
balloon valvuloplasty for tricuspid stenosis: Hemodynamic
and pathologic findings. Am Heart J. 1989;117:492.
Rabalino BB, Whitlow PL, Marwick T, et al. Percutaneous
balloon valvotomy for the treatment of isolated tricuspid
stenosis. Chest. 1991;100:867.
Shaw TRD. The Inoue balloon for dilatation of the tricuspid
valve: A modified over-the-wire approach. Br Heart J.
1992;67:263.
Barritt DW, Urich H. Congenital tricuspid incompetence. Br
Heart J. 1956;18:133.
Kincaid OW, Swan HJC, Ongley PA, et al. Congenital tricuspid
insufficiency: Report of two cases. Mayo Clin Proc. 1962;37:640.
Antia AU, Osunkeya BO. Congenital tricuspid insufficiency.
Br Heart J. 1969;31:664.
Becker AE, Becker MJ, Edwards JE. Pathologic spectrum of
dysplasia of the tricuspid valve: Features in common with
Ebsteins malformation. Arch Path. 1971;91:167.
Barr PA, Celermajer JM, Bowdler JD, et al. Severe congenital
tricuspid incompetence in the neonate. Circulation. 1974;49:962.
Boucek RJ Jr, Graham TP Jr, Morgan JP, et al. Spontaneous
resolution of massive congenital tricuspid insufficiency.
Bucciarelli R, Nelson RM, Egan EA II, et al. Transient
tricuspid insufficiency in the newborn: A form of myocardial
dysfunction in stressed newborn. Pediatrics. 1977;59:330.
Riemenschneider TA, Nielsen HC, Ruttenberg HS, et al.
Disturbances of the transitional circulation. Spectrum of
pulmonary hypertension and myocardial dysfunction. J
Pediatr. 1978;89:622.
Rowe RS, Hoffman T. Transient myocardial ischemia of the
newborn infant: A form of severe cardiorespiratory distress in
full term infants. J Pediatr. 1972;81:243.
Snider AR, Serwer GA, Ritter SE. Methods for obtaining
quantitative information from echocardiographic examination.
In: Echocardiography in pediatric heart disease. 2nd edition. St
Louis: Mosby. 1997.pp.223-24.
Snider AR, Serwer GA, Ritter SE. Abnormalities of ventricular
inflow. In Echocardiography in pediatric heart disease. 2nd
De Vega NG, De Rabago G, Castillon L, et al. A new tricuspid
repair: Short term clinical results in 23 cases. J Cardiovasc
Surg (Torino). 1973;Spec No:384.
Rabago G, De Vega ND, Castillon L, et al. The new De Vega
technique in tricuspid annuloplasty (results in 150 patients). J
Cardiovasc Surg (Torino). 1980;21:231.
Kanter KR, Doelling NE, Fyfe DA, et al. DeVega tricuspid
annuloplasty for tricuspid regurgitation in children. Ann
Thorac Surg. 2001;72:1344.
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71. Da Silva JP, Baumgratz JF, da Fonseca L, et al. The cone

reconstruction of the tricuspid valve in Ebsteins anomaly. The
operation: Early and mid-term results. J Thorac Cardiovasc
Surg. 2007;133:215.
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appearing in neonate. J Thorac Cardiovasc Surg. 1991;53:385.
73. Corno AF, Chassot PG, Payot M, et al. Ebsteins anomaly: One
and a half ventricle repair. Swiss Med Wkly. 2002;132:485.
74. Chauvaud S, Fuzelier JF, Berrebi A, et al. Bidirectional
cavopulmonary shunt associated with ventriculo and
valvuloplasty in Ebsteins anomaly: Benefits in high risk
patients. Eur J Cardiothorac Surg. 1998;13:514.
75. Chowdury UK, Airan B, Sharma R, et al. One and a half ventricle
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anomaly and Marfans syndrome. Can J Cardiol. 2010;26:e80.
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of Ebsteins anomaly: Selection of patients, early and late
operative results. Circulation. 1985;72:II70.
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variations in underdeveloped right ventricle related to
433
C hapter
30
Pulmonary Valve Diseases

Asha Moorthy, Jain T Kallarakkal
Introduction
Congenital pulmonary valve disorders could be stenotic or
regurgitant. Rarely the pulmonary valve could be absent or
atretic. The pulmonary valve disorder may be isolated or
associated with other congenital heart diseases (CHD).
Pulmonary valve anatomy

The pulmonary valve separates the right ventricular outflow
tract from the pulmonary artery. In normal conditions this
valve prevents regurgitation of the deoxygenated blood
from the pulmonary artery back to the right ventricle. It is a
semilunar valve and is located anterior, superior and slightly
to the left of the aortic valve. Pulmonary valve is formed by
three cusps, each with a fibrous node at the midpoint of the
free edges as well as lunulae, which are the thin, crescentshaped portions of the cusps that serve as the coaptive surfaces
of the valve. The cusps of the pulmonary valve are supported
by free-standing musculature with no direct relationship with
the muscular septum; its cusps are thinner and lack a fibrous
continuity with the anterior leaflet of the right atrioventricular
valve.1 The cusps of the pulmonary valve are defined by their
relationship to the aortic valve and are thus termed anterior or
non-septal, right and left cusps. They can also be defined by
their relationship to a commissure found in the pulmonary and
aortic valves and hence termed right adjacent (right facing),
left adjacent (left facing) and opposite (non-facing). The
pulmonary valve, like the other three cardiac valves, is formed
by the endocardial folds that are supported by the internal
plates of dense collagenous and elastic connective tissue and
are continuous with the cardiac skeleton.2
Pulmonary Stenosis
Isolated pulmonary valve stenosis is a form of acyanotic congenital malformation with normal or diminished pulmonary
blood flow. The atrial septum is usually intact; if not the defect
is usually a patent foramen ovale, although a secundum atrial
septal defect may coexist.
History
Pulmonary valvar or valvular stenosis is one of the more
common forms of congenital heart malformations and it has
been extensively studied since the original description of
pulmonary valve stenosis by John Baptist Morgagni in 1761.3
The anatomical details of the anomaly was described in his
classic monograph.
Incidence
Isolated pulmonary valve stenosis is found in 80 to 90 percent
of all patients with right ventricular outflow obstruction and 8
to 10 percent of patients with CHD.
Familial occurrence of pulmonary stenosis has been
reported. Campbell4 found a 2.1 percent incidence of cardiac
disease, usually pulmonary stenosis or tetralogy of Fallot
(TOF), in siblings of patients with pulmonary stenosis. In the
Second Natural History Study of Congenital Heart Defects, the
occurrence of definite and possible congenital heart defects in
1,356 siblings of 449 patients with valvar pulmonary stenosis
was 1.1 and 2.1 percent respectively.5
Embryology and Pathology

The exact embryologic process resulting in pulmonary valve
stenosis is not well understood. Maldevelopment of the distal
part of the bulbus cordis,6 fetal endocarditis7 and genetic factors
with multiple somatic abnormalities8 have been proposed.
In the classic form of pulmonary valve stenosis, the valve is
conical or dome shaped and two to four raphes may be visible,
but there is no separation into the valve leaflets.9 As primarily
there is an inherent medial abnormality, the pulmonary trunk
Etiology
The most common etiology of pulmonary stenosis is
congenital. Rarely, pulmonary stenosis can be acquired due
to rheumatic heart disease, infective endocarditis, carcinoid
syndrome etc.
Physiology
The main physiologic effect of valvar pulmonary stenosis is
a rise in right ventricular pressure, which is proportional to
the severity of the obstruction. This is accompanied by an
increase in muscle mass. Increased muscle mass may enable
the hypertensive right ventricle to maintain a normal stroke
volume. If the size of the stenotic orifice remains fixed, the
degree of obstruction becomes relatively more severe as the
individual grows. The right ventricle eventually may dilate
and fail. This process is exacerbated by the development of
tricuspid insufficiency in many patients. As right ventricular
output decreases with a failing ventricle, adequate tissue
oxygenation can be maintained only by increasing tissue
oxygen extraction. Any increase in oxygen demand, such as
exercise, may result in frank peripheral cyanosis. In patients
with a patent foramen ovale or atrial septal defect, central
cyanosis is observed as a result of right-to-left atrial shunting,
when the right atrial pressure exceeds the left atrial pressure.
Progressive hypertrophy and decreased compliance of the
right ventricle or myocardial failure with subsequent dilation
may lead to central cyanosis in some patients.
Clinical Features
Symptoms
Patients with moderate-to-severe pulmonary stenosis may
experience chest pain, syncope and even sudden death
with strenuous exercise. Decreased myocardial perfusion
caused by inadequate cardiac output during exercise,
leading to ischemia and ventricular arrhythmias, is thought
to be the mechanism for these events. Children with valvar
pulmonary stenosis usually exhibit normal growth and
development regardless of the severity of obstruction.
Infants with critical pulmonary stenosis are cyanotic at
birth.11 Neonates with critical PS present with cyanosis,
CHF, hypotension, feeding difficulty, tachypnea, without
appreciable murmur.
30
Pulmonary Valve diseases
is usually dilated. Less commonly, the valve may be diffusely

thickened with one, two or three leaflets and commissural fusion. The unicuspid or bicuspid pulmonary valve is generally
a feature of tetralogy of Fallot, and the stenosis is variable.
A distinct pathology, pulmonary valve dysplasia, where the
valves are trileaflet with markedly thickened cusps, composed
of disorganized myxomatous tissue, has been described in 10
to 20 percent of patients10 and found in most patients with
Noonan syndrome.
Secondary changes of pulmonary valve obstruction include
infundibular hypertrophy with or without dynamic subvalvar
obstruction, thickening of the tricuspid valve and chordal
attachments, tricuspid regurgitation, thickening and dilatation
of the right atrium. In many cases, a patent foramen ovale or,
less often an atrial septal defect is seen. Most patients develop
poststenotic dilation of the pulmonary artery trunk, sometimes
extending to the proximal left pulmonary artery. One notable
exception to this finding is patients with dysplastic pulmonary
valves. The degree of dilation is not necessarily proportional
to the severity of obstruction, often being more pronounced
in mild cases. Poststenotic dilation may result from the high
velocity jet of flow ejected through the small valve orifice.
Physical Appearance
Five physical appearances are relevant in patients with
pulmonary stenosis. Mobile dome-shaped pulmonary valve
stenosis is characterized by chubby, round, bloated face,
well developed fat deposits and erythematous digits. Noonan
syndrome is characterized by short stature, webbed neck,
pterygium colli, ptosis, hypertelorism, lymphedema, low-set
ears, low anterior and posterior hair lines, flat or shield chest,
pectus excavatum or carinatum, hyperelastic skin, inguinal
hernia, nevi, dystrophic nails, micrognathia, hypospadias and
small undescended or cryptorchid testes. Rubella syndrome is
characterized by cataracts, retinopathy, deafness, hypotonia,
dermatoglyphic abnormalities and mental retardation.
Williams syndrome is characterized by mental retardation,
small chin, large mouth, patulous lips, blunt upturned nose,
wide-set eyes, broad forehead, baggy cheeks and malformed
teeth. Alagille syndrome is characterized by prominent
overhanging forehead, deep set eyes and a small pointed
chin.
Pulse
Arterial pulse is reduced when, severe pulmonary stenosis is
accompanied by right ventricular failure and left ventricular
dysfunction.

Jugular venous a wave gets progressively larger as the
severity of pulmonary stenosis increases. Powerful right atrial
contraction generates a giant jugular venous a wave and a
presystolic liver pulse. With the advent of right ventricular
failure and tricuspid regurgitation, the v wave increases, the
Y descent becomes brisk and the liver manifests presystolic
and systolic pulsations.
435
Palpation
The thrill associated with pulmonary stenosis is maximum in
the second left intercostal space with radiation upward and to
the left, because the intrapulmonary jet is directed upward and
towards the left pulmonary artery. A right ventricular impulse
is palpated, when the fingertips are applied between the ribs
during full held exhalation or by applying a fingertip against
the diaphragm in the subxiphoid area.
Auscultation
The first heart sound is normal and in mild-to-moderate
cases it is followed by a pulmonary ejection click. The click
corresponds to the time when the doming pulmonary valve
reaches its open position. The more severe the stenosis, the
earlier in systole the click occurs, until it merges with the
first heart sound and becomes inaudible. The intensity of the
click varies with respiration, decreasing during inspiration
and increasing during expiration. The second heart sound
is usually split and the degree of splitting is proportional
to the degree of stenosis. The split may become fixed
in severe stenosis as a result of fixed stroke volume. The
intensity of pulmonary component decreases with increasing
obstruction. A fourth heart sound is heard at the left sternal
border with severe stenosis. The systolic murmur of valvular
pulmonary stenosis increases with severity, radiates over
the entire precordium and neck, characteristically heard in
the back and is ejection in quality with maximal intensity at
the upper left sternal border (Figure 1). Patients with severe
stenosis and right heart failure may have an unusually soft
murmur because of low cardiac output.
Diagnosis
Electrocardiogram
436
In mild pulmonary stenosis, slight rightward deviation of QRS

frontal axis and right ventricular conduction delay is usually
seen on the electrocardiogram (ECG).
In moderate pulmonary stenosis only 10 percent of patients
have a normal tracing. Right-axis deviation is usually present.
The R:S ratio in V1 is usually more than 4:1 and the R wave is
typically less than 20 mm. The T waves in the right precordial
leads are upright in approximately 50 percent of patients.
In severe pulmonary stenosis, the mean frontal QRS axis is
usually more than 110 degrees. A pure R, Rs or qR is usually
seen in right precordial leads and the R wave is usually more
than 20 mm. The R:S ratio in V6 may be less than 1. The
T wave may be upright or inverted in the right precordial leads
and the P waves are abnormally tall and peaked in lead II and
in right precordial leads.
In lead V1, the height of R wave in millimeters, multiplied
by 5 approximates the right ventricular pressure in mm Hg.
Figure 1: Schematic illustration of valvar pulmonic stenosis. In mild

stenosis, the ejection click (EC) is clearly separated from the first heart
sound (S1). The murmur starts with the click, peaks in early systole,
and ends way before the aortic component of the second heart sound
(A2). The pulmonary component of the second heart sound (P2) is
normal or decreased in intensity. In moderate pulmonic stenosis,
the click is closer to the first heart sound, the ejection murmur peaks
later in the systole and the murmur reaches A2 and the second heart
sound is widely split with soft pulmonary component. In severe valvar
obstruction, the click is either absent or occurs so close to S1 that it
cannot be heard separately, and the murmur peaks late in systole and
extends beyond the A2. The second heart sound is widely split with an
extremely soft or inaudible P2
In patients between 2 and 20 years of age, a pure R wave is

present in lead V112 (Figure 2).
In pulmonary stenosis, the electrocardiogram findings of left
axis deviation with right ventricular hypertrophy is suggestive
of Noonan syndrome (dysplastic pulmonary valve).
Chest X-ray
The most distinctive feature in valvular pulmonary stenosis
is a prominent main pulmonary artery resulting from poststenotic dilatation, which is present in 80 to 90 percent of the
cases. The apex of the heart is usually rounded and pointing
downwards (Figure 3). A left aortic arch is virtually always
present. When heart failure develops, marked cardiomegaly
results owing to right atrial and right ventricular enlargement
and pulmonary vascularity is decreased as a result of reduced
pulmonary flow.
Echocardiography
The two-dimensional echocardiogram clearly demonstrates
the typical features of the stenotic pulmonary valve from the
30
Figure 2: Elecrocardiogram of a 4-year-old girl with severe pulmonary stenosis showing right axis deviation with right ventricular hypertrophy
with strain pattern. The height of R in V1 is 40 mm. The patient had 180 gradient on echocardiogram which corresponds to the gradient
calculated by ECG (40 x 5 = 200)
include thickened and immobile leaflets, absence of doming,

hypoplastic valve annulus, supra-annular narrowing of the
proximal main pulmonary artery and absence of poststenotic
pulmonary artery dilation.
The Doppler echocardiogram allows quantitative assess
ment of the severity of pulmonary valve stenosis by estimating
the pressure drop across the pulmonary valve, which has
excellent correlation with direct pressure measurement at
catheterization (Figure 4).
Figure 3: Fluroscopic image in anterioposterior view in a 3 month old

infant with severe valvar pulmonic stenosis showing cardiomegaly with
right ventricle, right atrium and main pulmonary artery dilatation with
oligemia
standard and high parasternal short-axis and long-axis views

as well as the subcostal sagittal views. The leaflets are usually
thickened, doming with restricted systolic motion. Poststenotic dilation of the main and branch pulmonary arteries,
right ventricular hypertrophy and anatomy of the tricuspid
valve can be assessed. Features of dysplastic pulmonary valve
The right ventricular pressure compared with systemic arterial

pressure and the pressure gradient across the pulmonary valve
are the most important measurements made at catheterization.
A resting right ventricular pressure more than 35 mm Hg and
a pressure gradient across the pulmonary valve of more than
10 are considered abnormal. An end-hole catheter is used to
obtain carefully the withdrawal pressure recordings from the
pulmonary artery to the body of the right ventricle to assess
the severity and location of stenosis. The right ventricular
end-diastolic pressure may be normal, but usually is elevated
with severe obstruction or right ventricular failure. The right
atrial pressure is normal in mild-to-moderate obstruction, but
tall right atrial a waves are seen with severe obstruction.
Pulmonary artery pressure is normal in mild cases, but is
decreased and dampened in severe cases. This depression
437
Figure 4: Continuous wave Doppler from a 8-year-old boy with severe pulmonary stenosis
of pulmonary artery pressure is more marked in the main

pulmonary artery just beyond the valve than further distally
because of the Bernoulli effect.
In patients with normal cardiac output, classification of the
severity of pulmonary stenosis is routinely based on measurements of the right ventricular pressure and the pulmonary
valvular gradient.
Mild stenosis is characterized by a right ventricular
pressure less than half the left ventricular pressure or a valve
gradient less than 35 to 40 mm Hg. In moderate stenosis, the
right ventricular pressure is greater than half, but less than
75 percent of the left ventricular pressure or the gradient is
between 40 and 60 mm of Hg. Severe stenosis is defined as a
right ventricular pressure more than or equal to 75 percent of
the left ventricular pressure or a gradient more than 60 to 70
mm Hg.
Figures 5A and B: A. Fluoroscopy in lateral view shows Tyshak

Balloon across the stenotic pulmonary valve with a waist; B. Fully
inflated balloon with no waist
Treatment
Balloon Valvuloplasty
438
First described by Kan and associates in 1982.13 The technique

of balloon valvuloplasty is relatively easy. After obtaining
appropriate hemodynamic and angiographic information
about the severity and location of obstruction, an exchange
guidewire is introduced through an end-hole catheter and
positioned in the distal left pulmonary artery. A balloon is
chosen that is 20 to 40 percent larger than the angiographically
measured pulmonary valve annulus and it is positioned over
a guidewire with the valve at its midpoint. As the balloon in
inflated, a waist from the stenotic valve should be observed
initially and should disappear at full inflation (Figures 5A
and B). In patients with an annulus diameter of more than
20 mm, the double-balloon technique may be necessary, with

simultaneous inflation of two angioplasty balloons. A method
to calculate the effective diameter of two balloons was
described by Radke et al. Following balloon dilation, a careful
pullback with an end-hole catheter is performed to evaluate
the degree and site of any residual obstruction.14
Shortly after the introduction of pulmonary valvuloplasty
in children, the procedure was performed successfully in
neonates with critical pulmonary valve stenosis. Pulmonary
balloon valvuloplasty (PBV) is most risky and demanding
in newborns, but life saving as in this 15-day-old neonate,
2.5 kg, with a pulmonary valvar peak systolic gradient of 155
mm Hg (Figures 6A to C). Several technical advances, such as
the introduction of low profile balloons, upper limb approach
30
Figures 6A to C: Pulmonary balloon valvuloplasty (PBV) in a 15-day-old neonate
Figures 7A and B: Pulmonary balloon valvuloplasty (PBV) done with a loop in right atrium, like an upper limb approach. A. 3.5 20 mm
percutaneous transluminal coronary angioplasty (PTCA) balloon passed over 0.014 floppy PTCA guidewire; B. Stenotic pulmonary valve dilated
with 6 20 mm Tyshak balloon
(Figures 7A and B), have increased the success and safety of

balloon dilation in this group of patients, such that it is now
considered the treatment of choice. The use of angled-tip
catheters and high-torque wires has facilitated crossing the tiny
pulmonary valve orifice.
The short and intermediate-term results of pulmonary
valvuloplasty in children and adults with typical pulmonary
valve stenosis have been excellent.15 Long-term outcome has
been reported in smaller series of patients.16 The significantly
lower success rate for patients with dysplastic pulmonary
valves is not surprising given the anatomic features of these
valves. The mechanism of obstruction relief in patients with
typical doming pulmonary valves has been shown to be
commissural splitting, in most cases.
Most patients who have been treated with pulmonary
valvuloplasty have some degree of pulmonary insufficiency.
The incidence of moderate pulmonary insufficiency early
after valvuloplasty has been variably reported from less than
5 percent to as much as 24 percent at intermediate-term
follow-up.
Surgical Valvotomy
Since the advent of pulmonary valvuloplasty, surgical valvotomy
is reserved for patients with dysplastic pulmonary valve resistant
to dilation or patients with multiple levels of fixed obstruction.
Valvotomy can be achieved using either a closed or open
technique through the main pulmonary artery. Simple valvotomy
is ineffective, when the pulmonary valve is dysplastic. Partial
or more often total removal of the pulmonary valve may be
necessary. In addition, insertion of a trans-annular patch may be
necessary to enlarge the hypoplastic annulus and main pulmonary
artery. These patients are usually left with at least moderate
pulmonary insufficiency, which is well tolerated on follow-up.
Long-term relief of obstruction after pulmonary valvotomy is
excellent, and restenosis is uncommon.
Indications for the Procedure

Currently pulmonary balloon valvuloplasty is the first line
of treatment for pulmonary valve stenosis at any age.
439
Valvuloplasty should be performed in any symptomatic patient

as soon as the diagnosis is made including infants with critical
pulmonary valve stenosis, but if this is unsuccessful, surgery
should be performed without delay. Even asymptomatic
patients with severe obstruction should be treated with
valvuloplasty shortly after diagnosis. Patients with moderate
obstruction should undergo elective valvuloplasty, if the right
ventricular pressure is 50 percent of systemic or higher. No
intervention is necessary for patients with mild obstruction.
Conclusion
Isolated pulmonary valve stenosis is characterized by normal
or diminished pulmonary blood flow. Beyond infancy, mild
congenital pulmonary stenosis tends not to progress in
severity. Clinical findings in concert with Doppler studies
permit excellent non-invasive assessment of the severity.
Intervention for pulmonary stenosis has evolved from surgery
to catheter-based intervention. Balloon valvuloplasty for
patients more than 2 years provides excellent outcomes.
A systolic pressure gradient more than 40 to 50 mm Hg is
an indication for intervention. Balloon valvuloplasty with
oversized balloons especially in neonates tends to induce
pulmonary insufficiency. Pulmonary stenosis secondary
to dysplastic valve may require surgery with valvectomy
a transannular patch in those with a small annulus. Balloon
valvuloplasty is the procedure of choice for critical pulmonary
stenosis in neonates.
Pulmonary regurgitation
William Osler described pulmonary regurgitation inThe
Principles and Practice of Medicinein 1892. The distinctive
diastolic murmur of low-pressure pulmonary regurgitation
was characterized in 191017 and in 1936, isolated congenital
pulmonary valve regurgitation was reported with a review
of the literature.18 The morphology of the congenitally
malformed valve is variable. The basis of the valvular
insufficiency may reflect complete absence of the pulmonary
valve leaflets, rudimentary vestigial leaflets that do not
coapt or isolated deficiency of one of the pulmonary valve
leaflets.
Pathophysiology
440
Right heart hemodynamics is explained in Figure 8. Pulmonary

regurgitation is driven by the diastolic pressure difference
between the pulmonary artery and the right ventricle. These
pressure differences are often small. Hence small increments
in airway or intrathoracic pressure can increase pulmonary
regurgitation markedly. However, the most important
determinants are the right ventricular stiffness and right
ventricular afterload. A stiff right ventricle will raise the right
ventricular diastolic pressure and decrease the gradient for
pulmonary regurgitation. Ventricular stiffness is thought to

increase with hypertrophy or increased fibrosis.
Clinical features
Symptoms
Symptoms of right-sided heart failure can occur when the
severity and duration of the regurgitation result in right
ventricular enlargement and decompensation. Dyspnea on
exertion is the most common complaint. Easy fatigability,
light-headedness, peripheral edema, chest pain, palpitations,
and frank syncope may occur in patients with any cause of
right-sided heart failure and do little to elucidate the etiology
of the right-sided failure.
Jugular Venous Pressure

Jugular venous pressure is usually increased. Often, an
increased a wave is present, but this may be less apparent,
when significant tricuspid regurgitation with v dominant v
wave is also present.
Palpation
When right ventricular enlargement is present, a palpable
impulse (lift or heave) is usually present at the left lower
sternal border. Palpable pulmonary artery pulsation at the left
upper sternal border may be present in the setting of significant
pulmonary artery dilatation. With significant pulmonary
hypertension, pulmonic valve closure can be palpated.
Auscultation
The pulmonic component of the second heart sound (P2) is
inaudible in the absence of a pulmonic valve. In pulmonic
regurgitation due to pulmonary hypertension, P2is accentuated;
with increased right ventricular end-diastolic volume, the
ejection time is increased, P2is delayed and the S2split is
widened. A low-pressure regurgitant flow across the pulmonic
valve, as occurs when the pulmonary arterial pressure is
normal, is heard as a brief, decrescendo early diastolic
murmur at the upper left sternal border. It is made louder by
squatting or inspiration and softer by Valsalva maneuvers or
expiration. An S3or S4may be noted at the left mid-to-lower
sternal border because of the presence of right ventricular
hypertrophy or failure and is augmented by inspiration. The
Graham Steell murmur of pulmonary hypertension is a highpitched, early diastolic decrescendo murmur noted over the left
upper-to-left midsternal area and is a result of high-velocity
regurgitant flow across an incompetent pulmonic valve. The
regurgitant flow murmur may be present during the whole
of diastole because there is a pulmonary-to-right ventricular
pressure gradient throughout this time period. Typically, the
Diagnosis
Electrocardiogram
Volume overload of the right ventricle represented by terminal
r waves in lead V1 and aVR and S waves in lead I and V5-6
is the most common change. Atrial fibrillation is exceptional.
Chest X-ray
Plain radiographs change little with pulmonic regurgitation
unless tricuspid regurgitation also occurs, in which case
cardiomegaly and enlargement of the right-sided heart
contour are observed. Prominent central pulmonary arteries
with enlarged hilar vessels and loss of vascularity in the
peripheral lung fields (pruning) suggests severe pulmonary
hypertension.
Echocardiography
Two-dimensional echocardiography and M-mode echocardio
graphy reveal right ventricular hypertrophy and dilatation
and abnormal septal wall motion. In some cases, pulmonic
ring dilatation with poor valve leaflet coaptation may be
observed. Color flow Doppler echocardiography is the
mainstay for recognizing pulmonic regurgitation. In trivialto-mild pulmonic regurgitation, the jet is central and narrow.
In moderate-to-severe pulmonic regurgitation, the width of
the jet increases, as does the penetration of the jet into the
right ventricular outflow tract. In free or open pulmonic
regurgitation, color Doppler can miss the jet altogether due
to the brisk and laminar regurgitant flow. Using pulsed wave
and continuous wave Doppler, pulmonary artery systolic and
diastolic pressures can be calculated. Pulmonary artery systolic
pressure can be estimated (using continuous wave Doppler) in
the presence of tricuspid regurgitation by measuring the peak
regurgitant flow velocity across the tricuspid valve, converting
it to a pressure gradient (by use of the modified Bernoulli
equation) and then adding the gradient to an estimate of the
right atrial pressure. Pulmonary artery diastolic pressure can
be estimated by measuring the end-diastolic regurgitant flow
velocity across the pulmonic valve (at the QRS complex on
the ECG), converting it to a pressure gradient and then adding
the gradient to the estimated right atrial pressure. Pulmonary
arterial mean pressure can be estimated by converting the

early diastolic regurgitation velocity to a pressure gradient
and then adding it to the estimated right atrial pressure.
Treatment
Pulmonic regurgitation is seldom severe enough to warrant
special treatment because the right ventricle normally adapts
to low-pressure volume overload without difficulty. Highpressure volume overload leads to right-sided heart strain
and ultimately, heart failure. Underlying etiologies causing
severe pulmonic regurgitation, must be treated to prevent or
reverse right-sided heart strain and failure that may further
complicate the clinical picture. When right-sided heart
failure due to pulmonary regurgitation cannot be ameliorated
by medical management, appropriate options include
surgical reconstruction or replacement of the pulmonic
valve, preferably with a bioprosthetic valve. More recently,
percutaneous intervention for dysfunctional right ventricular
outflow tract conduits has become available. The intermediate
term results have shown that percutaneous bioprosthetic
valve implantation is a reasonable option for patients with
dysfunctional right ventricular outflow tract conduits,
especially those with high surgical risk.
30
murmur occurs in severe pulmonary hypertension, when the

pulmonary artery systolic pressure is more than 60 mm Hg.
The quality of this high-pitched early decrescendo diastolic
murmur is identical to that of aortic insufficiency. However,
the peripheral manifestations of aortic insufficiency are
absent. The associated findings of tricuspid regurgitation are
frequently present, prominent jugular venous pressure with
surging v waves, holosystolic murmur at the lower left
sternal border (louder with inspiration) and enlarged, pulsatile
liver.
Transcatheter Pulmonary Valve Replacement

A variety of implantable pulmonary valves are being
developed,21 but the Bonhoeffer valve is the most mature
technology. This consists of a bovine jugular venous
valve sewn into a stent mounted on a balloon (18 mm,
20 mm or 22 mm) and delivered via a custom designed
20F sheath. Techniques are being developed to allow
percutaneous insertion of pulmonary valves into the dilated
native right ventricular outflow tract by first reducing the
diameter of the right ventricular outflow tract by a cuff and
then delivering the valve into the cuff.22 The hemodynamic
and clinical benefits of this approach have yet to be
demonstrated.
Conclusion
The deleterious effects of chronic pulmonary regurgitation
are clearly seen as the syndrome of exercise intolerance
or arrhythmias associated with low pressure dilated right
ventricles. Along with pulmonary regurgitation right ventricular
dilatation is often seen. Percutaneous pulmonary valve insertion
is a significant advance, but the long-term fate is yet to be
determined.
Absent pulmonary valve syndrome

Total or subtotal absence of pulmonary artery leaflets is
defined as absent pulmonary valve (APV) syndrome. This was
first described by Chevers in 1847.19 APV may be the result of
441
6
and postnatally pathognomonic. In addition to these key

findings, typical features of the TOF, VSD, atrial septal defect,
coarctation of aorta and tricuspid atresia can be present.
Frequency
Absent pulmonary valve is a rare and severe disease,
particularly in the newborn and the fetus. The overall
frequency of APV is not known, because in epidemiological
studies APV is not categorized as a malformation on its own.
However, several reports quote a prevalence of 3 to 6 percent
of APV in patients with TOF.20
Clinical Description and Diagnostic Methods

Figure 8: Right heart hemodynamics in severe pulmonary regurgitation.
Premature tricuspid valve closure (PTC) occurs in mid-diastole, when
right ventricular diastolic pressure (RV; black line) exceeds right atrial
pressure (RA; purple line). Premature pulmonic valve opening (PPO)
occurs when right ventricular end-diastolic pressure rises above
pulmonary artery (PA) diastolic pressure
error or complete failure in valve development. Mild stenosis

of the pulmonary artery orifice and aneurysmal dilatation of
the main pulmonary artery as well as of the right or left or
both pulmonary artery branches coexist. Compression of the
major bronchi at the hilum is a secondary phenomenon and is
assumed to develop in fetal life.
Anatomical Variations
The spectrum of malformations to which APV may be
associated can be categorized into two types: APV with or
without ventricular septal defect (VSD).
The main clinical findings include pulmonary insufficiency,

ostial stenosis and bronchial obstruction secondary to
aneurysmally dilated pulmonary arteries. Clinical presentation
of infants, with either Fallot-type or non-Fallot-type APV,
is essentially the same and include air-trapping and CO2
retention, single S2, loud to-and-fro murmur on auscultation,
cardiac enlargement, aneurysmal hilar pulmonary arteries,
hyperinflation and dystelectasis of the lung lobes with shift
of the mediastinum on chest X-ray (Figure 9) and right
ventricular hypertrophy on ECG. Diagnosis is confirmed by
echocardiography in the subxiphoid long-axis and short-axis
views of aneurysmally dilated pulmonary arteries (Figure 10).
Pulmonary stenosis and insufficiency are shown by Doppler
color-flow (Figure 11). The clinical picture varies according
to onset and severity of symptoms, especially those of
respiratory insufficiency.
Thus, patients with APV are divided into two groups:
1. Adults and children without respiratory complications who
had corrective operation electively between 5 and 20 years.
Absent Pulmonary Valve with Ventricular Septal Defect

The most common form with VSD is the association with
TOF. The similarities with TOF include anterior deviation
of the infundibular septum in relation to the muscular septal
crest, malaligned VSD, overriding of the aorta, unobstructed
right ventricular infundibulam and aneurysmally dilated
pulmonary arteries.
Absent Pulmonary Valve without Ventricular Septal Defect
442
This is a less frequent form and muscular VSD may be rarely

observed; an association of a patent ductus arteriosus is
reported.
Absent pulmonary valve is not a single diagnostic
entity. It may occur as part of a range of cardiovascular
defects either simple or complex. However, the combination
of pulmonary insufficiency and bronchial obstruction by
aneurysmal pulmonary arteries is unique. It is both prenatally
Figure 9: Chest X-ray in a patient of tetralogy of Fallot with absent

pulmonary valve shows aneurysmally dilated pulmonary artery instead
of empty pulmonary bay
30
Figure 10: TTE in parasternal short axis view shows rudimentary

pulmonary valve (absent PV), color Doppler shows both pulmonary
stenosis (due to annular narrowing) and regurgitation. Ao = Aorta; LPA
= Left pulmonary artery; MPA = Main pulmonary artery; RPA = Right
pulmonary artery; RVOT = Right ventricular outflow tract.
In the fetus with non-Fallot type and large ductus, there is an

anomalous left-to-right shunt from the aorta across the ductus
into the pulmonary artery and together with the pulmonary
regurgitant flow into the right ventricle. In this condition, the
fetal circulation is compromised in two ways: run-off from
the aorta and volume overload of the right ventricle. The severe
negative effect on the right ventricular function resembles
that of severe aortic insufficiency on left ventricular function.
In all types, the full clinical picture may be complicated in
the prenatal period by non-immune hydrops fetalis and
polyhydramnios secondary to cardiac failure with the risk of
fetal or perinatal death or birth of a critically newborn. Thus,
prenatal diagnosis of APV is essential. Antenatal evolution
and progression of the disease requires sequential follow-up
studies and postnatal evaluation and treatment in specialized
centers. Immediate respiratory support and earlier corrective
operation will improve outcome.
Cardiac catheterization may be necessary to specify
additional hemodynamic and anatomic details. Magnetic
resonance imaging (MRI) and tracheobronchoscopy as
supplementary tools, especially in the evaluation of postoperative complications and persistent respiratory symptoms
due to reoccurrence of pulmonary artery dilation and bronchial compression or underlying tracheobronchial malacia.
Management
Figure 11: Transthoracic parasternal short-axis view at the basal level

with color Doppler demonstrates severe, hardly turbulent pulmonary
insufficiency (PI) in early diastole in a patient with absent pulmonary
valve
2. Infantile group presenting commonly as critically illnewborns with severe respiratory distress requiring
mechanical ventilation.
Recently, the fetus with APV became another important
group. During the first half of pregnancy, the diagnosis
seems to be incomplete. In the fetus with Fallot-type APV,
a distinct echocardiographic feature is the right-to-left shunt
during systole and diastole across the unrestricted VSD
secondary to the pressure-volume overload of the right
ventricle. Furthermore, the risk of survival of the fetus with
this condition in later pregnancy may be related to cessation
of the physiological flow from the pulmonary artery into the
descending aorta through the ductus arteriosus prior to its
premature closure.
The life-threatening symptom is respiratory distress in the

newborn. It occurs predominantly in the Fallot-type APV. Airway management as a primary procedure involves intubation,
mechanical ventilation and extracorporeal membrane oxygenation in some infants. It is usually performed under emergency circumstances. Urgent complete surgical repair should
relieve the compression of the tracheobronchial tree. This
is achieved by combined anterior and posterior plication
of the pulmonary arteries or by translocation of the pulmonary artery anterior to the aorta and away from the airways,
maneuver de Lecompte procedure.
Repair of pulmonary insufficiency and stenosis requires
placement of a valve conduit (homograft or heterograft) in the
right ventricular outflow tract. Repair in the Fallot-type APV
includes additional closure of the VSD with a patch. In infants
with non-Fallot APV, the ductus arterious must be closed.
Asymptomatic infants can undergo repair within the first 6 to
12 months. Repair should however not be delayed for too long
in order to avoid the harmful effect of the dilated pulmonary
arteries on the tracheobronchial tree. Apart from conduit
replacement in children as they grow, other reinterventions
may be required, mainly for persistent respiratory symptoms.
Midterm outcome for patients with Fallot-type APV who
survive the initial repair is favorable. Repeat plication of
pulmonary arteries and/or utilization of intrabronchial
expandable stents may improve the outcome in patients with
persistent airway compression who cannot be weaned from
the respirator because of severe tracheobronchial malacia.
443
Conclusion
Total or subtotal absence of pulmonary artery leaflets is defined
as absent pulmonary valve syndrome. It can be categorized
into APV with or without VSD. Major clinical findings
include pulmonary insufficiency, ostial stenosis and bronchial
obstruction. Surgical correction includes placement of a valved
conduit in the right ventricular outflow tract and surgical repair
to relieve the compression of the tracheobronchial tree.
To me the ideal doctor would be a man endowed with
profound knowledge of life and of the soul, intuitively
divining any suffering or disorder of whatever kind, and
restoring peace by his mere presence.
Henri Amiel
Acknowledgement
We express our thanks to Dr IB Vijayalakshmi, Professor of
Pediatric Cardiology, for providing some of the illustrative
images for this chapter.
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Magnetic resonance in a case of a newborn with pulmonary
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C hapter
31
Congenital Mitral Valve Diseases

Neeraj Awasthy, Radhakrishna S
Congenital mitral valve diseases are a heterogeneous group,

often complex and are commonly associated with other
congenital heart diseases (CHD) (Table 1). They are rare
as isolated lesions, occurring in approximately 4 of 1,000
children with CHD. The spectrum of mitral valve disease are
shown in Table 1. Mitral valve diseases have been subdivided
into stenotic, regurgitant or mixed lesions. This chapter will
focus on the regurgitant lesions and congenital mitral valve
prolapse. The mitral stenotic lesions have been dealt in
Chapter 27.
Table 1
Spectrum of congenital anomalies of mitral valve

1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.

Supramitral ring (SMR) or membrane

Hypoplasia of the mitral apparatus
Dysplasia of the mitral valve
Parachute mitral valve
Cleft mitral leaflet
Abnormal mitral arcade
Double orifice mitral valve
Accessory mitral valve tissue/orifice
Ebsteins anomaly of the mitral valve
Mitral valve prolapse
Mitral regurgitation due to other congenital causes:
i. Papillary muscle dysfunction due to ischemia
caused by:
Anomalous origin of the left coronary artery from
the pulmonary artery (ALCAPA)

ii. Cardiomyopathy
Dilated cardiomyopathy
Hypertrophic cardiomyopathy
Non-compaction of left ventricle

iii. Storage disease/infiltration
Hurler disease
Amyloidosis

iv. Connective tissue disorders
Embryology and Anatomy

Embryology
Formation of the atrioventricular (AV) valve is completed
early in embryologic development (by approximately 14
to 19 weeks of gestation). The mitral valve is formed from
endocardial cushions that originate both at the AV orifice and
from muscular tissue of the ventricular wall. This process
is driven by regulatory protiens that are expressed in genes
in the local myocytes in a time dependent manner. Specific
mutations altering the genetic milieu in which the AV valve
formation occurs results in congenital malformations of the
atrioventricular valves. The papillary muscles are derived
from the horseshoe-shaped myocardial ridge, which forms
along the left ventricular wall. Delamination and selective
apoptosis leads to the formation of deep trabeculae leading to
the formation of papillary muscles. Chordae tendineae form
from the process of selective apoptosis of the endocardial
cushions. These processes create the four major components
of the mitral valve appartus, which are the annulus, leaflets,
chordae tendineae and the papillary muscles.
Anatomy
The normal mitral valve consists of two leaflets and is
suspended from the fibrous mitral valve annulus at the
level of the atrioventricular junction (Figure 1). The mitral
annulus is derived from the fibrous skeleton of the heart. This
fibrous ring surrounding the mitral valve is part of a larger
fibrous structure, which attaches to the right and left fibrous
trigones, the membranous septum and the aortic root. As this
is discontinuous in the posterior aspect, there is an increasing
risk for posterior annular dilatation. There is fibromuscular
continuity between the mitral valve annulus and the aortic
valve. The anterior mitral leaflet is in continuity with the
Figure 1: Schematic diagram showing the mitral valve, well enclosed

in annulus fibrosus and the various components of the mitral valve
viz. Leaflets, chordae, papillary muscles and its insertion into the
ventricles. AML = Anterior mitral leaflet; PML = Posterior mitral
leaflet
446
noncoronary cusp and the left coronary cusp of the aortic

valve. Active contraction of the annulus fibrosus begins at
the onset of atrial contraction and continues through the
ventricular systole leading to a substantial reduction in the
annular orifice area. On further contraction of the muscle fibers
the mitral leaflets assume a concave shape, which contributes
to an effective seal. The mitral valve leaflets (anterior
and posterior) consist of collagen fibrosa and spongiosa
peripherally and mucoid myxomatous tissue centrally.
The anterior mitral leaflet is larger, sail-like and guards
approximately two-thirds of the left atrioventricular orifice,
but occupies only one-third of its annular circumference. The
height of the anterior mitral leaflet often is used clinically
to size the mitral valve prostheses. The posterior leaflet is
smaller, more rectangular and guards approximately onethird of the left atrioventricular orifice, but occupies about
two-thirds of its annular circumference. The posterior
leaflet is typically subdivided into three scallops, denoted
P1, P2, and P3. These scallops oppose the A1, A2, and A3
regions of the anterior mitral leaflet (Figure 2). The leaflets
free edge is termed the bare or membranous zone and the
remainder part of the leaflet is called the rough zone. The two
leaflets are separated by the anterolateral and posteromedial
commissures. The valve leaflets are normally prevented from
prolapsing into the left atrium (LA) by the tendinous cords,
the chordae tendineae. The chordae tendineae are a complex
network of collagenous cord-like structures that extend from
the free edges of the mitral valve leaflets and insert into the
papillary muscles. The two papillary muscles, the anterolateral
and posteromedial, arise from the ventricular free wall. They
Figure 2: The mitral valve with anterior and posterior components and
its relationship with the cusps of the aortic valve
are attached to the anterior and posterior mitral valve leaflets

via the chordae tendineae. Hence, ventricular geometry can
affect the function of the papillary muscles.
The four anatomic components of the mitral valve function
to allow unobstructed blood flow from the LA to the left
ventricle (LV) during diastole and to maintain competent
closure during systole. The leaflets open fully during the early
rapid-filling phase of diastole. They begin to close passively
as LV pressure and volume increase. Then, the leaflets reopen
briefly as atrial contraction occurs, adding additional volume
to the LV. During atrial contraction, annular contraction
effectively decreases the circumference of the mitral valve
by 20 to 30 percent throughout systole. Contraction of the
papillary muscles serves to maintain the length of the chordae
under the pressure that develops during systole.
Classification
The congenital mitral valve diseases can be classified according
to three criteria: hemodynamic, anatomic and functional. The
valves can be hemodynamically predominantly regurgitant or
stenotic. Anatomically, the congenital mitral valve anomalies
can be those with nondysplastic leaflets and those with
dysplastic leaflets. The annular dilatation can occur with
nondysplastic leaflet anatomy, with or without elongation
of the chordae or the papillary muscle. They can be seen in
anomalies with significant volume loading of the left ventricle
like in large ventricular septal defect or large patent ductus
arteriosus. The dysplastic leaflets usually have a lack of
valvular tissue.
hypoplasia. Group B is further subdivided into

parachute mitral valve, hammock mitral valve and
papillary muscle hypoplasia.
Congenital Mitral Regurgitation

Congenital mitral regurgitation (MR) is an uncommon condition
and is very rarely seen. Anything that disrupts any one or more
of the mitral valve apparatus is liable to cause regurgitation in
systole.
Congenital MR may result from an abnormality or disease
process that affects any one or more of the functional components
of the mitral valve apparatus (leaflets, annulus, chordae
tendineae, papillary muscles and the subjacent myocardium).
MR is associated with other congenital cardiac anomalies like
dysplasia of the valve, double orifice, deficient leaflet tissue,
isolated cleft of the mitral leaflet, atrioventricular septal defects,
displacement of the mitral valve like Ebstein type, an unguarded
mitral orifice and abnormal mitral arcade. The MR can occur
in the newborn due to papillary muscle infarction due to
myocardial ischemia. Papillary muscle ischemia and infarction
in children with critical aortic stenosis is well reported. It is
also seen in ALCAPA, coarctation of aorta and endomyocardial
diseases. MR can also occur in Marfan syndrome (Figures 3A
and B).
31
The anatomic classification by the STS-Congenital Heart

Surgery Nomenclature and Database Committee has classified
congenital mitral valve disease into four types. The type 1
lesions are supravalvar, type 2 lesions are valvar, with the
category divided into group A or annular defects and group B
or leaflet defects. Type 3 are subvalvar lesions with group A
involving abnormalities of the chordae tendineae and group B
involving defects of the papillary muscles. Type 4 are mixed
lesions.
The 1976 functional Carpentier classification of congenital
mitral valve disease is the most commonly utilized nomenclature. Carpentier and colleagues classified the lesions based
upon their work in 145 patients into three main types.
Type 1: Normal leaflet motion with valvar insufficiency
from a dilated or deformed annulus or by a defect
or cleft in the leaflet. These lesions are subdivided
into annular dilatation, cleft leaflet and partial leaflet
agenesis.
Type 2: Leaflet prolapse which is due to the absence or
elongation of the chordae or papillary muscles and
produces valvar insufficiency. These defects are
subdivided into chordal elongation, papillary muscle
elongation, and chordal agenesis.
Type 3: Restricted leaflet motion and hence mitral stenosis,
although valvar insufficiency can also be seen with
certain lesions. The stenosis is due to commissural
fusion, imperforation, thickening or shortening of
the subvalvar apparatus. These lesions are divided
into group A normal papillary muscles and group
B abnormal papillary muscles. Group A is further
subdivided into papillary muscle commissural fusion
and shortened chordae. This group also includes
excessive leaflet tissue, valvar ring and annular
Abnormalities of Valve Leaflets

Mitral regurgitation caused by involvement of the valve
leaflets occurs in many situations. Mitral valve prolapse
(MVP) involves both leaflets and chordae and may also
affect the annulus. Infective endocarditis can cause MR by
perforating valve leaflets; vegetations can prevent leaflet
Figures 3A and B: Echocardiography from a child with Marfan syndrome: A. Parasternal modified view showing myxomatous thickened
redundant leaflets of mitral valve; B. Apical four-chamber view showing prolapse of both leaflets of mitral valve (arrow). LA = Left atrium;
LV = Left ventricle; MV = Mitral valve; RA = Right atrium; RV = Right ventricle.
447
coaptation and valvular retraction during the healing phase

of endocarditis. Destruction of the mitral valve leaflets can
also occur in patients with penetrating and non-penetrating
trauma. The MR associated with drug exposure also results
from anatomical changes in the valve leaflets.
Abnormalities of the Mitral Annulus

The mitral annulus is saddle shaped and measures
approximately 10 cm in circumference in adults. It is soft
and flexible and contraction of the surrounding LV muscle
during systole causes the annular constriction that contributes
importantly to valve closure. The MR secondary to dilation
of the mitral annulus can occur in any form of heart disease
characterized by dilation of the LV, especially dilated
cardiomyopathy and also in post-tricuspid shunt lesions
causing LV volume overloading. LV submitral aneurysm
is a cause of annular MR commonly seen in sub-Saharan
Africa due to a congenital defect in the posterior portion of
the annulus. Diagnosis by transesophageal echocardiography
(TEE) and surgical repair have been reported.
Annular calcification may also be accelerated by an
intrinsic defect in the fibrous skeleton of the heart, as occurs
in the Marfan and Hurler syndromes. In these two latter
syndromes, the mitral annulus is not only calcified, but also
dilated, further contributing to MR.
Abnormalities of the Chordae Tendineae

The abnormalities of the chordae tendinae are important
causes of MR. Lengthening and rupture of the chordae
tendineae are cardinal features of the MVP syndrome. The
chordae may be congenitally abnormal; rupture may be
spontaneous (primary) or may occur as a consequence of
infective endocarditis, trauma, rheumatic fever or, rarely,
osteogenesis imperfecta or relapsing polychondritis. In most
patients, no cause for chordal rupture is apparent other than
increased mechanical strain. Chordae to the posterior leaflet
rupture more frequently than those to the anterior leaflet.
Patients with idiopathic rupture of mitral chordae tendineae
frequently exhibit pathological fibrosis of the papillary
muscles. It is possible that the dysfunction of the papillary
muscles may cause stretching and ultimately rupture of the
chordae tendineae. Chordal rupture may also result from acute
LV dilation, regardless of the cause. Depending on the number
of chordae involved in rupture and the rate at which rupture
occurs, the resultant MR may be mild, moderate or severe and
acute, subacute or chronic.
Involvement of the Papillary Muscles
448
Diseases of the LV papillary muscles are a frequent cause

of MR. Because these muscles are perfused by the terminal
portion of the coronary vascular bed, they are particularly
vulnerable to ischemia and any disturbance in coronary

perfusion may result in papillary muscle dysfunction. When
ischemia is transient, it results in temporary papillary muscle
dysfunction and may cause transient episodes of MR that
are sometimes associated with attacks of angina pectoris or
pulmonary edema. When ischemia of papillary muscles is
severe and prolonged, it causes papillary muscle dysfunction
and scarring, as well as chronic MR. The posterior papillary
muscle, which is supplied by the posterior descending branch
of the right coronary artery, becomes ischemic and infarcted
more frequently than does the anterolateral papillary muscle;
the latter is supplied by diagonal branches of the left anterior
descending coronary artery and often by marginal branches
from the left circumflex artery as well. Ischemia of the
papillary muscles is due to hypoxia, severe anemia, shock,
coronary arteritis of any cause or an anomalous left coronary
artery. Infact this is to be carefully looked for especially in
children. Infarcted and hyperechoic papillary muscle is
an important echocardiographic criteria and corroborative
evidence of ALCAPA.
Various other disorders of the papillary muscles may also
be responsible for the development of MR. These include
congenital malposition of the muscles; absence of one
papillary muscle, resulting in the so-called parachute mitral
valve syndrome and involvement or infiltration of the papillary
muscles by a variety of processes including abscesses,
granulomas, neoplasms, amyloidosis and sarcoidosis.
Left ventricular dysfunction: LV dilatation of any cause
including ischemia due to ALCAPA can alter the spatial
relationships between the papillary muscles and the chordae
tendineae and thereby result in functional MR. There may
be additional ischemic damage to the papillary muscles,
dilation of the mitral valve ring and/or loss of systolic annular
contraction contributing further to MR. The incidence and
severity of regurgitation vary inversely with the LV ejection
fraction and directly with the LV end-diastolic pressure.
Other causes of MR include obstructive hypertrophic
cardiomyopathy (HCM), the hypereosinophilic syndrome,
endomyocardial fibrosis, left atrial myxoma and various
congenital anomalies including cleft anterior leaflet.
Irrespective of cause, severe MR is often progressive, since
enlargement of the LA places tension on the posterior mitral
leaflet, pulling it away from the mitral orifice and thereby
aggravating the valvular dysfunction. Similarly, LV dilatation
increases the regurgitation, which in turn enlarges the LA and
LV further, causing chordal rupture and resulting in a vicious
circle; hence the aphorism MR begets MR.
Cleft mitral valve: This rare anomaly (Figures 4A and
B) was found by echocardiography in 10/13,400 children
(0.75/1,000). A cleft in the anterior mitral cusp (less often,
the posterior leaflet) is occasionally noted without an AV
septal defect. There is no gooseneck deformity and the
mitral annulus and leaflets are otherwise normal. The cleft
31
Figures 4A and B: Parasternal short-axis view from a patient with isolated cleft of mitral valve: A. Two-dimensional echocardiography showing
cleft in anterior leaflet of mitral valve (arrow); B. On color flow mapping, regurgitation jet through the cleft is seen. MV = Mitral valve
points anteriorly towards the LV outflow tract, unlike an

atrioventricular septal defect in which the cleft (commissure)
in the left atrioventricular valve points posteriorly towards
the inlet interventricular septum. Cleft leaflet could be termed
partial or complete depending upon its extension to mitral
valve annulus. One of the important reasons to make this
differentiation of isolated clefts from AV clefts is also that the
specialized conduction tissue differs so importantly between
these two lesions. About half of these clefts are isolated and
the rest associated with other congenital cardiac anomalies,
including secundum atrial septal defects. There is a variable
degree of MR that depends on the degree of separation of the
tissue on each side of the cleft and the chordal support, but
often clefts are not accompanied by significant regurgitation.
Double-orifice mitral valve: An accessory bridge or limbus
of tissue may partially or completely divide the mitral inlet
into two orifices, termed as DOMV. It can cause both mitral
stenosis (MS) and MR, with regurgitation in 45 to 50 percent
of the cases. These orifices are usually unequal, with the
smaller orifice directed towards the anterolateral commissure
(41%) or the posteromedial commissure (44%). In the latter,
atrioventricular septal defects are common (90%), and mitral
regurgitation is often present. This is described under LV
inflow obstructions obstructions (Chapter 27).
Accessory mitral orifice: This abnormality results from
a circular deficiency of mitral leaflet tissue. The size of the
orifice can vary and the border of the accessory orifice is

usually devoid of chordae tendineae. In some cases, chordae
may insert into an independent papillary muscle.
Accessory mitral orifice is best visualized in parasternal
short axis and subcostal four-chamber view with color Doppler
interrogation. An abnormal position and orientation of MR
jet may help to suspect this condition and warrants further
evaluation in different views. This condition is sometimes
associated with transposition of great arteries, partial
atrioventricular septal defect and interrupted inferior vena cava.
Mitral arcade: The tips of the two papillary muscles of the
left ventricle are connected by a fibrous cord to which the
free edge of the anterior leaflet is attached, either directly or
by short chordae tendineae. The entity was first described in
1967 by Layman and Edwards. The entity has also been called
Hammock mitral valve. In most patients, there is severe MR
from tethering of leaflet. In a few cases, MS has also been
described and involvement of tricuspid valve has rarely been
reported with AV valve regurgitation of both AV valves. The
age at presentation or death varies widely. Most patients
present in infancy, a few in early childhood and very rarely
in adults.
Ebstein's Anomaly of Mitral Valve: This is a rare anomaly
with very few published case reports. Here, the LA is dilated
and the posterior leaflet of mitral valve, which is dysplastic,
is displaced downward with normal insertion of anterior
449
mitral leaflet into the ventricular septum (above the septal

tricuspid leaflet). Few case reports have shown associated
thin left ventricular wall. This abnormality is best visualized
in apical, subcostal four-chamber views and in parasternal
long-axis view. The severity of MR can be assessed by color
and spectral Doppler interrogation.
Ebstein anomaly of mitral valve should not be confused
with Ebstein anomaly of left AV valve in association with
corrected transposition, where septal leaflet of morphologic
tricuspid valve is apically displaced.
The reported associations include Ebstein anomaly of
tricuspid valve, Marfan syndrome, double-outlet right ventricle, atrial septal defect, patent ductus arteriosus, coarctation
of aorta, hypoplasia of ascending aorta and valvular aortic
stenosis.
Pathophysiology
450
In mitral regurgitation, the normal blood flow from the LA to

the LV and subsequently to the systemic circulation is altered.
In the presence of MR, blood flows antegrade from the LV
into the aorta, and the regurgitant volume flows retrograde
from the LV into the LA. This causes a proportionate increase
in LV ejection volume. The regurgitant fraction re-enters
the LV, producing left ventricular volume overload. The LV
compensates via the Frank-Starling mechanism, resulting
in a greater ventricular stroke volume. The volume of the
regurgitant fraction depends on several factors, including
size of the orifice allowing regurgitation and the pressure
gradient between the LV and LA. This volume also depends
on the ventricular systolic pressure; therefore, the regurgitant
volume increases in situations that increase afterload, such
as aortic stenosis or hypertension. The regurgitant volume
varies directly with the LV systolic pressure and the size of the
regurgitant orifice is influenced profoundly by the extent of LV
and mitral annular dilatation. Since ejection fraction (EF) rises
in severe MR in the presence of normal LV function, even a
modest reduction in this parameter (< 60%) reflects significant
dysfunction.
During early diastole as the distended LA empties, there is
a particularly rapid descent in the absence of accompanying
MS. A brief, early diastolic LA-LV pressure gradient (often
generating a rapid filling sound [S3] and mid-diastolic murmur
masquerading as MS) may occur in patients with pure MR as
a result of the very rapid flow of blood across a normal-sized
mitral orifice.
As described previously, ventricular systole contributes
substantially to mitral valve function. Active contraction
at the level of the annulus both reduces the surface area
of the valve annulus and changes the shape of the valve
leaets in order to optimize valve function and contraction
of the papillary muscles further supports leaet position and
prohibits mitral insufciency. Therefore, systolic dysfunction
can independently cause or exacerbate mitral insufciency.
Clinical Features
Symptoms
The nature and severity of symptoms in patients with
MR relates to etiology, rate of onset and progression, LV
function, pulmonary artery pressure and the presence of
pre-existing valvular or myocardial diseases. Children with
minor degrees of MR are usually asymptomatic. Infants and
children exhibit signs and symptoms of congestive heart
failure relatively early, generally within 3 years of diagnosis.
These include failure to thrive, diaphoresis, pallor, tachypnea
and a predisposition to lower respiratory tract infections
or wheezing. Children may remain asymptomatic with no
complications of MR until the second or third decade of life.
Once pulmonary hypertension develops, complaints such as
dyspnea become more prominent with light activity. With
severe MR, children may experience limited growth and
failure to thrive. Hemoptysis can develop during the later
stages. An indolent course of MR may be deceptive because
of the ability of the heart to compensate for the altered
hemodynamics. This occurs because of changes in cardiac
pump loading such that increased diastolic filling increases
preload, whereas LV ejection, in part into the left atrium,
reduces afterload.
Physical Findings
There is increased precordial activity and a diffuse apical
impulse. The first heart sound is diminished and the
pulmonary component of the second heart sound is loud
and narrowly split when pulmonary hypertension is present.
In patients with severe MR, the aortic valve may close
prematurely, resulting in wide but physiologic splitting of
S2. A low-pitched S3 occurring 0.12 to 0.17 seconds after
the aortic valve closure sound, i.e. at the completion of the
rapid-filling phase of the LV, is believed to be caused by the
sudden tensing of the papillary muscles, chordae tendineae
and valve leaflets. The murmur may assume various
configurations dependent on the anatomy and severity. A
high-frequency, plateau-type blowing or harsh holosystolic
murmur is typically heard at the apex with radiation to the
axilla and back, but occasionally it is maximal anteriorly
at the left sternal border when the anterior leaflet is cleft
In patients with ruptured chordae tendineae, the systolic
murmur may have a cooing or sea gull quality, while a
flail leaflet may cause a murmur with a musical quality.
The systolic murmur of chronic MR not due to MVP is
intensified by isometric exercise (handgrip), but is reduced
during the strain phase of the Valsalva maneuver. A lowfrequency, apical diastolic murmur and third heart sound
may be present with more severe degree of valvular
insufficiency. Tachycardia is usually present with adequate
systolic blood pressure.
Electrocardiogram
Chest X-ray
Electrocardiography demonstrates left atrial and left ventricular

enlargement when significant mitral insufficiency is present.
The LA and LV are the dominant chambers enlarged in chronic

MR. The LA may be massively enlarged and forms the right
border of the cardiac silhouette. Pulmonary venous congestion,
interstitial edema and Kerley B lines are sometimes noted.
The holosystolic murmur of MR resembles that produced

by a ventricular septal defect. However, the latter is usually
loudest at the sternal border rather than the apex and is often
accompanied by a parasternal rather than an apical thrill. The
murmur of MR may also be confused with that of TR, but
the latter is usually heard best along the left sternal border,
is augmented during inspiration and is accompanied by a
prominent v wave and y descent in the jugular venous pulse.
When the chordae tendineae to the posterior leaflet of the
mitral valve rupture, the regurgitant jet is eccentric, often
directed anteriorly, so that it impinges on the atrial septum
adjacent to the aortic root and causes a systolic murmur that
is most prominent at the base of the heart. This murmur can
be confused with that of AS. On the other hand, when the
chordae tendineae to the anterior leaflet rupture, the jet is
usually directed to the posterior wall of the left atrium and the
murmur may be transmitted to the back.
Echocardiogram
Echocardiography is the most important imaging modality to
access congenital mitral valve insufficiency. Transthoracic
echocardiography (TTE) with Doppler imaging is indicated
to assess the mechanism of the MR and its hemodynamic
31
Investigations
severity (Figures 5A and B). The LV function can be assessed

from LV end-diastolic and end-systolic volumes and EF. The
evaluation of leaflet structure, function, chordal integrity,
the size of LA , LV, annulus, the regional and global LV
systolic function can be done by TTE. The mitral valve
apparatus, annulus, leaflets, chordae, and papillary muscles,
should be systematically assessed by echocardiography.
Doppler imaging should demonstrate the width or area of
the color flow MR jet within the LA, the intensity of the
continuous wave Doppler signal, the pulmonary venous
flow contour, the early peak mitral inflow velocity and the
quantitative measures of regurgitant volume, regurgitant
fraction and effective regurgitant orifice area. In addition,
the pulmonary artery pressures can be estimated from the
tricuspid regurgitation jet velocity. The echocardiogram in
patients with MVP is described in the next section. Studies
have demonstrated that a high level of accuracy can be
achieved when analyzing mitral valve pathology using
2D echocardiography and an incremental benefit can be
attained when combined with 3D imaging. Transesophageal
echocardiography provides greater detail than TTE.
Radionuclide Angiography
Although echocardiography is the imaging method most
suited for routine evaluation of structure, function and MR
B
Figures 5A and B: Various phases of the prolapsed mitral valve (in the present case the cause
of prolapse was ruptured mitral valve chordae)
451
severity, radionuclide gated or first pass blood-pool imaging

may be helpful in instances in which the echocardiographic
images are suboptimal or there is a discrepancy between the
clinical and the echocardiography information or there is a
need for more precise measurement of LV ejection fraction.
Cardiac Magnetic Resonance

Cardiac magnetic resonance (CMR) provides accurate
measurements of regurgitant flow that correlate well with
quantitative Doppler imaging. It is also the most accurate
non-invasive technique for measuring LV end-diastolic
volume end-systolic volume and mass. Although detailed
visualization of mitral valve structure and function is obtained
more reliably with echocardiography, CMR offers a promising
approach for more accurate assessment of severity of the
mitral regurgitation.
The cause of the regurgitation (e.g. prolapse of the mitral
valve) and a flail leaflet can often be distinguished by angio
graphy, but this assessment has been superseded by echocardiography in most institutions.
Natural History
452
The natural history of MR is highly variable and depends

on a combination of the volume of regurgitation, the state
of the myocardium and the cause of the underlying disorder.
Asymptomatic patients with mild primary MR usually remain
in a stable state for many years. Severe regurgitation develops
in only a small percentage of these patients, most commonly
because of intervening infective endocarditis or rupture of the
chordae tendineae. In patients with mild MR related to MVP,
the rate of progression in severity of MR is highly variable; in
most patients progression is gradual unless a ruptured chordae
or flail leaflet supervenes. Regurgitation tends to progress more
rapidly in patients with connective tissue diseases, such as the
Marfan syndrome, than in those with chronic MR of rheumatic
origin.
Atrial fibrillation (AF) is a common arrhythmia in patients
with chronic MR, associated with age and left atrial dilation
and its onset a marker for disease progression. Patients with
AF have an adverse outcome compared to patients who
remain in sinus rhythm and development of AF is considered
an indication for operative intervention, especially in patients
who are candidates for mitral valve repair. Because the natural
history of severe MR has been altered greatly by surgical
intervention, it is difficult now to predict the course of patients
who receive medical therapy alone. However, Horstkotte
and associates reported a 5-year survival of only 30 percent
in patients who were candidates for operation (presumably
because of symptoms), but who declined. Among patients
with severe MR resulting from flail leaflets, the annual
mortality rate is as high as 6.3 percent and at 10 years, 90
percent have died or undergone surgical correction. This latter

series included many patients who were initially symptomatic
or had LV dysfunction or AF and thus might be considered to
be at higher risk.
Double-orifice mitral valve has the best prognosis because
37 to 50 percent of these lesions have normal mitral valve
function. Even with mitral valve abnormal function surgery
was needed in only few cases. Patients with double-orifice
mitral valves have been described till older age, even upto
75 years. They had severe MR which was most often due to
late chordal rupture. Probably these adults had double-orifice
mitral valves had no or only minor symptoms.
Many older patients would be expected with cleft valves
if they have no significant regurgitation. In small series of
studies, children with cleft mitral valve with significant
regurgitation had a low survival.
For the rare Ebstein-like malformation, most patients
presented in early infancy with severe congestive heart
failure and the oldest and least severely affected patient had a
mitral valve replacement at the age of 2 years and 9 months.
There are no available studies of the age at death of untreated
patients with pure congenital MR of all types and even the
series reporting the age at clinical presentation give mean ages
and range, but not individual ages.
Even though there are probably many older patients with
milder congenital MR with no surgery, the outlook for MR
is better than for congenital MS. They are less likely to have
severe pulmonary venous and arterial hypertension and more
of them are suitable for repair rather than replacement. This
tendency was noted specifically in one series reported by
Daliento et al who found the mean age at presentation to be
1.4 years for mitral stenosis and 6.55 years for MR.
Treatment
Medical
The role of pharmacological therapy for MR remains another
subject of uncertainty and some debate. The medical therapy
is mainly aimed at increasing systemic cardiac output and
decreasing regurgitant flow. There are no clear guidelines
regarding when to initiate medical management. The
treatment is probably indicated when the LV begins to dilate.
In patients with moderate to severe regurgitation, afterloadreducing agents such as angiotensin converting enzyme
(ACE) inhibitors can improve cardiac output. Afterload
reduction may be the most beneficial therapy because it
reduces work on the heart by decreasing systemic arteriolar
resistance, thereby decreasing the regurgitant volume.
However, no studies have demonstrated that afterload
reduction actually delays (or eliminates) the need for surgery.
If the LA is markedly dilated or if pulmonary congestion
develops, diuretics are indicated.
Surgery
Mitral Valve Replacement
Mitral Valve Repair

The initial surgical approach to patients with congenital
mitral valve lesions is reconstructive surgery, as mitral valve
replacement in infants and small children is associated with
high mortality and reoperation rates. Repair spares the patient
the long term adverse consequences of valve replacement,
i.e. thromboembolic and hemorrhagic complications in the
case of mechanical prostheses and accelerated and premature
degeneration necessitating repeat valve replacement in the
case of bioprostheses. In addition, by preserving the integrity
of the papillary muscles, subvalvular apparatus and chordae
tendineae, mitral repair and valvuloplasty maintain LV
function to a relatively greater degree. The repair of mitral
insufficiency also depends on the cause. The congenital cleft
in the septal leaflet of the mitral valve can be closed with a
few sutures and the long-term result will be good. If the valve
annulus is dilated but LV is well preserved, an annuloplasty can
be done and the results are generally good. Techniques used to
treat annular dilation include reconstructing the annulus with
a prosthetic ring (Carpentier ring) and a rectangular resection
of a portion of the annulus with annulus plication. If there is
a flail mitral valve leaflet, artificial chordae can be inserted
and a plastic procedure can be performed on the leaflet.
However, prosthetic rings and artificial chordae have no
growth potential, and hence there are concerns about the use
of such prosthetic materials. In patients with a rigid prosthetic
ring, somatic growth of the heart may result in progressive MS
and proportional changes in the repaired valve may lead to
recurrence of regurgitation in patients with artificial chordae.
Surgery for chronic severe MR is indicated once symptoms
occur, especially if valve repair is feasible. Other indications for
early consideration of mitral valve repair include recent-onset
AF and pulmonary hypertension, defined as a PA pressure 50
mm Hg at rest or 60 mm Hg with exercise. Surgical treatment
of chronic severe MR is indicated for asymptomatic patients
when LV dysfunction is progressive, with LVEF declining
below 60 percent and/or end-systolic cavity dimension on
31
In infants and children, surgery for congenital mitral valve

disease is a major therapeutic challenge. There are many
technical difficulties due to the wide spectrum of morphologic
abnormalities and a high prevalence of associated cardiac
anomalies. Hence, the outcomes of surgical management of
mitral insufficiency are highly variable. As the anomalies are
usually complex, intervention is ideally postponed to allow
time for annular growth and tissue maturity. Children are also
more sensitive to insufficiency than adults. Surgery is needed
in patients with severe congestive cardiac failure and/or LV
dysfunction refractory to maximal medical therapy. It maybe
needed in the first months of life in some cases. Surgery should
be undertaken before the onset of left ventricular deterioration.
echocardiography rising above 40 mm. These aggressive

recommendations for surgery are predicated on the outstanding
results achieved with mitral valve repair, particularly when
applied to patients with myxomatous disease. Repair is feasible
in up to 95 percent of patients with myxomatous disease.
Long-term durability is excellent; the incidence of reoperative
surgery for failed primary repair is approximately one percent
per year for 10 years after surgery. For patients with AF, a LA
Maze procedure or radiofrequency ablation of the pulmonary
vein ostia is often performed to reduce the risk of recurrent
AF. In patients with significantly impaired LV function (EF
<30%), the risk of surgery rises, the recovery of LV
performance is incomplete and the long-term survival is
reduced.
Historically, mitral valve replacement in children has been

associated with high morbidity and mortality rates. As a
result, it is generally reserved for patients who have mitral
valve disease, which has failed at least one attempt at surgical
repair. Single center and multi-institutional long-term studies
have found 10-year survival rates ranging from 56 to 74
percent. More recent experience has found improved longterm survival rates, ranging from 83 to 91 percent, although
the need for repeat mitral valve replacement remains common.
Morbidities associated with mitral valve replacement include
arrhythmia, heart block, thromboembolic phenomena and
hemorrhagic complications of anticoagulation.
The late problems after mitral valve repair or replacement
are similar to those occurring after operating on stenotic
mitral valves. Some valves after repair still have or develop
so much regurgitation that the valve has to be replaced and
some prosthetic valves develop thrombus or other functional
difficulties and have to be replaced. The prognosis after
valve repair is much better than after valve replacement.
Valve repair by itself does not require anticoagulation for the
patient. The reasons for reoperation include severe residual
or recurrent MR or MS and for those with valve replacement
either deterioration of a bioprosthesis or thromboembolism
associated with a prosthetic valve.

Mitral valve prolapse (Figures 6A and B), also called as
systolic click-murmur syndrome, myxomatous mitral valve
disease, floppy-valve syndrome, billowing mitral leaflet
syndrome and Barlows syndrome. It is a relatively common
but highly variable clinical syndrome resulting from diverse
pathogenic mechanisms of the mitral valve apparatus. It is one
of the most common valvar anomalies. Prevalence of MVP
increases with age and is about 1 to 2 percent in pediatric
population. The prevalence of MVP is about 5 to 15 percent
in older age group.
453
Figures 6A and B: Transthoracic echocardiogram in parasternal long-axis view with color Doppler shows grade II mitral valve prolapse (MVP)
with mitral regurgitation (MR). LA = Left atrium; LV = Left ventricle
Pathology and Etiology
454
Macroscopic changes in MVP include excessive or redundant

mitral leaflet tissue with myxomatous degeneration and
greatly increased concentrations of acid mucopolysaccharide.
MVP is characterized by leaflet thickening, redundancy
with interchordal hooding, chordal elongation, and annular
dilatation. Both the anterior and posterior leaflets may be
involved, although the middle scallop of the posterior leaflet
is most frequently affected. Tricuspid and aortic valves
may be involved in 43 percent and 10 percent patients
respectively.
In most patients with MVP, the cause is unknown, but
in some it appears to be a genetically determined collagen
disorder. A reduction in the production of type III collagen
has been incriminated and electron microscopy has revealed
fragmentation of collagen fibrils. The disruption of collagen
bundles coupled with valve leaflets that are more distensible
and less rigid, predisposes to rupture of chordae. In many
patients, elongated, redundant or ruptured chordae tendineae
cause or contribute to the regurgitation. MVP may lead to
excessive stress on the papillary muscles, which in turn leads
to dysfunction and ischemia of the papillary muscles and
the subjacent ventricular myocardium. Rupture of chordae
tendineae and progressive annular dilatation and calcification
also contribute to valvular regurgitation, which then places
more stress on the diseased mitral valve apparatus, thereby
creating a vicious circle where in MR begets MR.
Apart from the primary myxomatous degeneration, MVP
is also associated with other connective tissue disorders like
Marfan syndrome, Ehlers-Danlos syndrome, adult polycystic
kidney disease, osteogenesis imperfecta, pseudoxanthoma
elasticum, straight back syndrome and Stickler syndrome. Other
common conditions associated with MVP include, annuloaortic
ectasia, ischemic heart disease, hypertrophic cardiomyopathy,

pectus excavatum, and in those whose body habitus is asthenic.
A disproportion between left ventricular cavity and the mitral
valve when LV cavity is small as compared to mitral valve is
causative for the functional prolapse as seen in patients with
hypertrophic cardiomyopathy or ostium secundum atrial septal
defect. MVP is seen in about 20 percent of patients with OSASD due to decreased LV volume and altered LV geometry,
which usually resolves on repair. Some studies describe MVP
as a condition in which heart appears trapped in chest cavity that
is small for its size leading to alteration in cardiac architecture
and distortion in mitral annulus.
Genetics
MVP is usually sporadic but some patients show familial
aggregation with autosomal dominant transmission with
variable penetrance and X-linked inheritance. Three different
loci on chromosomes 16, 11 and 13 have been linked to MVP,
but no specific gene identified. Mitral valve prolapse is not
seen in echocardiography of newborn babies.
Clinical Features
Mitral valve prolapse is more common in females and although
congenital is usually diagnosed in adolescent children and
young adults. The clinical course in MVP is often benign and
encompasses a broad spectrum of severities, ranging from only
a systolic click and murmur and mild prolapse of the posterior
leaflet of the mitral valve to severe MR due to chordal rupture
and massive prolapse of both leaflets. In many patients, this
condition progresses over years or decades. In others it worsens
rapidly as a result of chordal rupture or endocarditis.
Auscultation
Classic auscultatory findings are the most important feature
on which diagonosis is suspected and patient is refered for
echocardiogram. The most important finding is the mid- or late
(non-ejection) systolic click, which occurs 0.14 s or more after
the S1 and is thought to be generated by the sudden tensing
of slack, elongated chordae tendineae or by the prolapsing
mitral leaflet when it reaches its maximum excursion. Systolic
clicks may be multiple as different parts of leaflets prolapse at
different times. The click is associated with a high-pitched, late
systolic crescendo-decrescendo murmur, which occasionally is
whooping or honking and is heard best at the apex. The click
and murmur occur earlier with standing, during the strain of the
Valsalva maneuver and with any intervention that decreases LV
volume, exaggerating the propensity of mitral leaflet prolapse.
In other conditions with decreased venous return or increased
heart rate or increased contractility, the click and murmur also
occurs earlier. Conversely, squatting and isometric exercises,
which increase LV volume, diminish the prolapse and the clickmurmur complex is delayed, moves away from S1 and may
even disappear. In conditions with increased venous return or
decreased heart rate, the click and murmur occurs later. Some
patients have a mid-systolic click without the murmur; others
have the murmur without a click. Still others have both sounds
at different times. The most dramatic changes which can be
appreciated by continuous auscultation occurs on sudden

standing from the squatting position, when the systolic click
and murmur move to early systole, on a beat-to-beat basis as
the heart rate increases.
Investigations
Electrocardiography
Patients with MVP usually have normal ECG, but may show
inverted or biphasic T waves in inferior leads II, III and AVF
and or V5 and V6. There may be occasional evidence of
supraventricular or ventricular premature beats. Patients with
MVP show higher than normal incidence of left accessory
pathways and prolonged QTc. The clinical implications of
these findings and their prevalence in asymptomatic patients
with MVP is not clear.
31
Most patients are asymptomatic and remain so for their

entire lives. However, in North America MVP is now the
most common cause of isolated severe MR requiring surgical
treatment. Many patients have chest pain that is difficult to
evaluate. It is often substernal, prolonged and poorly related
to exertion and it rarely resembles angina pectoris. Chest pain
may be caused due to excessive stretch on chordae tendineae
leading to papillary muscle ischemia, coronary microvascular
perfusion anomalies, hyperadrenergic state with increased
myocardial oxygen demand and coronary vasospasm.
Arrhythmias, most commonly ventricular premature
contractions and paroxysmal supraventricular and ventricular
tachycardia, as well as AF, have been reported and may cause
palpitations, light-headedness and syncope. Sudden death is a
very rare complication and occurs most often in patients with
severe MR and depressed LV systolic function. There may
be an excess risk of sudden death among patients with a flail
leaflet. A constellation of features including atypical chest pain,
exertional dyspnea, palpitations, dizziness, syncope, panic
attacks and anxiety along with findings of low blood pressure,
thin build, and ECG changes have been termed mitral valve
prolapse syndrome.
Transient cerebral ischemic attacks secondary to emboli
from the mitral valve due to endothelial disruption have been
reported, though a causal relationship has not been established.
Infective endocarditis may occur in patients with MR and/or
leaflet thickening.
Echocardiography
Transthoracic echocardiography is particularly effective in
identifying the abnormal position and prolapse of the mitral
valve leaflets. Echocardiographic criteria of MVP is systolic
displacement of the mitral valve leaflets by at least 2 mm
into the LA superior to the plane of the mitral annulus in the
parasternal long-axis view. As mitral annulus is saddle shaped
and not planar, any prolapse in four chamber view should not
be used to diagnose MVP and the same should be confirmed
in parasternal long axis or two chamber view. Most cases
of prolapse involve the posterior middle scallop according
to Carpentiers nomenclature. M-mode echocardiography is
useful in measuring the thickness of the valve leaflets at the
midpoint of the EF slope and demonstrating the late systolic
posterior displacement of mitral leaflets. The long-axis view
can also be used to measure leaflet thickening during diastole
when the leaflets are slack. Patients with greater than 2
mm leaflet displacement and maximum leaflet thickness of
greater than 5 mm are considered to have classic MVP,
while those with leaflet thickness less than 5 mm have
nonclassic MVP.
Redundancy of the mitral valve leaflets is diagnosed on
the parasternal short axis view when the circumference of
the leaflets appears to be disproportionate to the chamber
size. Other features associated with MVP include dilated
annular dilation and chordal elongation. Color flow and
continuous wave Doppler imaging is helpful in revealing
and evaluating associated MR. TEE is indicated when more
accurate information is required regarding vegetations or
flail leaflets and routinely for intraoperative repair.
Management
All patients with suspected features should have a thorough
initial evaluation for correct diagnosis, risk stratification and
455
for associated other cardiac and non-cardiac conditions. Their

first degree relatives should be evaluated for MVP and other
connective tissue disorders.
Principles of management of pediatric patients of mitral
valve prolapse include:
To assure regarding benign nature of disease in majority of
patients and ensure that no undue restrictions are imposed.
Identification of patients who are at higher risk for
complications and preventing them.
To optimize the timing for mitral valve surgery, if necessary.
Most patients with mitral valve prolapse remain
asymptomatic throughout their lives and should be encouraged
to exercise regularly and may have clinical assessment every
3 to 5 years or earlier if any symptoms appear.
Symptomatic Patients
Patients with MVP and symptoms like palpitations or nonanginal chest pain, anxiety, or fatigue often respond to therapy
with -blockers. However, in many cases, the cessation of
stimulants like caffeine, alcohol, smoking and reassurance
may be sufficient. These patients may be sensitive to volume
depletion and chronic diuretic therapy should be avoided.
In patients with recurrent palpitations or history of syncope,
continuous or event-activated ambulatory ECG recordings
may establish the cause and guide management.
Upright tilt test may be useful in patients with dizziness or
syncope when vasodepressor/vasovagal cause is suspected .
Indications for electrophysiology study are similar to those
in general clinical practice and are necessary in patients with
supraventricular tachycardia as accessory atrioventricular
pathways may be common. Exercise testing is useful in
patients with palpitations and exercise-related symptoms.
Complications
Infective Endocarditis
MVP is the most common lesion associated with infective
endocarditis (IE). Patients with MVP have a three to eightfold
higher risk of developing IE, with an estimated incidence of
about 0.02 percent per year. Predictors of increased risk for
development of IE include male sex, age older than 45 years,
the presence of a systolic murmur, and leaflet thickening
and redundancy. In the absence of mitral regurgitation, the
incidence of IE is similar to that of the general population, but
in patients with mitral valve prolapse and a systolic murmur,
the risk increases to about 0.05 percent per year. The 2007
AHA Infective Endocarditis Guidelines specifically no longer
recommend that patients with MVP be given antibiotic for
IE, whether or not they have regurgitation or thickened valve
leaflets. But these guidelines have still not gained acceptance
456
with many physicians who continue to stick to contemporary

guidelines.
Sudden Cardiac Death

Sudden cardiac death (SCD) is a rare complication of MVP,
with an estimated incidence of 0.1 to 0.4 percent per year,
similar to the risk in the general adult population of the United
States.
Risk factors for SCD include history of recurrent syncope or
sustained supraventricular or complex ventricular arrhythmias
or family history of cardiac sudden death. Therapy with
b blockers may be useful in these patients.
Mitral Regurgitation
Severe mitral regurgitation resulting either from progressive
myxomatous degeneration or chordal rupture with flail leaflet
is the most common complication of MVP.
On echocardiography, the presence of thickened
leaflets, posterior leaflet prolapse, increased left ventricular
dimensions, higher systolic blood pressure, higher body
weight, older male predict a greater risk for development of
severe mitral regurgitation. By contrast, individuals with thin
leaflets have a very low-risk of developing significant mitral
regurgitation. The indications for repair/surgery are same as
for other forms of congenital MR.
Physical Activity
There is no evidence to demonstrate that strenuous exercise in
patients with MVP predisposes to sudden cardiac death that
otherwise would not have occurred. The Bethesda conference
report on eligibility recommendations for competitive
athletes with cardiovascular abnormalities dealt with a broad
spectrum of matters dealing with athletics. Several consensus
recommendations are appropriate to this discussion.
MVP patients with the following conditions are restricted to
low-intensity competitive sports only (class 1A): Arrhythmia
mediated syncope; Repetitive nonsustained or sustained
supraventricular tachycardia or frequent/complex ventricular
tachyarrhythmias on ambulatory Holter monitoring; Color
Doppler evidence of severe mitral regurgitation; Left
ventricular ejection fraction <50%.
Otherwise, MVP patients are permitted participation in
all competitive sports. Patients with syncope or presyncope
should not participate in competitive sports until the cause
of syncope has been defined and appropriately treated.
Patients with cardiac arrhythmia should have periodic
exercise tests performed and ambulatory ECG recordings
obtained while doing the type of exercise they are likely to
undertake.
Conclusion
Body and soul cannot be separated for purposes of treatment,

for they are one and indivisible. Sick minds must be healed
as well as sick bodies.
C Jeff Miller
Acknowledgement
We wish to thank Dr Milan for his assistance in preparing the
manuscript.
Suggested Reading
1. Carpentier A, Branchini B, Cour JC, et al. Congenital
malformations of the mitral valve in children. Pathology and
surgical treatment. J Thorac Cardiovasc Surg. 1976;72:854-66.
2. Creech O Jr, Ledbetter MK, Reemtsma K. Congenital
mitral insufficiency with cleft posterior leaflet. Circulation.
1962;25:390-94.
3. Sigfsson G, Ettedgui JA, Silverman NH, et al. Is a cleft
inthe anterior leaflet of an otherwise normal mitral valve an
atrioventricular canal malformation? J Am Coll Cardiol.
1995;26:508-15.
4. Zalzstein E, Hamilton R, Zucker N, et al. Presentation, natural
history, and outcome in children and adolescents with double
orifice mitral valve. Am J Cardiol. 2004;93:1067-69.
31
The mitral valve is the most complex of the hearts four

valves and is the one most commonly associated with disease.
Mitral valve prolapse is the most common but is not usually
a harmful condition, although it can lead to significant mitral
regurgitation in a small minority. Medical therapy may
provide symptomatic improvement in the cases with severe
regurgitation. Mitral valve repair is preferable to replacement
whenever possible.
5. Parr GV, Fripp RR, Whitman V, et al. Anomalous mitral arcade:

echocardiographic and angiographic recognition. Pediatr
Cardiol. 1983;4:163-65.
6. Grenadier E, Sahn DJ, Valdes-Cruz LM, et al. Two-dimensional
echo Doppler study of congenital disorders of the mitral valve.
Am Heart J. 1984;107:319-25.
7. Feindel CM, Tufail Z, David TE, et al. Mitral valve surgery
in patients with extensive calcification of the mitral annulus. J
8. Barber JE, Ratliff NB, Cosgrove DM, et al. Myxomatous
mitral valve chordae. I: Mechanical properties. J Heart Valve
Dis. 2001;10:320.
9. Kumanohoso T, Otsuji Y, Yoshifuku S, et al. Mechanism of
higher incidence of ischemic mitral regurgitation in patients
with inferior myocardial infarction: quantitative analysis of left
ventricular and mitral valve geometry in 103 patients with prior
myocardial infarction. J Thorac Cardiovasc Surg. 2003;125:135.
10. Levine RA. Dynamic mitral regurgitationmore than meets
the eye. N Engl J Med. 2004;351:1681.
11. Thourani VH, Weintraub WS, Guyton RA, et al. Outcomes and
long-term survival for patients undergoing mitral valve repair
versus replacement: Effect of age and concomitant coronary
artery bypass grafting. Circulation. 2003;108:298.
12. Enriquez-Sarano M, Schaff HV, Tajik AJ, et al. Chronic mitral
regurgitation. In: Alpert JS, Dalen JE, Rahimtoola SH (Eds.).
Valvular Heart Disease 3rd. Philadelphia: Lippincott Williams
and Wilkins; 2000. pp. 113-142.
13. Braunberger E, Deloche A, Berregi A, et al. Very long-term
results (more than 20 years) of valve repair with Carpentiers
techniques in nonrheumatic mitral valve insufficiency.
Circulation. 2001;104:I-I8.
14. Bishay ES, McCarthy PM, Cosgrove DM, et al. Mitral valve
surgery in patients with severe left ventricular dysfunction. Eur
J Cardiothorac Surg. 2000;17:213.
15. Remadi JP, Baron O, Roussel C, et al. Isolated mitral valve
replacement with St. Jude medical prosthesis. Long-term
results: A follow-up of 19 years. Circulation. 2001;103:1542.
16. Maskatia SA. Fellows forum. Congenital anomalies of the
mitral valve. Congenital Heart Dis. 2011;6:77-82.
457
C hapter
32
Mitral Atresia
INTRODUCTION
Mitral or left atrioventricular (AV) valve atresia patients
may have aortic atresia or a patent aortic root.1 Mitral atresia
coexisting with aortic atresia may be considered as a variant
of hypoplastic left heart syndrome (HLHS) and will not be
discussed in this chapter; this defect will be reviewed in
the chapter on HLHS (Chapter 47). This division, though
arbitrary, is also justified on the basis of different therapeutic
approaches for these two conditions; in HLHS patients almost
uniformly require Norwood procedure2 in the neonatal period
in contradistinction to mitral atresia with normal aortic root
patients, who require different types of therapeutic intervention
at varying ages depending upon the pathophysiology, largely
determined by the associated cardiac defects. Mitral atresia
with normal aortic root is a rare complex heart defect
characterized by atresia of the mitral or left AV valve and is
usually associated with several other abnormalities and is the
subject of this chapter. The term 'isolated mitral atresia' to
differentiate from mitral atresia/aortic atresia and aortic root
hypoplasia or HLHS has been used by some investigators, but
such use is discouraged.1
atresia with normal aortic root was reviewed early on by

Watson et al3 in 1960 and later in 1981 by Thiene et al.1
Atrioventricular Valves
Even though there have been earlier reports of mitral atresia

with normal aortic root, largest number of cases (n = 52)
were reported first in 1960 by Watson et al, consisting of 11
cases of their own and 41 from the literature.3 This is a rare
condition; Maude Abbott4 had only five cases in her 1,000
cases of congenital heart defects and Edwards5 had five cases
in a collection of 212 specimens of major cardiovascular
malformations.
Mitral atresia may be an absent atrioventricular connection or

an imper
forate valve membrane; this distinction was
emphasized by Anderson and Thiene6 although the
difference may simply be secondary to the timing of onset
of embryological insult, just has been postulated for tricuspid
atresia hearts7 and may not be clinically significant.6 In hearts
associated with ventricular inversion, the atretic valve may
be a morphologic tricuspid valve such as that seen in type
III, subtypes 1 and 5 of tricuspid atresia hearts,8 although
the physiology is that of mitral atresia. These considerations
justify the use of the term left atrioventricular valve atresia.
With absent atrioventricular connection, the atrioventricular
sulcus separates the muscular floor of the left atrium from the
ventricular myocardium beneath it;6 there may be a dimple
in the floor of the left atrium,9 representing the valve. In
imperforate valve membrane, the membrane separates the
left atrial and ventricular cavities. These hearts may have
primitive elements of mitral valve apparatus.9 Mitral atresia
may also be seen in patients with atrioventricular septal
defects (endocardial cushion defects) in that the common
atrioventricular valve occludes the entrance into the left
ventricle,9 in a manner similar to that seen with tricuspid
atresia.10 In the pathologic specimens (N = 30) studied by
Thiene and associates,1 24 had absent left atrioventricular
connection and six had imperforate left atrioventricular valve.
The tricuspid valve is patent, large or normal in size and
connects the right atrium to a right ventricle or a 'single'
ventricle.
PATHOLOGY
Atria
The description of pathologic features will be confined to

mitral atresia with normal aortic root. The pathology of mitral
The left atrium may be small and hypoplastic in most cases,

but the left atrial wall is thick and hypertrophied. Endocardial
EPIDEMIOLOGY
Atrial Septum
Patent foramen ovale or an atrial septal defect is usually
present; patent foramen ovale is seen in approximately twothirds and atrial septal defect in one-third.9 The atrial defect
may be restrictive and rarely, intact atrial septum may be
present; in such cases levoatriocardinal vein14,15 may partially
decompress the completely obstructed left atrium. Other
communications between left atrium and coronary sinus may
be seen.
Ventricles
Univentricular hearts are most common with mitral atresia
with normal aortic root; most of these are right ventricular
type and a few have two ventricles with atrioventricular
concordance. Double outlet right ventricle and double inlet
left ventricle with imperforate left atrioventricular valve,
though rare, have been reported. In the pathologic specimens
examined by Thiene et al,1 15 of the 30 specimens were right
ventricular type of univentricular heart, nine left ventricular
type, five were biventricular and one double inlet left ventricle.
When there are two ventricles, the majority of patients
have small left ventricles communicating with right ventricle
via a small ventricular septal defect (VSD). Approximately 10
percent of cases had normal sized left ventricles.3 The right
ventricle is always large and hypertrophied.
Ventricular Septum
In the presence of two ventricles, the majority have a small
VSD, although large VSDs have been reported.
Great Vessels
Transposition of the great arteries was stated to be
frequent,9,16,17 but was present only in 30 percent of cases
reported by Watson.3 By definition, the aortic valve and aortic
root are near normal in size. Right aortic arch, coarctation of
the aorta and interrupted aortic arch have been reported. In
the Watson series, right aortic arch was present in 8 percent
hearts, coarctation of the aorta was seen in 22 percent cases
and interrupted aortic arch was found in 4 percent specimens.3
Coarctation of the aorta and interrupted aortic arch were seen
only in subjects with normal pulmonary valve.
In the majority of patients, the pulmonary valve is normal
and not stenotic; however, valvar and/or subvalvar stenosis
or atresia may be present in 25 to 30 percent of cases. In
series analyzed by Watson and colleagues,3 pulmonary atresia
was seen in four and pulmonary stenosis in 11 (8 valvar, 2
subvalvar and 1 combined) out of a total of 52 cases. In another

clinical study of 40 patients, 11 (27%) had pulmonary stenosis
or atresia and 29 (73%) had no pulmonary stenosis.18 Of note,
coarctation of aorta has not been reported in association
with this lesion when pulmonary stenosis or atresia was
present;1,3,18 this is presumably because of fetal flow patterns
as reviewed elsewhere19 and in the chapter on tricuspid atresia
in this book (Chapter 28).
32
Mitral Atresia
fibroelastosis of LA may be present.3,11-13 The right atrium is

always enlarged and hypertrophied.
Other Associated Defects

Ductus arteriosus is patent in nearly 80 percent patients.9
Communications between left atrium and coronary sinus are
commonly seen. Persistent left superior vena cava may be
seen in some patients. Abnormalities of both systemic and
pulmonary venous return may be present especially when
associated with heterotaxy syndrome.
Extracardiac Anomalies
Major extracardiac anomalies are present in nearly half of the
patients. Heterotaxy (asplenia or polysplenia) may be seen in
nearly 25 percent of patients.3
PATHOPHYSIOLOGY
Pulmonary venous blood from the left atrium exits via the atrial
septal defect into the right atrium and mixes with systemic
venous return. If the interatrial communication is restrictive,
pulmonary venous congestion and edema develop. If the atrial
septum is intact, the neonate is unlikely to survive unless there
is an alternative drainage such as levoatriocardinal vein.14,15
Once in the right atrium, the blood is passed on to the right
or single ventricle via the tricuspid valve. The blood is then
distributed into the aorta and pulmonary artery; the relative
flows into the two circuits are dependent upon the resistances
offered by the respective circulations. This results in systemic
arterial desaturation in all patients with mitral atresia. The
degree of desaturation is proportional to the degree of right
ventricular outflow obstruction, which is either at valvar
and/or subvalvar level. In cases of pulmonary atresia, the
pulmonary blood flow is derived from either via the patent
ductus arteriosus or through aortopulmonary collateral
vessels.
CLINICAL FEATURES
Clinical presentation is largely dependent upon the patho
physiology related to the amalgamation of associated lesions
seen in these patients. The scenarios include pulmonary
venous congestion secondary to interatrial obstruction,
decreased pulmonary blood flow secondary to severe
pulmonary stenosis or atresia and increased pulmonary blood
459
flow causing volume overload and heart failure in the absence

of pulmonary stenosis.
These patients usually present as neonates (usually in
the 1st week of life) with cyanosis or difficulty in breathing.
Cyanosis in the newborn, in the presence of pulmonary
stenosis or atresia is due to diminished pulmonary blood flow
and complete-mixing of the pulmonary and systemic venous
returns in the right atrium and the right ventricle. Cyanosis
due to diminished pulmonary blood flow is manifested as the
patent ductus arteriosus begins to constrict. Cyanotic spells
are occasionally noted in infants. Features suggestive of
increased pulmonary blood flow and congestive heart failure
are presenting symptoms in nearly half of the patients; these
are the patients without any pulmonary stenosis. The clinical
features of congestive heart failure appear as the pulmonary
vascular resistance drops with the increasing age of the
baby. In babies with interatrial obstruction, tachypnea and/or
dyspnea along with cyanosis may be the presenting features;
these may be occur shortly after birth or weeks and months
following birth as and when the interatrial communication
becomes restrictive. In babies with intact atrial septum (rare)
the presentation will be immediately after birth.
Later during infancy, failure to thrive, irritability, lethargy
and dyspnea may be present. Exercise intolerance is present
in children who live beyond infancy. Clubbing may be present
later in infancy and childhood.3,18,20
Diminished femoral pulses may be seen in patients with
aortic coarctation and as mentioned above, coarctation of the
aorta is present in only patients who do not have pulmonary
stenosis. The precordial impulses show either hyperdynamic
right ventricle or right ventricular heave. Second sound is
often loud or may be single. Subjects with pulmonary stenosis
have long ejection systolic murmurs along the left sternal
border. Continuous murmur, related to high-velocity flow
across the restrictive atrial septal defect, may be heard in some
patients.9,21 Otherwise, there is no characteristic murmur
noted. Signs of congestive heart failure are evident in most
patients without associated PS. However, if there is severe
restriction of atrial septal communication, signs of pulmonary
edema may be seen instead.
INVESTIGATIONS
Chest X-ray
460
Chest X-ray findings are nonspecific and reflect the combined

effect of associated heart defects and status of pulmonary
blood flow. Cardiomegaly, with globular enlargement of the
heart is usually seen. Increased pulmonary vascular markings
are seen in subjects with increased pulmonary blood flow,
while the pulmonary vascular markings are diminished in
patients with pulmonary oligemia. In the presence obstruction
at the level of interatrial septum signs of pulmonary edema/
venous congestion may be noted.
Electrocardiogram
Tall, peaked P waves consistent with right atrial enlargement
are present in many patients. Right-axis deviation is seen
in most patients and a few cases (12%) may show left-axis
deviation. Right ventricular hypertrophy is seen in almost all
patients. Q wave in right precordial leads is commonly seen;
a qR pattern in right precordial leads is a fairly consistent
feature in one study.3
Echocardiography
Echocardiogram is useful in the diagnosis and provides nece
ssary information for planning effective clinical management.
Evaluation of cardiac anatomy in subcostal, apical, parasternal
and suprasternal notch views provides complete assessment.
Key structure to define is the crux cordis, the spatial relationship
between atrial and ventricular septae and the atrioventricular
(AV) junction.22 It is possible to visualize the atretic atrial floor
in cases with absent connection vs imperforate valve in cases
with imperforate valve membrane in the majority of patients,22
although this distinction may not be important in terms of
diagnosis or management. Another important distinction to
make is whether the patent right-sided AV valve represents one
AV valve, as in complete AV septal defect or it represents one AV
valve and the other AV valve is atretic (Figures 1A to D). This
determination is important with regard to clinical management.
In the former with complete AV septal defect, there is usually
no left atrial hypertension. In the latter, with mitral atresia, there
is a potential for a hypoplastic left atrium and the interatrial
communication should be evaluated for restrictive flow from
the left atrium to right atrium.
Another determination to make is the looping of the
ventricular mass. While d-looping is noted in majority of
hearts with this defect, l-looping of the ventricles have
been reported in approximately 20 percent of cases.18 In
the presence of l-loop, the left AV valve atresia, of course,
represents a tricuspid valve atresia with morphologic RV
underneath the left AV valve; however, the physiology is that
of mitral atresia.
Adequacy of atrial septal communication is assessed using
three criteria:
1. Diameter of the atrial level communication in 2-dimensional
image (Figures 1C and 2B).
2. Mean Doppler gradient using pulse and or continuous
wave signal.
3. Color Doppler signal (Figure 2A).
Mean Doppler gradient will depend on size of the
communication and the amount of pulmonary blood
flow at the time of evaluation. Apart from evaluating the
adequacy of atrial level shunt initially, this should be
performed at every follow-up study as well as after balloon
atrial septostomy or surgical septectomy since the atrial
communication may become inadequate over time.23
32
Mitral Atresia
Figures 1A to D: Selected video frames from an echocardiographic study of an infant with mitral atresia demonstrating atretic mitral valve
(AMV), indicated by arrows, in precordial long-axis view. A. and subcostal views; B, C and D. Closed C and open D tricuspid valve leaflets are
shown by arrows. Ventricular septal defect (VSD) in A and a very small atrial septal defect (ASD) in B is also shown. LA = Left atrium; RA = Right
atrium
The number (one or two), size and function of the

ventricle(s), size of the VSD, great artery origins and relationship and presence of stenosis or atresia of the pulmonary valve
may be determined in multiple views in a conventional manner; apical four-chamber and subcostal views are most helpful
in this regard. Suprasternal notch views should be scrutinized
along with Doppler interrogation to confirm or exclude aortic
coarctation.
Cardiac Catheterization and Selective Cineangiography

The diagnosis and assessment of associated defects can often
be made by good quality echocardiographic studies and cardiac
catheterization and angiography are rarely needed solely for
diagnostic purposes. The main reason for catheterization in
these babies is to relieve left atrial hypertension in cases of

restrictive patent foramen ovale or atrial septal defect by
balloon atrial septostomy, blade septostomy, static balloon
dilatation of the atrial septum or stent placement. These
interventions will be discussed below under management
section. Also, cardiac catheterization is indicated prior to
bidirectional Glenn and Fontan surgeries that these patients
will eventually require.
When cardiac catheterization is performed, left-to-right
shunt at right atrial level is demonstrated and the oxygen
saturations in the RV, aorta and pulmonary artery are similar.
Systemic arterial desaturation is always present and is
proportional to the degree of RV outflow tract obstruction.
Pressure pullbacks across the atrial septum should be
performed to ensure adequacy of the atrial septal defect.
461
Figures 2A and B: Selected video frames from subcostal views of an echocardiographic study of an infant with mitral atresia indicating a small
and restrictive atrial septal defect (ASD; arrow) in A. In B, color flow mapping of the same site shows color acceleration (arrow) across this area.
LA = Left atrium; RA = Right atrium
A mean pressure gradient in excess of 5 mm Hg is considered

significant, requiring intervention. The ventricular pressures
are at systemic level without any gradient across the aortic
valve. Pressure gradient across the pulmonary outflow tract
is present in patients with significant valvar or subvalvar
pulmonary stenosis. The pulmonary artery pressures are high
and are at systemic level in patients with no pulmonary outflow
tract obstruction, but are normal or decreased in subjects with
pulmonary stenosis. Pressure pullback recording across the
aortic arch may show pressure gradient in the descending
aorta in cases with aortic coarctation.
Injection of contrast material into the left atrium may
provide some clarity in the mitral atresia diagnosis (Figures
3 and 4). Selective cineangiography in the ventricle(s), aorta
and pulmonary artery are likely to define the associated
cardiac defects.
NATURAL HISTORY
462
In the clinical/pathologic review of 52 cases by Watson et al

in 1960,3 two were stillborn and 23 babies died during the
neonatal period. Average survival was 6 months. Only five
babies (10%) lived up to 1 year or more.3 In a more recent
study from Brazil which was published in 1991,24 reporting

outcome of a cohort of 23 patients, five babies died at ages
ranging from 11 days to 12 months, before any surgical
therapy could be undertaken. Remaining 18 patients (11 had
congestive heart failure and 7 had cyanosis due to pulmonary
stenosis) underwent palliative surgical procedures involving
surgical atrial septectomy, pulmonary artery banding or
Blalock-Taussig shunt. Twelve (66%) of the 18 patients
were alive at follow-up that ranged from 1 to 57 months.
Causes of death included heart failure (n = 1), cyanosis
(n = 3) and septicemia (n = 1). One patient has had Fontan
operation at the age of 10 years. Eleven of the 12 patients
were in New York Heart Association functional class I and
are awaiting further surgical procedures. Given the recent
developments in diagnosis and treatment of the neonate with
congenital heart defects, the current prognosis is likely to be
lot better than reported in the above two studies.
MANAGEMENT
Management is dictated by the clinical presentation. The
severity of cyanosis and level of oxygen saturation in
the newborn are largely dependent upon the severity of
Management at the Time of Initial Presentation
Mitral Atresia
Figure 3: Selected cine frames from a left atrial (LA) angiogram in

a left axial oblique (30 LAO and 30 cranial) view demonstrating
atretic mitral valve (AMV). Note the opacification of the coronary sinus
(CS) via a connecting (C) vein. Such communications have been
documented in the literature
Initial management of these babies is similar that used in

other cyanotic neonates.25 The infants temperature should
be monitored and neutral thermal environment maintained.
Ambient oxygen should be administered, if the infant is
hypoxemic. In cyanotic CHD patients including mitral
atresia, no more than 0.4 fraction of inspired oxygen (FiO2)
is necessary; higher levels of O2 do not increase O2 saturation
because of fixed intracardiac right-to-left shunting. In the
infants suspected of having pulmonary atresia or severe
stenosis, prostaglandin infusion (Prostaglandin E1 at a dose of
0.050.1 g per kilogram of body weight per minute) to open or
maintain patent ductus arteriosus should be promptly started.
Metabolic acidosis, defined as pH < 7.25 should be corrected
with sodium bicarbonate (usually 12 mEq/kg diluted half
and half with 5 or 10% dextrose solution) immediately. In
the presence of respiratory acidosis, appropriate suctioning,
intubation and assisted ventilation should be undertaken.
Since hypoglycemia can be a significant problem, the infants
serum glucose should be monitored. The neonates should
routinely receive 10 percent dextrose in water intravenously. If
hypoglycemia (< 30 mg/100 ml) is detected, 15 to 20 percent
dextrose solution should be infused. Calcium levels should
also be monitored and if hypocalcemia is detected, it should
be treated. Correction of hypovolemia and hypotension when
present should also be promptly instituted. Echocardiogram
should be performed at the earliest opportunity to establish a
complete diagnosis.
After initial stabilization of the baby, the management
depends upon the physiologic abnormality that the defect
complex produces.
32
Interatrial Obstruction
Figure 4: Selected cine frames from a left atrial (LA) angiogram in

a left axial oblique (30 LAO and 30 cranial) demonstrating atretic
mitral valve (AMV) in a patient who had previously undergone surgical
atrial septectomy. Note the restrictive opening (two small arrows) and
dilated pulmonary veins (PV). RA = Right atrium
pulmonary stenosis or atresia, adequacy of pulmonary blood

flow determined by pulmonary outflow tract obstruction, size
of patent ductus arteriosus, pulmonary vascular resistance and
degree of restriction at the atrial level shunt.
If there is a restrictive atrial level shunt, balloon atrial

septostomy may be urgently necessary. This may be accom
plished either by Rashkind balloon atrial septostomy26 in a
newborn or blade septostomy in an older infant.27,28 Since,
the left atrium is small and hypoplastic in the majority of
these infants, it may pose technical problems for balloon
and blade atrial septostomy.29 Static balloon dilatation of
the atrial septum30,31 with a balloon angioplasty catheter
(Figures 5A and B) may be used which may not only relieve
the obstruction, but also keep some restriction such that there
is no rapid fall in the pulmonary vascular resistance. Static
balloon dilatation is preferred by the authors.
In some patients, the atrial septum may be intact or have
a tight patent foramen ovale, which may not even allow
passage of a catheter. In such situations, puncture of the atrial
septum by Ross technique32 or radiofrequency perforation of
the atrial septum33-35 followed by static balloon atrial septal
dilatation30,31 or stent (Figures 6 and 7) implantation29,36-38
463
Figures 5A and B: Selected cineradiographic frames while performing static balloon dilatation of a markedly restrictive patent foramen ovale
demonstrating waisting (arrow) of the balloon. A. During the initial phases of balloon inflation which was completely abolished (B) at the conclusion
of balloon dilatation
464
may become necessary. These transcatheter methods may not

be feasible or successful in some infants and surgical atrial
septectomy is needed. Open atrial septectomy is considered
more appropriate than the closed, Blalock-Hanlon atrial
septectomy.18,20,39
There is evidence that atrial level opening that is adequate
early in the neonatal period may become restrictive with time. It
is suggested that all babies with this condition undergo balloon
atrial septostomy performed, if they have cardiac catheterization
prior to 1 month of age. In babies who did not require early
atrial septostomy or septectomy, serial echocardiograms should
be performed to assess adequacy of atrial septal defect. Atrial
septostomy or septectomy may be required laterespecially
in the group with unrestricted pulmonary blood flow or after
systemic-pulmonary artery shunt.18
of these patients will go into congestive cardiac failure and

this should be treated with adequate anticongestive measures.
As soon as a reasonable control of congestive heart failure is
achieved, pulmonary artery banding should be performed to
attain better control of heart failure, to prevent development
of pulmonary vascular obstructive disease and to reduce
pulmonary artery pressures to near normal level.
Increased Pulmonary Blood Flow with

or without Heart Failure
Increased Pulmonary Blood Flow along

with Interatrial Obstruction
As the transition occurs from fetal circulation in patients

without pulmonary stenosis or atresia, pulmonary blood flow
increases as the pulmonary vascular resistance drops. Some
This combination can occur frequently.20 We have demonstrated that rapid and predictable fall in pulmonary vascular
resistance occurs in patients who undergo relief of restrictive

In the subgroup of patients with decreased pulmonary blood
flow, placement of systemic-pulmonary artery shunt40,41
along with ligation of patent ductus arteriosus may become
necessary. This is required in all babies with pulmonary
atresia and in some babies with pulmonary stenosis.
32
Mitral Atresia
Figures 6A to D: Selected cineradiographic frames while implanting the stent across a markedly restrictive patent foramen ovale demonstrating
the position of the stent prior. A. During with a waist (W) of the balloon; B and at the conclusion C of stent implantation. Note the position of the
fully inflated stent (FI) before C and after D removal of the balloon
atrial level shunt by balloon or surgical atrial septostomy.20

Pulmonary artery band for such patients will prevent heart
failure and development of pulmonary vascular obstructive
disease and should be performed at the time of relieving atrial
septal obstruction.
followed by Fontan operation.44-46 Details of these surgical

palliative procedures for single ventricle repair are discussed
in chapters on Tricuspid Atresia (Chapter 28) and Hypoplastic
Left Heart Syndrome (Chapter 47) and will not be reviewed
here.
'Corrective' Surgery
CONCLUSION
At the present time, no definitive intracardiac repair is

feasible for these conditions. All mitral atresia patients are
likely candidates for single ventricle palliation and will need
staged palliation42,43 with bidirectional Glenn operation,42,43
Mitral atresia with normal aortic valve is a rare cardiac

anomaly associated with left atrial hypoplasia and has a
tendency to have restrictive atrial level communication. Early
balloon atrial septostomy and placement of pulmonary artery
465
Figures 7A and B: Selected video frames from subcostal views of an echocardiographic study of an infant with mitral atresia who had a stent
implanted one day (Figure 6) prior to the study, demonstrating the position of the stent (arrow) across the atrial septum. A. With color flow
mapping; B. Laminar flow (arrow) within the stent. LA = Left atrium; RA = Right atrium
band if there is unrestricted pulmonary blood flow become

main components of early palliative management. Systemic
to pulmonary arterial shunt may be necessary for patients with
pulmonary atresia or severe pulmonary stenosis. As the babies
grow, close attention should be paid to evaluate adequacy
of atrial septal defect by serial echocardiograms. Atrial
septostomy or septectomy may be necessary later in infancy,
if it were not required or not performed in the neonatal period.
Therefore, recognizing this constellation of cardiac defects
helps to guide early management decisions. Later 'corrective'
surgical therapy consists of bidirectional Glenn and Fontan
operations, similar to other single ventricle lesions.
When health is absent, wisdom cannot reveal itself, art
cannot manifest, strength cannot fight, wealth becomes
useless, and intelligence cannot be applied.
Herophilus
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466
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32
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467
c hapter
33
aortic valve diseases

Smita Mishra, Neeraj Awasthy
IntroductIon
The aortic valve (AV) is one of the semilunar valves of the
heart, normally located at the left ventriculoarterial junction.
It has a critical role in maintaining the fine coordination of
fluid mechanics between the systemic ventricle and systemic
arterial system during the entire cardiac cycle. Inherently, it is
tricuspid, i.e. guarded by three leaflets. However, occasionally
the number of leaflets differs, leading to a restrictive or
regurgitant valve.1,2 These numerical variations were known
in ancient era. In fact, Major Leonardo da Vinci was one of
the first to call attention to the aortic valve with two leaflets.3
Prevalence
The bicuspid aortic valve (BAV) is the most common abnormality of the aortic valve. It has an incidence of 0.03 to 0.34
per 1,000 live births and constitutes about 7 percent of all congenital cardiac malformations. The prevalence of congenital
BAV is 1.3 percent. Of that 2 percent patients will experience
significant aortic stenosis or regurgitation by adolescence.1,4-9
embryology1016
The embryonic truncus arteriosus is divided by the spiral
conotruncal septum. The normal right and left aortic leaflets
form at the junction of the ventricular and arterial ends of the
conotruncal channel. The non-septal leaflet (posterior) cusp
normally forms from additional conotruncal channel tissue.
The conotruncal channel tissue is subendocardial and needs
to undergo the process of cavitation and hollowing to form
the leaflets. In the 5th week of embryological development,
excess mesenchymatous tissue is absorbed to form an outline
of the aortic valve at the apex of the aortic vestibule. The
aortic valve cusps and sinuses are well formed by the 8th
week. The failure of any of the developmental steps leads
to isolated or combined malformation of the aortic valve
and the left ventricular outflow tract (LVOT). The theory

of hemodynamic moulding postulates that the failure of
development of cardiac structures is caused by diminished
blood flow through them. In fact, restrictive foramen ovale,
left ventricle, hypoplastic left ventricle (LV) and abnormal
mitral valve are often seen in association with aortic stenosis/
atresia and coarctation or interruption of arch.1,9-15
We will see later in the chapter that the AV forms an
important boundary of the LVOT and has a complex
relationship with membranous and muscular interventricular
septum and with both the mitral leaflets. Any embryological
malformation of these structures carry a composite anatomical
and therapeutic implications.16
genetIcs and FamIlIal InherItance1-4,14,17,18

There are compelling evidences of the familial occurrence of
aortic stenosis. It is known to occur with Turner syndrome
and Jacobsen syndrome. Non-syndromic occurrence occurs
sporadically following the pattern of multifactorial inheritance. However, the male predominance (male-to-female
ratio 3:1) as well as association of BAV with Turners
syndrome (45X chromosomal pattern) suggests an X-linked
etiology. A heritability study found no X-linkage but did find
linkage to chromosomal regions 5q, 13q, and 18q. Mutations
in the NOTCH1 gene (chromosome 9q) leads to signaling
abnormalities that may be responsible for the development
of a bileaflet aortic valve. Ellison et al studied an extended
family with BAV and found no evidence of linkage of BAV
in their pedigree to either the NOTCH1 gene or to the
chromosome 15 locus. They concluded that the disorder in
this family might be caused by a gene at a novel locus.13
Although aorta in patients with BAV have histopathological
findings similar to aorta in Marfan syndrome the underlying
genetic abnormality of Marfan syndrome, mutation in the
FBN1 gene that encodes fibrillin-1 and is not found with
BAV disease.
33
aortIc root: anatomIcal and FunctIonal asPects
Aortic VAlVe DiseAses
definition of the aortic root

As quoted in literature, Henle was the first person to introduce
the term arterial root to replace the term arterial ring. The
semilunar attachment of the valvar leaflets gives two types
of boundaries to the ventriculoarterial junction. First, the
morphological, which is a virtual ring and the second is the
hemodynamic or functional boundary along the attachment of
the semilunar valves.14-17
The aortic root can be defined as a cylinder, the wall of which is
made up of the aortic valvar sinuses along with the interdigitating
intersinusal fibrous triangles and with two small crescents of
ventricular muscle incorporated at its proximal end.14-17
extent of the aortic root
Aortic root extends from the basal attachments of the leaflets

within the LV to the sinotubular junction (STJ) (Figures 12
A and B).
components of the aortic root14-15

1.
2.
3.
4.
5.
6.
7.
Ventriculoarterial junction
Aortic annulus
Sinotubular junction
Interleaflet fibrous triangles
Sinuses of Valsalva
Aortic valve (AV leaflets)
Ostium of right and left coronary artery.
Ventriculoarterial JunctionAttachment of the

Aortic Root to the Heart
Attachment of the aortic root to the LVOT is such that
approximately two-third of the circumference of the lower
B
Figures 2A and B: A. Cartoon shows a bisected aortic root, and
illustrates how the semilunar attachment of the valvar leaflets
incorporates aortic wall in the intersinusal triangles, and ventricular
tissues at the base of each of the coronary aortic sinuses. Reprinted
with permission: Anderson R H14; B. Echocardiography aortic root in
long axis mid-transesophageal view. AV = Aortic valve; LA = Left atrium;
MV = Mitral valve; NCC = Non-coronary cusp; LVOT = Left ventricular
outflow tract; RCC = Right coronary cusp; RV = Right ventricle
part of the aortic root is connected to the muscular ventricular

septum. The remaining one-third, which is made up of part of
the non-coronary leaflet and part of the left coronary leaflet of
the AV, is in fibrous continuity with the anterior leaflet of the
mitral valve. The ends of this area of fibrous continuity get
thickened to form fibrous trigones. These trigones anchor the
aortic mitral valvar unit to the roof of the LV.14-17
Figure 1: Aortic rootattachment of the leaflets and interleaflet
fibrous triangles. LC = Left coronary ostium; LCC = Left coronary
cusp; NCC = Non-coronary cusp; RC = Right coronary ostium; RCC
= Right coronary cusp.
Aortic Annulus
The aortic annulus is a 3-pronged crown-like ring and has a
base formed by aortic annulus, a top formed by sinotubular
469
Sinotubular JunctionThe Outlet of the Aortic Root
congenitAl VAlVAr lesions
The STJ is the junction between the aortic root and ascending
aorta. It contains the sinus ridge and the sites of the attachment
of the peripheral zones of apposition between the aortic valve
leaflets.
The diameter of the aortic root at the level of the sinotubular
junction is 10 to 15 percent less than that at the level of
ventriculoaortic junction.14-20
Interleaflet Fibrous Triangles
Figure 3: Aortic valve leaflets forming a 3-pronged coronet. Ring 3 is

the virtual ring and forms the base of the crown by joining the basal
attachment points of the leaflets within the left ventricle. Ring 1 is the
true ring formed at sinotubular junction (STJ). The ring 2 represents
aortic attachment of leaflet at an imaginary plane and demonstrates
the pocket like attachment buttressed by the nodule of Arantius
junction, and in between a ring formed by pocket-like attachment of leaflets.
470
Echocardiographically, the annulus is well defined. To

understand this complex morphology of the aortic annulus,
we need to review the Figures 1 to 3. The ring joining the
hinge points of the valve in parasternal long-axis view is
designated as annulus, but factually an annulus is one of
the several such rings incorporated within the aortic root.
Evidently, aortic annulus is no discrete anatomic structure.
Surgically, the annulus is described as a semilunar crownlike structure demarcated by the hinges of the leaflets.
Furthermore, the aortic root contains at least 3 circular rings
and the leaflets are attached throughout the length of the
root in the three dimensional imaginary plane. Therefore,
the leaflets take the form of a three-pronged crown-like
ring, hinging on the supporting ventricular structures.
Therefore, the annulus has a base of the crown, the virtual
ring joining the basal attachment points of the leaflets
within the LV. This plane represents the outlet of the LVOT
(Figure 3, ring 3) or the inlet of the aortic root. The true
ring is formed at the STJ and forms at the top of crown. In
between these two rings, a third ring exists at a plane which
(Figure 3, ring 1) passes through the attachment of the leaflet
against the wall of the sinus of Valsalva. The scalloped
configuration of the hingelines of the leaflets (Figure 3,
ring 2) crosses the ventriculoarterial junction, leaving
interleaflet fibrous triangles between the sinuses that are
anatomically aortic, but hemodynamically ventricular. The
semilunar hinges also cross the anatomic ventriculoarterial
junction14-17 (Figures 2 and 3).
The two interleaflet triangles bordering the noncoronary leaflet

are also in fibrous continuity with the fibrous trigones, the
mitral valve, and the membranous septum. They project above
the ventricular mass like three prongs of a coronet in potential
communication with extracardiac space (Figures 1 and 2). The
triangles are thinner and less collagenous; and hence, are a
vulnerable site for aneurysm formation. The triangle between
the right and the noncoronary leaflets adjoins the interventricular
part of the membranous septum, which together with the right
fibrous trigone, forms the central fibrous body.14-17 The second
triangle lies between the noncoronary and left coronary cusp in
the area of the left-posterior aortic commissure. The left trigone
is a part of extensive curtain of the aortic-to-mitral valve fibrous
continuity. The third triangle present in between the right and
left coronary cusp, is least extensive.
Sinus of ValsalvaStructure and Function

Sinus of Valsalva are the three bulgings at the root of the aorta.
The aortic root has three bulgings in its circumferential wall
to accommodate the extra size of the valvar leaflet, known as
sinus of Valsalva. Normally, the right sinus of Valsalva projects
towards the right side of the intact interventricular septum.
Therefore, any ventricular septal defect (VSD) in the area may
create the impression that the aorta is overriding. In congenital
heart defects (CHDs) like tetralogy of Fallot, true override is seen
and the degree of override may vary from 15 to 95 percent. In the
en face view, the aortic valve in closed position shows triradiating
lines of apposition between the adjacent leaflets reaching to the
peripheral commissures, and encircled by the aortic wall.
As mentioned below, the opening and closing of the aortic
valve is related to the principles of fluid hemodynamics, i.e.
acceleration, vortex formation and subsequent deceleration of
the blood column. Along with that, there are changes in pressures
on both sides of the AV. The sinuses of Valsalva play a definitive
role in the dynamic interactions of the aortic root with the LV on
the one side and systemic vascular pressure on the other side.14-20
Aortic Valve
Structure of the aortic valve: As we know AV contains three
cusps or leaflets. In the normal AV, the cusps are symmetrical,
33
mobile, free upto the commissures so to achieve equal overlap

on closure. The AV is firmly anchored to the fibrous skeleton
of the base of heart within the aorta and the cusps are attached
in a semilunar fashion at their base to the scalloped annulus.
The wedged position of the AV allows it to be in continuity
with the anterior mitral leaflet14-20 (Figures 1 and 2).
Functioning of the aortic valve: The leaflets are attached
to the aortic root, in such a manner that they form pockets.
Moreover, the pocket shaped configuration of the cusp is
dependent on the suspension of the leading edges of the cusps
from the aortic wall above the anatomical aortic annulus and
is buttressed by the nodule of Arantius21 (Figure 1).
During the ventricular systole, when the valve opens,
the leaflets fall back into their sinuses without the potential
of occluding any coronary orifice and allows unobstructed
ejection of blood. These pockets expand when the systolic
pressure of the LV ceases to push them up and the aortic
diastolic pressure exceeds the LV pressure. This allows the
pocket of leaflets to expand with the diastolic aortic pressure
and ceased column of blood. In order to support a large diastolic
pressure difference, the cusps must close simultaneously
in all operating conditions and should not touch the wall of
the aorta. It can be postulated that a fluid dynamic control
mechanism exists which positions the cusps away from the
wall of the aorta without the need of subvalvar apparatus, and
the slightest reversed flow leads to efficient valve closure.14-23
Robicsek et al studied the functioning of congenital
BAVs and reported that, the anatomical length of the leaflet
edges is constant, but their functional length must change,
to match the geometry of full closure and opening. The
gradual folding and unfolding of the cusps is a necessity in
the process. As opposed to the normal tricuspid aortic valve,
the folding is not only excessive, but some folds and creases
persist throughout the cardiac cycle. They are also sharper
and shaped in more acute angles. The authors noticed that
to compensate for the leaflet length discrepancy in the
congenital BAVs between the full opening and full closure,
there is the extension of the area of approximation of the
cusps. This is achieved by an increased bulge (doming) of
the leaflet bellies, which allows the leaflet edges to either
fold or travel in an upward convex arch or both. They also
observed the geometrical alteration by which the line of
apposition deviates from the centre.24
Figure 4: Origin of coronary arteries from the facing sinuses.

LAD = Left anterior descending artery; LCC = Left coronary sinus;
PA = Pulmonary artery; RAA = Right atrial appendage; RCA = Right
coronary artery; RCC = Right coronary sinus.
It is exceedingly rare to encounter origin of a coronary artery

from the non-facing aortic sinus.14,15,25
hIstologIcal asPect oF aortIc valve

Each AV leaflet has a fibrous core, which has two
components1. Fibrosa made up of mainly collagens, 2.
Spongiosa, which has elastin. The two aspects of the covering
of the leaflets are known as arterialis and ventricularis
on the respective sides. The collagen bundles are aligned
circumferentially, parallel to the free margin, adding to the
undulations on the arterial aspect. Radially aligned collagen
fibers are found near to the hinge line. In the middle of the
free edge of each cusp on the ventricular surface, is a fibrous
mound made up of mass of elastic tissue that is called nodule
of Arantius. Coaptation of the three nodules ensures complete
central closure of the valve during diastole. It has been
demonstrated in the pig valve that the ventricularis contains
a considerable amount of sheet elastin, whereas the elastin
fibres in the fibrosa are arranged like tubular meshwork,
extended circumferentially across the leaflet.14,26,27
Origin of Coronary ArteriesConcept of Facing Sinuses
InterPlay oF Pressure dynamIcs

between lv and aorta
Two of the aortic sinuses give rise to the main coronary

arteries and the sinuses are termed as right (or anterior) and
left coronary (left posterior) sinuses (Figure 4). The third sinus
is conveniently termed as the non-coronary (right posterior)
aortic sinus. Universally, irrespective of the aortic and
pulmonary valve relationship, aortic sinuses adjacent to the
pulmonary valve (PV) gives origin to the coronary arteries.
Accordingly, they are described as the facing aortic sinuses.
During the systole, when the LV pressure exceeds the aortic

root pressure, AV opens to eject the blood. Precisely, the LV
in systole is the upstream chamber of the high pressure arterial
system. The diastole starts with isovolumic relaxation of the
ventricles. When the LV pressure decreases to less than the
aortic pressure, blood column moves backwards, leading
to closure of the AV. Interestingly, with closure of AV and
opening of the mitral valve, LV becomes the downstream
471
472
chamber for the low pressure pulmonary venous system.

To achieve this lowest pressure, the ventricle needs active
relaxation, a process, which requires energy. This active
relaxation creates a suction effect, which helps in the early
rapid filling phase of diastole. The atrial systole provides
atrial kick and the remaining left atrial blood is pushed
forward into the LV. To understand the mechanics of the
ventricle one must understand the concept of preload and
afterload. Often these terms create a lot of confusion.
Preload can be defined as all of the factors that contribute to
the passive ventricular wall stress (or tension) at the end of
diastole, and the term afterload can be defined as all of the
factors that contribute to the total myocardial wall stress (or
tension) during systolic ejection. The preload refers to the
stretch of the LV just before the onset of contraction. The
inflow of the atrial blood contributes to the preload of the
ventricle. During ejection phase, the aortic pressure almost
equalizes to LV and little gradient exists. The blood flows
unobstructed to the peripheral tissues.14,15,28-30
Physiologically, during each cardiac cycle, the aortic root
varies in symmetry and dimensions. Geometrically, aortic
root dimensions differed approximately by 12 percent during
the cardiac cycle in animal experiments. Recently, Heer et al
demonstrated the significant individual dynamic changes in
the dimensions of the aortic root in a study utilizing ECGgated multidetector computed tomography.30
The model of the aortic root was studied for its inherent
capacity to effectively withstand prolonged sheering forces
generated during the extreme change in pressures on either
side of the AV. Now it is known, that various anatomical
asymmetries customary at the level of the cusps give
mechanical advantage to the aortic root during the cardiac
cycle. Dagum et al published their experimental work in a
three-dimentional model of the bovine aortic root on how
it undergoes complex, asymmetric deformations during
the various phases of the cardiac cycle. The description
included strain happening at the aorto-ventricular and STJ,
as well as the elongation, compression, sheer and torsional
deformation of the aortic root.30 These deformations were not
homogeneous among the left, right, and non-coronary regions.
Furthermore, changes in the left ventricular volume, pressure,
and contractility affected the degree of deformation in a nonuniform manner in the three regions studied and these effects
varied during isovolumic contraction, ejection, isovolumic
relaxation and diastole.13,14,28-30
They concluded that the aortic valve repair techniques or
methods of replacement using unstented autograft, allograft,
or xenograft tissue valves that best preserve this normal
pattern of aortic root dynamics should translate into a lower
risk of long-term cusp deterioration.30A
Obstructive lesions of the aortic valve manifest as systolic
gradient between LV and aorta which in turn, increases the
left ventricular afterload. On the contrary, ineffective closure
of the AV exposes the aorta to the ventricular diastolic low
pressure and promotes reverse flow across the AV. The aorta
needs a constant diastolic pressure to maintain the mean

systemic blood pressures, so as to maintain the physiological
requirement of the peripheral tissues as well as to maintain the
coronary blood flow during the diastole. The incompetent AV
hinders these physiological necessities.
relatIonshIPs oF the aortIc root and Its

clInIcal ImPortance
aortic root and left ventricular outflow tract
The left ventricular outflow is a small area. This subaortic
area, also known as aortic vestibule, is smaller and less
well defined than right ventricular outflow tract (RVOT).
Anteriorly, it is formed by the muscular and membranous
ventricular septum. The posterior boundary is drawn mostly
by the free inferior margin of the anterior mitral leaflet that
forms a curtain between the inflow and the outflow of the LV.
Also, a small part of the posterior boundary is contributed by
the intervalvar septum and the posterior mitral leaflet where
it fuses with the AML.14-17
relationship of the right and left ventricular outflow

tracts to the aortic root
Despite the fact that RVOT and LVOT have significant difference
in length, at the base of the heart, aortic and pulmonary valve
can be seen almost at the same plane (Figures 5 and 6). This
is possible because the RVOT wraps circumferentially around
the LVOT. Therefore, the anterior wall of the LVOT shares
part of the posterior wall of the RVOT. This sharing of the
common wall exists beyond the semilunar valves. The main
pulmonary artery (MPA) and the proximal right pulmonary
artery, share their walls with the proximal ascending aorta.
Echocardiographically, this arrangement is described as cup
and saucer appearance seen in parasternal short-axis or basal
view, where the AV can be seen as a circle or cup. The right
and left atrium forms the posterior part of the saucer and the
tricuspid valve, RVOT, PV and MPA, all opening up in the
long-axis in this view, form the anterior and the lateral part. The
PV lies to the left and anterior to the AV. As described above,
the AV is in fibrous continuity with the AML.13,14,16,30
aortic root and membranous septum

The membranous interventricular septum is morphologically
an important area. Posteroinferiorly, it is related with the
tricuspid valve. The anterosuperior boundary is formed by the
AV (Figure 7). On the left side due to the higher attachment of
the mitral leaflet, the membranous septum is atrioventricular
and a defect in this area presents with a obligatory LV to RA
shunt. Due to this important relationship, the anatomy of this
area has enormous therapeutic importance. A septal defect in
this area may be complicated by aortic valve prolapse and
may cause an incompetent valve.
33
Figures 5A to c: A. Cartoon showing the base of the heartthe

left and right atrium, tricuspid valve, right ventricular outflow tract,
pulmonary valve and pulmonary artery, arranged clockwise, around
the centrally placed aortic valve (cup and saucer arrangement);
B. Parasternal short-axis view showing TV, RVOT and PV opening
up longitudinally, around the AV; C. 3D Echoparasternal short-axis
view showing the AV opening axis. AV = Aortic valve; LA = Left atrium;
PV = Pulmonary valve; RA = Right atrium; RVOT = Right ventricular
outflow tract; TV = Tricuspid valve.
Figures 6A and B: A. Aortic valve sharing place and fibrous ring with mitral valve (MV) and tricuspid valve (TV). The non-coronary cup is in close
contact with fibrous ring, with permission14; B. 3D echocardiography showing wedged position of aortic valve between mitral and tricuspid valve.
AV = Aortic valve; MV = Mitral valve; PV = Pulmonary valve; TV = Tricuspid valve. Image courtesy: Dr Nagendra Chauhan
473
Figure 8: Conduction system and its relationship

with the aortic valve
Figure 7: Membranous septum is the upper and posterior part of the
interventricular septum, which separates the aortic vestibule from the
lower part of the right atrium and upper part of the right ventricle and
is thin and fibrous
Literally, the aortic root is allied to all four cardiac

chambers, both interatrial as well as interventricular septum
and the conduction system. Therefore, both surgeons and
the interventional cardiologists must have a clear anatomical
understanding about it.3,14,15,17
aortic root and the conduction system

The most important surgical relationship of the aortic root,
nonetheless, is probably to the atrioventricular node and
the penetrating atrioventricular bundle (Figure 8). The
node, located in the wall of the right atrium at the apex of
the triangle of Koch, is relatively distant from the root. As
the conduction axis penetrates through the central fibrous
body, however, it is positioned at the base of the interleaflet
triangle between the non- and right coronary aortic sinuses.
The fibrous triangle between the right and the non-coronary
leaflets is the guide to the location of the atrioventricular
conduction bundle. After penetrating through the insulated
fibrous plane at the atrioventricular junction, the bundle then
branches on the crest of the muscular ventricular septum. The
left bundle branch fans out on the smooth LV side, whilst
the cord-like right bundle branch penetrates back through
the muscular septum, emerging out on the septal surface in
the environs of the medial papillary muscle. In this position,
therefore, the muscular axis responsible for atrioventricular
conduction should be relatively distant from most surgical
maneuvers carried out to replace or repair the aortic valve
and its supporting structures.31-33 Although, the lesions of the
aortic root like aneurysm and abscess can lead to compression
of the node or bundle (Figures 8 and 9).
474
table 1
Terminologies related to the aortic valve

Aortic sclerosis
It is defined as a irregular area of focal

thickening of the aortic valve without causing
obstruction.
Aortic override
When aorta straddles the ventricular septal

defect (VSD) and seems to arise from both
the ventricles.
Prolapse of the
aortic valve
Aortic valve can prolapse into the adjacent

VSD. The outpouching of the aortic valve
is seen below the hinge point of the valve
attachment.
Aneurysm
of sinus of
Valsalva
Aneurysm of sinus of Valsalva is dilatation

and outpouching of the sinus of Valsalva
(aortic wall). It is located above the hinge
point of aortic valve.
Aortico-left
ventricular
tunnel (ALVT)
ALVT is a extracardiac channel usually

connecting the aortic root above the right
coronary artery origin (tubular aorta) to the
left ventricle (90% cases), in relation to the
infundibular septum and the right sinus.
Sometimes its position may be unusual.
Normal
great vessel
relationship
Aortic valve is positioned to the right and

posterior, in relation to the pulmonary valve.
D-malposed
aorta
Aortic valve is positioned to the right and

side by side or anterior, in relation to the
pulmonary valve.
L-malposed
aorta
Aortic valve is postioned anterior and to the

left, in relation to the pulmonary valve.
Inversely
placed great
vessels
Aortic valve is positioned left and posterior,

in relation to the pulmonary valve (in situs
inversus).
Anterior aorta
Aortic valve is positioned directly anterior in

relation to the pulmonary valve.
Posterior aorta
Aortic valve is positioned directly posterior in

relation to the pulmonary valve.
33
Figure 9A and B: An older patient presenting with syncope and bradycardia. Complete heart block was detected.
Echocardiogram and computed tomography suggested a huge aneurysm of the noncoronary sinus
central PosItIon oF the aortIc root and Its

ImPlIcatIons In InterventIons
The aortic root and its adjacent cardiac structures are subject of
immense clinical interest because many surgical and catheter
interventions are performed, in this vicinity, to restore the
normal and natural functioning of the diseased heart. There
can be two kinds of cardiac interventions:
1. When the aortic root and aortic valve are directly
manipulated.
2. When interventional manipulation is in the adjacent
structures where the aortic root is used as a passage or to
anchor the artificial material.
when the aortic root and aortic valve are

directly manipulated
The aortic root and its components are continuously working
under high pressures and the resulting shear forces. There may
be inherent problems like numerical cuspal abnormalities or
abnormalities of the aortic root wall. Moreover, the functional
abilities of the aortic root may also decline due to the neonatal
or infantile surgical procedures like arterial switch, Ross
procedures or adult aortic root reconstruction.14,15,17,34,35
As we have learned that the aortic root has a mechanism
to make it physiologically effective in the presence of shear
forces, it is clear that all interventional methods are yet to be
differential to this innate ability. This may be the explanation
for the relatively rapid deterioration of the artificial material
in the aortic position. These facts must be considered, while
choosing the interventional steps and prosthesis.
The ballooning procedures are less interfering with
the natural functional abilities of the aortic root. But they
can interfere with the competency of the valve and can

culminate into the valve replacement procedure, in the long
run. The understanding of the aortic root and its dimensional
variation at different levels are significant. The sizing of the
aortic annulus at hinge points in 2D echocardiogram has to
be precise for the optimum choice of balloon.9,36
when manipulation is in the adjacent structures:

cardiac catheter and surgical Interventions37
Many catheter interventions, like device closure of atrial septal
defect (ASD), VSD, aortopulmonary window, ruptured sinus
of Valsalva or paravalvular leaks take place in or around the
aortic root. For example, in the device closure of ASD, wrong
choice or placement of device may lead to aortic perforation.37
A wrongly placed device for perimembranous VSD can lead to
deformation of the aortic cusp. Surgical complications can also
happen in the form of perforation or valvar dysfunction.38 Both
types of interventions may cause conduction abnormalities.
dIseases oF the aortIc valve

As mentioned above there are two typical processes that can
affect the aortic valve. One is aortic stenosis in which the
valve fails to open fully, thereby obstructing blood flow from
the heart and the second is aortic valve insufficiency, causing
increased LV preload due to regurgitation of blood from
aorta to LV during diastole. These two conditions frequently
coexist. Besides, pathological aortic root dilatation is also
seen frequently, in bicuspid valve disease.22-24,39-48
Common causes of aortic stenosis include rheumatic fever,
degenerative calcification and congenital diseases such as
BAV (Table 2).22-24,39-46,48 The spectrum of congenital aortic
475
table 2
Causes of aortic stenosis
stenosis (AS) ranges from mild AS to a severe form of the

disease, which may manifest in fetal life and terminates into
hypoplastic left heart.
The aortic root and aortic valve may have morphological
and positional abnormalities, as is shown in Table1.
Common causes of aortic regurgitation (AR) include
dilation of the aorta, infective endocarditis, myxomatous
degeneration of the AV and Marfan syndrome.22,23,38-43
Routinely, morphology of the AV is evaluated on echocardiography. The parasternal views (short-axis view at the
base of the heart and long-axis view) are used to determine
the morphology and number of cusps. Subcostal coronal view
with anterior tilt, apical four-chamber with anterior tilt and
parasternal long-axis views are particularly useful to define
the valve motion.17,22,23,41
Normal AV is tricuspid and has three leaflets of nearly
equal size. Three commissures form a Y-shaped pattern
in diastole. In systole, the leaflets open along these
commissures to create a wide, open triangular orifice
(Figures 10A). The congenital anomalies of AV comprise
a spectrum of deformities, which includes abnormal form,
size and the number of leaflets (Table 3).22-24,39-46,48 Normal
AV leaflets are thin and have unrestricted mobility. In
stenotic valves, leaflets are thickened and domed in systole.
Doming of valve leaflets during systole occur due to limited
cusps separation leading to restricted mobility of valve
cusps.14,15,17,22-24,38-43,46
valvar aortIc stenosIs
The Unicuspid Aortic Valve (Figures 11 and 12)
Valvar AS is the most common type of LVOT hindrance,

accounting for 70 to 91 percent of aortic obstructions. It is
caused by cusp deformities with or without narrowing of
the annulus. It may manifest early, in a neonate or later in
infants and children due to the progressive obstruction of the
inherently abnormal valve.22,23,38-43
The evaluation of valvar aortic stenosis should include:
a. Morphology of the stenotic valve
b. Dimensions of the aortic root
c. Severity of valvar obstruction
d. Left ventricular function
e. Associated anomalies.
A unicuspid valve can be of two pathological varieties

acommissural and unicommissural and can be seen in SAX
view. The acommissural valve is a rare anomaly and has a
single membrane-like leaflet with a central circular orifice.
Unicommissural unicuspid valves occur more frequently and
are the most common cause of symptomatic AS in neonates.
The orifice is typically eccentric and circular in systole
(Figures 11 and 12). In diastole, an eccentrically located
valve closure is seen with no raphae. The unicuspid valve is
generally stenotic in neonatal period though occasionally it
has sufficient redundancy and may be the cause of obstruction
in adult life.22,23,46
Congenital
Abnormal number of cuspsunicuspid,

bicuspid, tricuspid, quadricuspid, six-cuspid
Calcific or degenerative
Rheumatic valve disease
Other conditions:
476
morphology of stenotic aortic valve
Homogenous type II hyperlipoproteinemia

Metabolic (Fabrys disease)
Systemic lupus erythematosus
Alkaptonuria
Figures 10A and B: A. Centrally placed tricuspid aortic valve (Mercedes-Benz sign); B. Centrally placed bicuspid aortic valve.
LV = Left ventricle; RA = Right atrium; RV = Right ventricle

table 3
Morphology of the valve

Unicuspid aortic valve
Acommissural
Unicommissural
Bicuspid aortic valve
Fused right and left coronary cusps
Fused right and non-coronary cusps
Fused left and non-coronary cusps
Tricuspid aortic valve
Symmetrical cusps
Asymmetrical
Quadricuspid aortic valve (rare)
3 cusps equal size, one smaller
4 cusps of equal size
Pentacuspid aortic valve (very rare)
Figures 11A to c: A. Unicuspid valveunicommissural valve (toilet

seat shape); B. Unicuspid valveunicommissural valve (tear drop
shape); C. Unicuspid valveacommissural valve (only raphae seen,
no commissures seen reaching the wall of aorta and centrally stenotic
opening)
Congenital Bicuspid Aortic Valve

As we know that the BAV is one of the commonest congenital
malformation involving AV (Figures 10B and 13A to E).
It includes certain spectrum of different phenotypes that can
be comprehensively classified into three types (Type 0, 1
and 2) according to the number of raphes.47
Echocardiographic diagnosis of a BAV is based on
demonstration of two cusps and two commissures on direct
Figures 12 A to c: Unicuspid unicommissural aortic valve: A. Opened out ascending aorta showing a unicuspid aortic valve with severe
stenosis of its orifice in a pathological specimen. Arrow points to the single true commissure; B. Enface view on transthoracic echo; C. Computed
tomography angiography. Image courtesy (12A): Dr Pradeep Vaideeshwar
33
parasternal short-axis view. Additional short axis features that

support the diagnosis, include leaflet redundancy, infolding
and eccentric valve closure. In parasternal long-axis view,
an abnormal eccentric coaptation line with systolic leaflet
doming and an abnormal pattern of systolic opening is seen.
Though there is no fixed pattern of coronary artery origin
with BAV, usually the coronary arteries emerge from the anterior
sinus in case of anterior and posterior cusps with normally related
great vessels, and from posterior sinus in case of transposition of
great vessels. In presence of right and left cusps, left coronary
artery arises from the anterior part of the left sinus and the right
coronary from anterior part of the right sinus.
The majority of the BAV will cause no problems. This
condition is often undiagnosed until later in life when the
person develops symptomatic aortic stenosis. Aortic stenosis
occurs in this condition usually in patients in their 40s or 50s,
an average of 10 years earlier than it occurs in patients with
congenitally normal aortic valves.14,15,17,22-24,38-43,47-49
The fusion of the left and right coronary cusps results in a
bicuspid valve with two cusps positioned antero-posteriorly.
The fusion of the right and non-coronary cusps results in two
cusps positioned right and left and the two commmisures
having an anteroposterior orientation. Often fused commisures
called raphe is seen and in the closed position may give the
appearance of a tricuspid AV. It is only in systole that the valve
does not open along the abortive commisures. The development
of aortic valve stenosis is variable and may be related to the
valvar characteristics. The patients with anteroposteriorly
(as opposed to right-left) and eccentric (vs symmetric) valve
leaflets have faster rate of progression of aortic obstruction.43
Also, the patients with fusion of the right coronary and noncoronary leaflets are more likely to have AR. There are various
classifications of BAV based on the type of fusion of the cusps,
position of the raphae, orientation of the commisures as well as
other criteria like leaflets size and interleaflet triangles.47-49 Two
simple classifications are shown in the Figures 14A and B.47-49
Cheitlin et al,demostrated that in few cases of BAV
obstruction is secondary to the dysplastic cusps, and dysplastic
changes rather than the commissural fusion were responsible
for the observed aortic stenosis.42 These valves do not appear
amenable to valvotomy because obstruction is due to the
abnormal valve tissue.
477
Figures 13A to e: Bicuspid aortic valve: A. Morphology; B. Echocardiography in short axis showing the closed valve; C. Open valve; D. Excised
aortic valve (AV) in a case of aortic stenosis showing slightly unequal calcified semilunar cusps. Note raphae (arrow) in the larger cusp; E.
58 years male with ischemic heart disease showed bicuspid AV. Note atheromatous narrowing of the left circumflex artery LCA. Ao = Aorta;
LMC = Left main coronary artery; LV = Left ventricle; MV = Mitral valve; RCA = Right coronary artery. Image courtesy (13D and E): Dr Pradeep
Vaideeshwar
Figures 14A and B: Classification of Bicuspid aortic valve (base on refrence 47 to 49): A. By Sabet et al47; B. Roberts et al48. Rt = Right; Lt = Left
478
Pentacuspid Aortic Valve
left ventricle in aortic stenosis: some Facts
Pentacuspid aortic valves also have been described rarely in

case reports.55
a. The left ventricle response to AS includes LV remodeling

and myofibrillar hypertrophy with fibrosis.
b. The LV mass is not directly in proportional to the degree of
valvar obstruction.
c. The LV responds to AS by concentric hypertrophy (wall
thickness is increased disproportionately more than cavity
size) (Figures 16A to D).
Congenitally stenotic tricuspid AV has three aortic cusps. The

edges of the cusps are rolled or gnarled with varying degrees
of commissural fusion. This abnormality is often associated
with a narrowed aortic annulus. The annular hypoplasia or
myxoid dysplasia of tricuspid valve leaflets may also lead to
aortic stenosis.17,22,23,46
Quadricuspid Aortic Valve
eFFect oF aortIc stenosIs on leFt ventrIcle

The LV in AS undergoes the adaptive changes, which can be
defined as concentric remodeling, which results in normal
33
The quadricuspid AV is a very rare (0.013%) congenital anomaly.

Hurwitz and Robert classified the quadricuspid semilunar
valve based on the relative sizes of the four cusps. However,
no correlation has been found between anatomic variation and
functional status. Though aortic stenosis is rare, approximately
50 percent cases have aortic insufficiency. Aortic regurgitation
is more common with small accessory cusp.17,22,23,40,49
In parasternal short-axis view, four diastolic closure lines
are present forming a characteristic X pattern, and in systole,
four cusps open and form a rectangular configuration (Figures
15A and B). Color flow mapping shows presence of AR.
LV mass associated with an increased relative wall thickness.

This is usually calculated as 2 posterior wall thickness/LV
diastolic diameter and a value > 0.45 is abnormal.52
The stroke volume, cardiac output, baseline heart rate and
ejection fraction are normally maintained because of this
adaptation. However, after sometime, the ventricle starts failing
and stroke volume decreases and ventricle dilates. So, leftsided obstructive lesions must be ruled out before labelling a
patient with low ejection fraction as a case of cardiomyopathy.
These patients have an imbalance between the coronary blood
flow to the hypertrophied LV and the increased myocardial
oxygen demand owing to the pressure overload. The principal
determinants of subendocardial blood flow are the length of
diastole and the coronary artery driving pressure.51
Moderate hypertrophy allows for a lower heart rate,
increased diastolic volume and thus higher stroke volume. The
increased thickening of the ventricular muscle associated with
pathological conditions like AS results in decreased chamber
compliance. As a result, LV pressures are elevated, the end
systolic volume (ESV) is increased and the end diastolic
volume (EDV) is decreased, causing an overall reduction in
cardiac output.
Congenitally Stenotic Tricuspid Aortic Valve
B
Figures 15A and B: Quadricuspid aortic valve. Parasternal short axis view shows the valve. A. Closed position; B. Open position.
CA = Coronary artery ; LA = Left atrium; RA = Right atrium; RVOT = Right ventricular outflow tract
479
Figures 16A to D: A. PLAXmaladaptive concentric LVH (diastole), noncompliant LV. Note the hypo-dense area (arrow ) in myocardium of
LV free wall; B. PLAX (Systole)systolic obliteration of cavity leading to abnormal RWT (RWT-Relative wall thickness: ratio of the posterior
wall thickness plus septal thickness over LV internal dimension); C. PLAXturbulent flow at LVOT (systolic anterior motion of MV); D. M-mode
echosystolic anterior motion of MV. LV = Left ventricle; LVH = Left ventricular hypertrophy; LVOT = Left ventricular outflow tract; MV = Mitral
valve
d. This left ventricular hypertrophy (LVH), which is an

adaptive change is actually maladaptive and leads to
diastolic dysfunction and abnormal coronary flow and
can add up adversely, to the overall outcome. The animal
experiments have showed an advantage if this maladaptive
LVH can be prevented.52
e. In the older patient population, women have more wall
thickness than cavity size, while men have relatively less
thickening and more cavity space.52
f. The favorable role of drug therapy with statins, angiotensin
converting enzyme (ACE) inhibitors and certain other drugs
on the progression of AS in adults has been studied and
published but there is no such study in pediatric age group.52-54
clinical Presentation
480
Unicuspid valves generally present early in the neonatal age

group with severe AS. Usually, the results of the interventional
procedures are suboptimal. BAV may be diagnosed in patients
of any age. BAV may remain silent and be discovered as an
incidental finding on echocardiographic examination or at

autopsy. Only 2 percent of the patients with congenitally
malformed AV may experience clinically significant AS or
regurgitation by the adolescence.14,15,17,22,23,58,60
Children who develop early progressive, pathologic changes in the BAV are more likely to develop valve regurgitation
than stenosis.46,48
Many patients with abnormal AV may develop endocarditis
and may present with fever or systemic embolization at early
or late age.56,57
aortic stenosis in older children

Symptoms14,17,18,58,59,60
Grown up children are generally asymptomatic during
childhood. They have normal growth and development. The
most commonly reported symptoms are fatigability, exertional
dyspnea, angina pectoris and syncope. Easy fatigability is
the frequent symptom and has been reported in 15 percent of
Physical Examination14,17,18,59,60
Vital signs are normal except in children with severe AS and
congestive heart failure. However, the pulse in significant AS
is usually of different types. The pulse with anacrotic character,
(anacrotic pulse) gives the impression of interruption of the
upstroke of the carotid pulse. Aortic stenosis is likely to be
hemodynamically significant when the anacrotic notch is felt
immediately after the onset of upstroke. When an anacrotic
notch occurs very early on the ascending limb of the arterial
pulse, it can be appreciated in the radial pulse and suggests
moderate to severe AS. The pulse with delayed upstroke of the
ascending limb is called as pulsus tardus. A delayed peak of
pulse correlates with severity of AS. The pulsus parvus is a low
amplitude pulse. Also a thrill can be palpated in the ascending
phase of the carotid pulse which is known as carotid shudder.
In patients with mixed AS and AR, bisferiens pulse, pulse
with two systolic peaks, occurs when the regurgitation is the
predominant lesion. A carotid thrill is present in the presence
of AS. It correlates with severity of AS. The thrill may also be
present in cases presenting with a hyperdynamic circulation
and AR. However, pulses are brisk and good volume in the
absence of AS. The apical impulse is usually normal in mild
AS, but with increasing severity of the stenosis, the apical
cardiac impulse becomes more forceful. The presence of
a presystolic tap indicates forceful atrial contraction and
suggests elevated LV end-diastolic pressure. A suprasternal
notch thrill is palpable in as many as 85 percent of patients
with valvar AS. A precordial thrill is also usually present in
patients with moderate or severe obstruction.
The first heart sound is usually normal. Splitting of the
second heart sound may be narrow or absent owing to the
prolonged ejection time of LV and the resultant delayed A2.
However, sometimes this change may not be appreciable
clinically. In exceptionally severe cases, there may be
paradoxical splitting of the second heart sound. A paradoxical
split S2 occurs in any setting that delays the closure of the
aortic valve. Furthermore, fourth heart sound may be present,
indicating severe stenosis with LV diastolic dysfunction and
high end-diastolic pressures. Although the presence of a third
heart sound is common in children and adolescents with
normal hearts, it is more frequent in AS.
The constant ejection systolic click is a hallmark of the
bicuspid valve even if the valve is functionally normal.
Systolic ejection clicks occur in early systole and may result
from either the abrupt opening of the semilunar valves or
the rapid distention of the proximal aorta at the onset of

ejection. Aortic ejection clicks are usually best heard with
the diaphragm in the second right intercostal space or at the
apex. The aortic ejection click, usually, occurs immediately
before or coincident with the initial carotid upstroke. Unlike a
PV ejection click, timing and intensity of an aortic click does
not vary with respiration (constant ejection click). The aortic
ejection click must be distinguished from tricuspid component
(T1) of S1 and S4. The aortic click tends to disappear in the
presence of a calcific valve and severe stenosis. Nonetheless,
the presence of an ejection click and suprasternal notch thrill,
strongly suggests that the AS is valvar rather than subvalvar or
supravalvar.
The systolic crescendo-decrescendo systolic ejection
murmur of AS usually follows an early systolic ejection
click (Figure 17). The ejection murmur is generally loudest
at the upper right sternal border or in younger children at
the upper left sternal border, and it radiates into the neck
over the carotid arteries bilaterally. Increasing severity of
the stenosis is accompanied by a louder, harsher, and a late
peaking ejection murmur. In patients with AR, a diastolic
decrescendo murmur can be heard in the aortic area. The
presence of the systolic and diastolic murmur may be
misdiagnosed as a continuous murmur.17,18,53,59,60 There
are clinical findings with good sensitivity and specificity to
assess the severity of AS. They arelow volume of carotid
pulse, slow upstroke of carotid pulse, >3/6 delayed peaking
ejection systolic murmur, single second heart sound.
The valvar AS must be differentiated from supra and
subvalvar aortic stenosis, HOCM, valvar PS. The valvar
pulmonary stenosis is associated with variable ejection
click, soft delayed P2 and the area of murmur and radiation
is different. The character of pulse varies in three types of
AS. For example, supravalvar AS has differential pulses in
upper limbs (Coanda effect) and pulse in HOCM is double
peaked and brisk (spike and dome). In valvar AS, the type of
pulse is pulsus tardus. Dynamic auscultation is another way
to differentiate the three. Unlike in HOCM, the murmur of
valvar AS decreases on standing but increases in intensity
on squatting or on giving amyl nitrite. Valvar AS is usually
associated with constant ejection click which is suggestive of
BAV.
33
patients with mild AS and 31 percent of patients with severe

AS. Interpretation of the clinical significance of this symptom
is difficult. In severe AS, angina or syncope are reported in less
than 10 percent of patients even when peak-to-peak pressure
gradients are more than 80 mm Hg. However, when present,
angina or syncope suggests severe stenosis and mandates prompt
evaluation and treatment.14,17,18,59,60
InvestIgatIons
electrocardiography
In older infants and children, the resting electrocardiogram
(ECG) must be evaluated for voltage criteria of LVH. However,
the reflection of the presence or severity of AS may not be
well represented on ECG and it may be normal in one-third of
the patients, even if the peak-to-peak gradient is greater than
80 mm Hg. Similarly, ECG criteria for LVH, often fails to
correlate well with left ventricular mass calculated by other
481
Figure 17: Phonocardiogram: (A) Normal heart sounds; (B) Aortic stenosis; (C) Aortic regurgitation
modalities. The presence of LVH with ST segment depression

and T wave inversion in the left precordial leads (strain
pattern), though, less sensitive (< 25%) are fairly specific for
severe stenosis (Figure 18). The Holter monitoring of these
patients may help in recognizing the dysrhythmias. This is
important to know as there is evidence of a strong relationship
between ventricular arrhythmias and sudden death in patients
with AS.
The P wave is normal or bifid suggesting the presence of
mitral regurgitation (MR). The QRS axis may be normal. The
depolarization loop is clockwise with Q waves seen in the
inferior leadsaVF, III. LVH is represented by tall R wave
in lead II, aVF, deep S in V1, tall R waves in V5-6, deeply
inverted T waves also seen pointing against the QRS complex,
so called wide QRS-T angle. Various criteria for LVH in

respect to reference charts can be applied.60-62
In neonates and infants, there may be significant right
ventricular hypertrophy (RVH) and normal left ventricular forces.
In infants having hypoplastic LV, R wave in the left precordial
leads will be smaller. Increased left ventricular forces are not seen
in neonatal period. The P wave may be normal or bifid and T
waves may be inverted or flattened in lead I, aVL, V5, V6.60-62
radiology17,58,60
Heart size is usually normal or minimally enlarged on chest
radiograph in children with AS. The cardiac apex may be
rounded in the frontal projection and there may be posterior
482
Figure 18: Electrocardiogram in aortic stenosis shows left ventricular hypertrophy (LVH) with left ventricular strain pattern
Figures 19A and B: A. Plane X-ray in a case of bicuspid aortic valve

with severe AS in a 19-year-old male patient shows the post-stenotic
dilatation of ascending aorta (arrow), prominent aortic knuckle and
bulging, convex left ventricular (LV) contour; B. 15-day-old newborn
with severe AS, severe LV dysfunction (EF:15%) and PDA showing
cardiomegaly, LA enlargement and pulmonary venous hypertension.
AS = Aorti stenosis; LA = Left atrium; LV = Left ventricle; PDA = Patent
ductus arteriosus; RA = Right atrium.
heart borders and often with left atrium (LA) enlargement

(Figure 19B).17,60
Echocardiographic Evaluation for Aortic Valve2,17,22,23,41

As discussed above, a detailed echocardiographic evaluation
is warranted to evaluate the aortic valve and root, the
hemodynamic effect of AS, as well as the presence and absence
of associated lesions. Aortic root dimensions are assessed at
4 levels: the annulus, the sinuses of Valsalva, STJ, and the
proximal ascending aorta (Figure 20B). The parasternal
long-axis view is the best view to measure the AV annulus
and aortic root. Ascending aorta and arch can be measured in
suprasternal long-axis view.
In literature, it is now well established that the BAV is a
major abnormality found in cases with pediatric valvar AS
and also it is associated with major aortic abnormalities like
cystic medial necrosis, progressive dilatation of the aortic root,
coarctation of aorta, dissection of the aorta or carotid arteries.
Usually aortic abnormalities are associated with relatively larger
aortic annulus and normal or regurgitant AV (Figures 20 and 21).
The coarctation of aorta is more common with stenotic BAV.
Normally, blood flow across the aortic valve is laminar and
peak systolic velocity of blood flow across the valve rarely
exceeds 1.5 m/s. The ECG leads must be in place to recognize
the timing of the event and child must be quiet to avoid
inadvertent mistakes like recording of the velocity of MR jet.
To assess the severity of the AS, continuous wave Doppler
is the best modality (Figure 22A and Tables 4A and B). The
cursor must be aligned with the jet, to pick up maximum
velocity. Therefore, it must be placed beyond the narrow
orifice of valve, which is accountable for creation of the high
velocity jet. As mentioned earlier, by using color Doppler the
best alignment must be obtained. This endeavor may need
multiple echo views. The best view, in our experience, is
Figures 20A and B: A. The depiction of possible type and extent of bicuspid aortic valve (BAV) associated aortic abnormalities (shown on
3D reconstructed image); B. Echocardiogram in parasternal long-axis view shows dilated aortic root in an adult with BAV. Image courtesy:
Dr Apoorva Goyal
33
displacement of the cardiac silhouette in the lateral projection

in patients with LVH (Figure 19A). Left atrial enlargement, if
present, strongly suggests a severe degree of stenosis or presence
of associated lesions like MR or patent ductus arteriosus (PDA).
Pulmonary venous congestion and other signs of congestive
heart failure may be present in patients with severe stenosis
and left ventricular dysfunction. Ascending aortic enlargement
is a common finding in older children and in adolescents with
valvar AS (Figure 19A). Computed tomography (CT) scanning
or magnetic resonance imaging (MRI) accurately delineates
ascending aortic anatomy. Adults with congenital AV stenosis
frequently have radiographic evidence of valve calcification.
The latter two investigations are generally not warranted for the
diagnosis or management of AS.
Neonates with severe AS present with varying degree of
cardiomegaly, pulmonary venous hypertension, less sharp
483
Figures 21A to c: Computed tomography angiography in elderly woman: A. With non-obstructed bicuspid aortic valve (BAV) showing dilated
aortic root; B. BAV with no raphae; C. With non-obstructed BAVcoarctation of aorta. Image courtesy: Dr Apoorva Goyal
right upper parasternal view and to keep the probe along the
long axis of the ascending aorta and marker pointing towards
the neck. Angle correction should be avoided while taking
the gradients. In addition, the cursor must be kept away from
the mitral valve. A difference in timing of the systolic signals,
may distinguish between AS and MR (Figure 22A). The MR
signals starts during the isovolumic contraction and continue
throughout isovolumic relaxation. Figure 22B demonstrates
the overshooting LV pressure tracing in the catheterization
laboratory, suggestive of AS in a patient diagnosed on the
basis of high velocity signals on TTE.
Overestimation of the Gradient Across the AV

The velocity determination across the AV is flow related.
Hence, the conditions causing increased flow such as AR,
elevated cardiac output and heart rate, as seen in anemia,
anxiety, pregnancy and exercise, will increase the flow
velocity across the AV.17,18,23,41
Underestimation of the Gradient Across the AV

The AV velocities recorded when cardiac output is low such
as in left ventricular failure associated with neonatal or elderly
aortic stenosis, does not represent the severity of the AS.
Also, underestimation of true severity can occur due to a
non-parallel intercept angle. At higher velocities, a small error
may lead to significant underestimation of gradients because
of the quadratic relation between velocity and pressure
gradient.17,18,23,41
calculatIon oF the Pressure gradIent

484
Transvalvar pressure gradients are usually calculated from

the Doppler aortic velocity profiles, the peak gradient and the
mean gradient (Figure 22A). The peak gradient is determined

from the peak velocity using the modified Bernoulli equation
(p = 4V2) and mean gradient by squaring the instantaneous
velocities during the systolic ejection period.17,22,23,41
The catheter derived peak-to-peak gradient is the accepted
standard used for prognosis and to plan interventions. In
general, the Doppler measured peak gradient corresponds
to the catheter measured peak instantaneous pressure
gradient, which is fundamentally different from the peakto-peak catheter gradient. This correlation between the two
measurements is not nearly as close as with PV stenosis. In
some children, especially with moderate degree of stenosis,
two measurements can differ by 30 mm Hg. Mean gradients,
measured by averaging the instantaneous catheter or Doppler
gradients over the systolic ejection period, correspond more
closely to each other. The Doppler mean gradient has several
advantages over the Doppler peak instantaneous gradient:17,41
1. Doppler mean gradient is comparable to the mean pressure
gradient measured at the cardiac catheterization.
2. Doppler mean gradient is the average of all the peak
instantaneous gradients throughout the systole and is not
based on single peak velocity. Therefore, it can be obtained
with greater accuracy and reproducibility.
3. Mean gradient is less affected by transvalvular flow.
4. Mean gradient is the basis of calculation of valve area by
using Gorlin equation.
aortIc valve area

Aortic valve area can be measured by the following
methods: 17,22,23,41
1. Planimetery: The AV area can be measured by direct
tracing from the parasternal short-axis view at the level of
the great vessels on two-dimensional echocardiography.
33
Figures 22A and B: A. Doppler aortic valve (AV) mean gradient from
apical five chamber view showing the high-velocity jet; B. Recording
of valve gradient in the cath lab. Notice the difference between left
ventricular peak and AV peak gradient (dark area). Attribution: Creative
commons attribution/share
table 4A
table 4B
Severity of aortic stenosis17,18,23,41
Echocardiography in quantifying the severity of aortic stenosis
Mild
Moderate
Severe
Peak velocity
(meter/second)
< 3.0
3.04.0
> 4.0
Mean gradient (mm Hg)
< 25
2540
> 40
Ao valve area (cm2/m2)
1.50.8
0.80.5
< 0.5
AV area (cm2)
1.5
1.01.5
< 1.0
Ao = Aorta; AV = Aortic valve
To assess the severity of AS, the following echocardiographic

criteria are used:
1. Measurement of doppler pressure gradients17,18,23,41:
a. Peak instantaneous gradient
b. Mean pressure gradient
2. Measurement of valve area:
a. Direct planimetery in 2D echocardiography
b. Continuity equation
c. Proximal isovelocity surface area method from color
Doppler
3. indirect evidence of stenosis:
a. Left ventricular mass from 2D echocardiography
b. LV mass/volume ratio
c. LV acceleration time and acceleration time/ejection time
ratio
485
There are some limitations in pediatric patients. Those are:

a. Fast heart rate leading to limitation of frame rates
b. Error in measurement of small orifice
c. Irregular valve opening that are difficult to trace.
2. Aortic valve area by continuity equation:
CSA LVOT VTI LVOT
VTI AV
CSA = Cross sectional area of aortic valve
VTI = Velocity time integral
AV = Aortic valve
LVOT = Left ventricular outflow tract
(CSA AV) =
echocardiographic evaluation of diastolic

Function of left ventricle
Diastolic ventricular function is assessed by the filling
abnormalities of the LV. From the MV inflow Doppler
recordings, peak flow velocities, filling-rates, proportion
of flow in various phases of diastole may be assessed.
Comparative studies of these subjects with normal controls
have revealed higher E velocity, a much higher A velocity,
therefore an inverse E/A ratio. The percentage of total Doppler
area in the first-third of diastole was significantly lower and
the percentage of the total Doppler area under the A wave was
higher.41
tissue doppler Imaging in aortic stenosis63

Tissue Doppler has some role in assessing the ventricular
function. Bruch et al assessed 23 cases of moderate to severe
aortic stenosis by tissue Doppler and found that in patients
with AS, systolic (S) and early diastolic mitral annular
velocities (E) were significantly reduced in comparison to
control subjects (systolic, 5.5 +/ 1.2 vs 8.3 +/ 1.3 cm/s; early
diastolic, 5.6 +/ 1.6 vs 10.2 +/ 3.0 cm/s, P < .001 for both
comparisons), but ejection fraction, fractional shortening, and
cardiac index were normal. In patients with AS, LV pre-A
pressures (14 +/ 4 mm Hg)64 and end-diastolic pressures
were high (19 +/ 7 mm Hg). In such patients, the mitral E/E
ratio was significantly related to LV pre-A pressure (r = 0.75,
P < .001) and to LV end-diastolic pressure (r = 0.78, P < .001).
In patients with AS, an E/E ratio more or equal to 13 identified
the LV end-diastolic pressure greater than 15 mm Hg, with a
sensitivity of 93 percent and a specificity of 88 percent.
Infantile aortic stenosis17,64,65
486
The adverse effects of small inflow, outflow, and/or cavity size

of the LV are cumulative. The accuracy of prediction of the
outcome based only on preoperative anatomy indicates that
adequacy of valvotomy is not generally a limiting factor for
survival in this group of patients. It is possible to identify
subjects whose chance of survival is better after a Norwood
procedure rather than valvotomy, even if left ventricular

volume is not critically small.65
The critical AS presenting in neonatal period is a lethal
disease. Kim et al have highlighted the morphological
abnormalities found in critical AS.63 They examined the
postmortem specimen of two cases with critical AS and
reported an extreme pattern of myocardial abnormalities of two
types, one consisted of numerous clefts of intertrabeculated
spaces and endocardial fibroelastosis and other was
suggestive of myocardial ischemic changes. These findings
suggest that only functional and anatomical assessment is not
adequate to predict the outcome and there are more complex
morphological issues modifying the outcome.
Usually, critical AS does not manifest as fetal congestive
heart failure, but has many severe hemodynamic effects leading
to additional structural malformations. In view of the fact,
that these fetuses have a potential for developing hypoplastic
left heart syndrome, many centers are offering them fetal
valvotomy, a procedure to avoid the underdevelopment of the
left side of heart. Seemingly, these procedures are attractive
solutions to the CHDs with otherwise grave prognosis, yet
they have high procedural risk and limitations. The fetal
cardiac interventions are not allowed in India as of now.
The routine clinical examination and tests of the neonates
with critical AS, usually differ from older infants and children
and show involvement of the right heart instead of the left. This
is possible, as the two sides of the heart is directly connected
by the atrial communication as well as patent ductus. The
hepatomegaly, epigastric pulsation, right heart pulsation,
right ventricular dominance can be seen. Due to the presence
of pulmonary venous hypertension and relatively small
hypertrophied LV, radiological picture may mimic obstructed
total anomalous pulmonary venous connection or pneumonia.
The baby may have small failing LV, obstructive mitral valve,
MR, coarctation of aorta and PDA. Echocardiography will
provide the anatomical diagnosis, but then again, Doppler based
assessment of severity may be underestimated. The outcome of
aortic balloon valvuloplasty (ABV) may be suboptimal, but it
provides, a life saving palliation. Figures 23A and B show the
changes in myocardium and papillary muscles. Figures 23A
to D are TTE images of a 14-hour-old neonate with hydrops
fetalis on ventilator, who underwent successful balloon
valvuloplasty. The X-ray before ABV shows cardiomegaly
and after ABV shows reduction in cardiomegaly (Figures 23E
and F). The neonate was weaned off ventilator within 24 hours.
The ejection fraction (EF) improved from 35 to 55 percent. The
surgical intervention, in absence of proper artificial valve, has
poor prospects of success. The extensive procedures like Ross
operation provide alternative solutions. Left ventricular size
and its maladaptive concentric hypertrophy remains the biggest
concern for outcome of any intervention done for restoration of
biventricular morphology of the heart. Hence, with exceedingly
better results of Norwood and associated procedures, critical
analysis is desirable for selection of the procedure.
33
Figures 23A to F: A. Neonatal aortic stenosis. Transthoracic echocardiography (TTE) in apical four-chamber view shows dilated left ventricle
(LV) with concentric hypertrophy and changes in the papillary muscles; B. TTE in parasternal short-axis in 14 hrs old baby, shows pinpoint
aortic orifice (arrow); C and D. TTE (PSAX) shows increased valve area in same baby (post BAV); E. Pre-BAV X-ray chest in anteroposterior
view showing cardiomegaly; F. Post-BAV X-ray chest (same baby) showing improvement in cardiac size and improved PVH (pulmonary venous
hypertension), BAV = Balloon aortic valvuloplasty; PSAX = Parasternal short axis view.
There are several echocardiographic indicators to help

in diagnosis like the hypoplastic LV is usually globular and
does not extend to the cardiac apex. Additionally, LV inflow
dimension (hinge point of posterior mitral leaflet to cardiac
apex of less than 25 mm, mitral valve annulus diameter of
less than 9 mm, ventriculoaortic junction of less than 5 mm, all
measured from apical four chamber or long-axis view at end
diastole will indicate hypoplastic LV. Left ventricular crosssectional area measured in the parasternal long-axis view that
included the mitral valve, AV and left ventricular apex at end
diastole, of less than 2 cm2.
Rhodes et al analyzed the cases of critical AS applying one
risk scoring system with good predictive value.
Risk scoring system for biventricular palliation or repair in
critical AS:
For the four risk factors identified, the critical levels were:
1. A left ventricular long axis to heart long-axis ratio of 0.8 or
less
2. An indexed aortic root diameter of 3.5 cm/m2 or less

3. An indexed mitral valve area of 4.75 cm2/m2 or less
4. An LV mass index of 35 g/m2 or less.
They selected 65 babies up to 33 days of age out of which
46 underwent valvuloplasty as a first procedure. Outcome
was predicted with 95 percent accuracy when they used the
following equation:65
Score = 14.0 (BSA) + 0.943 (AoR/m2) + 4.78 (LAR)
+ 0.157(MVA/m2) 12.03
A score less than 0.35 is considered to be not compatible
with survival after two ventricle repair.
(BSA = Body surface area; AoR = aortic root dimencion
in cm indexed to BSA; LAR = ratio of long axis of LV to
long axis dimension of heart; MVA = mitral valve area [cm2]
indexed to BSA).
This scoring system has potential for errors and also presence of additional problems like MR may lead to fallacious
calculation.
487
rheumatic heart disease and aortic stenosis22,23,66,67
In developing countries rheumatic heart disease is not

uncommon. It is the most serious complication of rheumatic
fever. Acute rheumatic fever follows 0.3 percent of cases
of group A beta-hemolytic streptococcal pharyngitis in
children. Rheumatic AV characterized by three leaflets,
rolled up, thickened margins fusion of commissures between
the aortic leaflets. AV is the second most favored site for
rheumatic activity. It usually presents as combined lesions
and rarely as an isolated involvement. Rarely, it manifests
as purely a stenotic or regurgitant lesion. The rheumatic AS
is a poor candidate for balloon valvuloplasty and also for
Ross operation. Chokalingam et al reported the prevalence of
isolated AV disease as 4.5 percent in patients below 18 years.
echocardiographic evaluation of additional

abnormalities41
A PDA is seen in 20 to 65 percent cases of valvar AS. Coarctation
of aorta is found in 11 to 53 percent cases and stenosis of the
mitral valve in 25 percent cases. Other anomalies like VSD;
mitral valve abnormalities are also common.
role of exercise testing in the diagnosis

of aortic stenosis17,68
Exercise testing can identify a limited exercise capacity and
reveal symptoms in many (usually one-third) apparently
asymptomatic patients. The one year prognosis of patients
with a normal exercise test is excellent. In contrast, a positive
exercise test predicts the onset of a cardiac event in a sizeable
proportion of patients (Table 5).17,68
aortIc regurgItatIon14,15,17,18,22,23,59
Congenital AR is rare entity as an isolated lesion. It frequently
occurs in association with other congenital heart defects, aortic
root dilatation and infectious processes involving the aorta.
The causes of AR are listed in Table 6.
While evaluating the patient with AR, the following things
should be assessed on echocardiography:
1. Left ventricular outflow abnormality-cause of AR
2. Severity of regurgitation
3. Left ventricular dimensionsend systolic and end diastolic
4. Left ventricular systolic and diastolic function.
488
table 5
Criteria of an abnormal exercise test in patients with

asymptomatic aortic stenosis
Symptoms during exercise: dyspnea, angina, syncope or
near syncope
Fall in blood pressure or < 20 mm Hg rise in systolic blood
pressure during exercise
< 80% of normal level of exercise tolerance
> 2 mm ST segment depression during exercise
(horizontal or downsloping, in comparison to baseline, not
attributable to other causes)
Ventricular arrhythmias
table 6
Causes of aortic regurgitation

1. Primary congenital cardiac abnormality.
a. Aortic valve abnormality
- Quadricuspid aortic valve
- Bicuspid aortic valve
- Absence of aortic valve cusps (unguarded aortic orifice)
b. Aorticoleft ventricular tunnel
2. Connective tissue disorder with aortic root dilatation
- Marfans syndrome, Ehlers-Danlos syndrome
- Turner syndrome with aortic ectasia
3. Association with other forms of congenital heart defects
- Aortic valve prolapse with ventricular septal defect (doubly
committed, perimembranous)
- Dilatation of the aortic root as in tetralogy of Fallot
- Truncus arteriosus
4. Infectious processes of the aortic valve
- Bacterial endocarditis
- Rheumatic fever
cusps are redundant and prolapsing) should be defined.

Determination of the severity of regurgitation, ventricular
dimensions and ventricular function is very important before
taking the decision about management, regarding whether
patient will requires medical follow-up, valve repair or will
need aortic valve replacement. Aortic valve annulus and
aortic root size should be measured in the patient undergoing
AV replacement in parasternal long-axis view. If patient is
undergoing the Ross procedure then pulmonary root should
be measured in addition to aortic root measurement.
Etiology of AR in other heart defects for example, VSD
with AV prolapse (common association with doubly committed
VSD), subaortic stenosis and truncus arteriosus have been
discussed in the respective chapters (Table 7).46,48,57,58
left ventricular outflow abnormality leading

to aortic regurgitation
clinical Feature14,15,17,18,22,23,59
Parasternal long-axis view and parasternal short-axis view at

the level of great vessels are the best views to define the LVOT
abnormalities as described in Chapter 26. Aortic valve cusps
number and anatomy (rolled, gnarled and adequate or whether
Acute AR is a serious disease, which manifests with stormy

onset of acute left ventricular failure. However, chronic AR
is more common. The LV undergoes compensatory eccentric
hypertrophy, i.e. there is increase in both, cavity and wall
33
table 7
Differential diagnosis of aortic regurgitation

Aortico-left ventricular
tunnel
with organic valve disease
Pulmonary hypertension/PR
Graham Steell murmur
Heart sound
S1
Normal
Normal
Normal
Normal
S2
Normal split
Normal split
May be delayed P2 or
soft P2
Narrow or imperceptible split

P2 accentuated
S3
Usually not present in

isolated AR unless there
is myocardial dysfunction
Diastolic murmur
Site
Right and left lower

sternal border/apex
Right and left lower

sternal border/apex
2nd and 3rd intercostal at

left sternal border
2nd and 3rd intercostal at left

sternal border
Onset
Early diastolic
Has systolic and

diastolic component
Delayed diastolic
Early diastolic
Best heard
Diaphragm
Diaphragm
Bell
Diaphragm
Start with
A2
A2
After a clear interval from

P2
With loud P2
Intensity
High pitch
High pitch
Low pitch
High pitch
Posture
Better heard in leaning

forward
Shape
Decrescendo
Loud to-fro murmur

widely heard on chest
Crescendo-decrescendo
stop well before S1
Uniform throughout diastole
thickness. The chronic AR may occur due to variety of lesions.

However, AR is better tolerated in long term follow-up.
Clinically it presents with high systemic pulse pressure and very
low diastolic blood pressure. Sometimes, diastolic pressures
can approximate to zero in chronic severe AR. It represents
the inability of aortic root to maintain pressure in diastole due
to the incompetent AV which leads to increased LVEDP. The
significant AR is associated with central diastolic runoff of the
blood into the LV cavity, which in turn may be reflected in the
classical physical findings (Tables 7 and 8). 17,18,22,23,41,59,60
aortic root dilatation

Aortic root dilatation occurs in connective tissue disorders
such as Marfan syndrome, Ehlers-Danlos syndrome, Turner
syndrome and polyvalvular heart diseases. In connective
tissue disorders, aortic root dilatation is progressive.
Initially it involes sinus of Valsalva, ascending aorta, then
dilatation progresses to involve aortic annulus leading to
distortion of the AV and AR. While evaluating the patient
with connective tissue disorders such as Marfan syndrome,
aortic root measurements should be taken at four levels:
aortic annulus, sinus of Valsalva, STJ and ascending aorta
1 cm above the sinotubular junction and compared with age-
related normograms. They should be followed up serially. Any

undue dilatation or rapid increase in these parameters will
identify the patient at risk of development of aortic dissection
needing elective aortic root replacement procedure.45-48,50
Beppu et al reviewed current concepts of anatomic
classification, pathophysiology, natural history, and clinical
management of BAV disease with associated ascending aortic
aneurysms and suggested that optimal management of patients
with BAV disease and associated ascending aortic aneurysms
often requires a thoughtful approach, careful assessment of
risk factors.43
aortic regurgitation in aortic valve Prolapse in

ventricular septal defect
In the presence of perimembranous or doubly committed
VSD, AV may prolapse progressively, prohibiting coaptation
of the cusps and leading to incremental AR.
Saleeb et al reported that aortic cuspal prolapse and clinical
AR are not uncommon in patients with subaortic VSDs. They
studied hundred patients, with a mean age at VSD diagnosis of
0.1 +/ 0.5 years, with follow-up period of 7.1 +/ 10.1 years.
Aortic cuspal prolapse developed in 14 patients (14%) at a
mean age of 7.1 +/ 6 years (range 0.418.4). AR murmurs
489
490
table 8
Peripheral signs of aortic regurgitation

Signs
What they mean
Becker sign
Arterial pulsations in the retina
Mller sign
Systolic pulsations of the uvula in aortic regurgitation
Corrigan sign
Dancing carotids
de-Musset sign
Head nodding sign is aortic regurgitation
Bisferiens pulse
Bisferiens pulse is a more suggestive of free aortic regurgitation than a combination of aortic stenosis +
aortic regurgitation
Lighthouse sign
Flushing and blanching of the forehead
Locomotor brachii
Locomotor brachii is a prominent pulsation of the brachial artery seen in aortic regurgitation
Quincke sign
Presence of prominent nail bed capillary pulsations
Durozeiz murmur/sign
A stethoscope kept over the femoral artery picks up a systolic murmur with proximal compression and
diastolic murmur with distal compression. The diastolic murmur is specific.
Traube sign
Pistol shots sound can be heard over the femoral arteries and sometimes over the brachial arteries
Water hammer pulse
Collapsing pulse or water hammer pulse is noted in the radial artery, with upper limb lifted up passively
and felt by the palm of the hand.
Hills sign
Elevated systolic pressure and low diastolic pressure
Gerhardt sign
Hepatic pulsations
Rosenbach sign
Splenic pulsations
were heard in 6 patients (6%) at a mean age of 5.1 +/ 3.1

years, all of whom had aortic cuspal prolapse and underwent
VSD closure and aortic valvuloplasty. Mori et al published
the data of 99 consecutive patients with supracristal VSD and
found that the thirty patients (30%) had AV prolapse (VSD
+ AoVP group), and 31 patients (31%) had AoVP with AR
(VSD + AoVP + AR group). In the VSD + AoVP group, AoVP
was detected first by echocardiography at the age of 6.8 +/
4.2 years (mean +/ SD). In the VSD + AoVP + AR group, the
interval from detection of AoVP to the appearance of AR was
3.4 +/ 2.0 years.17,18,70,71
Why does prolapse occur in the adjoining VSD? The most
acceptable explanation is that this is the result of the interaction
between the anatomical defects and hemodynamic factors like
Venturi effect caused by a rapid blood flow through the VSD
in accordance to the Bernoullis theorem. With progress of
the disease, this syndrome is clinically subdivided into three
stages:
1. The prolapsing stage, which is characterized by the Venturi
effect
2. The reversible AR stage, which has AR and the Venturi effect
3. The irreversible AR stage in which the corrosion of the AV
is complete.72
Moreover, sometimes, the sinus of Valsalva may prolapse
without distorting the hinge point and and AV coaptation may
not be affected (Figures 24A and B).
Post-aortic valvuloplasty aortic regurgitation

Aortic regurgitation of varying degree is the usual finding
after balloon aortic valvuloplasty and sometimes may
lead to surgical intervention. Brown et al concluded in
their retrospective study that although, transcatheter aortic
valvuloplasty is effective for relief of congenital AS, there are
steady long-term hazards for surgical AV reintervention and
replacement that are independent of factors like age of initial
intervention or severity of AS. They followed up 563 patients
for a median follow-up period of 9.3 years. Survival free from
any aortic valve reintervention, was 89 1% at 1 year, 72
2% at 5 years, 54 3% at 10 years, and 27 3% at 20 years.
Freedom from AV replacement was 90 2% at 5 years, 79
3% at 10 years, and 53 4% at 20 years.73 In multivariate
analyses, lower post-dilatation AS gradient and lower grade
of post-dilation AR were associated with longer freedom from
AV replacement, but age, era, and pre-dilation AS severity
were not.17,73
Infective endocarditis and aortic regurgitation

Infective endocarditis can lead to acute or chronic AR,
depending upon the virulence of the bacteria. Aranki et al
published a retrospective study of 2,000 patients of whom
66 percent patients were those who underwent AV surgery
due to endocarditis of native valve.69 The operative mortality
33
Figures 24A and B: A. Parasternal long axis (PLAX) view showing aortic valve prolapse through perimembranous ventricular septal defect
(VSD). Note the prolapse is below the hinge point and the hinge point is dragged into VSD leading to loss of coaptation; B. PLAXshowing sinus
of Valsalva prolapsing through perimembranous VSD. Note the prolapse is above the hinge point and hence aortic valve position and coaptation.
AO = Aorta; LA = Left atrium; LV = Left ventricle.
for native valve IE was 7.4 percent.69 Endocarditis almost

eats away the valve in few of the cases. It may cause aortic
root abscess, embolization of vegetations and may leads to
complications involving various organs.
severIty oF regurgItatIon
With the use of two-dimensional echocardiography (left
ventricular dilatation, ventricular function), M-mode echocardiography (ventricular dimensions), color flow mapping,
and pulsed Doppler interrogation, severity of regurgitation
should be assessed (Figures 25A to D). Echocardiographic
criteria with the assessment of specific, supportive, and
quantitative parameters are given in Table 9. Table 10
describes the angiographic criteria for AR.
Calculation of effective regurgitant orifice (ERO) by
proximal isovelocity surface area (PISA) method was
originally used for MR. Now it is a valid method for
regurgitatant AVs also. Though, the procedure is cumbersome
and needs more time than other methods.
ventricular dimensions and ventricular Function

Left ventricular dimensions should be measured by traditional
M-mode done in parasternal long axis (PLAX) view. With
significant AR, left ventricular end-diastolic dimension will be
high because of the increased filling. Left ventricle end-systolic
dimension remains normal. Therefore, left ventricular fractional
shortening is increased. It shows capacity of LV to eject more
volume (normal stoke volume plus regurgitant volume). With
onset of LV failure, left ventricular end-systolic dimension starts
increasing. Intervention should be done before left ventricular
end-systolic dimension reaches 55 mm (in adults). The LVH is
a mechanical adaptation to both pressure and volume overload.

In AR, compensatory hypertrophy decreases wall stress;
however ultimately hypertrophic changes are detrimental as
they induce contraction and relaxation abnormalities. These
abnormalities lead to progressive inadequacy of coronary
vascular supply. Studies have shown that with same mass/
volume ratio, chances of arrhythmias are more in patients with
combined AR and AS than AS alone.17,23,41
natural hIstory oF aortIc valve lesIons17,18,75-77

Progression of gradient across the aortic valve
Despite the lack of very long-term intervention-free data,
natural history studies have provided important information.
Patients who present in infancy with AV stenosis generally
have more severe stenosis and higher mortality with or
without treatment. Twenty-five of the patients in the original
NHS-1 cohort were younger than 2-years-old; the 1-year
survival rate was 64 percent, and most had undergone surgical
interventions. In contrast, the 25-year survival in-patients who
were 2 years of age or older at the time of original enrollment,
was 85 percent. An earlier study by Campbell, published in
1968, found that the mean age of death in patients with AS was
35 years, with 40 percent mortality by age 30 and 60 percent
mortality by age. More than half of the patients who died had
sudden unexpected death, whereas most of the remaining
deaths were due to progressive congestive heart failure. The
notion that sudden death is extremely rare in the absence of
preceeding symptoms has been challenged by several recent
studies including NHS-2. About half of sudden death cases
from AS occurred during or immediately after exercise.
491
Figures 25A to D: A. Echocardiographic image in parasternal long-axis view shows bicuspid aortic valve with severe aortic regurgitation;
B. Continuous wave (CW) Doppler cursor at abdominal aorta in chronic aortic regurgitation (AR) showing systolic forward (above the baseline)
flow and pan-diastolic flow reversal (below the base line) s/o severe AR; C. CW Dopplermild AR; D. CW Dopplersevere AR. Image courtesy:
Dr Nagendra Chauhan
table 9
Grading of severity of aortic regurgitation
I. Specific signs
II. Supportive signs
III. Quantitative
Echocardiographic parameters
Mild
Moderate
Severe
a. Jet width/LVOT
< 25%
2564%
> 65%
b. Vena contracta
< 3 mm
36 mm
> 6 mm
c. Diastolic flow reversal in descending aorta
Early diastolic flow

reversal
Intermediate
prominent
holodiastolic
reversal
a. Pressure half-time
> 500 ms
200500 ms
< 200 ms
b. LV size
Normal
Enlarged
c. Deceleration slope
< 200 cm/sec2
200350 cm/sec2 >350 cm/sec2
a. RV (mL/beat)
< 30
3059
60
b. RF (%)
< 30
3049
50
< 0.10
0.10.29
0.30
c. EROA
492
(cm2)
EROA = Effective regurgitant orifice area; LVOT = Left ventricular outflow tract; RV = Regurgitant volume; RF = Regurgitant fraction. Modified from Zoghbi
WA, Enriquez-Sarano M, Foster E, et al. Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler
echocardiography. J Am Soc Echocardiogr. 2003 Jul;16:777-802.
table 10
Severity of aortic regurgitation on angiogram74

Mild
Contrast is visible in the left ventricle, but

it clears out during the emptying phase
of cardiac cycle
2+
Moderate
Contrast is visible within the entire left

ventricle and does not clear out during
the emptying phase of cardiac cycle
3+
Moderately
severe
Regurgitant contrast opacifies the left

ventricle and the opacification becomes
denser with each cardiac cycle
4+
Severe
The left ventricle is completely opacified

during the first cardiac cycle
Although mild AS may remain stable for many years,

ultimate progression is the rule.9 It may be greater in children
than in adolescents and adults because of the inability of the
valve orifice to increase in proportion to somatic growth.
The outcome is highly correlated with the initial gradient,
with those having higher gradients developing symptoms,
dying, or having valve replacement sooner than those with
lower gradients. In addition to the progression of AS, many
patients may develop significant and progressive aortic valve
regurgitation, particularly if they have had surgical valvotomy
or percutaneous balloon valvuloplasty.
changes in aortic root17,18,75-77

Isolated BAV seems to have a relatively benign course in
childhood. However, compared with those with a normal
AV, those with BAV disease have a higher prevalence and
faster rate of ascending aortic dilatation which may culminate
into dissection or rupture at a younger age. The fact that
pulmonary trunk shares this potential for abnormal dilatation,
suggests an embryological basis. The vascular smooth muscle
cells (VSMCs) that undergo apoptosis in the media of the
ascending aorta are of neural crest origin. There are 3 main
histopathological features described in literature to define
the formerly called cystic medial necrosis: noninflammatory
loss of VSMCs, fragmentation of elastic fibers, and increased
basophilic ground substance within cell-depleted areas of the
ascending aortic media. The pulmonary trunk demonstrates
same histological feature in patients with BAV disease. The
strong association between BAV and coarctation of aorta, both
with and without Turner syndrome, may indicate that BAV
disease involves the ascending aorta and aortic arch extending
to the ligamentum arteriosum, where most coarctations occur.
The convexity of the aorta is particularly affected by the
medial degeneration, demonstrating less collagen, greater
elastic fragmentation, and fewer VSMCs.
33
1+
There is definite phenotypic variance noticed in these

patients, mid ascending aortic dilatation is the commonest
pattern in BAV disease and is usually seen in older age,
whereas younger patients, particularly male gender, usually
present with aortic root dilatation. Serial echocardiographic
evaluation of aortic annulus, aortic root and ascending aorta
must be done. Once the ascending aorta reaches 4.0 cm,
annual imaging with echocardiography, MRI, or CT scan
is indicated. The question regarding the optimum timing of
prophylactic intervention is still unanswered. It is suggested
that elective surgical repair of BAV with associated aortic
dilatation should be done at a diameter of > 5.0 cm, with
even earlier intervention at > 4.5 cm in the subset of BAV
patients with factors of higher risk and at > 4.0 cm in those
with concomitant indication for AV replacement.
bacterial endocarditis78,79
Bacterial endocarditis risk has been reported to be as high as
1 percent per year, but is probably lower, based on the data
from NHS-2 where the incidence rate was 27.1 cases per
10,000 person years (0.27% per year). Although bacterial
endocarditis risk is present even in very mild aortic valve
stenosis, the incidence of endocarditis is higher in patients
with more severe stenosis. BAV endocarditis predominantly
occurs in young adults and there is a strong male dominance
(73100%). Staphylococci and viridans streptococci have
accounted for nearly three-quarters of the cases, as in native
valve endocarditis. Complications, especially heart failure and
valvular or myocardial abscesses are common. Most patients
require surgery, often on an emergency basis. Recent surgical
series show that 25 to 54 percent of all infected AVs are bicuspid.
management oF aortIc valve dIsease

medical management
In AS, medical management does not carry much role except
for decongestive therapy in failing heart and supportive
therapy like blood transfusion for very low hemoglobin or
ventilation for very sick children. The neonates presenting
early may get benefit from prostaglandin by keeping the PDA
open (see chapter 5 on duct dependent circulation). With the
use of prostaglandin infusion, transport can be easy.
There is a definite role for medical management in
regurgitant lesions of the AV. Unless systolic function
is abnormal, intervention is not recommended. Usually
vasodilator therapy is most effective as it decreases the
afterload and improves the end systolic contraction indices
and dimensions. Nowadays, ACE inhibitors are the drugs
of choice. In presence of moderate severe LV dysfunction
diuretic therapy is recommended.
493
Intervention in aortic stenosis78-87
Aortic Stenosis: Timing of Intervention82

For infants and older children
1. Left ventricular dysfunction: Immediate intervention by
balloon dilatation, irrespective of gradients (Class I).
2. Normal left ventricular function: Balloon dilatation if any
of these present:
i. Gradient greater than 80 mm Hg peak and 50 mm Hg
mean by echo-Doppler (Class I).
ii. ST-T changes in ECG with peak gradient of greater
than 50 mm Hg (Class I).
iii. Symptoms due to AS with peak gradient of greater
than 50 mm Hg (Class IIa). In case of doubt about
severity/symptoms, an exercise test may be done for
older children (Class IIb).
For neonates: Balloon dilatation if symptomatic or if there is
evidence of left ventricular dysfunction/mild left ventricular
hypoplasia (Class I), or if Doppler gradient (peak) greater than
75 mm Hg (Class IIa).
balloon dIlatatIon oF the

aortIc valve2,17,18,23,80-87
494
The balloon dilatation of aortic valve was first reported by

Lababdi et al in 1983 in children. Subsequent studies have
confirmed the efficacy and safety of this palliative technique
in neonates, infants and children. It has been accepted as
preferred mode of intervention in very small babies with
critical AS and borderline LV. McElhinney et al reported
good results in 113 babies who were <60 days of age and
were diagnosed to have critical AS.79 Echocardiography is
the mainstay for the evaluation of the aortic valve in valvar
AS. The technique besides giving accurate information on
gradients, left ventricular function, AR also accurately assesses
the valvar morphology. Measurement of the size of the aortic
annulus is most accurately done by echocardiography.
Procedure: The aortic valve is usually crossed through the
femoral approach although the carotid and rarely antegrade
transvenous approach through the PFO/ASD via mitral valve,
have also been attempted in neonates and infants. The valve
is most commonly crossed by a guide wire supported by a
catheter. The right Judkins, pigtail or the multipurpose catheter
are the most common catheters used as a support to the guidewire. After crossing the valve with the catheter the guide-wire
is changed to an extra-stiff J tipped wire. The balloon size
used should not exceed the aortic annular size. The balloon
valvuloplasty is accomplished by balloon inflation up-to 90100% of annulus size (Figure 26A and B). Following the
balloon valvotomy an accurate assessment of the gradient is
mandatory. The echocardiography is usually used to see the
valve area, gradient and presence of any newly developed
AR. A successful valvotomy is defined as fall in gradients of
more that 50 percent of predilatation values Figure 26 C and
D. In patients with left ventricular dysfunction normalization

of ventricular function following successful aortic valvotomy
may be associated with increase in gradients compared to
immediate post dilatation values. The procedural success
has been reported to be in between 88 to 96 percent. New or
increase in AR occurred in 10 percent of cases. Jindal et al
reported a series of 74 patients (age 120 years) with the follow
up of 212 years. The procedure was successful in 71 patients
(96%). The mean (+/ SD) reduction in peak-to-peak systolic
gradient (PSG) was 68.7 +/ 13.5%. No patient required
immediate surgical intervention. Survival after dilatation was
100 percent at 12 years. At follow up (mean 5.5 +/ 2.9 years;
range: 212 years), 20 percent of patients had restenosis and
21 percent had significant AR (grade > or = 3). Reintervention
was performed in 14 percent of patients. Severity of AR and
high residual stenosis immediately after balloon dilatation
were associated with the late event rates. The actuarial
intervention-free rates at 5, 7 and 12 years were 92.9 percent,
84.4 percent and 60 percent, respectively.83 According to
O Reich et al, independent predictors of unfavorable outcome
are the small aortic annulus, BAV, poor function of the LV or
mitral valve, and limited operator experience.86 Daehner et
al reported better success rate if the balloon is stabilized with
rapid right ventricular pacing or use of adenosine.87 Table 11
shows the differences between aortic vs pulmonary balloon
valvuloplasty.17,18,23,28
surgical Intervention2,17,18,23,84,88,89-95
In children valve replacement is always difficult as adequate
size of prosthesis may not be available. Ross procedure
remains the choice for small infants but there might be gross
aortic and pulmonary annulus mismatch and hence it may
not be very successful. Hence, the necessity to intervene in
a child with AR must be evaluated with utmost care. Ross
et al published their recommendations in 1985 and no major
change happened for small children since then. Criterias are:
ejection fraction < 40%; LV fractional shortening < 25%; LV
end-diastolic diameter 7 mm or 3.8 cm/m2 : LV endsystolic
diameter > 5 cm or 2.6 cm/m2, radius/wall thickness ratio at
end-diastole multiplies by systolic pressure > 600.88
Aortic valve repair is still not a very preferred mode of
treatment due to the poor outcome in long run, though shortterm results in good surgical hands are comparable to any
type of valve replacement. Patients with rheumatic valvular
disease appear to have an increased incidence of recurrence
and repair failure. There are various techniques of repair and
often a combined technique is used (Figures 27A to D).89-92
A good review was published by Carr et all comparing all the
methods in an online search and meta-analysis.89
aortic valve repair in aortic valve Prolapse

Boodhwani et al described their techniques of repair in
AV prolapse based on classification of type of the AVP
33
Figures 26A to D: A. Aortic root angiogram shows Prussian helmet appearance due to the doming of aortic valve (AV) with a negative shadow
caused by blood passing through a narrow orifice; B. BAV fluoroscopic image LAO 55 and cranial 15: inset (picture) image of ascending
aortogram, showing partial opening of stenosed bicuspid AV (negative shadow) and main image is showing balloon valvoplasty in the same view;
arrow indicating waist of balloon; C. Pressure tracings on the monitor shows the left ventricular (LV) pressure (red) is 176 mm Hg and aortic
pressure (green) is 90 mm Hg, gradient is 86 mm Hg; D. The pressure tracings after successful balloon dilatation the LV pressure dropped to
150 and aortic pressure increased to 130 mm of Hg.The gradient reduced to 20 mm Hg
table 11
Differences in approach between aortic vs pulmonary balloon valvuloplasty based on references

Aortic stenosis
Pulmonary stenosis
Annulus
Aortic annulus contains fibrous ring

(incomplete)
Muscular annulus
Balloon size
Usuall 90% of annulus, never above 100%
Usually 120% of pulmonary annulus, one may go even

above this size in few cases
Regurgitation
Regurgitation is not well tolerated and tend

to increase
Regurgitation is better tolerated. In severe case it may

create problem later
Postprocedure dynamic
obstruction
Normally there is no subaortic muscular

infundibulum hence unlike the pulmonary
stenosis no sudden increase in LV pressure
After successful balloon pulmonary valvuloplasty

hypertrophied sub pulmonary infundibulum goes into
spasm in absence of high systolic pressure produced
by stenotic pulmonary valve condition known as suicidal
right ventricle.. It is treated with volume and betablockers
Outcome
Success rate: 8896%
95100% (depending on case selection)
Chances of reintervention
Repeated procedures may be required and

future valve replacement may be needed
Mostly one time procedure in most of the cases.

Reintervention may be needed in dysplastic valves and
neonatal pulmonary stenosis
495
D
techniques.89-91
Figures 27A to D: Aortic valve repair

A. Leaflet suspension and subvalvular annuloplasty in aortic valve prolapse;
B. Restoring cup integrity; C. Leaflet extension using autologous pericardium; D. Triangular resection
associated with AR. They also defined the AV prolapse

echocardiographically.92
Normal AV cusp coaptation occurs approximately, at a
level, corresponding to the middle of the sinuses of Valsalva,
i.e. halfway between the ventriculoaortic junction and STJ. Cusp
prolapse, therefore, is strictly defined as the motion of the cusp
free margin below this level. The AV prolapse may involve a
single cusp or all the three cusps. The prolapse of cusp can be
appreciated relative to other cusps or absolute in relation to
physiological coaptation level.
aortic valve replacement 2,14,17,18,23,93-95
496
Aortic valve replacement is usually management of choice

in absence of a successful repair technique. The mechanical
valves have shown acceptable long-term results. Eventual
outcome of ballooning procedures or surgical repair is the
valvar replacement.
Type of Artificial Valves

The artificial valve are designed to imitate the purpose of the
native valves. There are two basic types of artificial heart
valve:
1. Mechanical valves
2. Tissue valves.
Mechanical Valve
Mechanical heart valves are more durable in comparison to
their bioprosthetic counterparts. Newer mechanical devices
are bileaflet structure and the struts and occluders are made
out of either with pyrolytic carbon. Usually, the sewing
ring cuff is Teflon, polyester or dacron. Replacement with a
mechanical prosthesis currently provides the most durable
result. Disadvantages associated with mechanical prosthesis
are the constant need for anticoagulation and lack of growth
potential. Evidently, these are the significant problems in small
33
children. These valves tend to produce noise. Postsurgical,

paravalvar leak and valve dysfunction may lead to reintervention (Figures 28A and B). The bacterial endocarditis
is more common in prosthetic valve than the native AV.
Arnold et al found good outcome after mechanical valve
replacement in 30 children. There was improvement in LV
ejection fraction, systolic and diastolic dimensions.93
Tissue or Bioprosthetic Valve

Tissue heart valves (bioprosthetic valves) are usually made
from animal tissues, either animal heart valve tissue or animal
pericardial tissue. The tissue is treated to prevent rejection and
to prevent calcification. In some cases, a human (cadaveric)
aortic valve can be implanted (homograft). The durability
of the homograft valves is probably the same as for porcine
tissue valves. Use of bioprosthetic valves, either homograft
or heterograft, avoids the need for anticoagulation, but valve
growth potential is still a major issue and longevity of these
valves is frequently poor, particularly in small children.
autograft: ross Procedure17,18,94,95
Figure 29: Ross proceduremain pulmonary artery with pulmonary

valve with sleeve of wall dissected out (pulmonary autograft) to be
sewn in place of removed diseased aortic valve and proximal end of
ascending aorta. A homo or heterograft with valve is then stitched
between distal MPA and space created by pulmonary valve removal.
LAA = Left atrial appendage; PA = Pulmonary artery
In some centers the Ross procedure (named after Dr Donald

Ross) or pulmonary autograft is the preferred operation,
particularly in infants and small children. The Ross procedure
involves replacement of diseased aortic valve by putting the
pulmonary autograft along with sleeve of main pulmonary
artery and placing a homograft or heterograft in place of the
patients original pulmonary valve (Figure 29). The pulmonary
autograft is advantageous as it is the patients own tissue, hence,
has growth potential and is not subjected to immunologic
degenerative changes. It is free from risks associated with
anticoagulation and has excellent hemodynamic characteristics.
Therefore, it is an excellent choice for children and young
adults needing AV replacement. Raja et al published their paper
about the series of 32 patients with mean age of 13 +/ 5.7 years

and a follow-up period of of 3 to 7 years. Actuarial survival
at 7 years was 94 2.5% and there was 100 percent freedom
from reoperation for autograft valve dysfunction or any
other cause. Balloon dilatation was required in 2 patients for
pulmonary homograft stenosis.94
The pulmonary homograft in the RVOT is regarded as the
limiting factor in the long term success of the Ross procedure.
However, modifications of the Ross operation have reduced
the incidence of pulmonary autograft dysfunction, and in
some cases the function of this valve remains excellent for
Figures 28A and B: A. Transesophageal echocardiography (TEE) midesophageal short-axis view mechanical prosthetic valve in situ
in aortic position; B. 3D echocardiography, short-axis view showing paravalvar leak seen. Image courtesy: Nagendra Chauhan
497
many years. The patients with rheumatic aortic valve are not
good candidate for Ross procedure.95
Percutaneous aortIc valve ImPlantatIon

Percutaneous AV implantation (TAVI) is a promising new
technique that is currently being developed as an alternative to
surgical valve replacement in adult patients who have severe
AS and are deemed inoperable. The TAVI was first reported in
1992 using a closed-chest pig model. After the demonstration
of feasibility of TAVI in 2002, it is now widely practiced, with
more than 20,000 patients treated worldwide, and the technique
has been recommended as an alternative strategy for patients in
high-risk surgical groups. Recently, in our institute, few cases
were done successfully. Although this technology is rapidly
developing, this procedure is not an option for children and
adolescents with congenital AS.96 Table 12 shows the various
types of aortic valves used for percutaneous implantation
(Figures 30A to D).
endocarditis in Prosthetic aortic valve97-99

Prosthetic valve endocarditis (PVE) is an endovascular,
microbial infection occurring on parts of a valve prosthesis
or on reconstructed native heart valves. It is recommended to
determine the involved valve::
a. A mechanical prosthesis
b. A bioprosthetic xenograft, stented or unstented
c. An allograft
d. A homograft, or
e. A repaired native valve with or without implantation of an
annular ring.
It has been suggested that, infections of the devices or lines
placed inside the heart, but not connected to the endocardial
structures should be classified as polymer associated infections
498
table 12
Various aortic valves for percutaneous implantation

Valve
Manufacturer
Mechanism
Cribier-Edwards
Edwards
Lifesciences
Balloonexpandable
CoreValve ReValving
System
CoreValve
Self-expanding
Edwards SAPIEN
Edwards
Lifesciences
Balloonexpandable
and PVE should be classified as either being acquired

perioperatively, and thus nosocomial (early PVE), or as
community acquired (late PVE). The proposed interval between
early and late PVE is one year.
Chances of having endocarditis is more when surgery is
done in patients with infective endocarditis (IE). The incidence
is relatively less in mechanical valve than bioprostheses. The
PVE is more frequent for prosthesis in aortic position than
mitral and for multiple implant.
Mechanical prosthetic infections originate from the
sewing cuff or from nearby located thrombi and culminate
into periprosthetic leaks, ring abscesses, invasion of adjacent
tissue. Bioprosthesis infections mostly are restricted to the
cusps leading to secondary bioprosthetic failure.
Staphylococci (especially novobiocin susceptible, coagulase
negative staphylococci), bacteria of the HACEK group, and
fungi occur more frequently in PVE. Streptococci and enterococci are found more frequently in native valve endocarditis.
As the risk for infection is much higher in patients with
prosthetic heart valves than in patients with valvar heart
disease, more intensive prophylaxis with prolonged duration
is needed in these patients. Patients may need surgical
intervention to avoid complications.
Figures 30A to D: Transcutaneous aortic valve implantation (TAVI)
aortic stenosis in Fetus100-104
Fetal aortic valvotomy

The first known fetal aortic valvuloplasty was performed in
1989. Since then experience is growing and many centers
worldwide, are performing it routinely. In India it is not been
done till date.100,101
The goal of intervention for fetal AS is to alter left heart
physiology and growth, sufficiently to allow postnatal
survival with a healthy biventricular circulation. In a recently
published experience, just over 30 percent of patients who
underwent technically successful fetal cardiac intervention for
this indication had a biventricular circulation from birth, and
another 8 percent were converted to a biventricular circulation
after initial univentricular palliation.102
Fetal aortic balloon valvuloplasty

Procedure
The procedure is performed at 21 to 32 weeks of gestation. It is
done under maternal local anesthesia and sedation. A needle is
inserted through the mothers abdominal wall, into the uterine
cavity under ultrasound guidance. Fetal analgesic is then
injected before advancing the needle through the fetal chest
wall into the LV of the fetus. A guide-wire is inserted through
the needle and across the aortic valve. A balloon catheter is then
inserted and inflated to dilate the stenotic valve. The catheter
and needle are withdrawn after the completion of procedure.
Fetal positioning is critical for success of the procedure.103
Goldstein et al reported the novel use of a pressure guidewire
during aortic valvuloplasty in a fetus at 21 weeks gestation
with critical AS and evolving hypoplastic left heart syndrome.
They demonstrated that this technique augments fetal safety
as it relates to operator awareness of catheter and wire
position (with continuous monitoring of pressure waveforms),
improves the intraprocedural fetal hemodynamic monitoring
and responsiveness to resuscitation. Also, it provides a rich
new data set of invasive fetal hemodynamics.104
safety of the Procedure

Though the various centre have claimed the good success rate
in fetal AS, the procedure is technically, ethically and morally
conclusIon
The alteration in number of cusps, leads to abnormal flow
pattern across the valve. Quadricuspid valves are usually
regurgitant. The bicuspid valves are common and may
be incompetent or stenotic. Unicuspid valves are often
stenotic and present early. Aortic valve and aortic root are
integrated structurally. The aortic root and its components are
specialized to withstand the high pressure sheering forces.
Hemodynamically, the aortic root has unique capability to
tolerate the deforming forces acting on two sides of aortic
valve. The LVOT and AV may have congenital and acquired
lesions, leading to dysfunction in sizable population of patients.
Aortic stenosis and regurgitation, infective endocarditis and
aortic dissection are the most common complications. The
recognition of the BAV as the culprit for isolated AV disease,
remains an important challenge to the clinicians, whereas
preoperative knowledge of valve morphology would be
helpful in planning the surgery. This lesion can manifest from
fetal to elderly age group. The rheumatic fever is anytime,
important etiological factor for combined aortic and mitral
valve disease. Recent technical advancements have fetched
tremendous refinement in diagnostic and interventional
abilities. All over the world, AV is repaired or replaced with
excellent results. For valvar AS in infants, children and
adolescents, ABV is preferred technique of palliation. Ross
procedure is the alternative surgical procedure for this group
as it may ensure the growth of pulmonary autograph at the
aortic position. The percutaneous valve implantations are
now routinely done for adults in many countries. Also, for
elderly patients with AS , there is scope for medical therapy to
modify the natural history of moderate AS. For pediatric age
group no modifying effect of drugs has been demonstrated
as yet. The fetal interventions are another attractive modality
and are being refined to improve success rate. The genetic
interventions and evolution of prosthetic materials, which
are more in concordance with aortic root physiology are the
future goals.105
33
Aortic stenosis in fetus may eventually present as hypoplastic

left heart syndrome and a careful evaluation is recommended.
In mid-gestation fetuses with AS and normal LV length,
reversed flow in the transverse aortic arch and foramen
ovale, monophasic mitral inflow, and LV dysfunction have
high probability of worst outcome. Nonetheless, these
physiological features may help in prognostication. With
growing experience worldwide, fetal interventions are done
to avoid this hemodynamic fate.
demanding. Fetal position and left ventricular size remain

the critical factors for technical success and good long-term
outcome of the procedure.102,103
Medicine heals doubts as well as diseases.

Karl Marx
acknowledgments
I am grateful to Dr KS Iyer Director, Pediatric cardiac
surgery, Dr YK Mishra, Director, Cardiac surgery for their
inputs regarding aortic valve surgery, Dr Apoorva Goyal,
senior consultant radiologist FEHI, for CT angio images
Dr Nagendra Chauhan, Sr Consultant, Medanta Medicity, for
3D images, Dr IB Vijayalakshmi and Dr Pradeep Vaideeshwar
for providing some of the images.
499
500
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Sec t i on
Diseases of the Aorta
C hapter
34
Coarctation of the Aorta

Bentham J, Wilson N
IntroDuCtIon
Coarctation of the aorta can be defined as an obstruction
in the descending aorta located most commonly at the site
of insertion of the ductus arteriosus. In practice, this is too
simplistic definition to be of clinical use and coarctation is
more appropriately viewed as a complex cardiovascular
disorder where aortic obstruction is only one part of a
generalized arteriopathy with life-long implications persisting after initial correction of the aortic obstruction. It is
without apology that the emphasis of this chapter falls
heavily on clinical management. The intention is to leave
the reader with sufficient knowledge to be able to devise a
management strategy for each of the diverse morphology of
arch obstructions encountered at any age as well as a longterm view of the need for surveillance and management of
complications often some years following initial treatment.
The illustrations also focus on these aspects using a casebased approach. Although, this allows the chapter to be more
focused even this is a formidable challenge. Many surgical
and interventional options exist with differing indications
dependent on whether presentation is in the neonatal period
or in later life; the location of obstruction (discrete, longer
segment or multiple level); the type of obstruction (native,
recoarctation or residual), the prevailing center experience
and availability of technology. It will quickly become
evident that no single approach is universally applicable and
interventional cardiologists and surgeons employ different
strategies to combat arch obstruction and the complications
that ensue. A thorough understanding of the nature and clinical
relevance of the arch obstruction informs these decisions and
time will be spent reviewing these factors in turn. Discrete
coarctation of aorta along with associated tubular hypoplasia
will be the main consideration with brief comments made
about associated lesions in so far as how the management
strategy adopted may need to be altered accordingly. At the
extreme end of severity is interrupted aortic arch, which will

be dealt with in chapter 35.
PrevAlenCe AnD etIology

Aortic arch obstruction is relatively common in newborn
infants1,2 with a higher incidence in the stillborn.3,4 Aortic arch
obstruction is most commonly secondary to coarctation of aorta
with an incidence approaching 1:2,000 live births. It also results
from hypoplastic aortic arch and aortic arch interruption.1,5
Although pathogenesis is likely to be multifactorial, the
genetic factors are clearly important with significantly higher
recurrence risks noted in family members and with notable
syndromic associations (Turner, Noonan and Williams-Beuren
syndromes in particular).6-8 Useful in prenatal counselling,
published recurrence rates of any congenital cardiac defect
given a first degree relative with coarctation of aorta are
increased by several orders of magnitude at between 6.5 to 10
percent.6,9-11 There is some suggestion of concordance for the
same or other left-sided phenotypes.9-11
MorPhology
The morphological spectrum of aortic arch obstruction is quite
varied. In neonates and infants accompanying a coarctation
shelf of ductal tissue there is usually aortic arch isthmus
and transverse arch tubular hypoplasia in contrast to a more
discrete stenosis distal to the left subclavian artery which is the
typical lesion in older patients (Figures 1 to 3).1,5 Like most
congenital heart defects, aortic arch obstruction occurs either
in isolation or in association with other cardiac anomalies
where the term complex rather than simple or uncomplicated
coarctation of aorta is employed.12,13 The main associations of
coarctation of aorta include bicuspid aortic valve, ventricular
septal defect (VSD) and aortic and mitral valve anomalies
(Figures 4 and 5). Coarctation of aorta may also complicate
Diseases of the aorta
figures 1a and B: Echocardiographic assessment of the arch anatomy of a newborn infant in preparation for surgical repair. A. A 2.5 kg oneday-old neonate who presented antenatally with ventricular and great artery disproportion. The left ventricle (arrow, LV) appears smaller than
the right and occasionally careful assessment of the LV, mitral valve, aortic valve and aortic arch dimensions are necessary to confirm suitability
for two ventricle repair. Although uncomplicated in this case, these decisions can be difficult; B. In the same infant as in (A) the ascending
and transverse arch appears adequately developed with coarctation clearly demonstrated distal to the left subclavian artery with a prominent
posterior shelf (arrow). There is still a large duct though this collection of findings should be sufficient for a surgical decision without need to
withhold PgE to allow ductal constriction to confirm arch obstruction. This infant underwent end-to-end anastomosis through lateral thoracotomy
on day three of life
506
figure 2: A neonate with coarctation and transverse and isthmus

arch hypoplasia. The aortic arch between the brachiocephalic artery
and left common carotid artery is hypoplastic. The arch after the
left common carotid artery is also small. An extended end-to-end
anastomosis was performed through a median sternotomy to achieve
a more satisfactory repair
figure 3: A neonate with coarctation and isthmus arch hypoplasia.

Here, there is transverse arch hypoplasia at 3 mm in a 3.5 kg neonate
(distance 2) with further tapering of the arch at the aortic isthmus to
2.4 mm (distance 4). As in Figure 2 an extended end-to-end
anastomosis was performed through a median sternotomy to achieve
a more satisfactory repair
complex congenital heart disease, notably transposition of

the great arteries, double outlet right ventricle, double inlet
left ventricle, tricuspid atresia and hypoplastic left heart
syndrome. Whether there is a sequence of anomalies from
discrete coarctation through tubular hypoplasia to interruption

is open to debate. Recognizing such a spectrum of disease as
well as the typical patterns of associated anomalies where
coarctation of aorta is a frequent accompanying feature led
PreSentAtIon
neonate
Increasingly, coarctation of aorta is diagnosed antenatally with
suspicion raised by marked ventricular or great vessel disproportion15 (Figures 1A and B). There is evidence for improved
outcome for these infants as prostaglandin E2 or E1 (PgE) can
be commenced in the hours following birth to maintain ductal
patency and systemic blood flow thus avoiding cardiovascular
collapse.16 These infants do however, continue to present diagnostic difficulty postnatally as ductal patency is maintained
such that aortic arch obstruction may not be immediately
evident on echocardiography. Often one can be confident to
proceed to treatment on the basis of echocardiographic morphological appearances of coarctation whilst if there is uncertainty
discontinuing PgE under close observation allowing ductal
constriction and aortic arch obstruction to develop before considering treatment is prudent (Figures 1 to 3).
Given the subtlety of the antenatal features of possible
coarctation postnatal presentation will remain frequent. Whether screening methods such as lower limb pulse oximetry
prior to neonatal discharge will increase detection of this
lesion remains to be proven.16 Clinical suspicion should be
raised by lower limb saturations less than 95 percent, an
upper-lower limb blood pressure difference of more than
20 mm Hg and weaker femoral pulses than the upper limb
pulses. When both upper and lower limb pulses are weak this
may result in diagnostic confusion and may reflect reduced
cardiac output from many causes, most commonly an infant
with pulmonary hypertension of the newborn, septicemia or
left heart obstructive lesions (aortic stenosis and hypoplastic
left heart syndrome). An aberrant right subclavian artery
(ARSA) could theoretically fail to detect both a difference in
upper limb and lower limb blood pressure or pulse oximetry
readings as the right subclavian artery may arise below the
site of coarctation. In practice, this is a rare association (less
than 3%). A bruit may be heard between the scapulae, but is
not typical of neonatal coarctation.
Any neonate presenting with cardiovascular collapse should
undergo cardiac evaluation as part of a diagnostic workup and
echocardiography forms the mainstay of diagnostic evaluation
of the aortic arch (Figures 4A to E). Such duct dependent
infants rarely present diagnostic difficulties and PgE can be
instituted as part of resuscitation. Not infrequently inotropes

are an important part of resuscitation in these circumstances
and occasionally emergency interventional or surgical relief
of obstruction is necessary (see below). Evidence for efficacy
from high dose PgE (doses greater than 20 ng/kg/minute) in
improving ductal patency and relieving aortic obstruction
is controversial with no convincing evidence for increased
efficacy at higher dose.17,18 Not all infants with coarctation of
aorta will be duct dependent and some will present in heart
failure as left ventricular function becomes impaired over the
early weeks to months of life. A smaller number of infants will
remain asymptomatic and present with a cardiac murmur.
older Child and Adult
34
CoarCtation of the aorta
Rudolph to speculate that a reduction in the volume of blood

passing through the ascending aorta in fetal life is causative in
the development of coarctation.14 Although other etiological
theories exist Rudolphs hypothesis is the most useful to
remember in clinical practice as coarctation of aorta and/or
transverse arch hypoplasia should be suspected until proven
otherwise, when there is potential for preferential ductal arch
over aortic arch flow during fetal life.
Older children and adults may present with systemic hypertension or a cardiac murmur. Less commonly they exhibit
complications of aortic obstruction including left ventricular
failure, infective endarteritis, intracranial hemorrhage, regurgitation of an associated bicuspid aortic valve, premature
coronary artery disease or aortic dissection or rupture.
IMAgIng
Chest radiography
The asymptomatic older child may demonstrate a prominent
aortic knuckle and rib notching. Rib notching is rare in early
childhood and most likely seen beyond 10 years of age. Chest
radiography is neither diagnostic nor prognostic, but may
contribute if there is complex disease.
echocardiography
The characteristic features of coarctation of aorta on
echocardiography is indentation of the posterior aorta by
a wedge or shelf of tissue (Figures 1 to 3). This can on
occasion be difficult to demonstrate in the presence of a large
patent ductus in an infant maintained on a PgE infusion.
Serial echocardiography may be required in this circumstance
with PgE discontinued. The transverse and isthmus arch
dimensions can be clearly defined by suprasternal views
with echocardiography. Doppler interrogation may not be
informative if ductal flow is large, but if the ductus is closed or
constricted classical features of acceleration with flow into and
through diastole are easily demonstrated. Considerable clinical
judgement may be required in borderline cases particularly in
the setting of complex hearts with multiple malformations.
Aortic arch obstruction will most likely progress over time
and the classical features of aortic arch obstruction are not
immediately apparent. Associated features need to be defined
by a full echocardiographic study as they will impact greatly
on the management strategy (Figures 4 and 5).
507
figures 4a to e: Associated findings in infants with coarctation can impact greatly on the treatment strategy adopted. A five-day-old infant who
presented collapsed and required resuscitation. A. M-mode study through the left ventricle. The left ventricle is dilated (left ventricle end diastolic
diameter 2.55 cm) and the cardiac function is impaired (fractional shortening 15%). (B1) There is persisting pulmonary artery hypertension
with severe elevation of pulmonary artery pressure (estimated at 64 mm Hg from TR jet velocity + RA pressure estimated from IVL diameter);
B. Mitral regurgitation is common in this scenario and interrogation for concomitant mitral valve anomalies is important; C. There is a large
ventricular septal defect (VSD, arrow) which extends from the inlet valves (arrow) to the outlet (D, arrow). There is a further apical VSD (red color
flow Doppler evident in (C) and a bicuspid aortic valve with dooming valve leaflets; E. With such a large VSD primary repair of coarctation and
VSD would involve increased risk of a long and difficult intensive care course. An end-to-end anastomosis and a pulmonary artery band was
performed after a period of stabilization on PgE. The VSD was subsequently closed at six months of age
Magnetic resonance Imaging

In the older child and adult, magnetic resonance imaging
(MRI) is more informative than echocardiography and is the
imaging modality of choice for planning intervention. MRI
is able to define accurately whether one or multiple sites of
obstruction exist, the proximity to the head and neck vessels
as well as the length of hypoplastic segments. MRI is also a
useful surveillance tool for complications following treatment
of coarctation and many units routinely perform MRI as part of
transition from pediatric to adult practice particularly if there
is a degree of systemic hypertension.19 Standard protocols
have been extensively published.
Computed tomography
508
Occasionally, computed tomography (CT) can be useful in

infants where there is diagnostic uncertainty about complex
aortic arch anatomy. Modern multislice scanners are able

to achieve sufficient resolution to be superior to MRI in
small infants and would be complimentary to detailed echocardiography albeit at the expense of radiation exposure.
General anesthesia is rarely required.
Angiography
With the advent of noninvasive imaging, angiography is
generally not required as a diagnostic tool in the evaluation
of native coarctation of aorta. Angiography is performed as
part of interventional treatment of coarctation of aorta in the
older child and adult but rarely in isolation. Occasionally,
diagnostic angiography is necessary to assess the adequacy
of repair and would form an important part of the interstage
assessment of aortic arch reconstructive surgery following the
Norwood procedure for example. The difficulty here however
is that, gradients obtained under general anesthesia bear little
Surgical treatments
figure 5: Associated findings in children with coarctation can

impact greatly on the treatment strategy adopted and careful for full
echocardiographic evaluation is essential. A two-year-old girl presents
with a cardiac murmur to her local pediatrician. Coarctation of aorta
and a volume loaded left heart was evident on echocardiography.
There was pulmonary hypertension and a large aortopulmonary
window was found (arrow). Repair of aortic coarctation by end-to-end
anastomosis and repair of aortopulmonary window was performed with
resolution of pulmonary hypertension in the days following surgery.
The aortopulmonary window had been missed by an incomplete
echocardiographic study at another institution
resemblance to gradients likely to be experienced by the

patient under stress. Consequently, an infusion of an inotrope
such as adrenaline may be required to reveal suspected residual
obstruction. In the setting of patients with univentricular
circulation, such diagnostic studies may be important when
considering higher risk interventions once other therapeutic
strategies have been exhausted.
InDICAtIonS for treAtMent

In infants with hemodynamic compromise the indication
for treatment is unequivocal. In older patients a consistent
systolic blood pressure gradient between the arms and legs
of more than 20 mm Hg may be considered as an indication
for treatment although this is not universally accepted.20,21
The gradient across the site of aortic obstruction will be
influenced by the degree of collateral vessel formation such
that gradient alone is not a good indication for treatment in
some patients. Systemic hypertension at rest or following
provocation with exercise greater than the 97th percentile for
age along with evidence of important luminal stenosis would
form indications for treatment in this group of patients.22 The
complexity of arch obstruction, the procedure related risk and
the likelihood of procedural success form important parts of
the joint cardiac and surgical discussion as to the timing and
The evolution of many surgical treatment strategies for

coarctation of aorta since the early 1940s highlights the fact
that each technique has its inherent advantages, disadvantages
and risk of long-term problems. Over the years, the primary
technique for most centers managing infant coarctation
remains end-to-end anastomosis having removed the segment
of obstructed aorta and all ductal tissue.23-26 From published
series no one technique is clearly superior as advocates of
alternative surgical strategies are able to achieve similar results.
There will be circumstances where options are limited and one
technique is preferred in view of the arch anatomy even if
associated with higher risk of complications. The capability to
offer more than one technique occasionally in the same patient
will be an important prerequisite of success in managing the
diversity of aortic arch obstructions encountered.
34
indications for intervention in each case. Debate exists over

whether residual gradients and obstructions are acceptable in
the absence of systemic hypertension given the serious nature
of the long-term prognosis for coarctation of aorta (see later
in this chapter). Further work to refine our understanding of
the risk factors for adverse outcome will better inform these
indications for treatment and repeat procedures.
End-to-End Anastomosis Including Extended Repair

End-to-end anastomosis has become the procedure of choice
for many centers managing infant and neonatal coarctation.27,28 The mortality rate in uncomplicated patients is very
low,23,29 but rises with more complex disease and associated
lesions.29,30 Residual obstruction in up to 34 percent of patients
is noted at early follow-up. Residual obstruction is strongly
associated with weight at the time of surgery.26,28-32,37 Whether
obstruction at follow-up can be defined as recoarctation
resulting from scar tissue formation or failure to adequately
treat the primary lesion is open to debate (Figures 6 to 9).
Managing tubular arch hypoplasia with an extended or end-toside repair may be preferable and highlights the importance of
careful pre-operative assessment.33
Subclavian Flap Repair

Concerns about inadequate relief of obstruction with subclavian
flap repair and the long-term risk of aneurysm formation has
rendered this technique less popular. Occasionally, subclavian
flap repair may be combined with end-to-end anastomosis to
more adequately treat long segment obstruction.33
Interposition Grafts, Bypass Tube, Extra-anatomic

Bypass Grafts
In older patients and adults, there is significant concern about
the ability to sufficiently mobilize tissue in a timely fashion to
509
figures 6a to f: A two-year-old child who presented in the neonatal period with coarctation (A-C) and underwent end-to-end anastomosis has
significant tubular hypoplasia of the aortic arch after the left common carotid artery (D-E). The arch hypoplasia was evident following neonatal
surgery. In view of the infants age, angioplasty was performed with modest improvement in caliber of the arch (F1). A. There is a large duct with
bidirectional flow evident on the pulse wave Doppler (inset figure, predominantly right-to-left flow); B. There is a posterior shelf as substrate for
an evolving coarctation (arrow) and relative hypoplasia of the arch between the left common carotid artery (LCCA) and the left subclavian artery
(*); C. There is a bicuspid aortic valve; D. At two years of age a 3D MRI reconstruction demonstrates the hypoplastic arch segment proximal to
the site of repair; E. An arch angiogram through a 4 French pig-tail catheter confirms the MRI findings and angioplasty is performed; F. A small
aneurysm at the base of the left subclavian artery is evident. In view of this childs age and aneurysm, the residual gradient was accepted with
a provisional plan for stent placement to the hypoplastic segment at greater than 25 kg
achieve an end-to-end repair of coarctation without occurring

significant risk of spinal cord ischemia from prolonged aortic
cross-clamp. For these reasons, interposition grafts and bypass
grafts are occasionally necessary to satisfactorily relieve
obstruction. With the advent of interventional options these
circumstances are becoming increasingly uncommon.
Patch Aortoplasty
510
Prosthetic patch aortoplasty is now seldom used as a primary

treatment because of the unacceptable risk of aneurysm
formation associated particularly with the use of Dacron
patches.34 Patch aortoplasty is however sometimes necessary
with complex arch obstruction in young patients particularly
in the context of early recoarctation (Figure 8).
Influence of Associated Lesions

The commonest associated findings with discrete coarctation
of aorta are bicuspid aortic valve and ventricular septal defect.
Bicuspid valves are rarely sufficiently stenotic to require surgical or interventional treatment in the neonatal period. In the
context of severe aortic stenosis, surgical valvotomy alongside coarctation repair might be preferred over interventional
balloon valvuloplasty and surgical arch repair as two separate procedures. VSDs are sufficiently common to frequently
influence surgical decisions. Large VSDs may be closed as
a primary procedure alongside aortic arch repair if the surgeon feels able to close the defect in a small heart without
significant morbidity. This will be consequent on the number
and morphology of the VSDs. Apical or large VSDs, which
34
figures 7a and B: Residual or re-coarctation is not uncommon following surgery. A. 3-day-old neonate presents with poorly palpable femoral
pulses and is found to have coarctation with a clearly evident posterior shelf associated with increased velocity with diastolic tail on continuous
wave Doppler interrogation (inset figure). End-to-end anastomosis is performed. At one year of age recoarctation is evident with discrete
obstruction; B. And a similar Doppler profile through the obstructed segment (inset figure)
figure 8: Residual or recoarctation is not uncommon following surgery

with the underlying arch anatomy being a critical factor in the likelihood
of recurrence. A three-month-old infant presents for follow-up following
end-to-end anastomosis repair of neonatal coarctation. There is
generalized hypoplasia of the aortic arch as well as the head and
neck vessels. No discrete obstruction is identified to guide therapeutic
intervention. The arch is augmented after the left subclavian artery
with a patch aortoplasty though the descending aorta is similarly small.
This infant most likely has a vasculopathy (no elastin mutation was
identified)
figure 9: Residual or recoarctation is not uncommon following surgery.

This hypertensive teenager was initially palliated as a low-birth-weight
infant with a turn down procedure of the left subclavian artery. The
coarcted segment is still evident. An 18 mm surgical interposition graft
was placed across the coarctated segment and the left subclavian
artery turn down left producing effectively a double aortic arch with a
satisfactory result
511
figures 10a to D: A 3 kg neonate presenting with coarctation of aorta (B) and a large apical muscular ventricular septal defect (A, VSD).
The aortic arch is repaired and a pulmonary artery band placed. The VSD closes spontaneously sufficiently that the pulmonary artery band
is removed in the catheter laboratory with an angioplasty technique at six months of age (C and C1). The aortic arch caliber is checked with
angiography (D). A. The large apical VSD is demonstrated (arrow); B. There is a posterior shelf evident after the left subclavian artery; C. In
preparation that the VSD may close spontaneously the surgeon has placed a clip to secure the pulmonary artery band that can be displaced
with an angioplasty balloon. The pulmonary artery band is demonstrated in this lateral angiogram. Angioplasty is then performed with a 12 mm
2 cm Tyshak II angioplasty balloon; D. An arch angiogram has been performed in lateral projection to confirm the integrity of the arch repair
512
may be more difficult to repair in a small heart whilst preserving satisfactory left ventricular function may be alternatively
treated by placement of a pulmonary artery band with the intention of further surgery at a later stage (Figures 10A to D).
recent technological advance have become the preferred

treatment option in older patients weighing more than 25 kg.
Interventional treatments
Balloon angioplasty is a controversial treatment for native

coarctation of aorta because of the damage to the aortic intima
and media that is necessary for satisfactory relief of stenosis
but which results in recurrent stenosis and appreciable risk of
dissection, rupture and long-term aneurysm formation.24,35,36 In
infancy, although efficacious in relieving stenosis there is good
evidence to support there being a higher risk of recurrence than
that found with surgical techniques.37-39 Balloon angioplasty
does have a place in managing the sick hemodynamically
compromised infant in allowing successful resuscitation and
to act as a bridge to definitive surgical repair at lower risk.40
There is appreciable morbidity associated with surgical repair

of coarctation of aorta including spinal cord damage, pleural
effusions, paradoxical hypertension and infection. Although
mortality is low, residual or recurrent aortic arch obstruction
is sufficiently common to remain an important concern.29
These surgical risks may increase for recoarctation. Lateral
thoracotomy is a painful surgical incision and recovery can
be prolonged. It is against this background that interventional
treatments for aortic arch obstruction have emerged and with
Balloon Angioplasty
for complications differ markedly between series. A single

randomized study included only 36 patients at an age range
of 3 to 10 years.42 There was a comparable reduction in
systolic gradients across aortic arch obstruction between the
two groups. As expected restenosis occurred more commonly
in the angioplasty group although this failed to reach
statistical significance. Neurological complications occurred
more frequently in the surgical group and aneurysms in the
angioplasty group. Late follow-up showed equivalence for need
for reintervention but an appreciable number of aneurysms
developed late in the angioplasty group.43
Stent Placement
34
Some centers also perform balloon angioplasty in lower-birthweight infants (less than 2.5 to 3 kg) in order to delay surgery
until an infant has grown and achieve a more satisfactory
surgical result (Figures 11A to D).33 Balloon angioplasty
should also be considered in children weighing less than
25 kg when faced with significant residual or early recurrence
of gradient.24,41 Some centers might consider balloon angioplasty in smaller children beyond infancy as a bridge to stent
placement when heavier than 25 kg thus avoiding the need
for surgery. The risks of complications in this setting may
be appreciable with the need for repeat procedures. In older
children and adults, primary stent placement is generally
preferred by most operators for management of recurrent
aortic arch obstruction following previous surgery.
It is difficult to make meaningful comparisons between
balloon angioplasty beyond infancy and surgery for treatment
of coarctation of aorta based on individual centers published
experience. Furthermore, follow-up protocols for surveillance
Endovascular bare metal stents have been used to treat recoarctation, native coarctation and aortic arch obstruction
for over a decade and were viewed as a potential solution to
the problems of aneurysm formation associated with balloon
figures 11a to D: Balloon angioplasty treatment of neonatal coarctation of aorta and childhood recoarctation of aorta. A. A 2.5 kg neonate
has been palliated with balloon angioplasty (B and B1, 8 mm 3 cm Tyshak II balloon) of coarctation as a bridge to surgical repair following
further weight gain; C. Significant re-coarctation following end-to-end anastomosis in a two-year-old child has been managed with angioplasty;
D. There is improvement in the caliber of the obstructed segment but further procedures are likely to be required to allow for further growth later
in childhood (stent placement)
513
angioplasty.44 Furthermore, bare metal open cell designed

stents potentially offer an effective solution for complex
arch obstruction in adults and older children where balloon
angioplasty is often ineffective because of elastic recoil and
surgery may require extra-anatomic bypass grafts. There
remains concern, however that bare metal stents are still
associated with aortic aneurysm formation with a long-term
risk of aortic rupture albeit less than the risk with balloon
angioplasty alone.45 Covered stents may thus be preferred
where possible (Figures 12 and 13).46-48 Covered stents
are, however, relatively contraindicated if placed in such a
position as to occlude head and neck vessels. Head and neck
vessels may be covered with a stent only after evaluation
of the circle of Willis and with the availability of vascular
surgical grafting. Complications relating to exclusion of the
left subclavian artery, even in adults, are rare.49,50
Placement of endovascular stents in infants and small
children (< 25 kg) remains a controversial therapy despite
improvements in methods of access, balloon and stent size
and the use of smaller and smaller sheaths.24,51 The fact that
children will by necessity, be committed to several future
cardiac catheter procedures because of need for stent redilation causes concern for most; thus preferring surgical
alternatives, balloon angioplasty or stent therapy only as a
bridge to definitive surgery later in childhood52,53 or potentially
as a bridge to adult size stent placement.54
Short-term published results for stent implantation to
successfully manage native and recurrent coarctation in
older children and adults suggest that stenting gives more
predictable and lasting results than balloon angioplasty. Death
has been reported between 0 to 1.4 percent and neurological
damage between 0 to 3.7 percent.45-48,55-61
The most frequent complication following interventional

stent placement relates to vascular access with need for large
sheaths. This has undoubtedly improved with technological
advances allowing delivery of stents through smaller and
smaller sheaths as well as vascular closure techniques. Whether
interventional treatments will become a panacea for managing
aortic arch obstruction from infancy to adult life remains to
be realised, but the adaptability of these techniques to varying
situations makes aortic arch intervention an important part of
a comprehensive cardiac program (Figures 13A to D).
PrognoSIS
The natural history of coarctation of aorta is extremely poor.
Campbell reported mortality in excess of 75 percent of patients
by 46 years of age.62 In the largest follow-up series of 646
patients who underwent treatment for simple coarctation of aorta
at the Mayo clinic between 1946 and 1981 the postoperative
10-year survival rate was 91 percent, falling to 84 percent at 20
years and 72 percent at 30 years. Earlier age at operation was
associated with improved survival.63 Causes of death included
premature coronary artery disease, left ventricular failure,
stroke, sudden cardiac death and ruptured aortic aneurysm.
Given such poor outcomes conservative management of
important residual gradients is not an attractive option. However,
whether these risks may be reduced by adequately treating
residual obstructions remains to be proven.64 Such a guarded
prognosis may in-part relate to a coexisting vasculopathy that
poses a significantly increased risk of systemic hypertension
throughout a patient's life.65-67 Life-long follow-up, treatment
of systemic hypertension and intermittent surveillance imaging
to detect occult obstruction and/or aneurysm are essential.
figures 12a to C: Interventional management of aortic coarctation in an eight-year-old child presenting with systemic hypertension. A. The 3-D
MRI reconstruction is helpful in planning the interventional procedure as there is a long segment coarctation. The appearances are similar to
those confirmed on angiography; B. and C. A covered Cheatham-platinum stent has been placed with immediate and complete resolution of arch
obstruction. No damage to the integrity of the aorta is evident, but periodic surveillance by MRI or CT imaging will be performed
514
34
figures 13a to D: Ruptured aortic arch with emergent interventional treatment in a 16-year-old child presenting to the emergency department
with back pain and hemoptysis following subclavian flap repair of coarctation of aorta during infancy. A. A chest radiogram was performed which
demonstrates a large aneurysmal dilatation of the aorta that was confirmed with computed tomography (B., arrow); C. Covered stent placement
was performed in preference to emergency surgery as this was felt to be the safer option. Despite covering the aneurysmal segment with multiple
covered stents an endoleak is still visible (arrow); D. The following day a long vascular stent graft was used to exclude the endoleaks. LAO - left
anterior oblique view
ConCluSIon
Coarctation of aorta can present in early infancy to adult life.
The lesion is highly variable and although surgical treatments
have proved and remain superior in infancy, interventional
treatments are emerging as the preferred strategy in older
children and adults. Early mortality for these treatments is
low, but morbidity over long-term follow-up is extremely
high with need for careful follow-up and surveillance for
complications. Whether the natural history can be modified
by a more aggressive interventional approach remains to
be proven, but given the poor long-term prognosis for this
condition, significant residual obstructions are best managed
by interventional techniques. There is an increasing reluctance
to accept even small gradients in the setting of systemic
hypertension with the hope of better survival for these patients
in the years to come.
The healing process demands more than science; it requires

mobilizing patient's positive expectations and stimulating faith in
physician's ministration. I know of few remedies more powerful
than a carefully chosen word. Patients crave caring, which is
dispensed largely with words. Talk, which can be therapeutic
is one of the underrated tools in a physician's armamentarium.
Bernard Lown, MD
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2008;18:405-14.
Chessa M, Dua JS, Carminati M. Long-term outcome after
balloon angioplasty of coarctation of the aorta in adolescents
and adults: is aneurysm formation an issue? Catheter
Cardiovasc Interv 2009;74:529.
Horlick EM, McLaughlin PR, Benson LN. The adult
with repaired coarctation of the aorta. Curr Cardiol Rep
2007;9:323-30.
34
41. Holzer CE, Jr. Gunshot wounds involving the abdominal aorta;
a report of two cases. Surgery 1948;23:645-52.
42. Shaddy RE, Boucek MM, Sturtevant JE, et al. Comparison of
angioplasty and surgery for unoperated coarctation of the aorta.
Circulation 1993;87:793-99.
43. Cowley CG, Orsmond GS, Feola P, et al. Long-term,
randomized comparison of balloon angioplasty and surgery
for native coarctation of the aorta in childhood. Circulation
2005;111:3453-456.
44. Forbes TJ, Moore P, Pedra CA, et al. Intermediate follow-up
following intravascular stenting for treatment of coarctation
of the aorta. Catheterization and cardiovascular interventions:
45. Chessa M, Carrozza M, Butera G, et al. Results and mid-longterm follow-up of stent implantation for native and recurrent
coarctation of the aorta. European heart journal 2005;26:2728732.
46. Kenny D, Margey R, Turner MS, et al. Self-expanding and
balloon expandable covered stents in the treatment of aortic
coarctation with or without aneurysm formation. Catheterization
and cardiovascular interventions: official journal of the Society
for Cardiac Angiography and Interventions 2008;72:65-71.
47. Butera G, Piazza L, Chessa M, et al. Covered stents in patients
with complex aortic coarctations. American heart journal
2007;154:795-800.
48. Tanous D, Collins N, Dehghani P, et al. Covered stents in the
management of coarctation of the aorta in the adult: initial
results and 1-year angiographic and hemodynamic follow-up.
International journal of cardiology 2010;140:287-95.
49. Caronno R, Piffaretti G, Tozzi M, et al. Intentional coverage
of the left subclavian artery during endovascular stent graft
repair for thoracic aortic disease. Surgical endoscopy 2006;20:
915-18.
50. Rehders TC, Petzsch M, Ince H, et al. Intentional occlusion
of the left subclavian artery during stent-graft implantation in
the thoracic aorta: risk and relevance. Journal of endovascular
therapy: an official journal of the International Society of
Endovascular Specialists 2004;11:659-66.
51. Patel HT, Madani A, Paris YM, et al. Balloon angioplasty of
native coarctation of the aorta in infants and neonates: is it
worth the hassle? Pediatr Cardiol 2001;22:53-7.
52. Mohan UR, Danon S, Levi D, Connolly D, Moore JW. Stent
implantation for coarctation of the aorta in children <30 kg.
JACC Cardiovasc Interv 2009;2:877-83.
53. Holzer RJ, Chisolm JL, Hill SL, et al. Stenting complex aortic
arch obstructions. Catheter Cardiovasc Interv 2008;71:375-82.
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stent placement is an acceptable alternative to reoperation
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517
C hapter
35
Interruption of Aortic Arch

Vijayalakshmi IB, Prasanna Simha Mohan Rao
introduction
Interruption of the aortic arch (IAA) is defined as the
congenital absence of the anatomical and luminal continuity
between the ascending and descending portions of the aorta.1,2
It is the ultimate expression of obstructive thoracic aortic
anomalies that begin with isthmic coarctation.3 The condition
is extremely rare and occurs in less than 1.5 percent of all the
congenital heart diseases (CHD).4 Prognosis of this anomaly
is very poor, unless it is diagnosed and repaired during the
neonatal period. IAA is extremely rare in adults.5
Historical review
The anomaly was first described by the Viennese surgeon,
Raphael Steidele in 1778.6 The classification of IAA by
Celoria and Patton7 refers to one of the three sites, two of
which were described in 1927 by Maude Abbott.8 Steidele
complex is occasionally applied as an eponym to this rare
malformation, which is characterized by complete anatomic
discontinuity or by an atretic fibrous strand between the
aortic arch and the descending aorta.9,10 In 1955, Merrill and
his associates performed the first known surgical correction
of type A IAA.11 The first successful one-stage correction of
type A IAA was performed by Barratt-Boyes et al in 1970.12
In 1975, Trusler and Izukawa reported correction of a type B
IAA in a 13 day baby.13
Embryology
The IAA develops as a result of abnormal formation of
the aortic arch system during the 5th to 7th week of fetal
development. The left fourth arch in the embryo forms the
transverse aortic arch from the left carotid to the ductal site.
The type B and type C IAA and rarely type A is due to the
abnormalities in the formation of this area. Type A IAA can
be due to the decreased flow across the arch and hence across
the isthmus. This in conjunction with right-to-left flow via

the ductus to the descending aorta leads to absence of the
isthmus.14 In patients with IAA, the right subclavian artery
(RSCA) is often malposed as it is also derived in part from
the fourth aortic arch. This anomaly is especially common in
patients with IAA type B, but it can also be associated with
COA or can be an independent anomaly.15
Pathogenesis
The exact cause of IAA is uncertain and several theories have
been proposed. Altered hemodynamics through the fourth
aortic arch and teratogenic exposure (bis-dichloroacetyl
diamine, isotretinoin) during the intrauterine period have been
proposed as its potential causes. Several mechanisms have
been suggested.
1. Abnormal involution of the third and fourth aortic arches.16
2. Decreased antegrade blood flow in the ascending aorta
due to the almost constant presence of ventricular septal
defect (VSD) and left ventricular outflow tract obstructions
(LVOTO).17
The malalignment of the conal septum with the resulting
subaortic stenosis is thought to be responsible for the in utero
involution of the ascending aorta and aortic arch (fourth aortic
arch) and there is reciprocal development of the pulmonary
artery and ductus arteriosus (sixth aortic arch).18 The degree
of the subaortic stenosis is therefore inversely proportional to
the size of the ascending aorta and directly proportional to the
size of the pulmonary trunk.18,19
Associations
The IAA seldom occurs as an isolated anomaly. In 98
percent of the cases, it is usually associated with additional
cardiovascular anatomic defects. The most common
associations are patent ductus arteriosus (PDA) and VSD,
which can be present in 97 and 90 percent of the patients
35
Figure 1: Diagramatical representation of the three types of interrupted aortic arch. DTA = Descending thoracic aorta; LCC = Left common
carotid; LPA = Left pulmonary artery; LSA = Left subclavian artery; RIA = Right innominate artery.
respectively.20-22 The IAA is associated with CHDs which

decrease the blood flow to the aortic arch as seen in LVOTO
including subaortic stenosis, bicuspid aortic valve and in
truncus arteriosus and aortopulmonary window.20,21 The
transposition of great arteries (TGA), double outlet right
ventricle, functional single ventricle, can also be associated
with IAA. Genetic abnormalities, such as DiGeorge
syndrome (chromosome 22q11.2 deletion syndrome), have
been found in 50 to 80 percent of patients with IAA.2,23 This
chromosomal abnormality is seen in up to 75 percent of
patients with type B defects and relatively rare in patients
with type A IAA.1
Pathology
At autopsy, the great vessels are usually related in a normal
fashion. The pulmonary trunk is larger than the ascending
aorta, which is often hypoplastic. The ductus continues as
the descending thoracic aorta (DTA) and a slender cord of
tissue without a lumen is the connecting interrupted segment
(Figure 2). On the contrary, in coarctation of aorta (COA),
the narrow segment between the left subclavian artery and
Classification
The classification of IAA by Celoria-Patton is based on the
site of the interruption (Figure 1).7
Type A: Distal to the left subclavian artery (1/3 of cases).
Type B: Distal to the left common carotid artery, between the
left subclavian artery and the left common carotid
artery (most common in nearly 2/3 of cases).
Type C: Proximal to the left common carotid artery, between
left common carotid artery and braciocephalic
(innominate) artery (least common in around 1%
of cases).
Each type is divided into three further subtypes:24
a. Subtype 1: Normal subclavian artery
b. Subtype 2: Aberrant subclavian artery
c. Subtype 3: Isolated subclavian artery that arises from the
ductus arteriosus.
These three types of IAA are distinct anatomical entities.
Shones complex having multiple obstructive lesions of the
left side of heart is implicated with this anomaly.
Figure 2: Autopsy specimen of aortic arch Interruption: The arch is

connected to the descending thoracic aorta (DTA) by a slender cord
of tissue (arrow) in interrupted segmentType A. The ductus (D)
continues as DTA. AA = Ascending aorta; LAA = Left atrial appendage;
LCCA = Left common carotid artery; LSA = Left subclavian artery; PT
= Pulmonary trunk; RBCA = Right brachiocephalic artery; RV = Right
ventricle. Image courtesy: Dr Pradeep Vaideeswar
519
Figure 3: Autopsy specimen of coarctation of aorta: Arrow points to

the narrow coarcted segment between left subclavian artery (LSA)
and insertion of the ductus arteriosus*, which appears to continue as
descending thoracic aorta (DTA). There is tubular hypoplasia. AA =
Ascending aorta; LAA = Left atrial appendage; LCCA = Left common
carotid artery; PT = Pulmonary trunk; RAA = Right atrial appendage;
RBCA = Right brachiocephalic artery; Image courtesy: Dr Pradeep
Vaideeswar
intracardiac communications. The differential cyanosis may

or may not be clinically appreciated.27
The patients with TGA and IAA type B exhibit a distinct
physiology that is dependent upon the following factors;
1. Intracardiac communications.
2. Pulmonary hypertension.
3. Lung pathology.
In the absence of intracardiac and extracardiac
communications, the neonate has parallel circulation with no
effective pulmonary and systemic blood flow.28 Refractory
cardiogenic shock will appear soon after birth and the only
chance of survival is a rapid atrial septostomy coupled with the
initiation of prostaglandin (PGE1). If only an insufficient atrial
communication exists, a cascade of increased pressure from
the left atrium through the pulmonary circulation is initiated.
At this point, a pulmonary artery to the descending aorta
shunt will occur across the PDA. In TGA as the pulmonary
artery is connected to the left ventricle, it carries the more
oxygenated blood. The lower half of the body will have higher
oxygen saturation compared to the upper part of the body in a
condition known as reversed differential cyanosis. In neonates
with significant lung disease and pulmonary hypertension due
to the pulmonary venous desaturation, reversed differential
cyanosis may not be apparent. In the presence of an aberrant
right subclavian artery arising after the interruption, the
oxygen saturation measured on the right arm may not be
different from those measured in the lower extremities.15
the insertion of the ductus arteriosus has a lumen and appears
to continue as the DTA (Figure 3). The right ventricle is
hypertrophied and somewhat dilated. The parietal band of the
crista supraventricularis is often absent. The aortic valve is
bicuspid in nearly half of the autopsied specimens.25 Other
multiple cardiac anomalies are usually present.
Pathophysiology
520
The IAA is a duct-dependent anomaly. The PDA is necessary

for the adequate blood supply to the descending aorta. The
neonate appears ill in the first few days of life and develops
cardiogenic shock, metabolic acidosis and multiorgan
dysfunction as the spontaneous closure of the PDA occurs.
The neonates with COA present with congestive heart failure
in the 2nd week of life, probably due to the presence of some
antegrade flow through the obstructed isthmus. In the setting
of an intact atrial and ventricular septum, the lower half of the
body will be supplied by the PDA with desaturated blood and
differential cyanosis will be present.26
The pathophysiology of IAA with VSD and/or atrial septal
defect (ASD) is different. A left-to-right shunt across ASD or
VSD level is present and the blood that is ejected from the
right ventricle and shunted through the PDA to the descending
aorta is less desaturated than the blood in patients without
The clinical presentation of IAA is similar to that in patients

with COA and they are usually clinically stable as long as the
PDA remains open. These neonates present on the first day
of life and become desperately ill whether they have other
major cardiac defects or not. They are in cardiogenic shock,
tachypneic, with increased work of breathing and may appear
terminally ill with multiorgan dysfunction. The neonates with
PDA may survive longer than a few weeks. They may or may
not be cyanotic, as this is dependent on the associated cardiac
defects.14
Pulse
Proper examination of the peripheral pulses gives a definite
clue to the diagnosis of IAA. However, the accurate
examination of all the pulses in a very sick neonate is often
difficult. All the pulses are well felt if the ductus is patent.
If lower limb pulses are feeble with a radio femoral delay, it
indicates the ductus is closed and patient has collaterals. If the
upper limb pulses are weak then severe LVOTO, ventricular
dysfunction and/or severe aortic stenosis must be suspected.28
If the left brachial pulse is diminished or absent, it indicates
that the left subclavian artery is arising from the descending
aorta distal to the interruption. The weak right brachial pulses
Diagnosis
Electrocardiogram
The electrocardiogram (ECG) changes are different in the two
groups of patients, the highly symptomatic neonate and the
asymptomatic older children. The ECG shows right axis deviation, right atrial enlargement, right ventricular hypertrophy.
Rarely biventricular hypertrophy is seen if there is an associated large VSD. Rarely QT interval may be prolonged, if there
is a associated DiGeorge syndrome with hypocalcemia.
Chest Radiography
The chest X-ray demonstrates cardiomegaly, with right
ventricular and right atrial enlargement. The pulmonary artery
is prominent. Pulmonary vascularity is increased or normal
depending on the presence or absence of intracardiac shunt.
Aortic knob is absent. Depending on the site of interruption,

either unilateral or bilateral rib notching may be seen in
older patients. Origin of one subclavian artery distal to the
interruption produces rib notching on the contralateral side.
Imaging
The echocardiography is the primary imaging technique for
characterizing cardiac abnormalities (Figures 4A and B), but it
is not the optimal method by which to evaluate the aortic arch
and descending aorta, as it might not allow differentiation of
IAA from severe aortic coarctation with a hypoplastic arch.4
The combination of echocardiography and magnetic resonance
imaging (MRI) or computed tomography (CT) (Figures 5A
to C) can enable definitive diagnosis of the interrupted aortic
arch and associated cardiac abnormalities.1,2,23
The diagnosis should be suspected on echocardiography
when there is a marked difference in size between the ascending
aorta and the main pulmonary artery, with a malaligned type of
VSD with a posterior deviation of the infundibular septum. The
morphology of the aortic arch and its branches can be visualized
from the suprasternal view.29 Simultaneous injection of contrast
in the descending aorta and aortic arch angiogram from the upper
limb approach can confirm the diagnosis of IAA. The MRI can
accurately characterize cardiovascular anatomy, including that
of the thoracic aorta and great vessels and coexisting cardiac
anomalies. In addition, MRI can also provide useful information
regarding cardiac chamber and valve function. Multiple MRI
techniques can be used to evaluate the thoracic aorta and heart in
cases of suspected IAA. MRI sequences can be performed both
with and without intravenous gadolinium-containing contrast
material. Unenhanced evaluation may include double, inversion
recovery fast spin-echo black-blood, gradient-recalled echo
white blood and balanced [e.g. 2D and 3D balanced-steady
state free precession (SSFP)] imaging sequences.1
35
may be present in patients with an aberrant right subclavian

artery arising below the interruption. If carotid pulses are
well felt, but both upper (brachial) and lower limb (femoral)
pulses are feeble or absent, it indicates that the interruption is
proximal to the left subclavian artery and the right subclavian
artery, which is anomalous in origin distal to the interruption.
If both upper limb vessels are well felt and both lower limb
vessels are poorly felt, it indicates both the subclavian arteries
are proximal to the interruption like in COA. Weak left upper
limb and femoral pulses with normal right arm and carotid
pulses indicates type B interruption and if carotids are weak,
it indicates type C interruption.
Usually there is a right ventricular type of apical impulse,
shifted laterally. Both the heart sounds are normal. Ejection
click is heard if the patient has a bicuspid aortic valve.
Significant murmurs are not heard in infants. Usual machinery
murmur of PDA is not heard as the pulmonary trunk, ductus
and the descending aorta are like one continuous vessel with
no pressure difference or runoff. Sometimes, a loud systolic
murmur due to either a VSD or LVOTO is audible along with
the features of poor systemic perfusion.
Preoperative Management
The preoperative management of IAA is similar to that of
critical COA. The neonate has to be treated promptly with
Figures 4A and B: A. Transthoracic echocardiography (TEE) in suprasternal view illustrates the interruption of aorta (IAA); B. TTE in high ductal
view illustrates the patent ductus arteriosus (PDA) continuing as the descending aorta (DAO). AAO = Ascending aorta; MPA = Main pulmonary
artery.
521
Figures 5A to C: Computed Tomography 3D images of interruption of aortic arch (IAA) type B. A. Anteroposterior view showing ascending aorta
(AAO) giving origin to innominate trunk (INN T) and left common carotid (LCCA) arteries with nonvisualization of aortic arch. Markedly dilated
main pulmonary artery (MPA) is seen; B. Direct left lateral view showing dilated MPA with patent ductus arteriosus (PDA) which continues as
descending thoracic aorta (DAO) with nonvisualization of the aortic arch. Note left subclavian artery (LSA) is seen arising from upper part of
DAO; C. Right posterior oblique view showing clearly visualized IAA distal to LCCA (type B) with ductus continuation of DAO. LA = Left atrium;
LPA = Left pulmonary artery; RPA = Right pulmonary artery; RV = Right ventricle. Image courtesy: Dr Hala ElMarsafawy
PGE1 and simultaneously the shock, hypoxia, hypercarbia

and acidosis should be treated. The goal of therapy is to
maintain optimal descending aorta perfusion with right-to-left
shunting across the PDA. This can be monitored by physical
examination (peripheral pulses, perfusion and urine output).
A preductal saturation above 90 percent and a postductal
saturation of approximately 70 percent signifies good gas
exchange and appropriate distribution of the cardiac output.28
Once the neonate has been stabilized, surgical correction
should be contemplated as soon as possible.
Surgery
522
The surgery for interrupted aortic arch depends on the type of

defect and the associated defects. The current preference is an
one-stage approach through the median sternotomy, though
a type A defect can be treated via lateral thoracotomy as an
exaggerated coarctation.
Correction via median sternotomy has been classically
done using profound hypothermia and circulatory
arrest. The advent of better aortic cannulae, innominate
artery perfusion and low flow cerebral perfusion with
deep hypothermia and with moderate hypothermia with
innominate artery perfusion can be done. Perfusion of the
lower body can be done via a second arterial cannula placed
through the pulmonary artery via the ductus arteriosus
with snaring of the ductus during cardiopulmonary bypass.
Adequate mobilization of the cerebral vessels and aorta is
needed to create a tension less repair. The aortic cannula is
passed through the innominate artery and selective cerebral
perfusion is instituted at the target temperature after snaring
the cerebral vessels. The ductus is divided and all ductal
tissue is removed and the left common carotid artery can

also be turned down after division. The distal left common
carotid artery is anastomosed to the right carotid artery.
Associated defects should be addressed. Care should be
taken to use irradiated blood in patients with associated
DiGeorge syndrome. Patients with an associate single
ventricle physiology will require arch reconstruction and a
pulmonary artery band to limit pulmonary blood flow, to
allow the patient to go through a staged Fontan pathway.
Type A interruption can be treated like a coarctation and
after mobilization, anastomosis can be done after excising
the ductal tissue. A reverse left subclavian flap can be used to
reconstitute the arch (Figure 6).
Figure 6: Interruption (Type A) repaired with a subclavian artery turn

down and augmentation with a Gore-Tex patch via a left thoracotomy
Prognosis
Conclusion
The IAA is a very rare CHD, which commonly appears in the
newborns as a critical disease and leads to death very early
in life without surgical palliation or total repair. IAA is rarely
encountered in an adult. Echocardiography with multislice
CT angiography appears to be a useful combined diagnostic
imaging method in patients with this congenital anomaly. The
accurate and early diagnosis of interrupted aortic arch and its
associated cardiovascular anomalies is profoundly important
for the patients survival.
Nature, time and patience are the three great physicians.
HG Bohn
Acknowledgments
The authors thank Dr Pradeep Vaideeswar, Professor
(Additional), Department of Pathology (Cardiovascular and
Thoracic Division), Seth GS Medical College, Mumbai,
India for the nice pictures of the pathological specimens of
IAA and COA and to Dr Hala ElMarsafawy, Professor of
Pediatrics and Pediatric Cardiology, Director of Cardiac
Catheterization Laboratory, Children Hospital, Mansoura
University, Mansoura, Egypt for the CT images. Also to Mr P
Madhusudan for the good schematic diagram.
References
1. Dillman JR, Yarram SG, DAmico AR, et al. Interrupted
aortic arch: spectrum of MRI findings. AJR Am J Roentgenol.
2008;190:1467-74.
2. Mishra PK. Management strategies for interrupted aortic
arch with associated anomalies. Eur J Cardiothorac Surg.
2009;35:569-76.
3. Perloff JK, Marelli AJ. Coarctation of the aorta and interrupted
aortic arch. Perloff JK, Marelli AJ. Clinical Recognition of
Congenital Heart Disease, 6th edition. Philadelphia. Saunders,

an imprint of Elsevier Inc. 2012. pp. 101-128.
4. Collins-Nakai RL, Dick M, Parisi-Buckley L, et al. Interrupted
aortic arch in infancy. J Pediatr. 1976;88:959-62.
5. Messner G, Reul GJ, Flamm SD, et al. Interrupted aortic arch
in an adult single-stage extra-anatomic repair. Tex Heart Inst J.
2002;29:118-21.
6. Steidele RJ. Sammlung Verschiedener in der chirurgisch
Praktik: Lehrschule Germachten Beobb. 1777;2:114-16.
7. Celoria GC, Patton RB: Congenital absence of the aortic arch.
Am Heart J. 1959;58:407-13.
8. Abbott ME. Congenital cardiac disease. Oslers modern
medicine. Philadelphia: Lea and Febiger; 1927.
9. Lie JT. The malformation complex of the absence of the arch
of the aortaSteideles complex. Am Heart J. 1967;73:
615-25.
10. Takashina T, Ishikura Y, Yamane K, et al. The congenital
cardiovascular anomalies of the interruption of the aorta
Steideles complex. Am Heart J. 1972;83:93-99.
11. Merrill DL, Webster CA, Samson PC. Congenital absence of
the aortic isthmus; report of a case with successful surgical
repair. J Thorac Surg. 1957;33:311-20.
12. Barratt-Boyes BG, Nicholls TT, Brandt PW, et al. Aortic
arch interruption associated with patent ductus arteriosus,
ventricular septal defect and total anomalous pulmonary
venous connection. Total correction in an 8-day-old infant by
means of profound hypothermia and limited cardiopulmonary
by pass. J Thorac Cardiovasc Surg. 1972;63:367-73.
13. Trusler GA, Izukawa T. Interrupted aortic arch and ventricular
septal defect. Direct repair through a median sternotomy incision
in a 13-day-old infant. J Thorac Cardiovasc Surg. 1975;69:126-31.
14. Keane JF, Fyler. Coarctation of aorta. In: Keane JF, Lock
JE, Fyler DC (Eds) Nadas Pediatric Cardiology. Saunders,
Philadelphia, PA; 2006. pp. 627-44.
15. Hastings LA, Nichols DG. Coarctation of the aorta and
Interrupted aortic arch. In: Nichols DG (Ed). Critical Heart
Disease: in Infants and Children. Philadelphia; Mosby; 2006.
pp. 641-48.
16. Conley ME, Beckwith JB, Mancer J, et al. The spectrum of the
DiGeorge syndrome. J Pediatr. 1979;94:883-90.
17. Rudolph A, Hoffman J. Rudolphs Pediatrics. 18th edition.
Appleton and Lange; Norwalk, CT: 1987. pp. 1382-63.
18. Luciani GB, Ackerman RJ, Chang AC, et al. One-stage
repair of interrupted aortic arch, ventricular septal defect,
and subaortic obstruction in the neonate: a novel approach. J
19. Konstantinov IE, Karamlou T, Blackstone EH, et al. Truncus
arteriosus associated with interrupted aortic arch in 50
neonates: a Congenital Heart Surgeons Society study. Ann
Thorac Surg. 2006;81:214-22.
20. Reardon MJ, Hallman GL, Cooley DA. Interrupted aortic arch:
brief review and summary of an eighteen-year experience. Tex
Heart Inst J. 1984;11:250-59.
21. Ho SY, Wilcox BR, Anderson RH, et al. Interrupted aortic arch:
anatomical features of surgical significance. Thorac Cardiovasc
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22. Everts-Suarez EA, Carson CP. The triad of congenital absence
of aortic arch (isthmus aortae), patent ductus arteriosus and
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150:153-9.
35
The IAA is invariably a fatal illness, with death occurring

within days of birth. If the condition is left untreated, 90
percent of the affected neonates die at a median age of 4 days.4
Type B IAA, major associated cardiac anomalies, low-birth
weight and young age at presentation are the chief risk factors
for death and the associated cardiac anomalies are the main
predictor of the outcome.
Early mortality is related to the patients condition, as well
as the associated anomalies and early mortality with a one
stage repair is between 10 to 20 percent. The overall survival
at 16-years has been found to be 59 percent in patients
with interrupted aortic arch; the survival rate increased to
approximately 70 percent in patients who had undergone
preoperative therapy and appropriate surgical techniques.28
Patients with associated truncus arteriosus can have an early
mortality of upto 67 percent in multicentric reports.
523
524
23. Yang DH, Goo HW, Seo DM, et al. Multislice CT angiography
of interrupted aortic arch. Pediatr Radiol. 2008;38:89-100.
24. Goo HW, Park IS, Ko JK, et al. CT of congenital heart
disease: normal anatomy and typical pathologic conditions.
Radiographics. 2003;23:S147-65.
25. Arey JC. Cardiovascular Pathology. Philadelphia: WB
Saunders 1981.
26. Matsui H, Adachi I, Uemura H, et al. Anatomy of coarctation, hypoplastic and interrupted aortic arch: relevance to
interventional/surgical treatment. Expert Rev Cardiovasc Ther.
2007;5:871-80.
27. Muoz R, Tsifansky M, Morell VO. Interrupted Aortic Arch.

In: Muoz R, Morell VO, Cruz EM, VetterlyVO (Eds). Critical
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London Limited; 2010. pp. 267-72.
28. McCrindle BW, Tchervenkov CI, Konstantinov IE, et al.
Risk factors associated with mortality and interventions
in 472 neonates with interrupted aortic arch: a Congenital
Heart Surgeons Society study. J Thorac Cardiovasc Surg.
2005;129:343-50.
29. Pongiglione G. Aortic arch interruption. Orphanet Encyclopedia. Februrary 2004.
c hapter
36
Vascular rings, slings

and other Anomalies
Maitri Chaudhuri
IntroductIon
Vascular rings are developmental abnormalities of the aortic
arch system, where vascular structures encircle and compress
the tracheobronchial tree and esophagus. Anatomically, this
encirclement may be complete or incomplete. By convention,
we call it as vascular ring when the encirclement is complete
and vascular sling when it is incomplete.1,2
HIstory
artery. They form an additional location of vascular ring

(Figure 1).
During normal development, the left arch and left ductus
persist whereas the right aortic arch, distal to the origin of right
subclavian artery (RSA) and the right ductus regress (Figures
2A and B). As a result, the proximal part of the embryological
right arch forms the brachiocephalic (innominate) artery,
which bifurcates into the right common carotid artery (RCCA)
and RSA. The embryological left aortic arch gives rise, in
sequence, to the left common carotid artery (LCCA) and left
subclavian artery (LSA).
The term vascular ring was coined by Robert Gross in 1945,

while describing the first successful division of a double aortic
arch.3 It is interesting to read Dr Gross first report:
In 1931, I performed an autopsy on a 5-month-old baby
who had wheezing respiration since birth. At this examination,
a ring of blood vessels was found encircling the intrathoracic
portion of the esophagus and trachea in such a way that the
esophagus was indented from behind whereas the trachea was
compressed on its anterior surface. The pathological findings
suggested that a division of some part of the so called vascular
ring during life probably would have relieved the pressure on
the constricted esophagus and trachea.
By 1950s, Dr Gross had repaired more than 50 such cases.
Embryology
normal development
The formation of vascular rings is best understood from the
hypothetical model of double aortic arch as proposed by the
eminent cardiac pathologist Dr Jesse E Edwards in 1948.4 In
this model, the ascending and descending aorta are connected
by symmetrical arches on each side, thus forming a complete
vascular ring around trachea and esophagus. Each arch gives
origin to ipsilateral common carotid and subclavian arteries.
Also on each side, corresponding ductus arteriosus is located
connecting the ipsilateral pulmonary artery and subclavian
Figure 1: This schematic diagram shows the hypothetical model for

double aortic arch as proposed by Jesse Edwards. LAA = Left aortic
arch; LCCA = Left common carotid artery; LPA = Left pulmonary
artery; LSA = Left subclavian artery; PT = Pulmonary trunk; RAA =
Right aortic arch; RCCA = Right common carotid artery; RPA = Right
pulmonary artery; RSA = Right subclavian artery. Courtesy: Reprinted
with permission from reference 1
Abnormal development
Diseases oF the aorta
By following this model, the abnormalities can be either

positional or due to the abnormal persistence of arch segments,
which should have otherwise regressed. The explanations for
individual anomalies are given in the text.
clAssIFIcAtIon oF VAsculAr rIng

complete Vascular ring
1. Double aortic arch.
2. Right aortic arch with aberrant left subclavian or
brachiocephalic artery and left sided ductus.
3. Left aortic arch with aberrant right subclavian or
brachiocephalic artery and right sided ductus.
4. Right aortic arch with mirror image branching and
retroesophageal left sided ductus between right sided
descending aorta and left pulmonary artery.
5. Circumflex retroesophageal aortic arch.
Incomplete Vascular ring or Vascular sling

Figure 2a: This schematic diagram illustrates the formation of a
normal left aortic arch with left sided ductus. The red bars indicate
the segments that regress. Courtesy: Reprinted with permission from
reference 1
1. Left aortic arch with aberrant right subclavian or brachiocephalic artery and left sided ductus.
2. Right aortic arch with aberrant left subclavian or brachiocephalic artery and right sided ductus.
3. Tracheal compression by innominate or left common
carotid artery.
IndIVIduAl AnomAlIEs
double Aortic Arch
Embryology
Double aortic arch is the tightest and most common vascular
anomaly.5 Embryologically, both the arches of the hypothetical
double arch model persist on two sides of the trachea, without
regression of any segment.
Morphology
Figure 2B: This schematic diagram illustrates that in continuation of

Figure 2A, the disappearance of right aortic arch distal to the origin of
the right subclavian artery (RSA), along with right sided ductus. LAA
= Left aortic arch; LCCA = Left common carotid artery; LPA = Left
pulmonary artery; LSA = Left subclavian artery; PT = Pulmonary trunk;
RAA = Right aortic arch; RBA = Right brachiocephalic artery; RCCA =
Right common carotid artery; RPA = Right pulmonary artery. Courtesy:
Reprinted with permission from reference 1
526
Here the ascending aorta arises normally, but as it leaves the

pericardium, it bifurcates into left and right arches, on either
side of trachea and then they join posteriorly to form the
descending aorta. The left arch passes anteriorly and to the left
of trachea and is joined by left ductus, where it becomes the
descending aorta. The right arch passes to the right and then
posterior to esophagus to join the left sided descending aorta,
thereby completing the vascular ring6 (Figures 3A and B).
right Aortic Arch

Right aortic arch is a common anomaly seen in 0.5 percent of
population.9 They are classified into the following types:
Right Aortic Arch with Mirror Image Branching
Figure 3a: This computed tomography angiogram shows the balanced

type of double aortic arch with ascending aorta bifurcating into right
and left aortic arches. Each arch is giving rise to ipsilateral common
carotid and subclavian arteries. AAo = Ascending aorta; LAA = Left
aortic arch; LCCA = Left common carotid artery; LSA = Left subclavian
artery; RAA = Right aortic arch; RCCA = Right common carotid artery;
RSA = Right subclavian artery.
Embryology: Mirror image branching arises due to abnormal

regression of embryonic left arch distal to the origin of LSA
(Figures 4A and B). The usual branching pattern is as follows
first branchleft brachiocephalic artery bifurcating into LSA
and LCCA, second branchRCCA, third branchRSA
(Figures 4C and D). This is particularly common with TOF
and truncus arteriosus. The ductus is usually left sided arising
from the base of left brachiocephalic artery and connecting to
the left pulmonary artery (LPA). This is the only anomaly of
right aortic arch, which is not associated with vascular ring.
Very rarely, the left sided ductus may have a retroesophageal
course if it arises from a right sided descending aorta and
connects to LPA. This will produce a complete vascular ring.
This is explained by abnormal regression of left arch distal to
36
Vascular rings, slings anD other anomalies
are equal (balanced) and in remaining 25 percent, the left arch

is dominant (left dominant). The apex of the larger arch is
located at a higher level. In the usual right dominant arch, the
portion of left arch distal to origin of LSA often regresses.
Associated cardiovascular anomalies like tetralogy of Fallot
(TOF) and transposition of great arteries are uncommon.8
Figure 3B: This figure shows the angiographic description of

double aortic arches, bifurcating into two equal sized left (L) and
right (R) aortic arches. AAo = Ascending aorta; C = Coronary artery;
LCCA = Left common carotid artery; LSA = Left subclavian artery;
RCCA = Right common carotid artery; RSA = Right subclavian artery.
Courtesy: Reprinted with permission from Dr Subramanyan Raghavan,
Dr Ravi Narayan. Indian Pediatr 2003;40:951-7
Occasionally, the descending aorta is right sided, where the left

arch passes behind the esophagus. Alternatively the descending
aorta may be a midline structure.7
In majority of cases, both the arches are patent. In 50
percent of cases, the right arch is larger than the left and is
called right dominant. In 25 percent of cases, the two arches
Figure 4a: The schematic diagram shows the hypothetical double

arch model with the two red bars showing the segments that regress.
Courtesy: Reprinted with permission from reference 1
527
Figure 4B: In majority of cases, the left sided ductus persists and the
left aortic arch regresses distal to the origins of left subclavian artery
(LSA) and the left ductus, along with the right sided arterial ductus. After
birth, the left sided ductus connects the base of left brachiocephalic
or subclavian artery to the left pulmonary artery. Persistence of right
sided arterial ductus is uncommon. LBA = Left brachiocephalic artery;
LCCA = Left common carotid artery; LPA = Left pulmonary artery; PT
= Pulmonary trunk; RAA = Right aortic arch; RCCA = Right common
carotid artery; RPA = Right pulmonary artery; RSA = Right subclavian
artery; Courtesy: Reprinted with permission from reference 1
Figure 4D: This computed tomography (CT) angiogram depicts a right

aortic arch with mirror image branching pattern in a 20-year-old lady
with tetralogy of Fallot with aortopulmonary collaterals from left internal
mammary artery. LCA = Left carotid artery; LIA = Left innominate
artery; LSA = Left subclavian artery; MAPCA = Major aortopulmonary
collaterals; RCA = Right carotid artery; RSA = Right subclavian artery;
Courtesy: Reprinted with permission from Dr Aysel Turkvatan, Ihtisas
Hospital, Turkey, Korean J Radiol. 2009;10:176-84
LSA and proximal to insertion of persisting left ductus plus

simultaneous disappearance of right ductus.10
Right Aortic Arch with Aberrant Left Subclavian Artery

with Left Sided Ductus
Embryology: This arises due to abnormal persistence of
right arch and abnormal regression of left aortic arch in the
segment between LCCA and LSA. The LSA originates from
the distal part of left arch. The distal remnant of the left arch,
along with aberrant LSA courses retroesophageally (Figures
5A and B). The distal remnant of the left fourth aortic arch
usually persists as a diverticular outpouching with the LSA
arising from its apex. This is called the diverticulum of
Kommerell.11
Figure 4c: This schematic diagram shows the usual branching

pattern in right aortic arch with mirror image branching. 1st branch:
left brachiocephalic artery bifurcating into left subclavian (LSA) and left
common carotid artery (LCCA), 2nd branch: right common carotid artery
(RCCA), 3rd branch: right subclavian artery (RSA). AAo = Ascending
aorta; LIA = Left innominate artery; LPA = Left pulmonary artery
528
Morphology: The first branch of the right arch becomes

the LCCA, followed sequentially by RCCA, RSA and the
descending aorta gives rise to aberrant left subclavian artery
(ALSA) as the fourth branch. The persistent arterial ductus is
usually left sided (Figure 5C).
This is the second most common type of vascular ring;
however, they are usually loose when compared to the double
arch. Associated cardiac anomalies are rare.12
36
Figure 5B: In the postnatal circulation, consequent to the closure of

the arterial ductus, the proximal part of the aberrant LSA, representing
the distal remnant of the left aortic arch usually persists, as the socalled diverticulum of Kommerell. LAA = Left aortic arch; LCCA =
Left common carotid artery; LPA = Left pulmonary artery; LSA = Left
subclavian artery; PT = Pulmonary trunk; RAA = Right aortic arch ;
RCCA = Right common carotid artery; RPA = Right pulmonary artery;
RSA = Right subclavian artery. Courtesy: Reprinted with permission
from reference 1
Figure 5a: This schematic diagram shows the morphogenesis of

a right aortic arch with aberrant origin of left subclavian artery and a
left sided arterial ductus. The hypothetical model of the double arch
is shown with the red bars indicating the segments that will regress.
LAA = Left aortic arch; LCCA = Left common carotid artery; LPA = Left
pulmonary artery; LSA = Left subclavian artery; PT = Pulmonary trunk;
RAA = Right aortic arch; RCCA = Right common carotid artery; RPA
= Right pulmonary artery; RSA = Right subclavian artery. Courtesy:
Figure 5c: Computed tomography (CT) angiogram showing right aortic arch with aberrant left subclavian artery (ALSA) in a 45-year-old
asymptomatic woman with anterior and posterior volume rendering images. LCA = Left carotid artery; RAA = Right aortic arch; RCA = Right
carotid artery; RSA = Right subclavian artery; RAA = Right aortic arch, arrows showing Kommerell diverticulum. Courtesy: Reprinted with
permission from Dr Aysel Turkvatan, Ihtisas Hospital, Turkey, Korean J Radiol. 2009;10:176-84
529
Figures 6a and B: These schematic diagrams show the mode of formation of the right aortic arch (RAA) with aberrant left subclavian artery
(LSA) and right sided arterial ductus, the pattern following the same format as for Figures 5A and B. In the fetal and postnatal circulations,
this arrangement produces a vascular sling on the right side of the trachea and esophagus. This is a rare combination. LAA = Left aortic arch;
LCCA = Left common carotid artery; LPA = Left pulmonary artery; PT = Pulmonary trunk; RCCA = Right common carotid artery; RPA = Right
pulmonary artery; RSA = Right subclavian artery. Courtesy: Reprinted with permission from reference 1
Right Aortic Arch with Aberrant Left Subclavian Artery with

Persistent Right Ductus
Right aortic arch with aberrant left subclavian artery with
persistent right ductus is a rare anomaly embryologically
explained by abnormal regression of left arch segment
between LSA and LCCA and disappearance of left ductus and
persistence of right ductus (Figures 6A and B).
This produces an incomplete encirclement or vascular
sling around right side of trachea and esophagus.
Right Aortic Arch with Aberrant Origin of Left Brachiocephalic Artery

This is rare and arises from abnormal regression of left arch
segment proximal to LCCA with persistent left ductus. Again
this produces a complete vascular ring.
left Aortic Arch with Aberrant right subclavian Artery

with Persistent left ductus
Left aortic arch with aberrant right subclavian artery with
persistent left ductus (PLD) is the most common anomaly of
the aortic arch; however, it is usually asymptomatic.
Embryology
530
Aberrant right subclavian artery (ARSA) with PLD occurs

when the embryological right arch has an abnormal regression
between origins of RCCA and RSA and disappearance of right

ductus (Figures 7A and B). The ARSA remains attached to the
distal part of right aortic arch. The ARSA and the remnant of
right aortic arch take a retroesophageal course. Previously this
anomaly was called arteria lusoria. Usually the left ductus
persists in this case and therefore an incomplete vascular ring
arises.
Morphology
The right subclavian artery originates as the last vessel of
the aortic arch, from the junction of the aortic arch with the
descending aorta. If the right ductus persists and the left one
disappears, then a complete vascular ring will be produced. The
ARSA courses behind the esophagus in 80 percent of cases,
between esophagus and trachea in 15 percent, and anterior
to trachea in remaining 5 percent (Figure 7C). The aberrant
subclavian artery is usually an isolated malformation, although
it is associated with cardiac malformations in 12 percent of
cases. The most frequent associated anomalies are TOF, aortic
coarctation, and interruption of the aortic arch.12
circumflex Aortic Arch

Circumflex aortic arch is a rare anomaly, where the aortic arch
and the proximal part of descending aorta are on contralateral
sides of the spine. Here, the aortic arch makes an additional
arch posterior to trachea and esophagus to reach the descending
aorta13 (Figures 8A and B).
36
Figures 7a and B: These schematic diagrams show the morphogenesis and postnatal structure of left aortic arch with aberrant origin of right
subclavian artery and left sided arterial ductus. In the hypothetical model, the red bars indicate the segments that regress. In the postnatal
circulation, a vascular sling is formed on the left side of trachea and esophagus. LCCA = Left common carotid artery; LPA = Left pulmonary
artery; LSA = Left subclavian artery; PT = Pulmonary trunk; RAA = Right aortic arch; RCCA = Right common carotid artery; RPA = Right
pulmonary artery; Courtesy: Reprinted with permission from reference 1
Figure 7c: Computed tomography (CT) angiogram showing left aortic arch with aberrant right subclavian artery in a 66-year-old lady with
dysphagia. 3D reconstruction show ARSA with diventiculum of Kommerell at its origin (white arrows). ARSA = Aberrant right subclavian artery;
LAA = Left aortic arch; LCA = Left carotid artery; LSA = Left subclavian artery; RCA = Right carotid artery. Courtesy: Reprinted with permission
from Dr Aysel Turkvatan, Ihtisas Hospital, Turkey, Korean J Radiol. 2009;10:176-84
This occurs more commonly with a right sided aortic arch.

The pattern of branching is as follows: 1st branchLCCA,
2nd and 3rd branchesRCCA and RSA respectively and the
terminal branch is the LSA arising at the point of transition
of the retroesophageal arch to the left sided descending aorta.
Hypoplasia of the retroesophageal segment of the arch is
common.
cervical Arch
The arch is called cervical when its apex reaches into the neck
above the clavicles. This produces a pulsatile swelling in the
neck. This can be associated with a retroesophageal arch or even
double aortic arch. This produces overcrowding of structures
within the narrow neck and causes respiratory compression.14
531
7
In patients with coexisting cardiac diseases, RAA with mirror

image branching is the most common lesion. This is almost
always associated with congenital cardiac anomalies. 1/4th
of TOF patients, especially those with pulmonary atresia and
1/3rd of truncus arteriosus have this pattern.
IncIdEncE oF dIFFErEnt tyPEs oF VAsculAr rIngs

Double aortic arch
40 percent
Right aortic arch + ligamentous left ductus
30 percent
Anomalous brachiocephalic artery
10 percent
Noncardiac anomalies are less common. However, these

patients should be screened for chromosome 22q11 deletion
syndrome.
Figure 8a: This schematic diagram shows a circumflex retroesophageal
aortic arch. The aortic arch and the proximal part of descending aorta
are on opposite sides of the spine. The aortic arch passes posterior
to trachea and esophagus to reach the descending aorta. LCCA =
Left common carotid artery; LSA = Left subclavian artery; LVA = Left
vertebral artery; PT = Pulmonary trunk; RCCA = Right common carotid
artery; RSA = Right subclavian artery; RVA = Right vertebral artery.
natural History
Untreated severe respiratory obstruction, especially starting
soon after birth, is fatal before the child reaches his first
birthday. Symptoms first presenting after 6 months of age are
less severe and rarely progressive, except when active chest
infection or aspiration occurs. Borderline symptoms may
disappear with growth of the child.16
Symptoms
Figure 8B: This 3D reconstructed computed tomography (CT)

angiogram shows a circumflex aortic arch. AAo = Ascending aorta;
DAo = Descending aorta; * = Retroesophageal circumflex arch
clInIcAl PrEsEntAtIon oF VAsculAr rIngs

Epidemiology
532
Vascular rings of aortic origin represent 1 to 3 percent of

all congenital heart diseases, although exact incidence may
be underestimated.15 ARSA is the most common anomaly
(0.5% of autopsy series). The incidence is especially high
(38%) among Trisomy 21 children with heart disease.
Symptoms depend on tightness of the ring and associated

tracheobronchomalacia. Respiratory symptoms manifest in
early infancy and esophageal symptoms develop later. The
earliest presentation is seen with children with double aortic
arch.
A. Manifestations due to upper airway, i.e. tracheobronchial
compression:
Inspiratory stridor characteristically worsened by
inspiration, exertion or crying and its severity fluctuates
with change in position. Stridor is accentuated in supine
than lateral position. Some infants prefer opisthotonic
posture to relieve tracheal compression.
Expiratory wheezing and tachypnea.
Hoarse cry.
Persistent barking coughseal bark cough17
Apnea especially in children with brachiocephalic artery
compression and in those with complete tracheal rings.
B. Manifestations due to esophageal obstruction:
Dysphagia usually to solids. This may be caused by
aneurysmal dilatation of diverticulum of Kommerell or
elongation of aorta.
Frequent aspiration pneumonitis
Dysphagia lusoriadifficulty in swallowing due to trick
of nature. In 1761, David Bayford performed autopsy on
a 63-year-old woman with lifelong swallowing problems
and noted an ARSA coursing posterior to esophagus and
thereby indenting it. He opined that this abnormal course
dIAgnostIc WorKuP
chest X-ray
The points to look for in suspected vascular rings are:18,19
a. Laterality of arch in posterioanterior view: The tracheal
air column usually shows a subtle indentation produced
by the aortic arch and is bent to the opposite side. This is
especially prominent for RAA. For beginners, the trick is
to trace back the arch from the shadow of descending aorta,
which usually forms a prominent vertical linear stripe along
the vertebral column. If the arch shadow and the descending
aortic shadows are on opposite sides, suspect double aortic
arch or circumflex retroesophageal aortic arch (Figures 10A
to C).
b. Pulmonary complications: Like pneumonia, hypoplasia,
compensatory emphysema, etc.
c. Anterior bowing of distal trachea in lateral view: If
there is a large retroesophageal mass like diverticulum of
Kommerell, the distal part of trachea is bowed forward by
the diverticulum.
d. Widened superior mediastinum: Cervical arch can be a
differential diagnosis.
36
of the artery caused deglutition problems and coined the

term dysphagia lusoria.
The ARSA is usually asymptomatic and occurs in 1 in
200 individuals. It usually does not cause stridor in infants.
However, if complications like aneurysmal transformation
or ectasia develop, deglutition problems are more likely
(Figures 9A and B).
barium Esophagogram
Figure 9a: This schematic diagram shows the mechanism of

dysphagia lusoria, where an aberrant right subclavian artery courses
posterior to esophagus and compresses it. LCCA = Left common
carotid artery; LSA = Left subclavian artery; RASA = Right aberrant
subclavian artery; RCCA = Right common carotid artery.
Although the use of barium esophagogram has been almost

abandoned in modern medicine, Baker and Berdon et al
had proposed a very efficient diagnostic algorithm based on
its findings (Box 1).20 The anterioposterior, right anterior
oblique, left anterior oblique views are fundamental (Figures
11A to C).
Figure 9B: This computed tomography (CT) angiogram shows left aortic arch with aberrant right subclavian artery from posterior view. It
is not a true ring. If the base of right subclavian artery gets dilated, then it causes compression to esophagus and is called arteria lusoria.
Courtesy: Reprinted from Siegel MJ, Smithius R. Vascular anomalies of aorta, pulmonary and systemic vessels, Radiology assistant, /www.
radiologyassistant.nl/en/
533
Figures 10a to c: A. This chest X-ray in frontal view shows a right sided aortic arch with arrow depicting the right arch. The tracheal air column
is displaced to the left by right arch. RAA = Right aortic arch, T = Trachea; B. This chest X-ray shows two paratracheal soft tissue densities (*) on
both sides of trachea in a patient with double aortic arch; C. This chest X-ray in lateral view shows anterior bowing of trachea. When the aortic
arch is right sided and an aberrant left subclavian artery arises from diverticulum of Kommerell (arrows), the diverticulum pushes forwards the
trachea
Figures 11a to c: A. Barium esophagogram in bilateral oblique view showing extrinsic impression (arrow) on posterior esophageal wall;
B. Barium esophagogram in lateral view showing bilateral posterior indentation (arrow) of the upper esophagus in a child with double aortic arch.
Arrow shows location of anomaly. Courtesy: Reprinted from Berrocal T, et al. Radiographics 1999;19:855-72); C. This barium esophagogram
shows the anterior compression of esophagus and arrow shows the location of anomalous left pulmonary artery coursing between the trachea
and esophagus. Courtesy: Reprinted from reference 20
Box 1: Diagnostic value of the barium esophagram in

vascular rings and sling20
Anterior tracheal
indentation
Posterior
esophageal
indentation
Vascular ring,
likely double arch
or RAA with ALSA
and persistent left
ductus
Normal trachea
Posterior
esophageal
indentation
ARSA with left arch

(dysphagia lusoria)
Posterior tracheal
indentation
Anterior
esophageal
indentation
Pulmonary arterial
sling
Anterior tracheal
indentation
Normal esophagus
Abnormal
brachiocephalic
artery
534
Echocardiogram
Echocardiogram is an important noninvasive, nonionizing,
widely available modality for definitive diagnosis of aortic
arch anomalies.21-23
a. Which view? The suprasternal short axis view, where
transducer is placed horizontally in the suprasternal notch
with an extended neck. Start with a downward angulation
and then gently sweep upwards to acquire the best view for
diagnosing aortic arch anomalies.
The ascending aorta, transverse and descending
thoracic aorta are best visualized in the suprasternal
long axis view. To obtain this view, the transducer
is placed in the suprasternal notch with the plane of
ultrasound beams oriented between the right nipple and
the left scapular tip.
Box 2: Various echocardiographic patterns in aortic arch anomalies
First branch of
aortic arch to
right
Then first branch

bifurcates into two: right
subclavian and right
common carotid artery
Normal left aortic

arch
First branch of
aortic arch to
left
Then 1st branch

bifurcates into two:
left subclavian and left
common carotid artery
Right aortic arch

with mirror image
branching
Left or Right
arch
But first branch does not

bifurcate
four arch vessels
demonstrated
Aberrant
subclavian artery
(suspect vascular
ring)
Double circle
Tracheal ring in center
Double aortic
arch (suspect
vascular ring)
Pulsatile mass
in neck
Transducer positioned
over mass and long
axis view shows long
ascending aorta
Cervical arch
magnetic resonance Imaging24,25

Magnetic resonance (MR) angiography is an alternative
non-invasive tool without the need for contrast material or
radiation exposure. However, this is time-consuming and
requires prolonged sedation in pediatric patients. Although
MR delineates the vascular anatomy excellently, the
technique gives limited information about airways and
esophagus.
bronchoscopy
Bronchoscopy is rarely done to identify the sites of vascular
compression. For example, rigid bronchoscopy in brachiocephalic artery syndrome shows compression from an anterior pulsating mass and the compression progresses from most
severe on the right to less severe on the left, following the
course of brachiocephalic artery as it passes from the right to
left. Pressing the bronchoscope anteriorly against the tracheal
wall will typically suppress the right radial or right carotid
arterial pulses.16,18
36
b. What to look for? The position of the aortic arch in relation

to tracheal rings and the origin and branching pattern of the
arch vessels.
c. The different echocardiographic patterns (Box 2) (Figures
12A to E):
mAnAgEmEnt
medical
cardiac catheterization and Angiography

Although once considered a gold standard, it role has been
largely limited now-a-days by the advent of newer diagnostic
modalities. The arch anatomy, branch vessels, aberrant
courses and hemodynamic data can be very clearly inferred,
but it gives limited information regarding type and level of
tracheobronchial and esophageal compression.
Precise diagnosis is very important for appropriate life
saving management strategy. In this direction echocardiography may not be adequate. Hence, angiogram and computed
tomographic angiogram could be more informative (13 A to C).
computed tomogram23,24
Multislice CT angiograms gives us excellent information
regarding both vascular structures and airways. One added
advantage is the need for minimal sedation. The real challenge
is to take images of diagnostic quality with lowest possible
doses of radiation. Use of 3D reconstruction allows more
elaborate spatial orientation and provides a definite road
map for surgery. However, a significant discrepancy in the
assessment of severity of airway narrowing between routine
CT and bronchoscopy is often found. This is because routine
CT fails to assess the dynamic changes in airway lumen
between inspiration and expiration and children often fail to
follow the instructions to hold breath or exhale!
Medical care is supportive and limited to treatment of

hypoxemia, recurrent pulmonary infections and supervised
feeding. Surgery is indicated in all symptomatic patients, as
mortality rates of 90 percent has been reported with isolated
medical management.26
surgical
Indications
The simple existence of vascular ring per se is not an
indication for surgery as the child may outgrow the symptoms
with increasing age and consequent increase in chest and neck
dimensions. However, presence of recurrent apneic spells,
pulmonary infections and persistent respiratory distress are
definite indications for surgery. Other potential complications
of unrepaired lesions include aortic aneurysm and dissection.27
The various surgical procedures in vascular rings is given in
Box 3.28
timing of surgery
The decision regarding when to operate depends on the
severity of symptoms and can be done in infancy for the most
severe cases. However, infants with minimal symptoms and
without significant respiratory obstruction can be managed
medically.
535
Figures 12a to e: A. Echocardiogram in suprasternal short axis view showing a left sided aortic arch with 1st arch vessel, i.e. brachiocephalic
artery (BCA) coursing towards the right and dividing into right subclavian and right common carotid arteries. B. Echocardiogram in suprasternal
short axis view showing a right sided aortic arch with 1st arch vessel, i.e. BCA coursing towards the left and dividing into left subclavian and
left common carotid arteries. C. This echocardiogram in suprasternal short axis view shows the double aortic arches on corresponding sides
of trachea. arrow shows the position of trachea; D. This subcostal echocardiographic view shows a double aortic arch with ascending aorta
bifurcating into right and left aortic arches after it becomes extrapericardial. E. This echocardiogram in suprasternal view shows left aortic arch
with aberrant right subclavian artery. The picture on left side shows a suprasternal short axis view where the 1st branch does not bifurcate but
instead continues upwards, forwards and right wards, characteristic of right common carotid artery. The picture on right side shows that on
inferior angulation of the transducer, the aberrant right subclavian artery arises from the distal portion of descending aorta on the left side of the
midline. Ao = Aorta; AAo = Ascending aorta; LAA = Left aortic arch; LCCA = Left common carotid artery; LSA = Left subclavian artery; RAA =
Right aortic arch; RCCA = Right common carotid artery; RSA = Right subclavian artery.
Figures 13a and B: A. Transthoracic echocardiogram in modified suprasternal view shows ascending aorta (AAO) bifurcating into right aortic
arch (RAA) and left aortic arch (LAA); B. Left ventricular (LV) angiogram in frontal view illustrates double aortic arch with PDA forming the
vascular ring. C.Volume rendered computed tomography angiogram of double aortic arch in a one and half year old child, illustrates bigger right
aortic arch (RAA) giving rise to right subclavian artery (RSA) and right common carotid artery (RCCA) and relatively smaller left aortic arch (LAA)
giving rise to left subclavian artery (LSA) and left common carotid artery (LCCA). AO = Aorta; DAO = Descending aorta; PA = Pulmonary artery.
Image courtesy: Dr. IB Vijayalakshmi
536
Box 3: Surgical Procedures in Vascular Rings28
Division of the smaller of the two

arches or the atretic arch by left
thoracotomy.
Right aortic arch and left

ligamentum arteriosum
Ligation and division of

Ligamentum by left thoracotomy.
Kommerell diverticulum, if found,
is ligated and left subclavian artery
is transferred to left carotid artery
by left thoracotomy
Left aortic arch and right

ligamentum arteriosum
Similar concept as above by right

thoracotomy.
Anomalous
brachiocephalic artery
Suturing of innominate artery to

posterior sternum through right
anterolateral thoracotomy
Circumflex
retroesophageal aortic
arch
Through midline sternotomy, the

retroesophageal part of arch is
divided and the mobilized aortic
arch is translocated to the other
side of trachea and anastomosed
to the descending aorta.
Aberrant right subclavian

artery
Usually no treatment is required
Box 4: Surgical Results (Excluding Associated Complete

Tracheal Rings)28
Number of patients
Mortality (%)
Van Son (1994)
39
2.6
Backer (1993)
249
3.6
Chun (1992)
39
5.1
Azarow (1992)
21
4.8
Marmon (1984)
54
1.9
Roesler (1983)
51
3.9
Arcinegas (1979)
53
3.8
special Postoperative care28,29

Aggressive respiratory care is the key to success in postoperative period in small infants. Use of continuous positive
airway pressure (CPAP) with infant breathing spontaneously
is advantageous. Post extubation, continued use of warm
and humidified oxygen administered by nasal prongs, chest
physiotherapy and gentle meticulous suctioning help to keep
the airway patent and mucosa undamaged The surgical results
of procedures done in vascular rings from various series, is
given in Box 4.28
PulmonAry ArtErIAl slIng

definition
Pulmonary arterial sling is a congenital anomaly, where the
left pulmonary artery (LPA), instead of arising from the main
History
Pulmonary arterial sling was first described in 1897 by
Glaevecke and Doehle during an autopsy of a 7-monthold baby, who died due to asphyxia.31 In 1958, Contro and
colleagues coined the term vascular sling to distinguish the
condition from vascular ring.32 Much later, Berdon et al
introduced the phrase ring-sling complex to emphasize the
often coexisting tracheal anomaly.33
Pathophysiology
The anomalous LPA exerts direct mechanical compression
on trachea, often the right bronchus is compressed and the
lower trachea is deviated to the left causing atelectasis and
hypoplasia of right lung and compensatory emphysema of
left lung. Sixty-five percent of patients have diffuse tracheal
stenosis, complete rings and tracheomalacia.33 Conversely,
one-third of patients with complete tracheal rings have
associated pulmonary arterial slings. In addition, patients
often have right and less frequently, left bronchomalacia.
An interesting feature seen in fourth-fifth of patients is
abnormal branching of tracheobronchial tree.33 Typically
the trachea bifurcates into right and left bronchus at a
lower level and with a wide angle between them producing
an inverted T appearance.1 The right upper lobe bronchus
originates separately from the trachea slightly above the
level of normal tracheal bifurcation. Almost all cases with
low inverted T bifurcation of airways, with or without a
separate origin of right upper lobe bronchus are associated
with narrowing of a long segment of lower airways above
the bifurcation. Rarely, the sling is associated with agenesis
of right lung.
36
Double aortic arch
pulmonary artery (MPA), arises extrapericardially from the

posterior aspect of right pulmonary artery (RPA) and then
takes a hairpin bend towards the left lung in the space between
trachea and esophagus. As a consequence, a vascular sling is
formed around the right side of trachea (Figure 14). This is
almost always associated with congenital tracheal stenosis
and complete cartilaginous tracheal rings with absence of pars
membranaceae posteriorly.30
Associations
Fifty percent of these children have cardiac abnormalities
mainly atrial septal efect, ventricular septal defect, patent
ductus arteriosus (PDA), TOF and left superior vena cava.
The PDA when present connects MPA to descending aorta
on left side of trachea and completes a vascular ring. The
anomalous LPA is often relatively hypoplastic than the
RPA. The extracardiac anomalies seen are imperforate anus,
congenital megacolon, biliary atresia and genitourinary
abnormalities.1
537
diagnostic Workup
Chest X-ray
a. Inverted T appearance of tracheal bifurcation at a level
lower than normal (Figures 15A and B).
b. Narrowing of trachea bronchus.
c. Variable combination of pulmonary hyperinflation
atelectasis. Hyperinflation of the entire right lung is
common in these patients.34
d. Asymmetric pulmonary vascularity (decreased on left side).
Barium Esophagogram
The anomalous LPA is seen as a rounded density between
air-filled distal trachea and barium-filled esophagus in lateral
view with anterior indentation of esophagus.35
Figure 14: This schematic diagram shows the classical pulmonary
arterial (PA) sling where the left pulmonary artery arises from the right
pulmonary artery instead of the pulmonary trunk. It also shows a left
sided ligamentum arteriosum connecting the left pulmonary artery to
the descending aorta. LPA = Left pulmonary artery; PT = Pulmonary
trunk; RPA = Right pulmonary artery. Courtesy: Reprinted with
permission from reference 1
clinical manifestations
Pulmonary arterial sling often presents within infancy, more
among males with obstructive respiratory symptoms like
stridor, wheezing and cough. Symptoms due to esophageal
compression are less common.
538
Echocardiogram36,37
a. Continuation of MPA as RPA without normal origin of
LPA in parasternal short axis view. The other differential
diagnosis of this are absent LPA and aberrant origin of LPA
from descending aorta. However, on tracing the RPA, the
LPA in this case can be demonstrated to arise from the RPA
(Figure 16).
b. Associated cardiac anomalies are diagnosed.
Cardiac Catheterization and Angiography

Although sparingly used now-a-days, this was a gold standard
in past. Angiography with injection of radiocontrast in
Figures 15a and B: The chest X-ray is compared with computed tomography (CT) thorax in a child with pulmonary arterial sling. Careful
observation shows two levels of tracheal bifurcation in the chest X-ray and confirmed in CT. The airway has two levels of bifurcations in the
mediastinum, with a narrow intermediary segment, characteristic of congenital stenosis due to complete cartilaginous rings. The arrows indicate
the narrowed vertical segment of the trachea between its upper and lower bifurcations. Courtesy: Reprinted with permission from reference 1
36
Figure 17: This angiogram shows the classical appearance of

pulmonary arterial sling in angiography, where the left pulmonary
artery (LPA) arises from the right pulmonary artery (RPA) and
then takes a tortuous circuit towards the hilum of the left lung.
PT = Pulmonary trunk
MPA in a steep oblique view with cranial angulation of 60

to 70 elucidates the origin and course of anomalous LPA
(Figure 17).38
of tracheobronchial involvement and efficacy of the surgery

done. Postoperatively, it is used to assess the tracheal surgery,
cause of endotracheal tube bleeding, cause of prolonged
ventilation etc.33
Computed Tomography with Three-Dimensional

Reconstruction
Figure 16: This echocardiogram in high left parasternal short axis view
reveals that the main pulmonary artery (MPA) continues as the right
pulmonary artery (RPA), without giving rise to a normal left pulmonary
artery (LPA). The LPA arises from the RPA behind the ascending
aorta. The LPA then makes a hairpin turn to the left side, encircling the
trachea from the right side. This anatomy can be appreciated when the
pulmonary trunk is followed as it moves to the right side. Ao = Aorta;
RV = Right ventricle; T = Trachea.
management of Pulmonary Arterial sling
Computed tomography with three-dimensional reconstruction

is especially important for all suspected cases of ring-sling
complex as it beautifully demonstrates both the vascular
and airway abnormalities. It guides the surgeon to plan
the appropriate surgical therapy (Figure 18). Furthermore,
complications of the pulmonary parenchyma like collapseconsolidation, hyperinflation etc. can also be assessed.
Medical
In 1954, Willis Potts reported the first surgical repair for

pulmonary arterial sling from childrens hospital, Chicago.
a. The surgical repair involves division and mobilization of
LPA from its origin in RPA and reimplantation of the LPA
into MPA and resection of all ductal tissue (Figure 19A).
The usual approach is through median sternotomy and
after establishment of cardiopulmonary bypass.40,41
b. The tracheal stenosis also needs to be corrected if more
than mild in severity. The various approaches are:
i. Short segment tracheal stenosis: Simple resection and
end-to-end anastomosis.
ii. Long segment stenosis: Tracheoplasty using a part of
rib cartilage or pericardial patch (Figure 19B). In a
long trachea, a piece of narrow segment from trachea
is resected and then the same segment can be used to
Magnetic resonance imaging (MRI) is probably less useful

than CT in this respect as it is time-consuming, requires
sedation and anatomical details of airways and lungs are not
elucidated as good as CT here.
Bronchoscopy
In many centers, a preoperative bronchoscopy is part of the
investigational protocol. Often external imaging of the trachea
may not show internal abnormalities like complete rings.
Bronchoscopy informs us about the level, length and degree
of luminal narrowing and allows precise surgical planning.
Also intraoperatively, it allows the surgeon to gauge the extent
a. General supportive care and treatment of chest infections.

b. Symptomatic children should undergo surgical correction
without delay.29,39
Surgical
539
Figure 18: This computed tomography angiogram shows the pulmonary arterial sling with anomalous origin of left pulmonary artery (LPA)
with abnormal tracheobronchial branching and stenosis. MPA = Main
pulmonary artery.
augment the tracheal lumen. This procedure is called

tracheal autograft41 and considered superior to other
autologous patch materials (Figure 19C).
Figure 19a: This schematic diagram shows the principle of surgical

management of pulmonary arterial sling. The origin of left pulmonary
artery (LPA) from the right pulmonary artery (RPA) is transected
and the RPA opening is repaired with interrupted prolene sutures.
An opening is made in main pulmonary artery (MPA) and the LPA is
reimplanted into MPA. The anticipated initial incision into the stenotic
trachea is shown by dotted line. Courtesy: Reprinted with permission
from reference 29
Postoperative Course
The success of surgery depends not only on the vascular
anastomosis made, but also on severity of preoperative airway
obstruction. Persistent airway obstruction, hemorrhage,
infections, edema and stenosis are usually seen in perioperative
period. In severe cases, the airway symptoms may persist even
1 year after surgery due to pre-existing tracheomalacia. This
fact needs to be discussed with the parents before surgery.
Rare postoperative complications include chylothorax and
vocal cord palsy secondary to recurrent laryngeal nerve damage.
The postoperative mortality rates are variable and mostly
caused by associated tracheal and bronchial abnormalities.
Survivors usually are free of significant symptoms in long-term
follow-up. However, they need to be monitored for stenosis
of reimplanted LPA. Marmon et al studied 17 asymptomatic
patients at a mean 6.1 years after surgery.25 No correlation was
found between age of diagnosis and surgery, type of vascular
lesion, or severity of presenting symptoms and abnormal
pulmonary function test. More long-term data is desirable,
using objective quantification of respiratory function, before
confirming the eventual curative nature of surgery.
otHEr cAusEs oF VAsculAr comPrEssIon

oF AIrWAys42,43
brachiocephalic Artery compression of Airways
540
Brachiocephalic artery compression of airways is a condition,

where the brachiocephalic artery arises from the aortic
Figure 19B: This schematic diagram shows the pericardial tracheoplasty technique. The trachea is opened anteriorly through the area
of complete tracheal rings. On cardiopulmonary bypass support,
the trachea is patched with autologous fresh pericardium anchored
with interrupted sutures. Courtesy: Reprinted with permission from
reference 29
arch far on the left side of midline and then courses to the
right and thus compresses the anterior wall of trachea. This
produces respiratory symptoms from stridor, cyanosis and
bradycardia. However, the symptoms are noted only if there is
a coexisting crowded superior mediastinum, either secondary
to cardiomegaly or dilated vessels, etc. The treatment in severe
cases involves surgical suturing of brachiocephalic artery to
sternum (Figures 20A and B) .
36
Absent Pulmonary Valve syndrome

This entity, most commonly associated with TOF, is associated
with aneurysmally dilated pulmonary arteries, which exert
direct mechanical compression of tracheobronchial tree. In
addition, the tracheobronchial tree is often inherently abnormal
including abnormal branching pattern, abnormal alveolar
architecture, etc. Surgical correction includes not only an
intracardiac repair but also plication and anterior translocation
of pulmonary arteries.
Posteriorly displaced Ascending Aorta

In this situation, the displaced ascending aorta may directly
compress on the right side of trachea.The posterior aorta also
Figure 20a: This schematic diagram shows the brachiocephalic

or innominate artery arising from the left side of midline and then it
courses in front of trachea and compresses the trachea. The arrow
shows the level of compression of the trachea
compresses the right pulmonary artery, which in turn presses

on the left and right main bronchus (Figure 21).
Figure 19c: This schematic diagram shows the principle of using

tracheal autograft. The trachea is opened anteriorly through the area
of complete tracheal rings. The mid-portion of the stenotic trachea
(usually 68 rings, 1.52.0 cm) is resected to be used later as the
autograft. Courtesy: Reprinted with permission from reference 29
Elongated Aortic Arch

The classic example is right aortic arch in congenitally
corrected transposition. Here, the ascending aorta is
L-posed and ascends to the left and then takes a long
transverse course in front of trachea to connect to the
descending aorta in the right posterior mediastinum. Once
the lungs are hyperinflated, they extend to the midline
behind sternum, pushing the mediastinal structures and
heart backward, further compromising the tracheal and
bronchial patency.
Figure 20B: This computed tomography angiogram shows brachiocephalic (innominate) arterial compression of trachea. The compression is
at the level of inlet of thoracic cage and is located at a much higher level than that caused by double aortic arch or right arch with aberrant left
subclavian artery. The white arrow shows the brachiocephalic artery, the black arrow shows the trachea and the white overhead shows the esophagus. Courtesy: Reprinted from Oddone M, et al. Multi-modality evaluation of the abnormalities of the aortic arches in children: techniques
and imaging spectrum with emphasis on MRI. Pediatr Radiol. 2005;35:947-60
541
7
development of human and mammalian embryos have never

been documented.
Isolated Origin of Left Subclavian Artery from Left

Pulmonary Artery
Isolated origin of left pulmonary artery from left subclavian
artery is another rare anomaly where the left subclavian artery
has no connection with the aorta and instead is connected to
left pulmonary artery via the left ductus (Figures 23A to C).
This is embryologically explained by the abnormal regression
of left arch segment both proximal and distal to the origin
of LSA from left arch. In fetal life, as the ductus is widely
patent, there is no problem. However, once the ductus closes
postnatally, this anomalous LSA may produce vertebral steal.45
Figure 21: This computed tomography angiogram in coronal section
shows how in unusual posterior displacement of ascending aorta (AA)
towards spine, the left bronchus gets squashed between the ascending
and descending aorta (DA). The arrow depicts the left bronchus. RV =
Right ventricle. Courtesy: Reprinted with permission from reference 1
diagnostic Algorithm for Vascular tracheoesophageal

compressive syndrome
The diagnositc algorithm for vascular tracheoesophageal
compressive syndrome is shown in Figure 24.
miscellaneous
Key messages
Double-barreled Aorta
Double-barreled aorta is a rare anomaly in which the ascending
and descending components of the aorta are connected by two
aortic arches on the same side of trachea (Figures 22A and B).
This is not to be confused with double aortic arch, where the
two arches are on the opposite sides of trachea.44
Previously, this was explained as persistence of fifth
aortic arch. However, modern embryologists disregard
this view as existence of fifth aortic arch during normal
a
542
1. Vascular etiology of tracheoesophageal compressive syndromes account for 1 to 3 percent of all congenital heart
diseases.
2. Persistent respiratory and feeding difficulties may prove life
threatening for small infants.
3. Diagnosis may be difficult as not all cases are symptomatic.
4. Multimodality evaluation of aortic arch and its branches
including CT and MRI adds to the diagnosis and surgical
planning.
5. Surgical treatment of anomalous vascular structures and
tracheal reconstruction gives excellent results in most of the
cases.
Figures 22a and B: The echocardiogram of the aortic arch in suprasternal view. A. Shows the double-barreled aorta in which an aortic arch
with dual lumen is found on the same side of trachea, in contrast to a double aortic arch. The computed tomography angiogram with 3D
reconstruction; B. Shows the same anatomy. The superior arch is atretic distal to the origin of left subclavian artery. (Courtesy: Reprinted with
permission from reference 1)
36
Figures 23a to c: Contrast-enhanced magnetic resonance angiograms reformatted in right anterior oblique. A. Left anterior oblique B. and
frontal C. Planes show that there is a right aortic arch (Ao) that gives rise to the left common carotid artery (LCA), right common carotid artery
(RCA) and right subclavian arteries (RSA) in sequence. The left subclavian artery (LSA) arises from the proximal left pulmonary artery (LPA)
through the left arterial ductus (two arrows). The right arterial ductus is patent between the right pulmonary artery (RPA) and the descending
aorta. Note that the right arterial ductus has an ampullary dilatation (asterisk) at its pulmonary arterial end. LV = Left ventricle; LVA = Left vertebral
artery; MPA = Main pulmonary artery; RA = Right atrium; RV = Right ventricle; RVA = Right vertebral artery. Courtesy: Reprinted from reference 1
I also thank Dr Aysel Turkvatan, Department of Radiology,

Ihtisas hospital, Ankara, Turkey, for sharing with us his article
and images on CT of congenital anomalies of aortic arch.
I express my thanks to Dr Carl Backer for allowing us to
reprint his schematic diagrams depicting principles of surgical
treatment of pulmonary arterial sling. I am also grateful to
Dr Devananda NS for kindly scrutinizing and revising the
surgical aspects of this chapter. Last but not the least, I am
thankful to Mrs Sindhu Vijayan for her secretarial help.
rEFErEncEs
Figure 24: The diagnostic algoithm for vascular

tracheoesophageal compressive syndrome
Let the young know they will never find a more interesting,
more instructive book than the patient himself.
Giorgio Baglivi
AcKnoWlEdgmEnts
I express my heartfelt gratitude to Dr Robert Anderson for his
kind permission to reprint the embryological cartoons depicting
development of aortic arch and their postnatal imaging.
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BD Neuhauser, MD. Radiology. 2000; 216:624-32.
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involving a double aortic arch with a right descending aorta.
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42. Kim YM, Yoo SJ, Kim TH, et al. Tracheal compression by
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Sec t i on
Cyanotic Heart Diseases
C hapter
37
Tetralogy of Fallot
R Suresh Kumar, IB Vijayalakshmi, Bhushan Chavan
Introduction
Tetralogy of Fallot (TOF) is a congenital heart defect, which
has four anatomical componentsnon-restrictive large
subaortic ventricular septal defect (VSD), infundibular
stenosis, overriding aorta and right ventricular hypertrophy.
TOF is the most common cyanotic heart defect seen in children
beyond infancy, accounting for a third of all congenital heart
disease (CHD) in this age group. Even though Stenson in
1671 and Sandifort in 1777 had made references to what
would eventually be called TOF, it was EtienneLouis Arthur
Fallot who first designated the four morphologic hallmarks
and outlined a clinical diagnosis. The term tetralogy of Fallot
was to take birth much later, in 1924, in the works of Maude
Abbot. The first surgical palliative aortopulmonary shunt
was done by Alfred Blalock and Helen Taussig in 1945.
In 1946, Potts described a descending aorta to pulmonary
artery (Potts-Smith) shunt. Ten years later, Lillehei in 1954
did the first intracardiac repair (ICR) with controlled crosscirculation. In 1962, Waterston described an ascending aorta
to pulmonary artery shunt. Kirklin in 1966 performed the first
ICR using transannular patch and valved conduits and he also
proposed the 50% rule. This rule is a standard practice now.
The Washington-Baltimore infant study found a prevalence
of 0.262 per 1,000 live births. The disorder may be associated
with extracardiac anomalies such as cleft lip and palate,
hypospadias and skeletal and craniofacial abnormalities.1
Embryology
Tetralogy of Fallot is characterized by underdevelopment of
the subpulmonary infundibulum. Failure of normal growth
of the subpulmonary infundibulum results in an obstructive
pulmonary outflow tract.2 Because the subpulmonary conus
is too small, it fails to fill with the help of the membranous septumthe interventricular foramen. Persistent patency of the interventricular foramen results in the typical
malaligned VSD of TOF. Paying tribute to the primacy of
the underdevelopment of the subpulmonary infundibulum,

Van Praagh called TOF, the monology of Stensen. The more
marked the anterior displacement of the conal septum, the
more pronounced is the aortic override. Often even the spiral septum is displaced anteriorly. This may explain anomalies of the pulmonary valve like bicuspid valve or stenosis/
atresia. It may also explain the unusually large aortic root
and ascending aorta in TOF.3
Pathology
The central abnormality in TOF is the hypoplasia of the
infundibular septum, which causes the septum to move
anteriorly and create an anterior malalignment type VSD. The
crista supraventricularis is displaced anteriorly relative to the
parietal and septal bands, narrowing the right ventricle outflow
tract (RVOT). The medial papillary muscle is not present. A
VSD, almost always large, is present just behind the anteriorly
displaced crista supraventricularis.The right sinus of Valsalva
is located at a higher position as compared to normal hearts
and the aorta can be easily entered from the right ventricle
(RV). When the infundibular stenosis is marked or severe the
overriding of aorta is to a very marked degree. The pulmonary
valve is commonly, stenotic. Very often it is bicuspid; in onefourth of cases, the pulmonary valve is atretic.3 Absence of
the pulmonary valve creates a unique syndrome, which is
discussed in chapter 30. Coronary abnormalities occur in 5
percent, anomalous origin of left anterior descending (LAD)
artery from the right coronary artery (RCA) being the most
common. The pattern of involvement of RVOT, pulmonary
valve and other anomalies assosciated with TOF are discussed in
Boxes 1A-E.4,5
Genetics
In most cases, TOF is sporadic and non-familial. The inci
dence in siblings of affected parents is 1 to 5 percent. TOF
could be a syndromic defect, often associated with chromosomal
Cyanotic Heart diseases
Box 1A: Pulmonary valve configuration

in patients with tetralogy of Fallot
Box 1E: Associated anomalies

in tetralogy of Fallot5
Bicuspid
66%
ASD
Tricuspid
15%
Persistent LSVC
Vestigial
Not Recorded
9%
8%
10%
Anomalous origin of LAD from RCA
4%
09%
Aberrant origin of right subclavian artery
0.3%
Vascular ring
0.2%
0.2%
0.2%
Juxtaposition of atrial appendages
0.2%
Based on the analysis 365 patients who underwent tetralogy of Fallot

surgery at Green Lane Hospital (GLH Series) between 1960-1978.
Congenital heart block

Absent RSVC
Box 1B: Prevalence of the pulmonary

valve lesion
Tethering alone
63%
Commissural fusion
14%
Tethering + fusion
06%
Vestigial valve
10%
Atretic valve
01%
Unrecorded
ASD = Atrial septal defect; LAD = Left anterior descending; LSVC =

Left superior vena cava; RCA = Right coronary artery; RSVC = Right
superior vena cava
06%

Box 1C: Patterns of right ventricular outflow tract

obstruction in tetralogy of Fallot
Isolated infundibular stenosis
Infundibular + valvular stenosis
26
26
Infundibular + valvular stenosis + annular stenosis
Diffuse right ventricular outflow tract hypoplasia

Dominant valvular stenosis
16
27
05

Box 1D: Patterns of coronary artery anomalies

in tetralogy of Fallot4
Single coronary ostium
LAD arising from RCA or right sinus of Valsalva

LCX arising from RCA
Large conus artery
Fistulas between coronary artery and PA or RA
4.2%

4.2%
0.8%
9.3%

1.7%
Anastomosis between coronary artery and the

bronchial arteries
Hypoplastic coronary artery
6.0%

0.8%
LAD = Left anterior descending ; LCX = Left circumflex; PA = Pulmonary

artery; RA = Right atrium; RCA = Right coronary artery
techniques have led to the identification of syndromes due

to submicroscopic defects, such as the microdeletion of
chromosome 22q11.2 (DiGeorge/Velocardiofacial syndrome).
Some series have reported 15 percent incidence of 22q11
microdeletion in TOF. Among single gene defects, Alagille
syndrome is known to be frequently associated with TOF. This
syndrome is due to mutations in the JAGGED1 gene. Several
conditions with multiple malformations have TOF as their
cardiac component. These include CHARGE (coloboma, heart
defect, atresia choanae, retarded growth and development, genital
abnormality, ear abnormality) syndrome, VACTERL (vertebral
defects, anal atresia, cardiac defects, tracheo-esophageal fistula,
renal anomalies, limb abnormalities) association and Goldenhar
syndrome (oculoauriculovertebral spectrum). Specific anatomic
characteristics can be detected in congenital heart defects
associated with specific syndromes. Patients with TOF and
22q11 microdeletion frequently have additional cardiac defects,
like right or cervical aortic arch, hypoplasia or absence of the
infundibular septum, absence of the pulmonary valve and
discontinuity and diffuse hypoplasia of the pulmonary arteries
(PAs). Patients with TOF and Down syndrome frequently have
a particularly large VSD in the inlet septum. Non-syndromic
TOF occurs sporadically in families, but multiple affected
family members may also be found. In the majority of the cases,
inhe
ritance is multifactorial, several genetic loci interacting
in association with environmental factors. Some of the genes
known to be involved in non-syndromic TOF are low-mutations
in NKX2.5 (4% of TOF cases), JAGGED1 and FOG2 (4% of
the cases). In practical genetic counselling, the recurrence risk
for congenital heart defect among siblings of patients affected
by TOF is about 3 percent.6
Clinical features
548
anomalies and monogenic syndromes. Chromosomal anomalies

are involved in about 12 percent of the cases, e.g. trisomy 21
(Down syndrome), trisomy 13 (Patau syndrome) and trisomy 18
(Edwards syndrome). Advances in cytogenetic and molecular
History
Tetralogy of Fallot is slightly more common in males than
in females.7 Patients with TOF most often present in infancy
Box 2A: Mechanism of cyanotic spells
37
Tetralogy of Fallot
with cyanosis due to right to left shunting of blood at the

level of the VSD.8 The degree of right ventricular outflow
tract obstruction (RVOTO) often correlates with the degree
of cyanosis and the timing of presentation. Thus patients
with mild pulmonary obstruction present late, perhaps even
in adulthood, the so-called pink TOF, while patients with
severe obstruction may present soon after birth on closure of
the ductus arteriosus.8,9 In less severe cases, cyanosis is first
noticed during crying.
Cyanotic spell is an important manifestation of TOF. The
tachycardia, immature vulnerable respiratory center and
dynamic subpulmonary obstruction is believed to be a major
factors behind the origin of the hypercyanotic spells. The
other important contributor being variations in the systemic
vascular resistance (SVR). The mechanism of spell is shown in
Box 2A and the various theories of mechanism of spell is
shown in Box 2B.10-13 Spell usually occurs in infants between
3 to 24 months of age.8,9 Typical spell is characterized by
progressive increase in the rate and depth of respiration,
deepening cyanosis, limpness or syncope. Convulsions,
cerebrovasclur accident and death are potential complications.
Spells are less common after 2 years. Initiated usually by
crying, feeding or bowel movement, spells are particularly
common after getting up from sleep. It is postulated that a
vulnerable respiratory center, which is particularly sensitive
after prolonged sleep, reacts to sudden increase in cardiac
output provoked by feeding, crying or straining to initiate
the vicious cycle of spell. Such actions lead to increased
venous return to the right heart. In presence of obstruction
to pulmonary flow, right to left shunt increases. This right
to left shunt leads to acidosis, which in turn stimulates the
respiratory center, provoking hyperpnea, further worsening
systemic oxygen saturation. A vicious cycle of progressive
hypoxia, acidosis and hyperpnea ensues. Infundibular spasm
secondary to increased sympathetic tone aggravates the
problem by increasing right to left shunt. The drop in SVR
with muscular activity is a major contributor to right to left
shunt.
Exertional dyspnea is common in the older child. A
characteristic posture older children with TOF assume to
increase pulmonary blood flow and to alleviate dyspnea is
squatting. Squatting is of diagnostic significance in TOF.
Squatting increases peripheral vascular resistance and thus
decreases the magnitude of the right to left shunt across the
VSD. Locking up the more desaturated lower limb venous
blood and displacing the better oxygenated mesenteric
venous blood into the right heart may be the other benefits
of squatting. Exertional dyspnea usually worsens with age.
Occasionally, hemoptysis may occur in the older child due
to rupture of bronchial collaterals. RV failure is uncommon
in TOF patients but the various circumstances in which the
patient can present with RV failure are given in Box 3
Box 2B: Theories for explanation of mechanisms

of cyanotic spells10-13
A. Wood's theory: Postulated that hypoxemic spells are
caused by spasm of the infundibulum of the right ventricle
which precipitates a cycle of progressively increasing right to
left shunting and metabolic acidosis.
B. Catecholamine release: Leads to increased myocardial
contractility and infundibular stenosis (both these theories
do not explain the cause of cyanotic spells in patients with
tetralogy of Fallot with pulmonary atresia).
C. Guntheroth's theory: Episodes of paroxysmal hyperpnoea
are the cause rather than the effect of cyanotic spells.
Hyperpnoea increases the systemic venous return leading
to right to left shunt as well as oxygen consumption through
increase work of breathing.
D. Kothari's theory: Argued against the other hypotheses
and suggested the role of stimulation of mechanoreceptors in
the right ventricle to be the cause of spells.
E. Morgans theory: Vulnerable respiratory centre which
over-reacts to hypoxic stimuli like crying, feeding causes
an increase in cardiac output and heart rate which in turn
increases venous return causing an increase in right to left
shunt across the ventricular septal defect which leads to a fall
in PaO2 and increase in PCO2. The respiratory centre overreacts to this stimulus and causes hyperpnea which again
increases the venous return, thereby causing a vicious cycle.
F. Youngs theory: It was proposed that the spell was
precipitated by an atrial tachycardia.
Clinical Examination
Most infants are smaller than expected for age. Cyanosis of
the lips and nail bed may be noticed at birth or may appear
later. Cyanosis in TOF is determined by the severity of
pulmonary stenosis and also to a lesser extent by systemic
549
Box 3: Causes of right ventricular failure

in tetralogy of Fallot
1. Pulmonary atresia with large systemic arterial collaterals
2. Accessory tricuspid leaflet tissue partially occluding the
ventricular septal defect making it restrictive and causing
supra systemic right ventricular pressure.
3. Absence of pulmonary valve causing combination of
stenosis (annular narrowing) and free pulmonary
regurgitation.
4. Systemic hypertension
5. Acquired calcific aortic stenosis or regurgitation of the
biventricular aortic valve
6. Infective endocarditis affecting the aortic valve
7. Hyperdynamic circulatory status like due to anaemia,
thyrotoxicosis
8. Adult tetralogy of Fallot with aortic regurgitation
to pulmonary collaterals. Infundibular stenosis worsens as

the infant grows so that a previously pink baby turns blue.
In the case of pulmonary atresia, cyanosis sometimes may be
absent due to systemic pulmonary collaterals. Clubbing may
be present after 3 months of life. General examination may
reveal subtle features of 22q11 microdeletion. Precordium
is quiet. S1 is normal, while S2 is single due to a faint
P2. Delayed and hesitant closure of the pulmonary valve
due to the slow pressure drop in the stenotic infundibular
chamber, associated valvar stenosis and the overrding aorta
all contribute to the single S2. A prominent ejection systolic
murmur, is heard at the mid and upper left sternal border.
The intensity of this murmur is inversely proportional to the
severity of stenosis. With more severe stenosis RV pumps
more into the aorta and less across the RVOT, decreasing the
murmur. The murmur disappears during a spell. An aortic
ejection click due to the dilated ascending aorta may be heard
over the apex. A continuous murmur below the left clavicle
denotes a patent ductus arteriosus (PDA). A more widely
heard continuous murmur, especially over the back, is due to
systemic-pulmonary collaterals.
Adult TOF
550
A large group of TOF patients are seen to survive to adulthood

without surgical correction and with the vast prevalence of
TOF the number of such patients presenting to a clinician
is increasing. Some of the studies have addressed the basic
difference in the pathophysiology and the presentation of these
patients. The largest study on adult TOF patients was done by
Abraham et al in which he evaluated the presentation of 147
patients, above the age of 18 with TOF. Cardiac catheterization
and selective cine angiography were performed in all. Cardiac
enlargement was seen in 25.8 percent of the patients, and 15.6
percent were in congestive cardiac failure; 9.5 percent had
systemic hypertension, and aortic regurgitation was present
in 6.7 percent. A reticular pattern in the lung fields due to

bronchial collaterals was seen in 23.1 percent. The incidence of
right aortic arch (19.9%), absent left pulmonary artery (2.8%),
absent right pulmonary artery (0.7%) and dextrocardia (1.4%)
is brought out. The right atrial mean pressure was increased
in 4.8 percent and a prominent a wave greater than 10
mm Hg was present in 10.9 per cent. The right ventricular
end-diastolic pressure was increased in 23.8 percent and the
left ventricular end-diastolic pressure in 25.9 percent of the
patients.This study clearly shows that a lot of clinical features
which are usually considered uncharacteristic in TOF patients
can be present in adult uncorrected TOF patients.14
Chest X-Ray
Plain films may classically show a "boot shaped" heart with
an upturned cardiac apex due to right ventricular hypertrophy
and concave pulmonary arterial segment. Lung vascularity is
decreased (Figures 1A and B ). A right aortic arch is present
in 25 percent.15
Electrocardiogram
Right ventricular hypertrophy and right axis deviation are the
salient features of TOF. Older children and adults may show
right atrial enlargement. Whereas the R wave in V1 is tall and
usually monophasic, R wave in V2 is much shorter the so
called sudden transition is characteristic (Figure 2). In patients
with pulmonary stenosis and restrictive VSD, right precordial
leads show deeply inverted T waves in right precordial leads.16
Left axis deviation denotes an inlet VSD.
Echocardiography
Echocardiography allows examination of all essential features
of tetralogy of Fallot and has a crucial role in diagnosis
and preoperative evaluation (Figures 3A and B). Complete
echocardiographic evaluation usually obviates the need for
further imaging. Most of the information can be achieved
with transthoracic echocardiography, but occasionally trans
esophageal echocardiography may be helpful for specific
questions raised by transthoracic echocardiography. A
complete study must address:
1. The location and number of VSDs
2. The anatomy and severity of RVOTO (Figures 4A and B).
The size and anatomy of the main pulmonary artery, the
pulmonary arterial confluence, and the proximal branch
pulmonary arteries, as far distally as possible, must be
demonstrated.
3. The coronary arteries must be imaged, specifically looking
for any major branch crossing the RVOT. The LAD arises
from the RCA and crosses the RVOT in 5 percent.
4. Aortic arch laterality must be shown. The presence of
any associated anomalies like atrial septal defect PDA,
additional VSDs must also be looked for.
37
Tetralogy of Fallot
Figures 1A and B: Chest X-ray in Tetralogy of Fallot (TOF): A. Classical boot-shaped heart with right sided aortic arch oligemia with empty
pulmonary bay; B. TOF with collaterals showing the reticular lacy appearance in the lung fields with right sided aortic arch.
Figure 2: Electrocardiography in tetralogy of Fallot shows right-axis deviation, tall R wave in V1, with sudden transition in V2 with deep S wave
Cardiac catheterization
Figures 3A and B: Echocardiography in tetralogy of Fallot. A. Fivechamber view shows large ventricular septal defect (VSD), overriding
of the aorta; B. Bidirectional shunt across the VSD.
Cardiac catheterization may be necessary in few cases to

further delineate the levels of right ventricular outflow
obstruction, branch pulmonary artery stenosis or hypoplasia,
coronary artery anatomy, presence of aortopulmonary colla
terals, and presence of additional VSD. The findings on
oximetry in patients with TOF is given in Box 4.
The hemodynamic findings at catheterization typically
reveal normal or only mildly elevated filling pressures. The left
and right ventricular systolic pressures are equal. Pulmonary
artery pressures are normal or low. The degree of right-to-left
shunting is best shown by the degree of systemic desaturation.
Angiographic assessment should be geared towards the
information that is needed; biplane angiography is ideal.
RV angiogram (anteroposterior [AP] cranial, shallow
551
8
Box 4: Salient features of oximetry run

RA, RV and PA saturations are similar to that of vena cava
MVO2 is markedly reduced to about 2040% in infants with
severe hypoxemia
PV saturation is near normal
LA saturation slightly decreased to that of PV especially
in pentalogy of Fallot
LV saturation reflects LA saturation
Aortic saturation greater than that of RV and less than that
of LV (may be markedly reduced to 4060%)
PA saturation higher than that of RV if PDA and/or multiple

collaterals are present
In patients with less severe infundibular stenosis the
MVO2 is nearly normal with a small increase in RVO2 and
slight decrease in LVO2
LA = Left atrium; LV = Left ventricle; LVO2 = Left ventricle oxygen
saturation ; MVO2 = Mixed venous oxygen saturation; PA = Pulmonary
artery; PDA = Patent ductus arteriosus; PV = Pulmonary vein; RA = Right
atrium; RV = Right ventricle; RVO2 = Right ventricle oxygen saturation
B
Figures 4A and B: A. Short-axis view showing infundibular stenosis
with turbulence; B. Right ventricle outflow tract gradient on Doppler is
81 mm Hg.
552
left anterior oblique [LAO] view) shows simultaneous

opacification of aorta and PA, RVOT obstruction and PA
anatomy (Figure 5). An aortic root injection will usually
provide adequate identification of the coronary arteries,
although selective injections may occasionally be needed.
The arch and descending aorta may also be seen in this view
and show a PDA or collateral vessels. If collateral vessels are
identified, selective injections are helpful to assess the areas
of the pulmonary bed that they supply and whether they are
the sole supply to these areas. The VSD is best seen from a
left ventricular injection in a long axial oblique projection.
Multidetector computed tomography (MDCT) angiography
is a safe and effective non-invasive technique to answer
questions remaining after echocardiography in patients with
TOF. Major aortopulmonary collateral arteries (MAPCA)
from all sources are best shown by this technique.17
The various indices for prediction of successful intracardiac
repair are given in Box 5.
Figure 5: Right ventricular angiogram in frontal view shows

trabeculated right ventricle (RV) with simultaneous opacification of
aorta (Ao) and pulmonary artery (PA) with severe infundibular stenosis
and pulmonary valvar and supravalvar stenosis
Medical Management
Medical mangement in TOF patients is directed towards
preventing cyanotic spells, avoiding problems associated
with anemia or polycythemia, preventing complications
from infection like brain abcess or infective endocarditis.
The general measures include correction of anemia by iron
supplementation and nutritional supervision. The child is
started on oral propranolol (14 mg/kg/day in three or four
divided doses) to prevent cyanotic spells until surgical
Nakata index: Sum of the cross sectional areas of the left

and right pulmonary arteries at their prebranching points
as related to body surface area. The normal Nakata index
is + 330 mm2 /m2. An index of more than 150 mm2 /m2 is
acceptable for complete repair without prior palliative shunt.
Tetralogy of Fallot with pulmonary stenosis should have an
index of more than 100 for surgery.
McGoon ratio: Ratio of the sum of the pre branching
diameters of the left and right pulmonary arteries to the
diameter of the descending aorta just above the level of the
diaphragm. Ratio above 1.2 is associated with acceptable
postoperative right ventricular systolic pressure in tetralogy of
Fallot.
Z-Score: The branch pulmonary artery diameter Z-score is the
most important determinant of surgical strategy, with the worst
figures being associated with no surgical options or palliative
surgery and the best figures leading to corrective surgery
Z = Observed dimension - Mean normal dimension/standard deviation
around mean normal dimension
correction is done. A cyanotic spell is usually self limiting and

lasts less than 15-30 minutes.
But sometimes they can be prolonged and require
emergency measures like:
1. Hold the child in knee chest position.This increases the
SVR and decreases the desaturated systemic venous
return.
2. Calm the child. The ideal sedative is morphine. It causes
respiratory centre suppression and sedation thereby
reducing hyperpnea. It reduces the ventilatory drive and
decreases systemic venous return (venodilator). This
will decrease the release of catecholamines, increase
the period of right ventricular filling by decreasing
the heart rate and relax the infundibulum. The dose of
morphine is 0.1 mg/kg and it can be given intravenous
(IV), intramuscular (IM) or subcutaneous. It may be
repeated after 5 minutes. The ventilation facilities
should be at hand. The other alternative sedatives
are: midazolam 0.050.1 mg/kg (IV, intranasal or
intrarectal) or dexmedetomidine 0.5 -1 mcg/kg IV or
infusion of 0.2 mcg/kg/hr or fentanyl 12 mcg/kg IV.
Ketamine has dual benefit of causing sedation and
increasing SVR. The dose is 0.25- 1.0 mg/kg IV or IM.
3. 100% Oxygen supplementation. This causes pulmonary
vasodilation and hence decreases the pulmonary
vascular resistance (PVR). The least aggravating
method of delivery should be used.
4. Establish immediate IV access to allow prompt
administration of fluids, which will improve right
ventricular preload. Initially, fluid is given as a bolus of
10-20 cc/kg, which may be increased to 60cc/kg. Bolus
fluid should be isotonic saline or colloid.
5. Sodium bicarbonate in a dose of 12 meq/kg IV is given

slowly to correct metabolic acidosis.This may reduce
the respiratory centre stimulating effect of acidosis
and may diminish the increase in pulmonary vascular
resistance caused by hypoxia and acidosis. It can be
repeated in 10-15 minutes.
6. Beta blockers like injection propanolol is given in
a dose of 0.1-0.2 mg/kg IV over 5 minutes and can
be repeated once after 15 minutes. It decreases the
heart rate, infundibular spasm and increases SVR. If
propanolol is not available then injection metoprolol
can be given in a dose of 0.1 mg/kg over 5 minutes.
Another short acting beta blocker which can be given is
injection esmolol in a dose is 0.5 mg (500 mcg)/kg over
1 minute and then as an infusion of 50 to 200 mcg/kg/
min up to 48 hours.
7. In refractory cases vasopressors can be given to
increase the SVR and promote the redirection of blood
flow through the pulmonary circulation. Phenylephrine
a alpha-adrenergic blocker can be given in a dose of 5 to
20 mcg/kg IV bolus, followed by an infusion of 0.1 to
0.5 mcg/kg/min.
8. Avoid any actions that agitate the baby like vigorous
examination, repeated attempts to venipuncture etc.
The drugs to be avoided are inotropes (e.g. digoxin,
dopamine, or dobutamine) and diuretics.
9. If the spell is persistent or refractory, then intubation
and mechanical ventilation maybe required.
10. A emergency Blalock-Taussig (BT) shunt / pulmonary
balloon valvuloplasty (PBV) may be required in
refractory cases.
The stepwise approach for management of TOF patient
who present in a cyanotic spell is given in Box 6.
37
Tetralogy of Fallot
Box 5: Indices for prediction of

success of intracardiac repair
CATHETER INTERVENTIONS IN TOF

Catheter based interventions can identify and apply the
most effective but least invasive solutions to most difficult
pathologies of TOF. Interdisciplinary approach can decide
on the best approach and combine interventional and surgical
alternatives for the best possible outcome resulting in fast
recovery, significantly reduce morbidity and mortality over
traditional surgery.
The various transcatheter interventions in TOF are:
1. Balloon dilatation of pulmonary stenosis.
2. Balloon dilatation and/or ductal stenting.
3. The coil closure of MAPCAs (Figures 6A and B).
4. Balloon dilatation of peripheral pulmonary artery stenosis
with or without stenting.
5. Balloon dilatation of blocked BT shunt.
6. Stenting of RVOT for infundibular stenosis by
balloon expandable stainless steel stents (Johnson &
Johnson).
7. Transcatheter pulmonary valve replacement.
553
Box 6: Infant with central cyanosis
554
37
Tetralogy of Fallot
Figures 6A and B: A. Selective angiogram in postoperative tetralogy of Fallot patient who

presented with hemoptysis and hypotension, shows multiple collaterals; B. Fluoroscopy shows
multiple Gianturco embolization coils (small arrows) along with sternal suture wires
Pulmonary Balloon Valvuloplasty

In patients with TOF, balloon dilatation of pulmonary
stenosis may be an effective palliative procedure in a subset
of patients, obviating the need for a palliative shunt. The
PBV is recommended if the patients size or cardiac anatomy
makes that patient an unsuitable candidate for total surgical
correction. The valvar obstruction should be a significant
part of the RVOTO obstruction. Also due to the multiple
obstructions in the RVOT, the subvalvar obstruction still
remains thus preventing flooding of the lungs after PBV.18
The supravalvar pulmonic stenosis, if discrete, can be
relieved by balloon dilatation. With the balloon dilatation,
immediate surgical intervention with high risk is avoided.
The result of surgery in TOF with branch pulmonary artery
stenosis varied from poor to catastrophy. Integrated approach
between cardiologists and cardiac surgeons with balloon
dilatation with or without stent have excellent results
(Figures 7A and B).
Advantages of Pulmonary Balloon Valvuloplasty

The various studies have shown favourable results with:
a. Substantial increase in saturation (SO2).
b. Growth of pulmonary valve annulus and pulmonary
arteries.
c. The need for transannular patch is reduced by 40 percent.
d. The high risk intracardiac repair (ICR) is postponed in
infants.
e. PBV in TOF acts as a safe bridge to surgery.
Disadvantages of Pulmonary Balloon Valvuloplasty

Pulmonary balloon valvuloplasty may not be successful in
all patients. Very rarely in severely hypoxic and sick patients
with very low SO2 the very attempt to cross the infundibulum
can precipitate the cyanotic spell.The mortality can occur due
to either cyanotic spell or tamponade in very sick infants.
INTERVENTIONS IN Blalock-Taussig SHUNT

In patients with a narrowed BT shunt, balloon angioplasty
with or without stent may improve pulmonary oligemia.
Improve systemic arterial hypoxemia and may obviate the
need for a second systemic-to-pulmonary artery shunt. The
BT stenosed anastomosis can be opened up with thrombolytic
therapy or balloon dilatation (Figures 8A to C). Balloon
dilatation was performed in 60 patients with various cyanotic
CHDs in a study.19 The results were good in 39 (65%)
patients, satisfactory in 19 (31.7%), and unsatisfactory in
only 2 (3%) cases. Complicated cases like pulmonary atresia
or hypoplastic pulmonary valve and pulmonary artery and
collaterals can benefit from a series of interventions prior to
surgery. Interdisciplinary approach avoids need for extensive
and prolonged open heart surgery and repeat surgery for
residual defect. It also improves the chances of full recovery
in complicated cases of TOF.
Surgery
The ideal age for TOF repair remains controversial. Most
centers prefer to operate by 1 year of age. Cases with
good anatomy could be operated much earlier, even in the
neonatal period. Transannular-transpulmonary approach is
usually followed.20 The various techniques of performing
intracardiac repair surgery in patients with TOF are given
in Box 7. Neonates and young infants with an unacceptable
level of oxygen saturation and/or hypercyanotic spells may
be palliated with a modified BT shunt. Although there is
555
B
Figures 7A and B: A. The pulmonary angiogram shows tight stenosis of left pulmonary artery (arrow);
B. The check angiogram after the balloon dilatation illustrates no stenosis
Figures 8A to C: A. Selective angiogram of left subclavian artery shows the stump of blocked Blalock-Taussig (BT) shunt (arrow); B. 4X30
balloon across the BT shunt (arrow); C. Selective angiogram of the reopened functional BT shunt illustrates good flow into left pulmonary artery
(LPA) in a one and half year old child of dextrocardia with tetralogy of Fallot. The saturations improved dramatically from 48 to 82 percent
some potential morbidity and mortality, many centers have

reported excellent outcome with this approach.21-23 The
various contraindications to performing an intracardiac repair
are given in Box 8. The various palliative procedures which
can be performed in TOF patients to augment the pulmonary
blood flow are given in Box 9. The difference between classic
and modified BT shunt has been discussed in Box 10.
Natural History
556
If left untreated, TOF results in progressive right ventricular

hypertrophy and right ventricular dilatation and threatens
survival. If pulmonary atresia is present as well, survival is
even poorer with only 50 percent of patients surviving to 1
year and only 8 percent of patients surviving to 10 years.
Survival without treatment is given in Box 11.
Long-Term Follow-up
Patients with repaired TOF have the potential to lead normal
lives with excellent cardiac function. Most survivors are in
New York Heart Association (NYHA) Class I or II. Some
patients have more symptoms on exertion. 90 percent of
patients with total repair develop progressive pulmonary
regurgitation (PR). Patients also may have some degree
of residual RVOTO and damage to the conduction system
of the heart. The incidence of bradyarrhythmias after
TOF repair has been drastically reduced in recent years.
The incidence of late atrial arrhythmias after TOF repair
is relatively high, about 30 percent, including atrial
fibrillation, flutter, focal or reentrant atrial tachycardia.25
Therefore, lifetime surveilance is recommended to assess
and monitor these risks and to recommend treatment. TOF
patients are at risk for sudden cardiac death with 1 to 5
Box 9: Palliative procedures augmenting

pulmonary blood flow
1. Transventricular approach: This was the earliest

approach which was used for RVOT resection but fell into
disrepute due to the high incidence of ventricular arrhythmias,
conduction system defects and right ventricular dysfunction.
This difference from other surgical approaches has been
proven in various follow up studies.
2. Transatrial approach: The transatrial approach for
tetralogy of Fallot repair was proposed by Hudspeth et al24
in 1963. This method has significant advantages as over the
transventricular approach for intracardiac repair. The salient
features of this method are:
Preservation of ventricular function
Decreased severity of PR
No risk of injuring branches of RCA
No scar on ventricle
Decreased arrhythmias
Adequate annulus is a must
3. Combined transatrial and transpulmonary approach:
The salient features of this approach are:
Small ventriculotomy
Blalock-Taussing shunt (classical): Subclavian artery to

pulmonary artery anastomosis (end-to-side). Infrequently, this
may lead to pulmonary hypertension.
Blalock-Taussing shunt (modified): Interposition graft
between subclavian artery and ipsilateral pulmonary artery.
Controlled augmentation of pulmonary blood flow. Usually
a 4mm Gore-Tex shunt is required early in infancy. Larger
shunts would be required for older patients, although the
possibility of repair should always be explored first.
Waterston shunt: Ascending aorta-to-main or right
pulmonary artery (side-by-side). No artificial material
used; shunt grows with the patient. May lead to pulmonary
hypertension. Infrequently, problems have been encountered
with pulmonary artery disruption, requiring extensive
arterioplasty.
37
Tetralogy of Fallot
Box 7: Surgical techniques

for intracardiac repair
Potts shunt: Descending aorta-to-left pulmonary artery

(side-by-side). Frequent complication with narrowing
and kinking of the left pulmonary artery at the site of the
anastomosis. The latter necessitates reconstructive surgery
during repair, occasionally through an additional thoracotomy,
which made this shunt unpopular.
Central interposition tube graft: A Gore-Tex graft is often
used for patients not suitable for early repair.
Minimizes RV dysfunction
Excellent exposure
Lower RVEDP, higher RVEF during isoprenaline infusion
Lower incidence of ventricular arrhythmias
Suitable for all patients
PR = Pulmonary regurgitation; RCA = Right coronary artery; RV = Right
ventricle; RVEDP = Right ventricle end diastolic pressure; RVEF = Right
ventricle ejection function; RVOT = Right ventricular outflow tract
Box 8: Contraindications to primary repair

Weight less than 3 kg (arbitrary and relative)
Severe hypoplasia of pulmonary annulus (Z value < 4)
Associated anomalies
Multiple ventricular septal defects
Anomalous coronaries especially if the left coronary
artery crosses the right ventricular outflow tract
Small pulmonary arteries are a relative contraindication
percent lifetime incidence. Risk factors for sudden cardiac

death include older age at repair, male sex, advanced NYHA
class, repair via atriotomy, complete heart block beyond the
third postoperative day and QRS duration greater than 180
milliseconds. A large follow up series which had assessed
the long term follow up of TOF patients post ICR is given in
Box 12. The indications for repeat surgery in these patients
is given in Box 13
Infundibular resection (Brock procedure) or closed

pulmonary valvotomy: Often effective palliative procedure
from an earlier surgical era.
Relief of RVOT obstruction without VSD closure or with
fenestrated VSD closure: In patients with multiple pulmonary
artery stenoses or hypoplasia.
RVOT = Right ventricular outflow tract; VSD = Ventricular septal defect
Reoperation may be required in 7 to 10 percent of

patients after TOF repair.26-28 Freedom from reoperation is
88 percent at 30 years. Reoperation is indicated for residual
RVOTO, residual VSD or PR. The most common reason
for reoperation is progressive pulmonary regurgitation for
which pulmonary valve replacement is done. PR results from
transannular patching or pulmonary valvotomy. Pulmonary
valve replacement is indicated for severe PR when there is
cardiomegaly, progressive RV dilatation, QRS duration >180
milliseconds,17,29,30 or RV volume in magnetic resonance
(MR) angiography exceeding 150 ml/m.3
Pulmonary valve replacement stabilizes right ventricular
size and QRS duration and improves symptoms of congestive
heart failure; data are conicting as to whether right ventricular
function improves postoperatively.31,32 Several long-term
follow-up series have reported gross measures of functional
status and quality of life (QOL) at late follow-up: 90 to 95
percent of patients report being in NYHA class I or II, 71 to 85
percent are employed, 17 to 25 percent take routine medications
and 50 percent participate in recreational sports.26-28
557
Box 10: Classic v/s modified Blalock-Taussig shunt

CLASSIC BLALOCK-TAUSSIG SHUNT (CBTS)
1 year
66%
Anastomosis is done between the subclavian artery

or the subclavian branch of the innominate artery and
the pulmonary artery, usually on the side opposite the
descending aorta.
3 years
50%
10 yrs
25%
20 yrs
11%
30 yrs
6%
40 yrs
3%
Advantages
It requires no prosthetic material
Predictability of blood flow
Subclavian artery diameter prevents the excessive flow
to pulmonary arteries and prevents congestive heart
failure
Ease of closure during corrective surgery
Potential adaptive growth of anastomosis
Disadvantages
Requires careful, lengthy dissection
Can cause distortion of the peripheral pulmonary artery
Blood supply to the ipsilateral arm is compromised which
may result in a discrepancy in growth and strength.
Thrombosis of shunt (small size)
Neurologic (rare): recurrent laryngeal nerve injury, phrenic
nerve injury, Horner syndrome
Subclavian Steal syndrome
MODIFIED BT SHUNT
Prosthetic graft material is interposed between the subclavian
artery and the pulmonary artery.
Advantages
Can be performed on either side
Subclavian blood supply to the arm is preserved
Kinking of the subclavian artery is not a problem
Excellent patency rates: 90% at 2 years
Prevent mutilating effects of CBTS
Pulmonary artery distortion less likely
Can be performed < 3 months age
Disadvantages
May be more difficult than classic BT shunts to take down
Leakage of serous fluid through PTFE in chest
Pseudoaneurysm formation which can lead to fatal
hemoptysis
Conclusion
558
Box 11: Survival without treatment in patients

with tetralogy of Fallot
The timing of surgery in TOF needs to be decided based on

the clinical status of the baby and the institutional experience.
The word total intracardiac repair is misleading as the child
could have residuae, sequelae and complications that may
appear at any time during subsequent life. Hence, life-long
follow-up is mandatory, even though the majority of patients
can expect near normal life span with good quality of life.
MR angiography may assume an important role in follow-up.
Box 12: Postsurgical follow up26

In a group of 490 children who survived past the first year of
surgery in Germany, actuarial survival rates were:
10 years: 97%
20 years: 94%
30 years: 89%
36 years: 85%
The most common cause of death was sudden death (n = 13),
followed by congestive heart failure (n = 6).
Box 13: Indications for re-intervention

1. Symptoms of right heart failure
2. RV enlargement or evidence for RV dysfunction, especially
if pulmonary regurgitation is present
3. Clinically significant arrhythmias (atrial or ventricular)
4. Progressive aneurysmal dilation of an RV outflow tract
patch
5. Onset or progression of tricuspid regurgitation
6. Residual VSD with shunt > 1.5 : 1
7. Residual patent arterial-pulmonary shunts leading to LV
volume overload
8. Residual RV outflow tract obstruction or pulmonary
stenosis with systolic RV/LV 0.67
9. Significant aortic insufficiency with evidence of LV
dysfunction
10. Dilated aortic root > 5.5 cm
LV = Left ventricle; RV = Right ventricle; VSD = Ventricular septal defect
Symptoms are the body's mother tongue; signs are in a

foreign language.
John Brown
Acknowledgment
We express our thanks to Dr Navin Agrawal, Sri Jayadeva
Institute of Cardiovascular Sciences and Research,
Bengaluru, for providing the various charts for this chapter.
References
37
Tetralogy of Fallot
1. Behrman RE, Kliegman RM. Nelson Essentials of Pediatrics.

5th edition. Philadelphia, Pa.: Saunders; 2006.
2. Van Praagh R, Van Praagh S, Nebesar RA, et al. Tetralogy of
Fallot: Underdevelopment of the pulmonary infundibulum and
its sequelae, report of a case with cor triatriatum and pulmonary
sequestration. Am J Cardiol. 1970;26:25-33.
3. Van Mierop LHS. Developmental aspects of tetralogy of Fallot.
Singapore Med J. 1973;14:166-68.
4. Dabizzi RP, Caprioli G, Aiazzi L, et al. Distribution and
anomalies of coronary arteries in tetralogy of Fallot.
Circulation. 1980 ;61:95-102.
5. Kirklin JW, Blackstone EH, Kirklin JK, et al. Surgical results
and protocols in the spectrum of tetralogy of Fallot. Ann Surg
1983;198:251-65.
6. MC Digilio. Genetic basis of tetralogy of Fallot - 2008.
EUROGENE portal. Jan 2009.
7. Starr JP. Tetralogy of Fallot: Yesterday and today. World J
Surg. 2010;34:658-68.
8. Gatzoulis MA, Webb GD, Daubeney PEF, (Ed). Diagnosis and
management of adult congenital heart disease. 2nd edition.
London: Churchill Livingstone; 2011.
9. Wyszynski DF, Graham TP, Correa-Villasenor A (Eds).
Congenital Heart Defects: From Origin to Treatment. Oxford
University Press, New York, 2010.
10. Wood P. Attack Of Deeper Cyanosis And Loss Of Consciousness
(Syncope) In Fallots Tetralogy. Br Heart Journal 1958;20:2826.
11. Guntheroth WG, Morgan BC, Mullins GL, Physiologic Studies
Of Paroxysmal Hyperpnea In Cyanotic Congenital Heart
Disease. Circulation 1965;31: 70-6.
12. Kothari S.S., Mechanism Of Cyanotic Spells In
Tetralogy Of Fallot--The Missing Link?, Intl. Journal Of
Cardiology,1992;37:1-5.
13. Young D, Elbl F. Supraventricular tachycardia as cause of
cyanotic syncopal attacks in tetralogy of Fallot. N Engl J Med.
1971;284:1359-60.
14. Abraham KA. Tetralogy of Fallot in adults. A report on 147
patients. Am J Med. 1979;66:811-6.
15. Siwik ES, Erenberg F, Zahka KG, Goldmuntz E. Tetralogy of
Fallot. In Allen HD, Driscoll DJ, Shaddy RE (Eds). Moss and
Adams Heart Disease in Infants, Children, and Adolescents:
Including the Fetus and Young Adults. Lippincott. Williams
and Wilkins, Baltimore, MD 2008.pp 888-910.
16. Kasar PA, Ravikumar R, Varghese R, et al. Computed
tomographic angiography in tetralogy of Fallot. Asian
Cardiovasc Thorac Ann. 2011;19:324-32.
17. Karl TR. Tetralogy of Fallot: Current surgical perspective. Ann
18. Rao PS. Pulmonary valve in cyanotic heart defects with

pulmonary oligaemia. In Percutaneous Interventions for
Congenital Heart Disease. Sievert H, Qureshi SA, Wilson N,
Hijazi Z (eds). Informa UK Ltd. 2007. 197-200.
19. Alekian BG, Petrosian IuS, Podzolkov VP et al. Catheter
therapy of congenital cardiovascular defects. Vestn Rentgenol
Radiol. 1995;2:16-26.
20. Karl TR, Sano S, Pornviliwan S, et al. Tetralogy of Fallot:
Favorable outcome of nonneonatal transatrial, transpulmonary
repair. Ann Thorac Surg. 1992;54:903-7.
21. Gladman G, McCrindle BW, Williams WG, et al. The modified
Blalock-Taussig shunt: Clinical impact and morbidity in
Fallot's tetralogy in the current era. J Thorac Cardiovasc
Surg.1997;114:25-30.
22. Stewart RD, Backer CL, Young L, et al. Tetralogy of Fallot:
Results of a pulmonary valve-sparing strategy. Ann Thorac
Surg. 2005;80:1431-38.
23. Makaryus AN, Aronov I, Diamond J, et al. Survival to the
age of 52 years in a man with unrepaired tetralogy of Fallot.
24. Hudspeth AS, Cordell AR, Meredith JH, et al. An improved
transatrial approach to the closure of ventricular septal defects.J
Thorac Cardiovasc Surg. 1962 Feb;43:157-65.
25. Murphy JG, Gersh BJ, Mair DD, et al. Long-term outcome in
patients undergoing surgical repair of tetralogy of Fallot. N
Engl J Med. 1993;329:593-99.
26. Nollert G, Fischlein T, Bouterwek S, et al. Long-term survival
in patients with repair of tetralogy of Fallot: 36-year follow-up
of 490 survivors of the first year after surgical repair. J Am Coll
Cardiol. 1997;30:1374-83.
27. Norgaard MA, Lauridsen P, Helvind M, et al. Twenty-to-thirtyseven year follow-up after repair for tetralogy of Fallot. Eur J
28. Harrison DA, Harris L, Siu SC, et al. Sustained ventricular
tachycardia in adult patients late after repair of tetralogy of
Fallot. J Am Coll Cardiol. 1997:30;1368-73.
29. Gatzoulis MA, Clark AL, Cullen S, et al. Right ventricular
diastolic function 15 to 35 years after repair of tetralogy
of Fallot: Restrictive physiology predicts superior exercise
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replacement after correction of Fallots tetralogy. Thorac
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32. Therrien J, Siu SC, McLaughlin PR, et al. Pulmonary valve
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559
C hapter
38
Pulmonary Stenosis
with Interatrial Communication
Vijayalakshmi IB
DefInItIon
Pulmonary stenosis (PS) with reversed interatrial shunt is
called Trilogy of Fallot or Trilogie de Fallot.1 This eponym
has been applied to a triad of pulmonary stenosis, intra-atrial
septal defect and a closed interventricular septum (IVS).
This combination results in right-to-left shunt at the atrial
level causing cyanosis. This syndrome of pulmonary valve
stenosis with patency of the foramen ovale is a distinct
entity though readily confused clinically with the tetralogy
of Fallot (TOF).
HIStorICal revIew
Pulmonary valve stenosis with a patent foramen ovale (PFO)
was described in 1769 by Giovanni Battista Morgagni2 and in
1848, Thomas Peacock3 published Contraction of the Orifice
of the Pulmonary Artery and Communication Between the
Cavities of the Auricles by a Foramen Ovale. In 1950 Joly
et al termed this condition as Fallots Trilogies.1
anatomy
Pulmonary stenosis is usually valvar in nature. Occasionally,
the stenosis can be subvalvar (infundibulum) or supravalvar
(pulmonary artery and its branches).4-7 The right to left shunt
through the interatrial communication is either a PFO or an
ostium secundum atrial septal defect (ASD).4,8-11 It is less
commonly through the ostium primum12 or sinus venosus
ASD.13 Rarely there is anomalous pulmonary venous
connection.14
PatHoPHySIology
The physiological consequences of this pathology of PS with
right-to-left shunt through a ASD or PFO depends on the
degree of stenosis and size of interatrial communication.8,15
The severely cyanosed patients invariably have severe PS
with PFO or small restrictive ASD.
The stenosed pulmonary valve places a tremendous load

on the right side of the heart due to difficulty in expulsion
of blood into the pulmonary artery. This leads to right
ventricular hypertrophy (RVH) and progressive increase
in the systolic pressure. This gradually leads to increase in
the diastolic pressure within the right ventricle (RV) as it is
unable to empty itself completely. The force of the right atrial
contraction increases and this causes a presystolic right to
left shunt at the atrial level. This stretches the margins of the
PFO or increases its patency.16 The volume of unoxygenated
blood shunting from right to left is large enough for visible
cyanosis to be seen. The cyanosis is at first transitory, then
becomes persistent and deepens as the patient grows older.
As the volume of shunt increases, polycythemia appears.10
Subsequently, as the RV fails, tricuspid regurgitation (TR)
occurs and this further decreases the pulmonary blood flow.
Retarded growth and development are consequences of RV
failure that begins in infancy or early childhood.16 The child
is cyanotic, but in congestive heart failure.
ClInICal featureS
The primary symptom is dyspnea on exertion which is mainly
due to the decreased pulmonary blood flow and is usually
present from early life. As the shunting of blood through
the foramen ovale from the right atrium to the left becomes
established, the pulmonary blood flow further diminishes and
hence exertional dyspnea becomes more pronounced. The
exertional dyspnea generally precedes the onset of cyanosis
and is out of proportion to the cyanosis. Cyanosis of varying
degree can present from birth to later in life. Patients with
critical PS present with cyanosis at birth. Sometimes, the
cyanosis can be obvious only during exercise. Patients can
present with easy fatigability or due to a murmur. In the TOF
patients, the cyanosis and dyspnea are directly proportionate
to each other and usually appear in early infancy.10 In the
degree of cyanosis, trilogy of Fallot patients occupy an
intermediate place between TOF and Eisenmenger syndrome.4
The symptoms of giddiness, light-headedness and syncope are
restrictive ASD, except for the conspicuous thrill and systolic

murmur of PS. In patients with RV failure, the murmur is short
and soft and a murmur of TR is audible. Liver enlargement
and pulsations are manifestations of the RVH. Table 1 shows
the differences between Tetralogy and Trilogy of Fallot.
eleCtroCarDIogram
Electrocardiogram is similar to that of severe PS. The right
atrial (RA) enlargement is seen as tall, peaked P waves in
lead 2 and in V1, V2. The right axis deviation and RVH are
the usual findings. In patients with suprasystemic RV systolic
pressure, there is a qR pattern in V1 with tall R waves in the
right and midprecordial leads with deep inversion of T waves
table 1
The differences between tetralogy and trilogy of Fallot.
Tetralogy
Trilogy
1.
Anatomy
Non-restrictive VSD with overriding aorta

with anterocephalad deviation of outlet
outlet septum with infundibular stenosis
Pulmonary valvar stenosis with PFO/

restrictive ASD with right to left shunt with
intact IVS
2.
Cyanosis
Occurs 23 month after birth, all cyanotic by

58 years, even on rest
Usually in late childhood, puberty or

adulthood, mild cyanosis appears on
exertion initially
3.
Spell or squatting
Usual
Unusual
4.
Erythema of tips of fingers

and toes
Absent
Present
5.
JVP Giant a wave
Absent
Present
6.
RV impulse
Absent (quiet precordium)
PSH, powerful and sustained
7.
Presystolic impulse
Absent
Present
8.
Systolic thrill
Absent
Present in the second left ICS
9.
Second heart sound
Single A2
Wide splitting, diminished P2
10.
S4
Not audible
Audible (RV S4)
11.
Murmur
Grade 3/6 ESM in third left ICS, intensity

of murmur decreases with increase in
infundibular stenosis
Grade > 3/6 loud, long ESM beyond

A2 in second left ICS, TR murmur in RVF
12.
Ejection sound
Eddy sounds may be heard
Pulmonary EC may be heard
13.
ECG
P waves normal, RAD,

QRSno notching or slurring
RVHmonophasic R in V1 with sudden
transition in V2, T waves normal
Tall peaked P waves, RAD

(20%extreme RAD)
QRSoccasionally terminal slurring,
Gross RVH with strain pattern with T wave
inversion
14.
Chest X-ray
Boot-shaped heart with RVH, no RAE,

oligemic lung fields, pulmonary bay empty,
right-sided aortic arch in 25%
Oligemic lung fields with cardiomegaly,

RAE, RVH, MPA prominent
38
pulmonary stenosis with interatrial communication
typically related to effort. In these patients, death is usually

from RV failure and less commonly from hypoxia, cerebral
abscess or infective endocarditis.4 Physical under development
coincides with the catabolic effects of right ventricular failure.
The clinical features are cyanosis and clubbing and there
is precordial bulge due to RVH during early childhood.
There is parasternal heave and prominent a waves in the
jugular venous pulse. In patients with RV failure, v wave
may become prominent especially if TR is present. The long
ejection systolic murmur is heard maximal in the pulmonic
area of grade 4-5/6. The pulmonary component (P2) of the
second sound is soft in intensity due to the severe stenosis of
the pulmonary valve. Mild to moderate pulmonary stenosis
with non-restrictive ASD clinically resembles an isolated non-
561
Contd...
cyanotic heart diseases
Contd...
Tetralogy
Trilogy
15.
Cath and RV angiogram
Shows simultaneous opacification of dilated

aorta and small pulmonary arteries, mainly
infundibular stenosis
Dilated RV with dysfunction, valvar

stenosis, poststenotic MPA dilatation
16.
Management
Blalock-Taussig shunt, Intracardiac repair
PBV with or without ASD device closure/

surgery
ASD = Atrial septal defect; EC = ejection click; ECG = Electrocardiogram; ESM = Ejection systolic murmur; ICS = Intercostal space;
IVS = Interventricular septum; JVP = Jugular venous pulse; MPA = Main pulmonary artery; PBV = Pulmonary balloon valvuloplasty;
PFO = Patent foramen ovale; PSH- parasternal heave; RAD = Right axis deviation; RAE = Right atrial enlargement ; RV = Right
ventricle; RVF = Right ventricular failure; RVH = Right ventricular hypertrophy; TR = Tricuspid regurgitation; VSD = Ventricular septal
defect.
with upward convexity of the ST segments and deep S waves

in left precordial leads.16 In patients with true ASD, there is an
rsR or Rsr pattern17 (Figure 1).
CHeSt raDIograPHy
The chest X-ray is similar to that of severe isolated PS. There
is cardiomegaly due to RA and RV enlargement. The main
pulmonary artery is dilated due to poststenotic dilatation. The
chest X-ray in these patients are in an intermediate position
between the small shadows of the pulmonary vessels in TOF
and the very prominently dilated and congested pulmonary
vessels of the Eisenmenger syndrome.4 The lung fields are
oligemic and is more pronounced with RV failure. The RV
apex is not boot-shaped as in TOF as the size of the left
ventricle is not reduced16 and the pulmonary bay is not
empty. On fluoroscopy, rocking boat effect is seen in
the anteroposterior view as first the RA, forming the right
heart border, contracts forcefully and then the hypertrophied
RV, forming the left heart border, contracts. The height
562
of R wave in V1 multiplied by 5 gives the transvalvar

gradient.
eCHoCarDIograPHy
The transthoracic 2D echocardiography (TTE) with continuous
wave Doppler and color flow is adequate for both the anatomic
and physiologic diagnosis. The TEE is similar to that in severe
PS. M-mode shows RVH with thick interventricular septum
(Figure 2). The systolic doming of the thickened pulmonary
valve can be visualized in the parasternal short-axis view.
The continuous Doppler is used to assess the pulmonary
valve gradient (Figure 3A). The subcostal four chamber view
shows interatrial septum bulging towards left atrium with a
PFO or ASD (Figure 3B). The color flow imaging shows the
right-to-left shunt. Also one can assess RVH, RV function
and the severity of TR. The pulmonary annulus, the size of
the ASD and its rims can be measured by TTE. This helps in
selecting the size of the balloon and device for non-surgical
transcatheter management.
Figure 1: Electrocardiogram shows right axis deviation with right atrial and ventricular hypertrophy with rsR pattern in right precordial leads.
38
Figure 2: M-mode shows right ventricle hypertrophy and

hypertrophy of interventricular septum
CarDIaC CatHeterIzatIon anD angIograPHy

Cardiac catheterization and angiography is usually not
done for diagnostic purpose. But it is done for therapeutic
evaluation and interventional therapy for trilogy of Fallot.
On right heart catheterization the RV tracings may show
alternans if there is RV dysfunction. Due to severe TR and
large RA, entering the RV could be difficult with regular right
heart catheters. With Sims catheter, RV can be entered either
with 0.018 straight Terumo or percutaneous transluminal
coronary angioplasty (PTCA) floppy wire. The stenotic
pulmonary valve can be crossed and with Tyshak balloon of
appropriate size, the valve can be dilated. The reduction in
the gradient across the pulmonary valve can be measured by
multitrack catheter passed on the guide wire. If the patient
has ASD of significant size, then in the same sitting, the
device closure can be done. But if there is a stretched PFO
it can be left alone. In one study, 16 children of trilogy of
Fallot were treated with the percutaneous balloon pulmonary
valvuloplasty and device closure of ASD. All of the 16
patients were treated successfully, without any complication.
After therapy, right ventricular systolic pressure decreased
from (81 26) mm Hg to (38 12) mm Hg and systolic
pressure gradient across the pulmonary valve decreased
from (68 24) mm Hg to (15 13) mm Hg immediately.
The ASD diameter was 3 to 16 (10.3 8.4) mm by TTE. The
diameter of the occluder selected was 8 to 20 (12.4 8.2)
mm.18 Interventional therapy for trilogy of Fallot is safe,
easy and effective.
Surgery
Although surgery is the traditional management, it carries higher
morbidity and mortality than catheter-based interventions.
pulmonary stenosis with interatrial communication
Figure 3a: 12 year-old cyanotic boy with anasarca with Hb22.8

gms%, PCV71.5% and SaO248%. Transthoracic echocardiography
showed atrial septal defect (1.6 cm) with right to left shunt with severe
pulmonary stenosis. Continuous wave Doppler showed 102/64 mm
Hg gradient across the pulmonary valve despite right ventricular
dysfunction
Figure 3B: Transthoracic echocardiographic apical four-chamber view

shows giant right atrium (RA) with bulging of interatrial septum towards
left atrium (LA), severe tricuspid regurgitation (TR) with hypertrophied
right ventricle (RV), small atrial septal defect (ASD) with right to left
shunt. LV = Left ventricle
In one Chinese series, in which the surgical results of 42 adults

with this condition were described with one mortality. Surgical
repair involves ASD closure, right ventricle outflow tract
resection, pulmonary valvotomy and transannular patching.19
Chinese surgeons have also described an on-pump beating
heart technique for this operation.20
ConCluSIon
Pulmonary valve stenosis with a right-to-left shunt through
a PFO is accompanied by a conspicuous systolic murmur,
except for the disarmingly soft murmur of pinpoint pulmonary
valve stenosis and RV failure. Mild or intermittent cyanosis
or digital erythema precedes persistent cyanosis. Symptoms
can be appreciable even when cyanosis is mild. Giddiness,
light-headedness and syncope are typically related to effort.
In severe PS with PFO, early balloon valvotomy is indicated.
563
cyanotic heart diseases
564
If PS is progressive, valve is dysplastic, and annulus is very

narrow, then the surgical valvotomy with transannular patch
with surgical closure of ASD is indicated.
The two best physicians of them all Dr. Laughter and
Dr. Sleep.
Gregory Dean Jr.
10.
11.
12.
referenCeS
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2. Morgagni J. Seats and causes of diseases. London, Millar &
Cadell in the Strand and Johnson and Payne in Pater-Noster
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3. Peacock T. Contraction of the orifice of the pulmonary artery
and communication between the cavities of the auricles by the
foramen ovale. Transactions of the Pathological Society of
London. 1848;1:200.
4. Selzer A, Carnes WH, Noble CA Jr, et al. The syndrome of
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8. Roberts WC, Shemin RJ, Kent KM. Frequency and direction
of interatrial shunting in valvular pulmonic stenosis with
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or outflow obstruction. An analysis of 127 patients treated by
valvulotomy. Am Heart J. 1980;99:142-8.
9. Arnett EN, Aisner SC, Lewis KB, et al. Pulmonic valve
stenosis, atrial septal defect and left-to-right interatrial shunting
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Engle MA, Taussig HB. Valvular pulmonic stenosis with
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Ordway NK, Levy 2nd L, Hyman AL, et al. Pulmonary stenosis
with patent foramen ovale. Am Heart J. 1950;40:271-84.
Rudolph AM, Nadas AS, Goodale WT. Intracardiac left-toright shunt with pulmonic stenosis. Am Heart J. 1954;48:80816.
Hardy WE, Gnoj J, Ayres SM, et al. Pulmonic stenosis and
associated atrial septal defects in older patients. Report of three
cases, including one with calcific pulmonic stenosis. Am J
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Neptune WB, Bailey CP, Goldberg H. The surgical correction
of atrial septal defects associated with transposition of the
pulmonary veins. J Thorac Surg. 1953;25:623-34.
De Castro CM, Nelson WP, Jones RC, et al. Pulmonary
stenosis: cyanosis, interatrial communication and inadequate
right ventricular distensibility following pulmonary valvotomy.
Am J Cardiol. 1970;26:540-3.
Perloff JK, Marelli AJ. Pulmonary stenosis with interatrial
communication. In: Perloff JK, Marelli AJ (Eds). In: Clinical
Recognition of Congenital Heart Disease, 6th edition.
Philadelphia PA: Saunders; 2012. pp. 273-82.
Sathpathy M. Pulmonary stenosis with interatrial septal defect.
In: Sathpathy M (Ed). Clinical Diagnosis of Congenital
Heart Disease, Jaypee Brothers Medical Publishers; 2008.
pp. 270-2.
XIE Q,GAO L,WANG Z et. al. Interventional Therapy and
Therapeutic Evaluation for Trilogy of Fallot. Journal of
Applied Clinical Pediatrics. 2006;23: http://en.cnki.com.cn/
Article_en/CJFDTOTAL-SYQK200623009.htm.
Li NF. Surgical treatment of trilogy of Fallot in 42 adults.
Zhonghua Wai Ke Za Zhi. 1993;31:118-9.
Mo A, Lin H, Wen Z, et al. Efficacy and safety of on-pump
beating heart surgery. Ann Thorac Surg. 2008;86:1914-8.
C hapter
39
Pulmonary Atresia with

Ventricular Septal Defect
Anurakti Srivastava, Anil Sivadasan Radha, Girish Warrier
INTRODUCTION
Pulmonary atresia with ventricular septal defect (PA-VSD)
constitutes a group of diverse malformations but lacks a uniform definition and is used interchangeably, albeit wrongly
with Tetralogy of Fallot- pulmonary atresia (TOF-PA).
It is best defined as a group of congenital cardiac
malformations in whom there is lack of luminal continuity
and absence of blood flow from either ventricle and the
pulmonary artery, in a biventricular heart that has an opening
in the interventricular septum. In its severe form, there is either
partial or complete absence of the native pulmonary arteries.1
NOMENCLATURETHE HISTORY
This malformation was initially considered a truncus arteriosus
type IV in the classification by Collett and Edwards. In the
same year, 1949, Manhoff and Howe used the term absence of
the pulmonary artery for the condition, where the pulmonary
blood supply was entirely derived from the systemic arteries.
Based on the embryological considerations, the term absent
sixth aortic arch was used by Stuckey and associates. The term
pseudotruncus was used by Bharati and associates in 1975,
to describe patients with PA-VSD. The term pseudotruncus
was subsequently felt to be inappropriate by Van Praagh and
associates because of its vagueness. The term major aortopulmonary collateral arteries (MAPCA) was first used by
Macartney, Deverall and Scott to differentiate them from the
bronchial arteries.1
PREVALENCE
as the cause of the velo-cardiofacial syndrome, which typically

consists of TOF along with facial and aural anomalies, cleft
palate, and developmental delay. About 10 percent of patients
with 22q11 deletion have PA-VSD.2 Factors such as maternal
insulin dependent diabetes mellitus, phenylketonuria, ingestion
of retinoic acids or trimethadione have been implicated in
increased risk of PA-VSD in the fetus.3
EMBRYOLOGICAL BASIS
The etiology and pathogenesis of the pulmonary circulation
was studied by Kutsche and Van Mierop, who concluded
that in PA-VSD the pulmonary ostium becomes atretic
much earlier in development, shortly after the truncoconal
partitioning but before the closure of the ventricular septum.
On the other hand, in pulmonary atresiaintact ventricular
septum (PA-IVS), pulmonary atresia occurs much later after
the cardiac septation has been completed. This explains why
in PA-IVS blood flow is provided by the ductus arteriosus into
the well developed, main and confluent branch pulmonary
arteries and there are no MAPCA(s), whereas in PA-VSD the
pulmonary circulation is so heterogeneous and highly variable
with the high incidence of MAPCA(s).4,5
MORPHOLOGY
Pulmonary atresia exists when there is either complete
obstruction or absence of the communication normally present
between the cavities of the ventricular mass and the pulmonary
arteries.6
Ventricular Outflow Tract
The lack of uniformity in classifying these patients makes

it difficult to provide precise prevalence and incidence data.
Tetralogy of Fallot (TOF) with pulmonary atresia constitutes
15 to 20 percent of TOF and is known to be associated with
deletions of chromosome 22q11. Such deletions are established
The ventricle terminates blindly against an atretic pulmonary

valve or against imperforate muscle. The obstructive form can
sometimes be produced by an imperforate pulmonary valve.
More usually, the blockage of the pathway is muscular, either
Stenosis of the systemic arterial channels pulmonary

arteries may be hypoplastic.
Interventricular Communication
Figures 1A to C: Anatomy of ventricular outflow tract in pulmonary

atresia-ventricular septal defect (PA-VSD). A. Imperforate pulmonary
valve or valvular atresia; B. Muscular atresia; C. Extreme form
absence of pulmonary trunk
at the entrance to or at the distal end of the subpulmonary

infundibulum. The extreme form is represented by the
absence of all the intrapericardial pulmonary arteries. In
the most common pattern, the muscular outlet septum fuses
directly with the parietal musculature of the right ventricle,
thus obliterating the ventriculo-pulmonary junction. In a
small number of cases, the atresia is found at the mouth of the
muscular infundibulum and the pulmonary valve itself may
then be patent (Figures 1A to C).3,7-9
Pulmonary Artery
The pulmonary trunk is either a vestigial cord or a hypoplastic
funnel-shaped channel that widens as it approaches the
bifurcation. The proximal pulmonary arteries are hypoplastic
and may be discontinuous.7
When the pulmonary valve is imperforate, the pulmonary
trunk is present and patent to the level of the ventriculopulmonary
junction. In many other cases, the pulmonary trunk itself is
atretic. In extreme cases, it is recognisable only as a fibrous
strand. When the right and left pulmonary arteries are present,
usually they are confluent. The right and left pulmonary
arteries can be nonconfluent, but one of them usually retains its
connection to the remnant of the pulmonary trunk.10,11
CALIBER OF CENTRAL Pulmonary artery
566
The caliber of the central pulmonary artery12 is directly related

to:
Amount of blood flow
Connection of ductus or collaterals
Ductus/collaterals connect proximal to the central
pulmonary artery or lobar branches pulmonary artery
is mildly hypoplastic or normal.
Multiple collaterals anastomose more distally at the
segmental or subsegmental levels pulmonary arteries
are more likely to be hypoplastic.
The entire right ventricular output enters the systemic

circulation via the nonrestrictive malaligned ventricular
septal defect (VSD) roofed by the dilated aorta. It can be
perimembranous with a fibrous posteroinferior border or
can extend to be doubly committed or juxta-arterial. It can
have entirely muscular borders, when the posteroinferior
limb of the septomarginal trabeculation fuses with the
ventriculoinfundibular fold. The VSD can become restrictive
or may close because of the accessory tricuspid valve tissue,
in which case the hypertensive ventricle is hypertrophied with
reduced intracavitary volume.9,13
Aorta
The biventricular aorta is dilated and often continues as a
right aortic arch. It is related to the aorta receiving the entire
cardiac output as well as to the inherent medial abnormality.
The incidence of right aortic arch is as high as 50 percent in
cases of TOF-PA.3,13
Collaterals
In PA-VSD, the lungs are perfused by systemic to arterial
collaterals, which are essential for survival. The term collateral
artery refers only to the vessel connecting the aorta with a
pulmonary arterial segment.14 The pulmonary circulation
in PA-VSD is characterized by extreme heterogeneity and
variability in terms of origin of the blood flow, the presence
or absence of the native pulmonary arteries (NPA), the
presence or absence of MAPCA(s) and the distal distribution
of the pulmonary blood flow with frequent arborization
abnormalities. The type of intracardiac malformation is not
predictive of the pulmonary circulation.15,16
A MAPCA is a large tortuous collateral artery, which almost
always arises from the anterior surface of the descending
aorta just beneath the carina or subclavian arteries, loops
independent of the course of the bronchus to the lung and
connects with intrapulmonary arteries at the posterior aspect
of the hilum.12,15
The NPA may be severely hypoplastic, either confluent or
nonconfluent or may be completely absent. They may derive their
blood flow from either the ductus arteriosus, communicating
MAPCA(s) or both.17-20 Rabinovitch and associates21 have
categorized systemic pulmonary collateral arteries into three
types (Figure 2), based on their site of origin as well as the way
they connect to the pulmonary circulation. These are direct
aortopulmonary collaterals, indirect aortopulmonary collaterals
and true bronchial arteries (Table 1).21
39
Table 1
Characteristics of systemic collateral arteries21

Bronchial
Direct aortic branch
Indirect aortic branch
Origin
Aorta, Thoracic branches

of aorta, systemic collateral
arteries
Descending aorta
Descending thoracic aorta, Subclavian

artery, abdominal aorta or its branches,
coronary arteries
Anastomosis
Intrapulmonary
Hilar, additional intrapulmonary
Extrapulmonary; additional
anastomoses to subpleural intra-acinar
arteries
Course
Follow bronchi or spread

over pleural surfaces
Continue as a single vessel followed

by distribution similar to segmental
pulmonary arteries
Variable distribution
Embryological
considerations
Bronchial arteries develop

in the 9th gestational
week, after the paired
intersegmental arteries have
been resorbed. The bronchial
artery branches become
the dominant collateral
blood supply when atresia
develops later in gestation
Originate from the intersegmental

Become prominent later in life
branches of the dorsal aorta, which are
normally present during the 3rd and
4th week of gestation, when looping
and conoseptal alignment occur.
Development of atresia at this time
results in persistence of the connections
between the intrapulmonary arteries
and the local intersegmental arteries
Reasons for
embryological
basis
Large bronchial artery

branches are not coexistent
with direct aortic branches
1. The site of anastomosis is at the

hilum
2. The stenosis at the anastomotic
site probably represents an attempt
at involution of the intersegmental
artery
3. Direct aortic branches may provide
the major blood supply to a lobe or a
segment of a lobe
4. The largest collateral arteries (in
effect, the direct aortic branches) are
associated with the smallest central
pulmonary arteries
Collateral-Pulmonary Artery Anastomosis
Aortic branches are found coexistent

with bronchial artery branches but not
with direct aortic collaterals
Pulmonary Atresia with Ventricular Septal Defect
Characteristic
Table 2
anastomosis:22
Types of the collateral-pulmonary artery

1. END TO END with intrapulmonary arteries.
Peripheral histologic appearance like pulmonary artery
Changes position in relation to bronchi
2. END TO SIDE in hilum of lung (50% patients).
Into a complex manifold including hilar portion of
the pulmonary artery from which inter and intralobar
pulmonary arteries distribute distally; central pulmonary
arteries are filled retrogradely
Sometimes central pulmonary arteries do not
communicate with collaterals
3. END TO SIDE to central pulmonary artery.
4. END TO END with hilar portion of ipsilateral pulmonary
artery.
Comparison of ductus and systemic collateral arteries as sources

of pulmonary blood flow in PA-VSD14
Ductus
Systemic collateral arteries
Widely patent in fetus,

so pulmonary artery size
normal at birth
Stable source of pulmonary

blood flow
Sole precarious source
Multiple
Postnatal ductal narrowing/

closure
Progressive stenosis may make

them inadequate for patient as
he grows
Normal intrapulmonary
distribution and flow
Hyperperfusion of some areas

and hypoperfusion of somepulmonary vascular bed exhibits
pulmonary arterial disease as
well as stasis/thrombosis
Ductus
The pulmonary arteries are supplied primarily, if not
exclusively by a long, narrow, sigmoid shaped ductus
arteriosus i.e. structurally a muscular systemic artery
similar to a systemic arterial collateral with few differences

(Table 2).14 This ductal structure is appropriate for
intrauterine flow, which is directed from the aorta into the
pulmonary artery. It is also termed vertical ductus as it
567
8
i. Type ANPAs are present. Pulmonary blood flow is

supplied by the patent ductus arteriosus (PDA). There are
no MAPCA(s).
ii. Type Bboth NPAs and MAPCA(s) are present.
iii. Type Cthere are no NPAs. The pulmonary circulation
is supplied by MAPCA(s) only (Figures 3A to C).
Somerville Classification15 (Based on Degree of

Development of Central Pulmonary Artery) (Figures 4A to D)
i. Type 1: Complete pulmonary artery development.
ii. Type 2: Pulmonary trunk atretic. Right and left pulmonary
arteries present, but they may be unconnected.
iii. Type 3: Pulmonary trunk and one pulmonary artery
atretic. In the lung without the pulmonary artery, the
intrapulmonary arteries are perfused by systemic arteries.
iv. Type 4: Absence of pulmonary trunk and both pulmonary
arteries. Both lungs are perfused by systemic arteries.
Castaneda and Colleagues (in TOF-PA) (Based on

Anatomy of Pulmonary Circulation)
Figure 2: Types of systemic collateral arteries and their anastomosis
with the pulmonary segments21. SCA = Systemic collateral artery
arises from undersurface of arch and descends vertically

down to supply the pulmonary artery.
To confluent central pulmonary artery (80%). Intrapulmonary arteries of both lungs normal
Nonconfluent pulmonary arteries with U/L ductus.
Lung supplied by ductus has unifocal blood supply and
normal arterial distribution, while contralateral lung has
multifocal blood supply with fragmented pulmonary arterial
distribution (arborization abnormality)
Nonconfluent pulmonary arteries with B/L ductus (rare).3
VARIATIONS
i. Group I: The pulmonary circulation is through the ductus

arteriosus into the native, confluent pulmonary arteries,
Figures 3A to C: Classification of PA-VSD based on pulmonary blood

supply. A. Tye A; B. Type B; C. Type C. APC = Aortopulmonary collateral;
NPA = Native pulmonary artery; PDA = Patent ductus arteriosus.
Sometimes, we find ductus arising from its usual location

opposite the subclavian artery origin which may be because of
the obliteration of the ventricle-pulmonary artery connection
later in gestation and may represent inflammation/ infection as
the implicating process.
CLASSIFICATION
Congenital Heart Surgery and Database Project
Pulmonary atresia-ventricular septal defect (based on pulmonary blood supply)1
Figures 4A to D: Classification of PA-VSD based on development of

the central pulmonary artery. A. Type 1; B. Type 2; C. Type 3; D. Type 4
Classification can be based on either pulmonary circulation or

on intracardiac anatomy.
Based on Pulmonary Circulation
568
Based on Intracardiac Anatomy1

This level of definition defines intracardiac anatomy, the atrioventricular (AV) connection, and the ventriculo-arterial (VA)
connection.
high flow and pressure and prevents changes of excessive

muscularity and intimal hyperplasia. An anastomosis without
a stenosis in a large collateral can lead to severe pulmonary
vascular changes. In most patients, the intra-acinar arteries are
smaller than normal. In patients who have large, surgically
created shunts of long duration, the intra-acinar arteries may
be fewer in number, of greater muscularity and with severe
occlusive changes of intimal hyperplasia. The number of
alveoli is reduced in almost all patients.22-24
Pulmonary arterial disease tends to develop in segments
which are centrally connected and progresses at accelerated
rate. It is termed as pulmonary arterial disease as it can not
be judged how much of the pulmonary vascular resistance
is due to hypertensive vascular disease and how much due
to hypoplasia and stenosis of the distal pulmonary arteries
and collaterals. The quantum of effective pulmonary blood
flow depends on progressive intimal fibroplasia and the long
tortuous course of vessels.22
CLINICAL PRESENTATION
PA-VSD, AV Concordance
PA-VSD, AV concordance, VA concordance: TOF, PA
PA-VSD, AV concordance, VA discordance: transpositon
of great arteries (TGA), VSD, PA
PA-VSD, AV concordance, double outlet right ventricle
(DORV), PA
PA-VSD, AV concordance, double outlet left ventricle
(DOLV), PA
PA-VSD, AV Discordance
PA-VSD, AV discordance, VA concordance: Isolated
ventricular inversion, PA-VSD
PA-VSD, AV discordance, VA discordance: Corrected
TGA, PA-VSD
PA-VSD, AV discordance, DORV, PA
PA-VSD, AV discordance, DOLV, PA
HEMODYNAMICS
Presence of a large non-restrictive VSD ensures equal
biventricular pressures and allows complete mixing of the
systemic and pulmonary venous blood in the aorta. Thus,
relative flow in the systemic or pulmonary circuits depends
on the relative resistances offered by these circuits. The
pulmonary vascular resistance is a complex interplay of the
number of collaterals, their course and blood flow through
them, the extent of intrapulmonary anastomosis and the
presence of areas of narrowing in the collaterals.
The spectrum of presentation ranges from cyanosis evident

after ductal narrowing/closure in a neonate to congestive
cardiac failure in a pink child with increased pulmonary
blood flow through large ductus or MAPCAs. Some children
have balanced circulation and present late with cyanosis and
exertional dyspnea. Digital clubbing and failure to thrive
may be evident. Few children can present due to facial
dysmorphism or features of 22q11 deletion.3,9,11
Most of the children have a quiet precordium unless there
is excessive pulmonary blood flow. As biventricular pressures
are equal, generally there is no right ventricular lift. The first
heart sound is normal, the second heart sound being single
(A2) loud and may be palpable. S3 can be heard if there is
excessive pulmonary blood flow. Sometimes, a vascular
ejection click can be appreciated due to the dilated aortic
root. Loud, localized continuous murmur often is predictive
of a ductus, while widespread continuous murmurs suggest
MAPCAs. Continuous murmurs may not be heard in the
setting of reduced flow through collaterals as well as in the
presence of pulmonary arterial disease.9,13
39
with the main pulmonary artery being present. No

MAPCA(s).
ii. Group II: The pulmonary circulation is through the
ductus arteriosus into the native, confluent pulmonary
arteries, with the main pulmonary artery being absent. No
MAPCA(s).
iii. Group III: The NPAs are very hypoplastic and do not supply
all the bronchopulmonary segments. There are MAPCA(s)
supplying a variable degree of pulmonary parenchyma.
The NPAs receive their blood flow either through a ductus
arteriosus or from communicating MAPCA(s).
iv. Group IV: There are no NPAs, with the entire pulmonary
blood supply provided by MAPCA(s).
INVESTIGATIONS
Electrocardiogram
Electrocardiogram (ECG) shows a right atrial abnormality
and a right ventricular hypertrophy with mean frontal QRS
axis +100 to +180 degrees, in contrast to PA-IVS where there
is left axis deviation.13
Pulmonary Arterial Disease
Chest X-ray
Narrowing at the site of anastomosis with a pulmonary artery

apparently protects the peripheral intra-acinar arteries from
A posteroanterior chest radiograph shows an empty pulmonary

bay due to hypoplastic pulmonary trunk. The heart size and
569
pulmonary vascularity depend on the pulmonary blood flow.

Children with balanced circulation show a normal sized
cardia with apparent normal pulmonary vascularity. Children
with excessive pulmonary blood flow have cardiomegaly
and excessive pulmonary vascularity. Cyanosed children
usually have a normal sized cardiac silhouette with patchy
lung markings depending on collateral supply. Some areas
of lung might be underperfused while some might be
overperfused.3,8,9,13 Rarely, pulmonary atresia and a large
vertical patent ductus arteriosus which, while acting as the
only source of pulmonary blood supply, can compress the left
main bronchus, causing hyperinflation of the left lung.25
Abrupt change in the caliber of aorta or its branches gives

an insight into the origin of the collateral arteries.
Transthoracic echocardiography can serve as a sensi
tive and specific diagnostic test for the detection of aorto
pulmonary collaterals in infants with TOF/PA. The extent
of aortopulmonary collaterals is inversely related to the
diameters of the central pulmonary arteries. The presence
Echocardiography
Detailed echocardiographic evaluation is necessary for
establishment of diagnosis and to plan further management.
In nutshell, echocardiography is helpful:
To see whether pulmonary arteries are confluent
To see pulmonary artery caliber
To ascertain presence of collaterals and delineation of their
origins
To see unusual origins of collaterals
To plan for a roadmap for catheterization and transcatheter
palliation (PDA stenting)
In post procedural assessment
Parasternal long-axis view as well as subcostal views
very well show the dilated aorta over-riding the crest of the
ventricular septum (Figure 5). The ventricular outflow tract
can be profiled in paraternal short axis views as well as in
subcostal views to see a blindly ending muscular infundibulum
(Figure 6). High parasternal and suprasternal views best depict
the ductal and branch pulmonary artery anatomy (Figures 7
to 9). Color flow Doppler helps in diagnosing imperforate
pulmonary valve as well as in assessing the presence of
collateral arteries.26
570
Figure 5: Subcostal view showing a large VSD and over-riding

aorta. IVS = Interventricular septum; LV = Left ventricle; RV = Right
ventricle; VSD = Ventricular septal defect.
Figure 6: Subcostal view showing a blindly ending muscular

infundibulum. IVS = Interventricular septum; LV = Left ventricle; RV
= Right ventricle.
Figure 7: Suprasternal long-axis view showing large vertical ductus

with distal constriction arising from undersurface of aortic arch and
supplying pulmonary arteries arteries (PA).
Computerized Tomography
Diagnostic Cardiac Catheterization and Angiography

Figure 8: Modified suprasternal view for simultaneous imaging of
ductus and the pulmonary artery confluence. LPA = Left pulmonary
artery; RPA = Right pulmonary artery.
Analysis of the pulmonary artery anatomy is the single most

important aspect of diagnostic imaging of patients with PAVSD. Right ventricular (RV) angiogram in frontal view
illustrates blunt right ventricular outflow tract (RVOT) and
pulmonary arteries faintly visualised in a late phase, opacified
through the collaterals (Figures 14A to D). Catheterization
in patients with PA-VSD is directed towards determining
details of the aortopulmonary collateral supply to the lungs
and the size of the true pulmonary arteries.30-32 Accurate
characterization of dual supply by collaterals and true
pulmonary arteries versus single supply by collaterals is
important in planning the surgical approach to be used.33
Cardiac catheterization is aimed to:
Computerized tomography (CT) helps in comprehensive

evaluation of different anatomic structures, including the
heart, pulmonary and systemic thoracic vasculature, lungs,
and abdomen, when evaluating patients with PA-VSD. Ductal
and branch pulmonary artery anatomy can be well delineated
(Figures 10 to 12). Multiplanar and 3D CT reconstruction
images can improve communication of anatomic details
to clinicians (Figure 13). Multi-detector computerized
tomography (MDCT) has proved to be an invaluable
diagnostic and decision-making tool as a compliment to
echocardiography and increasingly as a substitute for invasive
angiography in the management of PA-VSD.29
39
Figure 9: Suprasternal long-axis view with color Doppler showing flow

through large patent ductus arteriosus (PDA) supplying pulmonary
arteries (PA)
of a branch pulmonary artery diameter Z score less than

2.5 or a PDA diameter less than 2 mm is the most sensitive
and specific marker for the presence of one or more collaterals.27
Cases with confluent and good sized pulmonary arteries,
single ductus arteriosus and normal pulmonary venous connec
tions may be considered good candidates for a palliative
procedure without further invasive study.28
Figure 10: Axial CT section showing confluent pulmonary arteries supplied

by ductus. LPA = Left pulmonary artery; RPA = Right pulmonary artery.
571
Figure 13: 3D CT reconstruction delineating ductal anatomy
Figure 11: Sagittal CT section showing large ductus supplying

pulmonary arteries (PA)
ANATOMICAL DELINEATION
Detailed analysis of pulmonary supply
Assess size of NPAs and the extent of its arborization
into lung parenchyma
Type of systemic-pulmonary collateral and its
significance in terms of segmental supply by selective
canulation
Identify degree of intercommunication between various
vascular pathways by selective balloon occlusion34
(Figure 18).
METHODS
Figure 12: VR CT angiogram in a 15 months old child with PA/VSD

showing nonconfluent pulmonary arteries arising from the aorta.
Image Courtsey: Dr Madhav Hegde
572
Determine source (s) of pulmonary blood flow

Delineate size and distribution of true pulmonary arteries
(Figure 15)
Ascertain extent of collateral blood supply to lungs (Figures
16 and 17)
True pulmonary artery pressure and resistance.
1. Retrograde arterial approach is easy. A descending

aortogram in anteroposterior projection gives a non
selective detailing of number and size of collaterals. The
collaterals can then be selectively catheterized and injected
to get an idea of segmental supply.
2. Pulmonary venous wedge angiography is helpful in
delineating true pulmonary artery in levophase especially
if the NPAs are inaccessible (Figure 19).
3. Photographic subtraction of appropriately chosen large film
angiograms can serve to delineate sources of pulmonary
blood flow.35,36
Cardiac Magnetic Resonance Imaging

Gadolinium enhanced three-dimensional magnetic resonance
angiography (Gd-MRA) has been shown to noninvasively
and accurately evaluate various lesions of the vascular
system. Magnetic resonance angiography can delineate all
39
Figures 14A to D: A. angiogram through the vertical duct shows confluent pulmonary arteries with ostial stenosis of left pulmonary artery; B.
Aortic arch angiogram shows multiple aortopulmonary collateral arteries (MAPCAs) supplying both lungs and with non-confluent pulmonary
arteries; C. Descending aorta angiogram shows confluent pulmonary arteries with dual supply to the left lung; D. Selective angiogram shows
Blalock-Taussig (BT) shunt opacifying the confluent pulmonary arteries. AO = Aorta; PA = Pulmonary artery. Image courtsey: Dr IB Vijayalakshmi
sources of pulmonary blood supply in cyanotic congenital

heart disease with pulmonary stenosis and/or atresia as well
as provide accurate assessment of pulmonary artery size for
planning corrective surgery.37 Magnetic resonance imaging
in pulmonary atresia provides an alternative non-invasive
method of obtaining much of the anatomical information
required to plan surgical treatment and should reduce the need
for invasive angiography in these patients, besides depiction
of the pulmonary arterial anatomy.38
Cardiovascular magnetic resonance (CMR) may also
provide hemodynamic information by obtaining additional
velocity-encoded phase-contrast cine sequences. In patients
with pulmonary atresia, flow volume measurements in the
ascending aorta and in each pulmonary vein can be used to
estimate the pulmonary to systemic blood flow ratio (QP/QS

= QPV/(QAO-QPV)) and the amount of blood flow to each
lung. The contribution of a PDA or large aortopulmonary
collateral to the pulmonary blood supply may be assessed, but
investigation of all aortopulmonary collaterals would be tedious
and imprecise if they are small. With optimisation of current
CMR techniques for imaging neonates, it should be possible to
measure flow volumes with sufficient accuracy in vessels larger
than 2 mm diameter. Contrast-enhanced magnetic resonance
angiography (CE-MRA) is a useful diagnostic tool in clinical
routine for the preoperative evaluation of the morphology of
the pulmonary arteries and pulmonary circulation in neonates
with pulmonary atresia. In most cases additional diagnostic
cardiac catheterization can be avoided.39
573
574
Figure 15: Pulmonary artery angiography of native pulmonary arteries

supplied by a vertical ductus. LPA = Left pulmonary artery; RPA =
Right pulmonary artery.
Figure 16: Angiography through injection in left subclavian artery

showing an indirect aortic collateral
Figure 17: Aortic root angiogram in left anterior oblique projection

showing pulmonary artery originating from coronary artery. LMCA =
Left main coronary artery; MPA = Main pulmonary artery.
Figure 18: Balloon occlusion to facilitate delineation of coronary to

pulmonary artery supply. LMCA = Left main coronary artery. MPA =
Main pulmonary artery.
PRENATAL DIAGNOSIS
MANAGEMENT
Pulmonary atresia-ventricular septal defect can be diagnosed

by fetal echocardiography with a high degree of accuracy.
However, it can be difficult to determine the morphology
of the central pulmonary arteries and to locate the source of
pulmonary blood supply.40
Pulmonary atresia-ventricular septal defect remains one of

the most challenging groups to manage. The quest for optimal
management of this complex anomaly is, as yet, an ongoing
process. The treatment of PA-VSD has been largely determined
by the morphology of the pulmonary circulation (Figure 20).
Systemic-pulmonary Shunts
Patent Ductus Arteriosus Stenting

Figure 19: Pulmonary venous wedge angiography showing opacification
of native pulmonary arteries in levophase. LPA = Left pulmonary artery
Patent ductus arteriosus stenting is an attractive alternative

to surgical palliative shunt operations. With the use of the
current coronary stents and hardware, it is now feasible to
stent most ducts, even though there is considerable variability
in their morphology and location. The procedure is often
done on children on prostaglandin therapy, which needs
to be discontinued at the start of the procedure for stent
stability. The access is often femoral, but axillary, brachial
and carotid may be required, when the duct is vertical. The
procedure is usually accomplished with a 4 to 5 French
access and the current dictum is to stent the whole length of
the duct and to achieve good apposition with the ductal wall
(Figure 21). The patients should be on close follow up and on
antiplatelet therapy. The complications are many, like acute
stent thrombosis, stent migration, bleeding and hemodynamic
instability during procedure, differential perfusion and
pulmonary overcirculation.45-49
Neonatal shunting regimen (modified BT shunt), without

MAPCA translocation, for patients with PA-VSD and
MAPCAs, provides encouraging results with excellent early
survival.42 The initial surgical creation of an aortopulmonary
window (Mee Shunt or the Australian Shunt) in carefully
selected patients can increase the size of the true pulmonary
arteries, making these patients better candidates for eventual
intracardiac repair.43 These patients are to be rigorously
followed up as the pulmonary artery sizes can go up rapidly
and cause overcirculation and can result in pulmonary arterial
disease.23,24 They have to be converted to the definitive surgery
as soon as possible. Pulmonary artery rehabilitation allows
complete repair in the majority of patients in dedicated centers.44
39
Unifocalization
Figure 20: Plan for management of PA-VSD. Type A- Restoration of

neonatal pulmonary blood flow by systemic to pulmonary (S-P) shunt
or patent ductus arteriosus (PDA) stenting followed by intracardiac
repair (ICR). They can go for neonatal ICR, if feasible. Type B and
C- Treatment strategy is individualized and involves unifocalization
procedures, establishing ventricle-pulmonary artery continuity and
closure of ventricular septal defect. Cases where biventricular repair
is not feasible, one can follow the usual strategy for a single ventricle
pathway in suitable patients
Pulmonary Artery Rehabilitation

A strategy aiming at the development of native pulmonary arteries
and a biventricular repair is feasible in most cases and should
be done early in life, since long term future of true pulmonary
arteries may possibly be better than flow through the collaterals.41
The unifocalization procedures are designed to improve

the arborization pattern of the central pulmonary arteries.
Systemic collateral arteries are essentially arterial conduits
connecting the systemic circulation to the true pulmonary
arterial segments. This allows their use for the purposes
of increasing pulmonary arterial runoff from the central
pulmonary arteries. Systemic collateral arteries that connect
freely with the central pulmonary arteries (communicating)
can be interrupted, whereas those that do not have
unrestricted connections with the central pulmonary arteries
(non-communicating) must be detached from their origin,
mobilized and connected surgically to the central pulmonary
arteries or their branches.
Pulmonary reperfusion injury is common after the
unifocalization procedure. Severity of MAPCA stenosis and
bilateral unifocalization are associated with the development
of reperfusion injury.42
575
8
via anastomosis of collaterals to other collaterals and to the

native pulmonary arteries.61
Complete Repair
Figure 21: Aortic injection showing coronary stent in position

across the vertical ductus into pulmonary artery
It involves establishing continuity between ventricle and

pulmonary arterial confluence along with closure of VSD.
If main pulmonary artery is present, repair can usually be
performed by opening the atretic segment and performing a
reconstruction with a transannular patch, avoiding a conduit,
not unlike a standard tetralogy repair. Even in the presence
of discontinuity between the right and left pulmonary artery,
establishment of a pulmonary artery confluence by direct
anastomosis can be achieved. In recent years some groups,
have increasingly favored a primary neonatal intracardiac
repair.
Ventricular Septal Defect Closure

Multistaged
A staged surgical approach yields low overall mortality and
acceptable hemodynamics after complete repair.50
A different type of strategy using two stage procedure
with stage one including left major aortopulmonary collateral
unifocalization and modified Blalock-Taussig shunt from
left posterolateral thoracotomy; stage two comprising right
unifocalization, ligation of the shunt, followed by VSD
closure and RVOT reconstruction can be effective with good
outcome, thus offering an alternative surgical approach in the
treatment of PA-VSD and MAPCAs.51
The Clamshell approach in complex TOF/PA provides
simultaneous exposure of bilateral central and peripheral
pulmonary artery lesions and intracardiac pathologic
conditions. This procedure appears safe and may decrease the
number of operations required to complete repair of TOF/PA
in selected patients.52
Single Stage
576
In the earlier period, patients with PA-VSD were treated with

conventional multistage procedure. Previously published
data showed that multistage procedure required a median of
three procedures (range 2 6) before complete repair. A onestage that completes unifocalization and repair from a midline
sternotomy approach reduces the number of operations
and hospitalization and hence may be more cost effective
than multistaged procedures.53-58 Final correction can be
accomplished in early infancy with acceptable morbidity and
mortality. The initiation of normothermic cardiopulmonary
bypass greatly facilitates dissection of collaterals and prevents
hypoxemia.59 Single stage complex unifocalization early in
life, preferably by 6 months of age, with maximal use of
native tissue in the reconstruction yield excellent functional
results,60 with emphasis on native tissue-to-tissue connections
Postoperative right ventricular systolic pressure (RVSP) is

a marker for whether VSD closure can be physiologically
tolerated. If the VSD is closed and there is subsequent
suprasystemic RV pressure, morbidity and mortality are high.
Preoperative anatomic evaluation has been used to determine,
which patients will have a successful complete repair.
Data utilized are the total number of incorporated pulmonary
segments or a pulmonary segment artery ratio (PSAR) after
unifocalization. More recently, a combined area index for
all MAPCAs and the central pulmonary artery, i.e. total
neopulmonary artery index (TNPAI) has been suggested and
seems to be promising.62
But preoperative anatomic findings have not always
predicted postoperative functionality.
A functional measurement of pulmonary vascular perform
ance may be more predictive of post reconstruction pressures.
Reddy et al described an intraoperative pulmonary blood
flow study that measured mean pulmonary artery pressure
simultaneous to pumping blood flow through the unifocalized
pulmonary arteries at a cardiac index of 2.5 L/min per m2. A
mean pulmonary artery pressure less than 30 mm Hg was
thought to allow successful VSD closure at a reasonable
RV pressure. An intraoperative pulmonary blood flow study
is an opportunity to obtain data on the functionality of the
entire pulmonary vasculature once it has been unifocalized
but before closing the VSD. It offers the possibility for more
refined decision-making, regarding the appropriateness
of VSD closure.63 The integrated approach to total repair
of pulmonary atresia, VSD and major aortopulmonary
collaterals by preoperative calculation of total neopulmonary
arterial index, RVOT reconstruction (when required) and
intraoperative flow study may lead to optimal results.64
The VSD can be closed with fenestration if RVSP is high.
The fenestration can be tackled later by transcatheter
means.
TECHNICAL CONSIDERATIONS
FUNCTIONAL SINGLE VENTRICLE

In selected patients with functional single ventricles and
MAPCAs, the pulmonary vascular bed can be reconstructed
sufficiently to allow for cavopulmonary connections. Venous
flow to the pulmonary vasculature decreases cardiac volume
load and is likely to increase life expectancy and quality of life
for these patients.71
OUTCOME
The outcomes are negatively affected by neonatal age and
low body weight and positively affected by simultaneous or
staged ventricular septal defect closure. Finally, chromosome
22q11 deletion remains an independent variable affecting
survival.72
1. PDA stenting.
2. Coil embolization of MAPCAs in lung segments with dual
supply.
3. Balloon dilatation/ stenting of stenosed pulmonary arteries/
MAPCAs.
4. VSD closure of fenestration.
5. Stenting of stenosed conduits.
Conclusion
Pulmonary atresia with ventricular septal defect and
MAPCAs is a complex and rare lesion in which considerable
morphologic variability exists regarding the sources of
pulmonary blood flow. The therapeutic approaches have
included unifocalization, shunting, coiling of collateral
vessels, and heart/lung transplantation. The results have
been variable and frustrating. An individualized approach
based on the morphology of the pulmonary arterial supply
has a low rate of reoperation and mortality. As there is further
advances in genetic understanding and technology, there is
considerable promise for development of future therapies.
39
1. Conduits: The integrity of the pulmonary vascular bed is a

major issue in the management of pulmonary atresia with
MAPCAs. Most staged approaches use circumferential
nonviable conduits in the central and peripheral
pulmonary circulation, which limits growth potential and
the ability to perform complete repair in early infancy.
Aggressive and creative reconstructive techniques to
maximize native tissue-to-tissue connections and avoid
nonviable conduits has shown better results.65 Although
homografts are seen to be the gold standard for conduits
in the right ventricle to pulmonary artery (RV-PA)
position, they too are affected by structural degeneration.
Lately, there have been reports of tissue engineering to
grow sheets of pluripotent cells, which can then convert
to pulmonary arterial tissue. However these are still in
the experimental stage. There has also been interest in
providing viable scaffolding for new overgrowth of native
tissue. Once again, these are still to be evaluated for their
use in patients.
2. Right ventricular decompression: Important questions must
be asked regarding the long-term behavior of conduits and
anastomoses to the pulmonary arteries and regarding the
fate of the pulmonary arterioles. Although the limitations
of prosthetic conduits of all types are well understood, of
greater concern is the adequacy of the right ventricular
decompression after complete intracardiac repair.
Persistent stenosis at numerous sites of the reconstructed
pulmonary vasculature often results in less than ideal peak
right to left ventricular systolic ratios. In addition, there
is a distinct possibility of pulmonary vascular obstructive
disease affecting in variable degree the different pulmonary
arterial segments.66-70
SUMMARY OF TRANSCATHETER PROCEDURES

IN Pulmonary atresia with ventricular
septal defect
But science is the collection of nature's answers.

Sir Gavin de Beer
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579
C hapter
40
Pulmonary Atresia with Intact

Ventricular Septum
Marhisham Che Mood, Mazeni Alwi
INTRODUCTION
In a congenital cardiac malformation where there is a combination of major lesions, pulmonary atresia features commonly. This may be hearts with two-ventricle physiology such as
tetralogy of Fallot with pulmonary atresia, transposition of
great artery with ventricular septal defect and pulmonary atresia, or those with single ventricle physiology such as tricuspid
atresia, and those in association with atrial isomerism.
Pulmonary atresia with intact ventricular septum (PAIVS)
denotes an isolated abnormality of the right ventricular outflow
tract, i.e. complete obstruction of forward flow from the right
ventricle into the pulmonary arteries. However, the range of
pathology embraced by this diagnosis, its management and
long-term outcome are far from simple that the designation
tends to suggest. While echocardiography allows accurate
diagnosis of this congenital lesion even in fetal life,
angiography remains an important imaging technique to fully
describe the anatomic details. Even with advances in cardiac
surgery, interventional techniques and intensive care unit
(ICU) care today, PAIVS remains a management challenge to
the team that dedicates itself to the care of infants and children
with congenital heart disease (CHD).
Incidence
From the various hospital data, PAIVS makes up from 0.71 to
2.5 percent of children with CHD.1 At the National Heart Institute, Kuala Lumpur, from 2000 to 2010 PAIVS makes up 1.1
percent of all new cases seen annually. Accurate data on the inci
dence of this malformation in the population is scant. The Baltimore Washington Infant study reported an incidence of 8.1 per
100,000 live births for the period 1981 to 1989.2 In the modern
era, the United Kingdom (UK) and Ireland Collaborative Study
on PAIVS was a comprehensive population based study on this
disease that provides valuable data on the incidence, morphologic details, the various management strategies and outcome.3
The incidence of this malformation over a 5 year study period

was 4.5 per 100,000 live births.
From our own hospital data, right heart hypoplasiaa
great part of which falls under the spectrum of PAIVS
is more common than hypoplasia of the left heart, which
encompasses the variants of hypoplastic left heart syndrome
and some neonates with critical aortic stenosis in the setting of
a small left ventricle. This appears to be the shared experience
of other large centers in Asia. Whether this is a reflection of
the true incidence in the population remains to be validated in
a well-conducted population-based study.
However, the incidence of PAIVS in modern population
based studies must be interpreted in light of the impact that
fetal echocardiography service has made. This is a diagnosis
that can be made readily in fetal life and it is one of the
commoner causes for termination.4 From the same UK and
Ireland population-based study, 86 fetal diagnosis were made
at a mean of 22 weeks gestation, leading to 53 terminations
(61%).
MORPHOLOGY
Right Ventricle
Although the designation of the disease suggests an anomaly
primarily of the right heart outflow, PAIVS generally
involves other structures of the right heart and in a small,
but significant subgroup of patients, the coronary arterial
circulation as well. There is a remarkable morphologic
heterogeneity in PAIVS particularly with regard to the right
ventricle (RV) and right ventricular outflow tract (RVOT).
This morphologic variation represents a continuum from a
near-normal RV to one where there is very severe hypoplasia
of the RV,5-10 and somewhat outside of this continuum are
those with very severe tricuspid regurgitation (TR) due to
associated severe Ebsteins anomaly, with thinned out and
markedly dilated right ventricle.11
Qualitative and Quantitative Evaluation, Classification
Membranous Atresia, Tripartite RV, Mild RV Hypoplasia

At one end of this spectrum are hearts where the RV is
near normal in size and morphology. The inlet, trabecular
and infundibular components are well developed and the
pathologic abnormality is a thin membranous imperforate
valve (Figures 1A and B). This can perhaps be considered
40
Pulmonary Atresia with Intact Ventricular Septum
Because of the diversity of RV morphology and size, some

sort of classification and quantitative assessment would be
useful in understanding the nature of the disease, planning
its management and counseling parents in regard to longterm prognosis. Beyond the earlier, simplistic classification
of the RV size as small or large, De Levals morphologic
classification into tripartite, bipartite and unipartite RV
according to the number of parts of the RV not obliterated
by muscular overgrowth remains a useful guide in describing
the RV and subsequent management.9 For a more quantitative
assessment of the RV size, the diameter of the tricuspid valve
(TV) normalized to body surface areathe Z scorehas been
advocated by the Congenital Heart Surgeons Society (CHSS).12
However the normogram used is based on Rowlatts 'normal'
data obtained from postmortem measurement of formalin fixed
specimens.13 The UK and Ireland collaborative study used the
normograms based on echocardiographic data of 125 normal
children by Daubeney.14 For a given TV diameter, there is a
wide discrepancy between the Z score values derived from
the 2 normograms, the former understandably giving less
marked departure from the normal values due to shrinkage of
formalin-fixed specimens. The tricuspid/mitral annulus ratio
and RV inlet length Z scores are also helpful in giving an idea
of the RV size.15,16
the extreme end of the critically stenotic pulmonary valve.

Nevertheless the RV size is seldom 'normal' as hypertrophy
of the RV myocardium causes mild hypoplasia and reduction
of the RV cavity.1,17-19 In this group of patients the TV is
often normal in appearance although mild dysplasia with
regurgitation is not uncommon. Its dimension as measured by
annulus size is smaller than normal and the TV/mitral valve
annulus ratio is > 0.75. In this group of patients the TV Z-score
is > 2.0 as calculated by the normogram by Rowlatt.13 In
some patients the trabeculations in the RV infundibulum are
prominent and may cause dynamic obstruction once the valvar
atresia is abolished.20 Occasionally, there is fixed subvalvar
muscular obstruction caused by abnormal muscle bundles that
will require additional intervention in the form of surgery
(Figure 1C).
Usually, in hearts with mild RV hypoplasia and membranous
atresia the coronary circulation is normal, i.e. there is no
persistence of RV-coronary sinusoidal communication or
RV-coronary arterial connections. However, there are few
instances where these connections exist in hearts with this
very favourable anatomy. From the UK and Eire collaborative
study, this subgroup make up 58.7 percent of the entire cohort
and our own observation is very much in accordance with
this.3
Muscular Atresia, Very Severe RV Hypoplasia (Unipartite)

At the other end of this continuum is the RV which is severely
hypoplastic on account of complete or near obliteration of the
infundibulum by muscle, i.e. 'muscular' atresia.9,17,21,22 Often,
what appears to be complete obliteration of the infundibulum,
upon probing with a catheter at angiography may reveal a tiny
slit reaching up to the valve annulus (Figure 2). However it is
doubtful if this can be refashioned into a functioning RVOT.
Figures 1A to C: Membranous atresia with well-developed right ventricle (RV): A. RV angiography in anteroposterior projection showing inlet,
apical trabecular and infundibular components of the RV. The infundibulum (INF) is widely patent, but ends blindly at the valve. A dilated right
ventricle is opacified by moderate tricuspid regurgitation; B. Simultaneous injection in the infundibulum and aorta opposite the patent ductus
arteriosus (PDA) in lateral projection showing very thin, membraneous valve. Arrow shows well-developed main pulmonary artery sinuses
'cupping' over the membranous valve and annulus; C. Fixed stenosis due to thick muscle bundles in the subvalvar area (arrow), resulting in
failure of RV decompression. The atretic valve has been opened with radiofrequency valvotomy and balloon dilatation
581
Figures 2A and B: Muscular atresia with generally hypoplastic right

ventricle (RV): A. RV angiogram in anteroposterior (AP) projection
showing mainly an inlet component of the RV. The outlet component
is merely a slit that extends towards where the valve annulus should
normally be (thin arrow). An RV-coronary connection with stenosis is
seen (broken arrow); B. RV angiogram in AP projection of another
patient with muscular atresia with severely hypoplastic RV. 2 large
RV-coronary connections are seen (arrows)
Figures 3A and B: Membranous atresia with moderate right ventricle

(RV) hypoplasia (intermediate): A. RV angiogram in anteroposterior
projection showing an overall small RV, but three components of the RV
are present. The apical trabecular component is the least developed.
Numerous minor RV-coronaries connections are present; B. Bipartite
RV- the inlet and outlet components are well-developed, but the apical
trabecular component is virtually obliterated by muscles except for
some intertrabecular recesses. There is mild tricuspid regurgitation
The trabecular component, except for slits of inter-trabecular

spaces is also virtually obliterated by muscle, leaving a severely
attenuated inlet part of the RV guarded by a TV, which has a
hypoplastic annulus. These are hearts whose RV is unlikely
to be able to support the pulmonary circulation independently,
hence destined for single ventricle management pathway. This
subgroup made up 7.7 percent of the UK and Eire collaborative
study3 whereas it appeared to make up a far higher proportion
in one hospital based study.23
There is a strong correlation between muscular atresia of
the infundibulum and severe RV hypoplasia with the presence
of major RVcoronary arterial connections. Some of these
are associated with major obstructions and interruptions of the
proximal coronary arteries, making the coronary circulation
RV dependent (Figures 2A and B).24-26
Minor connections < 2 mm are not uncommon, but ectatic

connections may also be present. In our series of 143 patients,
25.9 percent were categorized as those with 'intermediate'
subgroup or having bipartite RV.27 With adequate opening
of the atretic valve, the well-developed infundibulum allows
unobstructed flow into the pulmonary arteries.
Moderate RV Hypoplasia, Bipartite RV, Membranous

Atresia (Intermediate)
582
Between the two ends of the continuum are gradations of

RV cavitary hypoplasia. In some of these patients, the three
components of the RV are moderately hypoplastic due
to muscular overgrowth significantly reducing the apical
trabecular component and the infundibulum. However, we also
observe that in others only the apical trabecular component is
virtually obliterated save for slits of inter-trabecular spaces
whereas the inlet and the infundibulum are reasonably well
developed, i.e. a bipartite RV. The infundibulum ends blindly
with membranous atresia (Figures 3A and B). We term this
group of patients as intermediate RV. The TV Z score may
not be as satisfactory as those with favourable anatomy, giving
values between 2.0 to 5.0 and, so are the other values of RV
dimensions such as inlet length and TV/mitral valve annulus
ratio. The occurrence of RV-coronary arterial connections
in this subgroup also lies somewhat in between the two.
Thinned and Dilated RV, Ebsteins Anomaly or

Dysplastic Tricuspid Valve
Somewhat outside this continuum of RV morphology from
near normal RV to the severely hypoplastic, unipartite RV
are the rare patients with PAIVS in association with severe
Ebsteins anomaly or dysplasia of the TV. The RA and
atrialized RV are markedly dilated giving rise to a 'wall to
wall' heart. The remaining part of RV and infundibulum
are also markedly thinned and dilated, ending blindly in
an atretic pulmonary valve with a small annulus. This may
account for up to one-sixth of patients with PAIVS.11 In the
UK and Eire collaborative study this made up 5.4 percent.3
RV-coronary arterial connections are virtually unknown in
this subgroup.
Right Atrium, Right Ventricle and Tricuspid Valve

The tricuspid valve too often exhibits a range of abnormalities
from the severely stenotic valve with very small annulus
to the severely dysplastic valve or frank Ebsteins anomaly
causing severe regurgitation.5 Even when the valve apparatus
appears normal, a mild degree of TR is often seen due to the
high RV pressure.
The RA is often mildly dilated in the presence of a
competent TV due to poor RV compliance. When there is
severe TR due to dysplastic valve or Ebsteins anomaly, the
RA will be markedly dilated.
Patent Ductus Arteriosus, Pulmonary Arteries

and Pulmonary Valve
Coronaries Arteries
A peculiar feature of PAIVS is its association with
ventriculo- coronary connections between the RV and
subepidcardial coronary arteries.24-26 These may be major
fistulous communications with ectatic coronary arteries
or minor communications. Reports on the incidence of
ventriculo- coronary connection vary greatly. Giglia in 1992
reported an incidence of about one third,30 whereas Calder
reported 60 percent incidence in a postmortem series.31 The
UK and Ireland collaborative study reported major fistulae
in 33 patients and minor in 28 from a cohort of 183 patients,
giving total incidence of 45.8 percent.3 Minor connections
were defined as slight filling of non-dilated coronary
arteries with RV angiogram whereas 'major' describes
prominent filling of one or more, usually dilated, coronary
arteries with retrograde filling of the aorta. A phenomenon
associated with major ventriculo-coronary connections is
the RV-dependent coronary circulation (RVDCC). This is
due to coronary arterial interruption, absent aortocoronary
connection or unequivocal stenosis of one or more of the
coronary arteries.12,17,25,32-34 Markedly ectatic coronary
arteries are also considered in this category by many as
RV decompression would result in major coronary steal
through the ectatic vessels to the RV. Modern angiography
and catheter interventions afford some insight into this.
In our limited experience, given that major RV-coronary
connections are very uncommon in those with membranous
atresia (and hence bipartite or tripartite RV) as long as
there is no RVDCC due to obstruction or interruption,
RV decompression causes these major connections to
immediately disappear with no untoward ischaemic events
taking place (Figures 5A and B).
Major ventriculo-coronary connections are generally seen
in patients with diminutive RV cavity and muscular atresia
of the infundibulum whose RV is categorized as 'unipartite'.
The tricuspid valve is often competent and the RV severely
hypertensive. From the CHSS study a more negative tricuspid
Z score correlated with the presence of these connections.12
However major ventriculo-coronary connections may also
be present in patients with less severe RV hypoplasia where
the infundibulum is patent and the atresia limited to the valvar
level (Figure 5C).
Such major ventriculo-coronary connections in the
setting of a hypertensive RV predispose to coronary arterial
obstructive lesions, leading to ischaemia and infarction later
in life or with sudden RV decompression procedures in the
neonatal period.1
The patent ductus arteriosus (PDA) is almost always present

providing the sole source of pulmonary blood flow. Hence,
PAIVS is generally a duct-dependent cyanotic heart disease.
However in rare cases the pulmonary blood supply is by major
aortopulmonary collaterals. The PDA morphology is often
nearly similar to isolated PDA where it is short and arises from
the proximal descending aorta, inserting onto the dome of the
main pulmonary artery (MPA). However, not uncommonly the
PDA resembles that of other cyanotic CHD where it arises more
proximally from underneath the aortic arch, often long and may
be tortuous in this configuration and inserts onto the proximal
part of the left pulmonary artery (LPA) with the potential of
causing LPA stenosis following ductal constriction.28,29
In hearts with mild RV hypoplasia, the main and branch
pulmonary arteries are often mildly hypoplastic or near- normal
in dimensions, with well-developed sinuses 'cupping' over the
membranous valve with near-normal annulus size (Figure1B).
In those with more severe RV hypoplasia especially of the
RVOT, the annulus is small and the valve plate is thick and
non-doming. The pulmonary root and sinuses are not as well
developed (Figure 4).
In hearts with 'muscular' atresia of the infundibulum, the
pulmonary root and annulus may be severely hypoplastic,
but nevertheless the branch pulmonary arteries tend to be
confluent and fairly well developed.
40
CLINICAL PRESENTATION AND FINDINGS

Figure 4: Simultaneous angiogram of right ventricular outflow tract
and descending aorta opposite the patent ductus arteriosus in lateral
projection showing well-developed infundibulum, but thick valve plate
(arrow) and poorly developed main pulmonary artery sinuses
The pulmonary circulation in PAIVS is ductus dependent,

except in the rare cases where systemic-to-pulmonary
collateral arteries supply the pulmonary blood flow. Hence,
583
Figures 5A to C: Right ventricle (RV)-coronary connections: A. A major communication to the right coronary artery (RCA). A mild narrowing is
noted (arrow), but the entire RCA and aortic root is opacified; B. Communication to the left coronary artery. A severe stenosis is seen (broken
arrow) distal to the major branches. It is assumed that the left coronary is not RV dependent as the major branches are perfused antegradely
from the aorta; C. A major communication to the RCA is seen (thick arrow) with no obvious stenosis and numerous minor communications.
Bipartite RV with a well-developed infundibulum, but the apical trabecular component is virtually obliterated
the presentation of infants with this disease correlates with

constriction and closure of the ductus arteriosus, which
generally takes place in the neonatal period. Cyanosis is
the most common presentation. Occasionally, especially in
communities with limited access to medical care, these infants
may present in a critical state with low output and acidosis
consequent to severe hypoxemia.
As fetal cardiac service is increasingly becoming a
norm, fetal diagnosis of PAIVS allows early transfer to
specialized cardiology unit, minimizing the problems related
to late diagnosis.14 Management plan can also be formulated
antenatally with the interventional and surgical team. Infants
with PAIVS in association with severe Ebsteins anomaly and
wall-to-wall heart may present with severe profound hypoxemia
that respond poorly to prostaglandin as the compressed lungs
may be underdeveloped and hypoplastic.35-37
As with many other cyanotic heart disease presenting in the
neonatal period, physical signs are generally inconspicuous
apart from cyanosis. The murmur from the ductus arteriosus
may not be readily audible in all patients. The presence of
significant TR may provide additional signs such as an
enlarged liver and a high pitched pansystolic murmur over the
lower left sternal edge.
Chest X-ray
Features that may suggest the diagnosis of PAIVS are right
atrial enlargement in cases where there is significant TR,
and an oligaemic lung fields. This however may be difficult
to distinguish from normal in the neonate. The appearance
of wall-to-wall heart, a feature of severe Ebsteins anomaly,
should also raise the possibility of coexisting true, anatomic
pulmonary atresia (Figure 6).
INVESTIGATIONS
Electrocardiogram
584
The Electrocardiogram (ECG) in PAIVS characteristically

displays a QRS axis that is less rightward than normal, i.e.
between 30 to 90, and adult precordial pattern rather
than the usual right ventricular hypertrophy.5 The tall peaked
P-waves of right atrial enlargement may be present.
Figure 6: Postero-anterior chest radiograph showing a 'wall to wall'

heart in a neonate with PAIVS in association with severe Ebsteins
malformation of the tricuspid valve
Imaging and HemodynamicsEchocardiography,

Echocardiography
The diagnosis of PAIVS can be readily made by
echocardiography.38-40 Except for hearts where the RV is
nearly normal in size and appearance, the features of a
hypertrophied RV with reduced cavity guarded by a small
tricuspid valve on the 4-chamber view are immediately
striking and Doppler evaluation of the pulmonary flow
confirms the diagnosis of absence of forward flow from the
RV occasioned by complete obstruction. However, much
more than confirmation of diagnosis, echocardiographic
examination should be performed methodically to fully
describe the morphology and derive some quantitative data
for the initial plan of management.10
First and foremost, the nature of the outlet atresia should
be determined, whether it is membranous atresia with patent
infundibulum, or the entire infundibulum is obliterated by
muscle ('muscular atresia'). If it is membranous atresia,
evaluation about the size of the infundibulum should be
made and whether prominent muscle bundles are present in
subvalvar area which may result in incomplete abolition of
obstruction following RV decompression procedures.
The RV morphology should also be described and
categorized whether the partsinlet, apical-trabecular and
outletare present, well developed or otherwise obliterated
with muscle. Unipartite RV is where the RV cavity is severely
Figures 7A and B: EchocardiographyA. Apical four-chamber view

of a patient with PAIVS. The tricuspid valve annulus is small (8 mm)
compared to the mitral valve (14 mm). The apical trabecular component
is attenuated. The right atrium is dilated with the atrial septum bowing
to the left. B. Color Doppler showing severe tricuspid regurgitation
40
The wide anatomic spectrum of PAIVS, embracing hearts

whose RV is near-normal to those with severe RV hypoplasia,
which is unlikely to be functional as an independent pump
for the right heart circulation means that the management
strategy will be radically different from one subgroup to the
other, i.e. two-ventricle pathway with excellent medium term
outcome for patients with favourable morphology and the
single ventricle pathway with its attendant late morbidities
and attrition for patients at the other end of the anatomic
spectrum. Hence, merely confirming the diagnosis, whilst not
difficult, is insufficient. Detailed evaluation particularly of
the RV morphology and size is essential for the appropriate
management strategy of each individual patient.
Echocardiography provides excellent information for
this initial decision making. However, angiography, a very
invasive technique in a fragile newborn, remains an essential
imaging technique that confirms the echocardiography
findings and complements what the latter is unable to provide
with certainty. In the modern era, as interventional catheterbased therapies play a major role in the first line management
of PAIVS in at least half of the patients, i.e. those with
membranous atresia, the place of cardiac catheterization in
diagnosis and therapy becomes all the more central.
hypoplastic, with only a very small inlet guarded by a small

TV. The apical trabecular component is obliterated as is the
outlet, i.e. muscular atresia.
In hearts where the atresia is membranous with all three
parts fairly well-developed, this is termed a tripartite RV. In
between is the bipartite RV where there are well-developed
inlet and infundibulum with membranous atresia, but the
apical trabecular part is virtually obliterated by muscle.
For quantitative evaluation of RV size, the TV diameter in
diastole is measured and its Z value derived from available
normograms.13,14 The RV inlet length Z-score (TV annulus
to apex at ventricular end-diastole) and area Z-score at enddiastole with maximal area bordered by RV endocardium are
additional measurements that may be useful in defining the
degree of RV hypoplasia.15 The ratio of tricuspid to mitral
valve diameters in diastole is also useful as it provides an
immediate comparison between the RV and LV sizes.16 While
assessing the RV, large ventriculo-coronary connection may
be readily identified by color Doppler, but its entire course and
obstruction, if present, can only be ascertained by angiography.
Apart from measuring the TV diameter, the valve apparatus
should also be examined as stenosis, dysplasia and Ebsteins
malformation are common associations. The degree of TR and
RA dilatation should be described and an estimate of the RV
systolic pressure can be obtained by Doppler CW (Figures 7A
and B).
The pulmonary valve annulus and pulmonary artery
dimensions should also be measured. The PDA morphology
and dimensions as described earlier should be noted
especially if PDA stenting is to be offered as part of the initial
treatment. However PDAs that are long and tortuous may not
be adequately visualized by echocardiography.
Finally, in patients with severe Ebsteins malformation,
it should be determined whether the atresia is functional or
pathologic in nature. Color Doppler by means of documenting
pulmonary regurgitation often allows this distinction to be
made.11
585

Although echocardiography can readily confirm the diagnosis
and provide anatomic details that would be important for
management strategy, PAIVS is one condition where cardiac
catheterization and angiography remains an essential part
of the initial evaluation.1 This is particularly so for centers
where catheter based therapy plays a prominent role in the
management of this disease.
Firstly, even if the size and morphology of the RV can be
obtained by echocardiography, detailed characterization of the
RV such as the degree of obliteration of the apical trabecular
zone and the RVOT may be difficult. Intertrabecular spaces
in this region may not be obvious. In the RVOT, presence of
muscle bundles that reduce the infundibular cavity or cause
fixed subvalvar obstruction, the size of the pulmonary valve
annulus, thickness of the atretic valve plate and the dimension
of pulmonary artery root can only be detailed accurately by
angiography. In hearts with diminutive unipartite RV, a tiny
slit-like infundibulum is not uncommonly present when RV
angiography is performed (see Figure 2A). This impacts on
ones decision whether transcatheter perforation of the atretic
valve and RV decompression by balloon dilatation would be
the appropriate management.
Another reason for angiography remaining an essential
imaging technique is for the detailed evaluation of ventriculocoronary connections (see Figure 5).17,35 Whilst large ectatic
connections can be seen by echocardiography without
difficulty, the dimensions, course and more importantly the
presence or otherwise of stenoses, interruptions and absent
aortic-coronary connection of this abnormality is beyond the
capability of this otherwise excellent non-invasive imaging
technique. Minor connections may not be detected by
echocardiography. Similarly echocardiography is limited in
its capability for full characterization of the PDA morphology,
an important consideration when PDA stenting is planned as
alternative to conventional systemic-pulmonary shunt.41,42
Additionally, cardiac catheterization provides important
hemodynamic data such as RV systolic pressure, central
venous pressure (CVP), aortic pressure, LV end-diastolic
pressure and systemic oxygen saturation.
MANAGEMENT
Pulmonary artesia with intact ventricular septum (PAIVS)
being a duct-dependent lesion, survival beyond the neonatal
period or early infancy is not possible without intervention
except in the rare cases where aortopulmonary collaterals
provide a stable source of pulmonary blood flow. Intravenous
PGE1 infusion to maintain ductal patency is an important first
line treatment. Acidosis, hypothermia and poor peripheral
perfusion should be corrected when present. For preterm
586
infants or those small for gestational age, prolonged PGE1

infusion may be necessary before it is considered safe or
feasible for surgical or catheter intervention. In our own
experience, it is best for the infant to achieve a weight of
3.0 kg before any form of intervention is considered.
Today, better understanding of the wide morphologic
variation of the disease, as well as advances in surgical and
interventional techniques have led to better early survival and
at least medium term outcome of this disease.8,9,12,17,23,43-48
In patients with the most favorable anatomy with
membranous atresia and all three parts of the RV being well
developed, RV decompression in the neonatal period with
either surgical valvotomy or transcatheter method would often
be the only procedure required, and thereafter it is reasonable
to expect normal two-ventricle circulation with no further
procedures required at least until early adult life. However this
may apply to only about half of PAIVS patients.
In the remainder, multiple interventions, either surgical or
transcatheter, will be required at least in the first few years
of life. Hence, a good teamwork between the interventional
cardiologist, cardiac surgeons and the rest of the care givers
involved is essential in the management of these patients.
From the outset the parents should be counselled regarding
the nature of their infants specific morphologic details, the
likely clinical course and the long-term treatment plan and
goals, which may require significant revisions along the way
according to the outcome of preceeding treatments.
The desired goal is to achieve eventual two-ventricle
circulation with all intracardiac and extracardiac shunts
(PFO/ASD and Blalock Taussig shunt/PDA stent) closed,
obstruction to RV outflow virtually abolished and significant
tricuspid valve regurgitation corrected. However this goal is
perhaps realistically achievable in only 50 to 60 percent of
patients. Some patients from the outset appear destined for
the single ventricle track and in between are those in whom it
is reasonable to set the objective of two ventricle-circulation
at the first assessment but eventually this may need to be
downgraded to what is termed '1 ventricle circulation'
when the RV does not grow sufficiently after successful RV
decompression. Cardiac transplantation may be advocated in
the rare cases of severe RV hypoplasia with major ectatic RVcoronary connections and RVDCC and in those with extreme
Ebsteins anomaly with wall-to-wall heart, it may be wise to
offer compassionate care.
Our management algorithm is based on morphologic
evaluation by echocardiography and RV angiography. As
described in the foregoing sections there is a spectrum of
RV size and morphology. For making clinical decisions and
long term plan and counseling, it is practical to categorize
patients as having good RV size and morphology, severe RV
hypoplasia with muscular atresia and in between these two
extremes, those with 'intermediate' RV.10
40
Good Right Ventricular Size and Morphology
Figures 8A to D: PAIVS with membranous atresia-valvotomy with

balloon dilatation. A. Simultaneous right ventricular angiogram
and aortogram opposite the patent ductus arteriosus showing thin
membranous with well-developed infundibulum, valve annulus and
main pulmonary artery (MPA) sinuses. The tip of a Judkins right
catheter is placed underneath the valve plate; B. The tip of the
perforating wire is in the MPA lumen (arrow); C. Initial balloon dilation
with a 3.0 mm coronary balloon D. final dilation with an 8.0 mm balloon
In this subgroup all three parts of the RV are well-developed,

with membranous atresia of the valve plate being the major
abnormality. The TV Z score based on the normogram by
Rowlatt should measure >2.0 and the TV/MV diameter ratio
be > 0.75. Some degree of TR is often present. Subvalvar
fixed stenosis due to abnormal muscle bundle may be present.
Major RV-coronary connection may be present, but very
uncommon.
In this group of patients pulmonary valvotomy to
decompress the RV and achieve unobstructed flow into the
pulmonary arteries is the principal treatment. This can be done
by conventional surgery or by transcatheter intervention. This
should be performed at presentation unless the patient is born
premature or of low birth weight for gestation. A weight for
3.0 kg is a reasonable minimum weight, below which it is
advisable to maintain ductal patency with PGE1 infusion.
Surgery may be in the form of transventricular valvotomy,
open transpulmonary valvotomy or RV outflow patch/
reconstruction especially when the RVOT and valve annulus
is small or fixed subvalvar stenosis is also present.46,49-53 There
is considerable morbidity and mortality to these procedures
especially with the more extensive RVOT reconstruction. Not
uncommonly, Blalock Taussig shunt (BT shunt) is performed
concomitantly with RV decompression as a significant
number of patients remained hypoxic after unobstructed flow
into the pulmonary arteries has been established, even in
patients whose RV appear only mildly hypoplastic.50,54 This
may be explained by reduced RV compliance in patients with
PAIVS where the RV is generally hypertrophied. Routine
'prophylactic' BT shunt avoids the need for unplanned
reintervention early following the initial surgery. Otherwise
the patient may need to be on PGE1 infusion for a few weeks
until RV compliance improves significantly.
In the early 1990s transcatheter valvotomy and balloon
dilatation provided alternative to conventional surgery.
Perforation of the atretic valve with laser wire and the sharp
stiff end of the coronary guidewire were reported at nearly
the same time.55-57 The former is bulky, the initial capital
outlay is expensive and poses risk of retinal injury to catheter
laboratory staff, requiring them to wear protective goggles.
The latter, due to its stiffness affords little control for accurate
perforation of the valve and may instead cause perforation of
the RVOT, sometimes with major consequences. Perforation
with radiofrequency (RF) wire has rendered the above two
methods largely obsolete as better control and accurate
perforation can be achieved, and the RF generator is
inexpensive, small and portable.20,58,59
Once valvotomy is successful, the valve is progressively
dilated with a coronary balloon followed by the appropriate
sized balloon for annulus size (Figures 8A to D). This
technique has gained acceptance in many institutions today.
Perforation of the RVOT or dissection of the pulmonary artery
wall due to inaccurate positioning of RF wire are potential

major complications.18
Uncommonly, despite seemingly good RV size and adequate
RV decompression, the patient remains deeply cyanosed due
to poor RV compliance. A BT shunt or PDA stenting can be
performed to augment pulmonary blood flow. Otherwise the
patient may remain hospital bound for weeks on PGE1.60
The medium-term outlook is excellent with adequate RV
decompression. Normal or near normal RV growth can be
expected and further interventions often not required at least
until early adult life, where progressive pulmonary or TR
may require to be addressed surgically. However, restenosis
of the pulmonary valve may occur requiring repeat balloon
dilatation. It is well known that concomitant fixed subvalvar
stenosis may coexist and requires RVOT reconstruction.20 In
general, if the patient is stable, it is reasonable to delay surgical
reintervention until the infant is at least 4 to 6 months of age
when the risk of mortality and morbidity is lower. Additional
problems that may also require surgical reintervention is
significant TR.
Severe Right Ventricular Hypoplasia

with Muscular Atresia
For patients at the other end of the spectrumthose with
severe RV hypoplasia where there is muscular atresia of the
infundibulum, the apical trabecular part obliterated by muscles
587
588
and only a diminutive inlet is present guarded by a very small

tricuspid valve, RV decompression is not likely to be feasible
at the outset. Repair towards single-ventricle circulation is the
appropriate management plan.10 Added to the problem of a
non-functional diminutive RV is the presence of RV-coronary
connections in a significant number of patients in this group,
some with RVDCC. After a successful Fontan completion,
long-term exposure of the coronary arteries to very high
RV pressures may lead to early, progressive coronary artery
disease, ischaemia and infarction.
The first procedure is creation of a systemic pulmonary
shunt, which invariably in todays surgical practice is the
modified BT shunt. Neonatal BT shunt is a commonly
performed procedure for lesions with duct-dependent
pulmonary blood flow. However, the diagnosis of PAIVS is
an independent risk factor for mortality and morbidity. In
a recent publication from the STS database, the discharge
mortality for PAIVS patients was 15.6 percent, compared
to 7.2 percent for the overall group of neonatal BT shunts.61
However this risk was not further stratified according to the
presence or otherwise of major RV-coronary connections
and RV dependent coronary circulation. Because of this high
mortality risk for neonatal BT shunt, our preference in patients
with this morphology is to stent the PDA, a far less invasive
procedure.10 In general, the PDA in PAIVS is not as complex
as those in other cyanotic heart disease. They may be more
elongated than isolated PDA and arise further proximally from
the aortic arch, but exceeding tortuosity is not common. PDA
stenting can generally be performed without great technical
difficulty.62,63 Unlike other cyanotic heart disease, the PDA in
PAIVS intends to insert onto the dome of main pulmonary
artery rather than proximal left pulmonary artery, making late
LPA stenosis a less common problem. In our opinion, a PDA
that inserts onto the proximal LPA is a contraindication for
PDA stenting because of the above problem, in which case
surgical systemic-pulmonary shunt is the preferred initial
palliation. LPA stenosis often eventually occurs in this setting
but ductal stenting accelerates the process. Another advantage
of PDA stenting is that balloon atrial septostomy can be
performed at the same time if the inter-atrial communication
appears restrictive. Durability of palliation afforded by PDA
stenting generally is shorter compared to surgical shunt
because of neointimal proliferation.41
As the first stage of single ventricle repair, the bidirectional
Glenn shunt needs to be performed at 12 months. Occasionally
this has to be performed even earlier, at 4 to 6 months due
to very restrictive flow through the stented PDA. Fontan
completion is generally performed at 4 to 6 years of age.
Because of the risk of premature coronary artery disease
and high risk of BT shunt, transplantation is another option
for patients with muscular atresia, diminutive unipartite RV,
major RV-coronary connections and RVDCC. However,
with improved survival with Fontan surgery and the inherent
problems with transplantation, this is hardly considered

today.23,64,65
Intermediate Right Ventricular

There is a significant proportion of patients whose RV size and
morphology fall between the two extremes, what we would
term 'intermediate' RV.10 These patients have reasonably well
developed infundibulum and the atresia is at valvar level,
which is often thin and membranous, but may be thicker than
the usual. The inlet part is also well developed, albeit with
the tricuspid valve diameter smaller than those with the most
favourable morphology, but not diminutive as those with
unipartite RV and muscular atresia. The TV Z score generally
falls between 2.0 to 5.0 and the TV/MV diameter ratio of
0.50 to 0.75. However, the apical trabecular part is virtually
obliterated by muscles except for slits of inter-trabecular
spaces. Minor RV-coronary connections are not uncommon
but major connections may also be present. Because of
fairly well developed infundibulum and atresia limited to
the valve, even though valve annulus and infundibulum
may be smaller than those with favourable anatomy above,
RV decompression is feasible and it is reasonable to have
the objective of biventricular circulation pathway at the first
evaluation. This means RV decompression by conventional
surgery or transcatheter valvotomy and balloon dilatation as
the first procedure. Surgically, RVOT reconstruction is more
often required because of a tendency for smaller valve annulus
and subvalvar muscle bundle to be present. However because
of the smaller RV cavity due largely to near-obliterated apical
trabecular part, the patient may remain severely hypoxic even
after an adequate RV decompression. A BT shunt should also
be created at the time of RVOT reconstruction.
Our preference is to perform RF valvotomy and balloon
dilatation to decompress the RV and concomitantly stent
the PDA to tide the patient over in the expectation that in a
significant proportion of patients the RV will grow sufficiently
and complete biventricular circulation will be achieved
(Figures 9A to E).27 With pulmonary blood flow from RV and
the stented PDA, if the patient remains clinically stable we
would closely monitor until 3 to 4 years of age. If the RV
has grown adequately as assessed by echocardiography and
angiography and the patient is clinically pink, we would close
all shunts (PFO and stented PDA) by transcatheter method
and consider that biventricular circulation has been achieved.
Often, flow through the stented PDA would be very restrictive
by this time and if the PFO is also restrictive, this procedure is
not required.
In patients in whom there has been sufficient RV growth,
it is often the apical trabecular part that manifests this most
remarkably. However other patients may not exhibit as good
RV growth and cyanosis persists. They should be considered
for one and half ventricle circulation, where a bidirectional
40
Figures 9A to E: PAIVS with moderate right ventricle (RV) hypoplasia. Radiofrequency (RF) valvotomy, balloon dilatation and concomitant
elective patent ductus arteriosus (PDA) stenting. A. RV handshot showing bipartite RV with fairly well-developed infundibulum with membranous
atresia (thick arrow) and inlet component (thin arrow). Muscle bound apical trabecular component of RV (area within dotted lines). Except for
the intertrabecular recesses, the cavity is virtually obliterated. Membranous atresia seen. RV: AO pressures = 153:73 mm Hg; B. RV angiogram
following RF valvotomy and balloon dilatation. Transient reactive spasm reduces RV outflow tract cavity; C. PDA crossed with a balloon mounted
coronary wire retrogradely; D. Stent expanded and covering the full length of the PDA; E. RV angiogram 4 years post RF valvotomy and PDA
stenting showing a well-developed RV, unobstructed pulmonary blood flow, no branch pulmonary artery stenosis and regression of muscular
overgrowth resulting in a well-formed cavity of apical component of RV. Excellent overall growth of RV; 'tripartite' end state. The PDA stent is
hardly visible
Glenn shunt is created, PDA stent divided and PFO

closed.12,66-68
Additional problems such as subvalvar stenosis and TR are
tackled preferably at the same time. Only short and medium
term data is available, but this approach appears a reasonable
strategy for this group of patients with 'intermediate' RV.27
Thinned and Dilated Right Ventricular, Ebsteins

Anomaly, Severe Tricuspid Regurgitation
The final subgroup of PAIVS patients are those associated
with severe Ebsteins malformation or dysplasia of the TV,
leading to very severe TR, thinned out RV and grossly dilated
right heart chambers, i.e. the 'wall-to-wall heart'. While early
and medium term survival of those with diminutive RV and
major RV-coronary connections have improved significantly
with single ventricle palliation, the prognosis for those
severely dilated thinned out RV remains very poor.11,43,69
Instead of conventional surgery with the construction of BT

shunt and repair of the TV, RVOT reconstruction + reduction
of the grossly dilated right chambers, the technique advocated
by Starnes has shown some commendable, if mixed results.70
This involves converting the TR to atresia and the construction
of BT shunt, followed later by single-ventricle palliation.
Starnes original patients were those with severe Ebsteins
with functional pulmonary atresia, but fundamentally the
technique can be equally applied to those with anatomic
atresia of the pulmonary valve. Nevertheless this subgroup of
patients, whose grossly dilated and thinned out RV falls outside
the continuum of mild to very severe hypoplasia, continues
to have the poorest prognosis when major improvement in
medium term survival has been achieved for the others.
One of the attractive, potential merits of fetal intervention
is alteration of natural course of disease. If fetuses who can
be predicted to develop grossly dilated right heart and severe
tricuspid regurgitation can be identified, perhaps this is one
589
indication for such a procedure.71,72 However, apart from

accurate diagnosis and 'patient' (fetus) selection, there are
major issues of competence and training of the fetal cardiology
team, service organization and of ethics that make this still an
experimental procedure.
PROGNOSIS AND LONG-TERM SURVIVORS

OF pulmonary atresia with INTACT
ventricular septum
Pulmonary atresia with intact ventricular septum remains
among lesions that have higher risks for morbidity and lower 1
and 5 year survival. Low birth weight, unipartite RV, significant
RV dilatation/Ebsteins anomaly and greater severity of
coronary arterial abnormalities and earlier era of surgery
are the commonly cited independent risk factors.12,43,69,73
However, with better understanding of the remarkably varied
anatomy of PAIVS and management strategies based on RV
morphology, the outlook for these patients has continued to
improve. Advances in surgical techniques, ICU care and the
less invasive transcatheter techniques have also in a large
measure contributed to the current medium term results. It
remains to be seen, however, what happens to these patients
in the long term.
Present adult survivors of PAIVS belong to an earlier
surgical era and data is understandably scant. In a 12 year
study of 20 adult survivors of PAIVS, John et al reported five
deaths and all patients required reinterventions. 74 12 patients
had single ventricle anatomy and received Fontan operation or
palliative shunts and the remainder had 2 ventricle repair. The
highest number of reinterventions were in the biventricle repair
group, consisting of multiple pulmonary and TV replacements
and repairs, RV-PA conduit replacement, RVOT reconstruction,
treatment of shunt-related RPA stenosis and mitral valve repair
or replacement. In the single ventricle patients reoperation
were Fontan revision and conversion, fenestration and shunt
revision or creation of an additional systemic-pulmonary shunt.
Although these patients were operated in an earlier era,
the study highlights the multiple reinterventions that many
patients from the current era will likely need to undergo in
adult life due to the associated pathologies involving the
TV and pulmonary regurgitation that commonly results
following transcatheter or surgical valvotomy. However,
in the setting of two ventricle circulation, it is gratifying
to learn that late pulmonary valve replacement for severe
pulmonary regurgitation can be performed in PAIVS patients
with excellent results, although results of TV repair suggest
a need for further refinement of current surgical technique.75
Conclusion
590
In the last 2 decades there has been a tremendous improvement

in the understanding of the morphology of PAIVS, one that
is characterized by a remarkable diversity ranging from
essentially a near normal RV with membranous atresia of

the pulmonary valve to a complex malformation where the
RV is almost obliterated by muscles except for a diminutive
inlet cavity and frequently associated with major RV-coronary
connections. Between the extremes are hearts with varying
degrees of RV cavitary hypoplasia particularly involving the
apical and infundibular parts, abnormalities of the tricuspid
valve and less severe forms RV-coronary connections.
Echocardiography has played a major role in the
understanding PAIVS morphology and morphometry of
the right heart structures such as the size of the TV and RV
inlet length allows a semi-quantitative assessment of the
severity RV underdevelopment. However PAIVS is one
condition where the invasive cardiac catheterization remains
an essential imaging tool especially in the evaluation of RVcoronary connections. This is particularly so in the current
era of interventional cardiology where pulmonary valvotomy
with balloon dilation, and to certain extent PDA stenting are
the preferred initial management in many centers.
A better understanding of the RV morphology allows
formulation of management strategies that will result in
the best outcome for the patients. Although the 2-ventricle
circulation is desirable, this is only achievable in only about
60% of patients. For patients with the most severe form of
the disease, clearly the single-ventricle track is the only
viable option, with the attendant late problems following the
Fontan operation. Premature atherosclerosis due to coronary
arteries perfused by hypertensive RV in those with RVcoronary connections is an added facet of late survival. The
1 ventricle is an attractive option for those with moderate
RV hypoplasia where the bidirectional Glenn shunt partially
off loads the RV while maintaining pulsatile flow into the
pulmonary circulation.
The outlook for many patients with PAIVS is better today
than it was 2 to 3 decades ago. However, for many who
survive into adult life with 2-ventricle circulation, progressive
tricuspid regurgitation and pulmonary regurgitation are likely
to lead to re-interventions after many years of reasonably
normal survival. Transcatheter valve therapies are likely to
change how this will be managed in the near future.
The coming decades would be interesting to watch as
the cohort of patients from the current era reach adulthood,
especially those with 1 and single ventricle circulation.
It is not always in a physician's power to cure the sick; at
times the disease is stronger than trained art.
Ovid
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Pulmonary atresia with intact ventricular septum: management
593
C hapter
41
Double Outlet Right Ventricle

Vimala J, Vijayalakshmi IB, Prasanna Simha Mohan Rao
Introduction
Double outlet right ventricle (DORV) is a term that
encompasses a wide range of cardiac malformations with
varied clinical presentation. DORV comprises 1 to 3 percent
of all congenital heart defects.1 The congenital heart surgery
nomenclature and database project has defined DORV as
a spectrum of congenital heart diseases, in which both the
great arteries arise entirely or predominantly from the RV.2
This spectrum ranges from ventricular septal defect (VSD)
with overriding aorta at one end to DORV with subpulmonic
VSD (Taussig-Bing anomaly), which resembles transposition
of great arteries (TGA) at the other end. The clinical
manifestations vary depending on the relationship of the great
vessels to each other and location of the VSD and the presence
or absence of stenosis of the semilunar valves. Though an
attempt to classify DORV was attempted by Neufield, the
widely accepted classification was described in 1972 by Lev
and Bharati.2
Double outlet right ventricle can be diagnosed:
1. If the aorta and the pulmonary artery are related to the
morphologic RV either by both arising from the conus/
infundibulum
2. One great artery arising from the conus and the other
great artery having fibrous continuity with only the right
ventricular portion of the atrioventricular (AV) valve.
Embryology
In the developing heart persistence of a primitive relationship
of the truncoconal structures with the ventricles without
leftward shifting results in DORV with the primitive VSD
(bulboventricular defect) persisting as the only outlet of the
left ventricle.3,4 Neural crest cells have been implicated in the
formation of the aorticopulmonary septum of the developing
outflow tract. Partial ablation of the cardiac neural crest has
been shown to lead to normal aorticopulmonary septum with
the aorta and pulmonary trunk malaligned with respect to

the ventricles resulting in DORV, dextroposed aorta and/or
tetralogy of Fallot (TOF).5
Genetics
In most cases, the defect is sporadic in nature and there is no
identifiable genetic cause. A small number of familial cases
have been reported and the defect has been produced in animal
models by the deletion of particular genes, especially those
associated with neural crest migration. 22q11 micro deletion
has been associated with some cases of DORV.6 In a literature
survey of 140 case reports of DORV; various chromosomal
anomalies were reported in 40 percent of the patients.1
Morphology
Ventricular septal defect is the only outlet of the left ventricle
and is an integral part of DORV. It is usually unrestrictive. In
10 percent of cases, the VSD is restrictive and in 13 percent
of cases, VSDs are multiple. Rarely, it may be absent when
the DORV is part of a complex anomaly associated with
hypoplasia of the mitral valve and left ventricle.2 DORV as
part of a univentricular heart shall not be discussed in this
chapter.
Position of the Ventricular Septal Defect

The location of the VSD is described in relation to the great
arteries. It is described as subaortic, subpulmonary, doublycommitted or non-committed (remote). These terms do not
strictly mean that one of the borders of the VSD is formed
by any of these great arteries. This relationship of the VSD
to the great arteries has a special implication in the clinical
manifestation and also surgical management.
41
Figure 1: Double outlet right ventricle with subaortic ventricular

septal defect. A = Anterior ; Ao = Aorta; IS = infundibular septum;
P = Posterior; PA = Pulmonary artery; RA = Right atrium; RV = Right
ventricle; SMT= Septomarginal trabeculation.
Subaortic ventricular septal defect: This is the most

common type. The VSD is located beneath the aortic valve and
is separated from it by the presence of subaortic conus (Figure
1). About three-fourths of the patients with subaortic VSD
have bilateral conus and a little less than one-fourths have
only subpulmonary conus. Most patients with mitral-aortic
continuity have either subaortic or doubly-committed VSD.7
Subpulmonary ventricular septal defect (Taussig-Bing
anomaly): About 30 percent of cases who undergo surgery
have subpulmonary VSD (Figure 2).8 These VSDs are large
and lead to early development of pulmonary arterial hypertension. Bilateral conus or only subaortic conus occur with
equal frequency. If there is a subpulmonary conus, the VSD
is separated from the pulmonary artery by a variable distance;
if there is pulmonary-mitral continuity with no subpulmonary conus the pulmonary valve will override the VSD (also
called as juxta-pulmonary VSD). If subpulmonary conus is
present, the infundibular septum (conus) is so oriented that it
does not form a part of the interventricular septum, but serves
to commit the VSD to the pulmonary artery. Hypertrophy of
the infundibular septum and parietal band may give rise to
subaortic obstruction and may be the cause for the aortic arch
obstruction, which is commonly associated with the TaussigBing anomaly.
Non-committed (remote) ventricular septal defect: The
term non-committed was introduced by Lev et al in 1972.8
These VSDs are far from either the aorta or the pulmonary
artery. They are separated from the great arteries by muscular
tissue (Figure 3). Though some have described DORV with
remote VSD as VSD separated from both the great arteries by
a distance more than the aortic diameter or as both the great
Figure 2: Double outlet right ventricle with subpulmonic ventricular

Figure 3: Double outlet right ventricle with remote ventricular

vessels arising 200 percent from the RV and a double conus9; the
term noncommited/remote or uncommitted is not anatomical,
but only descriptive that the VSD is at a considerable distance
away from the outflow tracts. These are either inlet VSDs
without perimembranous extension, muscular VSDs or even
any of the other VSDs, where the conus is long and separates
the VSD from the great arteries. The inlet VSDs may occur as
part of the DORV with atrioventricular canal defect. Remote
VSDs are present in 10 to 20 percent of patients who undergo
surgery.2
595
8
the left-sided conus. Since, the VSD is almost always

subaortic in these cases, it is considered amenable to
corrective surgery.7
Pulmonary Stenosis
Pulmonary stenosis is commonly seen in association with
DORV with subaortic VSD or doubly-committed VSD. It
occurs in approximately 70% of patients with malposition of
great arteries. It is not commonly associated with the TaussigBing type of DORV. Though more often the obstruction is at
the infudibulum, obstruction at the valve, annulus and main
pulmonary artery levels may also be seen; pulmonary atresia
has also been reported.2
Figure 4: Double outlet right ventricle with doubly committed
ventricular septal defect. A = Anterior ; Ao = Aorta; IS = infundibular
septum; P = Posterior; PA = Pulmonary artery; RA = Right atrium;
RV = Right ventricle; SMT= Septomarginal trabeculation.
Doubly-committed ventricular septal defect: It is reported

in 10 percent of patients with DORV, who have been surgically
treated.2 The VSD lies beneath the aortic and the pulmonary
valves (Figure 4). The pulmonary and aortic valves are conti
guous as the infundibular septum is absent. The conus may be
deficient bilaterally or a single conus may be present beneath
both the great arteries.
Great Artery Relationship

The great artery relationships fall into two basic categories,
spiraling normally related great arteries or parallel great
arteries. This classification is important to determine the
appropriate type of corrective surgery.
Normally Related Great Arteries

The great arteries are normally related and spiral around each
other. The aorta is right and posterior to the pulmonary artery.
The VSD in these cases is usually subaortic.2
Parallel Great Artery Relationships
596
i. Rightward and side-by-side aorta: The VSD is usually

subpulmonary.
ii. Right and anterior aorta: In a study by Guo et al, in 50
percent of angiographically studied patients, the aorta
was either directly to the right or right and anterior to
the pulmonary artery.10
iii. Aorta directly anterior to the pulmonary artery.
iv. Left and anterior aorta (Lmalposition): This is the least
common great artery position. The aorta arises from
Subaortic Stenosis
As described earlier, subaortic obstruction is seen in about a third
of the cases of DORV with subpulmonary VSD. The subaortic
obstruction may be caused by the narrowed left ventricular
outflow tract (LVOT), AV valve tissue or accessory valve tissue.
Aortic arch obstruction may be present in such patients.2
Coronary Artery Anomalies

In DORV, the left coronary artery arises more posteriorly
and the right coronary artery arises more anteriorly. When
the aorta is right and anterior, the coronary artery anatomy
appears similar to that of TGA with RCA arising from the
posteriorly facing sinus and the LCA arising from the anterior
facing sinus.2 The origin and proximal course of the coronary
arteries vary depending on the proximity of the facing sinuses
to the atrioventricular or the interventricular grooves.11 Single
coronary artery has been reported in upto 11 percent of the
patients with DORV.12 In all cases of DORV with L-malposition
of the great vessels, the right coronary artery passes anterior to
the pulmonary outflow tract, which is of surgical significance.7
Conduction System
In DORV, the AV node lies in the usual position of the AV
septum. The bundle of His lies along the posteroinferior
margin of the VSD in DORV with juxtatricuspid defects like
the subaortic, subpulmonary and doubly-committed VSDs.
When the defect is separated by muscular tissue from the
tricuspid valve, the bundle runs within the muscular tissue and
is not present at the posteroinferior part of the VSD.2
The clinical manifestations of DORV vary depending on the site
of the VSD, relationship of the great arteries to each other and to
41
VSD Type
VSD type (DORV with subaortic VSD without pulmonary
stenosis, DORV with doubly-commited VSD without pulmo
nary stenosis). The blood from the left ventricle is directed
into the aorta through the VSD. Hence, the presentation
is similar to children with a large VSD and pulmonary
hypertension. These children present with poor feeding
and poor weight gain. They may have mild cyanosis or no
cyanosis at all. These children are likely to develop early
pulmonary arterial hypertension.
Figure 5: Parasternal long-axis shows double outlet right ventricle with

large nonrestrictive ventricular septal defect with pulmonary stenosis.
Ao = Aorta; LA = Left atrium; LV = Left ventricle; PA = Pulmonary
artery; RA = Right atrium; RV = Right ventricle.
the VSD and the presence or absence of stenosis of the semilunar valves. The clinical presentation of DORV may be classified
as the VSD type, tetralogy of Fallot (TOF) type, transposition of
the great arteries (TGA) type, and remote VSD type.2
TOF Type
TOF type (DORV with subaortic VSD and pulmonary stenosis,
DORV with doubly-commited VSD and pulmonary stenosis).
The clinical picture is similar to that of TOF. Cyanosis is
present from early months of life; a systolic murmur is audible
in the new born period. These children may have progressively
worsening cyanosis with cyanotic spells.
TGA Type
TGA type (DORV with subpulmonary VSD without pulmonary
stenosis). The clinical presentation is similar to that of TGA
with VSD. The children are cyanosed in the newborn period
and develop worsening breathlessness, poor feeding and poor
weight gain. Associated coarctation may be present and such
children may present with heart failure in the early newborn
period.
Remote VSD Type

Remote VSD type: They present like patients with single
ventricle. Children have mild cyanosis and the pulmonary
blood flow may be balanced, increased or decreased.
Investigations
Electrocardiogram shows right ventricular hypertrophy
and in some cases biventricular hypertrophy. Conduction
abnormalities may be found.9
Chest X-ray findings vary widely depending on the type of
DORV. At one end of the spectrum, radiological features may
resemble that of VSD with moderate enlargement of the heart
with varying degree of increased vascularity. At the other end,
the heart may be 'boot-shaped' with decreased vascularity
resembling TOF. In DORV with L-malposition, the left upper
border of the cardiac silhouette shows a bulging vascular

shadow with no discrete pulmonary segment observed.7,10
Two-dimentional echocardiography shows both great
arteries arising from the anterior RV. The features in parasternal
long-axis view (Figure 5) are inability to identify a great
artery arising from the left ventricle and the lack of continuity
between the anterior mitral leaflet and any semilunar valve
caused by the conus. The conus is seen either as a dense echo
(fibromuscular) or as a muscular conus separating the two
valves and producing a separation and a more superior postion
of the semilunar valve.13 There is no other outflow to the left
ventricle other than the VSD. The left ventricular outflow tract
may have a tunnel-like configuration. There is hypertrophy of
the RV.
Identifying the location of the VSD is essential in
planning the type of surgical intervention. Subaortic or
subpulmonary defects can be seen in parasternal or subcostal
long and short-axis views. Doubly-committed VSD is seen
as a defect that is nearly equally committed to both the
great arteries. Non-committed VSDs are usually complete
AV septal defects and isolated or multiple muscular VSDs.
These are best seen in the apical or subcostal four chamber
views. A restrictive VSD may be seen as an anatomically
small defect with turbulent flow and causes LVOT
obstruction. The degree of restriction may be assessed by
doppler echocardiography.14
In the parasternal short-axis view, the features are
simultaneous imaging of both great arteries in an anterior
location and lack of a clockwise wrap around of the aorta by
the right ventricular outflow tract. A double-circle appearance
of the great arteries may be seen. The great arteries may be
side-by-side, D-malposed or L-malposed.15
Transesophageal echocardiography (TEE) would furnish
extra details about the position of the VSD and its relationship
597
to the great arteries. Longitudinal planes would delineate

the right and left ventricular outflow tracts and the great
arteries. These views demonstrate the typical features of
the predominant commitment of both great arteries to the
RV. Additional defects of the AV valves and their chordal
attachments may also be delineated well by TEE.
Fetal echocardiography: Careful visualization of the four
chamber view and outflow tracts in fetal echocardiography
is diagnostic.16 The VSD is almost always seen in the four
chamber view. While viewing the outflow tracts, both the
great vessels are seen arising from the RV and are often seen
to be side-by-side (Figure 6).
Figure 6: Fetal echocardiography outflow tract view shows double

outlet right ventricular with subpulmonary ventricular septal defect
(Taussig-Bing). Ao = Aorta; LV = Left ventricle; PA = Pulmonary artery;
RV = Right ventricle; VSD = Ventricular septal defect.
A
598
Angiographic Illustrations
There are 16 possible variations of DORV based on the great
artery relationships and the location of the VSD and it may be
associated with pulmonary stenosis or with pulmonary artery
hypertension (Figures 7A and B). The various illustrations
include a case of dextrocardia with situs inversus with DORV
(Figures 8A and B).
The side-by-side relationships of the great arteries with
subaortic VSD is the most frequently encountered type of
DORV (Figure 9A). The aorta is to the right of the pulmonary
artery (Figure 9B). The aortic valve and the pulmonary valve
are at approximately the same horizontal level. The VSD is
the only outlet from the LV, hence it is an obligatory shunt. To
do the LV angiogram one has to have a patent foramen ovale
or an atrial septal defect (Figure 10) or a large VSD.
The true subpulmonary VSD, the Taussig-Bing anomaly,
is relatively rare. The great arteries are in a side-by-side
relationship (Figure 11). Because pulmonary stenosis does not
occur in these cases, the pulmonary trunk is markedly dilated.
The VSD is anterosuperior (supracristal) and immediately
subjacent to the pulmonary valve (subpulmonary VSD).
The right ventricular angiogram demonstrates that the great
arteries are in a side-by-side relationship The classic finding
on the early phase of the right ventricular angiogram is a high
VSD related directly to the pulmonary valve.
The doubly committed, subaortic and subpulmonary, VSD
is closely related to both semilunar valves and lies in a superior
position, The VSD is quite large and extends in an oblique
course beneath both great arteries. On angiogram one cannot
differentiate this type from the Taussig-Bing anomaly because
on the lateral view of the RV this VSD is high, anterior,
superior and directly related to both semilunar valves. It is
Figures 7A and B: A. Right ventricle (RV) angiogram shows simultaneous opacification of both the great arteries with post stenotic dilatation
of main pulmonary artery; B. RV angiogram in double outlet RV with pulmonary hypertension shows simultaneous opacification of both the
great arteries with dilatation of pulmonary artery due to pulmonary hypertension. Ao = Aorta; LV = Left ventricle; MPA = Main pulmonary artery;
PA = Pulmonary artery.
41
Figures 8A and B: A. Left ventricle (LV) angiogram in right anterior oblique view in a one-year-old boy with dextrocardia with situs inversus,
double outlet right ventricle (RV), shows smooth-walled LV with ventricular septal defect committed to aorta (Ao), which is to the right of
pulmonary artery (PA) and with a right sided aortic arch (mirror image dextrocardia). B. RV angiogram in frontal view illustrates simultaneous
opacification of PA (dilated due to post stenotic dilatation) and aorta (Ao), with long segment narrowing of left pulmonary artery (LPA - arrow)
and its upper lobe branch.
Figures 9A and B: A. Left ventricle (LV) angiogram in frontal view in a case of double outlet right ventricle with large ventricular septal defect
(VSD) (right heart catheter has entered LV through the VSD) illustrates the side-by-side relationship of the great arteries with both the pulmonary
valve (PV) and the aortic valve (AV) at the same level; B. LV angio in a frontal view shows VSD committed to the aorta (Ao) and aorta is to the
right of the pulmonary artery (PA)
impossible to recognize whether the VSD is related to the

pulmonary valve or to both semilunar valves.
The DORV with remote VSD, as a case with multiple VSDs
not committed to both the great arteries, is illustrated in Figure
12. The angiographic findings other than the great artery
relationships, are not different from those observed with sideby-side great arteries and remote VSD. The malposition of the
aorta can be seen in both frontal and lateral views (Figure 13 A
and B). The left ventricular angiogram also demonstrates that
the VSD is the only outlet from the left ventricle.
The relationship of the great arteries may be observed i.e.

aorta right and anterior or aorta to the right of pulmonary valve,
aorta anterior to the pulmonary valve, aorta left and anterior
to the pulmonary valve.10 In DORV with L-malposition,
aortography shows left sided anterior ascending aorta with
right coronary artery passing anterior to the pulmonary
valve.7
Computed tomography angiography and magnetic
resonance imaging: The spatial relationship between semilunar
valves and VSD can be accurately assessed by CT angiography
599
Figure 10: Right heart catheter through atrial septal defect entered
left ventricle (LV). The LV angiogram in left lateral view shows the
ventricular septal defect committed to the aorta (Ao)
Figure 11: Left ventricle (LV) angiogram in left anterior oblique view
illustrates subpulmonic ventricular septal defect opacifying dilated
pulmonary artery (PA) more than the aorta (Ao), that is to the right and
anterior (Taussig-Bing anomaly)
Figure 12: The left ventricle (LV) angiogram in left lateral view illustrates two ventricular septal defects (VSDs) opacifying the trabeculated
right ventricle (RV), in turn opacifying both the great arteries simultaneously, indicating that VSDs are not committed to both the great arteries.
Ao = Aorta; PA = Pulmonary artery.
600
A
Figures 13 A and B: Right ventricle (RV) angiogram in double outlet RV (DORV) with malposed side by side great arteries, running parallel to
each other. B:RV angiogram in DORV with anterio-posterior malposition of the great arteries
41
Figure 14: Computed tomographic angiogram illustrates double outlet

right ventricle with aorta anterior and side by side with pulmonary
artery
(Figure 14) and magnetic resonance imaging (MRI) and could

provide additional information to the conventional imaging in
the assessment of VSD. MRI would provide accurate additional
anatomic information, which would be helpful in presurgical
planning and in follow-up of patients.17
Management
There is no specific medical management for DORV.
Those infants who are having congestive heart failure need
decongestive therapy.
Surgery for Double Outlet Right Ventricle9,18-21

Surgery for DORV has got two requirementsclosure of
the VSD and unobstructed outflow from the corresponding
ventricles to the great arteries. An adequately sized ventricle
is a necessary caveat for a biventricular repair in DORV.
Since both great arteries arise from the RV, the outflow path
will necessarily have to be through the VSD. The position
of the VSD (in relation to the great arteries) is the primary
determinant of the hemodynamic status of the child. The status
of the pulmonary arteries are also to be considered.
A subaortic VSD with pulmonary stenosis acts like a TOF
and if there is no pulmonary stenosis, it behaves like a VSD. A
subpulmonic VSD makes the child behave like a transposition
with a VSD. A doubly committed and a non-committed VSD
will behave depending on how the blood streams to the
great arteries. Apart from the VSD, the relation of the great
arteries, outflow tract obstructions, chordal connections of the
tricuspid valve and the distance between the pulmonary valve
and the tricuspid valve will also determine the management.
The tricuspidtopulmonary annulus distance has been shown
to be a useful predictor for the feasibility of intraventricular
baffle repair (Figure 15).21 The size of the ventricles will also
determine whether a biventricular repair or a univentricular
Figure 15: Separation between the tricuspid valve (Tric. V) and

pulmonary valve (PV) is critical in determing the anatomic suitabilty
for an intraventricular baffle repair. A. There is adequate separation
between the PV and Tric. V so that the pathway from the ventricular
septal defect (VSD) to the aorta is unobstructed. B. When PV is very
close to Tric. V a Rastelli repair may be appropriate. PV lies within
the baffle necessiating division and oversewing of main pulmonary
artery. C. Separation of the Tric. V and PV is less than the diameter of
the aortic annulus. Intraventricular repair is likely to result in subaortic
stenosis either immediately or postoperatively. AV = Aortic valve;
PA = Pulmonary artery; RV = Right ventricle. Reprinted with permission
from reference 21.
repair will be possible. In extremely unroutable VSDs, a

single Fontan correction may be used if the pulmonary artery
size and vascular resistance permits.
Double Outlet Right Ventricle Subaortic VSD

Without Pulmonary Stenosis
An intraventricular tunnel repair is possible in most patients.
The patch forms a tunnel and in essence forms a part of the
LVOT and so has to be liberal so as to not cause subaortic
stenosis. Initial inspection should be done and the possibility
of transposing any obstructing tricuspid chordae has to be
planned. If the VSD is small, suitable enlargement by excision
of the superior and lateral margins are done, to avoid the
conduction system. A suitable patch or portion of a tube graft
is used to construct a nonobstructive tunnel. If the generous
patch were to cause RVOT obstruction, then augmentation of
the RVOT with a patch may be required.
Double Outlet Right Ventricle Subaortic VSD with

Pulmonary Stenosis
If the pulmonary artery size is inadequate then the child may
need an aortopulmonary shunt to enable growth of the pulmo
nary arteries to enable intracardiac repair later.
This can be equated to a TOF repair. If the override is not
excessive and the RV infundibular narrowing is not excessive,
601
a liberal VSD patch and if required RVOT patching to allow

unobstructed right ventricular outflow, can be done. If the
override is excessive and there is annular narrowing, then a
transannular patch or an RV to pulmonary artery conduit (all
the more if there are major coronaries crossing the RVOT)
may need to be implanted.
mortality and in the current era associated arterial switch

has reduced the mortality by reducing the complexity of the
tunnel. A DORV with subaortic VSD has a current mortality
of that of a VSD or a tetralogy repair. The introduction of the
arterial switch for the Tausig-Bing anomaly has reduced the
mortality from as high as 50 percent to 515 percent.
Double Outlet Right Ventricle with

Doubly Committed VSD
Conclusion
These cases can usually be managed like a DORV with a

subaortic VSD.
Double outlet right ventricle with a subpulmonic VSD

The Taussig-Bing anomaly presents a unique problem,
where the pulmonary valve is interposed between the aorta
and the VSD necessitating a circuitous patch as described
by Kawashima (especially, if the great vessels are sideto-side), after resecting the subpulmonic infundibulum to
allow reaching the aorta which may necessitate closing the
pulmonic orifice at times with an RV to pulmonary artery
conduit, if the distance between the pulmonary valve and
the tricuspid valve is not sufficient to allow an unobstructed
pathway. More commonly the subpulmonic VSD is converted
into a subaortic VSD by performing an arterial switch and
now the intraventricular tunnel is shorter, the probability of
subaortic stenosis is reduced and the need for a conduit is
avoided.
Double Outlet Right Ventricle with an Uncommitted VSD

The repair is dictated by the position of the VSD. A circuitous
tunnel repair may be needed and an arterial switch may be
combined to make the baffle less circuitous. Attention to the
conduction system needs to be kept in mind during the baffling
procedure. Multiple patches to create the circuitous baffle
has been described by Barbero Marciel. In complex DORV,
where routing may not be easy or impossible, a variation of
the Fontan operation may be adopted.
Complications
Severe hemolysis can occur due to the circuitous patch.
Residual VSDs, heart blocks and late onset of LVOT obstruction
can occur. Damage to the septal arteries and left anterior
descending artery can occur during enlargement of a restrictive
VSD. Patients with RVOT conduits are exposed to all the late
complications related to conduit implantation and stenosis.
Results
602
Double outlet right ventricle being a wide spectrum has

a differing mortality. Uncommitted VSDs have a higher
The prognosis of DORV with pulmonary stenosis resembles

that of TOF. In the Taussig-Bing type of DORV, course of
events are worse than TGA with large VSD. A number of
surgical maneuvers have achieved satisfactory anatomical
repair and long-term survival.The precise timely diagnosis is
very important.
The physician's highest calling, his only calling, is to make
sick people healthy -- to heal, as it is termed.
Samuel Hahnemann
Acknowledgment
I would like to express my thanks to Dr Bhushan Chavan for
his help in completion of this chapter and Ms Sujatha for her
secretarial help.
References
1. Obler D, Juraszek AL, Smoot LB, et al. Double outlet
right ventricle, etiologies and associations. J Med Genet.
2008;45:481-97.
2. Walters HL 3rd, Mavroudis C, Tchervenkov CI, et al.
Congenital Heart Surgery Nomenclature and Database Project:
double outlet right ventricle. Ann Thorac Surg. 2000;69:
S249-63.
3. Angelini P, Leachman RD. The spectrum of double outlet
right ventricle: An embryologic interpretation. Cardiovasc
Dis. 1976;3:127-149.
4. Angelini P. Embrology and congenital heart disease. Tex Heart
Inst J.1995;22:1-12.
5. van den Hoff, Moorman AFM. Cardiac neural crest: the holy
grail of cardiac abnormalities? Cardiovasc Res. 2000 ;47:2126.
6. Wilkinson J. Double outlet right ventricle. Orphanet
Encyclopedia, Feb 2005.
7. Lincoln C, Anderson RH, Shinebourne EA, et al. Double outlet
right ventricle with L-malposition of the aorta. Br Heart J.
1975;37:453-63.
8. Belli E, Serraf A, Lacour-Gayet F, et al. Double-outlet right
ventricle with non-committed ventricular septal defect. Eur J
9. Lacour-Gayet F, Haun C, Ntalakoura K, et al. Biventricular
repair of double outlet right ventricle with non-committed
ventricular septal defect (VSD) by VSD rerouting to the
pulmonary artery and arterial switch. Eur J Cardiothorac Surg.
2002;21:1042-8.
16. Kim N, Friedberg MK, Silverman NH. Diagnosis and prognosis of fetuses with double outlet right ventricle. Prenat Diagn.
2006;26:740-45.
17. Beekmana RP, Roest AA, Helbing WA, et al. Spin Echo MRI
in the evaluation of hearts with a double outlet right ventricle:
Usefulness and limitations. Magn Reson Imaging. 2000;18:24553.
18. Harvey JC, Sondheimer HM, Williams WG, et al. Repair of double
outlet right ventricle. J Thorac Cardiovasc Surg. 1977;73:611-15.
19. Brawn WJ, Mee RB. Early results for anatomic correction of
transposition of the great arteries and for double outlet right
ventricle with subpulmonary ventricular septal defect. J Thorac
20. Delius RE, Rademecker MA, de Leval MR, et al. Is a high risk
biventricular repair always preferable to conversion to a single
ventricle repair? J Thorac Cardiovasc Surg. 1996;112:1561-69.
21. Sakata R, Lecompte Y, Batisse A, et al. Anatomic repair of
ventriculoarterial connection associated with ventricular septal
defect. I: Criteria of surgical decision. J Thorac Cardiovasc Surg.
1988;95:90-95.
41
10. Guo W, Lin ML, Gu ZQ, et al. Double outlet right ventricle,
a clinical-roentgenologic-pathologic study of 28 consecutive
patients. Chest. 1984;85:526-32.
11. Uemura H, Yagihara T, Kawashima Y, et al. Coronary arterial
anatomy in Double-outlet right ventricle with subpulmonary
VSD. Ann Thorac Surgery. 1995;59:591-97.
12. Ewing S, Silverman NH. Echocardiographic diagnosis of
single coronary artery in double-outlet right ventricle. Am J
Cardiol. 1996;77:535-9.
13. Hagler DJ, Tajik AJ, Seward JB, et al. Double outlet right
ventricle: wide-angle two dimensional echocardiographic
observations. Circulation. 1981;63:419-28.
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Left Ventricle. In Moss and Adams' Heart Diseases in Infants,
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603
C hapter
42
Truncus Arteriosus
INTRODUCTION
Truncus arteriosus is a rare cyanotic heart disease classified
as one of the conotruncal anomalies and is characterized by
i. A common arterial trunk originating from base of the
heart ii. The common arterial trunk gives rise to the aorta,
pulmonary artery and coronary arteries.1 Truncus arteriosus is
thought to result from failure of septation of the conotruncus
portion of the heart tube during embryonic development.
Truncus arteriosus is most commonly associated with a
large ventricular septal defect (VSD) in the conal septum.
Pulmonary arteries originate from the common arterial trunk.
In most clinical series, truncus arteriosus accounts for
less than 1 percent of all congenital heart defects. However,
it constituted 2.8 percent of autopsy cases, as seen in Boston
Cardiac Registry.2 Even a higher incidence of 7 percent was
reported from an earlier autopsy series from the same institution.3
Variability in incidence probably reflects the nature of the study
subjects, clinical vs autopsy and the institution. Overall, truncus
arteriosus remains a rare congenital heart defect.
Truncus arteriosus was first reported by Wilson in 17984 and
the features were confirmed in the next century by Buchanan
in 1864.5 Lev and Saphir proposed basic morphologic criteria
defining the anomaly in 1942.1 Collett and Edwards6 proposed
a classification in 1949, based on previously published reports.
An alternative classification was proposed by van Praagh in
1965.7 He later revised his own classification in 1975.8
In this chapter, we will discuss embryology, genetics,
pathologic features, classification, natural history, clinical
features, differential diagnosis, noninvasive and invasive
evaluation, management and outcome of treatment of truncus
arteriosus.
EMBRYOLOGY
Primitive truncus arteriosus is a segment in the heart tube
between the ventricles and branchial arches. During normal
development, tissue swellings (anterior and posterior

cushions) appear inside the side walls of the truncus arteriosus
and form the spiral septum separating truncus arteriosus into
the aorta and main pulmonary artery. The twisting descent of
the spiral septum accounts for twisting of the great arteries
between themselves. Spiral septum also contributes to the
formation of conal septum below the semilunar valves. Failure
of formation of spiral septum leads to truncus arteriosus. Since
this is a defect of spiral septum, the resultant VSD is in the
conal septum and does not involve the membranous septum.
Occasionally, the membranous septum may also be deficient.
But typically, the VSD in truncus arteriosus is a conal septal
VSD. As a result, tricuspid valve annulus is separated from
the edge of VSD by a small portion of ventricular septum that
forms the posteroinferior portion of septomarginal band.
Aortic arch, patent ductus arteriosus and pulmonary
arteries are derived form from 3rd, 4th and 6th branchial or
aortic arches with contributions from other primitive arteries
such as seventh intersegmental artery. As a consequence,
there can be associated defects involving all these vessels
including coronary arteries. There is also a suggestion that
main pulmonary artery is not only formed by separation of the
truncus by spiral septum, but also by additional contribution
from 6th branchial arches, that extend into proximal portions
of left and right pulmonary arteries.
Theories on development of truncus arteriosus include the
following:
1. Abnormal flow during the bilocular stage of the heart
tube: There is spiraling of blood flow returning from
inferior (IVC) and superior (SVC) vena cavae, when the
heart is in the bilocular stage. Disturbance of this flow may
predispose to abnormal or lack of development of spiral
septum.
2. Abnormal migration of cardiac neural crest cells from
the occipital region to the primitive truncus and 3rd,
4th and 6th branchial arches areas: If the number of
cardiac neural crest cells fall below a certain critical value,
GENETIC ASSOCIATIONS
Conotruncal anomaly is one of the better-studied areas
of cardiovascular developmental genetics. There is a
high association with DiGeorge syndrome with 22q11
microdeletion identified using fluorescent in situ hybridization
(FISH) technique. Reviewed by multiple authors,11-14 22q11
microdeletion is noted in 20 to 33 percent of patients with
truncus arteriosus. There is a high association with right
aortic arch. Of the 251 patients who were screened for 22q11,
microdeletion was positive in 50 percent of patients with
interrupted aortic arch, 35 percent of truncus arteriosus and
16 percent of tetralogy of Fallot.14 Similarly, five of 15 (33%)
consecutive patients with truncus arteriosus were positive for
22q11 detection.11 Associated features in DiGeorge syndrome
include dysmorphic facies, thymic and parathyroid hypoplasia,
skeletal and renal abnormalities and developmental delay.
Velocardiofacial syndrome is another genetic association
characterized by presence of facial features including cleft lip
and palate, learning difficulties and heart defect.
PATHOLOGY
Common Arterial Trunk
originate separately and directly from the common arterial

trunk. Several classifications have been proposed based on the
nature of pulmonary artery anatomy and are discussed below.

Conal septal or infundibular VSD is the rule. In echocardio
gram, it appears as though the single truncal valve overrides
the ventricular septum. The septal band is intact and so, is part
of the membranous ventricular septum. Therefore, typically
this is a conal septal VSDjust as in tetralogy of Fallot.
Distal infundibular septum is defective resulting in a large
VSD. The right posterior/inferior division and left anterior/
superior division of the septal band form the inferior border of
the VSD. There have been only two of 47 cases, reported by
van Praagh,7 which did not have a VSD.
42
Truncus Arteriosus
the spiral septum does not develop. Ablation of cardiac

neural crest cells in chick embryos has resulted in high
incidence of persistent truncus arteriosus.9
3. Cardiac neural crest cells express PAX3 gene: PAX3
gene mutation may be responsible for development of
truncus arteriosus. However, the basis of the types of
truncus arteriosus cannot be explained with this theory, at
this time.10 Several other candidate genes have also been
proposed as etiology for truncus arteriosus.
VSD accompanies truncus arteriosus in almost all cases,
except for very rare reports.7 Typically the VSD in truncus
arteriosus is a conal septal defect and is large in size. The
ventricular septum appears malaligned in an echocardiogram,
due to the single truncal valve overriding the VSD. Typically,
the VSD does not involve the membranous portion of the
ventricular septum. This portion of ventricular septum is
usually intact leaving a piece of ventricular septum separating
the edge of the conal septal VSD and tricuspid valve annulus.
There may be associated abnormalities of tricuspid valve
including its anterior leaflet and medial papillary muscle,
coronary arteries, pulmonary arteries and aortic arch branches.
Pulmonary Arteries
The main pulmonary artery (PA) usually arises from the left
posterolateral portion of the common arterial trunk (as in
type I). The right and left pulmonary arteries may arise from
back (as in type II) or side (as in type III) of common arterial
trunk directly. When the right and left pulmonary arteries have
separate origins, one of the pulmonary arteries may be absent;
seen in 16 percent cases in one series.15 In the Mayo clinic
series, in 80 percent of cases with single pulmonary artery, the
pulmonary artery was absent on the side of aortic arch. This
is in contradistinction to what is noted in tetralogy of Fallot,
where when a PA is absent, it will be on the side opposite from
that of aortic arch.
Pulmonary artery after its origin may criss-cross in cases of
truncus arteriosus coexisting with interrupted aortic arch, i.e.
left PA originates to the right of right PA and crosses to the left
side.16
Truncal Valve
Most commonly, truncal valve has three leaflets (67%).
Quadricuspid truncal valve occurs in 24 percent of cases.
Bicuspid truncal valve is noted in 7 percent. Unicuspid
truncal valve has been rarely reported. When there are three
or four leaflets, they are usually similar in size. Truncal valve
regurgitation is more common, while truncal valve stenosis
is rare.7
Coronary Ostial Anomalies
Presence of a single arterial trunk originating from base of

the heart is the hallmark of this defect. The pulmonary artery
originates from the common arterial trunk either as a common
(main) pulmonary artery first and then branch into right and
left pulmonary arteries or the right and left pulmonary arteries
Location of the coronary ostia may be abnormal; the most

common abnormality being a high-origin of the coronary
artery and location above the wrong commissure or cusp.
Rarely, coronary ostial stenosis has been noted.
605
Table 1
Aortic Arch
Right aortic arch is present in 33 percent of
cases.2,7
Conduction System
Sinoatrial (SA) and atrioventricular (AV) nodes are in their
usual location. AV bundle passes to the left of the central
fibrous body. Left bundle courses posterior to the membranous
ventricular septum along the left side of the ventricular septum.
Right bundle travels along the ventricular septal summit usually
intramyocardiallysomewhat deeper from the edge of VSD
and becomes subendocardial at the level of moderator band.
This is the case when membranous ventricular septum is intact.
However, when the VSD involves both membranous septum and
conal septum, the right bundle usually travels subendocardially,
along the left side of posterior-inferior rim of VSD and is
vulnerable to injury during surgical closure of VSD.17
Incidence of associated anomalies in truncus arteriosus.

(Compiled from Kirklin and Barrat-Boyes,18 Russell HM, et al,19
Bohuta, et al20 and Goldmunz12.
Associated anomaly
Anomalous origin of right or left subclavian artery or

innominate artery
10%
Interrupted aortic arch
~ 10%
Left superior vena cava to coronary sinus
6%
ASD (moderate or large)
10%
Additional VSD
4%
Mitral valve anomalies (hypoplasia, stenosis or

double-orifice)
10%
Complete atrioventricular septal defect
2%
Extracardiac anomalies
10%
DiGeorge syndrome
33%
Ventricles
Right ventricular (RV) hypertrophy and enlargement are
always present. Left ventricular (LV) outflow is usually
normal. VSD usually is large. However, in rare occasions,
VSD can be restrictive. If the overriding truncal valve is
committed primarily to the right ventricle, thus resembling
a posterior deviation of the ventricular septum, there is a
potential to develop LV outflow tract obstruction when VSD
is closed. Such VSD may need enlargement during surgical
repair. Significant truncal valve regurgitation is also a reason
for LV enlargement.
Associated Defects
Associated cardiac defects include right aortic arch, interrupted
aortic arch, atrial septal defect, persistent left SVC and others
(Table 1).11,18-20 Normal pulmonary venous return was seen
in all, but one of 47 cases in Van Praagh series.7 Associated
noncardiac defects occurred in approximately 21 percent of
cases, as seen in Van Praagh series.7
CLASSIFICATION
Even though several classifications exist, two classifications
of truncus arteriosus have been commonly followed. Collett
and Edwards6 classification is more widely used than that of
Van Praagh.7,8
Classification 1 (1949)
606
Collett and Edward classification6 is based on the degree of

main PA development and of the origin of pulmonary arteries
(Figure 1, top): Type Ithe spiral septum is partially formed,
therefore, there is partial separation of aorta and main PA.

Distal to the origin of main PA from the common arterial
trunk, both aorta and main PA are identifiable. Short segment
of main PA gives rise to both branch pulmonary arteries.
This type is seen in 48 to 68 percent of cases. Type IIno
main PA is present. Branch pulmonary arteries arise from the
back portion of the common arterial trunk very close to each
other. This type is seen in 29 to 48 percent. Type IIIno main
PA is noted. The two branch pulmonary arteries arise from
the side of the common arterial trunk. This type is seen in
6 to 10 percent of cases.21 Type IVthere is no main PA.
Branch pulmonary arteries arise from different parts of the
aorta. This type is also called pseudotruncus and is thought to
be part of pulmonary atresia with VSD.21 Commonly the left
PA originates from the undersurface of the arch and right PA
originates from mid-thoracic descending aorta, approximately
from the level of lung hilum.
Van Praagh classification7 is somewhat more complex.
Initially, truncus arteriosus is classified on the basis of
presence or absence of VSD; type Awith VSD. Type
Bwithout VSD. Since there have been very rare reports
of truncus arteriosus without VSD, type B is practically
nonexistent, except for the rare, single cases reported in the
literature. Type A is subdivided into four subtypes (Figure 1,
middle). A1main PA arises from the common arterial trunk
and then, bifurcates into branch pulmonary arteries (similar
to type I of Collette and Edward classification). A2absence
of main PA. Branch pulmonary arteries arise directly from
the common arterial trunk. Type A2 includes type II and
III of Collette and Edward classification. Type A3left PA
42
Truncus Arteriosus
Figure 1: Diagram illustrating various classifications described, including those of Collett and Edwards,6 Van Praagh,7 Modified Van Praagh8
(Adopted in Nomenclature Project 200022) and the most recent Simplified19. See text for detailed description
originates from aortic arch. Right PA originates from the

common arterial trunk. Type A4 truncus arteriosus with
interrupted aortic arch. Descending aorta receives blood flow
from a persistent ductus arteriosus.
Types A1 to A3 display well-developed branchial arch four
and poorly developed arch six. This results in absent Patent
ductus arteriosus (PDA). Type IV displays a poorly developed
arch four and well-developed arch six leading to hypoplasia,
coarctation, or interruption at the level of aortic isthmus and a
large PDA. Since type A4 is rare, presence of PDA in truncus
arteriosus is an uncommon finding. Overall, PDA was present
in 30 percent of cases with truncus arteriosus. However, PDA
is commonly noted, when there is associated arch hypoplasia,
coarctation or interruption of aorta. Thus, when there is a
large aorta present, PDA is usually absent (91%). Conversely,
PDA was present in all cases with small aorta with or without
coarctation or interruption.7
Congenital Heart Surgery Nomenclature and Database Project,
200022 proposes a unified classification (Figure 1, middle).
Very recently, a simplified categorization of common arterial
trunk has been proposed by the surgical group in Chicago, in
collaboration with Prof RH Anderson.19 This group proposes to
classify truncus arteriosus into only two categories, namely aorticdominant or pulmonary-dominant types (Figure 1, bottom). This
is based on the observation that among the 28 autopsy specimens
examined, 20 specimens were aortic-dominant. Pulmonarydominance was less common and was associated with presence
of a discrete aorta, which was hypoplastic and a PDA supplied
majority of flow to the descending aorta. In addition, only in the
pulmonary-dominant category, did the pulmonary arteries arise
from the side of common truncus and the aortic component is
identifiable as a discrete structure within the pericardial cavity.
Incidence was similar in 42 clinical case series from Chicago, in
which 38 were aortic-dominant type and four were pulmonarydominant type. Even though this classification is simplified, it is
fairly new and has not come into clinical use.
Figure 1 summarizes the above classifications. The
preference of the authors of this chapter is Collett and
Edwards classification.
607
Clarification of Related Terminology

Pseudotruncus is a term introduced by Bharati and associates
in 1974.21 The term refers to type IV truncus in Collett and
Edwards classification, in which pulmonary arteries originate
from descending thoracic aorta. This also refers to the subtype
of pulmonary atresia with VSD, where pulmonary arteries
are discontinuous and arise from aortic arch and descending
thoracic aorta, respectively. These may be aortopulmonary
collateral arteries rather than native pulmonary arteries. Use of
this term is discouraged in the nomenclature project paper.22
Hemitruncus refers to a condition with origin of a
pulmonary artery from ascending aorta. Again, use of this
term is discouraged in preference to more specific description
of the lesion. This also probably is a subtype of pulmonary
atresia with VSD with major aortopulmonary collateral
arteries rather than a subtype of truncus arteriosus.
Use of both pseudotruncus and hemitruncus are also
strongly discouraged by the authors of this chapter due to lack
of developmental basis for these terms.
NATURAL HISTORY
Natural history for survival without intervention is poor
in children with truncus arteriosus. Without surgical repair,
only 50 percent survive beyond 1 month, 30 percent survive
beyond 3 months, 18 percent survive beyond 6 months and
12 percent survive beyond 1 year.18 Cause of death during
neonatal period is congestive heart failure from large left
to right shunting and/or truncal valve regurgitation. Some
patients develop endocarditis or brain abscess, causing their
death.6 Children who survive to 1 year of age do so, because
of pulmonary artery stenosis and therefore, partial or complete
protection of the pulmonary vasculature from exposure to
systemic arterial pressure and consequent decreased risk for
development of pulmonary hypertensive vascular changes.
Therefore, there is low mortality after 1 year in this subgroup
of patients. Very few patients survive infancy and early
childhood with significant left-to-right shunting and yet, not
develop pulmonary vascular disease. This constitutes half of
survivors beyond 1 year or <5 percent of all infants born with
truncus arteriosus.23 When pulmonary vascular obstructive
disease (pulmonary vascular resistance > 9 Woods units m2)
develops during infancy or later, there is good chance for such
patients to survive into their teens without surgical repair.24
However, pulmonary vascular occlusive disease develops
gradually and Eisenmenger syndrome eventually occurs,
leading to death.
CLINICAL FEATURES
608
Presenting symptoms include features of heart failure in the

first few weeks of life consisting of tachypnea, tachycardia,
irritability, poor feeding and poor weight gain. Rarely,
respiratory distress occurs due to bronchial compression

from dilated common trunk, especially when associated
with interrupted aortic arch (usually right main bronchus) or
between anteriorly placed left pulmonary artery and posterior
portion of aortic arch (usually left upper lobe bronchus). Babies
with interrupted aortic arch or coarctation of aorta may present
precipitously when the ductus arteriosus closes in the neonatal
period. Such patients may constitute approximately 10 percent
of the patients with truncus arteriosus. Manifestations would
include circulatory collapse, metabolic acidosis, respiratory
distress and cyanosis. Absent femoral pulse will be part of the
physical finding.
Mild cyanosis may be present from decreased pulmonary
blood flow due to either pulmonary artery ostial stenosis or high
pulmonary vascular resistance, that is usual in neonatal period.
Cyanosis resolves when the pulmonary vascular resistance
decreases with transition to neonatal circulation. Features of
increased pulmonary blood flow and heart failure will develop
as the baby gets older, unless severe anatomic stenoses of
pulmonary arteries keep the pulmonary blood flow at a low
level. Recurrent respiratory infections and failure to thrive
occur just as with other infants with large left-to-right shunting.
In older children, cyanosis develops again as Eisenmenger
syndrome occurs with development of pulmonary vascular
obstructive disease.
Large volume pulse due to diastolic reversal of flow in the
aorta from continued diastolic flow into the pulmonary arteries
may easily be detected. Hyperdynamic precordium occurs.
Precordial bulge occurs due to right ventricular enlargement
and hypertrophy. Signs of respiratory distress occur with large
left-to-right shunting. However, if the pulmonary blood flow
is normal or diminished due to anatomic pulmonary artery
stenosis or persistence of high pulmonary vascular resistance,
the child will present without features of heart failure or
respiratory distress. There may be mild cyanosis, however.
Auscultation reveals normal to loud S1. Systolic click will
be present from truncal valve abnormalities or dilated common
arterial trunk. Second sound will be single. Systolic ejection
murmur with or without a thrill from pulmonary artery stenosis
or truncal valve stenosis may be present. Similar murmur is also
heard when there is increased pulmonary blood flow through
nonstenotic branch pulmonary arteries. With severe pulmonary
artery stenosis, this murmur may be continuous. Presence of a
high frequency, early diastolic decrescendo murmur indicates
truncal valve regurgitation. This is a discrete murmur although,
may be very low in intensity. This should not be confused
with a diastolic rumble from increased pulmonary blood flow,
due to increased flow across the mitral valve; this is a middiastolic event. In rare cases of restrictive VSD, VSD murmur
may be heard. Liver enlargement is present with heart failure,
secondary to a large left-to-right shunt.
side. In older children with pulmonary vascular disease,

cardiomegaly and pulmonary plethora diminish with time.
Infants with Heart Failure
Electrocardiogram
Infants with heart failure usually have mild cyanosis and

the differential includes transposition of great arteries with
VSD, double outlet right ventricle, tricuspid atresia with large
VSD (with or without transposition of great arteries), single
ventricle without pulmonary stenosis and total anomalous
pulmonary venous return (TAPVR). In tricuspid atresia,
left axis deviation and LV dominance are noted in the ECG.
Paucity of LV forces may be present in ECG in TAPVR.
Absent pulmonary artery segment in chest X-ray will support
either truncus or transposition of great arteries. However,
there can be a normal-appearing pulmonary artery segment in
type I truncus arteriosus, where the small common pulmonary
artery segment may produce a PA segment shadow on chest
X-ray. Right aortic arch supports the diagnosis of truncus
arteriosus. Echocardiographic features are diagnostic for each
of the conditions mentioned above.
Normal QRS axis (rightward or normal quadrant) and RV

hypertrophy are noted early. LV hypertrophy develops later.
Often, biventricular hypertrophy is present at the time of
diagnosis. P pulmonale develops later. Thus, none of the ECG
features are diagnostic in truncus arteriosus.25
Older Infant and Children with Continuous Murmur and

Evidence of Increased Pulmonary Blood Flow
Aortopulmonary window or PDA should be considered in
the differential. Mild cyanosis is present in the children
with truncus and may be too subtle to be recognized. Small
or absent PA segment, if present in chest X-ray will support
truncus arteriosus. Echocardiographic features are distinctive.
Children with Cyanosis

In cyanotic children, differential diagnosis will include
tetralogy of Fallot, pulmonary atresia with VSD, tricuspid
atresia, atrioventricular septal defect with pulmonary stenosis
and double-outlet right ventricle with pulmonary stenosis.
Echocardiographic findings are diagnostic.
NONINVASIVE EVALUATION
Chest X-ray
Marked cardiomegaly and pulmonary plethora are present
in most infants. In type I truncus, there may be a normal PA
segment visible. In other types, the PA segment is diminutive
or absent, giving the appearance of a narrow superior
mediastinum. Right aortic arch is noted in approximately
33 percent of truncus arteriosus patients. Comma sign in
left upper mediastinal border indicating high origin or high
arching of left pulmonary artery may be recognizable in type
III truncus.2 Absent unilateral pulmonary artery from truncus
may cause pulmonary oligemia and smaller thorax on that
42
Truncus Arteriosus
DIFFERENTIAL DIAGNOSIS BASED

ON CLINICAL FEATURES
Echocardiography
Echocardiography is the most important study that provides
the diagnosis, as well as most of the information necessary
for surgical planning. In neonates and infants, no further
investigations are necessary, unless there were specific
unanswered questions exist after echocardiography.
Objectives of echocardiography include demonstration of
single great artery from the ventricles, conal septal VSD, over
riding truncal valve, truncal valve anatomy, pulmonary arteries,
PDA and other associated anomalies including interrupted
aortic arch, anomalies of the origin of aortic arch branches,
abnormalities of coronary artery origins, persistent left SVC,
additional VSDs, tricuspid and mitral valve anomalies,
if any. It is important to differentiate truncus arteriosus
from pulmonary atresia with VSD and aortopulmonary
window.26 Echo findings should enable determination of the
type of truncus arteriosus and its physiology. Systematic
echocardiographic evaluation of truncus arteriosus is welldescribed in multiple echocardiography text books such as by
Snider and Ritter.27
Parasternal long-axis view (Figure 2) shows the characteristic
conal septal VSD with apparent overriding of aorta (truncus).
Inability to show the second outflow tract and valve
(pulmonary valve) is a feature that helps to distinguish this
entity from tetralogy of Fallot. Anteriorly, the common arterial
trunk does not have continuity with infundibular septum.
Posteriorly, there is fibrous continuity between truncal valve
and mitral valve. The branch pulmonary arteries will be seen
to arise from the posterior and leftward aspect of the common
arterial trunk. Color Doppler study will provide an assessment
of truncal valve stenosis and regurgitation.
Parasternal short-axis view helps to evaluate truncal valve
anatomy regarding number of valve leaflets (Figure 3), stenosis
or regurgitation. Pulmonary valve is undetectable. Location
of the VSD should also be confirmed. Characteristically,
the membranous ventricular septum is intact with the conal
septal area deficient (between 12 Oclock and 2 Oclock in
parasternal short-axis view (Figures 4A and B). Overriding
of the common truncal valve may be unequal across the
ventricular septal defect creating an impression of anterior
or posterior deviation of the ventricular septum. Posterior
609
A
Figure 2: Parasternal long-axis view showing common arterial trunk
(TA), ventricular septal defect (arrow) and truncal valve overriding
ventricular septum. LV = Left ventricle; RV = Right ventricle
Figure 3: Parasternal short-axis view showing the cross-sectional view

of truncal valve. In this example, the truncal valve has three, dysplastic,
moderately thickened leaflets. LA = Left atrium; RV = Right ventricle
610
deviation of ventricular septum towards the LV has the

potential to develop LV outflow tract obstruction after repair.
Therefore, should be looked for. Coronary arteries will arise
from the common trunk.
Branch pulmonary arteries can be assessed further in this
view (Figures 5A and B). In type I truncus, the main pulmonary
artery will arise from the left side of the common trunk and
branches into right and left pulmonary arteries. In type II truncus,
the two branch pulmonary arteries arise from the posterior
aspect of common arterial trunk. When the appearance of
pulmonary artery branching is difficult to distinguish between
type I and II, it has become an unrecognized clinical practice
Figures 4A and B: A. Parasternal short-axis view showing the

ventricular septal defect (VSD) (arrow). VSD is conal septal VSD
with intact membranous portion of the ventricular septum (arrow);
B. Color Doppler imaging shows right-to-left shunting (arrow)
across the conal septal VSD in this echocardiogram performed at
1 day of age, upon presentation with mild cyanosis. LA = Left atrium;
RA = Right atrium; RV = Right ventricle
Figures 5A and B: A. Parasternal short-axis view showing origin of

main pulmonary artery from the truncus (TA). The main pulmonary
artery (MPA) bifurcates into right (RPA) and left (LPA) pulmonary
arteries; B. Color Doppler imaging shows nonturbulent flow in both
pulmonary arteries. RCA = Right coronary artery
to refer to it as type 1.5! In type III, branch pulmonary arteries

arise separately from either sides of the common arterial
trunk. Frequently, these origins are far apart such that they
may not be seen in one frame. A combination of parasternal
short- axis view and suprasternal views may have to be used to
demonstrate each of the two branch pulmonary arteries.
Apical and subcostal views confirm the findings regarding
VSD (Figure 6), truncal valve anatomy and function.
42
Truncus Arteriosus
Figure 6: Apical four-chamber view demonstrating a conal septal

VSD (ventricular septal defect) with an overriding truncal (T) valve.
Differential diagnosis for this appearance would include both truncus
arteriosus and pulmonary atresia with VSD. Similar appearance may
be seen in interrupted aortic arch with VSD as well. LV = Left ventricle;
RV = Right ventricle
These views may confirm the inability to demonstrate

pulmonary valve and demonstrate branch pulmonary arteries
(Figures 7A and B). In newborn, subcostal sagital view
may also help to evaluate aortic arch. Suprasternal notch
view is useful in assessing aortic arch anatomy, sidedness
and its branches, PDA and branch pulmonary arteries. PDA
is absent in majority of cases. When PDA is present with
interrupted aortic arch, this may be lead an inexperienced
echocardiographer to mistake the large PDA for an aortic
arch and miss the diagnosis of interrupted aortic arch. Paying
careful attention to presence or absence of head and neck
branches may help to avoid such misstep. Right aortic arch
and interrupted aortic arch are the common associations.

Magnetic resonance imaging (MRI) is noninvasive and is useful
in the following situations in truncus arteriosus management
definition of pulmonary artery origins, definition of aortic
arch and branching pattern, etc. when echocardiography
cannot determine the exact anatomy. Differentiation from
aortopulmonary window may be easier. Compared to cardiac
catheterization, MRI also spares use of radiation.
Figures 7A and B: Apical four-chamber view dual frames consisting

of (A) 2D image and (B) color Doppler image obtained by a more
anterior tilt of the transducer from the previous figure. These images
demonstrate main pulmonary artery (MPA) originating from the left
side of the truncus arteriosus (TA) and bifurcating into right (RPA) and
left (LPA) pulmonary arteries
Objectives of Catheterization
Objectives of catheterization include definition of aortic
arch and its branches, identification of pulmonary artery
anatomy, coronary anatomy if necessary and hemodynamic
statequantification of pulmonary blood flow and pressures
and estimation of pulmonary vascular resistance and its
reversibility in older infants and children.15
Catheter Course
In current clinical practice, the diagnosis of truncus arteriosus
is usually known at the time of catheterization. The catheter
usually passes easily from RV to truncus arteriosus and into
either branch pulmonary arteries or via PDA into descending
aorta. Pitfalls in interpretation of the catheter passage include
lack of recognition of either an aortopulmonary window in
which the catheter may have passed through the window from
main PA to aorta or a truncus arteriosus with interrupted aortic
arch in which the catheter has passed from truncus via PDA
into descending aorta. Cannulating each branch pulmonary
artery for pressure measurement is necessary to evaluate any
stenosis at their origin. If cannulating each branch pulmonary
artery is difficult using the venous catheter via RV, this can be
accomplished using the retrograde, arterial catheter.28
Hemodynamic Evaluation
Catheterization and Angiography

In neonates and infants, cardiac catheterization is only
required when echo and MRI do not provide the information
necessary for surgical planning.
Measurement of pulmonary artery pressures is important in

the overall evaluation. Evaluation of pulmonary vascular
resistance and demonstration of its reversibility becomes a
crucial entity in older unoperated children being considered
611
for surgical correction. There are practical difficulties in

obtaining representative samples for oxygen saturation and
PO2 to use in calculating pulmonary and systemic blood
flows by Fick principle. In type I and II truncus, it is usually
assumed that there is good mixing of RV and LV Blood,
although there can be streaming of blood leading to a 5 to
10 percent difference in oxygen saturation between truncal
arterial and PA samples. Calculation of pulmonary blood flow
is difficult when the pulmonary arteries have separate origins
(type III and IV truncus) and if one lung is supplied by aortopulmonary collateral arteries. Administration of 100 percent
oxygen and/or inhaled nitric oxide is used to determine
reversibility of pulmonary arterial hypertension. When 100
percent oxygen is used, PO2 should be measured in addition
to oxygen saturation, because the dissolved oxygen level will
no longer be negligible in Fick calculations for systemic and
pulmonary blood flows. In order to estimate relative blood
flow to each of the lungs, nuclear quantitative lung perfusion
scans may be used. However, this technique has not been
formally studied or validated for this application.
Figure 8: Selected cine frame in anteroposterior view of an angiogram

from the truncus arteriosus (TA) demonstrating the origin of the main
pulmonary artery (MPA) and dividing into right (RPA) and left (LPA)
pulmonary arteries. The features are consistent with Collett and
Edwards type I truncus
Angiography
Ventriculography
Relative sizes, additional VSDs, relationship of VSD to truncal
valve/arterial trunk should be defined.
Truncal Root Angiography

Truncal root angiography will delineate truncal valve, number
of cusps, truncal valve regurgitation, anatomy of truncus
arteriosus, pulmonary artery relationships and probably
origins and coronary arteries. When a common pulmonary
artery is present, it is usually noted at the leftward and
posterior part of the common arterial trunk. Figures 8 and 9
illustrate angiographic features of type I and type II (Collett
and Edwards) truncus.
Diagnosis of Aortic Interruption

Diagnosis of aortic interruption can be difficult with
angiography. Attention must be paid to each branch of the
aortic arch. A large PDA may be mistaken for aortic arch and
the ascending aorta for innominate artery. Confirming the
position of each of the aortic arch branches helps to correctly
interpret aortic arch anomalies.
612
Figures 9A and B: Selected cine frames in (A) anteroposterior

view and (B) left anterior oblique view of an angiogram from the
truncus arteriosus (TA). Note: The origin of right (RPA) and left (LPA)
pulmonary arteries from posterior aspect of TA, consistent with Collett
and Edwards type II truncus
observations made from echocardiography and during the

catheterization itself.
Thoracic Aortogram
This will show any aortopulmonary collateral arteries to the
lungsespecially, only one PA is identified to originate from
aorta or truncus.
Selective Pulmonary Angiograms
Pulmonary Venous Wedge Angiogram
Special views may be needed if origins of the pulmonary

arteries are to be shown. The ideal camera angles will vary
in each patient and need to be determined based on various
Pulmonary venous wedge angiogram may become necessary

to identify native pulmonary arteries when these are not
visualized otherwise.
42
MANAGEMENT
Truncus Arteriosus
Medical Management
Medical management depends on the status of pulmonary
blood flow. When there is increased pulmonary blood
flow and congestive heart failure, therapy is indicated
to address heart failure. Diuretics and digoxin should be
used in adequate doses. Afterload reducing agents such
as captopril may be used, if necessary. High calorie diet
may be necessary in infants who show signs of increased
pulmonary blood flow and heart failure. For infants and
children who are slightly cyanotic and not have features
of increased pulmonary blood flow, active therapy may not
be necessary. But, close follow- up will be needed, while
waiting for surgery. Surgery may be postponed if the patient
stabilizes and gains weight. But, surgery should preferably
be performed in early infancy for the fear of development of
pulmonary vascular changes.
Surgical Management
Palliative procedure, if necessary, will be pulmonary artery
banding. PA banding may be technically difficult depending
upon the length of the common PA. Banding individual
pulmonary arteries is fraught with difficulty in getting the
appropriate size band for each vessel. Banding of the PA is
largely abandoned in the current day management.
Surgical repair upon diagnosis is the usual approach in
the current era. Exact timing of surgery may vary depending
upon the specific features in each patient. Since the only
approximately 10 percent of patient survive first year without
surgery and there is a risk of rapid development pulmonary
vascular obstructive changes, surgical repair usually is
performed in early infancy if not as newborn.
Principles of surgery include closure of VSD, separation
of the pulmonary arteries from the common arterial trunk and
connecting them to RV-PA conduit and closing the defect in
the common arterial trunk (Figure 10). Usually, truncal valve
does not require any surgical intervention, unless there is
significant stenosis or regurgitation.
When there is associated interrupted aortic arch, surgical
repair has to be performed as newborn after initial stabilization
on prostaglandin infusion. Surgical mortality is relatively high,
when a combined repair of truncus arteriosus and interrupted
aortic arch need to be performed. Presence of truncal valve
regurgitation at presentation greatly worsens the prognosis for
surgical outcome and survival. Surgical options include truncal
valve repair, truncal valve replacement using homografts or
mechanical valves; these have not produced good results, but
may be necessary.
Figure 10: Schematic diagram of surgical repair of truncus arteriosus

consists of separation of pulmonary arteries (PAs) from the common
arterial trunk and connecting the pulmonary arteries to the right
ventricle (RV) via a valved conduit, which is usually a homograft.
Ventricular septal defect closure, which is part of this surgery is not
shown in this figure. LV = Left ventricle; RA = Right atrium
Postoperative Management
In addition to the usual postoperative care, immediate post
operative treatment includes management of episodes of
pulmonary hypertensive crises. Considerable precautions
are taken to avoid pulmonary hypertensive crisis by keeping
the baby sedated with ample analgesics and sedatives. Some
institutions routinely use muscle relaxants at least for the first
night of surgery. Nitric oxide is used as needed. Ventilatory
strategy to maintain alkalosis and avoiding hypoxia and
hypercarbia is instituted.
There is also significant morbidity from pulmonary artery
stenosis, usually at the distal anastamosis of the conduit
in the postoperative period. Such stenosis may need cardiac
catheterization and angiography to demonstrate the stenosis.
Stenting of the distal RV-PA conduit or proximal branch
pulmonary arteries (Figures 11 and 12) is an option in this
period. Balloon angioplasty of such conduit/pulmonary artery
stenosis is not advisable due to fresh suture lines.
Outcome of Treatment
Early Surgical Outcome
In a recent review of Society of Thoracic Surgeons database
between 2000 and 2009 in 63 centers, 572 surgeries had been
613
Long-term Surgical Outcome
Figures 11A and B: Bilateral branch pulmonary arteries stenosis prevented recovery during postoperative period in this newborn after repair
of truncus arteriosus. Stenosis of right (RPA) and left (LPA) pulmonary
arteries are shown in A and B, respectively. Bilateral stents were placed
in RPA and LPA shown in the lateral view freeze frame in Figure 12
Figure 12: Lateral view freeze frame of stents placed at the origin
of both RPA and LPA in the baby shown in Figure 11. Relief of
bilateral branch pulmonary artery stenosis enabled weaning from
positive pressure ventilator and postoperative recovery in this infant.
PA = Pulmonary artery
performed at a median age of 12 days.29 Surgical mortality for

truncus arteriosus repair was 10 percent. Truncus arteriosus
repair along with truncal valve repair was performed in 37
babies. Mortality for this group was higher at 30 percent.
Repair of truncus arteriosus and interrupted aortic arch was
performed in 38 babies in whom a mortality of 60 percent
was noted. In four babies, valve surgery was performed as
second surgery after an initial truncus repair. None of these
four babies survived.29 Single center experience of combined
repair of truncus arteriosus and interrupted aortic arch
from Melbourne, Australia in a cohort of 16 patients, who
underwent surgery between 1985 and 2007 revealed an early
mortality of 12.5 percent.20
614
In the study referred to above20 median follow-up in 13 patients

was 18.2 years. No late deaths were recorded. However,
there were multiple reoperations and catheter interventions.
Thirteen patients underwent 25 reoperations and five catheter
interventions. Freedom from reoperation at 1 month was 69
percent, at 3 years 54 percent, at 5 years 30 percent, at 10 years
11 percent and 0 percent at 15 years. Most of the reoperations
were for replacement of RV-PA conduits; freedom from RVPA conduit replacement was 85 percent at 1 month, 63 percent
at 3 years, 40 percent at 5 years , 11 percent at 10 years and 0
percent at 15 years. Some patients also required surgery of the
truncal valve.20
Long-term (20 years) outcome after surgery (operated
between 1975 and 1995) from California was reported in
1997.30 They studied 165 patients who survived after surgery.
Median age at operation was 3.5 months (range of 2 days to 36
years). Median follow-up period was 10.2 years (maximum 20
years). Twenty-five patients were lost to follow-up. Twentythree late deaths occurred. Survival after hospital discharge was
90 percent at 5 years, 85 percent at 10 years and 83 percent in
15 years. Most of the late deaths were related to reoperations.
Independent risk factor for nonsurvival was preoperative
presence of moderate or severe truncal valve regurgitation. In
addition, 107 patients underwent 133 conduit replacements and
26 patients required 30 truncal valve replacements. Freedom
from truncal valve surgery in the absence of any prior truncal
valve repair was 95 percent at 10 years. Overall, long-term
results are good among children who survived to discharge.
Similar results were reported from Germany with a followup of 10 years.31 Patients operated between 1987 and 1997 were
studied. There were 46 patients in the cohort with a median
age of 62 days and a median weight of 3.4 kg at operation.
Among associated anomalies, coronary anomalies were the
commonest (n = 16); truncal regurgitation was noted in 12 and
interrupted aortic arch in five. Two hospital deaths were noted
(both with severe truncal regurgitation and interrupted aortic
arch) and one death at 4 months after surgery. No late deaths
were reported. Freedom from RV-PA conduit reoperation at
five years was 43 percent when aortic homograft was used
and 73 percent when pulmonary homograft was used.
The predictor of reoperation among the patients was use of a
smaller homograft size.32 Also, presence of preoperative truncal
regurgitation at moderate or higher level, need for truncal valve
repair and concomitant repair of interrupted aortic arch were
predictors of poor outcomeboth short-term and long-term.
Successful pregnancies have occurred in patients who have
had truncus repair in the pastespecially when the individual
is in good functional state. Prepregnancy counseling
should include checking the status of 22q11 microdeletion.
Alternative Surgical Approaches

In a series of 32 patients, 17 had conventional RV-PA conduit and
13 had a conduit created using LA appendage and monocuspid
valve.33 Mortality rates were similar between these two groups.
However, reintervention rate at a mean follow-up of 40 months
was significantly lower in the non-conduit group; five of 11
in conduit group had conduit replacement, while only two
of nine in non-conduit, group required replacement. Lesser
RV outflow gradient and better growth of branch pulmonary
arteries were also noted in the non-conduit group. Whether
or not this advantage at short-term follow-up33 holds up at a
longer-term follow-up remains to be seen.
range 0.530.83) was associated with higher re-intervention

rate. Freedom from conduit reoperation at 1 year was 92
percent and at 2 years, 76 percent. Development of PA stenosis
was considered secondary to surgery rather than preoperative
reason, because the pulmonary arteries were adequate in size
prior to surgery.34
We utilize balloon angioplasty and/or stenting of branch
pulmonary arteries and/or the conduit (Figures 13 to 15) to
relieve the right ventricular outflow tract obstruction and
attempt to reduce the right ventricular pressure to less than
half systemic level. Balloon angioplasty35 and stents36,37
appear to prolong the life of the conduit and lengthen the
interval between conduit replacements.
Recently, older candidates with conduit stenosis and/or
regurgitation have an option of transcatheter valves such as
Bonhoeffer,38 Melody (Medtronic, Inc. USA)39 or Edwards
Sapien (Edward Lifesciences Inc)40 valves. Short-term
results are encouraging for these valves. While transcatheter
42
Truncus Arteriosus
Depending upon the results, appropriate counseling of the risk

of the genetic and associated defect in the offspring must be
provided. Follow-up with specialist cardiologist during and
after pregnancy should be done.
Long-term Sequelae after Surgical Repair

Right Ventricle-Pulmonary Artery (RV-PA) Conduit
Obstruction, Regurgitation and Branch PA Stenosis
The RV-PA conduit obstruction, regurgitation and branch PA
stenosis can develop in early postoperative period and late after
surgery. In a recent study from Boston Childrens Hospital, a
cohort of 156 children who underwent truncus arteriosus repair
was studied.34 Reinterventions were required within 2 years
in 106 children; 73 were therapeutic catheter interventions
consisting of balloon dilatation and/or stent placement in RVPA conduits (n = 29), pulmonary arteries (N = 31) and both (N
= 13). Thirty-six children required surgical reintervention for
replacement of RV-PA conduit. Freedom from reintervention at
1 year was 68 percent and at 2 years, 48 percent. In multivariate
analysis, use of smaller conduit size (hazard ratio 0.66/mm;
Figures 13A and B: Selected cineangiographic frames in a sittingup (15-degree left anterior oblique and 30-degree cranial) view
demonstrating severe stenosis of the junction of the conduit with the
pulmonary artery (arrow in A). Following stent implantation (arrow in B)
the right ventricular pressure decreased and the gradient across this
region abolished. Note: Normal sized right (RPA) and left (LPA) branch
pulmonary arteries. MC = Marker pig-tail catheter; RV = right ventricle
Figures 14A to C: Selected cine frames in the lateral view demonstrating stenosis of the conduit (arrow in A), which is wide open
following stent implantation (arrow in C). Stent (St) before the contrast injection is shown in B. RV = Right ventricle
615
8
conclusion
Figure 15: Selected cineradiographic frame in the posterior-anterior

view demonstrating stents in both right (RPA) and left (LPA) pulmonary
arteries. There was no significant conduit obstruction at the time of
placement of RPA and LPA stents
valve implantations will avoid need for surgical valve

replacement, it remains to be seen how much of an influence
that these transcatheter valve implantation procedures have in
the life-time of a given patient.
Truncal Root Dilatation and Truncal Valve Regurgitation

Truncal root dilatation and truncal valve regurgitation occur
in most of the patients. In a recent study of a cohort of 78
patients, the mean truncal root diameter Z-score was 5.1
2.3. No dissection or rupture occurred. However, six patients
underwent aortic root surgery for aortic root dilatation
associated with truncal valve regurgitation and LV dilatation.41
Myocardial Dysfunction
Myocardial Dysfunction may develop from repeated surgical
procedures, conduit dysfunction, delayed surgery and myocardial ischemia.
Arrhythmias
Arrhythmias though rare can occur, also an important disorder
after surgical repair.
Progressive Pulmonary Vascular Disease

616
In patients with delayed detection, pulmonary vascular

obstructive disease may develop.
Truncus arteriosus is one of the conotruncal anomalies

with high association with 22q11 microdeletion/DiGeorge
syndrome. The diagnosis is relatively simple and can
often be suspected on clinical features and confirmed by
echocardiography with a rare need for cardiac catheterization
and selective cineangiography. Surgical correction by VSD
closure and insertion of RV-PA conduit, usually a homograft
in early infancy is the current management option. Outcome
depends on defect type, pulmonary artery anatomy, aortic
arch anomalies and truncal valve function. After surgery,
these patients may need multiple reinterventions both for
replacement of RV-PA conduit and transcatheter therapy
for pulmonary artery rehabilitation and to address conduit
dysfunction. Overall, surgical outcome has improved over the
past several decades. Successful pregnancy is probable. Risk
of recurrence of the genetic and cardiac defect in the offspring
depends on genetic testing in the mother. Appropriate
counseling should be provided to prospective mothers with
repaired truncus arteriosus.
The physician should look upon the patient as a besieged
city and try to rescue him with every means that art and
science place at his command.
Alexander of Tralles
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28. Rudolph M. Congenital heart diseases of the heart: Clinicalphysiologic considerations. 2nd edition. Armonk, NY. Futura
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with outcomes of persistent truncus arteriosus. J Am Coll
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34. Lund AM, Vogel M, Marshall AC, et al. Early reintervention
on pulmonary arteries and right ventricular outflow tract after
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replacement of pulmonary valve in a right-ventricle to
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medium-term outcomes after transcatheter pulmonary valve
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arteriosus for surgical correction: Anatomic and hemodynamic
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20. Bohuta L, Hussein A, Fricke TA, et al. Surgical repair of
truncus arteriosus associated with interrupted aortic arch:
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21. Bharati S, McAllister HA Jr, Rosenquist GC, et al. The surgical
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617
C hapter
43
D-transposition of Great Arteries

Suresh Rao, Swati Garekar
Introduction
Transposition of the great arteries (TGA) is the most common
cause of a cyanotic newborn. Its management has been one of
the amazing success stories as far as the treatment of various
complex congenital heart defects in the last two decades is
concerned. The advances in medical science has converted
a lesion with a very high mortality if left untreated, to one
where the child with TGA today can look forward to having
a reasonably normal lifestyle and hopefully longevity. This
treatise will discuss pure or isolated transposition of the
great arteries, i.e. a lesion with atrioventricular concordance,
ventriculoarterial discordance, two good sized ventricles
and atrioventricular valves, with either an atrial septal
defect (ASD), ventricular septal defect (VSD) or patent
ductus arteriosus (PDA) as a single associated anomaly or a
combination of anomalies.
Transposition of the great arteries means that the origin
of the great arteries from the heart is reversed. In simple
terms, the aorta originates from the right ventricle (RV) and
the pulmonary artery originates from the left ventricle (LV),
while the atrioventricular (AV) connections are normal (AV
concordance with ventriculoarterial (VA) discordance).
Specifically, D transposition of the great arteries implies
that the aortic valve is D related to the pulmonary valve
(to the right and anterior) in the setting of ventriculoarterial
discordance. However, VA discordance with variable
semilunar valve relationship has been described. As long as
the pathophysiology and the management pathway is the same
as classic D-TGA, these variations are still called transposition
of the great arteries.
Embryology and Inheritance

Transposition of great arteries is believed to be due to
abnormal presence and growth of the subaortic infundibulum.
This is absent in normal hearts. This infundibulum pushes the
aortic valve anteriorly and to the right. At the same time the
subpulmonary infundibulum fails to develop. TGA is usually
an isolated defect. Complex TGAs are more likely to be
associated with extracardiac anomalies. An Italian multicenter
study found a 10 percent recurrence risk of congenital heart
disease (CHD) in families with a child with TGA. This study
looked at 370 consecutive patients with TGA. The most
common CHDs reported were D-TGA, L-TGA, tetralogy of
Fallot and VSD.1 The finding of congenitally corrected TGA
(L-TGA or double discordance) in family members suggest a
common causative gene for these defects. This is against the
traditional classification of D-TGA under conotruncal defect
and L-TGA under looping defects.
The genetic mechanisms and several mutations have
been implicated as the cause of discordant ventriculoarterial
connections.The genes which maybe involved are the growth
differentiation factor-1 gene, the thyroid hormone receptorassociated protein-2 gene and the gene encoding the cryptic
protein.2
Incidence
Transposition of great arteries is a common form of congenital
heart anomaly occurring in 1:2000 to 4500 births and
accounting for 7 to 8 percent of all congenital heart defects.
Male to female ratio is 2:1, increasing to more than 3:1 for
TGA with intact ventricular septum.3,4
ETIOPATHOGENESIS
The exact etiology of this disease is still unknown. The
associated risk factors, namely gestational diabetes
mellitus, maternal exposure to rodenticides, herbicides, and
maternal use of antiepileptic drugs have been postulated.2
Isolated TGA is called a simple TGA. It could be
associated with a large VSD (up to 45% of cases). The types
of VSDs seen are commonly perimembranous, muscular
Pathophysiology
Because of the reversed connections, the venous blood
(deoxygenated blood) returning from the body goes back
to the body as the RV leads out to the aorta. Similarly, the
oxygenated or pure blood returning from the lungs via the
left atrium and LV goes back to the lungs via the pulmonary
artery (circulation in parallel). This form of circulation is
incompatible with life after the baby is born, unless there
is mixing at the atrial, ventricular or arterial level. Of
these three, the atrial level mixing is the most effective
in getting some left atrial blood out to the aorta and also
some deoxygenated right atrial blood out to the pulmonary
artery. TGA is a circulation where the net pulmonary
blood flow is increased (presence of bronchopulmonary
collateral circulation). Hence, children with TGA and with
the associated hypoxia, develop accelerated pulmonary
vascular disease if left untreated. The several anatomic and
functional factors and the extent of intercirculatory mixing
(Box 1), influences the clinical manifestations and course of
the disease.5
Simple transposition of great arteries usually presents in
the neonatal age group with severe cyanosis. The pulse
oximetry reading may show values of less than 40 percent.
This extremely low saturation can be confirmed by an arterial
blood gas. In a simple TGA, reverse differential cyanosis
will be present: the postductal saturation will be higher than
the preductal one. On auscultation, the S1 may be loud; S2
appears single. There may be a soft 2/6 ejection systolic
murmur along the upper sternal border. There is no diagnostic
auscultatory finding unfortunately. For the pediatrician
handling a neonate presenting with severe cyanosis, the other
differential diagnosis are pneumonia and/or sepsis. Absence
of respiratory distress, clear lung fields on chest radiograph
and absence of septic markers will make cyanotic CHD
the number one differential. Presence of a VSD is not an
insurance against cyanosis, as flow of blood across the VSD
will be predominantly unidirectional.
The neonate, who escapes detection of cyanosis will present
in infancy/early childhood with failure to thrive. If there is
subpulmonary valvar obstruction, a murmur may be the
presenting sign. In complex TGAs with increased pulmonary
blood flow, the infant presents with signs and symptoms of
congestive heart failure.
The one who survives to early and mid childhood have
degrees of pulmonary stenosis (PS) and become increasingly
cyanotic as the PS progresses with growth and suffer the
complications of polycythemia and hyperviscosity syndromes.
43
d-transposition of great arteries
and malalignment (30% each). When coarctation or arch

interruption is associated with TGA it is called a complex
TGA. About 20 percent of isolated TGAs have some form
of left ventricular outflow tract obstruction (LVOTO) and
this is usually dynamic. TGA with VSDs have a 30 percent
incidence of LVOTO and this is usually fixed. The common
causes include mitral valve tissue; posterior deviation of
the conal septum and accessory tricuspid valve tissue
protruding in from the VSD.5
Other rarer defects of the heart like a hypoplastic ventricle,
an aortopulmonary window, total anomalous pulmonary
venous connection, complete atrioventricular septal defects or
valvular deformities may also be seen.3,4 Coronary anomalies
are also very common in complex TGA. The most common
variation is origin of the circumflex artery from the right
coronary artery (16% incidence).
Natural History
A neonate with untreated TGA and insufficient mixing channels
(PDA/ASD/VSD) will succumb to hypoxia. The ones with
sufficient mixing will show a retarded physical and mental
growth and succumb to ill effects of hypoxia and polycythemia.
Overall, approximately 30 percent of neonates will have expired
by age 1 month and 90 percent by age 1 year.6
Diagnosis
Box 1: Physiological Clinical classification in
transposition of great arteries5
TGA (IVS or small VSD) with increased PBF and small
intercirculatory shunting
TGA (large VSD) with increased PBF and large intercirculatory
shunting
TGA (VSD and LVOTO) with restricted PBF
TGA (VSD and PVOD) with restricted PBF
IVS = Interventricular septum; LVOTO = Left ventricular outflow
obstruction; PBF = Pulmonary blood flow: PVOD = Pulmonary
vascular obstructive disease; TGA = Transposition of great arteries;
VSD = Ventricular septal defect.
In the current era, TGA is diagnosed by transthoracic

echocardiography. Almost all anatomic features and even
coronary arterial anomalies may be picked up by this imaging
modality. With improvements in fetal echocardiographic
techniques, TGA may be diagnosed with certainty in the
fetus as early as 14 weeks of gestation. On echocardiography,
a detailed and complete segmental analysis is essential
(Figures 1A to C). Attention to AV valve annulus size,
ventricular size, description of the kind (if any) of
subpulmonary obstruction, morphology of the semilunar
valves (especially the pulmonary valve-the future aortic
valve), size discrepancy of the main pulmonary artery versus
619
620
the ascending aorta, coronary artery anatomy (low parasternal

window) helps to avoid surprises on the operating table. An
anomalous coronary artery can be suspected if in any view, a
coronary is seen coursing posterior to the pulmonary artery.
A few classifications for description of the coronary artery
anatomy exist. We describe the coronary arteries in terms of
arising from sinus 1 (leftward sinus) and sinus 2 (rightward
sinus). The normal coronary artery arrangement would thus
be described as 1LC 2R. A description in words of what is
seen on echocardiography most often conveys the anatomy
better than complicated classification systems. This is
especially true, when images are suboptimal and there is a
suspicion of anomalous coronary. A mention must be made of
any intramural course or juxtacommissural origin.
It is indeed very rare that cardiac catheterization is done for
TGA. The indication for cardiac catheterization in TGA is to
assess LV and RV pressure and suitability for arterial switch in
patients who present late and noninvasive assessment shows
borderline LV size. The only practical indication seems to be to
Figures 1 A to C: A. D-TGA: parasternal long axis view of the left

ventricle giving rise to a great artery that dives posteriorly; indicating
that it is the pulmonary artery; B. D-TGA: parasternal short axis view of
the ventricles: preserved left ventricle: septum is convex towards RV;
the wall thickness of the left ventricle is preserved; C. D-TGA: slightly
upwards tilted parasternal long axis view: the two great arteries arising
parallel to each other in 2D and color Doppler. LA = Left atrium; Left
ventricle; PA = Pulmonary artery; RV = Right ventricle
assess pulmonary artery pressure and response to vasodilators

in cases of late presentation when a palliative repair is being
comtemplated. The derived value of pulmonary vascular
resistance is fraught with assumptions. Computed tomography/
magnetic resonance imaging (CT/MRI) maybe useful and
indicated in those rare cases where an abnormal aortic arch
(coarctation or interruption) is not visualized to satisfaction.
A chest radiograph in the neonate with TGA will show a clear
lung field, normal heart size and a narrow superior mediastinum
(as the great arteries lie on top of each other) (Figure 2). In the
infant, increased pulmonary vascularity and mild cardiomegaly
will be seen (Figure 3). In fact, severe cyanosis accompanied
by (paradoxically) increased pulmonary vascular markings on
chest radiograph is a pointer to the diagnosis.
An electrocardiogram in the neonate may appear normal.
Gradually, right ventricular hypertrophy manifests as upright
T waves in the right precordial leads along with right axis
deviation. There may be absence of q waves in the precordial
leads (Figure 4).
43
Figure 3: Chest radiograph of an infant with transposition of great

arteries and a large ventricular septal defect
Figure 2: Chest radiograph of a neonate with transposition of great

arteries and intact interventricular septum
Figure 4: Twelve lead electocardiogram of a neonate with transposition of great arteries
Management of Transposition of
Great Arteries
The management of transposition of great arteries in a neonate
is surgical.
All treatments and other modalities of interventions are
performed to make the neonate a better candidate for surgery.
Neonatal care involves ensuring that the peripheral
circulation is preserved. Monitoring and maintenance of
peripheral temperature, pulses, capillary refill time and
urine output is essential. Laboratory tests to assess brain
(ultrasound), kidneys (blood urea nitrogen, creatinine) and
liver function tests should be performed. Prostaglandin
infusion is begun if the atrial level communication is not

effective in maintaining peripheral saturation around 75
percent and higher. If this does not help, balloon atrial
septostomy is performed on an emergency basis. An
adequate balloon atrial septostomy enables one to stop the
prostaglandin drip thereby preventing its side effects (apnea,
peripheral edema, tissue edema, rash). Occasionally, giving
oxygen to the neonate may improve oxygenation as well.
The aim is to regulate the pulmonary and systemic vascular
circuits so that adequate mixing is achieved.
The surgical corrective procedure of choice in the neonatal
period and early infancy in simple and most of the complex
transpositions is the arterial switch operation (ASO).
621
Arterial Switch Operation

Jatene arterial switch operation is an open heart surgical
correction, where the VA discordance is restored to normal.
The ascending aorta and the main pulmonary artery are
transected and then anastomosed to the semilunar valve of the
correct ventricle. The coronary artery origins from the original
aortic valve sinuses are mobilized as buttons (ostia surrounded
by sinus tissue) and then translocated to a new place on the
neoaorta. The Lecompte maneuver brings the main pulmonary
artery anterior and the ascending aorta posteriorly. Other
associated lesions like ASD, VSD, PDA and in few cases,
left ventricular outflow obstructions like coarctation, arch
hypoplasia or interruption are also corrected.
In effect, the arterial switch operation is a very good
functional correction, though not strictly anatomical in
nature as thought so earlier, as the altered semilunar valve
relationships, such as being anteroposterior in nature persists
even after the correction. This has a role to play in long-term
morbidities seen after this corrective surgery.
ATRIAL SWITCH OPERATION

The other alternative corrective proceduresSenning or
Mustard are the atrial switch operations. This is so called
as the circulatory correction is done at the atrial level, so that
the venous blood from the vena cava reaches the pulmonary
artery via the mitral valve and the LV and the pulmonary
venous blood reaches the aorta via the tricuspid valve and
the RV. The RV with the tricuspid valve is the systemic
ventricle and the mitral valve with the LV is the pulmonary
ventricle. Though this serves to correct the hypoxia of TGA,
the unphysiological VA relationships give problems in the
long-term in terms of tricuspid valvular regurgitation and
systemic ventricular dysfunction along with varieties of
atrial arrhythmias related to suture lines in the atria.
Timing of Surgery
622
In a child with TGA with intact septum, in the normal course

of progression after birth, the LV, which had an equal mass
with the RV at birth, undergoes regression commensurate with
the fall in the pulmonary vascular resistance. This renders the
LV incapable of supporting the systemic circulation and face
the systemic vascular resistance, leading to its failure. Hence,
it mandates that the ASO be performed before the regression
of the LV sets in, which is ideally within a fortnight after birth
or atleast by a month of age. Hence the earlier the correction
is done, the better for the child with TGA and an intact
septum. It has been observed that babies with small atrial
level communications have better preserved LV myocardium.
This is probably due to the LV seeing more volume of blood
as compared to a situation where there is a large ASD. On
echocardiogram, regression of the LV manifests as a banana-
shaped LV cavity in cross-section (interventricular septum

bowing into the LV cavity); posterior wall thickness of less
than 0.3 cm and LV mass less than 35 g/m2.7 Suitability for
arterial switch surgery is therefore based on LV cavity being
atleast D shaped in systole and LV posterior wall thickness
being atleast 0.3 cm in diastole. The mass of the LV on 2D
echocardiography is as calculated from the formula:
LV mass=1.05 {[5/6A1 (L+t)] [5/6 A2 L]}
where 1.05 is the specific gravity of the myocardium. L=long
axis length of the ventricular cavity obtained from the 4
chamber apical view. t=calculated mean LV wall thickness.
t=(A1/) (A2/ ) where A1 is the total area enclosed by
the LV epicardium in short axis end diastolic frame. A2 is the
total area enclosed by the LV endocardium in short axis end
diastolic frame.
In cases of TGA with a large VSD or PDA, the LV does
not regress as it remains at a high pressure. Hence in these
situations, ASO could be delayed to around a month or two,
when the indication would be increasing pulmonary blood
flow and failure to thrive.
In the subset with LVOTO and those found fit for an ASO,
the LVOTO serves to forestall LV regression and allows an
elective ASO to be carried out.
There are reports of stretching the age limit of primary
ASO in TGA with intact ventricular septum to 3 to 6 months
of age. These would be instances where the presentation of
the infant is late. The risks and mortality are higher and so
is the need for some form of left ventricular support for a
time period postoperatively. The long-term behavior of these
ventricles is unknown at the present time. It is hoped that they
adapt like the neonatal LVs, unlike those trained LVs, where
long-term dysfunction is common.
For the older patients with TGA and large VSD with
pulmonary hypertension, it has been the experience of
the authors that children upto 2 to 3 years of age can be
operated upon expecting a low morbidity and mortality post
operatively. For the slightly older children, it has been our
practice to measure pulmonary artery pressure directly in the
cardiac catheterization laboratory and see the response of the
pressure to oxygen. A fenestration in the atrial or ventricular
septum is placed in borderline cases. Use of oral pulmonary
vasodilators (sildenafil, bosentan) postoperatively. has helped.
Contraindications for an Arterial Switch Operation

Absolute
1. Pulmonary annular stenosis.
2. Subvalvar LVOTO, which cannot be resected (nonaccessory mitral valve tissue).
3. A deformed pulmonary valve other than a plain bicuspid
valve.
4. A regressed LV seen beyond infancy.
5. Hypoplasia of ventricles.
Relative
Other Options
In a TGA with intact ventricular septum, with a regressed LV
in infancy, a rapid two staged ASO could be attempted with
success. A preliminary pulmonary artery banding to train the
LV with ASO a week later is performed.4
More recently, there have been reports of ductal dilatation
and stenting to keep the LV prepared by subjecting the LV
to volume overload and increasing its afterload due to the
ensuing pulmonary arterial hypertension.8
However, in children beyond infancy with a regressed
LV, an atrial switch repair in the form of a Senning operation
could be performed successfully with low risk and a good
palliation.
In TGA with fixed LVOTO in the form of subvalvar,
valvar, annular or suprannular stenosis with a VSD, a Rastelli
procedure with VSD routing to aorta and establishment of
RVpulmonary arterial (PA) continuity with a conduit is the
usual norm. Many modifications of this procedure in the form
of aortic translocation and/or pulmonary translocation have
been described.
Another option in infants with TGA/VSD and LVOTO has
been the REV operation which routes the VSD to the aorta
and establishes RVPA continuity without a conduit. Residual
pulmonary regurgitation in varying degrees is seen after this
form of repair.9
Result
Currently the results of surgery for TGA is most gratifying
in both early and late periods.8 A lesion with a 100 percent
mortality, if untreated has been converted to one with a near
100 percent chance of success after surgical correction with a
good quality of life and growth in these children.10
More than 95 percent of children with simple transposition
can be corrected by an ASO successfully with predictable
results.
The mortality of complex transposition after surgical repair
too is below 10 percent currently in most large series.
Atrial switch operation (Senning) operation has a reported
mortality of around 2 percent.
Actuarial survival after an ASO is reported to be 98 percent,
93 percent and 91 percent at 1, 3 and 5 years respectively across
all forms and severity of TGA. Freedom from reoperation was
95 percent, 90.5 percent and 83 percent at the same points.
The presence of a VSD adversely affected survival. Predictors
of reintervention included VSD, coronary anomalies, aortic
coarctation, LVOTO or moderate PS.9
43
Complex coronary artery anatomy.
correcting the TGA physiology by an atrial switch operation

or an ASO leaving the VSD untouched could convert them to
an Eisenmengerized VSD situation, removing the unfavorable
hemodynamics of a TGA in the process. This results in better
oxygenation and may probably retard the pulmonary vascular
disease progression once the hypoxic and polycythemic stimuli
have been removed. Use of oral pulmonary vasodilators
(sildenafil and bosentan) may help as well.
Long-Term Issues postcorrection
What is the Place of Balloon Atrial Septostomy

in Current Practice?
Balloon atrial septostomy (BAS) is regarded as one of the
procedures that changed the face of survival in neonates with
TGA. It helps to promote mixing across the interatrial septum
and improves the effective pulmonary blood flow and the
oxygenation leading to survival.
Despite the initial benefits, recent reports of embolism
have dampened the enthusiasm to use this procedure.9
Also, the ability to do the ASO successfully soon after
birth has also limited the indications for a balloon atrial
septostomy.
Current Indications
1. To stabilize preoperatively before an ASO.
2. To stabilize before transfer to a higher center.
Palliative Surgery
In those cases of TGA with a large VSD presenting at a very
late stage with fixed elevated pulmonary vascular resistance,
The arterial switch operation too, which was considered a

cure and an anatomical correction in the early era, has
certain inherent flaws that may cast a shadow in the longterm.
Even though the ASO has a better long-term survival
when compared with the atrial level corrections, freedom
from reoperation in the long-term is inferior to the Senning
operation for simple transpositions in some reports.10
The long-term issues identified are as follows:
1. Compromised neurodevelopmental, behavioral and
neuropsychiatric outcomes: These manifest as gross and
fine motor and language developmental delay, learning
disabilities, hyperactivity and attention deficit disorders.
This is seen in a minority of patients.
2. Suprapulmonary valvar and bifurcation stenosis: 10 to 30
percent incidence; particularly in those with TGA, VSD and
aortic arch anomalies. On echocardiography, the branch
pulmonary arteries are seen straddling the ascending aorta
on either side. It is easy to appreciate how the straddled
position hampers the growth of the bifurcation of the
pulmonary arteries.
623
3. Neoaortic regurgitation: Approximately 5 to 10 percent,

the incidence rises over the years. The grade is trivial to
mild in the majority of patients. It is more likely to be
severe in patients with complex TGA and in those, who
have had prior pulmonary artery banding procedure.
4. Coronary artery issues, symptomatic/asymptomatic:
Approximately 5 percent. Some centers perform coronary
angiograms periodically (every 5 years) to assess the growth
and anatomy. Apart from the concern of ischemia, another
aspect is the disruption of autonomic nervous supply and its
long term impact on vasodilatory capacity during exertion.
Lifelong follow-up is essential and a thorough annual
physical examination coupled with a 12 lead ECG and a complete
echocardiogram is recommended. At an appropriate age, an
exercise stress test should be made an annual requirement.
Conclusion
Isolated TGA as a congenital anomaly can be treated surgically
today with a high degree of success. However, the excitement
of the arterial switch operation being a cure has been
dampened by the long-term issues being seen as the follow
up has increased. Not withstanding these issues, children with
TGA after the ASO, particularly for simple TGA, can look
forward to a life of normal growth, activity, with a very good
quality of life and in sinus rhythm, much unlike those with
the atrial switch operations. Recognizing the long-term issues
encountered, it is mandatory to keep operated children under
lifelong follow-up.
There are in fact two things, science and opinion; the former
begets knowledge, the later ignorance
Hippocrates
624
References
1. Digilio M, Casey B, Marino B, et al. Complete transposition
of the great arteries. Patterns of Congenital Heart Disease in
Familial Precurrence. Circulation. 2001;104:2809-14.
2. Martins P, Castela E. Transposition of the great arteries.
Orphanet J Rare Dis. 2008;13:3-27.
3. Kouchoukos N, Blackstone E, Hanley F, et al. Cardiac Surgery
3rd edn. Churchill Livingstone, Elsevier; 2003.
4. Sellke Frank, Pedro del NIdo, Scott J Sullivan. Sabiston and
Spencer Surgery of the Chest, 8th edn. Saunders Elsevier;
2010.
5. Wernovsky G. Transposition of the great arteries. In:
Moss and Adams Heart Disease in Infants, Children,
and Adolescents: Including the Fetus and Young Adults,
7th edn. Allen HD, Driscoll DJ, Shaddy RE, Feltes TF
(Eds). Lippincott Williams & Wilkins, Philadelphia; 2008.
pp.1039-87.
6. Liebman J, Belloc NB, et al. Natural history of transposition of
the great arteries. Anatomy and birth and death characteristics.
Circulation. 1969;40:237-62.
7. Lacour-Gayet F, Piot D, Planche C, et al. Surgical
management and indications of left ventricular retraining
in arterial switch for transposition of the great arteries
with intact ventricular septum. Eur J Cardiothorac Surg.
2001;20(4):824-29.
8. Sivakumar K, Francis E, Krishnan P, et al. Ductal Stenting
retrains the left ventricle in TGA with IVS. J Thorac Cardiovasc
Surg. 2006;132:1081-86.
9. Richard A Jonas. Comprehensive Surgical Management of
Congenital Heart Disease. JR Soc Med. 2004;97(8):407-08.
10. Horer J, Schreiber C, Cleuziou J, et al. Improvement in
long-term after hospital discharge but not in freedom from
reoperation after the change from atrial to arterial switch
for transposition of great arteries. Thorac Cardiovasc Surg.
2009;137:347-54.
C hapter
44
Congenitally Corrected Transposition

of the Great Arteries
English C Flack, Neeru Kaushik, Thomas P Graham
Introduction
Congenitally corrected transposition of the great arteries
(ccTGA) is a complex defect remarkable for its significant
anatomic abnormalities that nonetheless result in hemo
dynamically stable physiology. It is a rare defect that combines
atrioventricular (AV) discordance with ventriculoarterial
discordance. In ccTGA the atria are connected to the opposite
ventricle (left atrium to right ventricle via a tricuspid valve)
and the ventricles are connected to the discordant great artery
(right ventricle to aorta). Thus oxygen rich, systemic blood
is circulated by the morphologic right ventricle (RV) and
deoxygenated blood returns to the right atrium to be pumped
out the morphologic left ventricle (LV) to the lungs (Figure 1).
The defect is therefore corrected because of the physiologic
flow of blood through the body. For the purposes of this review,
univentricular hearts, those with common AV valves and those
with aortic atresia will not be discussed.
Incidence and Genetics

The incidence of ccTGA in patients with congenital heart
disease (CHD) is approximately 0.5 percent with a slight
male predominance.1,2 Although a specific genetic defect is
yet to be defined for ccTGA, the recurrence risk of either type
of transposition (corrected or non-corrected) for siblings of
ccTGA patients is 2.6 percent. The overall recurrence risk for
any type of congenital heart defect is 5.2 percent in siblings of
ccTGA patients.2 This recurrence risk of more than 5 percent
is higher than expected, given that the typical recurrence risk
for unaffected parents to have an additional child with CHD is
thought to be 1 to 3 percent.3
Anatomy
The most common segmental alignment in ccTGA is that of
{S, L, L}, representing atrial and visceral situs solitus (right-sided
inferior and superior vena cavae returning deoxygenated blood
to a right sided atrium), L-looped ventricles (the morphologic

LV with mitral valve positioned on the right) and L-transposed
great arteries (aorta arising off the left-sided morphologic RV
and therefore situated anterior and leftward of the pulmonary
artery). The RV serves as the systemic ventricle and in the
absence of other defects, oxygen saturation is normal. The
most common positions of the heart in the chest are levocardia
(apex to the left) or mesocardia (midline). Patients with levo-or
mesocardia and visceral situs inversus have a high likelihood
of ccTGA and therefore must carefully be assessed for atrial,
ventricular and arterial concordance. Dextrocardia, in which
the apex of the heart is to the right, occurs in approximately 20
percent of patients.1 In cases of dextrocardia with mirror-image
anatomy the anatomic designation is {I, D, D}.
Associated Defects
The most common associated defects in ccTGA are ventricular
septal defects (VSDs), which occur in 60 to 80 percent of cases,
pulmonary stenosis (PS) in 30 to 50 percent and tricuspid
valve (TV) anomalies in 14 to 56 percent. The VSDs are
usually large, perimembranous and subpulmonary in location.
Muscular inlet defects as well as multiple VSDs may also be
seen. Pulmonary stenosis, more appropriately referred to as
left ventricular outflow tract obstruction (LVOTO), may be
caused by fibromuscular tissue, valvar stenosis, or aneurysmal
tissue of the membranous ventricular septum. The associated
combination of LVOTO and VSD represents the largest group
of ccTGA patients. TV anomalies can occur along a varied
spectrum. Ebsteinoid malformations of the TV generally
represent the most clinically severe form. Furthermore, as the
TV is subjected to systemic pressures, even normally formed
valves display progressive regurgitation with age. Less
common defects occurring in association with ccTGA include
atrial septal defect, patent ductus arteriosus, pulmonary
atresia, double outlet RV, aortic regurgitation, mitral valve
abnormalities and subaortic stenosis.1,4,5
Figure 1: Congenitally corrected transposition of the great arteries.

IVC = Inferior vena cava; LA = Left atrium; LV = Left ventricle; MPA
= Main pulmonary artery; RA = Right atrium; RV = Right ventricle;
SVC = Superior vena cava.
Coronary Arteries and Cardiac Veins

The coronary arteries are inverted in ccTGA, as described by
Ismat et al.6 Just as the morphologic LV is situated on the
right side of the heart, the morphologic left coronary artery
arises from the right aortic sinus. The morphologic right
coronary artery similarly arises from the left posterior aortic
cusp and supplies the left-sided morphologic RV. The rightsided coronary (the morphologic left main coronary artery)
bifurcates into the anterior descending artery, which lays in the
interventricular groove and the circumflex branch that courses
posterior to the heart in the right AV sulcus. Additional rare
anomalies have been described, in which both main coronaries
arise from a single ostia or one main coronary gives rise to the
other (i.e. anterior descending off the right coronary artery).4,6
The cardiac veins generally correspond to ventricular and
coronary anatomy as described in a pathological series by
Bottega et al.7 In their series, prominent venous collaterals
were commonly noted on ccTGA specimens allowing
the morphologic LV to drain via Thebesian veins into the
coronary sinus. The coronary sinus then emptied as normal
into the right atrium. These venous structures are often dilated
which can be of benefit in providing access to both ventricles
in some percutaneous procedures.7
Conduction System
626
Conduction system abnormalities are common in ccTGA.

The conduction system often consists of dual AV nodes and
inversion of AV bundles. An increasing incidence of AV block,
at a rate of approximately 2 percent per year, occurs even in the

absence of surgical repair and is more likely in the presence of
an intact ventricular septum.8,9 Anderson et al10 consistently
demonstrated the finding of an anterior and right-sided AV
node that was situated anterolateral to the mitral-pulmonary
valve junction. This node connects to the morphologic (rightsided) LV by a descending bundle of conduction tissue that
travels anterior and lateral to the pulmonary outflow tract. The
bundle branches are inverted, each typical of the morphologic
ventricle they serve. In the presence of a subpulmonary VSD
the descending AV bundle is located on the anterosuperior
and anteroinferior borders of the defect. This is in contrast
to concordant hearts {S,D,S} in which the conduction bundle
travels along the posteroinferior margin of the VSD. Many
ccTGA patients also have a posteriorly-situated AV node,
which is often hypoplastic, in addition to a functional anterior
node. Depending on the alignment of the interatrial and
interventricular septae this posterior node may or may not
have connections to the ventricles. Patients with appropriate
alignment of the atrial and ventricular septae may be more
likely to have two AV nodes with corresponding conduction
bundles present. Invading fibrosis of the proximal AV node
bundle as well as distal conduction bundles have been
described on pathological specimens from older patients with
correlating ECG findings of complete heart block, suggesting
fibrotic invasion is involved in the development of AV
block.8,10
Natural History and Outcome

The natural history of ccTGA depends largely on the presence
of associated defects. Patients under 5 years of age who also
have a VSD, LVOTO and/or TV abnormalities represent the
highest frequency of non-surgical deaths. However, patients
with isolated ccTGA (no associated lesions) may survive
into their 4th and 5th decades.11,12 Nevertheless, many of
these patients will demonstrate one or more complications
including rhythm disturbances, tricuspid regurgitation (TR)
and congestive heart failure (CHF). Approximately 2 to 4
percent of ccTGA patients have ventricular pre-excitation
(Wolff-Parkinson-White syndrome) and should undergo
radiofrequency ablation of accessory pathways in cases of
symptomatic re-entrant tachycardia. Atrial tachycardias such
as atrial fibrillation and flutter often occur with increasing age,
atrial enlargement and following surgical repair where suture
lines and scars may support focal re-entrant circuits.
Prieto et al13 suggests that outcome is dependent on
morphology of the TV (the systemic AV valve), as this was the
only predictor of severe regurgitation and RV dysfunction in
a cohort of ccTGA patients described after mean follow-up of
20 years. The authors concluded that severe TV insufficiency
leading to RV dysfunction has the greatest impact on longterm survival in both operated and unoperated patients. In
patients who underwent surgical intervention for ccTGA,
Diagnosis
Just as the natural history is largely dependent on defects
associated with ccTGA, so is timing of presentation.
Prenatal Diagnosis
Fetal diagnosis in CHD continues to improve. However,
the fetus with ccTGA and mild or no additional intracardiac
anomalies may be overlooked by routine ultrasound screening.
Distinct features notable on prenatal ultrasound that may
improve detection of ccTGA are the parallel course of the
great arteries in combination with dextrocardia, abnormal
insertion of the papillary muscles and/or an abnormal TV.18-20
A retrospective review by Wan et al. found no difference in the
number of cardiac interventions, timing of surgery or survival
between a cohort of ccTGA patients diagnosed prenatally
(n = 14) and postnatally (n = 26). However, because 70
percent of this cohort required cardiac intervention prior
to 3 years of age, the authors suggest prenatal diagnosis is
important for preparation and counseling of the family.21
A recent review of 11 cases of fetal ccTGA diagnoses
describes the use of four-dimensional echocardiography
and spatiotemporal image correlation (STIC), in which the
relationship of the great arteries can be assessed in several
different orthogonal planes by placement of a reference
dot on images reconstructed from acquired volume data
sets.22
Early Presentation and Diagnosis

Diagnoses in infants and children often occur during
evaluation for a murmur, as VSDs are commonly associated
lesions. In cases of large VSDs or severe TV regurgitation,
some infants may present in CHF with diaphoresis, pallor,
tachypnea, inability to gain weight, hepatomegaly and a gallop
on examination. Auscultation of the ccTGA patient may also
reveal a loud, single second heart sound (S2) at the left second
intercostal space, with absence of S2 over the right second
intercostal space.23 The presence of a VSD combined with
LVOTO may lead to a cyanotic presentation from decreased
pulmonary blood flow. However, some degree of LVOTO
may protect the lung bed in patients with large VSDs and
may delay a CHF presentation despite the normal decrease in
pulmonary vascular resistance.
44
Congenitally Corrected Transposition of the Great Arteries
20-year survival rate was 90 percent for patients with competent

TVs, whereas survival was only 35 percent for patients with
severe TV insufficiency. Furthermore, patients who were
diagnosed with severe TV insufficiency demonstrated a rapid
deterioration in clinical status with RV failure occurring on
average 5 years after onset of insufficiency.13 By 45 years
of age 67 percent of ccTGA patients with associated defects
will have developed CHF, as shown in Figure 2, whereas
only 25 percent of ccTGA patients without associated lesions
will have progressed to CHF by this age.14 In some cases
patients may remain relatively asymptomatic through early
and mid-adulthood. However, the frequent development of
complications in the 4th and 5th decades often culminates in
the progressive development of RV (systemic) dysfunction
and heart failure, requiring aggressive medical management
and possible surgical intervention.12
It is well-established that compensatory hypertrophy
of the systemic RV leads to overall decreased capillary
density with myocardial perfusion defects.15,16 However,
to what degree these perfusion defects commonly lead to
myocardial infarction and scarring in patients with systemic
RV is unclear.17 Additional evaluation is required to further
determine the association between impaired coronary flow,
perfusion defects, and resulting myocardial dysfunction,
which may reside at the level of the cardiac myocyte. It is
possible that ccTGA patients with preserved systemic RV
function may have more favorable microcirculation and
coronary arterial reserve allowing adequate perfusion in times
of increased metabolic demand.
Late Presentation and Diagnosis
Figure 2: Freedom from congestive heart failure (CHF) in group I

(associated lesions, n = 125) and group II (no significant associated
lesions, n = 50) as a function of increasing age. p = .0013. Courtesy:
Reprinted from Journal of the American College of Cardiology,
number 36, volume 1, long-term outcome in congenitally corrected
transposition of the great arteries: a multi-institutional study, pp. 25561, copyright 2000 with permission from Elsevier
If there are no additional associated defects ccTGA may go

unnoticed until adolescence or adulthood. Case reports have
even cited incidental findings and late diagnoses of ccTGA
in adults in the 5th to 8th decades of life.24-27 A cohort of
patients with ccTGA over 18 years of age who presented to
an adult CHD clinic over a 15 year period is described by
Beauchesne et al.28 Sixty-six percent of these patients were
over 18 years of age when diagnosed and 17 percent of the
cohort was over 60 years of age at the time of diagnosis.
Common reasons for referral in such patients included
abnormal electrocardiograms (ECGs) and cardiomegaly
on chest radiographs as well as complete heart block and
murmurs.12,28
627
Evaluation
Chest Radiograph
The Chest X-ray (CXR) in ccTGA patients with mesocardia
or levocardia typically demonstrates a straightened upper-left
cardiac border secondary to the leftward-positioned ascending
aorta (Figure 3A). This is in contrast to the usual appearance
of the pulmonary artery and aortic knob along the left upper
cardiac border in normal hearts. The right pulmonary artery
is often more apparent than normal on CXR because of its
rightward displacement. Dextrocardia usually occurs with
normal abdominal situs and, as stated previously, occurs
in 20 percent of ccTGA patients (Figure 3B). The presence
of abdominal situs solitus and dextrocardia should raise
suspicion of ccTGA. In the patient without any associated
defects, an atypical cardiac position on an otherwise normal
CXR may be the only indication of ccTGA. However, marked
cardiomegaly, left atrial enlargement, and an increase in
pulmonary vascular markings may be present in patients with
a large VSD and significant left to right shunt. A CXR with
impressive cardiomegaly and left atrial enlargement may also
be indicative of an ebsteinoid malformation of the TV. The
presence of pulmonary stenosis or atresia will demonstrate
darkened lung fields from attenuated pulmonary blood flow.
Overall, the degree of cardiomegaly and amount of visible
pulmonary vascularity is dependent on the presence and
direction of shunting, as well as the severity of LVOTO.29
Electrocardiogram
The electrocardiogram (ECG) in patients with ccTGA is
most significant for a superior QRS axis and atypical septal
Figure 3B: Chest X-ray of infant with dextrocardia and ccTGA. Note:
The position of the cardiac apex pointed to the right. The left heart
border is straightened because of the leftward-positioned ascending
aorta. The thymic shadow is seen over the right mediastinum.
activation. As discussed previously, the conduction system

in ccTGA consists of inverted AV bundles. Therefore, the
septum is activated from right to left, demonstrated by the
presence of septal Q waves in the right precordial leads (QR
pattern in leads V4R and V1) and absence of Q waves in the
left precordial leads (rS pattern in lead V6) (Figure 4). In fact,
undiagnosed ccTGA patients with such a pattern on ECG have
been incorrectly diagnosed with remote inferior infarcts.25,30
Pre-excitation may be observed in those patients with ccTGA
and Wolff-Parkinson-White. Finally, varying degrees of AV
block may be present, as well as patterns of right or left-sided
chamber enlargement.
Echocardiography
628
Figure 3A: Chest X-ray of a 6-year-old child with ccTGA and complete
heart block. There is levocardia and abdominal situs solitus. The
upper-left cardiac border is straightened secondary to the leftwardpositioned ascending aorta. A permanent pacemaker is present with a
transvenous lead situated in the ventricle.
Transthoracic echocardiography (TTE) as an imaging modality

is relatively inexpensive, widely available and non-invasive.
As with many types of CHD, TTE is the first line and most
useful modality in the diagnosis of ccTGA. The anatomical
designation (most commonly {S,L,L} as discussed previously),
is assigned by demonstrating atrial position, ventricular looping
and arterial looping. Morphology of the RV is seen on TTE by
the presence of coarse trabeculations and a moderator band,
whereas the LV has a smooth-walled endocardium and a
funnel-shaped appearance. The level of the TV is inferior to
the MV, which may also give a clue to ventricular inversion
(Figure 5). In evaluation of the outflow tracts, the aorta in ccTGA
is usually anterior and to the left of the PA. Once the diagnosis
of ccTGA is made through demonstration of discordance
between atria and ventricles as well as ventricles and great
arteries, several anatomic objectives should be defined in the
44
and what type of surgical repair is necessary.31 Transesophageal

echocardiography (TEE) has been shown to have greater
accuracy over TTE in correctly defining atrial situs and chordal
AV valve attachments in adult patients with ccTGA.32 TEE is
also more useful for investigation of intracardiac vegetations in
cases of suspected endocarditis and in evaluation of thrombus
in the atrial appendages, which may be applicable to the ccTGA
patient with sustained atrial arrhythmias.
Figure 4: Electrocardiogram of a 5-year-old child with ccTGA, pulmonary stenosis, and complete heart block. Note: The presence of septal Q
waves in the right precordium (lead V4R) with absent left septal Q waves (leads V5V6), as well as right ventricular hypertrophy with deep S
waves in the lateral precordium (lead V1). There is ventriculophasic variation in the sinus rate, so the atrial rate is not completely regular.
Figure 5: Transthoracic echocardiogram (apical four-chamber view) in

ccTGA shows the inferior hinge point of the left-sided atrioventricular
valve (TV) opening into a morphological right ventricle (RV). In
comparison, the superior level of the right-sided atrioventricular valve
(MV) hinge point is seen as well as valvar attachments to a papillary
muscle within the morphologic left ventricle (LV)
TTE evaluation. Semilunar and AV valve morphology as well as

presence and severity of regurgitation warrant full description.
Coronary origins should be identified and their proximal
courses described. The degree of LVOTO is important as well
as any additional defects present, as these will impact whether
Rather than a modality for diagnosis, cardiac catheterization

is typically reserved for the postsurgical patient who would
benefit from an intervention such as LV to pulmonary
artery (PA) conduit dilation or stent placement. For patients
undergoing surgical palliation for complex ccTGA anatomy,
catheterization is performed to assess pressure, function,
and valve regurgitation prior to surgery (Figures 6A to D).
Most interesting, however, is the adult patient who presents
with ischemic heart disease and is discovered on cardiac
catheterization to have ccTGA after abnormal catheter passes
or inversion of coronary arteries on angiography.25
Cardiac Magnetic Resonance Imaging

Cardiac magnetic resonance imaging (cMRI) is now used in
many types of CHD to further define anatomy and to quantify
ventricular function and volume (Figure 7). For initial diagnosis,
cMRI may be helpful in patients with restricted TTE windows,
629
Figures 6A to D: Cardiac catheterization of unrepaired 4-year-old ccTGA patient: A. Morphologic left ventricle (LV), anterior-posterior projection.
A catheter is positioned antegrade from the inferior vena cava and into the right-sided morphologic LV. Contrast fills the LV, main pulmonary artery
(MPA) and pulmonary arteries. There is discrete subvalvar pulmonary stenosis and thickened pulmonary valve leaflets; B. Lateral projection.
Contrast from the LV flows through the posteriorly positioned, stenotic LV outflow tract, across the pulmonary valve, and fills the pulmonary
arteries; C. Morphologic right ventricle (RV), anterior-posterior projection. A catheter is positioned retrograde in the aorta (Ao) and into the
left-sided morphologic (RV). Contrast fills the trabeculated RV, the aorta and descending aorta (dAo). Closed-arrows indicate the circumflex
artery. The left anterior descending coronary artery is not seen in this still frame image; D. Lateral projection. Contrast fills the RV, ascending,
and descending aorta. Bold arrows indicate the course of the right coronary artery. LPA = Left pulmonary artery; RPA = Right pulmonary artery.
630
to define visceroatrial situs, and to delineate complex associated

defects. In patients with interruption of the inferior vena cava,
systemic return from the lower body can be difficult to delineate
by echocardiography, but is well-defined by cMRI. Because
echocardiographic evaluation of RV function in ccTGA patients
is limited by geometric assumptions, cMRI has become the gold
standard for RV function and volume assessment. TV morphology
can often be clarified through cMRI. Prior to performing
anatomic surgical repair in a ccTGA patient beyond infancy,
cMRI can be useful in evaluation of the LV, with delineation
of mass, volume and ejection fraction. Furthermore, if there are
concerns about the degree of LV dysfunction, perfusion studies
with delayed enhancement MRI may be performed to directly
investigate scarring of the LV myocardium prior to committing
this ventricle to systemic workload. Cardiac MRI may therefore
be a useful modality for evaluation of ccTGA patients not only

as an adjunct to TTE for initial diagnosis, but also for assessment
prior to surgical repair or for serial follow-up of the systemic RV.
If the presence of a cMRI-incompatible pacemaker or prosthetic
valve precludes assessment by cMRI, computed tomography
(CT) scans can depict anatomy, but cannot yield functional data
in the manner of a cMRI.33,34
Exercise and Stress Testing

Cardiopulmonary exercise testing by treadmill is an important
adjunct for ccTGA patient evaluation and management. In
those patients able to perform treadmill tests, exercise capacity
is determined through minute ventilation, carbon dioxide
production and oxygen consumption. Impaired exercise
capacity in ccTGA patients has been shown to correlate

with diastolic dysfunction and elevated RV filling pressures
as estimated by tissue Doppler imaging.35 Cardiopulmonary
exercise testing in combination with gadolinium-enhanced
MRI has been utilized to demonstrate RV myocardial fibrosis
hypothesized to be responsible for RV dysfunction.36 Systemic
RV function can also be evaluated by dobutamine stress testing,
in which cMRI is performed at baseline and with dobutamine
infusion. Objectively defining the capacity of the systemic
RV to respond to stress may guide treatment on both initial
and follow-up evaluations.37,38 Sequential testing, performed
either by cardiopulmonary exercise testing or by dobutamine
stress test, is useful to assess overall cardiopulmonary function
and response to medical or surgical therapy.
Management
Medical Management
Medical mangement of CHF in the ccTGA patient with a
systemic RV has been extrapolated from CHF therapy for
LV failure. This primarily includes -adrenergic receptor
blockade (-blockers), diuretics and afterload-reducing
agents with an angiotensin-converting enzyme (ACE)
inhibitor.39 Digoxin may also be useful for its inotropic
and antiarrhythmic effects. Angiotensin receptor blockade
with losartan was evaluated in a multicenter, randomized,
placebo-controlled clinical trial by Dore and colleagues,
but was found to have no improvement on exercise capacity
and no reduction in neurohormonal levels in patients with
systemic right ventricles.40 In general, evidence-based
Surgical Management
Indications for surgical ccTGA management in patients of all
ages continues to evolve and most often is determined on a
case-by-case basis. Beauchanese et al. described a cohort of
44 unrepaired adult ccTGA patients. Of these, the 30 patients
who required surgical intervention had significantly larger
pre-operative cardiothoracic ratios on chest radiographs and had
moderate to severe or severe systemic AV valve regurgitation.
The difference in ejection fraction of the systemic ventricle
between the operated and unoperated groups was not statistically
significant.28 As discussed previously and depicted in Figure
2, nearly 2/3 of unrepaired ccTGA patients with associated
defects will have developed CHF by the age of 45 years.14
Even asymptomatic adults with ccTGA have been shown by
echocardiography to have RV dysfunction based on tissue
Doppler quantification techniques.46 Thus the natural evolution
of ccTGA for the majority of patients is eventual RV dysfunction
and TV regurgitation. It is postulated that progression to failure
in a systemic RV is unavoidable because the RV and TV are
not anatomically suited to withstand the systemic pressure for
which the LV and MV are intended. One mechanism thought
to contribute to progressive RV decompensation is worsening
TR from annular dilation and/or displacement of the septal
leaflet of the TV as the RV remodels to accommodate systemic
afterload. Depending on the age of presentation and extent of
associated lesions, surgical repair may include one or more
of several approaches, which can be divided into the classic
or physiologic repair or a more anatomic repair, typically
referred to as the double switch operation (Table 1).
44
Figure 7: Axial oblique, T2-weighted cardic magnetic resonance

image (cMRI) of the cardiac four-chamber view in a ccTGA patient with
levocardia. The right atrium (RA) empties into a right-sided, smoothwalled, morphologic left ventricle (LV). A star (*) labels the entrance
of a left pulmonary vein into the left atrium (LA), which empties into a
trabeculated, left-sided, morphologic right ventricle (RV)
therapy for optimal CHF treatment in patients with systemic

RV is lacking. As an adjunct to medical therapy or in cases
where medical therapy has failed, cardiac resynchronization
has emerged as an option for patients with impaired
systemic RV function and widened QRS morphology on
ECG. Increased QRS duration as a result of bundle branch
block or conventional pacemaker is typically greater than
120 to 140 ms with some patients having QRS duration
greater than 200 ms. This electromechanical dyssynchrony
creates inefficiency in ventricular ejection and restoring
synchrony has been shown to decrease QRS duration with
improvement in RV filling time, ejection fraction and overall
CHF symptoms.41-43 Takemoto et al. reports the use of
transvenous permanent para-Hisian pacing in an 8-year-old
with ccTGA. Restoration of cardiac synchrony decreased the
QRS duration from 198 to 94 ms, decreased interventricular
conduction delay from 137 to 37 ms and improved the patients
CHF symptoms from New York Heart Association (NYHA)
class III to NYHA class II over a period of 6 months.44 A
significant limitation in cardiac resynchronization therapy
includes difficulty in percutaneous lead delivery, although
this has successfully been accomplished even in ccTGA cases
of dextrocardia.45
631
Table 1
Surgical repair and palliation for congenitally corrected transposition of the great arteries: classic and anatomic pathways for ccTGA
with associated defects.
Classic/Physiologic Pathway
Associated defect
Palliation/repair
VSD
VSD closure
VSD + PS
VSD closure + PS relief
VSD + PS/atresia
Biventricular Repair
VSD closure + LV PA conduit
VSD + PS/atresia +
Straddling AV valves
Hypoplastic RV
Unbalanced AVSD
Univentricular repair
Systemic to pulmonary artery shunt
Bidirectional Glenn
Fontan
Tricuspid regurgitation
TV repair or replacement
Anatomic Pathway
Associated defect
Palliation/repair
VSD with normal PV
VSD closure
Senning/Mustard (atrial switch)
Arterial switch
VSD + PS with normal PV
VSD closure + PS relief

Atrial + arterial switch
VSD + PS/atresia
Atrial switch + Rastelli procedure
Restrictive or absent VSD + PS
Atrial switch + Nikaidoh procedure
Hypoplastic RV or severe RV dysfunction
Hemi-Mustard-BDG modified atrial switch
Infants and children: PAB for LV training + atrial/arterial switch
AV = Atrioventricular; AVSD = Atrioventricular septal defect; BDG = Bidirectional Glenn; LV = Left ventricle; PA = Pulmonary artery; PAB = Pulmonary
artery band; PS = Pulmonary stenosis; PV = Pulmonary valve; VSD = Ventricular septal defect;
Classic/Physiologic Repair
632
In patients with a VSD and no LVOTO, classic or physiologic

repair may include VSD closure only. Specific techniques must be
employed in ccTGA patients to avoid damage to the conduction
system during VSD closure. Because the AV conduction
bundle descends along the anterior rim of the VSD and travels
along the septal side of the right-sided morphologic LV, it is
recommended to suture the VSD patch along the morphological
right ventricular aspect of the septum. The surgical approach
should be via a right atriotomy and right-sided mitral valve.
Ideally the VSD patch will lie partially on the morphologic
LV septal aspect (to avoid damage to the TV superiorly) and
partially on the morphologic RV aspect of the septum inferiorly
(to avoid damage to the main conduction bundle).47 Physiologic
repair may also include relief of PS, which sometimes requires
placement of a conduit between the LV and PA. There is,
however, the possibility that decreasing LV pressure by VSD
closure and/or PS relief may allow the ventricular septum to
realign towards the LV, resulting in displacement of the TV
septal leaflet and increasing TR.48,49 In a cohort of 123 patients
with ccTGA presenting for classic biventricular repair over 33
years, the surgical group undergoing repair of VSD plus PS
demonstrated the greatest survival whereas patients requiring

TV replacement at their initial operation exhibited the shortest
survival. Risk factors for death in the VSD group with or without
PS relief included preoperative RV end diastolic pressure
greater than 17 mm Hg and complete heart block. Survival rates
at 1-, 5-, 10, and 15-years for patients who underwent classic
repair were 84 percent, 75 percent, 68 percent and 61 percent,
respectively, although 17 of the 113 patients in this subgroup
underwent Fontan and achieved 100 percent survival in shortterm follow-up (Figure 8). In patients for whom biventricular
repair was contraindicated, such as patients with straddling
AV valve tissue, inaccessible or multiple VSDs or unbalanced
complete AV canals, the univentricular pathway with Fontan
was chosen.50 More recently Bogers et al. confirmed that a
classic repair in which the RV remains the systemic ventricle
results in significant incidence of reoperation and overall
suboptimal survival.51
Anatomic Repair Double Switch Operation

The anatomic or Double Switch (DS) operation was
developed in response to unsatisfactory outcomes after the
classic repair. Components of the DS include arterial switch
44
with coronary artery transfer, VSD closure if necessary,

and interatrial baffle by Senning or Mustard procedure.
The Senning and Mustard operations, referred to as an atrial
switch, serve to direct systemic venous flow to the TV and RV
and pulmonary venous flow to the MV and LV. By restoring
the LV and MV to the systemic circulation, the DS operation
offers the opportunity to improve long-term outcome. Before
committing the LV to the systemic workload, however, various
criteria must be met that afford the LV the greatest likelihood
of success. This includes preoperative LV pressure that is 80
to 100 percent systemic and normal LV wall thickness and
function for a systemic LV.52,53 In the absence of LVOTO,
pulmonary hypertension or an unrestrictive VSD, the
morphologic LV requires training prior to committing it to the
systemic ventricle in the DS. LV training has been performed
by placement of a pulmonary artery band (PAB) which is
then serially tightened until the pressure load for the nave LV
nears systemic pressure. Median banding time for the purpose
of LV retraining has been reported on average to be 13 to
14 months53-55 although can be considerably less in younger
patients. Morphologic LV reconditioning with PAB in patients
with systemic RV after atrial switch for dextrotransposition
of the great arteries (dTGA) has been described by Poirier
et al.53 PAB was performed in this population prior to
anatomic correction or as bridge to transplant, and the success
rate of completing adequate LV retraining was significantly
less in patients beyond 12 years of age (20 percent of patients
over 12 years completed the protocol, whereas 62 percent
of patients less than 12 years were able to complete the
PAB protocol, p = 0.02).53 While there is no well-defined
standard for age of PAB placement in this setting, it is

apparent that candidacy for LV training with PAB beyond
adolescence is questionable. LV dysfunction and failure can
occur immediately or within days or weeks following PAB
placement if the band is too restrictive. Reports of late LV
dysfunction in ccTGA patients who underwent DS operation
even after successful LV retraining by PAB placement are
also of concern.56
The combination of progressive systemic RV dysfunction
and TR has lead to the consideration of a variation in DS
operation for patients with LVOTO. Rather than combining
the atrial and arterial switches, the Senning or Mustard atrial
switch procedure is combined with a Rastelli operation, in
which the LV outflow is baffled from the LV through a large
VSD to the aorta and a conduit is placed from the RV to the
PA. This operation is technically challenging and subject to the
need for conduit replacements as well as possible reoperation
for interatrial or interventricular baffle obstructions. Specific
to the Senning/Rastelli operation, risk factors associated with
death include longer cardiopulmonary bypass and aortic
cross-clamp times and there is an increased risk of complete
heart block and ventricular dysfunction if the existing VSD
requires enlargement.57,58 Nevertheless, intermediate results
in a small group of ccTGA patients with VSD and LVOTO
who underwent this form of anatomic repair suggest good
biventricular function and mild or no AV valve insufficiency
up to 17 years postoperatively.59 Aortic root translocation
in combination with the atrial switch has also been reported
for anatomic repair in patients with LVOTO.60 After atrial
rerouting, the aortic root is harvested, obstruction in the LVOT
Figure 8: Operative survival in ccTGA patients. Fontan pathway (dotted line; n = 17), VSD surgery (solid line; n = 76) and TV surgery (dashed
line; n = 14). Numbers of patients at risk are in parentheses. Error bars indicate 70 percent confidence limits. TV = Tricuspid valve; VSD =
Ventricular septal defect. Courtesy: Reprinted from the Journal of Thoracic and Cardiovascular Surgery, vol. 129, no. 1, long-term outcome of
surgically treated patients with corrected transposition of the great arteries, pp. 182-191, Copyright 2005 with permission from Elsevier
633
is relieved, LeCompte maneuver of the pulmonary arteries is

performed, and the aortic root is reanastomosed to the original
location of the pulmonary artery. A conduit or pericardial
patch is then used to reconstruct the RVOT. This variation
of anatomic repair, commonly referred to as the Nikaidoh
procedure, may be suitable for patients with restrictive VSD
not amenable to the Rastelli operation.61
An additional variation in the DS for patients with severe
RV dysfunction, hypoplasia of the RV or abnormal right
atrial anatomy includes a modified atrial switch termed the
hemi-Mustard/bidirectional Glenn, which is performed
in combination with either an arterial switch or a Rastelli
procedure. In this operation only the IVC return is baffled to the
TV. The SVC is reimplanted into the pulmonary artery creating
a cavo-pulmonary Glenn shunt and the SVC portion of the
RA is oversewn. Midterm outcomes from the hemi-Mustard/
Glenn as reported by Malhotra et al.62 are favorable and hold
several advantages over the traditional Senning or Mustard
atrial switch. The authors report a prolonged lifespan of the RV
to PA conduit due to volume-unloading of the RV, increased
intra-atrial space for pulmonary venous return (and therefore
less risk of pulmonary venous obstruction) and less risk for
arrhythmia with the reduction in intra-atrial suture lines.62 It
remains to be seen if the hemi-Mustard/bidirectional Glenn
variant of the DS will prove favorable in long-term studies.
Tricuspid Regurgitation
634
Although it is reasonable to medically manage mild TR

with anticongestive therapy and afterload reduction, surgical
intervention is indicated in cases of moderate or moderate to
severe TR. TV repair for ccTGA patients is rarely successful,
and most patients require valve replacement. This can prove
problematic in young children because of the relatively large
prosthesis needed to allow for growth. Palliation with PAB
may therefore be reasonable in infants and young children,
since it has been shown that severe TV insufficiency
leading to RV dysfunction has the greatest impact on longterm survival.13,48 Several groups have concluded that TV
replacement should be considered at the earliest sign of
RV dysfunction and recommend operation before systemic
ventricular ejection fraction (EF) decreases below 40 to
44 percent, as low preoperative systemic EF has been shown
to correlate with poor outcome.63,64
As an additional alternative, Metton and associates
advocate the use of PAB in asymptomatic ccTGA neonates
and infants with intact ventricular septum to maintain rather
than train the LV.65 In Mettons group the TV was not repaired
at PAB placement, as it was thought that PAB placement
(with subsequent elevation in LV pressures and alteration of
the septal geometry) may improve TR that was present prior
to banding.54 This mechanism is described by Kral Kollars
et al.48 in 14 patients who underwent PAB for LV retraining
(median age 1.1 years, range 012 years). Eleven of the 14

patients had an increase in LV pressure of 2/3 systolic RV
pressure with PAB and demonstrated significantly decreased
TR as the LV geometry became more spherical and the
interventricular septum shifted toward the RV. Patients who
underwent classic ccTGA repair with procedures that reduced
LV pressure below that of the RV, such as VSD closure with
LV to PA conduit placement, demonstrated significantly
increased TR postoperatively.48
Outcomes: Physiologic vs Anatomic Repair

Alghamdi and associates66 published a meta-analysis of 11
non-randomized studies totalling 124 ccTGA patients and
compared in-hospital mortality between physiologic and
anatomic repair. Patient age at time of repair ranged from 3
months to 55 years with 41 percent of patients undergoing
definitive repair prior to 1995. Thirty patients underwent
physiologic repair, 69 underwent Rastelli-type anatomic
repair, and 25 received anatomic repair with the standard
double switch operation. The Rastelli-type anatomic repair
had significantly lower hospital mortality, while operation
before 1995 demonstrated an increased mortality risk.66 A
large risk analysis performed by Shinoka et al.58 combined
ccTGA patients with a group of systemic RV patients with
discordant AV connections, (n = 189) and compared longterm results of definitive surgical repair with respect to
hospitalization, late mortality and reoperation. Risk factors
for hospital death included preoperative moderate TR and
intraoperative cardiopulmonary bypass time of over 240
minutes. The presence of TR was also a risk factor for late
mortality. Risk for reoperation was highest in patients with
preoperative cardiomegaly (cardiothoracic ratio of > 0.6)
at least a moderate degree of TR, operative need for VSD
enlargement, and weight less than 10 kg. Although survival of
patients undergoing classic repair without TR was satisfactory
in comparison to anatomic repair, patients with ccTGA and
discordant AV connections with TR demonstrated improved
survival with anatomic repair.58 More recently Lim and
colleagues67 report results from a multicenter study including
167 patients who underwent biventricular ccTGA repair. Of
the patients studied, 123 underwent physiologic repair (ASD
or VSD closure, TV surgery and/or pulmonary ventricle to
PA conduit placement), and 44 underwent anatomic repair
(atrial + arterial switch or atrial + interventricular rerouting
procedure) over the years 1983 to 2009. Long-term results
of biventricular repair revealed an estimated survival of
83.3 percent 0.05 percent at 25 years. The incidence of
complete heart block was lower for the anatomic repair
group and there was a late mortality of 5.9 percent after
physiologic repair in comparison to 0 percent after anatomic
repair. Freedom from systemic AV valve and ventricular
dysfunction was significantly higher after anatomic repair.
Follow-up and Special Considerations

Patients with ccTGA require lifelong outpatient follow-up and
should be seen by a pediatric or adult congenital cardiologist
every 1 to 2 years. Evaluation should include an ECG at each
visit to monitor for AV block with periodic Holter monitor
evaluation as well. Cardiopulmonary exercise testing is
performed to assess overall function as well as response to
medical or surgical therapy. RV function in the unrepaired
or physiologically repaired ccTGA patient must be closely
monitored by echocardiography even in asymptomatic
patients.46 Cardiac MRI with cine data used to quantify RV
volume, mass and ejection fraction is the best modality to
serially quantify RV function and should be performed every
3 to 5 years.
Pregnancy
Pregnancy in the ccTGA patient is generally well tolerated
except in the presence of maternal NYHA class III-IV
symptoms, moderate or severe AV valve regurgitation, or
poor ventricular function (EF < 40 percent). Evaluation of
pregnancy outcome in 22 women with ccTGA revealed 50
live births in 60 total pregnancies (83 percent). However,
the rate of miscarriage in the ccTGA mothers was higher
than the general population.68 A recent cohort of patients by
Gelson and colleagues69 revealed high maternal and neonatal
morbidity in women with systemic RVs with a significant
number of babies born small for gestational age. Although
cyanosis in women with ccTGA has been shown to be a risk
factor for miscarriage, the women in the cohort of Gelson et
al. were normally saturated.69,70 The risk of congenital heart
defects in the offspring of mothers with ccTGA has not been
defined.
Heart Transplant
Heart transplantation may be considered in patients who
have end-stage RV failure, significant LV dysfunction
and pulmonary valve abnormalities precluding successful
DS operation or uncontrollable arrhythmia.52 For patients
undergoing surgical intervention, poor preoperative EF of the
systemic ventricle has been shown to predict the eventual need
for transplantation.28
Conclusion
The debate continues over efficacy and long-term follow-up in
physiologic vs anatomic repair for ccTGA. Recent outcomes
data is leaning in favor of anatomic correction, in which
systemic function is restored to the LV. However, the age and
eligibility of pulmonary artery banding for LV retraining is
yet to be standardized as is the optimal timing for anatomic
correction. In the asymptomatic infant, pulmonary banding for
maintenance of LV function bears further evaluation as well.
Thus the complex combination of factors in the management
of ccTGA patients requires individualized assessment of
each patient with incorporation of multiple modalities for
assessment and follow-up.
As to diseases, make a habit of two thingsto help, or at least,
to do no harm.
Hippocrates
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44
The authors concluded that anatomic repair is superior to

physiologic repair in patients with two adequately sized
ventricles. However high risk groups such as those patients
with RV dysfunction or the need for LV training warrant
careful selection prior to undergoing anatomic repair.67
Taken together, these outcomes favor anatomic over classic/
physiologic repair with careful preoperative assessment of
TR for the purpose of risk stratification.
635
636
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17. Fratz S, Hauser M, Bengel FM, et al. Myocardial scars
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18. McEwing RL, Chaoui R. Congenitally corrected transposition
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ventricular structural alternans and markers of adverse clinical
outcome in adults with systemic right ventricle and either
congenital complete (after Senning operation) or congenitally
corrected transposition of the great arteries. Am J Cardiol.
2006;98:1277-82.
37. Dodge-Khatami A, Tulevski, II, Bennink GB, et al. Compar
able systemic ventricular function in healthy adults and
patients with unoperated congenitally corrected transposition
using MRI dobutamine stress testing. Ann Thorac Surg.
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50. Hraska V, Duncan BW, Mayer JE, et al. Long-term outcome of

surgically treated patients with corrected transposition of the
great arteries. J Thorac Cardiovasc Surg. [Comparative Study].
2005;129:182-91.
51. Bogers AJ, Head SJ, de Jong PL, et al. Long-term follow-up
after surgery in congenitally corrected transposition of the
great arteries with a right ventricle in the systemic circulation.
J Cardiothorac Surg. 2010;5:74.
52. Duncan BW, Mee RB. Management of the failing systemic
right ventricle. Semin Thorac Cardiovasc Surg. 2005;17:
160-69.
53. Poirier NC, Yu JH, Brizard CP, et al. Long-term results of left
ventricular reconditioning and anatomic correction for systemic
right ventricular dysfunction after atrial switch procedures. J
Thorac Cardiovasc Surg. [Clinical Trial Comparative Study
Controlled Clinical Trial Multicenter Study]. 2004;127:
975-81.
54. Ly M, Belli E, Leobon B, Kortas C, et al. Results of the double
switch operation for congenitally corrected transposition of the
great arteries. Eur J Cardiothorac Surg. [Evaluation Studies].
2009;35:879-83; discussion 83-4.
55. Winlaw DS, McGuirk SP, Balmer C, et al. Intention-to-treat
analysis of pulmonary artery banding in conditions with a
morphological right ventricle in the systemic circulation with a
view to anatomic biventricular repair. Circulation. [Evaluation
Studies]. 2005;111:405-11.
56. Quinn DW, McGuirk SP, Metha C, et al. The morphologic left
ventricle that requires training by means of pulmonary artery
banding before the double-switch procedure for congenitally
corrected transposition of the great arteries is at risk of late
dysfunction. J Thorac Cardiovasc Surg. [Comparative Study].
2008;135:1137-44, 44 e1-2.
57. Gaies MG, Goldberg CS, Ohye RG, et al. Early and
intermediate outcome after anatomic repair of congenitally
corrected transposition of the great arteries. Ann Thorac Surg.
[Comparative Study]. 2009;88:1952-60.
58. Shinoka T, Kurosawa H, Imai Y, et al. Outcomes of definitive
surgical repair for congenitally corrected transposition of the
great arteries or double outlet right ventricle with discordant
atrioventricular connections: risk analyses in 189 patients. J
Thorac Cardiovasc Surg. 2007;133:1318-28, 28 e1-4.
59. Horer J, Haas F, Cleuziou J, et al. Intermediate-term results
of the Senning or Mustard procedures combined with the
Rastelli operation for patients with discordant atrioventricular
connections associated with discordant ventriculoarterial
connections or double outlet right ventricle. Cardiol Young.
2007;17:158-65.
60. Kwak JG, Lee CH, Lee C, Park CS. Aortic root translocation
with atrial switch: Another surgical option for congenitally
corrected transposition of the great arteries with isolated
pulmonary stenosis. J Thorac Cardiovasc Surg. 2010;139:
1652-53.
61. Morell VO, Jacobs JP, Quintessenza JA. The role of aortic
translocation in the management of complex transposition of
the great arteries. Semin Thorac Cardiovasc Surg Pediatr Card
Surg Annu. 2004;7:80-4.
44
38. Fratz S, Hager A, Busch R, et al. Patients after atrial switch

operation for transposition of the great arteries can not increase
stroke volume under dobutamine stress as opposed to patients
with congenitally corrected transposition. Circ J. [Comparative
Study]. 2008;72:1130-35.
39. Winter MM, Bouma BJ, Groenink M, et al. Latest insights
in therapeutic options for systemic right ventricular failure: a
comparison with left ventricular failure. Heart. [Comparative
Study Research Support, Non-U.S. Govt Review].
2009;95:960-63.
40. Dore A, Houde C, Chan KL, et al. Angiotensin receptor
blockade and exercise capacity in adults with systemic right
ventricles: a multicenter, randomized, placebocontrolled
clinical trial. Circulation. [Multicenter Study Randomized
Controlled Trial Research Support, Non-U.S. Govt].
2005;112:2411-416.
41. Diller GP, Okonko D, Uebing A, et al. Cardiac resynchronization
therapy for adult congenital heart disease patients with a
systemic right ventricle: analysis of feasibility and review
of early experience. Europace. [Research Support, Non-U.S.
Govt]. 2006;8:267-72.
42. Janousek J, Tomek V, Chaloupecky VA, et al. Cardiac
resynchronization therapy: a novel adjunct to the treatment
and prevention of systemic right ventricular failure. J Am
Coll Cardiol. [Evaluation Studies Research Support, Non-U.S.
Govt]. 2004;44:1927-31.
43. Kordybach M, Kowalski M, Hoffman P. Heart failure in a
patient with corrected transposition of the great arteries. When
is biventricular pacing indicated? Acta Cardiol. [Case Reports].
2009;64:673-76.
44. Takemoto M, Nakashima A, Muneuchi J, et al. Para-Hisian
pacing for a pediatric patient with a congenitally corrected
transposition of the great arteries (SLL). Pacing Clin
Electrophysiol. [Case Reports]. 2010;33:e4-7.
45. Malecka B, Bednarek J, Tomkiewicz-Pajak L, et al. Resyn
chronization therapy transvenous approach in dextrocardia and
congenitally corrected transposition of great arteries. Cardiol J.
[Case Reports]. 2010;17:503-08.
46. Bos JM, Hagler DJ, Silvilairat S, et al. Right ventricular
function in asymptomatic individuals with a systemic right
ventricle. J Am Soc Echocardiogr. [Controlled Clinical Trial].
2006;19:1033-037.
47. Jonas RA. Congenitally corrected transposition of the
great arteries. In: Jonas RA (Ed). Comprehensive Surgical
Management of Congenital Heart Disease London: Hodder
Arnold; 2004. pp. 483-96.
48. Kral Kollars CA, Gelehrter S, Bove EL, et al. Effects of
morphologic left ventricular pressure on right ventricular
geometry and tricuspid valve regurgitation in patients with
congenitally corrected transposition of the great arteries. Am J
Cardiol. 2010;105:735-39.
49. Said SM, Burkhardt HM, Schaff HV, et al. Congenitally
Corrected Transposition of the Great Arteries: Surgical Options
for the Failing Ventricle and/or Severe Tricuspid Regurgitation.
World Journal for Peditratic and Congenital Heart Surgery.
2011;2:64-79.
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of the great arteries: rationale and midterm results. J Thorac
63. Mongeon FP, Connolly HM, Dearani JA, et al. Congenitally
corrected transposition of the great arteries ventricular function
at the time of systemic atrioventricular valve replacement
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[Comparative Study Research Support, Non-U.S. Govt].
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64. Van Son JA, Danielson GK, Huhta JC, et al. Late results of
systemic atrioventricular valve replacement in corrected
transposition. J Thorac Cardiovasc Surg. 1995;109:642-52;
discussion 52-3.
65. Metton O, Gaudin R, Ou P, et al. Early prophylactic pulmonary
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Studies]. 2010;38:728-34.
66. Alghamdi AA, McCrindle BW, van Arsdell GS. Physiologic

versus anatomic repair of congenitally corrected transposition of
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67. Lim HG, Lee JR, Kim YJ, et al. Outcomes of biventricular repair
for congenitally corrected transposition of the great arteries. Ann
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women with congenitally corrected transposition of great
arteries. J Am Coll Cardiol. 1999;33:1692-95.
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C hapter
45
Common Atrium
Kiran VS, Sunita Maheshwari
common atrium
Virtual absence of atrial septum is a rare congenital anomaly,
which may occur in isolation or as a part of complex
heterotaxy syndromes. It occurs in less than 1 percent of
all congenital heart diseases (CHDs).1 In 1907, Young and
Robinson described this entity as a part of their series on the
malformations of human heart.2
IS IT SAME AS SINGLE ATRIUM?

The terms common atrium and single atrium have been used
interchangeably in the literature. Some authors suggest that
single atrium is to be applied to the defects with complete
absence of atrial septum, absence of interventricular
communication and absence of malformations of the
atrioventricular (AV) valves, while common atrium is to be
applied to the defects with complete absence of the atrial
septum with malformations of the AV valves.7
These semantic confusions3-5 were sorted out and now
both the terms refer to the complete absence of the interatrial
septum.6
In this chapter, we will focus on both common atrium
and single atrium, avoiding detailed overlap with AV
malformations and heterotaxy syndromes, which are dealt
separately in Chapter 20 and 10 respectively.
COMMON ATRIUM AND ISOMERISMS

The complex heterotaxy syndromes are usually associated
with common atrium.
entering ipsilateral sides of the common atrium separate from

the inferior vena cava (IVC) attachment. Anomalies of the
pulmonary venous return occur in nearly all cases of right
isomerism. If the veins return to the atrium, it is usually to
a common collector in the roof of the common atrium. The
coronary sinus is usually absent in such situations. When there
is a persistent left superior vena cava (SVC), it drains directly
into the left upper corner of the common atrium. Also, the
coronary venous blood drains directly into the left side of the
common atrial cavity. This partly explains the mild desaturation
that is commonly encountered in such instances.8,9
Left Isomerism
Common atrium occurs in almost one-third of left isomerisms.
This complex is usually associated with polysplenia, interrupted
IVC (which sometimes pose serious problems in determining
atrial situs) and anomalous pulmonary venous connection to
both sides of the common atrium. 8,9
SYNDROMES ASSOCIATED WITH COMMON ATRIUM

Ellis van Creveld syndrome: A strong association between
single atrium and postaxial hexadactyly (Figures 1A and B)
has been reported10 and indicates a diagnosis of Ellis van
Creveld syndrome.
Ivemark syndrome consists of intracardiac anomalies,
abnormal lobation of the lungs and abdominal heterotaxy.11
In an interesting observation, Spencer and colleagues
reported common atrium in two pairs of conjoint twins.12
CLINICAL MANIFESTATIONS
Right Isomerism
There is an almost 50 percent incidence of common atrium
in right isomerisms. This complex is usually associated with
asplenia, midline liver with both right and left hepatic veins
Here, we shall concentrate on the single atrium without

associated lesions. In common atrium with complex lesions,
the symptoms and findings of coexisting complex lesions
supersede that of the atrial component.
Figures 1A and B: Ellis-Van Creveld syndrome: A. Postaxial hexadactyly of the hands with hypoplastic nails; B. Peg teeth and malocclusion
640
When the entire atrial septum is virtually absent, there is

a mandatory admixture of blood received from systemic and
pulmonary circulations into the atrial cavity. This explains the
mild desaturaion that can be noticed. However, in the setting
of right isomerism, the degree of desaturation may be higher
for reasons explained earlier.
Symptoms of high pulmonary blood flow predominate
in infancy. As in any non-restrictive atrial septal defect, the
compliance of the corresponding ventricles will determine the
direction and magnitude of the flow out of the single atrial
cavity. The presenting features include dyspnea on exertion,
fast breathing, failure to thrive, suck-rest-suck cycles and
excessive sweating. As a general rule, the symptoms occur
earlier and progress faster than isolated atrial septal defects
(ASD) or primum defects. When the pulmonary vascular
resistance is normal, precordium appears active. Apical
impulse would be prominent and of right ventricular type.
Second heart sound would reveal a wide split and no change
with respiratory cycle. The extent of pulmonary hypertension
would determine the loudness of the pulmonary component
of second heart sound. Precordial auscultation would reveal
an ejection systolic murmur with its typical crescendodecrescendo quality at the left upper sternal border. The same
murmur can be appreciated at the back and sometimes in the
axillae. One can also appreciate a mid-diastolic murmur in
left lower sternal border. This murmur has a soft-quality and
is often described as absence of silence. The mid-diastolic
murmur is due to the increased blood flow across the tricuspid
valve when the pulmonary vascular resistance and the right
ventricular functions are normal. Not infrequently, common
atrium is associated with an abnormal mitral valve. Clefts
in the mitral valve leaflets are common in such settings. The
resultant mitral regurgitation (MR) can produce a pansystolic
murmur. This will add to the overall volume load on heart.
INVESTIGATIONS
After a meticulous clinical examination, one should proceed
to the basic battery of investigations, which would add to the
diagnosis and management decisions.
Electrocardiography
The 12-lead electrocardiography (ECG) shows same pattern
as partial AV canal defect or a primum ASD. Rhythm is
usually sinus, but in the setting of an abnormal situs, one may
come across various degrees of conduction blocks including
complete heart block. The P waves in lead II, III and AVF can
be both tall and broad. Prolongation of PR interval is noted
in upto two-thirds. This is a manifestation of increased intraatrial conduction time.13 The mean QRS axis may show left
axis or superior axis, ranging from minus 30 degrees to minus
120 degrees. The QRS can be notched in the inferior leads
and a typical rsR pattern is observed in V1. QRS pattern may
suggest volume overload of right ventricle. However, with
advancing age, it may also show pressure overload pattern due
to increasing pulmonary vascular resistance. In the presence
of normal pulmonary vascular resistance and right ventricular
function, even a significant MR is unlikely to show a left
ventricular volume overload pattern in the ECG (Figure 2).
Chest Radiograph
A well taken chest radiograph in posteroanterior projection is
an invaluable tool in management decisions. Cardiomegaly is
evident. Right atrial enlargement and right ventricular apex
45
Common Atrium
Figure 2: Electrocardiography of a patient with common atrium shows left axis deviation, rsR' in V1, notched QRS in inferior leads
Figure 3: Chest X-ray in posterioanterior view shows cardiomegaly

with dilatation of right atrium and right ventricle
Figure 4: Echocardiography in four-chamber view showing complete

absence of the interatrial septum in 8 years old girl with common
atrium (CA) with both atrioventricular valves (arrow) at the same level,
with a mid-muscular ventricular septal defect. LV = Left ventricle;
are usual, even in the presence of significant MR. Pulmonary

vascularity pattern may help in deciding the operability.
Plethoric lung fields suggest clear operability, whereas
oligemic lung fields are against it. However, one should not
confuse pulmonary venous congestion with plethoric lung
fields (Figure 3).
abnormal patterns of pulmonary and systemic veins. Apical

four chamber is diagnostic (Figure 4).
If the IVC is uninterrupted, a long, redundant eustachian
valve tissue might be seen wandering in the common atrial
cavity. It should not be confused with residual septal tissue.
Apical four-chamber view is useful in assessing the
ventricular cavities and the av valves. When one of the
ventricles looks unusually small, measuring the annuli of AV
valves and comparing them against the Z-score charts would
be useful in deciding feasibility of two-pump repair. The view
also provides good 2D assessment of AV valve morphology.
Color-Doppler assessment of the AV valves will help in
Echocardiography
Subcostal imaging is best suited to make an accurate diagnosis.
Both coronal and sagital planes help in delineating the absence
of interatrial septum and also in establishing the normal and
641
642
quantifying the regurgitation and the direction of jet, details

of which are very useful in planning a surgical strategy. ColorDoppler of the pulmonary veins with scales set to optimal
Nyquist limit will help in quantifying the venous return,
which is an indirect marker of operability.
Every echocardiographic examination should also encompass
all the other views to rule out any other coexisting anomaly. It is
not uncommon to find cases in which a coexisting large ductus
or aortopulmonary window was missed. Hence, even after
establishing the diagnosis from subcostal and apical views, it is
still important to do a meticulous evaluation via parasternal and
suprasternal windows to determine the presence and absence of
coexisting anomalies.
Role of 3D echocardiography: The utility of 3Dtransthoracic and 3D-transesophageal echocardiography
(TEE) are well established in the evaluation of atrial septal
defects, especially in deciding the utility of transcatheter
device closures. However, the same cannot be extrapolated
for single atrium. With some effort, additional information
can be obtained regarding the venous drainages. With
advanced software, volumetrics can be assessed using 3D
echocardiography enabling the shunt calculations.
pulmonary vascular pressures, the right ventricular compliance

is much superior to that of left ventricle. In consequence, the
pulmonary blood flow (Qp) is higher than systemic (Qs). The
ratio would reduce in the same proportion as pulmonary to
systemic vascular resistance increases. With advancing age,
the likelihood of operability comes down.
Once the diagnosis is confirmed, the objective is to get the

anatomical repair early, preferably by 6 to 12 months of life.
It is pertinent to make use of any modality of investigation
which helps surgical decision making. An asymptomatic child
with normal pulmonary artery pressures need not be given any
medication other than watchful observation. Judicious use of
diuretics and angiotensin converting enzyme inhibitors can
be advocated in symptomatic children, more so if av valve
regurgitation is an issue. Digoxin is best avoided, especially
when the status of the sinus node is unclear.16 For those
with postoperative pulmonary artery hypertension, targeted
therapy for pulmonary hypertension may be beneficial.14 The
surgical results are termed good to excellent by most of the
authors.17,18 Even advanced age is not a contraindication to
operation.19
Splenic status is an important determinant of outcome. In
asplenia or reduced splenic function, use of irradiated blood,
special precautions to ensure sepsis free handling, dedicated
staffing, judicious isolation and limitation of visitors in the
perioperative period would add to the success of the procedure.
Common atrium can present technical challenges to the
surgeon, even when the anatomical details are well delineated.
It should be remembered that the surgeon is not just closing
an ASD here, but is actually reconstructing the entire atrial
septum. The most common material used to achieve this
is pericardium. This patch is usually diverted leftward to
incorporate the left SVC orifice on the right side of the
patch. Issues like absence of coronary sinus take away the
landmark of conduction system for the surgeon on the table.
This compels the surgeon to take the sutures on the tricuspid
Development of pulmonary vascular obstructive disease

in single atrium is much faster than that in isolated
secundum ASD or partial AV canal defect of primum
variant. Whether development of early pulmonary
vascular disease in some common atrium patients is due
to a genetic predisposition (related to coexisting abnormal
substrate in the lung or congenital abnormalities in the
pulmonary arterial vasculature) or an association with
idiopathic pulmonary hypertension is unknown. Due to
the rarity of condition and the eventual paucity of data
on the natural history of common atrium and pulmonary
vascular disease, determining which patients with common
atrium will develop early pulmonary vascular obstructive
disease remains challenging.14 Hence, the threshold for
operability testing is low in many centers. However, with
advent of better echocardiographic techniques and noninvasive volumetrics assessment by magnetic resonance
imaging (MRI) and 3D echocardiography the need for
catheterization studies has significantly come down. Since
the developing countries may still see many unevaluated
and untreated grown-up CHD patients, catheterization
studies may become essential to get the correct picture.
The mixing of pulmonary and systemic venous returns
is near complete due to lack of any interface between them.
However, the relative flow of this mixture via AV valves
depends on the individual compliances of corresponding
ventricles, which is determined by the vascular resistances
of the distal vascular beds. Hence, in the presence of low
Cardiac Computed Tomography and Magnetic

Resonance Imaging
Cardiac computed tomography (CT) evaluation with contrast
study is useful in delineating the systemic and pulmonary
venous courses. However, CT cannot delineate the intracardiac
defect, nor can it assess the volumetrics. However, MRI of
heart can provide data that 2D-echocardiography cannot. MRI
can indicate the lack of atrial septum, amount of shunting, size
and function of both ventricles, along with anatomical details
of pulmonary and systemic veins and coexisting lesions.15
With all these faculties up its sleeve, MRI may serve as the
primary imaging modality in the future.
TREATMENT
Conclusion
Common atrium and single atrium are two different
terminologies and there should not be any nosological
confusion. Common atrium is a part of complex coexisting
anomalies, whereas single atrium is isolated. Syndromic
associations are well known. Presentation is similar to that of
ASD, albeit earlier and with evidence of cyanosis. Evaluation
should consist of a careful search for coexisting anomalies,
especially of the pulmonary, systemic venous drainage and
the AV valves. Early surgical correction around 1 year of age
is recommended. Surgical results are good and age should not
be a deterrent as long as the patient is operable.
Wherever the art of medicine is loved,

there is also a love of humanity
Hippocrates
Acknowledgment
We wish to thank Dr IB Vijayalakshmi, Professor of Pediatric
Cardiology, for providing all the images.
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CL (Eds). Pediatric cardiac surgery, 2nd edition. St Louis;
Mosby, 1994. pp. 193-200.
7. Levy MJ, Salomon J, Vidne BA. Correction of single and
common atrium, with reference to simplified terminology.
Chest. 1974;66:444-46.
8. Anderson RH,Webb S, Brown NA. Defective lateralisation in
children with congenitally malformed hearts. Cardiol Young.
1998;8:512-31.
9. Van Praagh S, Santini F, Sanders SP. Cardiac malpositions
with special emphasis on visceral heterotaxy (asplenia and
polysplenia syndromes). In: Fyler DC (Ed). Nadas pediatric
cardiology. Philadelphia Hanley and Belfus; 1992. pp. 589-608.
10. Digilio MC, Marino B, Giannotti A, et al. Single atrium,
atrioventricular canal/postaxial hexadactyly indicating Ellis
van Creveld syndrome. Hum Genet. 1995;96:251-53.
11. Gutgesell HP. Cardiac malposition and heterotaxy. In: Garson
A, Bricker JT, Fisher DJ, Neish SR (Eds). The science and
practice of pediatric cardiology. 2nd edition. Baltimore:
Williams and Wilkins; 1998. pp. 1539-61.
12. Spencer R, Robichaux WH, Superneau DW, et al. Unusual
cardiac malformations in conjoint twins. Pediatr Cardiol.
2002;23:631-38.
13. Fournier A, Young ML, Garcia OL, et al. Electrophysiologic
cardiac function before and after surgery in children with
atrioventricular canal. Am J Cardiol. 1986;57:1137-41.
14. Ferdman DJ, Brady D, Rosenzweig EB. Common atrium and
pulmonary vascular disease. Pediatr Cardiol 2011;32:595-98.
15. Piaw CS, Kiam OT, Rapaee A, et al. Use of non-invasive phase
contrast magnetic resonance imaging for estimation of atrial septal
defect size and morphology: a comparison with transesophageal
echo. Cardiovasc Intervent Radiol. 2006;29:230-34.
16. Wu MH, Wang JK, Lin JL, et al. Cardiac rhythm disturbances in
patients with left atrial isomerism. Pacing Clin Electrophysiol.
2001;24:1631-38.
17. Murphy JG, Gersh BJ, McGoon MD, et al. Long-term outcome
after surgical repair of isolated atrial septal defect. Follow-up
at 27 to 32 years. N Engl J Med. 1990;323:1645-50.
18. Roos-Hesselink JW, Meijboom FJ, Spitaels SE, et al. Excellent
survival and low incidence of arrhythmias, stroke and heart failure
long-term after surgical ASD closure at young age. A prospective
follow-up study of 2133 years. Eur Heart J. 2003;24:190-97.
19. Inoue T, Kawamura J, Takeda M, et al. An elder case of
common atrium: surgical repair in a 56-year-old man [in
Japanese]. Kyobu Geka. 1991;44:793-96.
20. Pan-Chih, Chen-Chun. Surgical treatment of atrioventricular
canal malformations. Ann Thorac Surg. 1987;43:150-54.
45
Common Atrium
valve posteriorly to be carried on to right atrial wall beyond

the tricuspid annulus. Some surgeons have used the base of
the mitral valve to anchor sutures.20
A well reconstructed interatrial septum does very well
in the postoperative period.17 The decision to continue
medications would depend upon the postoperative normaliz
ation of hemodynamics. However, it should be noted that
all children with altered splenic function should receive
life-long prophylaxis and vaccination against encapsulated
bacteria and preferably, annual influenza vaccine. This should
be emphasized to parents at the time of discharge and reemphasized during follow up visits. It is useful to get all this
practical information on patient care printed on a handy card
and issued to the parents for their reference.
643
C hapter
46
Single Ventricle
Devananda NS, Maitri Chaudhuri
IntroduCtIon
As early as 1699, Chemineau1 described a heart composed of
two auricles, but only one ventricle. The univentricular heart
has since then fascinated the medical community. Unique
in its complexity and scope, the univentricular heart has
sparked intense debates about embryology and nomenclature,
challenged our understanding of cardiovascular physiology
and hemodynamics and inspired some of the most creative
surgical and interventional approaches in human history.
nomenClature, hIStory and ConSenSuS

defInItIon
The nomenclature of the univentricular heart is still a
controversy. The terms single and common ventricle were used
interchangeably by Abbott, Taussig and Edwards.2-4 Maurice
Lev5 published an exhaustive paper on Single or Primitive
Ventricle in 1969. The various terms used to describe these
hearts include single ventricle, univentricular heart, double
inlet ventricle, univentricular atrioventricular connection,
cor triloculare biatrium (well-formed atrial septum), cor
biloculare (rudimentary or absent atrial septum), common
ventricle, and functionally single ventricle (Figure 1).2-6
To understand this anomaly, we can compare this with a
normal heart, where there are two atria and each atrium connects
to its own ventricle. Also a well-developed ventricle is tripartite7
having an inlet portion (from atrioventricular valve annulus to
insertion of papillary muscles), an outlet portion (supporting
semilunar valve) and a trabecular/apical zone (extending from
inlet to outlet) (Figures 2 and 3). The hearts considered in this
topic are those, where the atrial chambers functionally connect
to only one ventricle, which is well-developed and dominant.
The debate started with the use in classical descriptions of
the term single ventricle. As pointed out by Van Praagh,8 the
so called univentricular heart also has an additional incomplete
or rudimentary ventricle that lacks a proper atrioventricular
connection. In late 1970s and early 1980s, Anderson et al9
attempted to clarify the confusion surrounding these hearts by

dividing them into the following:
1. Univentricular heart of the left ventricular (LV) type:
Where dominant chamber is of LV morphology and
rudimentary chamber had morphologic features of RV
trabecular zone (Figure 4).
2. Univentricular heart of the right ventricular (RV)
type: Where dominant chamber is of RV morphology and
rudimentary chamber had morphologic features of LV
trabecular zone.
They also proposed that a chamber must receive greater than
or equal to 50 percent of an inlet to be classified as a ventricle
whereas the chamber need not have an outlet to qualify as
same. Chambers receiving < 50 percent of inlet were termed
rudimentary chambers. Rudimentary chambers possessing
an outlet were called outlet chambers, whereas those only
having a trabecular zone were termed trabecular pouches.
Figure 1: The figure shows an extremely rare congenital malformation:

The true single ventricle, which has both a double inlet and double
outlet. The apical trabeculations are extremely coarse and the
ventricular morphology is indeterminate. The inset shows the bizarre
conduction system with a sling of conduction axis connecting dual
atrioventricular nodes, and giving rise to a solitary strand, which
activates the ventricular mass. Courtesy: Reprinted with permission
from reference 16
Figure 3: The figure shows a morphological LV, which is also tripartite.

In contrast to Figure 2, the apical trabeculations are smooth. The solid
red line indicates the atrioventricular junction, while the dotted red
line indicates the ventriculoarterial junction. Courtesy: Reprinted with
permission from reference 16
Figure 4: The left hand panel shows a double inlet and double
outlet from morphological left ventricle (LV), which is the functional
single ventricle. The right hand panel demonstrates the presence of
a rudimentary right ventricle (RV), identified from its coarse apical
trabeculations. Courtesy: Reprinted with permission from reference 16
46
Single Ventricle
Figure 2: The figure shows a morphological RV, which is tripartite: an

inlet, apical trabecular and outlet portions. The apical trabeculations
are coarse. The solid red line indicates the atrioventricular junction,
while the dotted red line indicates the ventriculoarterial junction.
Subsequently, Van Praagh10 and colleagues protested

against this arbitrary definition of ventricles and challenged
the term univentricular heart as in reality these hearts had
two ventricular masses. They proposed these hearts should
be classified on the basis of the embryological development
and continued to use the term double inlet left ventricle and
Tricuspid Atresia.
In 1984, Anderson11 et al responded by introducing the
term univentricular atrioventricular connection to
describe hearts in which both inlets (whether patent or not)
are primarily committed to one dominant ventricle.
Thus, according to Van Praagh, a single or common
ventricle is one ventricular chamber that receives both the
tricuspid and mitral valves or a common atrioventricular
valve. So, this definition excludes tricuspid and mitral atresia.
Andersons system likewise emphasizes the nature of the
connections between the atrial and ventricular structures,
asserting that the unifying criterion for univentricular hearts is
that the entire atrioventricular junction is connected to only one
chamber in the ventricular mass. A second ventricular chamber,
if present, will lack any atrioventricular connection and hence
be rudimentary. This system makes the distinction between
hearts with a double inlet ventricle versus hearts with absence
of an atrioventricular connection, but acknowledges that
because a heart with absence of one atrioventricular connection
is also a univentricular heart, then tricuspid atresia is among
those anomalies associated with a univentricular heart.
The final consensus of the STS-Congenital Heart Surgery
Database Committee12 and the European Association
for Cardiothoracic Surgery was that the nomenclature
proposal for single ventricle hearts would encompass
hearts with double inlet atrioventricular connection,
both double inlet left ventricle (DILV) and double inlet
right ventricle (DIRV), hearts with absence of one
atrioventricular connection (mitral atresia and tricuspid
atresia), hearts with a common atrioventricular valve and
only one completely well-developed ventricle (unbalanced
common atrioventricular canal defect), hearts with
only one fully well-developed ventricle and heterotaxia
syndrome (single ventricle heterotaxia syndrome) and
finally other rare forms of univentricular hearts that do
not fit in one of the specified major categories. Despite the
recognition that hypoplastic left heart syndrome (HLHS)
is a common form of univentricular heart, with a single
or dominant ventricle of right ventricular morphology,
the current nomenclature and database proposal includes
it in an entirely separate section. Also, it is recognized
that a considerable variety of other structural cardiac
malformations such as pulmonary atresia with intact
ventricular septum, biventricular hearts with straddling
atrioventricular valves and some complex forms of
double outlet right ventricle (DORV), may at times be
best managed in a fashion similar to that which is used to
treat univentricular hearts. However, we are not going to
discuss the latter group or HLHS in this chapter.
645
cyanotic Heart diSeaSeS
With this short history, we recommend the readers to follow

their own preferred school of morphology. We have tried
to follow Professor Andersons method of describing these
hearts by sequential segmental localization in this chapter.
defInItIon
As per the congenital heart surgery nomenclature and
database project,12 single ventricle anomalies are defined as
a heterogeneous group of cardiac malformations that have in
common the feature that only one of the chambers within the
ventricular mass is capable of supporting independently and/
or in combination the systemic and/or pulmonary circulations.
This excludes those cardiac anomalies where even in the
presence of two well-developed ventricles, the heart may be
considered as non septable like a very large ventricular septal
defect (VSD) where treatment strategy is similar to that of
univentricular hearts.
anatomICal deSCrIptIon of unIVentrICular

heartS
Figure 5: This long axis section of a heart with double inlet left ventricle
(DILV) shows the relative position of the rudimentary right ventricle and
ventricular septum with respect to inlets. The incomplete RV is located
superior to dominant LV. The two inlet valves (yellow arrows) leading
to LV are posteroinferior to the ventricular septum (star). Courtesy:
Morphologically, the univentricular hearts can be broadly

classified into two categories:
I. True Univentricular Heart.
II. Hearts with One Big and Another Rudimentary
Ventricle.
true univentricular heart

Very occasionally, the instance of a single chamber5,13 within
the ventricular mass without any anatomic evidence of a
second chamber has been reported. This heart with a solitary
ventricle has both a double inlet as well as a double outlet. The
ventricular morphology is best described as indeterminate and
shows extremely coarse trabeculations. The developmental
basis is as yet not understood, however it is reasonable to
propose that it represents failure of ballooning of separate
apical components for the morphologically right and left
ventricles as proposed by Christoffels14 et al.
hearts with one Big and another rudimentary

Ventricle15-17
Most of the univentricular hearts belong to this group. There
are two important morphological aspects to be understood:
Question I: Does the Rudimentary Chamber Really Matter?
646
Identification of ventricular morphology is the first-step

in determining the type of atrioventricular connections
and eventually the ventricular function. This also helps in
determining the location of ventricular septum and orientation
of conduction tissues. This is important for the surgeon during
preoperative planning (Figures 5 and 6).
Figure 6: This long axis section of a heart with double inlet right
ventricle (DIRV) shows the opposite relationship to Figure 5. Here the
rudimentary LV is located posteroinferiorly. The yellow arrow shows
the atrioventricular valve which is anterosuperior to the ventricular
septum (star). Courtesy: Reprinted with permission from reference 16
Question II: Which is the Dominant Ventricle?

This decision is based on morphology of the ventricle and not
on position. The first morphologic principle states that left
ventricles have relatively smooth internal walls and lack chordal
attachments of the atrioventricular valves to the rudimentary
septal surface. Right ventricles are more heavily trabeculated
and generally have chordal attachments of the atrioventricular
valve to the septal surface. The second principle states that
the ventricular chamber that includes an infundibulum giving
rise to a great artery represents the morphologic right ventricle.
As a corollary, the ventricular chamber having a direct arterial
GenetICS21-24
epIdemIoloGy18-20
natural hIStory25,26
Accepting the lack of uniform nomenclature and classification

system, a New England registry in 1980 reported the incidence
of univentricular heart to be 54 cases per million live births.
Recent estimates are still higher. The commonest subtype was
HLHS, followed closely by tricuspid atresia. The Figure 8
diagrammatically summarizes the approximate prevalence of
common types of single ventricles.
In the largest series of unoperated patients (n = 83) Moodie

et al reported that 70 percent with dominant single left
ventricles died before age 16, with an annual attrition rate of
4.8 percent. The natural history is even bleaker for patients with
univentricular hearts of right ventricular morphology, with 50
percent survival 4 years after diagnosis. The most common causes
of mortality were arrhythmias, congestive heart failure (CHF)
Excluding HLHS, the other subtypes of univentricular heart

including DILV, single inlet, common inlet and complex single
ventricle heterotaxy syndromes are thought to be polygenic in
nature, with recurrence and transmission risks far below that
expected from Mendelian inheritance. The risk to siblings and
offspring of affected individuals is generally in the order of 2
to 5 percent.
Figure 7: Schematic representation to show the possible segmental combinations that can result in a functionally univentricular heart.
Courtesy: Reprinted with permission from reference 15. Dom. LV = Dominant left ventricle; Dom. RV = Dominant right ventricle; UV =
Univentricular
46
Single Ventricle
connection without an intervening infundibulum represents

a morphologic left ventricle. Rarely, we find ventricles with
primitive or indeterminate morphology.
Additionally, each class of univentricular heart may have
associated abnormalities of atriovisceral situs, of one or both
atrioventricular valves, of one or both semilunar valves and
of the relations (transposition or malposition) of the great
arteries. All these have been diagrammatically summarized in
the Figure 7.
647
Figure 8: Autopsy of 60 univentricular hearts excluding tricuspid and mitral atresia
Prevalence of common types of single ventricles20
and sudden unexplained death. Ammash and Warnes reviewed

their experience with 13 unoperated adults with univentricular
hearts to determine, which characteristics permitted long-term
survival. 11 patients had DILV with transposed great arteries,
1 patient had DILV with normally related great arteries and 1
patient had tricuspid atresia. The oldest patient was 66 years
old. All had either moderate-to-severe pulmonary stenosis or
pulmonary hypertension. The left ventricular ejection fraction
was normal (n = 11) or mildly depressed (n = 2) and no patient
had more than mild atrioventricular valve regurgitation.
Twelve patients reported good functional capacity and worked
full- or part-time. Thus, despite the overall grim prognosis in
unoperated patients, some adults with DILV, transposition of
the great arteries and well-balanced circulations may survive
into their seventh decade with acceptable functional capacity
and preserved ventricular function.
become critical as the ductus closes. In patients with mild

to moderate pulmonary stenosis, they present like tetralogy
of Fallot. They may be relatively asymptomatic,with mild
to moderate cyanosis, clubbing and attain adulthood with
retarded growth.
Clinical features
Aortic component of S2 is loud due to the anterior aorta.

The second heart sound is single or narrow split or normally
split. In patients with pulmonary hypertension there is no
split and it may appear as single S2. The systolic murmur
is audible along the mid or lower left sternal border. The
systolic murmur is decrescendo in patients with increased
PBF. A systolic ejection murmur is present in those with
subpulmonary stenosis. The murmur vary inversely in length
and loudness according to the degree of stenosis. The diastolic
murmurs can be heard in patients with single ventricle with
increased PBF. There can be an apical mid diastolic rumble
due to increased flow across the left atrio ventricular valve.
In patients with pulmonary hypertension, Graham Steell early
diastolic murmur of pulmonary regurgitation may be present
along the upper left sternal border.
The clinical features,timing and type of presentation of single

ventricle, depends on the associated lesions and degree of
outflow obstruction. The most frequent presenting symptom is
cyanosis since birth. They can also present for heart murmurs,
CHFand neonatal shock. The patients with single ventricle
with increased pulmonary blood flow (PBF) present in early
infancy with signs and symptoms of typical of large left to
right shunts like CHF and failure to thrive. Cyanosis may not
be very obvious if the patient has increased PBF. In patients
with associated aortic obstruction, the CHF is worsened.
648
In neonates with single ventricle and subpulmonary stenosis/

atresia marked cyanosis, metabolic acidosis develops and they
The LV type of single ventricle patients have a LV type

of apical impulse. It can be hyperdynamic in patients with
increased PBF. There can be a visible, palpable impulse
in the third left intercostal space (due to inverted outlet
chamber). The second heart sound is loud and palpable
(anterior aorta). The systolic thrill at left sternal border is
indicative of subaortic stenosis. The single ventricle of RV
type have a subxiphoid RV impulse. There is no impulse in
the third left intercostal space as there is no underlying outlet
chamber.
atrioventricular Connections31
eChoCardIoGraphIC dIaGnoSIS of
unIVentrICular heart27-29
As we have discussed before, the univentricular hearts

can be of LV dominance, RV dominance or primitive/
Indeterminate morphology. The best view having to evaluate
this is parasternal short-axis view. The Table 1 and Figure 9
summarizes the findings.
Ventriculoarterial Connections
The different connections possible are concordant,
discordant, double outlet from main or outlet chamber and
single outlet. However, certain combinations are seen more
frequently.
For example, nearly 86 percent of univentricular hearts with
LV dominance30 have discordant ventriculoarterial connections.
We have to carefully exclude outflow tract obstruction of the
great artery arising from the outlet or rudimentary chamber.
Only 14 percent of DILV hearts have normally related great
arteries called Holmes heart.
In univentricular hearts of RV dominance, the common
pattern is DORV from main chamber or single outlet with
pulmonary atresia.9
Double Inlet Connections

The most common univentricular hearts have double inlet
connection, which is usually due to both atrioventricular
valves draining into a common ventricular chamber (88%)
or rarely by a common atrioventricular valve (12%). Usually
common atrioventricular valve is associated with heterotaxy
syndromes (asplenia or polysplenia).
The double inlet is best visualized in short axis and four
chamber echocardiographic views (Figure 10). In DILV, there
is no intervening inlet septum between the right and left
atrioventricular valves; therefore these valves may actually touch
one another when they open in diastole (kissing atrioventricular
valves) and both valves are in continuity with posterior great artery.
Single Ventricle
type of univentricular heart
Atrioventricular connections can be of the following three types:

a. Double inlet.
b. Absence of an atrioventricular connection.
c. Straddling atrioventricular valves.
46
Absence of an Atrioventricular Connection9

Either the right or left atrioventricular connection is absent. In
absent connection, the floor of the atrium is entirely muscular
table 1
Echocardiographic diagnosis of univentricular hearts

Type
Relation of rudimentary chamber

to main chamber
Orientation of trabecular septum
AV valves
LV dominance
Anterior with either D/L loop
Anterior
Posterior to trabecular septum
RV dominance
Posterior
Posterior
Anterior
Primitive
No rudimentary chamber
No trabecular septum
AV = Atrioventriclular; LV = Left ventricle; RV = Right ventricle
Figure 9: Guide for echocardiographic diagnosis of univentricular hearts
649
Figure 10: An apical four-chamber echocardiographic view of double

inlet left ventricle (LV) showing both mitral and tricuspid valves
draining into morphological LV which is dominant. The star (*) shows
the location of the interventricular communication between dominant
LV and rudimentary right ventricle (RV)
and separated from the main ventricle by an atrioventricular

sulcus. There is no small chamber situated beneath the atretic
connection and no evidence of septum at the level of crux of
the heart (Figures 11 and 12).
This is in contrast to imperforate connection, where a small
rudimentary chamber is situated beneath the imperforate valve
and there is a definite ventricular septum oriented to the crux
of the heart. Absence of an atrioventricular connection is more
common than imperforate atrioventricular valve.
Common Inlet Ventricle9
Figure 11: An echocardiogram in apical four-chamber view showing

atretic tricuspid valve (*), concordant left atrioventricular connection
and mild mitral regurgitation. Left ventricle (LV) is dominant
Figures 12a and B: The figures represent autopsy specimens of

absent atrioventricular (AV) connection: left hand panel. A. Shows
classical tricuspid atresia and right hand panel; B. Shows mitral
atresia. The remaining atrioventricular connection is concordant.
In this common inlet ventricle case, the atrioventricular

connection is through a common atrioventricular valve
(Figures 13A and B). This condition is commonly seen in
heterotaxy syndromes. Convention dictates that if greater than
75 percent of a common atrioventricular valve annulus empties
into one ventricular chamber, a common inlet connection is
present. The atrioventricular valve has free-floating leaflets
and can override or straddle the trabecular septum.
evaluation of Interventricular Communication

(Synonyms: Bulboventricular foramen, VSD and outlet
foramen)
The bulboventricular foramen is the orifice through which
the main ventricular chamber feeds blood to the rudimentary
outflow chamber. If the chamber supports the pulmonary
flows like situation in Holmes heart, then restriction of the
bulboventricular foramen restricts PBF. However, in majority
650
Figures 13a and B: A subcostal four-chamber view showing complete

AV canal defect with common atrioventricular valve (*), common
atrium (CA), unbalanced ventricles with dominant left ventricle (LV)
and relatively hypoplastic right ventricle (RV)
Area =
diameter 1 diameter 2
4
When the area of the bulboventricular foramen is greater

than 2 cm2/m2 BSA, the foramen is always considered as nonrestrictive. In patients with area lesser than 1 cm2/m2 BSA,
during the initial palliation, the restrictive bulboventricular
foramen may need to be enlarged. In patients with area of
bulboventricular foramen between 1 to 2 cm2/m2 BSA, a
guarded waiting policy is justified. In patients, in whom the
bulboventricular foramen is anatomically smaller though nonrestrictive by Doppler recordings, a close echocardiographic
watch is justified.
Assessment of the Systemic Veins

In every patient with univentricular circulation, it is
mandatory to be precise about the systemic and pulmonary
venous anatomy before planning the surgery. Systemic venous
anomalies commonly present as bilateral superior vena cava
or as interrupted inferior vena cava (IVC) as in left isomerism.
Assessment of the Pulmonary Veins

Anomalies of pulmonary venous return are also common
anomalies in single ventricular patients, especially in the
setting of heterotaxy syndromes. These anomalies have
serious repercussions on the outcomes of Glenn shunt
and extracardiac Fontan surgeries. In single ventricular
physiology with reduced PBF, the anomalous pulmonary
venous drainage may not show florid signs since the
pulmonary venous drainage will also be proportionately
low. The echocardiographer should make serious attempts
to trace all the pulmonary veins meticulously and ensure
that no individual pulmonary vein drains anomalously into a
chamber other than the atria. In case of confusion, one should
not hesitate to obtain an angiogram to confirm the pulmonary
venous pathway.
To summarize, the check list while doing an echocardiogram
of univentricular heart is represented in the following
schematic diagram given in Figure 14.
SurGICal manaGement of SInGle VentrICle

In general, the surgical management of hearts with single
ventricle anatomy involves a combination strategy based
upon palliative and physiologically corrective procedures
(Figure 15).
Palliative procedures are those which correct the imbalance
between pulmonary and systemic blood flows, without
separating the two circulations. Physiologically, corrective
procedures are those that completely separates the pulmonary
and systemic circulations (creating in series circulations),
thus achieving the goal of unloading the systemic ventricle
and maintaining near normal systemic arterial saturation.
46
Single Ventricle
of instances since the rudimentary outflow chamber supports

the aortic circulation, restriction of bulboventricular foramen
results in subaortic obstruction.
Matitiau32 et al reported a method to calculate the area of
bulboventricular foramen. Since the foramen is almost never
circular in shape, its diameter was measured in two orthogonal
planes (short- and long-axis views: diameter 1 and diameter
2 respectively) and then the area was calculated from this
formula:
hemodynamICS of SInGle VentrICle

and fontan CIrCuIt33
A normal postnatal cardiovascular system consists of a
doublepulmonary and systemiccircuit, connected in
series, powered by a double pumpthe right and left heart.
However, in a univentricular heart, the single ventricle
has to maintain both the systemic and pulmonary blood
circulations, which are not connected in series but in parallel.
There are two main disadvantages: 1. arterial desaturation and
2. chronic volume overload to the single ventricle. Such a
chronic volume overload has significant effects on the single
ventricle namely:
Dilatation of atrium and ventricle
Eccentric hypertrophy
Spherical remodeling with reorientation of wall fibers
Annular dilatation causing progressive atrioventricular
valve regurgitation.
Thus, the hemodynamic problems in univentricular hearts
arise from:
Inherent mechanics of a single ventricle (lack of
interventricular coupling and volume overload to single
ventricle)
Mechanics of morphological RV versus morphological LV
Morphology and functional state of atrioventricular valves
Degree of mixing within single ventricle
Pulmonary vascular resistance (PVR)
Presence and degree of pulmonic or subaortic stenosis
In 1971, Francis Fontan from Bordeaux, France,
reported a new approach to the operative correction of these
malformations. In a Fontan circulation, the systemic
venous return is connected to the pulmonary arteries without
an interposing ventricle and all shunts at venous, atrial,
ventricular and arterial levels are interrupted. In such a circuit,
the postcapillary energy is no longer wasted into the systemic
veins, but collected and used to push the blood through the lungs.
Advantages of a Fontan circuit are (near) normalization
651
Figure 14: Schematic diagram showing the checklist while doing an echocardiogram
of univentricular heart. CHF = Congestive heart failure.
of the arterial saturation and adjustment of chronic volume

overload at the cost of chronic systemic venous hypertension
and congestion. The cardiac ouput is decreased as compared to
normal subjects, both at rest and during exercise. Typically, the
cardiac output is no longer determined by the heart, but rather
by transpulmonary flow (itself regulated by PVR). Thus, the
circuit runs on autopilot, with little interference possible by
the clinician. Cardiac output can be increased by improving
flow to and into the lungs or by bypassing the lungs with a
fenestration. The effect of pulmonary vasodilators is usually
very modest (Figures 16A to C).
652
Is every fontan Circuit alike?

The Fontan operation (Figures 17A to C) was first used in 1968
for the repair of tricuspid atresia and was described by Fontan34
and Baudet in 1971. It diverted the systemic venous return to the

pulmonary artery (PA) and included the insertion of an aortic or
pulmonary homograft valve, at both the inflow and outflow of
the right ventricle. Some time later, Kreutzer35 and colleagues
described in a simple way the use of pulmonary valve at the
connection of the right atrium to the PA. These operations
collectively called as Atriopulmonary plexy were based on
the principle that the right atrium can act as the pump for the
pulmonary circulation. This concept was later questioned.
In 1987, de Leval36 et al proposed a major variation that
consisted of an end-to-side direct anastomosis of the superior
vena cava to the undivided right PA and using a conduit that
is created inside the atrium, the IVC is also drained to the
PA: Lateral Tunnel Technique. In the majority of cases,
the lateral tunnel is created by insertion of a semicylindrical
polytetrafluorethylene (PTFE) baffle incorporating a small
46
Single Ventricle
Figure 15: Surgical management of single ventricle
portion of the lateral atrial wall. In some patients, the

lateral tunnel can be created by autologous material from
the interatrial septum. Its advantages are decreased risk of
thrombosis, decreased blood stasis and exposure of a limited
portion of right atrium to the high venous pressures, thus
reducing the risk of arrhythmias. In addition, the coronary
sinus remains in the low-pressure atrium allowing unimpeded
myocardial venous drainage.
Marcellati 37 in 1990 popularized the use of an extracardiac
interposition graft between the transected IVC and PA:
Extracardiac Fontan. It allows for better preservation
of ventricular and pulmonary function because it requires
minimal or no cardiopulmonary bypass. In addition, it avoids
right atrial incisions and extensive atrial suture lines. This
reduces the risk of injury to the sinus node and the incidence
of postoperative arrhythmias. However, since the extracardiac
tunnel is created either by homograft or conduit, it has no
growth potential and is at risk for obstruction by thrombus
formation or neointimal hyperplasia. The usual size of
conduit used is 18 mm and above. This is to allow a uniform
extracardiac conduitinferior vena cava transition. Usually a

slightly oversized conduit is required in younger children to
allow for vessel growth in relation to somatic growth. Our
institutional protocol is to perform it at a minimum age of
around 3 years and weight of about 15 kg.
The latter two procedures namely Lateral Tunnel
technique and Extracardiac conduits are named as Total
Cavopulmonary Connection (TCPC). TCPC surgeries offer
laminar blood flows and are hydraulically more efficient than
older versions.
In patients with infrahepatic interruption of the IVC (as
in left isomerism), only the hepatic veins drain into the right
atrium. Blood from the lower body reaches the superior caval
vein via the azygos vein. In these patients, a bidirectional
cavopulmonary anastomosis (Kawashima operation)38 will
result in an almost complete Fontan palliation, redirecting
blood from the superior vena cava as well as from the azygos
vein to the pulmonary arteries and leaving only the hepatic
veins draining into the systemic circulation (Figures 18
and 19).
653
a
B
B
c
Figures 17a to c: Variations of Fontan surgery. A. The modified classic
Fontan; B. The intracardiac lateral tunnel Fontan; C. The extracardiac
Fontan. In (A), the modified Blalock-Taussig shunt, shown in white, was
taken down and oversewn. In (C), permanent atrial epicardial pacemaker
leads are illustrated in gray. Courtesy: Reprinted from reference 51
c
Figures 16a to c: This schematic diagram depicts the hemodynamics
of single ventricle and Fontan surgery. A. The normal cardiovascular
circulation. The pulmonary circulation (P) is connected in series with
the systemic circulation (S). The right ventricle maintains the right
atrial pressure lower than the left atrial pressure, and provides enough
energy to the blood to pass the pulmonary resistance; B. The patient
with a univentricular heart. The systemic and pulmonary circuits are
connected in parallel, with a considerable volume overload to the single
ventricle (V). The width of the line reflects the degree of volume load.
There is complete admixture of systemic and pulmonary venous blood,
causing arterial oxygen desaturation; C. The Fontan circulation. The
systemic and pulmonary circulations are connected in series. The right
atrium (RA) or systemic veins are connected to the pulmonary artery
(PA). The volume overload to the single ventricle is now less than
expected for body surface area. In the absence of fenestration, there is
no more admixture of systemic and pulmonary venous blood, but the
systemic venous pressure is notably elevated. Ao = Aorta; LA = Left
atrium; LV = Left ventricle; RV = Right ventricle. Courtesy: Reprinted
from reference 34
paradox of fontan Circulation39
654
In a normal circulation, a good hemodynamic state is

characterized by low pressures, especially in the IVC (< 10 mm
Hg), with the mean PA pressure being at least 15 mm Hg in order
for the pulmonary vascular network to be patent according to
the West zones. The paradox in the Fontan circulation is the

coexistence of systemic venous hypertension and pulmonary
arterial hypotension. It should be emphasized that the driving
force of the circulating blood volume between systemic and
pulmonary veins is the pressure gradient between central
venous pressure and the left atrium, assisted mechanically by
the thoracic muscles and the respiratory function.
Ideal patient for fontan operation

The original criteria for the Fontan operation, set by
Choussat40 and his colleagues for patients with tricuspid
atresia, were particularly strict.
Original Criteria Proposed for Fontan Completion

(Ten Commandments)
Age greater than or equal to 4 to lesser than 15 years

Normal sinus rhythm
Normal systemic venous return
Normal right atrial volume
Mean PA pressure lesser than or equal to 15 mm Hg
Pulmonary arteriolar resistance lesser than 4 Wood units/
m2 body surface area
Pulmonary artery to aortic diameter ratio greater than or
equal to 0.75
46
Single Ventricle
Figure 18: This subcostal sagittal echocardiographic view shows

interrupted IVC with azygos continuation (Az) posterior to descending
aorta (D Ao)
Figure 19: This schematic diagram shows Kawashimas modification

in patients of univentricular heart with interrupted inferior vena cava
(IVC). Ao = Aorta; HV = Hepatic vein; PV = Pulmonary veins; SVC =
Superior vena cava.
Left ventricular ejection fraction greater than or equal to

0.60
Competent mitral valve
Absence of PA distortion.
With increasing experience, the criteria have become more
flexible. Preoperatively impaired ventricular function and
elevated pulmonary arterial pressures are currently considered
as the two most important commandments.
Figure 20: This suprasternal echocardiogram in a post Glenn child

shows the laminar flow in Glenn shunt (SVC connected to RPA with
arrow depicting the site of anastomosis). RPA = Right pulmonary
artery; SVC = Superior vena cava.
Figure 21: This angiogram taken during pre-Fontan evaluation depicts

selective injection into right-sided Glenn shunt (GS) by an end-hole
multipurpose 4F catheter (C) showing opacification of confluent,
adequate sized right pulmonary artery (R) and left pulmonary artery (L)
with good arborization peripherally. The stump of main pulmonary artery
(M) is seen but the pulmonary valve is atretic. The multipurpose catheter
was introduced by percutaneous selective access of ante-cubital vein
Cardiac Catheterization for pre-fontan evaluation41,42

The focus of cardiac catheterization for pre-Fontan evaluation
is on the following:
1. Patency of the Glenn shunt with analysis of PA anatomy
(Figures 20 to 22): PA size and distortion, confluence
stenosis (stenosis > 50% as compared to adjacent segment),
presence or absence of anomalously draining pulmonary
veins in levophase and any significant decompressing
venovenous collaterals (> 2 mm).
2. Inferior vena cava angiogram (Figure 23) to rule out
interrupted IVC/ stenosis/duplication of IVC and drainage
pattern of hepatic veins.
655
8
than 85 percent and lesser than 75 percent signify increased

and decreased PBF, respectively.
The two most important cath data required by surgeon
are PA pressure and PVR. It is mandatory to calculate
both and not be satisfied after recording PA pressures
alone.
Is Cardiac Catheterization Mandatory before Fontan?
Figure 22: This angiogram taken in a post bidirectional Glenn shunt

child presenting with cyanosis depicts an end-hole catheter (C) passed
from ventricle (V) across pulmonary artery (PA) band into Glenn shunt
with a significant descending venovenous collateral decompressing
the Glenn shunt
Figure 23: This antegrade venous catheterization was done as part

of Pre-Fontan evaluation showing an uninterrupted IVC draining into
heart. IVC = Inferior vena cava; L = Liver; S = Spine.
656
3. Ventriculogram to detect ventricular contractility, atrioventricular valve regurgitation, systemic outflow obstruction,
presence or absence of antegrade flow from ventricle to
pulmonary artery.
4. Hemodynamic evaluation: PA systolic, diastolic and
mean pressures, PVR and ventricular end-diastolic pressures.
If one assumes a pulmonary venous oxygen saturation of
96 percent and normal systemic blood flow, the arterial oxygen
saturation reflects total PBF. As a rule of thumb, values greater
Those who argue that catheterization is not necessary, suggest

that cardiac MRI provides anatomical information of similar
quality. But the consensus opinion is that routine preoperative
cardiac catheterization must be done before Fontan operation.
This is the only valid method to measure PVR. Also if
abnormal aortopulmonary or venovenous collateral vessels
are identified, they can be embolized at the same instance.
Sequelae of fontan operation43-45

Forty years on from the first use of the Fontan operation, the
perioperative mortality has stabilized between 3 to 5 percent.
Early morbidities include pleural and pericardial effusions,
low cardiac output, sinus node injury and pulmonary and
systemic venous obstructions.
However, Fontan himself reported an early gradual decline
of the functional state of this neocirculation, which affects the
long-term survival. Even in ideal circumstances, the overall
survival at 5, 10 and 15 years after surgery was 86 percent,
81 percent and 73 percent respectively. Long-term follow-up
after lateral tunnel procedure documented a freedom from
failure of 87 percent at 10 years. Long-term follow-up after
extracardiac Fontan revealed an overall 10-year survival of
92.4 percent 2.1 percent. Multivariate analysis identified
severe infection during the early postoperative period and
a high pulmonary arterial pressure during the preoperative
period as independent risk factors for patient mortality. The
Kaplan-Meier estimate for freedom from reoperation was
82.4 percent plus or minus 4.1 percent at 10 years. Freedom
from arrhythmia was 85.1 percent plus or minus 4.4 percent
at 10 years and freedom from thromboembolism at 10 years
was 92.9 percent plus or minus 1.9 percent. 95.2 percent of
survivors were in NYHA class I.
The factors that led to improvement in the surgical outcome
are use of more energy-efficient circulation with introduction
of TCPC techniques, decrease in use of aortic clamp, minimal
use of extracardiac circulation, use of fenestration, preliminary
volume unloading operations like bidirectional Glenn shunt
and concomitant clamping of any aortopulmonary collaterals.
Data shows that the extracardiac conduit procedure
provides superior hemodynamics compared to the intraatrial lateral tunnel technique. This hemodynamic advantage
is markedly enhanced by the use of conduitsuperior vena
cava offset, particularly at high physiologic flow rates as in
exercise. These data suggest additional justification for the
use of extracardiac conduit procedures for final completion of
46
Single Ventricle
Figure 24: This schematic diagram depicts a lateral tunnel procedure

with fenestration (arrow). Ao = Aorta; LT = Lateral tunnel; LPA = Left
pulmonary artery; RPA = Right pulmonary artery; SVC = Superior vena
cava.
Pulmonary vein bed congestion

Thromboembolic episodes
Worsening cyanosis due to:
Existence of surgically created communication (fenestration)
Development of collateral arteriovenous circulation
(systemic and pulmonary)
Decreased exercise tolerance
Cognitive disorders
Protein-losing enteropathy (PLE)
Progressive liver failure
Plastic bronchitis.
Mair et al48 studied the preoperative risk factors contributing
to long-term complications and reported them as:
The age of the patient before surgery
Existence of previous palliative surgical procedures
The anatomy of the complex congenital disease
Heterotaxy syndromes
Elevated PA pressure before surgery
Significant regurgitation of the atrioventricular connection
NYHA class III/IV before surgery.
Complications post-fontan operation

the Fontan circulation.
In a subgroup of patients at increased risk (young
age at operation, increased mean PA pressure and PVR,
raised ventricular end-diastolic pressures and significant
atrioventricular valve regurgitation) a small fenestration can
be created in the intra-atrial tunnel at the time of TCPC to
allow a protective right-to-left shunt (Figure 24). The potential
benefits are a lower central venous pressure and better single
ventricle preload, albeit at the expense of a right-to-left shunt
and mild cyanosis. These benefits were found to be greatest in
the immediate postoperative period when, as a consequence
of cardiopulmonary bypass and myocardial ischemia,
myocardial function was impaired and elevated PVR was a
problem. This modification has improved operative survival
rates among high risk patients and shortened duration of
pleural effusions and length of hospital stay.46 A considerable
percentage of small fenestrations will close spontaneously
later on. In patients with persistently patent fenestration and
mild cyanosis it remains controversial whether interventional
occlusion is required later. In patients with increasing
cyanosis during exercise, transcatheter device occlusion of
fenestration is recommended in the presence of appropriate
hemodynamics.47 It should not be done in patients with
preoperative risk factors, residual PA distortion or anastomotic
stenosis, significant atrioventricular regurgitation and signs of
systemic ventricular dysfunction.
On the other hand, the main factors associated with longterm morbidities are:
Progressive ventricular dysfunction
Systemic venous hypertension
Right atrial distension
Functional Status and Exercise Tolerance49

More than 90 percent of all hospital survivors are in NYHA
functional class I/II. Most patients do well educationally and
can pursue a variety of professional careers. However, with
time there is a progressive decline of functional status in some
subgroups.
Ventricular Function33
All studies reported the ventricle of a functionally univentricular
heart to be dilated, hypertrophic and hypocontractile. It can be
caused by the congenital malformation itself, previous surgical
interventions or the very abnormal working conditions of the
ventricle at various stages of palliation, both before and after
Fontan.
During the first month after birth, the ventricle is always
volume overloaded. This leads to dilatation and spherical
configuration, cardiac overgrowth and eccentric hypertrophy.
By performing Fontan operation, the preload is reduced to
levels well below normal for BSA (5070%) and even more
when expressed in relation to ventricular size (2570%). The
ventricle thus undergoes a transition from volume overloaded
and overstretched, to overgrown and severely underloaded.
Thus, the Fontan ventricle shows systolic and diastolic
dysfunction. It may enter into a vicious cycle whereby the
low preload leads to remodelling, reduced compliance, poor
ventricular filling and eventually declining cardiac output.
This phenomenon of progressive disuse hypofunction occurs
at a chronic preload of less than 70 percent of the due
preload.
657
The congenital malformation may itself predispose to

ventricular dysfunction. The morphological LV with its
ellipsoid shape and complex fiber orientation is tuned to handle
systemic pressure for a lifetime. But the morphological RV
and even more the indeterminate primitive ventricle fails after
few years of systemic loading. Futhermore, a tricuspid valve
or common atrioventricular valve poorly tolerates the initial
volume overload and starts regurgitating shortly. The treatment
of ventricular dysfunction in the setting of Fontan circuit is
very frustating for a cardiologist. Several studies, both acute
and chronic, have shown little impact of inotropes, afterload
reducers, vasodilators and beta-blockers, as these have no
impact on the reduced preload which is the main limiting factor.
arrhythmia50-52
The incidence of arrhythmias post-Fontan surgery ranges
between 10 to 40 percent and reported even up to 10 years later.
Etiology
Many older Fontans have atrial wall incorporated into the
circuit causing progressive atrial dilatation and wall stress;
furthermore, most of them also had atriotomy and possible
injury to the sinus node or innervation. The lateral tunnel
technique per se is a risk factor, leading to the development
of arrhythmias due to the suture lines placed inside the
atrium. Heterotaxy syndromes are also prone to rhythm
disorders. Bradyarrhythmias have also been observed in
patients undergoing the extracardiac tunnel technique. Atrial
pacing has been suggested in order to avoid moderate degree
bradyarrhythmias.
658
Types
The commonest arrhythmias are sinus node dysfunction
(prevalence 1316%), intra-atrial re-entrant tachycardia
(Figure 25) or atrial flutter. They are usually refractory to
anti-arrhythmics and in the acute setting, quickly deteriorate
to clinical cardiac failure. Cardioversion with direct current
(DC) shock is the safest immediate therapy. Subsequently, the
clinician should obtain a complete hemodynamic evaluation
in every patient with new tachycardia, as this may be the first
manifestation of pathway obstruction. Full anticoagulation
should also be started. Long-term treatment involves
medication and ablation. The best long-term treatment is
conversion of the older Fontan types to an extracardiac
cavopulmonary connection, together with a right atrial maze
and a reduction plasty (combined with dual chamber epicardial
pacemaker if indicated). In refractory atrial tachyarrhythmias,
but no other indication for surgical revision, transcatheter
ablation approach may be tried with repeat procedures as
required.
Ventricular arrhythmias are extremely rare and usually
caused by severe ventricular dysfunction.
Severe hypoxemia: post fontan53-56

Patients with a Fontan circulation are slightly desaturated
with baseline pulse oximetry values 94 percent plus or minus
2 percent. This is because the hepatic veins and coronary sinus
still drain into the atrial chambers. However, in the setting
of severe desaturation, the following anatomical substrates
should be ruled out: a large fenestration, intrapulmonary
arteriovenous fistulae and abnormal systemic venous channels
Figure 25: A 12-lead electrocardiogram in a post-Fontan patient with tricuspid atresia showing recurrent persistent intra-atrial
re-entrant tachycardia with a ventricular response rate of 167 beats/minute
residual left-to-right Shunt

Residual left-to-right shunt can happen due to large
aortopulmonary collaterals, persistent antegrade flow from
ventricle to pulmonary artery and failed occlusion of previous
shunts. A large left-to-right shunt produces volume overload
and stress on the single ventricle. The rule of thumb is that
if angiography of a systemic vessel gives rise to pulmonary
capillary blush and opacification of pulmonary veins, it should
be occluded percutaneously.
Ventricular failure57
Ventricular failure is mostly seen around 8 years after the initial
Fontan surgery, although it has been reported both earlier
and later. The etiology is multifactorial like morphology of
dominant ventricle, valve regurgitation, etc. But the unique
feature is the combination of decreased preload and increased
afterload (as systemic and pulmonary circulation are again in
series) in a Fontan circuit.
Even asymptomatic patients demonstrate abnormal cardiorespiratory response to exercise which is best unmasked by
Dobutamine stress test.
As we have discussed before in the hemodynamics
section, the role of inotropes, vasodilators and beta-blockers
is limited. Prompt repair of structural anomalies like
atrioventricular valve regurgitation, relief of outflow tract
obstructions, correction of PA stenosis are helpful. In endstage situations, orthotopic heart transplantation is the only
answer.
46
Single Ventricle
draining into the pulmonary venous atrium (for example, a left

superior caval vein to the left atrium). Detailed angiography
of supra and infradiaphragmatic systemic veins should be
done. These connections can be occluded percutaneously in
the majority of cases.
The development of pulmonary arteriovenous malformations is described in up to 25 percent of patients post-Glenn shunt
leading to progressive cyanosis and exercise intolerance. The
probable etiology is exclusion of hepatoenteric flow (Factor
X) from the pulmonary circulation. These malformations
are often multiple and diffuse. Recent reports noted the
reversal of pulmonary arteriovenous malformations following
redirection of hepatic venous flow to the pulmonary circulation
thromboembolic events58,59
Symptomatic systemic venous and arterial thromboembolisms
have a reported incidence of 3 to 20 percent. Literature
review reveals a bimodal peak of increased incidence of
Figures 26a and B: Selective pulmonary angiography of the right lower lobe in a patient with tricuspid atresia and unidirectional Glenn shunt.
A. Multiple pulmonary arteriovenous malformations; B. One residual pulmonary arteriovenous malformation after transcatheter coil occlusion.
Courtesy: Reprinted from reference 51
659
lymphatic dysfunction60,61
Pathogenesis
Figure 27: Subcostal echocardiographic view of the right atrium (RA)

in a patient with a modified classic Fontan for D-transposition of the
great arteries, multiple muscular ventricular septal defects, a functional
single ventricle and atrial tachyarrhythmias. The arrow indicates a welldelineated thrombus in the dilated right atrium. Courtesy: Reprinted
from reference 51
660
thromboembolism: one at 1 year and another around 10

years postsurgery.
Increased systemic venous pressure, low velocity flow
within the systemic venous atrium and pulmonary circulation,
low cardiac output and dehydration contribute to the risk of
thrombus formation. In addition, liver dysfunction (Protein C,
Protein S and antithrombin III deficiency), increased platelet
reactivity and PLE may alter the balance between pro- and
anticoagulant factors (Figure 27).
Massive pulmonary thromboembolism is the most common
cause of sudden out-of-hospital death in patients with a Fontan
circuit. Chronic multiple pulmonary microemboli may lead to
pulmonary vascular obstructive disease, which may appear
late but is particularly lethal in a Fontan circulation.
There is no consensus, however, regarding the postoperative mode and duration of prophylactic anticoagulation, since
no large scale randomized control studies have been performed. Routine anticoagulation with coumadin is performed
by some institutions irrespective of the type of the modified
Fontan procedure and potential risk factors. Many centers,
however recommend aspirin for uncomplicated patients and
full anticoagulation34 in presence of previous thrombi, low
cardiac output (frequently associated with spontaneous contrast on echo), congestion, dilation of venous or atrial structures and arrhythmia, PLE, etc.
Keeping in mind the bimodal presentation of thromboembolism, our protocol is to administer oral anticoagulants
for 1 year postsurgery, then switch over to oral antiplatelets
and finally restart oral anticoagulants from 10 years post
surgery onwards.
A Fontan circulation operates at/just beyond the functional

limits of the lymphatic system. The superior vena caval
pressure is elevated and its runoff decreased, impeding
drainage of the thoracic duct. Leakage in the interstitium causes
lymphedema or pulmonary edema, a very lethal complication
in the early postoperative period. Leakage into the thorax or
pericardium will lead to chylothorax or chylopericardium, a
complication which usually only occurs in the perioperative
period, but rarely thereafter because of adhesions. Intestinal
lymphangiectasia with leakage of lymphocytes, chylomicrons
and serum proteins (albumin and immunoglobulin) into the
gut leads to PLE, the most frequent lymphatic problem in
long-term follow-up. Leakage of chyle into the bronchus leads
to plastic bronchitis, most frequently diagnosed at necropsy.
Clinical Presentation of PLE

The common clinical manifestations are edema, ascites,
immunodeficiency, fatigability and hypocalcemia. The
diagnosis is confirmed by low serum albumin and positive
fecal 1 antitrypsin. In an international multicenter study of
3029, patients with Fontan repair between 1975 and 1995,
PLE occurred in 3.8 percent. The prognosis is very poor with
5 and 10 year survival rates of 59 and 20 percent, respectively.
Etiology
Problems in Fontan circuit (gradient at connection, poor
design), problems of pulmonary vasculature (increased
PVR, hypoplasia, distorted PA anatomy) or cardiac problems
(atrioventricular valve regurgitation, myocardial dysfunction)
are frequently identified. An autoimmune or inflammatory
cause, sometimes triggered by an infection, has also been
isolated in some cases. Hypoxemia induced pulmonary
vasoconstriction was reported to be associated with PLE in
patients living at high altitudes.
Treatment Strategies
Clinical resolution of PLE is rare (< 1%). The following
therapies have been tried:
1. A diet high in calories, high protein content and medium
chain triglyceride fat supplements with low salt content
is usually recommended.
2. Diuretics for peripheral edema.
3. Protein infusions (albumin, globulin) on a weekly or
monthly basis.
4. In some patients, specific anti-infection measures are
necessary (chronic antibiotics, vaccines).
plastic Bronchitis
Plastic bronchitis is a very rare, but potentially lethal
complication occurring weeks to months after Fontan
surgery causing obstruction of major airways with solid
fibrinomucoid material. Persistent segmental atelectasis,
large airway obstruction or expectoration of tenacious mucoid
material should prompt early diagnostic and therapeutic
bronchoscopic lavage. Treatment is very difficult and similar
to PLE.
output, limited exercise tolerance, relapsing tachycardia,

PLE and/or plastic bronchitis. As explained before, treatment
with inotropes, vasodilators, and diuretics show little
result. A more aggressive approach aimed at optimising the
Fontan circuit (stenting of stenosis, embolising collaterals,
conversion of older Fontans to TCPC, right atrial maze for
intractable arrhythmias, creation of fenestration, etc.) is
needed. In refractory cases, heart transplantation is the only
option.
46
Single Ventricle
5. Inotropes or systemic vasodilators fail to improve

ventricular function.
6. Corticosteroids, heparin and octreotide have been
occasionally useful.
7. Resection of the most affected part of the gut.
8. Surgical correction of stenosed anastomotic sites, leaking
atrioventricular valves, late takedown, etc. carries a high
mortality.
9. Cardiac transplantation with consequent immunosuppressive therapy has been tried in refractory cases. This
often cures the PLE, but also has its own significant disadvantages.
10. Catheter interventions: Balloon dilatation/stent implantation of residual PA stenosis, embolization of left-toright shunts and fenestration of Fontan circuit has been
tried in PLE. Of these, fenestration almost always improves PLE, but with the risk of progressive cyanosis.
SuGGeSted folloW-up of poSt-fontan patIentS

Post-Fontan patients should be followed up by a specialist
team and the observation parameters in our institute are:
Clinical assessment including blood pressure and resting
pulse oximetry
12 lead electrocardiogram
Echocardiogram with color Doppler (Figures 28 and 29)
and Tissue Doppler imaging
Blood for complete blood count, prothrombin time (PT)
and INR (International Normalized ratio), liver function
tests
Exercise tolerance with Treadmill test
Holter monitoring if arrhythmias
Additional
work-up
include:
Transesophageal
echocardiography, cardiac MRI, cardiac catheterization
and Electrophysiological study (EPS).
reproduction: pregnancy62,63
Most females after Fontan repair have normal menstrual
patterns. However, normal pregnancy is associated with
30 to 40 percent increase in cardiac output and circulating
blood volume and decrease in systemic vascular resistance by
24 weeks of gestation. Also a hypercoagulable state is present.
These changes lead to increase in systemic venous pressure
and may trigger right heart failure in a post-Fontan lady. The
risk of right-to-left shunt, venous thrombosis and pulmonary
embolism is increased. Successful pregnancy is rare. Studies
reveal that an oxygen saturation of lesser than 85 percent was
predictive of increased risk.
The risk of the fetus having congenital heart disease is
currently unknown, as women with cardiac malformations
amenable to Fontan surgery have rarely had offspring. For
most malformations the risk will probably vary between 5 to
10 percent.
failing fontan64,65
A Fontan circulation may become failing and unbearable
because of persistent congestion with edema, low cardiac
Figure 28: Subcostal echocardiogram showing laminar flow in

extracardiac Fontan conduit (arrow). V = Inferior vena cava
661
Key Messages
1. Nearly 10 percent of congenital cardiac malformations

belong to functionally univentricular heart.
2. The prognosis is extremely poor if left untreated.
3. The current therapy is a staged surgical approach
called Fontan palliation which routes the systemic
venous circulation to pulmonary circulation without an
interposing ventricle.
4. Long-term follow-up post Fontan surgery reveals late
attritions due to arrhythmias, ventricular dysfunction
and unusual clinical syndromes of plastic bronchitis and
protein losing enteropathy.
5. Cardiac transplantation is the only final hope for failing
Fontan patients.
Figure 29: The echocardiogram in apical four-chamber view in a

patient of tricuspid atresia status post-Fontan surgery shows the
Fontan tunnel (T) with arrow showing mosaic flow through the
fenestration in Fontan circuit
ConCluSIon
referenCeS
The long-term results of the Fontan operation performed

in low risk patients show good overall results: hypoxia is
eliminated, volume overload is abolished and chronic systemic venous hypertension is usually tolerated. Survival of
patients undergoing a completion TCPC in the current era is
excellent. However, various common and uncommon morbidities gradually deteriorate the quality of life. Preliminary
unloading of the single ventricle by bidirectional Glenn shunt
gives an overall better result of ultimate Fontan completion.
However, every clinician should remember that a Fontan
operation remains an imperfect solution for a complex
cardiovascular problem.
It is health that is real wealth and not
pieces of gold and silver
Mahatma Gandhi
aCKnoWledGment
662
Circulation 2007 (reference 49). Our endeavor was to look

at univentricular heart and Fontan surgery from a practical
and clinical point of view. The interested readers are invited
to go through the individual reference articles for a more
comprehensive understanding. Fontan surgery is still evolving
in its techniques and management and is probably one of the
most fascinating topics in congenital heart disease.
We sincerely thank Professor Robert Anderson for permission

to reprint from his exhaustive collection of morphological
images of single ventricle. In addition, we thank him for
allowing us to deliberate and realize the true meaning
of functional single ventricle. We also acknowledge the
contribution of Dr Gewellig towards establishing an
explanation of hemodynamics of single ventricle. His
article (reference 33) is a must read item for any student of
pediatric cardiology. We also acknowledge the beautiful
review on univentricular heart published by Khairy et al in
1. Peacock TB. Malformations of the heart. In: Peacock TB (Ed).

On Malformations of the Human Heart: With Original Cases.
London: John Churchill; 1858. pp. 10-102.
2. Abbott ME. Atlas of congenital cardiac disease. New York:
American Heart Association; 1936. pp. 50-2.
3. Taussig HB. Cardiovascular anomalies: a single ventricle with
a diminutive outlet chamber. J Tech Methods. 1939;19:120.
4. Edwards JE. Congenital malformations of the heart and great
vessels. In: Gould SE (Ed). Pathology of the heart, 2nd edition.
Springfield: Charles C Thomas; 1960. p. 335.
5. Lev M, Liberthson RR, Kirkpatrick J, et al. Single (Primitive)
Ventricle. Circulation. 1969;39.
6. Marin-Garcia J, Tandon R, Moller JH, et al. Common (single)
ventricle with normally related great vessels. Circulation.
1974;49:565-73.
7. Anderson RH, Becker AE, Wilkinson JL. Proceedings:
morphogenesis and nomenclature of univentricular hearts. Br
Heart J. 1975;37:781-2.
8. Van Praagh R, Ongley PA, Swan HJ. Anatomic types of
single or common ventricle in man: morphologic and
geometric aspects of 60 necropsied cases. Am J Cardiol.
1964;13:367-86.
9. Anderson RH, Tynan M, Becker AE. Echocardiography of
the univentricular heart. In: Lundstrom N-R (Ed). Pediatric
echocardiography cross sectional, M-mode, and Doppler,
Amsterdam; 1980, Elsevier/North Holland Biomedical.
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in five hundred consecutive patients: factors influencing
early and late outcome. J Thorac Cardiovasc Surg. 1997;114:
376-91.
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fenestration on outcome of the modified Fontan operation.
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influence the development of atrial flutter after the Fontan
operation. J Thorac Cardiovasc Surg. 1997;113:80-6.
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12. Jacobs ML, Mayer JE, Jr. Congenital Heart Surgery Nomenclature and Database Project: single ventricle. Ann Thorac Surg.
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heart. Devel Biol. 2000;223:266-78.
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of congenital heart disease: an analysis of 6,640 consecutive
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with truncus arteriosus in siblings. Am Heart J. 1981;102(3 Pt
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of univentricular atrioventricular connection, J Am Coll
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of double inlet ventricle: evaluation of the interventricular
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Increasing cyanosis early after cavopulmonary connection
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desaturation after total cavopulmonary shunt operations. Br
Heart J. 1995;74:282-6.
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children with functionally univentricular hearts. Arch Dis
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PLE study group. J Thorac Cardiovasc Surg. 1998;115:
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risk factors for development of protein-losing enteropathy
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outcomes after the Fontan repair. J Am Coll Cardiol. 1996;28:
763-7.
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failing Fontan: lateral tunnel versus extracardiac conduit. Ann
Thorac Surg. 2005;80:1445-51.
C hapter
47
Hypoplastic Left Heart Syndrome

P Syamasundar Rao, Srilatha Alapati
INTRODUCTION
The term hypoplastic left heart syndrome (HLHS), initially
proposed by Noonan and Nadas,1 describes a spectrum of
cardiac abnormalities characterized by marked hypoplasia of
the left ventricle (LV) with atresia or severe stenosis of aortic
and/or mitral valves (MV) and hypoplasia of the ascending
aorta and aortic arch. The ventricular septum is usually
intact. The left atrium is small and a patent foramen ovale or
secundum atrial septal defect is usually present. A large patent
ductus arteriosus supplies blood to the systemic circulation. It
is associated with coarctation of the aorta in most cases. This is
the same disorder characterized as hypoplasia of the aortic tract
complex by Lev.2 Prior to 1980s, the only choice for HLHS
patients is comfort care and it contributed to a large proportion
of the cardiovascular mortality occurring in the first month of
life. Since the description of surgical palliation by Norwood3,4
in the early 1980s and of allograft cardiac transplantation
by Bailey5 in the mid-1980s, the interest in this lesion has
remarkably increased. In recent era, there are several available
treatment options for this condition, but there is still an ongoing
debate regarding the best approach for the palliation.
supply adequate coronary blood flow in a retrograde fashion.

Coarctation of the aorta may be present in a significant number
of patients with HLHS,3,6-8 but interrupted aortic arch is rare.
The right heart (i.e. right atrium, right ventricle, pulmonary
arteries) is markedly enlarged.
The left atrium is small reflecting limited blood flow in
utero. The atrial septum is usually thickened and there is
anomalous attachment of septum primum to the left atrium
and this makes the foramen ovale to be small and restrictive.
The septum primum is usually deviated more posteriorly
and to the left.9,10 Rarely, there may be intact atrial septum
(Figure 1) and the condition of these patients is usually
much more critical at birth. Ventricular septal defect is not
PATHOLOGICAL ANATOMY
The HLHS is associated with hypoplasia of the left heart
and enlargement/hypertrophy of the right heart. Similar to
other congenital heart defects, HLHS also has a spectrum
of severity.6 In the most severe form, aortic valve and MV
are atretic, with a diminutive ascending aorta and markedly
hypoplastic LV. The MV may be atretic, hypoplastic or
severely stenotic. The atretic MV consists of fibromuscular
tissue instead of a membrane. In cases with stenotic MV, the
left ventricular cavity is usually small and may be associated
with endocardial fibroelastosis. The aortic valve may be
unicuspid or bicuspid with severe stenosis or atretic. The
ascending aorta is usually hypoplastic and measures 2 to 3 mm
or less in diameter. Though it is very small, it is sufficient to
Figure 1: Subcostal echocardiographic view of the atrial septum with

color flow imaging in an infant with hypoplastic left heart syndrome
demonstrating intact atrial septum. The flow in the superior vena cava
(SVC) is shown and no patent foramen ovale is seen. LA = Left atrium;
RA = Right atrium
CyanotiC Heart diseases
considered to be an integral part of HLHS, although it may

be present in the syndrome of mitral atresia with normal
aortic root. A patent ductus arteriosus is usually present and is
required for survival.
Severely hypoplastic LV may also be present in hearts with
double-outlet RV with mitral atresia, unbalanced complete
atrioventricular canal and other complex heart defects; in
some studies, these variants constitute as many as 25 percent
of HLHS cases.11,12
PRENATAL CIRCULATION
In a normally formed fetus, highly saturated inferior vena
caval blood is preferentially shunted into the left atrium via
the patent foramen ovale and from there into the LV and aorta.
The superior vena caval blood containing desaturated blood
is directed towards the tricuspid valve (TV), and RV and
from there into the pulmonary arteries, ductus arteriosus and
descending aorta. By contrast, in HLHS the oxygenated blood
from the placenta is returned to the inferior vena cava (IVC)
and instead of shunting across the patent foramen ovale into
the left atrium, it mixes with the superior vena caval blood
in the right atrium. The pulmonary venous drainage from left
atrium gets shunted across the atrial septum into the right
atrium because of MV obstruction. Right ventricle receives
a mixture of vena caval and pulmonary venous and coronary
sinus blood.13,14
Because of widely patent ductus arteriosus and high
pulmonary vascular resistance in the fetus, only a small portion
of the blood from the RV enters the lungs. Most of the blood
is directed into the aorta via the ductus. Once in the aorta,
the blood gets distributed into the brachiocephalic vessels,
ascending aorta and descending aorta. The quantitative
distribution into these different vascular beds depends on their
relative vascular resistances. The ascending aortic blood flows
in a reverse direction and supplies the coronary arteries.
POSTNATAL CIRCULATION
666
The newborn infant with HLHS has a complex cardiovascular

physiology. Fully saturated pulmonary venous blood
returning to the left atrium cannot flow into the LV because
of atresia, hypoplasia, or stenosis of the MV. Therefore,
pulmonary venous blood must cross the atrial septum. This
blood mixes with desaturated systemic venous blood in the
right atrium and from there transmitted into the RV. The RV
then must pump this mixed blood to both the pulmonary and
the systemic circulations that are connected in parallel, rather
than in series, by the ductus arteriosus. Blood exiting the RV
may flow into the lungs via the branch pulmonary arteries or
into the body via the ductus arteriosus.
The relative flows to the pulmonary and systemic circuits
depend on the relative resistances of the two vascular beds.
Following birth, pulmonary vascular resistance (PVR)
decreases, this allows a higher percentage of the right
ventricular output to go to the lungs instead of the body.

Although increased pulmonary blood flow results in higher
oxygen saturation, systemic blood flow is compromized.
When the systemic blood flow decreases below a critical
level, the perfusion becomes poor and metabolic acidosis
and oliguria may develop. There is also decreased flow to
the coronary arteries and brain, with a risk of myocardial or
cerebral ischemia respectively. Alternatively, if pulmonary
vascular resistance is significantly higher than systemic
vascular resistance, there will be hypoxemia.
In summary, the postnatal circulation in HLHS depends on
three major factors:
1. Adequacy of interatrial communication.
2. Patency of the ductus arteriosus.
3. Level of pulmonary vascular resistance.
EPIDEMIOLOGY
The incidence of HLHS is 0.16 to 0.36 per 1,000 live
births.15 It comprises 1.2 to 1.5 percent of all congenital heart
defects.16, 17 HLHS accounts for 7 to 9 percent of all congenital
heart disease diagnosed in the first year of life.12 Before
surgical treatment was available, HLHS was responsible
for 25 percent of cardiac deaths in the neonatal period.12
The recurrence risk of HLHS in families with one affected
child is 0.5 percent and the recurrence risk for other forms of
congenital heart disease in families is 2.2 to 13.5 percent.18-20
Bicuspid aortic valve was identified in 5 to 11 percent of
first-degree relatives of affected probands. The incidence of
HLHS is higher in patients with Turner syndrome, Noonan
syndrome, Smith-Lemli-Opitz syndrome and Holt-Oram
syndrome. Certain chromosomal duplications, translocations
and deletions are also associated with HLHS.
GENDER
The HLHS is more common in males than in females, with a
55 to 70 percent male preponderance.
AGE AT PRESENTATION
Babies with HLHS typically present within the first 24 to
48 hours of life. Presentation occurs as soon as the ductus
arteriosus begins to constrict, which decreases the systemic
blood flow, producing shock and, without intervention, causes
death. Infants with pulmonary venous obstruction (absent or
restrictive patent foramen ovale) may present even sooner.
Very rarely, an infant with persistence of high PVR and widely
open ductus arteriosus may present later, because of balanced
pulmonary and systemic circulations.
MORTALITY/MORBIDITY
Without surgery, HLHS is uniformly fatal, usually within the
first 2 weeks of life. As alluded to above, survival for a longer
CLINICAL FEATURES
History
The fetus grows and develops normally because the fetal
circulation is not significantly altered.11,21 Pregnancies are
typically uncomplicated. Most neonates are born at term and
initially appear normal.
In the current era, especially in the developed countries,
most of HLHS cases are diagnosed prenatally with an
abnormal four-chamber view in the screening obstetric
ultrasound.22 Prenatal diagnosis of the disease allows adequate
time for parental counseling and as well as delivery planning
at a tertiary care hospital, which also avoids transport-related
morbidities. Following delivery, patient should be started
on prostaglandin E1 (PGE1) to maintain ductal patency and
should have an echocardiogram to confirm the prenatal
diagnosis of HLHS and to assess the adequacy of the atrial
septal communication.
In neonates with no prenatal diagnosis of HLHS, the time
of presentation depends on degree of atrial level restriction,
ductal patency and the level of PVR. Most neonates are born
at term and initially appear normal. As the ductus arteriosus
begins to close (normally over the first 2448 hours of life),
symptoms of cyanosis, tachypnea, respiratory distress, pallor,
lethargy, metabolic acidosis, and oliguria develop. Without
intervention to reopen the ductus arteriosus, death rapidly
ensues. Similar symptomatology may be expected if a
precipitous drop in PVR occurs.
Occasionally, respiratory symptoms and profound
cyanosis are apparent at birth (25% of cases). In these
infants, significant obstruction to pulmonary venous return

(a congenitally small or absent (Figure 1) patent foramen
ovale) is usually present.
PHYSICAL FINDINGS
Before the initiation of PGE1 infusion to reestablish patency
of the ductus arteriosus, infants may exhibit signs of
cardiogenic shock, including the following: hypothermia,
tachycardia, respiratory distress, central cyanosis and pallor,
poor peripheral perfusion with weak pulses in all extremities
and hepatosplenomegaly.
After re-establishment of systemic blood flow via the
ductus arteriosus, signs of shock resolve, with the infant in
more stable condition, but with tachycardia, tachypnea, and
mild central cyanosis. If coarctation of the aorta is present,
arterial pulses in the legs may be more prominent than those
in the arms, particularly the right arm. Other findings are
prominent right ventricular impulse, normal first heart sound
and a loud, single second heart sound. Usually no murmur is
noted; however, a nonspecific, soft, systolic ejection murmur
along the left sternal border; high-pitched holosystolic
murmur at the lower left sternal border, indicating tricuspid
regurgitation and diastolic flow rumble over the precordium,
indicating increased right ventricular diastolic filling may be
heard.
47
HypoplastiC leFt Heart syndrome
period occurs rarely and is related to persistence of the ductus

arteriosus along with balanced systemic and pulmonary
circulations.
Following the Norwood procedure, overall success
(survival to hospital discharge) is approximately 75 percent.12
Success rates are higher (85%) in patients with no or low
number of preoperative risk factors and lower (45%) in
patients with important and/or multiple risk factors. The risk
factors for poor result include prematurity and major noncardiac malformations. Other identified risk factors include
surgery in older infants, significant tricuspid regurgitation and
pulmonary venous hypertension. High Aristotle scores are
also associated with poor prognosis.
Orthotopic heart transplantation results in early and longterm success similar to that of staged reconstruction. Among
low-risk patients who undergo staged reconstruction or
transplantation, actuarial survival at 5 years is approximately
70 percent.
Most studies report neurodevelopmental disabilities in
a significant number of patients who survive either staged
surgical reconstruction (Norwood/bidirectional Glenn/Fontan)
or cardiac transplantation.
Laboratory Studies
Chest X-ray
The findings on chest X-ray are generally nondiagnostic, but
reflect the volume of pulmonary blood flow and degree of
atrial level shunting. With restrictive atrial shunt there will
be evidence of pulmonary edema, while with nonrestrictive
atrial level shunt, there will be cardiomegaly and increase
pulmonary vascular markings (Figure 2).
Electrocardiogram
The electrocardiogram may not be diagnostic in neonates.
Right axis deviation and right ventricular hypertrophy are
common, but not distinctly different from the electrocardiogram
of the normal neonate. Decreased left ventricular forces may
be noted in the left precordial leads.
Echocardiogram
Echocardiography is the test of choice for diagnosing HLHS.
Two dimensional imaging readily shows the hypoplastic
LV and aorta (Figures 3A and B) and enlarged right atrium,
RV and main pulmonary artery (Figures 3 and 4). The
degree of hypoplasia of the left heart structures is variable,
as demonstrated for the size of the LV in Figures 5A to F.
667
8
Evaluation of the aortic arch and thoracic aorta for evidence of

coarctation and interruption of aortic arch is important.
Doppler and color flow Doppler are important in assessing
the hemodynamics. High Doppler velocity across the atrial
septum indicates restrictive interatrial communication
(Figures 6A and B). Doppler interrogation of the transverse
arch shows retrograde systolic flow (Figures 7A and B); this
finding indicates ductal-dependent systemic circulation and
supports left ventricular inadequacy for biventricular repair.
Two-dimensional and Doppler echocardiographic features
are sufficiently characteristic of HLHS, so that cardiac
catheterization and angiography are no longer necessary for
diagnosis of this anomaly.
Other Imaging Studies
Figure 2: Chest roentgenogram in an infant with hypoplastic left heart

syndrome demonstrating cardiomegaly and increased pulmonary
vascular markings
668
Magnetic resonance imaging (MRI) and computed tomography (CT) scan studies are not necessary because the echo
is adequate to define most of the issues related to HLHS.
Rarely, these studies may become necessary to define the
pulmonary artery, aortic arch or pulmonary venous anomalies.
At most institutions, routine head ultrasound to exclude
central nervous system abnormality and abdominal ultrasound
to evaluate for renal anomalies are performed prior to the
Norwood procedure or heart transplantation.
Figures 3a and B: Two-dimensional echocardiographic precordial (A) long-axis view and (B) short axis view of the heart in a patient with
hypoplastic left heart syndrome showing the hypoplastic left ventricle (LV), an enlarged and hypertrophied right ventricle (RV) and a small
ascending aorta (AAo). Large main pulmonary artery (MPA) and patent ductus arteriosus (PDA) are also shown. AoV = Aortic valve; LA = Left
atrium
47
Figures 4a and B: Two-dimensional echocardiographic short-axis views of a heart in a patient with hypoplastic left heart syndrome showing
hypoplastic left ventricle (LV), an enlarged and hypertrophied right ventricle (RV), enlarged right atrium (RA), large main pulmonary artery (MPA)
and wide open patent ductus arteriosus (PDA) and small aortic valve (AoV)
Figures 5a to F: Two-dimensional echocardiographic apical four-chamber views of the hearts of different patients with hypoplastic left heart
syndrome demonstrating varying sizes of the hypoplastic left ventricle (LV). Enlarged right ventricle (RV) and right atrium (RA) are also seen.
LA = Left atrium
669
Figures 6a and B: Subcostal views of the atrial septum in a patient with hypoplastic left heart syndrome demonstrating a restrictive patent
foramen ovale (PFO) (arrow) in the right-hand panel B. and turbulent flow across the PFO in the left-hand panel; A. LA = Left atrium;
RA = Right atrium
670
Figures 7a and B: Two-dimensional echocardiographic, suprasternal notch, long-axis view of the aortic arch: A. in a patient with hypoplastic left
heart syndrome. This still frame shows markedly hypoplastic ascending aorta (AAo), serving only to deliver blood in a retrograde fashion to the
coronary arteries. The descending aorta (DAo) is tortuous and the appearance is suggestive aortic coarctation. Retrograde flow (arrow) in the
arch of the aorta; B. is suggestive of ductal-dependent systemic circulation
Other Lab Studies

Complete blood count (CBC) count, WBC count with differential, electrolytes, blood urea nitrogen (BUN)/creatinine,
liver function tests, arterial blood gases, lactic acid and karyotype may be performed as indicated.
CARDIAC CATHETERIZATION AND ANGIOGRAPHY
CATHETER INTERVENTIONS
As indicated above, cardiac catheterization is rarely necessary for

diagnostic purposes in the newborn period; it may be performed
in cases with markedly restrictive interatrial communication or
intact atrial septum. In these cases, transcatheter opening of the
atrial septum23-25 is undertaken to create an atrial septal defect
to relieve left atrial hypertension and pulmonary edema before
the stage I surgical (Norwood procedure).
Routine cardiac catheterization at age 6 months prior to
bidirectional Glenn or hemi-Fontan operations is performed.
This is to obtain hemodynamic data, to calculate PVR, to
evaluate the size and pressures in the pulmonary arteries and
to assess the suitability for next stage procedure. Angiograms
are obtained to assess the right ventricular function, tricuspid
regurgitation and also to assess the branch pulmonary
artery anatomy (Figures 8A and B) and to rule out recurrent
aortic coarctation and aortopulmonary collateral vessels. If
significant collateral vessels are found they may be occluded
with coils at the same time. Similarly, balloon angioplasty of
aortic coarctation is performed as indicated.
In the neonate, obstruction at the level of patent foramen

ovale may be relieved by balloon/blade atrial septostomy.23-25
In most cases, balloon/blade atrial septostomy is not possible
because of hypoplastic left atrium; static dilation of the atrial
septum with a balloon angioplasty catheter can be done to
relieve the obstruction.25-27 If the atrial septum is extremely
thick with a markedly restrictive atrial septum, stent (Figures
12A and B) implantation25,28,29 to keep the atrial septum open
may become necessary.
In some patients, the atrial septum may be intact or have
a very small patent foramen ovale that may not even allow
passage of a catheter. In such situations, puncture of the atrial
septum by a Brockenbrough technique30,31 or by radiofrequency
perforation32 followed by static balloon atrial septal dilatation
or, preferably, stent implantation25,28,29 may be performed.
In patients with hypoxemia due to clotted Blalock-Taussig
(BT) shunts after stage I palliation and if the patient is not
47
Cardiac catheterization is also a standard procedure before

the Fontan conversion operation. Hemodynamic data to
calculate PVR and transpulmonary gradients are obtained to
assess the suitability for next stage procedure. Angiograms are
obtained in similar fashion to pre-Glenn catheterization. The
pulmonary artery angiograms are done via superior vena cava
(Figure 9). Coil embolization of collateral vessels (Figures 10
and 11) is usually done at this time.
Figures 8a and B: Selected cineangiographic frames of an infant with hypoplastic left heart syndrome following Norwood procedure with
Blalock-Taussig (BT) shunt demonstrating good-sized right (RPA) and left (LPA) pulmonary arteries. A. Mild narrowing of the proximal RPA
(arrow) and of different infant after Norwood procedure with Sano shunt; B. Demonstrating good-sized RPA and LPA. In B, the catheter C. is
positioned into the Sano shunt via the right ventricle with its tip at the junction of Sano shunt with the pulmonary arteries
671
Figure 9: Selected frame from superior vena caval cineangiogram in an

infant with hypoplastic left heart syndrome following Norwood procedure
with subsequent bidirectional Glenn procedure demonstrating right
(RPA) and left (LPA) pulmonary arteries and no obstruction at the
superior vena cava (SVC) pulmonary artery junction. A stent placed
previously for relieving interatrial obstruction is seen in the background.
ASD = Atrial septal defect
672
ready for next stage procedure, balloon dilation33-35 or stent

placement36,37 within the BT shunt can be done to improve
the oxygenation. Similar interventional procedures may also
become necessary in cases with obstruction of Sano shunts.38,39
If there is recurrent aortic coarctation, balloon angioplasty
may help relieve the obstruction and decreases right ventricular
afterload.40
If significant branch pulmonary artery stenosis or main
pulmonary artery stenosis is noted before a bidirectional
Glenn or Fontan conversion or after Fontan repair; pulmonary
artery rehabilitation is done either by balloon angioplasty or
by placement of intravascular stents.41,42
If aortopulmonary collateral vessels are noted, they can be
occluded (Figures 10 and 11) in the catheterization laboratory
by coil embolization.43,44 The occlusion of collaterals prior
to stage II and III palliation, is recommended to reduce right
ventricular volume overload.
Following completion of Fontan procedure, some patients
may develop recurrent pleural effusion, liver dysfunction, plastic
bronchitis or protein-losing enteropathy.45 In these patients,
following exclusion of obstructive lesion in the Fontan circuit,
puncture of the conduit wall by a Brockenbrough technique
followed by static balloon dilatation or stent implantation
may be beneficial. In patients with fenestrated Fontan, the
fenestration may be closed by transcatheter methods.46-48
Figures 10a and B: Selected cineangiographic frames from left internal mammary artery (LIMA) injection demonstrating collateral flow into the lungs:
A. which was completely abolished; B. after implanting two coils (C1 and C2). Sheath (Sh) in the superior vena cava inserted thorough the right
internal jugular vein in a patient with prior bidirectional Glenn procedure is seen
47
Figures 11a and B: Selected cineangiographic frames from a distal branch of left subclavian artery demonstrating collateral flow into the lungs:
A., which was completely abolished; B. after implantation of a coil (C3). C1 and C2 are coils to occlude collateral flow from left internal mammary
artery (Figures 10A and B)
Figures 12a and B: Selected video: A. and cineradiographic; B. frames of an infant with hypoplastic left heart syndrome demonstrating stent
placed in the markedly restrictive interatrial septum. ASD = Atrial septal defect; LA = Left atrium; RA = Right atrium; RV = Right ventricle
673
NATURAL HISTORY
The natural history of untreated patients with hypoplastic left
heart syndrome is uniformly poor. If untreated more than 95
percent infants with HLHS die within the first month of life.
HLHS accounts for 25 percent of deaths due to cardiac reasons
in the first week and 15 percent of cardiac deaths during
first month of life. If pulmonary and systemic resistances
are balanced, survival for 4 to 6 years has been reported
sporadically. The patients usually die from congestive heart
failure, myocardial ischemia and pulmonary vascular disease.
MANAGEMENT
A thorough explanation of different treatment approaches
supportive care, multistage surgical palliation, cardiac
transplantation, including their advantages and disadvantages,
should be provided to the parents. Occasionally, some anatomic
features favor one choice over the others. In the presence of
severe TV or pulmonary valve anomalies, the multistage
surgical approach is not likely to be beneficial; cardiac
transplantation is the only surgical choice. In most cases, the
choice of treatment is based on the parents preference. While
such a decision is being made, the infant should be stabilized
as discussed in the next section.
If supportive care is chosen by the parents, they need strong
emotional support, because the condition is fatal without
active treatment.
Preoperative Medical Care
674
In situations where prenatal diagnosis of HLHS by fetal

echocardiography is made, it is advisable to have the baby
deliver at an institution, where tertiary care, including
neonatal cardiac surgery, is performed routinely. There was
some suggestion in the past that elective cesarean delivery
may provide better outcomes. A recent study examining this
issue found that there was no hemodynamic advantage for
elective cesarean delivery section over vaginal delivery.49
Successful preoperative management encompasses addressing three main aspects:
1. Providing adequate systemic flow.
2. Limiting pulmonary overcirculation.
3. Provide adequate egress of pulmonary venous return from
the left atrium.
In HLHS, the blood flow to systemic circulation (coronary
arteries, brain, liver and kidneys) mainly depends on the
patency of ductus arteriosus. Treatment with PGE1 should be
initiated immediately after HLHS is diagnosed or suspected,
to establish ductal patency and ensure adequate systemic
perfusion. The patients physiologic state often directs initial
PGE1 dosing. For patients who present in shock with suspected
ductal closure or a restrictive duct, initial dose will range from
0.05 to 0.1 mcg/kg/minute. Once ductal patency is ensured,
the infusion rate may be gradually decreased to a dose of

0.02 mcg/kg/minute. One should strive to maintain ductal
patency with the lowest effective PGE1 dose to minimize the
dose-dependent side effects of PGE1 such as hypotension,
prompting volume resuscitation and apnea and respiratory
depression, requiring mechanical ventilatory support.
The PVR of a newborn is slightly less than the systemic
vascular resistance and begins to fall soon after birth. In
the patient with HLHS, decreased PVR causes progressive
increase in pulmonary blood flow with a concomitant decrease
in systemic blood flow. When severe, this results in systemic
hypoperfusion, metabolic acidosis and shock.
After establishing ductal patency, maneuvers should be
used to minimize systemic vascular resistance and maximize
PVR. It should be noted that maneuvers to increase PVR have
been more efficacious. Intubation and mechanical ventilation
with sedation and paralysis permits hypoventilation to
elevate the partial pressure of carbon dioxide (PaCO2). The
chief metabolic factor that appears to influence pulmonary
resistance in patients with HLHS is arterial PCO2 and should
be maintained in the range of 45 to 50 mm Hg. Metabolic
acidosis should be corrected with sodium bicarbonate. The
hematocrit should be maintained between 40 to 45 percent
to provide adequate oxygen carrying capacity and to increase
the blood viscosity; the latter may also serve to elevate PVR.
Supplemental oxygen to increase the oxygen saturations
should be avoided.
Subambient oxygen (FIO2 of 1519%) with supplemental
nitrogen or carbon dioxide may be used to elevate PVR;
although this is an attractive concept, it should not be pursued
for long periods, because severe pulmonary hypertension may
complicate the postoperative course. However, this does not
seem to adversely affect the pulmonary vasculature on longterm follow-up.50
Because of obstruction at the mitral valve, pulmonary
venous blood must cross the atrial septum via a patent
foramen ovale (PFO) and mix with desaturated systemic
venous blood in the right atrium. In some patients, the PFO
may be restrictive. Mild restriction is acceptable and may be
beneficial in that it may maintain high PVR and promote good
systemic flow. Severe restriction may cause severe hypoxemia
and pulmonary edema. Periodic monitoring by echo-Doppler
studies is recommended. In contrast to other patients with
HLHS, the patients with severe obstruction at PFO and
patients with intact septum do not show diastolic flow reversal
in the ductus arteriosus. When severe restriction develops,
transcatheter interventions to enlarge the atrial septal defect
may be performed. While Rashkind balloon septostomy and
Park blade septostomy are conventional methods to open atrial
septum, these may not be feasible because of hypoplastic left
atrium. Static dilatation of the atrial septum25-27 with a balloon
angioplasty catheter may be used, which may not only relieve
the obstruction, but also keep some restriction such that there
is no rapid fall in the pulmonary vascular resistance. Rarely
Surgical Care/Multistage Surgery

Sinha,21 Caylor51 and Dotty52 and their associates proposed
various palliative operations; however, significant survival
was not achieved, until Norwood and associates3,4
demonstrated that a multistage operative approach could
be used to treat HLHS. The concepts and procedures
described by Fontan,53 Kreutzer,54 de Leval55 and others56,57
initially to address tricuspid atresia were extended to treat
other cardiac defects with a functionally single ventricle,
including HLHS.
The purpose of surgical reconstruction of HLHS is to
eventually separate the pulmonary and systemic circulations
to achieve a Fontan circulation. The right ventricle becomes
systemic ventricle, while the flow to the lungs is via the Fontan
connections. The multistage reconstruction is accomplished in
the three stages:
Norwood Procedure (Stage I)

Norwood procedure is performed in the first week of life
following stabilization in the neonatal intensive care unit. The
Norwood procedure3,4 consists of:
1. Atrial septectomy to provide unrestricted blood flow across
the atrial septum.
2. Ductal ligation.
3. Anastmosis of the main pulmonary artery to the aorta with

or without homograft material in order to provide systemic
blood flow.
4. Addressing aortic coarctation, if present and
5. Aorta-to-pulmonary artery shunt, most commonly, a
modified BT shunt to provide pulmonary blood flow.
Some surgeons have modified the procedure further by
insertion of a Gore-Tex graft in the right ventricular outflow
tract, connecting it to the pulmonary artery (instead of conventional modified BT shunt) as initially described by Sano and his
colleagues.58,59 The perceived advantage of Sano shunt is the
avoidance of aorto-pulmonary runoff resulting in higher coronary and systemic perfusion pressures, which may potentially
lessen the incidence of ventricular ischemia. Early hemodynamic studies60,61 documented higher diastolic perfusion pressures.
However, both single institutional61 and multi-institutional62
studies comparing the two techniques have not demonstrated
significant advantage of one technique over the other.
Postoperative management: It begins in the operating room
with separation from cardiopulmonary bypass. If there is no
umbilical arterial catheter, a peripheral indwelling arterial line
should be inserted. Milrinone is started at maintenance dose
of 0.05 mcg/kg/min in the operating room. Inotropic support
is initiated and the patient is weaned from cardiopulmonary
support, with adjustment of inotropic support as necessary.
Temporary epicardial atrial and ventricular pacing wires
are placed. In patients with excessive myocardial edema,
cardiopulmonary instability or mediastinal bleeding, the
chest is left open, with a patch of silicone elastomer sutured
to the skin for coverage of the incision.63,64 After stabilizing
the patient hemodynamically, closure of the chest may be
performed in the intensive care unit. If the chest is open,
mechanical ventilation and milrinone is continued until
chest closure and then, they may be weaned. The ventilator
settings commonly used in immediate postoperative period
are pressure regulated, volume controlled mode and positive
end expiratory pressure of 3 to 5 mm Hg.
In the intensive care unit, infants are usually monitored with
surface electrocardiograms, pulse oximetry, central venous
pressures and near infrared spectroscopy. Arterial blood
gases and echocardiograms are usually done intermittently
as needed. The usual problems encountered in immediate
postoperative period are:
1. Low cardiac output: It can occur usually in the first 24 to
48 hours after Norwood procedure. Typical findings are
tachycardia, hypotension, oliguria and metabolic acidosis.
In these particular situations, the arterial and mixed venous
saturation difference can be a sensitive predictor of low
systemic blood flow. The potential causes of low systemic
cardiac output are:
a. Globally decreased ventricular function.
b. Elevated pulmonary systemic flow ratio (Qp : Qs),
adequate saturation with maldistribution of flow.
c. Atrioventricular (AV) valve regurgitation.
47
stent implantation25,28,29 may become necessary. Sometimes,

it may be impossible to stabilize them medically or in the
cardiac catheterization laboratory and such patients may
require emergency surgery.
Infants should remain in room air with acceptable oxygen
saturation (by pulse oximetry) in the low 70s. Ventilation with
high fraction of inspired oxygen (FiO2) should be completely
avoided, as supplemental oxygen decreases the PVR resulting
in increased pulmonary blood flow and decreased systemic
perfusion. In these settings, even though the peripheral blood
oxygen saturation is higher, oxygen delivery to the tissues is
lower and metabolic acidosis ensues. The exception to this
is the infant with severe hypoxemia caused by pulmonary
venous hypertension.
Inotropic support is indicated only in severely ill neonates
with concurrent sepsis or profound cardiogenic shock and
acidosis. The administration of inotropes can adversely
affect the balance between pulmonary and systemic vascular
resistance and should be weaned off as soon as the baby is
stabilized. While overall cardiac output may be increased,
peripheral perfusion can decrease with inotropic support and
may become deleterious. Diuretics can be used to manage
pulmonary overcirculation before surgery.
It is important to recognize that the status of PVR can
change rapidly and close monitoring of the patients, until
Norwood procedure with interventions several times a day
may become necessary. Renal and hepatic failure due to poor
perfusion should be recognized and treated.
675
676
The combination of AV oxygen saturation difference and

echocardiographic evaluation of ventricular function and
AV valve regurgitation is important in establishing the
cause and initiation of treatment. Infant with decreased
ventricular function may benefit from increasing the
inotropic support, where as infants with adequate function,
but high QP : QS benefit from maneuvers to increase the
PVR and/or by lowering the systemic vascular resistance.
2. Cyanosis: The possible reasons for cyanosis include,
a. Pulmonary venous desaturation from lung pathology
(pneumothorax, pleural effusion, pneumonia, infection,
pulmonary edema)
b. Systemic venous desaturation (anemia, low systemic
cardiac output)
c. Decreased pulmonary blood flow (elevated PVR,
pulmonary venous hypertension, restrictive the atrial
septal defect, distortion of pulmonary arteries, small or
occlusion of systemic to pulmonary artery shunt).
Pulmonary venous desaturation is evaluated typically
with chest radiograph and auscultation. Systemic venous
desaturation can be evaluated by mixed venous oxygen
saturation and hemoglobin and hematocrit. Sometimes
cardiac catheterization may be necessary to identify the
anatomic (shunt related) or physiologic (PVR related)
causes of decreased QP : QS ratio.
3. High oxygen saturation: Infants with high oxygen
saturations more than 90 percent, typically have low PVR
and pulmonary blood flow in excess of systemic blood
flow. Also, evaluation for arch obstruction is important,
since distal obstruction will force more blood through the
shunt and increase the Qp at the expense of Qs.
In the intensive care unit, the management mainly depends
on optimizing the cardiac output (inotropic and lusitropic
support) and optimizing the nutrition as soon as possible and
removing the unnecessary indwelling catheters early. Since
the babies with HLHS may not have been fed orally prior to
surgery, suck and swallow coordination may be delayed.
Follow-up: Upon hospital discharge, most infants receive
digoxin to augment cardiac function, minimal diuretics to help
manage right ventricular volume overload and aspirin to prevent
thrombosis of the shunt. If significant tricuspid regurgitation is
present, afterload reduction with captopril11 should be used.
Caution should be exercised in patients receiving diuretic
therapy to avoid intravascular volume depletion that might
reduce total cardiac output, as well as increase the risk of
shunt thrombosis owing to hyperviscosity. Oxygen saturation
is typically 70 to 80 percent in room air and should not be
of concern. Periodic (every 4 week or as clinically indicated)
cardiology evaluations are essential for detection of potential
complications such as aortic arch obstruction, adequacy of
the BT or Sano shunt, atrial septal defect obstruction and
significant tricuspid regurgitation. In patients with HLHS after
Norwood, the RV is volume overloaded and has to generate
systemic pressures. In the presence of aortic obstruction, the

right ventricular systolic function may decrease rapidly. The
physical examination and femoral pulses can be misleading in
these cases, because of obligatory runoff through the systemic
to pulmonary artery shunt.
The incidence of interstage mortality is 5 to 15 percent.65
The presence of a restrictive atrial communication, aortic arch
obstruction, obstructed shunt flow, pulmonary artery distortion
and AV valve insufficiency are associated with interstage
mortality.65 Commonly acquired childhood gastrointestinal
or respiratory diseases, which result in hypovolemia and/
or acute hypoxemia have also been implicated as causes for
interstage death.65 After successful stage I palliation, any
of the above-mentioned pathologic processes can lead to
increased metabolic demands and an unfavorable oxygen
supply/demand relationship, placing the infant with minimal
myocardial reserve at even greater risk for mortality, until
progression to cavopulmonary anastomosis. Therefore,
transitioning infants to home after stage I palliation warrants
ongoing vigilance well beyond the initial early postoperative
period. Careful home surveillance and optimal nutrition with
good growth may reduce inter-stage mortality.66,67
Bidirectional Glenn Procedure (Stage II)

Bidirectional Glenn procedure is usually performed 6 months
following Norwood procedure. Prior to bidirectional Glenn,
cardiac catheterization is performed to assess right ventricular
function, pulmonary artery size and anatomy, PVR and
coarctation of the aorta. Transcatheter occlusion of collateral
vessels, balloon angioplasty/stent of branch pulmonary artery
stenosis and balloon angioplasty of aortic coarctation are
performed as indicated.
The bidirectional Glenn procedure consists of performing
an anastomosis between the SVC and the right pulmonary
artery, end-to-side, so that venous return from the upper part
of the body flows directly into both lungs. If a persistent
left SVC is present, especially in the absence of or a small
bridging innominate vein, bilateral bidirectional Glenn shunts
should be performed. In the hemi-Fontan, the SVC-right atrial
junction is either closed with a patch or SVC is constricted
with polydioaxanone thread that is reopened during the next
stage. Blood from the IVC continues to drain into the right
atrium. The BT or Sano shunt that was placed at stage I is
liagated.
Repair of pulmonary artery narrowing, if present and
addressing TV regurgitation, restrictive atrial septum and
any other abnormalities should be undertaken at the time of
bidirectional Glenn.
Follow-up after stage II: The follow-up after bidirectional
Glenn is also necessary, although the infants are more stable
than after Norwood. Interstage mortality68 also exists, but not
as high as seen between stages I and II.
Fontan Procedure (Stage III)
47
Fontan procedure is performed approximately 12 months after

the bidirectional Glenn or an approximate patient weight of
15 kg. Again, prior to the Fontan procedure, cardiac
catheterization is performed to examine the same issues outlined
in bidirectional Glenn section. Transcatheter interventional
procedures should be performed, as necessary. The need
for occlusion of collateral vessels is more frequent prior to
Fontan than prior to bidirectional Glenn. We routinely perform
descending aortic and selective left and right subclavian artery
cineangiograms to detect collateral vessels.
In Fontan procedure, blood flow from the IVC is
directed to the pulmonary arteries either via a lateral tunnel
procedure55 or via an extracardiac conduit.69 Extracardiac
conduit diversion of inferior vena caval blood into the right
pulmonary artery is currently preferred by most surgeons.
To address the growth issue related to extracardiac Fontan,
some surgeons use autologous pericardial roll grafts. At the
conclusion of the procedure, systemic venous blood returns to
the lungs passively without passing through a ventricle.
Fenestrated Fontan: Choussat et al70 devised criteria for
successful Fontan operation. Many cardiologists and surgeons
have modified these criteria. These factors should be identified
at the time of preoperative evaluation and include elevated
pulmonary artery pressure (mean pressure >18 mm Hg) or
resistance (> 4 Wood units/m2), distorted or small (McGoon
ratio of 1.8 or less) pulmonary arteries, poor ventricular
function (end-diastolic pressure above 12 mm Hg), significant
tricuspid regurgitation and others. Patients violating these
criteria are at a higher risk for poor prognosis following
Fontan operation than patients within the set limits. In this
high-risk group, a concept of leaving a small atrial septal
defect open to facilitate decompression of the right atrium was
proposed. Billingsley, Laks and their associates71,72 advocated
closure of the atrial defect by constricting the preplaced
suture in the postoperative period, while Bridges et al73 used
a transcatheter closure techniques. Improvement in cardiac
index, decreased postoperative pleural effusions and systemic
venous congestion and possibly shorter hospitalization
have been observed after fenestration, but at the expense of
systemic arterial hypoxemia. Although the fenestrated Fontan
was initially conceived for high-risk patients, it has since been
used in patients with modest or even low risk.
Follow-up after Fontan: Periodic follow-up after Fontan is
recommended. Inotropic and diuretic medications should
be weaned. Afterload reduction with an angiotensinconverting enzyme inhibitor is presumed to be beneficial and
recommended. We use platelet-inhibiting doses of aspirin to
prevent development of thrombi in the conduit, while some
cardiologists utilize warfarin anticoagulation. While most
patients do well after the multistage surgery, several problems
have been observed during follow-up.
Arrhythmias which were common problems in patients with
atriopulmonary connection type of Fontan are less frequent
in total cavopulmonary connections. Obstructed pulmonary

outflow pathways, persistent shunts and systemic venous
congestion including protein-losing enteropathy45,74 may
occur. Symptoms and signs indicative of obstruction to Fontan
pathways should be promptly scrutinized. Poor echo windows
make non-invasive evaluation difficult and therefore, cardiac
catheterization and angiography may become necessary.
Identified obstructive lesions should be treated with balloon
angioplasty, stenting,75 or even surgery, as necessary. A
persistent shunt, secondary to intentional fenestration should
be closed46,75-77 six to 12 months after fenestrated Fontan
surgery, preferably by a transcatheter device (Figures 13A and
B). Test occlusion of the fenestration is desirable to ensure
that adequate cardiac output is maintained after occlusion.
Sometimes, systemic venous to left heart collateral vessels
cause arterial desaturation and these should be closed by coils
or devices (Figures 14A and B), as appropriate.
Protein-losing enteropathy,45,74 though less commonly seen
than in the past, carries a high (75%) mortality. It appears to be
related to loss of protein in the bowel by lymphatic distention
secondary to increased systemic venous pressure, although this
can occur in patients with reasonably normal pulmonary artery
pressures for the Fontan procedure; however the cause of proteinlosing enteropathy is unknown. Symptoms include diarrhea,
edema, ascites and pleural effusion. Decreased albumin in the
serum and increased a1-antitrypsin in the stool are present. If there
is evidence for obstruction of the Fontan pathway, it should be
relieved. Medium-chain triglyceride diet and parenteral albumin
supplementation may help to stabilize the situation. A number of
treatment options have been explored and include prednisone,
regular high-molecular-weight heparin, low-molecular-weight
heparin, an elementary diet, calcium replacement, somatostatin,
high-dose spironolactone, sildenafil and resection of localized
intestinal lymphangiectasia (if demonstrated), all with variable
success. Because protein-losing enteropathy appears to be a fatal
complication of the Fontan procedure, aggressive management
is suggested. In these patients with so called failed Fontan,
after excluding and addressing obstructions and residual shunts
apart from other conventional treatment, consideration for;
1. Reduction of conduit pressure by creation of defect in the
conduit to allow right-to-left shunt.75,78
2. Atrioventricular sequential pacing.79,80
3. Cardiac transplantation81,82 should be given.
However, most patients do well after the Fontan procedure.
Surgical Care/Cardiac Transplantation

Heart transplantation is another surgical option,5 used as an
alternative to multistage surgery. The infant should receive
continuous infusion on PGE1 to keep the ductus arteriosus
patent, while waiting for a donor heart to become available.
Nearly 20 percent of infants listed for cardiac transplantation
die, while waiting for a suitable donor organ. Furthermore,
following successful heart transplantation, all patients require
multiple medications for immune modulation and prevention
677
B
Figures 13a and B: Selected cineangiographic frames from a conduit angiogram in a patient who had a fenestrated Fontan procedure
demonstrating right-to-left shunt across the fenestration opacifying the left atrium which was successfully occluded with an Amplatzer device;
B. with no residual shunt. Previously implanted stent (St) to relieve left pulmonary artery stenosis and coil (C) to occlude collateral vessel and
sternal (S) wires are also seen. PC = Pigtail catheter in the descending aorta; RPA = Right pulmonary artery
of graft rejection, frequent outpatient surveillance to identify

rejection early and multiple hospitalizations for treatment of
infection and suspected rejection. Periodic endomyocardial
biopsy is required for more precise monitoring. However,
the long-term survival following both surgical approaches is
similar. At most institutions heart transplantation is no longer
the first option for management of HLHS patients.
EMERGING THERAPIES
Hybrid Approach to Hypoplastic Left Heart Syndrome
678
Banding of both the branch pulmonary arteries via median

sternotomy and implanting stent in the ductus arteriosus is
performed initially.83 At the time of the second stage, aortic
arch is reconstructed, atrial septectomy carried out and
bidirectional Glenn shunt performed. This appears to shift

some of the early mortality of Norwood to stage II. This is
followed by Fontan conversion with an extracardiac conduit.
Although reduction of early mortality is theoretically feasible,
larger experience with this approach than is currently available
is necessary prior to general adaptation of this method of
management of all HLHS patients. Some comparisons of
hybrid with conventional Norwood84,85 did not demonstrate
significant difference. Other new approaches such as double
shunt technique for hybrid palliation86 are being attempted.
Prevention by Fetal Intervention

Fetal echocardiographic studies have shown development of
HLHS in fetuses initially found to have severe/critical aortic
stenosis. Fetal intervention to relieve aortic valve stenosis
47
Figures 14a and B: A large venovenous collateral vessel; A: arising from the undersurface of the left innominate vein (LIV) is occluded
with an Amplatzer vascular plug (AVP), demonstrating its complete closure in B
(by balloon aortic valvuloplasty) may promote normal

development of the LV.87 Further experience/research into this
type of approach is needed.
Catheter-assisted Fontan
Konert et al88 proposed a staged surgical-catheter approach;
they performed a modified hemi-Fontan procedure instead
of bidirectional Glenn shunt that is later completed by
transcatheter methodology. This reduces the total number of
operations required. This concept has not been tried for postNorwood HLHS patients.
PROGNOSIS
The survival rate of infants treated with both multistage
surgery and cardiac transplantation is similar to that of infants
with other complex forms of congenital heart disease in which a
two-ventricle repair is not possible. The major mortality is at the
time of Norwood, stage I. Overall survival at hospital discharge
after the Norwood procedure is nearly 75 percent.89 Success rates
are higher in uncomplicated cases and lower in cases in whom
significant preoperative risk factors are present, such as age
greater than 1 month, significant tricuspid insufficiency, pulmonary venous hypertension, associated major chromosomal
or noncardiac abnormalities, prematurity and high Aristotle
scores (> 20).90 Survival after the bidirectional Glenn/hemiFontan and Fontan operations is nearly 90 to 95 percent. The
actuarial survival rate after staged reconstruction is 70 percent

at 5 years. Neurodevelopmental prognosis is not known; however, abnormalities are reported.91,92 Approximately 20 percent
of infants listed for cardiac transplantation die, while waiting for
a donor heart. After successful transplantation, the survival rate
at 5 years is approximately 80 percent. When the preoperative
mortality is considered, the overall survival rate after cardiac
transplantation is approximately 70 percent, or similar to the results for staged reconstruction.
SUMMARY AND CONCLUSION

Hypoplastic left heart syndrome (HLHS) is an assortment
of left heart anomalies including a very small left ventricle
with under development of the mitral and aortic valves and
a small and hypoplastic aorta. A patent foramen ovale and a
patent ductus arteriosus are usually present and are necessary
for survival. Coarctation of the aorta may also be present.
Pulmonary venous blood crosses the atrial septum and mixes
with systemic venous blood in the right atrium and from there
passed on into the right ventricle and the pulmonary artery.
The pulmonary and the systemic circulations are connected
in parallel by the ductus arteriosus and the blood exiting the
right ventricle is distributed into the lungs via the branch
pulmonary arteries and into body via the ductus arteriosus.
HLHS comprises 1.2 to 1.5 percent of all congenital heart defects and is a uniformly lethal unless it is promptly identified,
treated with PGE1 and surgically palliated. They are clinically
679
identified either by prenatal ultrasound or present after birth

with symptoms as the ductus begins to close. The time of
presentation depends on the degree of atrial level obstruction,
ductal patency and the level of pulmonary vascular resistance.
The diagnosis can usually made with echo-Doppler studies.
The initial management of HLHS is by prompt infusion of
PGE1 to keep the ductus open. Balancing the pulmonary and
systemic circulation to maintain sufficient systemic perfusion
and ensuring adequacy of the patent foramen ovale for easy
egress of the left atrial blood while waiting for surgery are the
next tasks.
Surgical management is either by multistage surgical procedures, consisting of Norwood procedure (stage I) in the neonatal
period, hemi-Fontan or bidirectional Glenn procedure (stage II)
at about six months of age, and Fontan conversion (stage III)
one or more years later or by orthotopic heart transplantation.
Currently, the actuarial survival rate of infants treated with these
surgical approaches is 70 percent at 5 years and is similar to that
of infants with other complex forms of congenital heart disease
in whom a two-ventricle repair is not possible. Continued follow-up both after Fontan conversion and orthotopic heart transplantation is mandatory to address problems associated with
both these modalities of treatment.
Disease is war with the laws of our being, and all war, as a
great general has said, is hell.
Lewis G Janes
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63. McElhinney DB, Reddy VM, Parry AJ, et al. Management and
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64. Tabbutt S, Duncan BW, McLaughlin D, et al. Delayed sternal
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survival of patients undergoing palliation of hypoplastic left
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Sec t i on
9
Congenital
Cardiomyopathies
C hapter
48
Dilated Cardiomyopathy
Bhanu Duggal, Munde K
Cardiomyopathies are diseases of the heart muscle, characterized by abnormal findings of chamber size and wall
thickness, or functional contractile (systolic or diastolic)
dysfunction. In 1980, World Health Organization (WHO) defined cardiomyopathies as heart muscle disease of unknown
cause. However in clinical practice, the term has been used
to define left ventricular (LV) dysfunction due to different
etiologies. Hence, the 1995 WHO/International Society and
Federation of Cardiology (IFSC) classification is based on
global anatomic description of chamber dimensions in systole and diastole and the classification has been expanded to
include all diseases affecting the heart muscle.1
American Heart Association (AHA) expert consensus panel
(2006) defined cardiomyopathies as a group of diseases of the
myocardium associated with mechanical and/or electrical
dysfunction, which usually exhibit inappropriate ventricular
hypertrophy or dilation, due to a variety of etiologies that
frequently are genetic.2
The European Society of Cardiology (2007) position
statement however stated that cardiomyopathy is a heart
muscle disorder, in which heart muscle is structurally and
functionally abnormal in the absence of coronary artery
disease, hypertension, valvular disease and congenital heart
disease. Thus, they confirmed the morphofunctional approach
of WHO, but removed ischemic, hypertensive, valvular and
congenital etiologies and did not include electrical disorders.3
Definition
Thus, dilated cardiomyopathy (DCM) is defined as an ejection
fraction of less than 55 percent, in some studies less than
45 percent, in the presence of increased LV dimensions (enddiastolic size more than 115 percent of that calculated for
age and body surface area)3 or an increased end-diastolic
volume of more than 100mL/m2, which cannot be explained
by coronary artery disease, hypertension, or valvular disease.4
The right ventricle may also be dilated with reduced ejection
fraction, but this is not essential for the diagnosis.
Etiology
The number of cardiac or systemic processes that can lead
to this condition is remarkably varied. Ischemia, valvular
involvement, hypertension and congenital defects must be
excluded in every case of dilated cardiomyopathy.
Dilated cardiomyopathy can be primary, i.e. confined to
the heart muscle or secondary, i.e. one in which myocardial
involvement is secondary to a generalized systemic disorder.
A number of conditions lead to the dilated phenotype (Box
1). In 50 percent of the patients no identifiable cause is found,
hence the term idiopathic dilated cardiomyopathy.5
Familial forms make up 30 percent of DCM. The phenotype
in monogenetic forms is determined by the mutation itself,
but it can be modified by the transmission mode, penetrance,
environmental influence, current or changing immune status,
polymorphism and other confounders and thus explains in
part the different functional status.6
Inflammatory and Postinfective Subtype

Inflammatory and postinfective subtype are considered as
secondary cardiomyopathies and .The World Health Federation
(WHF) updated the conventional Dallas classification by the
introduction of immunohistochemical methods. Myocarditis
was defined as a process charecterised by an inflammatory
infilterate of the myocardium.The WHF committee choose
a minimum of 14 infiltrating leukocytes/mm2. The most
common etiologies in Europe have shown an epidemiological
shift from enterovirus and adenovirus to parvovirus B19,
human herpesvirus 6 (HHV6), and cytomegalovirus (CMV).7
Pathophysiology
Dilated cardiomyopathy represents the final common
morphologic outcome of various biological insults. The
etiology of the clinical phenotype of dilated cardiomyopathy
comprises genetic, autoimmune and viral factors. Most likely
Congenital cardiomyopathies
Box 1: Causes of dilated cardiomyopathy

Ischemic cardiomyopathy (must be excluded)

Stress-induced cardiomyopathy
Tachycardiomyopathy
Infectious cardiomyopathy
Viral cardiomyopathy
Human immunodeficiency virus (HIV) infection
Chagas disease
Lyme disease
Kawasaki disease
Genetic causes of dilated cardiomyopathy
Inherited syndrome
Hypertrophic cardiomyopathy (end-stage disease)
Left ventricular non-compaction.
Toxic causes of cardiomyopathy.
Drugs: Alcohol, cocaine
Medications: Chemotherapeutic agents (anthracycline),
antiretroviral drugs, chloroquine.
Trace elements.
Electrolyte abnormalitiesHypocalcemia,
hypophosphatemia, uremia.
Peripartum cardiomyopathy
Metabolic: Endocrine diseases (e.g. hyperthyroidism,
hypothyroidism, myxedema, hyper and
hypoparathyroidism), diabetes mellitus.
Collagen vascular disease: Systemic lupus erythematosus
(SLE), scleroderma, giant cell arteries.
Infiltrative disorders: Hemochromatosis, amyloidosis,
glycogen storage disease.
Nutritional deficiencies: Thiamine, carnitine, selenium.
Obstructive sleep apnea.
Neuromuscular disordersDuchenne dystrophy, myotonic
dystrophy.
Immunologic disorders: Serum sickness, transplant
rejection.
all three factors interplay to a different extent. Myocyte

injury due to various factors enlisted in Box 1, myocarditis,
autoimmune mechanism triggered secondary to myocardial
inflammation or other environmental factors lead to myocyte
necrosis and fibrosis. Myocyte failure and cytoskeletal
uncoupling, cause the chambers to become dilated. According
to Laplaces law, increased diameter increases wall stress and
causes further mechanical disadvantage. The hypertrophied
cells exposed to continued stress eventually become fibrotic
and inadequate to maintain cardiac function (Figures 1A to D).
Thus, myocardial dysfunction can cause a vicious cycle leading
to more myocardial dysfunction in a process termed adverse
ventricular remodeling. DCM is associated with complex
remodeling of one or both ventricles, resulting in a change
of the ventricle shape and the architecture of the myocardium
fibers. This eventually leads to a decreased cardiac output and
consequently activation of the neurohormonal axis (Figure 2).
Epidemiology
Dilated cardiomyopathy is a common and largely irreversible
form of heart muscle disease with an estimated prevalence
of 1:2500.8 Dilated cardiomyopathy is the most common
cardiomyopathy worldwide and accounts for 60 percent of all
cardiomyopathies. It is the third most common cause of heart
failure and the most frequent cause of heart transplantation.
Intensive investigations can reveal a specific associated cause
in 50 percent of the patients, remaining 50 percent are assigned
the diagnosis of exclusion, idiopathic DCM.9
The prevalence in the general population remains undefined.
This disorder develops at any age, in either sex and in people
of any ethnic origin. In adults, DCM arises more commonly in
686
Figures 1 A to D: DCM-Gross/Micro: A. Globular appearance of the heart due to dilatation of right and left ventricles. The apex is rounded and
formed by both ventricles. B. Multiple pale brown thrombi (arrow) attached to the endocardium of dilated right ventricle (RV). TV = Tricuspid
valve; C. Large fresh mural thrombus (arrow) attached to the septal region of left ventricle (LV). D. The striking feature is an increase in the
interfiber connective tissue with stretched and attenuated fibers. Note: Presence of large nuclei indicative of accompanying hypertrophy. Ao =
Aorta; AV = Aortic Valve; PT = Pulmonary trunk; RA = Right Atrium; RAA = Right atrial appendage; TV = Tricuspid valve; Courtsey: Dr Pradeep
Vaideeshwar
48
Figure 2: Neurohormonal activation in heart failure.
men than in women. In children, the yearly incidence is 0.47

cases per 100,000 per year overall, but it is higher in boys
than in girls (1.32 vs 0.92 cases per 100,000, p < 0.001) and in
babies younger than 1 year than in children (8.34 vs cases per
100,000, 95 percent confidence interval 7.21 to 9.61).10
Clinical Features
Patients may present in early childhood, though most present
during the 4th and 5th decades of life.
In general, symptoms are manifested when disease has
progressed to end-stage with significant myocardial fibrosis.
Symptoms related to congestive heart failure such as dyspnea,
fatigue, angina, pulmonary congestion and low cardiac output
are the usual presenting features. Suspicion of myocarditis
and postinfectious DCM may be raised by the presence of
chest pain, exertional dyspnea, fatigue, syncope, palpitations,
ventricular tachyarrhythmias and conduction abnormalities or
by acute congestive heart failure/cardiogenic shock associated
with LV dilation and/or segmental wall motion abnormalities
and ST-T changes on electrocardiogram (ECG). Angina is a
feature frequently found in parvovirus B19-associated heart
disease.11
The disease is usually progressive. Mitral regurgitation
and ventricular arrhythmias can develop in the course of
the disease. MR is secondary to LV dilatation. Ventricular
arrhythmias have been associated with myocardial fibrosis
and hemodynamic stress, both of which contribute to
re-entry phenomenon critical to the development of
arrhythmias. About 40 percent of DCM patients die suddenly.
In idiopathic DCM, 70 to 95 percent have frequent and

complex ventricular premature complexes (VPCs) and 40 to
80 percent have unsustained ventricular tachycardia (VT). In
VHeFt study 25 to 30 percent of patients with unsustained VT
did not have symptoms.12
Physical findings depend upon the severity of LV dysfunction
as well as right ventricular dysfunction. If cardiac output is
reduced, low arterial pressure, tachycardia and cool extremities
develop. Bilateral basal crepitations due to pulmonary venous
congestion may be evident in auscultation. The apex beat may
be displaced laterally due to the dilated LV. Auscultation of the
heart may reveal S3 and/or systolic murmur of MR secondary
to LV dilation. Right ventricle involvement presents with signs
and symptoms of venous congestion and a murmur of tricuspid
regurgitation. Cachexia and peripheral edema typically arise
late in the course of the disease. Additionally, peripheral edema
and ascites are late signs in children.
Thromboembolism
Thromboembolism often complicates the clinical course of
patients with DCM and could be the first presentation. At least
11 to 13 percent patients experience embolic episodes. Emboli
occur in order of decreasing frequency in pulmonary, renal,
spleen or cerebral circulations.13
Diagnosis
Diagnosis is dependent on patients history, clinical examination and imaging, i.e. echocardiography or cardiac magnetic
687
resonance imaging (MRI) features of DCM or heart failure

or both.
also helps in assessing the severity of the disease.14 These

features are included in Box 2.
Chest Radiographs
Biomarkers
Chest radiographs often show cardiomegaly and increased

pulmonary vascular markings that are consistent with
pulmonary edema.
Biomarkers include inflammatory markers C-reactive

protein, tumor necrosis factor (TNF), markers of oxidative
stress (oxidized low-density lipoproteins, myeloperoxidase),
extracellular matrix remodeling (matrix metalloproteinase,
procollagen type I and III), neurohormones (brain natriuretic
peptide {BNP}, endothelin I), markers of myocyte injury
(troponins) and myocyte stress (natriuretic peptides). For
a biomarker to be useful, accurate, repeated measurements
should be possible at a reasonable cost and its measurement
should help in guiding therapeutic management.15
Horwich et al reported that cardiac troponin I was
detectable ( 0.04 ng per milliliter) in approximately half of
240 patients with advanced, chronic heart failure without ischemia.16 In another study, cardiac troponin T levels greater
than 0.02 ng per milliliter in patients with chronic heart failure
were associated with a hazard ratio for death of more than
4.17 After adjustment for other variables associated with poor
prognosis, the presence of cardiac troponin I remained an
independent predictor of death.14 Logeart et al reported that,
in patients hospitalized for decompensated heart failure, the
predischarge level of BNP was a strong and independent
predictor of postdischarge outcomes.18
Although elevated levels of several neurohormones can be
used to predict adverse outcomes in patients with heart failure,
they are relatively unstable in plasma and may be difficult to
measure on a routine basis.
Electrocardiography
Electrocardiography, another standard diagnostic test, can
show sinus tachycardia, ST-T wave changes, Q waves,
conduction disturbances, bundle-branch block, left atrial
and ventricular hypertrophy or ectopy (Figures 3A and B),
including supraventricular tachycardia, atrial fibrillation or
ventricular arrhythmias. New onset left bundle branch block
(LBBB), wide QRS > 120 msec may be associated with poor
prognosis.13
Echocardiography
Echocardiography is a Class I diagnostic test for DCM and
LV dilatation with depressed ejection fraction is required
for diagnosis (Figures 4A and B). Apart from the primary
diagnostic criteria, secondary features on echocardiography
Box 2: Echocardiographic parameters

in dilated cardiomyopathy
Left Ventricular Dilatation
Assessment of left ventricular internal dimension (LVID)
Left ventricular volumes
Sphericity index (ratio of long axis to minor axis)
Functional MR
Left ventricular thrombus and spontaneous echo contrast
(SEC) may be seen (Figure 5A and B)
LVEF: M-mode: EPSS and B-hump, 2D (Simpsons, 3D Echo)
Left Atrial Dilatation
Left atrial dimensions (indicator of raised left atrial filling
pressures)
Stasis of blood in left atrium
Pulmonary Hypertension
Right Ventricular Dilatation and Dysfunction
LV Diastolic Dysfunction
Mitral E/A Ratio (Response to Valsalva)
Restrictive pattern indicates poor prognosis
Deceleration Time
Annular Doppler Tissue Velocity
E/e
688
EPSS = E point septal separation; LVEF = Left ventricular ejection

fraction.
Endomyocardial Biopsy
Endomyocardial biopsy (EMB) is a procedure carrying
sufficient risk, which limits its use to patients in whom
it has been shown to have therapeutic implications. A
thorough medical history regarding the onset and disease
program is required. Rapidly progressive disease over 1
month (giant-cell myocarditis, lymphocytic myocarditis),
heart failure of less than 3 months duration with new onset
conduction abnormalities (2nd or 3rd degree AV block
or ventricular arrhythmias) or acute onset heart failure
with rapidly deteriorating ejection fraction and failure to
stabilize the patient with conventional treatment, requires
EMB. Other group of patients who are candidates for
EMB are those in whom laboratory investigations indicate
presence of autoimmune disease or if infiltrative and storage
disorders are suspected and non-invasive test findings are
inconclusive.19 From EMB samples, identification of the
causative virus by its viral genome with PCR has been
useful to establish the cause of acute myocarditis and has
clarified that some cases of dilated cardiomypathy are the
result of chronic myocarditis. Additionally, this diagnostic
48
B
Figures 3A and B: A. 12-lead electrocardiogram (ECG) in a 13-year-old boy with DCM shows sinus tachycardia with left axis with poor R wave
progression; B. ECG in an 11-year-old boy with DCM shows normal sinus rhythm with normal axis, right bundle branch block, q waves in lateral
leads and fractioned QRS inferior leads suggestive of scarring
Figures 4A and B: A. The M-mode in 5-year-old boy of DCM shows dilated left ventricle (LV); B. Apical four-chamber view shows
dilated left atrium (LA), LV with a ejection fraction of 38 percent. RA = Right Atrium; RV = Right Ventricle. Courtsey: Dr IB Vijayalakshmi
689
Figure 5A and B: A. Transthoracic echocardiography in apical four chamber view in a 12-year-old girl with dilated cardiomyopathy with reduced
left ventricular (LV) function (EF - 30%) shows dilated spherical LV with a organised clot in the apex. B.Spontaneous echo contrast (SEC) is seen
due to the sluggish circulation. LA = Left atrium; LV = Left ventricle.RA = Right atrium; RV = Right ventricle. Image courtsey: Dr IB Vijayalakshmi
approach sometimes enables improved treatment strategies

and accuracy of prognosis.
690
Functional changes in DCM are easily quantified using MRI.

MRI provides a valuable alternative to echocardiography
in the diagnostic work-up of patients with limited windows
as well as in patients with right ventricular involvement. It
provides a more accurate delineation of the endocardial border
and LV volumes and may be a useful tool for monitoring drug
therapy. In black blood images, the end-diastolic volumes of
DCM are more than 140 ml for LV and more than 150 ml
for RV; these figures may be more accurate, if indexed for
body surface area. Pilot studies reveal that it could prove
to be a useful tool in differentiating acute and chronic
alterations of the myocardium. Comparing global myocardial
enhancement with skeletal muscle enhancement early after
gadolinium administration is of use to depict generalized
myocardial hyperemia, which can be found in patients with
myocardial inflammation not only in the acute phase, but also
in chronic forms of myocarditis.20,21 Besides, myocardial
T1 mapping techniques are appealing for the depiction of
diffuse myocardial fibrosis and represent a valuable addition
to the late gadolinium enhancement (LGE) MRI technique.
Shortening of the myocardial T1 relaxation time is related to
the amount of myocardial collagen deposition. Performing
fast gradient-echo sequences using multiple increasing
inversion times (e.g. 501,000 ms) before and after contrastmedium administration at the blood/myocardium equilibrium
phase, allows the decay in myocardial signal intensity to be
measured and T1 maps to be generated with the use of curve
fitting techniques.
A cardiac MRI should also include late-enhancement

images, which are important for tissue-characterization
and can help differentiate dilated ischemic CMP from nonischemic DCM.
Treatment
Aim of treatment is to alleviate the symptoms, prevent the
disease progression to decompensated heart failure and
complications of thromboembolism and sudden cardiac death.
Angiotensin-converting Enzyme Inhibitors

All patients regardless of symptoms should be started on
angiotensin-converting enzyme (ACE) inhibitors, because of
survival benefit. The drug is initiated in a low dose and the drug
should be uptitrated once in every 1 or 2 weeks to achieve the
trial dose of these drugs. Renal function and serum potassium
should be assessed 1 or 2 weeks after initiation of the drug and
after uptitration. As there is an uncertainty of benefit with the
drugs at lower doses, one tries to achieve this target endpoint,
if tolerated, to maximize benefit.22,23
-blockers
They upregulate b1-receptor density, blunt norepinephrine
and renin production and mitigate production of deleterious
cytokines. Large scale clinical trials have demonstrated about
35 percent reduction in mortality. However, only 3 drugs, i.e.
bisoprolol, carvedilol and metoprolol have shown mortality
benefit in clinical studies and hence these are the drugs
recommended in heart failure. The ACC/AHA guidelines
recommend the use of these -blockers in heart failure,
Angiotensin Receptor Blockers

A large meta-analysis of 24 randomized trials showed
superiority of angiotensin receptor blockers (ARBs) to
placebo in patients with intolerable side effects with ACEinhibitors and their non-inferiority to all cause mortality or
hospitalizations when compared to ACE inhibitors. Valsartan
Heart Failure Trial (Val-HeFT) suggested that addition of
valsartan in patients already receiving treatment with ACEIs
and -blockers was associated with a worse outcome. Thus,
neurohormonal blockade beyond a certain extent is not
associated with any benefit, but may be harmful.26,27
Combination of Hydralazine and Nitrates

Nitrates increase nitric oxide production and hydralazine
sustains these levels. Hence, the combination is associated
with vasodilatation and reduced afterload, but the mortality
reduction is less than that of ACEIs and ARBs.25 In patients
with renal insufficiency, or persistent hypertension in the
presence of optimal doses of -blockers and ACE-inibitors
addition of a fixed dose isosorbide dinitrate (37.5 mg
hydralazine and 50 mg isosorbide dinitrate) and hydralazine
combination is associated with improved survival and
decreased hospitalization as seen in A-HeFt trial.29,30
Digoxin
Digoxin has a sympathoinhibitory effect and Digitalis
Investigation Group (DIG) trial has demonstrated a reduction
in hospitalization for heart failure. No mortality benefit was
seen and the benefit in women was less than that for men.
Hence, the addition of a low dose of the drug may benefit
symptomatic patients and trough digoxin levels should be
checked to minimize the risk of toxicity.31
Statins
The elevated aldosterone levels seen in patients with heart

failure promote sodium retention, electrolyte imbalance
as well as endothelial dysfunction leading to myocardial
fibrosis. Both the selective agent eplerenone and non-selective
antagonist spironolactone significantly reduce the mortality
and hospitalizations. These should be introduced in New York
Heat Association (NYHA) Class III and IV patients, but one
must monitor potassium levels carefully.28
Dilated cardiomyopathy is a multifactorial and progressive

disease indicating that important pathogenetic mechanism
remain active and unmodified by currently available treatment.
In view of probable role of cytokines and inflammation in
DCM, statins with their pleiotropic effect may provide an
alternative treatment option in patients with this condition.
In the universe (RosUvastatiN Impact on VEntricular
Remodeling, LipidS, and CytokinEs) study, high-dose
rosuvastatin (40 mg/day) did not result in a significant
improvement in LV ejection fraction relative to placebo.
Attorvastatin 80 mg has been shown improvement in the LV
function and excercise tolerence in DCM due to improvement
in endothelial dysfunction and anti inflamatory effects.
Candidates for statin therapy with DCM should be in New
York Heart Association Class II or III and should have normal
or increased levels of lipid.32
Diuretics
Complications
Goal of diuretic therapy is to eliminate clinical evidence of

fluid retention, such as elevated jugular pressure and peripheral
edema. The most commonly used loop diuretics is furosemide.
Bumetanide and torsemide are more potent and may be started.
Thiazide diuretics may be added for a synergistic effect, if
clinically indicated. The diuretic dose needs to be carefully
adjusted as a higher dose can cause volume depletion and
precipitate ACE inhibitor-induced hypotension, while lower
dosing can lead to recurrence of symptoms. Therefore, the
therapy has to be tailored to each patient and they should be
educated to daily monitor their weight and regulate the dose.
Complications such as arrhythmias and thromboembolic

events can be reduced with prophylactic medications. Rate
control in atrial fibrillation can be achieved by -blockers and
digoxin. Avoid calcium channel blockers. If symptoms persist,
then Class III antiarrhythmic drugs defetilide and amiodarone
have been found to be safe and effective.33 Amiodarone is
another medication that clinicians may use to treat arrhythmias,
such as atrial fibrillation and supraventricular arrhythmias,
there is no benefit in mortality in patients with ventricular
arrhythmias.34 Reduction of thrombus formation within the
dilated chambers may be necessary to prevent thromboembolic
Aldosterone Antagonists
48
excluding patients with relative contraindications to -blocker

therapy, i.e. heart rate < 60 bpm, prolonged PR interval,
conduction system defects, reactive airways, peripheral arterial
disease as well as systemic hypotension and evidence of fluid
retention. -blockers with intrinsic sympathomimetic activity
and agents like bucindolol have not shown survival benefit.24,25
Clinical trials have shown a dose dependent improvement
in LV function and reduction in mortality and hospitalizations
with -blocker use. Thus, -blocker dose should be started
in a very low dose and the dose should be doubled every 2
weeks until the target dose is reached or symptoms become
limiting. The patient should be informed that -blockers may
lead to an increase in symptoms for 4 to 10 weeks before any
improvement. Though inpatient initiation is associated with
a higher compliance, it should not be initiated on patients
with minimal evidence of fluid retention or those on recent
intravenous therapy.
691
events. Anticoagulants, such as warfarin, are indicated for

patients with a history of previous thromboembolic events,
severe systolic dysfunction or ventricular dilatation, though
the benefits for warfarin treatment must outweigh the risks.
Immune-Mediated Therapy
Controversy continues about the immune mediated therapy
for myocarditis. In view of the chronic inflammatory
nature of the disease and the effects of the immune
system, immunomodulatory therapy might be beneficial.
However, non-selective therapy has not proved useful. One
of the largest randomized, controlled treatment trials, the
Myocarditis Treatment Trial35 failed to show the benefit
from immunosuppressive therapy additional to heart
failure therapy. There was neither a difference in mortality
nor an improvement of LV ejection fraction after 1 year of
treatment with prednisone and with either azathioprine or
cyclosporine versus placebo. These results might be due to
a lack of consensus in interpretation of EMB findings. No
immunohistology for the detection of inflammatory cells and
no molecular biological analyses of EMB were used for the
detection of infectious agents.
Better efforts are required to distinguish viral from noninfectious autoimmune forms of the disease in order to guide
appropriate treatment. Molecular biological detection of
cardiotropic viruses can be performed by nested polymerase
chain reaction (PCR)/real time-PCR from EMB. Finally,
this contemporary diagnostic repertoire is essential for the
selection of DCM patients who will likely to benefit from
immunosuppression or antiviral interferon (IFN) treatment.
The molecular biological diagnosis of viral genomes comprises
PCR for the qualitative evaluation, quantitative PCR (qPCR)
for the determination of viral loads and sequencing for the
analysis of viral genotypes. Treatment with IFN-beta in
patients with myocardial enteroviral or adenoviral persistence
and LV dysfunction showed an elimination of viral genomes
in all patients and an improvement of LV function in 15 of 22
patients.6 In the subsequent placebo-controlled, randomized,
double-blind, Europe wide multicenter Betaferon in patients
with chronic viral cardiomyopathy study, the treatment with
Betaferon significantly reduced the viral load (enteroviruses)
in the myocardium and significant improvement in NYHA
class and patient global assessment was seen.36
Immunoglobulin Treatment
692
The rationale to use immunoglobulin (Ig) in viral myocarditis

results from their antiviral and immunomodulating effects.
In recent onset of myocarditis or DCM, only children with
acute myocarditis showed an improvement of LV function and
survival in the 1st year after treatment.
Virus negative inflammatory myocarditis, there is
evidence that removal of circulating antibodies by immuno
adsorption and subsequent IgG substitution improved cardiac

function, hemodynamic parameters (cardiac and stroke
volume index) and systemic vascular resistance .
The tailored immunosuppressive inflammatory cardiomyopathy (TIMIC-immunosuppressive therapy in patients
with virus-negative inflammatory cardiomyopathy) study37
was the first randomized, placebo-controlled trial in which
all EMB were studied for inflammation by histological and
immunohistological criteria. Molecular biological analyses
were performed in all biopsy specimens to exclude viral
infection. A significant improvement of LV ejection fraction
and a decrease in LV dimensions resulted from immuno
suppressive therapy with prednisone and azathioprine.37
Patients with fulminant viral myocarditis and hemodynamic
compromise at presentation are more likely to experience
complete recovery than patients with acute myocarditis,81 if
aggressive pharmacological and/or mechanical circulatory
support is initiated early during the fulminant phase.38 In
patients with cardiac sarcoidosis or giant cell myocarditis,
prognosis depends probably on an early initiated treatment
(immunosuppressive therapy or heart transplantation).39
Device Therapy in Heart Failure

Device therapy is indicated in symptomatic patients on
optimal drug therapy. Mechanical dyssynchrony, defined
as non-synchronous contraction between the walls of the
LV (intraventricular) or between the ventricular chambers
(interventricular) impairs systolic function, adversely affects
ventricular filling, increases wall stress and worsens mitral
regurgitation. Dyssynchrony is defined by widening of
QRS complex on the ECG. The indications for cardiac
resynchronization therapy (CRT) are summarized in Table 1.
This therapy has been shown to restore the coordination
and relaxation of the cardiac chambers which results in
favorable cardiac remodeling and improves survival in this
population.40 However, up to a third of patients do not have
any clinical benefit with present recommended criteria.
These patients could have identifiable reasons for a poor
response. Thus, their drug doses, compliance to medications
and fluid restriction, underlying arrhythmias, LV lead
position, optimization of atrioventricular timings must be
reviewed.
Table 1
Indications for cardiac resynchronization therapy

RT indicated if all 3 criteria (below) are fulfilled.
C
LVEF 35%
QRS duration of > 120 msec
NYHA II-IV symptoms with optimal medical therapy
Consider CRT if both criteria given below are fulfilled.
LVEF 35%
NYHA II-IV symptoms with frequent right ventricular pacing
Implantable Cardioverter-defibrillator
Left Ventricular Assist Device

Studies have found that the left ventricular assist device (LVAD)
normalises hemodynamics, improves progressive dysfunction
of the heart, improves exercise tolerance and allows patients to
become outpatients. On closer look, it was observed that patients
with non-ischemic DCM on optimal doses of ACE inhibitor
and -blocker therapy and shorter duration of disease process,
responded favorably to ventricular assist devices. Various
ventricular assist devices exist at present; some are stationary,
others ambulatory and some are fully implantable. Use of
ventricular assist devices has significantly improved survival of
adults and children with DCM with end-stage disease who are
awaiting heart transplant. The total artificial heart is used for
destination therapy (use of long-term mechanical circulatory
support in patients with end stage heart failure, without the
intention of eventual heart transplantation).43,44
Stem Cell Therapy

Interest in the use of stem cell therapy as a treatment for endstage DCM has increased during the past decade. Several studies
have documented beneficial effects of stem cell transplantation
in patients who have depressed left ventricular systolic
dysfunction after myocardial infarction. However, concern has
grown that this approach might only result in paracrine growth
factor stimulation or improvement in myocardial scaffolding
without generation of new myocardium.51,52
Cardiac transplantation is needed in extreme cases. At
present, transplants are reserved for patients with the most
severe disease those needing inotropes and usually mechanical
ventilatory and mechanical device support.
48
Sudden Cardiac Death (SCD) may occur in nearly 30

percent of patients with nonischemic dilated cardiomyopathy
(NICM).41 The risk is highest in patients with aborted SCD
and unexplained syncope. In a meta-analysis of 5 primary
and secondary trials a risk reduction of 31 percent in all cause
mortality was seen, however as mortality on optimal medical
therapy is as low as 7 percent, this figure translates to 2 percent
per year.42 Moreover, as implantable cardioverter-defibrillator
(ICD) does not cause any symptomatic improvement, patients
in NYHA Class IV or with life expectancy of less than 6
months are not candidates for the device. Thus, the ICD
treatment needs to be individualized.
non-ischemic disease remains problematic. For these reasons,

gene-based therapies such as gene therapy, stem-cell therapy
and targeted treatments are being investigated.
Lifestyle Management
Exercise Training
Exercise training is recommended as an adjunctive treatment
in patients with heart failure. HF-ACTION trial controlled
trial investigating outcomes of exercise training) investigated
short and long-term outcomes of a supervised exercise
program in heart failure and confirmed a decrease in mortality
and increase in patients sense of well-being in these patients,
however, in the presence of acute myocarditis one must
abstain from active sport. The duration of abstinence advised
by Bethesda Conference Task Force is 6 months.53,54
Surgical Treatment
Sleep Disorders
In DCM, surgical treatment is an option in patients with failed

medical treatment and not eligible for device implantation.
However, the surgical option should be offered before patient
becomes inotrope dependent as at this stage surgical outcome is
not good. Severe functional MR patients undergo surgical mitral
valve annuloplasty as well as Maze procedure, if indicated.45
The mortality benefit outcome remains controversial. Results
of the AMADEUS46 and CARILLON47 trials also show
feasibility of percutanoues mitral valve annuloplasty, with
a decrease in functional mitral regurgitation. The Batista
procedure12 or partial left ventriculotomy, is useful in patients
with end-stage dilated cardiomyopathy.48 Other interventions
include surgical ventricular restoration by recreation of the
elliptical shape of the LV by volume reduction with a sizing
balloon, achieving a volume of 55 to 60 mL per m2 bodysurface area. Favorable benefits have been seen in patients
undergoing a volume reduction of the left ventricle by at least
30 percent with a goal to improve the biophysics of the LV and
reduce the stimulus for unfavorable remodelling.49,50
Although improved outcomes in DCM and heart failure
have been achieved, improving outcomes for patients with
Obstructive sleep apnea is associated with periods of hypoxia

and adrenergic surge and hence, is an independent predictor
of worsening of heart failure. Treatment with nocturnal
continuous positive airway pressure (CPAP) improves
6 minutes walk test and improved ejection fraction.55
Although improved outcomes in DCM and heart failure
have been achieved, improving outcomes for patients with
non-ischemic disease remains problematic. For these reasons,
gene-based therapies such as gene therapy, stem-cell therapy
and targeted treatments are being investigated.
Prognosis
Predictors of increased likelihood of death or need for
cardiac transplantation include syncope, right ventricular
systolic dysfunction, elevated pulmonary artery pressure, and
advanced NYHA functional class. Elevated levels of Fas, Fas
ligand, TNF, and IL-10 as well as immunohistologic signs
of inflammation (CD3 and/or CD68), are also predictors
of increased risk of death. The Seattle Heart Failure Model
incorporates a broader range of patients along with multiple
693
clinical predictors, laboratory data, and medical therapy,

correlates well with 1-, 2-, and 3-year survival, similar to the
Framingham Coronary Heart Disease Risk Model and is able
to predict the mode of death in heart failure: pump failure vs
SCD.56 Less information is available on the natural history of
myocarditis in children. Other clinical risk factors in patients
with suspected myocarditis are low systolic, diastolic and
mean arterial blood pressures as well as high heart rate. A
prolonged QRS duration > 120 ms has also been shown to
predict for cardiac death or heart transplantation in patients
with suspected myocarditis.
Specific Cardiomyopathies
Peripartum Cardiomyopathy
Peripartum cardiomyopathy is a disorder, in which initial LV
systolic dysfunction and symptoms of heart failure develop
between the late stages of pregnancy and early postpartum
period, typically within 1 month of predelivery and 5 months
postdelivery.57 Its causes and pathogenesis are poorly
understood. The disorder is common in some countries and rare
in others. In most patients with this disorder, molecular markers
of an inflammatory process are identified. Affected women
generally present clinically with typical signs and symptoms
of heart failure; signs of thromboembolism are also frequent.
Conventional heart-failure treatment is typically used. Effective
treatment reduces mortality rates and increases the number of
women who fully recover LV systolic function. Outcomes for
subsequent pregnancies after peripartum cardiomyopathy are
better for women who have fully recovered heart function
compared with those who have persistent LV dysfunction.
Fetal Cardiomyopathy
Familial dilated cardiomyopathy is now thought to account

for upto 50 percent of idiopathic dilated cardiomyopathy
(IDC). Most of these cases (>90%) are thought to have
autosomal dominant inheritance, although X-linked and
autosomal recessive forms have been identified. This requires
a sufficient family history to identify at least two first-degree
family members with IDC. This is difficult as the disease is
variable with age dependent penetrance even within the family.
Although up to 50 percent patients with IDC may have familial
DCM (FDC) by history, a genetic test may identify the disease
in only 10 percent causes.58
Systolic and diastolic fetal cardiac function have become part

of the routine evaluation of the fetal heart. In series of neonates
and infants, cardiomyopathy was observed in about 2 to 7
percent, but probably during the fetal life the prevalence is higher
6 to 11 percent. The high intrauterine loss, occurring in
one-third of affected fetuses, likely accounts for these
differences. Fetal echocardiography, B and M-mode is the
main diagnostic tool and it is useful for the therapeutic
orientation and to determine the neonatal outcome. A
hemodynamic evaluation can be performed by Doppler
mode. Cardiomyopathies can be isolated or associated with
other cardiac and non-cardiac malformations. All the studies
confirm a great variability of DCM in the fetal age as for the
anatomical and functional forms, etiology and hemodynamic
impact with different final outcome. Genetic, metabolic,
infective and cardiac diseases may present with DCM.
Ventricular dysfunction may be progressive in utero and after
birth, but possibility of improvement or even normalization
of the LV. dysfunction is known in all forms of DCM,
idiopathic, postinfective or in non-compaction of LV. The
outcome is worse in presence of fetal hydrops, significant
atrioventricular valve regurgitation, for the earlier age at
presentation and when diastolic dysfunction is associated
with systolic dysfunction. Unfortunately, a poor outcome
is observed in most, particularly in DCM, with only a few
therapeutic options available. Detailed evaluation of fetal
and maternal condition provide prognostic information for
prenatal counselling and may lead to improved outcome.61
Lamin A/C Mutation
Conclusion
Lamin A/C mutation is thought to be the cause in 10

percent of FDC cases. The earliest finding in this disease
Dilated Cardiomyopathy appears to be the most common

form of cardiomyopathy in children. Dilated cardiomyopathy
Left Ventricular Non-compaction

Left ventricular non-compaction has been discussed in
Chapter 49.
Familial Dilated Cardiomyopathy
694
is a conduction system disorder. 18 percent of patients less

than 10 years of age had delayed intracardiac conduction.
92 percent of patients presenting at more than 30 years of
age had conduction system disease and 44 percent required
pacemaker placement. In early stages, they have an ECG
with low amplitude P waves, prolonged PR interval and
relatively normal QRS complex.59 Subsequently they
develop atrial fibrillation and DCM. A high incidence of
thromboembolic events has been noted in 30 percent these
patients. Presence of conduction system disease indicates
progressive fibrosis. Meune et al implanted ICDs in 19
patients who had lamin A/C mutations and indications for
pacemaker and found that 42 percent patients received
shocks. As the data are controversial about appropriateness
of shocks.60 Knowledge of patients family history of SCD
indicates a low threshold for SCD41 which is associated
with conduction system disease. The mechanisms that are
responsible for the development of this disease, conduction
system abnormalities and skeletal myopathy are being
established.
The greatest mistake in the treatment of diseases is that

there are physicians for the body and physicians for the soul,
although the two cannot be separated.
Plato
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48
represents a common expression of myocardial damage that

has been produced by a variety of yet unestablished myocardial
insults. The demographics and underlying causes have been
difficult to ascertain, particularly in children. Arrhythmias form
an important mode of death. ACE-inhibitors and -blockers
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therapy is now useful in symptomatic patients but in end stage
disease, cardiac transplantation is the only option.
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mortality and morbidity in patients with heart failure.N Engl J
Med.1997;336:525-33.
32. Bielecka-Dabrowa A, Mikhailidis DP, Hannam S, Aronow WS,
Rysz J, Banach M. Statins and dilated cardiomyopathy: do we
have enough data?. Expert Opini Investig Drugs. 2011;20:31523.
33. Kopecky SL MD, Litin SC. Clinical Pearls in Cardiology.
Concise review for Physicians. Mayo Clin Proc. 2010;85:
473-8.
34. Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau
R et al. Amiodarone or an implantable cardioverter-defibrillator
for congestive heart failure. Sudden Cardiac Death in Heart
Failure Trial (SCD-HeFT) Investigators. N Engl J Med.
2005;352:225-37.
35. Mason JW, OConnell JB, Herskowitz A, Rose NR, McManus
BM, Billingham ME, et al. A clinical trial of immunosuppressive
therapy for myocarditis. The Myocarditis Treatment Trial
Investigators. N Engl J Med 1995;333: 269-75.
36. Kindermann I, Barth C, Mahfoud F, Ukena C, Lenski M,
Yilmaz A et al. Update on myocarditis. J Am Coll Cardiol.
2012;59:779-92.
37. Frustaci A, Russo MA, Chimenti C. Randomized study on the
efficacy of immunosuppressive therapy in patients with virusnegative inflammatory cardiomyopathy: the TIMIC study. Eur
Heart J. 2009;30:1995-2002.
38. McCarthy RE 3rd, Boehmer JP, Hruban RH, Hutchins
GM, Kasper EK, Hare JM, et al. Long-term outcome of
fulminant myocarditis as compared with acute (nonfulminant)
myocarditis. N Engl J Med. 2000;342:690-5.
39. Wu LA, Lapyere AC 3rd , Cooper LT. Current Role of
Endomyocardial Biopsy in the Management of dilated
Cardiomyopathy and Myocarditis. Mayo Clin Proc 2001;76:
1030-8.
40. Mullens W, Grimm RA, Verga T, Dresing T, Starling RC,
Wilkoff BL, et al. Insights from a cardiac resynchronization
optimization clinic as part of a heart failure disease management
program. J Am Coll Cardiol. 2009;53:765-73.
41. Kadish A, Dyer A, Daubert JP, Quigg R, Estes NA, Anderson
KP, et al. Prophylactic defibrillator implantation in patients
with nonischemic dilated cardiomyopathy. N Engl J Med.
2004;350:2151-8.
42. Desai AS, Fang JC, Maisel WH, Baughman KL. Implantable
defibrillators for the prevention of mortality in patients with
nonischemic cardiomyopathy: a meta-analysis of randomized
controlled trials. JAMA. 2004;292:2874-9.
43. Miller LW, Pagani FD, Russel SD, ohn R, Boyle AJ, Aaronson
KD, et al. Use of a continuous-flow device in patients awaiting
heart transplantation. N Engl J Med 2007;357:885-96.
44. Rose EA, Gelijns AC, Moskowitz AJ, Heitjan DF, Stevenson
LW, Dembitsky W et al. Long-term mechanical left ventricular
assistance for end-stage heart failure. N Engl J Med. 2001;345:
1435-43.
45. Tulner SA, Steendijk P, Klautz RJ, Tops L, Bax JJ, Versteegh
MI, et al. Clinical efficacy of surgical heart failure therapy by
ventricular restoration and restrictive mitral annuloplasty. J
Card Fail. 2007;13:178-83.
46. Siminiak T, Hoppe UC, Schofer J, Haude M, Herrman JP,
Vainer J, et al. Effectiveness and safety of percutaneous
coronary sinus-based mitral valve repair in patients with
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47. Schofer J, Siminiak T, Haude M, Herrman JP, Vainer J, Wu JC,
et al. Percutaneous mitral annuloplasty for functional mitral
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48. Abe T, Fukada J, Morishita K. The Batista procedure: fact,
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49. Koyama T, Nishina T, Ono N, Sakakibara Y, Nemoto S, Ikeda
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50. Isomura T. Surgical treatment for heart failure: left ventricular
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stem cells: the spectrum of myocardial progenitor cells in the
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Nathoe H, et al. Cell therapy for myocardial regeneration. Curr
Mol Med. 2009;9:287-98.
53. OConnor CM, Whellan DJ, Lee KL, Keteyian SJ, Cooper
LS, Ellis SJ, et al. Efficacy and safety of exercise training in
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SJ, et al. Effects of exercise training on health status in patients
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58. Mestroni L, Rocco C, Gregori D, Sinagra G, Di Lenarda A,
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59. Hershberger RE, Hanson E, Jakobs PM, Keegan H, Coates K,
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2002;144:1081-6.
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Features and outcomes in utero and after birth of fetuses with
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C hapter
49
Non-compaction of the Ventricles

Vijayalakshmi IB
Introduction
trabeculations being appreciably coarser in the morphological

right ventricle (RV) than in the morphological LV.
The ventricular non-compaction or spongy myocardium is

a very rare congenital cardiomyopathy. This is a disorder
of endomyocardial morphogenesis with trabeculations that
are increased in prominence and number, with excessive
intramyocardial spaces communicating with the ventricular
cavity.1 It represents an arrest of the normal maturation
process of the myocardium, which could be considered
an atavistic throwback, since it is the normal anatomy of
the reptile heart. This congenital cardiomyopathy carries
a high risk of morbidity and mortality due to malignant
arrhythmias, thromboembolic episodes and pump failure of
the heart.2 Non-compaction of the ventricular myocardium
is the morphological hallmark of a rare familial or sporadic
unclassified heart disease of heterogeneous origin. It results
presumably from a congenital developmental error and has
been traced back to single point mutations in various genes,
especially, mutation in the b-myosin heavy chain gene.3
Spongy myocardium has almost invariably been associated
with other congenital cardiac malformations.4
Morphology
The ventricular walls of both ventricles in the normal heart are
made up predominantly of a compacted layer of myocardial
fibers set in a matrix of supporting connective tissue.5 The noncompaction of the left ventricle (LV) consists of a meshwork
of numerous prominent muscle bands called trabeculations in
the left ventricular apex and to a variable extent the apical
aspect of the left ventricular free wall with deep intertrabecular
recesses (Figure 1). These trabeculae account for more than
half of the wall thickness in the affected areas. Typically,
the two-layered appearance of the myocardium is an outer
thin compact layer and a non-compact trabeculated thick
endocardial layer, with deep intertrabecular spaces, mostly
near the right and left ventricular apex, below the papillary
muscle level and also the apical portion of the septum. The
Nomenclature
Numerous synonyms have been used to describe this
abnormality, like spongy myocardium, spongiform cardiomyo
pathy, non-compaction, hypertrabeculation or persisting
myocardial sinusoids. The recently recognized myocardial
malformation more commonly known as ventricular noncompaction is a fascinating disorder, characterized by the
presence of an extensive trabeculated myocardial layer
reinforcing the luminal aspect of the compact portion of the
ventricular wall. According to the World Health Organization
(WHO) denition, cardiomyopathies are classied by the
dominant pathophysiology or if possible, by etiological or
pathogenetic factors.6 Although the cause of isolated ventricular
non-compaction is not fully elucidated, the disease is thought to be
a morphogenetic abnormality involving an arrest of compaction
of the loose myocardial meshwork during fetal ontogenesis.
This implies that isolated ventricular non-compaction should
be present at birth in all patients, a notion supported by two
previous reports.7,8 Since isolated ventricular non-compaction
has so far lacked a pathophysiological characterization, this
congenital anomaly has been unspecically assigned to a
heterogeneous group of unclassied cardiomyopathies. The
classication serves to bridge the gap between ignorance and
knowledge. This type of congenital cardiomyopathy has not
been fully understood so far and remains unclassified by the
WHO, although it is thought to have some individual features.
In 2006, the American Heart Association classified this entity as
a primary cardiomyopathy of genetic origin.9
Incidence
Left ventricular non-compaction (LVNC) was once considered
a rare form of myocardial disorder.10-13 The morphological
pattern of LVNC has been seen both as an isolated finding and
Figure 1: Histopathological examination shows an opened out left ventricle (LV) showing
a markedly trabeculated wall in the middle and apical portions of the ventricle. Note:
Small anterior papillary muscle (APM), poorly formed group of posterior papillary muscle
(PPM) and thickened leathery appearance of anterior leaflet of mitral valve (MV). This
11-year-old boy had been initially diagnosed as a case of rheumatic mitral regurgitation.
Image courtesy: Dr Pradeep Vaideeswar
698
also in association with other congenital anomalies. Isolated LVNC is now being recognized with increasing frequency, with various echocardiographic studies reporting
its finding in between 0.05 percent and 0.24 percent.7,8,14-17
Ritter et al15 suggested that the incidence is 0.05% in
adults. Pignatelli et al17 from the Texas Childrens Hospital, reviewed about 50,000 echocardiograms performed
in over 26,000 patients from 1997 to 2002 and found
36 patients with the isolated form of the malformation. Over
this period, the same group diagnosed 344 cases of cardiomyopathy, and/of which non-compaction accounted for one-tenth
of their cases of cardiomyopathy, a proportion very similar to
that calculated by Nugent et al in Australia.18 Oechslin et al16
estimated that isolated LVNC was seen in 0.0014 of all patients referred to their department of echocardiography over a
period of 14 years. Although these contemporary data suggest
that isolated LVNC is an extremely rare form of cardiomyopathy, we must now accept that it is being recognized with
increasing frequency, so we may need to revise our views in
the light of emerging findings.
If ventricular non-compaction does not coexist with other
cardiovascular pathologies it is called isolated ventricular
non-compaction. Although the LV is most commonly
affected (62%), both ventricles can be influenced in some
cases (2238%).19 In a study, 22 patients (76%) had isolated
ventricular non-compaction and only the LV was affected in
all of them.20
In isolated ventricular non-compaction, coexisting cardiac
anomalies that cause excessively high pressure exposure of
the ventricle during intrauterine development are absent.

In particular, various forms of semilunar valve obstruction
or left ventricular outow tract obstruction have to be ruled
out. A similar persistence of non-compacted myocardium is
frequently reported in patients with congenital left or right
ventricular outow tract obstruction and is referred to as spongy
myocardium or persisting sinusoids that communicate with
the coronary arteries.4,21-26 (Figure 2A) By contrast, isolated
ventricular non-compaction is a genetically heterogeneous
congenital disorder characterized by a pattern of excessively
prominent trabecular meshwork and deep intertrabecular
recesses in the absence of other structural heart diseases.2,27,28
Furthermore, while the persisting sinusoids are enlargements
of the coronary vessels (comparable with hemangioma), the
recesses in isolated ventricular non-compaction have no
connection with the coronary circulation.16,23 (Figure 2B). In
fact they are recesses covered by endocardial lining continuous
with the ventricular cavity, predisposing to local thrombus
formation.
Historical review
Although described as early as 1932, the disorder was
largely unrecognized until the widespread availability of
echocardiography, which has enhanced the detection. It was
Dusek et al4 who provided one of the earliest substantial
descriptions of the entity that probably represents what
we now call ventricular non-compaction. They called
it postnatal persistence of spongy myocardium with an
49
Figures 2A and B: A. Right ventricular angiogram in a neonate with pulmonary atresia with intact ventricular septum
showing persisting sinusoids communicating with the right coronary artery (RCA) and left coronary artery (LCA); B.
Left ventricular angiogram in right anterior oblique view shows non-compaction of the left ventricle (LV) with ventricular
septal defect (arrow) opacifying dilated trabeculated right ventricle (RV). The trabeculae are not connected to the
coronary circulation
embryonic blood supply. In 1990, Chin and his colleagues

described for the first time, morphologically underdeveloped
papillary muscles and non-compacted internal myocardial
layers, consisting of more than 50 percent of the ventricular
wall thickness in their patients.8 Though described as highly
fatal in early childhood, it has been reported in as old as
94-year-old patient.29
However non-compacted apex in which non-compaction
of both right and left ventricular apexes and septum is
extremely rare and hardly reported in the literature. Robert
Anderson says, this is what is known to happen in the chicken
heart, but thus far there has been no evidence to suggest a
similar mechanism in human. Hence, its cause, development,
clinical course and treatment are fields of further research
in future.
Genetics
Analysis of genetic linkage and mutation has revealed that
mutations in the gene G4.5, which encodes tafazin and maps to
chromosome Xq28, are responsible for this myocardial disorder
in some patients being allelic with Barth syndrome.30-36 In this
regard, G4.5 was initially identified as the gene responsible for
Barth syndrome, an X-linked mitochondrial disease affecting
cardiac and skeletal muscle.37,38 These mutations produce a
wide phenotypic spectrum of cardiomyopathies, including
dilated cardiomyopathy, X-linked infantile cardiomyopathy,
and X-linked endocardial fibroelastosis.36 Ichida et al7 found
a mutation in -dystrophin in some of their patients. Chen
et al. found a novel splice acceptor site mutation of intron 8 of
G4.5 in one family with severe X-linked LVNC, but without the
other usual findings of Barth syndrome.34 Pauli et al39 identified
deletion of chromosome 5q in a child with previously repaired
congenital heart disease, facial dysmorphism and LVNC. Vatta
et al40 in contrast, have shown that in some patients with either
dilated cardiomyopathy or LVNC, a mutation in Cypher-Zasp,
a gene encoding a protein i.e. a component of the Z-line in
both skeletal and cardiac muscle, may be causal. It may also
be pertinent that mice lacking FKBP12 have normal skeletal
muscle, but have a severe dilated cardiomyopathy and a
condition suggestive of LVNC.41 Clinical studies suggest
that LVNC is often familial with predominantly autosomal
dominant inheritance. It has been linked to mutations in several
genes including ZASP,40 a dystrobrevin36 and tafazzin.36,42
The disease can present throughout life with progressive left
ventricular systolic dysfunction.
Left ventricular non-compaction is certainly known
also to be a part of various syndromes, including the Barth,
Noonan, Roifman, Melnick-Needles, Nail-patella, TorielloCarey and other uncommon syndromes.14,37,38,43-51 Analysis
of the Roifman syndrome, characterized by a constellation
of antibody deficiency, spondyloepiphyseal dysplasia, facial
dysmorphism, growth retardation and retinal deficiency,
suggested an X-linked pattern of inheritance.45 The etiology
of the Toriello-Carey syndrome, first reported in 1988,
is unknown, but both X-linked and autosomal recessive
inheritance have been suggested.46,51 In one case, a 3-yearold boy was diagnosed both with the Toriello-Carey syndrome
and non-compaction, with ultrasound confirming a similar
constellation in his unborn sibling.51
699
700
Embryology
The heart is the first organ to form and function in the vertebrate
embryo.52-61 In this respect, Kirby58 has writtenHeart
development in all vertebrates from fish to humans follows
the same general pattern: fusion of the myocardium and
endocardium in the ventral midline to form a simple tubular
heart.
Before the fifth week of intrauterine life, the myocardium
forms a loose network of fibers and sinusoids, which are in
continuity with the ventricular cavity. Subsequently, the
meshwork of fibers become compacted and the sinusoids
disappear. Pathological arrest of this compaction process leads
to the persistence of ventricular hypertrabeculation, so called
spongy myocardium or LVNC.62 In 1990, Chin et al described
a group of eight patients with non-compaction, which was
not associated with other congenital cardiac abnormalities.8
But recently the childhood form of non-compaction was first
described in association with other congenital abnormalities
such as cyanotic congenital heart disease, coronary artery
anomalies and both right and left ventricular outflow tract
obstruction.4,15,26 Furthermore, it may be associated with
neuromuscular abnormalities. Others suggest that it is more
common and that its prognosis is better than expected.63
During mammalian embryonic heart development,
the ventricles undergo a series of morphogenetic
developments.64-66 Ventricular trabeculation and compaction
are two of the many essential steps for generating a
functionally competent ventricular wall.67 Simplistically,
development of the ventricular wall has four distinct stages.
Stage I, is the formation of single-cell layered myocardium
at an early developmental stage. Following induction via
adjacent endoderm, lateral mesoderm gives rise to an early
tubular heart. The heart at this stage is composed of one cell
layer of myocardium and one cell layer of endocardium lining
the lumen.64,68 Stage II, is the formation of a trabeculated and
compact myocardium at the early mid-gestation stage. As the
myocardium thickens, cardiomyocytes along the inner wall
form sheet-like protrusions into the lumen to give rise to the
trabecular myocardium, while the outside layer of myocardium
becomes organized into compact myocardium. Ventricular
trabeculation has been suggested to facilitate oxygen and
nutrient exchange and to enhance force generation to match
the increasing blood ow in developing embryos.64,67 Stage
III, myocardial compaction, occurs at the late mid-gestation
stage. As development proceeds, the trabecular myocardium
becomes compacted towards the myocardial wall and
contributes to forming a thicker, compact ventricular wall.
Stage IV, is the formation of a mature and multilayered spiral
myocardium during the late fetal and neonatal stage.66,69
Following the formation of primitive trabecular ridges
the myocardium undergoes extensive expansion either by
recruitment of cardiomyocytes from the myocardial wall
into the trabecular ridges or via cellular proliferation within
the trabecular cardiomyocytes. In support of the cellular

recruitment mechanism, proliferative activity is consistently
higher within the compact myocardium, as there is a gradient
of decreasing proliferation and increased differentiation
from the outside of the heart toward the lumen and trabecular
side.70-73 This balance of proliferation and differentiation
is critical to the formation of a functionally competent
ventricular wall. The hypertrabeculation is likely to be the
result of altered regulation in cell proliferation, differentiation
and maturation during ventricular wall formation.
The fetal heart muscle has a non-compacted appearance
between the 4th and 18th week of development and this
is important for the nutrition of its cells. The spongy
myocardium is supplied predominately by diffusion of blood
in the heart that flows into the spaces between the muscle
bands. Later and simultaneously with the development of the
coronary arteries, which will eventually take over carrying
blood to the heart muscle, development of the muscle bands
appears to go backwards. The thickness of the compacted
wall and the mass of the heart muscle is then increasing
and hence the pumping function is increasing too. The final
appearance is that of a compacted muscular wall of the
heart with minor muscle bands close to its inner surface.
Therefore ventricular walls of both ventricles in the normal
heart are made up predominantly of a compacted layer of
myocardial fibers set in a matrix of supporting connective
tissue.5 Rana et al in their study on fertilized chicken egg
state that component ballooning from the initial linear heart
tube is destined to become the LV, the ventricular septum
and the adjacent trabeculations. Most importantly, their
study shows that the RV, in essence, has comparable origins
in mammals and birds, allowing direct extrapolation of
findings in birds to mammalian cardiac development.74 It is
of interest to note that, in the evolution of the vertebrates,
myocardial non-compaction is advantageous and indeed
necessary, for the circulatory function of some fish and yet
its presence is decidedly disadvantageous for man.23,75,76
Ventricular non-compaction, a genetically heterogeneous
disorder,77 may affect both ventricles and apical septum,
may be associated with many diverse forms of congenital
cardiac malformations. This apical non-compaction entity
was detected in the fetus of 24 weeks gestation with
muscular ventricular septal defect (VSD) (Figure 3). This
patient came back to us after delivery and the infant did have
apical non-compaction along with a large VSD and patent
ductus arteriosus.
Clinical Findings
Patients with LVNC may have normal ventricular function,
hemodynamics and may lead a normal life. Patients may
present at any age from infancy to older than 94 years.29
The clinical manifestations may include heart pump failure,
arrhythmias and thromboembolic events.14
Diagnosis
Figure 3: Fetal echocardiography in a 24 weeks gestation fetus shows

midmuscular ventricular septal defect with apical non-compaction
Echocardiography
Ichida et al7 suggest that this difference may be accounted

for by the fact that LVNC in their patients was detected
incidentally during a screening study of an entire population
of Japanese children. Whether the extent or degree of
hypertrabeculation has a role in determining the timing of
presentation and severity of clinical course, is also uncertain,
although this has been suggested.8,78 Because of the known
genetic heterogeneity,79 it is yet to be determined if a specific
genetic marker may contribute to either the severity or timing
of presentation. In 27 percent of cases, extracardiac diseases
mainly mental and motor retardation were found in a study.
The most common complaints at admission were due to heart
failure (69%). The mortality rate was 21 percent and death
was caused by cardiac failure and sepsis.20
The diagnosis of non-compaction is mostly based on the

morphologic features of the left ventricle.81,82 Echocardiography
has been the routine initial non-invasive diagnostic test to detect
LVNC and is still the diagnostic test of choice.83,84 There is
little consensus on the diagnostic criteria of non-compaction.
The extent of non-compaction has also been adopted as a
diagnostic criterion for non-compaction. Several authors have
stipulated diagnostic thresholds using various measures of noncompaction.8,16,77,85 A number of echocardiographic definitions
for the diagnosis of LVNC have been proposed (Table 1). Two
are based on an analysis of fewer than 45 patients with what
appeared to be a common phenotype; the third is extrapolated
from a post-mortem study examining the number of prominent
trabeculations.8,85,86 Although all definitions attempt to describe
the morphology of the condition, they differ substantially in
The literature shows quantification and diagnosis of LVNC may

be neither easy nor objective in many cases and has recently
been a topic of significant debate. This endomyocardial
morphogenesis is characterized by numerous, excessively
prominent ventricular trabeculations and deep intertrabecular
recesses of the myocardium, more prominent at the apex of the
ventricle. Diagnosis has now moved from the autopsy table to
recognition during life, albeit the debate continues with regard
to the features displayed by angiography, echocardiography,
computed tomography (CT) and magnetic resonance imaging
(MRI) that permit unequivocal recognition.80 One can use any
of the three imaging modalities to confirm the diagnosis.
49
Table 1
Diagnostic criteria for left ventricular non-compaction

Author
Chin et
Criteria
al8
Jenni et al85
LVNC is defined as a ratio X/Y 0.5

X = distance from the epicardial surface to the trough of the trabecular recess
Y = distance from the epicardial surface to peak of the trabeculation
These criteria focus on trabeculae at the left ventricular apex on the parasternal short axis and apical views
and on left ventricular free wall thickness at end diastole.
1. A two layered structure with a thin compacted layer and a thick non-compacted layer measured in end
systole at the parasternal short axis views. LVNC is defined by a ratio of N/C > 2.
N = non-compacted layer of myocardium.
C = compacted layer of myocardium.
2. Absence of coexisting cardiac structural abnormalities.
3. Numerous excessively prominent trabeculations and deep intratrabecular recesses.
4. Recesses supplied by intraventricular blood on color Doppler.
Stollerberger et al86 1. More than 3 trabeculations protruding from the left ventricular free wall, apical to the papillary muscles,
visible in a single image plane.
2. Intertrabecular spaces perfused from the ventricular cavity visualized on color Doppler imaging.
701
702
their approach. The method proposed originally by Chin et al8

evaluates the size of trabeculations in relation to the thickness
of the compacted wall in different echocardiographic views and
at different levels of the LV in end-diastole. In this study to
quantify the depth of penetration of the intertrabecular recesses
with two-dimensional echocardiography, X to Y ratio has been
developed (Figure 4). This ratio quotient is of the distance
between the epicardial surface and trough of a trabecular
recess (represented by X) and the distance between epicardial
surface and peak of the trabeculae (represented by Y). LVNC is
defined when the ratio of X/Y 0.5. The schematic diagram of
diagnostic features of biventricular non-compaction with Swiss
cheese interventricular septum is shown in Figure 4. Jenni and
coworkers85 have proposed a method that relies on the detection
of the two myocardial layers, non-compact and compact,
in short-axis views of the LV in end-systole. LVNC, in this
instance, is defined by the ratio > 2 between non-compacted to
compacted layers. The third definition, proposed by Stollberger
et al.86 determines the number of prominent trabeculations
visible in the apical views of the LV in diastole.
The diagnosis of spongy myocardium is challenging, as it
has to be differentiated from muscle bundles. Discrete muscle
bundles, more than 2 millimeter in diameter, that stand out
against the background of the left ventricular endocardium, has
been reported in 68 percent of normal hearts and are virtually
always two to three or less in number. In contrast, in noncompaction, there are numerous prominent trabeculations and
conspicuous is the trabecular recesses that penetrate deep into

the ventricles. The echocardiographic pattern is characteristic
and diagnostic.87,88 Echocardiography, nonetheless, is less
than perfect for the diagnosis of non-compaction, since the
adequacy of the investigation depends very much on the
experience and knowledge of the investigator. Non-compaction
of the apex and the septum are seen as Swiss cheese appearance
(Figure 5).
Transthoracic echocardiography (TTE) is also useful in
detecting associated lesions like multiple muscular VSDs
and supramitral ring along with non-compaction (Figures 6
and 7). A case of probable apical non-compaction in young
man with biventricular non-compaction associated with
VSD and having undergone surgery at the age of two years
for coarctation of aorta, who presented with heart failure is
reported.89 The evidence of non-compacted myocardium in
both left and right ventricular apex was made with intracardiac
echocardiography performed during the electrophysiologic
study for arrhythmia is reported. This method has allowed the
diagnosis of non-compaction of the ventricular myocardium
due to its high resolution. Color Doppler showed trabecular
recesses in communication with the ventricular cavity that
could not be identified with transthoracic echocardiography.90
Thromboembolic events have been reported in 21 percent to
38 percent of patients with non-compaction and chest pain in
19 percent.8,15,16 The thrombus can be detected in LV (Figure
8A) or thrombus could be in RV. One of our patient with
Figure 4: Schematic diagram of diagnostic features of non-compaction of the apex.

LA = Left atrium; LV = Left ventricle; RA = Right atrium; RV = Right ventricle.
49
Figure 6: 8 years old asymptomatic boy with multiple muscular ventricular septal defects, supramitral ring, non-compaction of the apex.
LA = Left atrium; LV = Left ventricle; M = Supramitral ring; RA = Right
atrium; RV = Right ventricle; VSD = Ventricular septal defect.
Figure 5: Echocardiogram in a 2 years old boy with situs inversus,

dextrocardia, double outlet right ventricle showing non-compaction of
the apex with Swiss cheese appearance of septum. LV = Left ventricle;
Figures 8A and B: A. TTE shows non-compaction of the left ventricle

with large organized clot; B. Shows multiple soft mobile clots in right
ventricle. LA = Left atrium; LV = Left ventricle; RV = Right ventricle.
Figures 7A and B: A. Apical four-chamber view in a 3-year-old boy

shows large midmuscular ventricular septum defect, non-compaction
of left ventricle, septum and right ventricle. There is a thin epicardial
layer and an extremely thickened endocardial layer with prominent
trabeculations and deep recesses; B. Color Doppler imaging shows
blood flow through ventricular septum defect and from the ventricular
cavity into the deep recesses
biventricular non-compaction with severe aortic stenosis with

biventricular dysfunction had multiple, mobile soft clots in
the RV (Figure 8B).
Contrast echocardiography might improve the sensitivity

of diagnosing non-compaction due to improved contrast
between myocardium and blood pool. Echocardiography
poses inherent problems in assessing the left ventricular
apex, known to be the most commonly non-compacted
area.91 Furthermore, patients may be misdiagnosed as having
apical hypertrophic cardiomyopathy.7,92 Involvement of the
RV also remains controversial, first because of the more
trabeculated nature of the RV itself and secondly, due to
problems with echocardiographic access to the RV behind the
sternum. Previous echocardiographic studies have reported
right ventricular involvement in less than half of patients with
unequivocal non-compaction of the LV.15,62,93,94 In our own
experience based on cardiac magnetic resonance imaging, some
degree of right ventricular non-compaction is seen in almost all
patients with LVNC. Additionally, a large proportion of patients
with non-compaction show a distinct increased angle of
insertion of the apex of the RV, as viewed in the horizontal longaxis view. This phenomenon can also be recognized in several
previous publications describing non-compaction.17,95,96
703
Septal affection in left ventricular hypertrabeculation/

non-compaction is a finding, predominantly in children
and adolescents. Patients with septal left ventricular
hypertrabeculation/non-compaction have a poor prognosis.14
Some limited data suggests that similar cardiac features can
be acquired, but these observations are of dubious clinical
value as we are not sure whether non-compaction was present
from birth or it occurred later due to underlying disease. In
fact, the presence of multiple apical defects has received
previous comment in the setting of non-compaction. A series
of nine adults, in two families, with isolated non-compaction
of the ventricular myocardium involving the left ventricular
apex is reported, in whom there were no associated lesions.97
This is in contrast to our experience of 62 cases with apical
non-compaction who all had associated congenital cardiac
malformations, that made the pump failure worse. In our
series of apical non-compaction, we have considered from the
stance of clinical and imaging characteristics of patients with
possible management, in the setting of associated congenital
cardiac disease, causing further burden on the heart.
Angiography
Left ventriculography is rarely required today to make the
diagnosis of non-compaction. But angiogram is required
in associated complex congenital heart disease to know the
pulmonary artery pressure as in a 2-year-old boy with situs
inversus, dextrocardia, double outlet right ventricle with
severe infundibular stenosis showing non-compaction of
the apex, septum and the LV (Figure 9). Nonetheless, with
angiography, left ventriculography in diastole shows a double
contoured LV; the inner contour defining the true left ventricular
cavity with dense opacification and the outer contour defining
the non-compacted layer with less dense opacification.
Figure 9: Right ventricular angiogram in a 2-year-old boy with situs

inversus, dextrocardia, double outlet right ventricle with severe
infundibular stenosis showing non-compaction of the apex, septum
and left ventricle
Magnetic Resonance and Computed

Tomographic Imaging
704
The other modalities for imaging are now increasingly used

in diagnosis, particularly CT and MRI.98,99 The TTE showed
unusual non-compaction of the apex and septum with a tunnellike septal defect (Figure 10) but MRI was more useful.
Sometimes prominent muscular trabeculations with deep
intertrabecular recesses in the apex is well demonstrated by
cardiac MRI of both the ventricles. The Swiss cheese VSD in
both TTE and MRI resemble the delta of the river (Figures 11A
to C).
Magnetic resonance cine imaging, by using so-called steady
state free precession sequence (SSFP), is increasingly used
because of its ability to clearly visualize the compacted and
non-compacted layers.77 This technique shows a wider extent
of disease and a greater ratio of non-compacted to compacted
myocardium, when compared to echocardiography in cases with
LVNC.77 Interestingly, the non-compacted layer is demarcated
Figure 10: Transthoracic echocardiography in parasternal longaxis view with color Doppler shows long track like ventricular septal
defect. AO = Aorta; LV = Left ventricle; RV = Right ventricle; VSD =
Ventricular septal defect.
internally by an interrupted layer of tissue. The trabeculations

hang from this layer towards the compacted layer, appearing
like a cascading necklace. It has also been suggested that the
delayed hyperenhancement technique might be able to visualize
the necrotic or fibrotic myocardium that could be the focus
of the ventricular arrhythmia.95 Another advantage of MRI
49
Figures 11A to C: A. The picture of delta of Nile river; B. Cardiac magnetic resonance image of both the ventricles showing prominent
muscular trabeculations with deep intertrabecular recesses in the apical portion of septum and ventricles, resembling delta of the river;
C. Transthoracic echocardiography in a Swiss cheese interventricular septum which resembles delta of the river. LV = Left ventricle; RV
= Right ventricle.
Figures 12A and B: Transthoracic echocardiography in 4-year-old boy with situs inversus, dextrocardia, bicuspid aortic valve, severe aortic
stenosis shows non-compaction with left ventricular dysfunction (EF 35%). AO = Aorta; LA = Left Atrium; LV = Left ventricle.
is that its intrinsically three-dimensional nature permits the

assessment of all cardiac segments. Sequences based on the use
of contrast then allow the assessment of myocardial perfusion
and the evaluation of myocardial fibrosis.100 This modality
also allows visualization of left ventricular thrombus.101,102
Computed tomography, however, is of limited value, because it
is not possible to assess regional and global ventricular function
and furthermore, the technique depends on the use of radiation.
The utility of electrographically gated CT, nonetheless should
be investigated. Cine MRI in four-chamber and two-chamber
views shows an interrupted layer of tissue delineating the
non-compacted layer of myocardium from the left ventricular
cavity. The trabeculations are seen as fine strands extending
from the compacted myocardium towards the thin layer of
tissue. The abnormal non-compacted myocardium is thickest

in the apex. It extends to the atrioventricular junction along
the free wall, while the basal one-third of the septum is not
involved.
Differential diagnosis
Once the dilated and hypertrophic variants of cardiomyopathy
are excluded from consideration, there are relatively few
further potential diagnosis for myocardial non-compaction.
It is, of course, necessary to exclude the false diagnosis of
normal left ventricular trabeculations as non-compaction, as
we discussed earlier. It is also necessary to distinguish noncompaction from the acquired changes seen in the setting
705
of lesions such as pulmonary atresia with intact ventricular

septum. Another potentially misleading condition is the
appearance of layered mural thrombus of the LV simulating
non-compaction.14 It has also been suggested that mycotic
invasion of the heart can produce the appearance of abnormal
trabeculations,103,104 while rarely an intramyocardial hematoma
may mimic isolated LVNC.105 The question has also been
asked as to whether LVNC can be a cardiac manifestation
of Fabry disease.106 In this respect, while the appearances of
hypertrophic cardiomyopathy are well-documented in patients
with Fabry disease, to the best of our knowledge there is no
data supporting unequivocally the association of this inborn
metabolic disorder with LVNC.
The WHO classication of cardiomyopathies should
reconsider, inclusion of isolated ventricular non-compaction
as a distinct cardiomyopathy. This would improve not only the
knowledge, but also the awareness of this disorder and thus,
facilitate its diagnosis, as even a skilled echocardiographers
eye sees better, while knowing what to look for.85
outcome
Many of the early clinical reports emphasized the dismal
outcomes of patients with isolated LVNC,7,8,14-17,62,85,98,
107-115 focusing on the egregious nature of the often malignant
accompanying arrhythmias. Increasing clinical experience
has modified to some extent this bleak outlook.17,98 In some
asymptomatic patients, isolated LVNC has been found as an
incidental finding.116,117 In others it has been recognized in the
sixth and seventh decades of life and beyond. Yet the disorder
certainly has the potential for a poor outcome. Even for those
patients presenting in the first year of life with depressed left
ventricular contractility, with some recovery of ventricular
function, recovery can be transient.
In 27 percent of cases in a study, extracardiac diseases,
mainly mental and motor retardation were found. The most
common complaints at admission were due to heart failure
(69%). The mortality rate was 21 percent and death was
caused by cardiac failure and sepsis.20
MANAGEMENT
706
A variety of medical therapies have been utilized in those

symptomatic patients with congestive heart failure, including
cardiac glycosides, diuretics, inhibitors of angiotensin
converting enzyme and afterload reducing agents. In those
suspected of having an underlying mitochondrial myopathy,
a metabolic cocktail has been used.17 Beta-blockers has also
been used with some success.118 Some patients have needed
cardiac transplantation.119 Disturbances of rhythm have
been treated in standard fashion, while some have implanted
defibrillators for severe ventricular arrhythmias recognized as
predisposing to sudden death.120,121 Surprisingly, patients with
complex congenital cardiac malformations coexisting with
non-compaction seem less troubled with severe disturbances

of rhythm.
Cerebrovascular accidents certainly contribute to comorbidity in patients with isolated LVNC, the unusual
hypertrabeculations not only reducing ventricular
function, but also creating a nidus for formation of mural
thrombus.7,8,14-17,98,110-115 It is difficult, however, precisely to
determine the incidence of adverse neurological events. It has
been suggested that patients should at least be placed on a
protocol of oral anticoagulation once the diagnosis of isolated
LVNC is made. Of course, if a patient has sustained and
unequivocal thromboembolic event, then full anticoagulation
with low-molecular-weight heparin is advised.7,8,16,17 The
successful interventions for the associated lesions, which
could be a ray of hope in these patients with pump failure and
reduce the morbidity and postpone the mortality. The balloon
dilatation can be done for critical aortic stenosis and coarctation
of aorta. In our series of cases of apical non-compaction, two
situs inversus dextrocardia patients underwent successful
interventions. One 4 year old boy underwent aortic balloon
valvuloplasty (Figure 12 A and B) and another 8 years old
girls mid-muscular VSD was closed with Amplatzer duct
occluder II (Figure 13 A and B). Non-compaction of the
ventricle with associated aorto-left ventricular tunnel closed
by Amplatzer duct occluder is reported for the first time in
world literature.122 This patient had hemolysis for five days.
Hemolysis probably can be minimized if a custom made
device is used to t the anatomy of the tunnel. Aorto-right
ventricular tunnel in biventricular non-compaction has
been closed with Amplatzer duct occluder II.123 Associated
multiple VSDs can be closed by device to reduce the volume
overload and pump failure in ventricular non-compaction
(Figures 14 A and B). Surgery in ventricular non-compaction
with associated lesions carry high risk. Therefore non-surgical
transcatheter interventions are better options for post surgical
residual VSDs.
FUTURE
The currently increased awareness of the condition has
recently led to frequent reports in the medical literature
of people having the features of non-compaction, but
the clinical significance of this has to be evaluated with
caution. High priority should be given to establishing
standard nomenclature and diagnostic criteria for future
research.82,124,125 Genetic testing of the most clinically
affected individuals, echocardiographic or cardiac MRI
screening of all first degree relatives and obtaining family
history for at least three generations, need to be implemented
in clinical practice, to further understand the influence of
genetic mechanisms in this disorder. Finally, the clinicians,
imaging specialists, geneticists and pathologists all need to
contribute their scientific knowledge to define this elusive
entity called ventricular non-compaction.126-128
49
Figures 13A and B: A. Left ventricular angiogram in right anterior oblique view in
an 8-year-old girl with dextrocardia shows non-compacion of the left ventricle with
mid-muscular ventricular septal defect; B. Transthoracic echocardiography in apical
four-chamber view with color Doppler shows non-compaction with the Amplatzer duct
occluder II in situ with no residual shunt
Figures 14A and B: A. Left ventricular angiogram in left anterior oblique view illustrates
non-compaction of left ventricle (black arrows), mid-muscular ventricular septal defect (VSD)
opacifying right ventricle; B. 6 6 Amplatzer duct occluder II in situ. Left ventricular angiogram in
left anterior oblique view shows no residual VSD in a 8 months old, 5 kilogram infant. LV = Left
ventricle; RV = Right ventricle.
Conclusion
Ventricular non-compaction, a genetically heterogeneous
disorder,78 may affect both ventricles, may be isolated or may
be associated with many diverse forms of congenital cardiac
malformations. It has been identified in patients with a variety
of syndromes. When confined to the LV, patients may present
like those with idiopathic dilated cardiomyopathy or less
frequently with restrictive physiology, this latter physiology
perhaps more common in children. The entity has now been

recognized in the fetus and also in the octogenarian, with
many patients presenting or identified in adults. The peculiar
association of LVNC with many kinds of neuromuscular
disorders is well-established, but the reasons for this
association have not been clarified. The prognosis for the
symptomatic patient is generally poor, with progression to
chronic cardiac failure and death. Some patients with isolated
LVNC will die suddenly due to arrhythmias, thromboembolism
707
and left ventricular dysfunction. The recently recognized

myocardial malformation with non-compaction of both the
ventricular apex and septum is almost always associated
with other hemodynamically significant congenital cardiac
malformations, which worsen the pump failure, pre-existing
with the non-compaction. Non-surgical interventions or
surgical correction of associated lesions though difficult is
feasible and can reduce the morbidity and possibly postpone
mortality. Some symptomatic patients may benefit from
orthotopic cardiac transplantation, if medical therapy fails to
stabilize the condition.
Life is short, the art long, opportunity fleeting, experiment
treacherous, judgment difficult.
Hippocrates
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83. Frischknecht B, Attenhofer Jost CH, Oechslin EN, et al. Validation of noncompaction criteria in dilated cardiomyopathy, and
valvular and hypertensive heart disease. J Am Soc Echocardiogr. 2005;18:865-72.
84. Tamborini G, Pepi M, Celeste F, et al. Incidence and
characteristics of left ventricular false tendons and trabeculations
in the normal and pathologic heart by second harmonic
echocardiography. J Am Soc Echocardiogr. 2004;17:367-74.
85. Jenni R, Oechslin EN, Attenhofer Jost C, et al. Echocardiographic
and pathoanatomical characteristics of isolated left ventricular
noncompaction: a step towards classification as a distinct
cardiomyopathy. Heart. 2001; 86:666-71.
86. Stollberger C, Finsterer J, Blazek G. Left ventricular
hypertrabeculation, noncompaction and association with
additional cardiac abnormalities and neuromuscular disorders.
Am J Cardiol. 2002;90:899-902.
87. Vijayalakshmi IB, Sumangala BV, Chitra N. Echo in aortoventricular tunnel with non-compaction of Ieft ventricle. Journal
of the Indian Academy of Echocardiography. 2001;7: 238.
88. Vijayalakshmi IB. Role of Echocardiography in Rarest
Congenital Heart Disease in Journal of Indian Academy of
89. Tatu-Chitoiu A, Bradisteanu S. A rare case of biventricular
non-compaction associated with ventricular septal defect and
descendent aortic stenosis in a young man. Eur J Echocardiogr.
2008;9:306-8.
90. Ficili S, Pandozi C, Galeazzi M, et al. Noncompacted
ventricular myocardium: characterization by intracardiac echo.
J Cardiovasc Med (Hagerstown). 2011;12:294-6.
91. Moon JC, Fisher NG, McKenna WJ, et al. Detection of apical
hypertrophic cardiomyopathy by cardiovascular magnetic
resonance in patients with non-diagnostic echocardiography.
Heart. 2004;90:645-9.
92. Chung T, Yiannikas J, Lee LC, et al. Isolated noncompaction

involving the left ventricular apex in adults. Am J Cardiol.
2004;94:1214-6.
93. Corrado G, Santarone M, Miglierina E, et al. Isolated
noncompaction of the ventricular myocardium: a study in an
adult male and literature review. Ital Heart J. 2000;1:372-5.
94. Koo BK, Choi D, Ha JW, et al. Isolated noncompaction of
the ventricular myocardium: contrast echocardiographic
findings and review of the literature. Echocardiography.
2002;19:153-6.
95. Korcyk D, Edwards CC, Armstrong G, et al. Cardiac-enhanced
cardiac magnetic resonance in a patient with familial isolated
ventricular non-compaction. J Cardiovasc Magn Reson. 2004;
6:569-76.
96. Weiss F, Habermann CR, Lilje C, et al. MRI in the diagnosis of
non-compacted ventricular myocardium (NCVM) compared to
echocardiography. Rofo. 2003;175:1214-9.
97. Chung T, Yiannikas J, Lee LC, et al. Isolated noncompaction
involving the left ventricular apex in adults. Am J Cardiol.
2004 1;94:1214-6.
98. Ali SKM, Godman MJ. The variable clinical presentation and
outcomes for noncompaction of the ventricular myocardium
in infants and children, and under-diagnosed cardiomyopathy.
99. Hamamichi Y, Ichida F, Hashimoto I, et al. Isolated
noncompaction of the ventricular myocardium: ultrafast
computed tomography and magnetic resonance imaging. Int J
Card Imaging. 2001;17:305-14.
100. Gebker R, Paetsch I, Wahl A, et al. Ventricular non-compaction.
Eur Heart J. 2004;25: Cover Image.
101. Barkhausen J, Hunold P, Eggebrecht H, et al. Detection and
characterization of intracardiac thrombi on MR imaging. Am J
Roentgenol. 2002;179:1539-44.
102. Petersen SE, Timperley J, Neubauer S. Left ventricular thrombi
in a patient with left ventricular non-compaction visualisation
of the rationale for anticoagulation. Heart. 2005;91:e4.
103. Stllberger C, Preiser J, Finsterer J. Histological detection
of intramyocardial abscesses in Candida sepsis mimicking
left ventricular noncompaction/hypertrabeculation on echo
cardiography. Mycoses. 2004;47:72-5.
104. Stllberger C, Preiser J, Finsterer J. Candida sepsis with

intramyocardial abscesses mimicking left ventricular
noncompaction. Eur J Echocardiogr. 2004;5:76-8.
105. Stllberger C, Finsterer J, Waldenberger FR, et al.

Intramyocardial hematoma mimicking abnormal left ventricular
trabeculation. J Am Soc Echocardiogr. 2001;14: 1030-2.
106. Stllberger C, Finsterer J, Voigtlander T, et al. Is left ventricular
hypertrabeculation/noncompaction a cardiac manifestation of
Fabrys disease? Z Kardiol. 2003;92:966-9.
107. Jenni R, Rojas J, Oechslin E. Isolated noncompaction of the
myocardium. N Engl J Med. 1999;340:966-7.
108. Weiford BC, Subbarao VD, Mulhern KM. Noncompaction of
the ventricular myocardium. Circulation. 2004;109:2965-71.
109. Oechslin E, Jenni R. Guest editorial. Isolated left ventricular
non-compaction: increasing recognition of the distinct, yet
unclassified cardiomyopathy. Eur J Echocardiogr. 2002;3:
250-51.
110. Halbertsma FJ, vant Hek LGEM, Daniels O. Spongy
cardiomyopathy in a neonate. Cardiol Young. 2001;11:45860.
120. Celiker A, Kafali G, Dogan R. Cardioverter defibrillator

implantation in a child with isolated noncompaction of the
ventricular myocardium and ventricular fibrillation. Pacing
Clin Electrophysiol. 2004;27:104-8.
121. Seres L, Lopez J, Larrousse E, et al. Isolated noncompaction
left ventricular myocardium and polymorphic ventricular
tachycardia. Clin Cardiol. 2003;26: 46-8.
122. Vijayalakshmi IB, Chitra N, Prabhu Deva AN. Use of a

Amplatzer Duct Occluder for closing an aortico-left ventricular
tunnel in a case of noncompaction of left ventricle. Pediatr
Cardiol. 2004;25:77-9.
123. Vijayalakshmi IB, Chitra N, Ashish A . Closure of Aorto-right
ventricular tunnel with Amplatzer Duct Occluder II. Accepted
for publication in Journal of Invasive Cardiology on September
21st 2012.
124. Lurie PR. The perspective of ventricular noncompaction as
seen by a nonagenarian. Cardiol Young. 2008;18:243-9.
125. Anderson RH. Ventricular noncompactiona frequently

ignored finding? Eur Heart J. 2008;29:10-1.
126. Stollberger C, Finsterer J. Pitfalls in the diagnosis of left

ventricular hypertrabeculation/noncompaction. Postgrad Med
J. 2006;82:670-83.
127. Nair SB, Khattar RS. Isolated left ventricular non-compaction:
an emerging cause of heart failure in adults. Postgrad Med J.
2009;85:202-7.
128. Engberding R, Yelbuz T, Breithardt G. Isolated noncompaction
of the left ventricular myocardium. A review of the literature
two decades after the initial case description. Clin Res Cardiol.
2007;96:481-8.
49
111. Neudorf UE, Hussein A, Trowitzsch E, et al. Clinical features

of isolated noncompaction of the myocardium in children.
112. Kohl T, Villegas M, Silverman N. Isolated noncompaction of
ventricular myocardium detection during fetal life. Cardiol
Young. 1995;5:187-9.
113. Winer N, Lefevre M, Nomballais MF, et al. Persisting spongy
myocardium: a case indicating the difficulty of antenatal
diagnosis. Fetal Diagn Ther. 1998;13:227-32.
114. Moura C, Hillion Y, Daikha-Dahmane F, et al. Isolated

non-compaction of the myocardium diagnosed in the
fetus: two sporadic and two familial cases. Cardiol Young.
2002;12:278-83.
115. Guntheroth W, Komarniski C, Atkinson W, et al. Criterion for
fetal spongiform cardiomyopathy: restrictive pathophysiology.
Obstet Gynecol. 2002;99:882-5.
116. Tsui KL, Chan KK, Leung TC, et al. Isolated ventricular noncompaction presenting with ventricular tachycardia. Hong
Kong Med J. 2003;9:137-40.
117. Elshershari H, Okutan V, Celiker A. Isolated noncompaction
of ventricular myocardium. Cardiol Young. 2001;11:
472-5.
118. Toyono M, Kondo C, Nakajima Y, et al. Effects of carvedilol
on left ventricular function, mass and scintigraphic
findings in isolated left ventricular non-compaction. Heart.
2001;86:e4.
119. Stamou SC, Lefrak EA, Athari FC, et al. Heart transplantation
in a patient with isolated noncompaction of the left ventricular
myocardium. Ann Thorac Surg. 2004;77: 1806-8.
711
C hapter
50
Restrictive Cardiomyopathy
Bhanu Duggal, Neeraj Raghani
Restrictive cardiomyopathy (RCM) is a clinical and

hemodynamic syndrome resulting from an infiltrative
process involving the myocardium and/or subendocardium.
It is characterized by restrictive filling and reduced diastolic
volume of either one or both the ventricles with normal or near
normal systolic function. In such cases the input of a normal or
small volume of blood into the affected ventricle is followed
by a disproportionate increase in intracavitary pressure, i.e.
the ventricle compliance curve is shifted to the left.1
It may occur due to endomyocardial fibrosis (EMF), idiopathic
interstitial myocardial fibrosis or as a cardiac manifestation
of systemic disease such as scleroderma, amyloidosis, ChurgStrauss syndrome, cystinosis, sarcoidosis, lymphoma, Gaucher
disease, hemochromatosis, Fabry disease, hypereosinophilic
syndrome and various neuromuscular disorders.2
Prevalence
Restrictive cardiomyopathy is much less frequent than dilated
or hypertrophic cardiomyopathy. A nationwide epidemiologic
survey in Japan found a crude prevalence of 0.2 per 100,000
people.3 It is the cause of less then 3 percent cases of diastolic
heart failure in adults and 5 percent in children.4
Clinical Features
Symptoms
As the ventricles are stiff and have restrictive filling, the
ventricular diastolic and resultant atrial, jugular and pulmonary
venous pressures are increased. This produces symptoms
of pulmonary and/or systemic venous congestion (dyspnea,
orthopnea, edema, abdominal distension) depending on the
affected ventricle. The under filled ventricles cause symptoms
of decreased cardiac output like dyspnea on exertion, chest pain
and easy fatigability. The patient may give history of palpitations
or syncope due to associated arrhythmias or conduction defects,
which are often observed in these disorders.5
Associated History
A detailed history should be taken to rule out an underlying
disorder or potential causes of RCM.
History: Drug treatment (long-term chloroquine treatment,6
L-tryptophan, anthracycline, doxorubicin), radiation for a
previous malignancy, history of diabetes, hepatic problems,
arthritis for hemochromatosis, weight loss, renal or hepatic
problems for amyloidosis, pulmonary problems for scleroderma;
allergic rhinitis or nasal polyps for Churg-Strauss syndrome;
muscle weakness and wasting for neuromuscular disorders
should be elicited.
Family history: RCM has an autosomal dominant pattern
in desminopathy, Noonan syndrome and unspecified skeletal
myopathy. It is an autosomal recessive disorder associated
with musculoskeletal abnormalities. Familial occurrence of
the idiopathic variety has also been reported.
Physical examination: Reveals systemic and pulmonary
venous congestion. The most common signs are jugular
venous distension (52%), systolic murmurs (49%), pulmonary
rates (18%), ascites (15%) and edema (15%). The jugular
venous pressure (JVP) is elevated (52%) with prominent y
descent. A low pulse volume due to reduced stroke volume and
tachycardia, can be seen in severe cases. The apical impulse is
not displaced and filling sounds marking the abrupt cessation
of rapid early diastolic filling (S3) can be present. A fourth
heart sound (S4) can also be present. Hepatomegaly, ascites
and pedal edema are common clinical findings.
Other clinical findings to rule out associated clinical disorders
include skin fibrosis and Raynauds phenomenon in scleroderma,
hyperpigmentation in hemochromatosis; macroglossia and
hepatosplenomegaly in amyloidosis and storage disorders;
skeletal abnormalities in Gaucher disease, myeloma; muscle
weakness and wasting in neuromuscular disorders.
Chest radiography usually shows cardiomegaly as atrial
enlargement and pericardial effusion can produce an enlarged
cardiac silhouette (Figure 1). A double shadow because of
enlargement of left atrium and pulmonary artery trunk may be
seen. Pulmonary venous congestion appears in nearly all the

patients (86%).7
Electrocardiography (ECG) is abnormal in 98 percent of the

patients. The ECG findings corroborate with the enlargement
or hypertrophy of the particular chambers. It usually shows
evidence of atrial enlargement. Criteria for ventricular hyper
trophy may be seen. Repolarization abnormalities especially
notched and biphasic T waves, obliquely elevated and late
peaking ST segments, which may prolong the QT interval
are seen especially in children. Amyloidosis is a contrasting
example with low voltage ECG seen in all the leads.
Figure 1: Chest X-ray posteroanterior view shows cardiomegaly,

double shadow due to right atrial (RA) enlargement and pericardial
effusion (PE) beyond the RA and left ventricle (LV) border (arrows)
Blood Test
50
restrictive cardiomyopathy
Electrocardiography
Atrial and ventricular arrhythmias and conduction

disturbances are frequent (Figure 2). Atrial fibrillation is
common in idiopathic restrictive cardiomyopathy. ST-T
abnormalities are seen in 80 percent cases, atrial fibrillation
74 percent, intraventricular conduction delay (19%) and the
ECG is only rarely normal (2%). Atrioventricular block or
a tachybrady syndrome requiring pacemaker implantation
suggests RCM due to neuromuscular disorders such as
desminopathy, myofibrillar myopathy, distal myopathy with
rimmed vacuole, chloroquine myopathy or an unspecified
myopathy. Familial RCM has been associated with
atrioventricular blocks.8
Peripheral blood eosinophilia may indicate hypereosinophilic

syndrome and Churg-Strauss syndrome. The anemia and
thrombocytopenia may indicate Gaucher disease; serum
electrolytes, hepatic enzymes and renal function tests
detect hepatic or renal dysfunction. Elevated serum muscle
enzymes may indicate neuromuscular disorders; serum
and urine protein analysis may reveal gammopathies
(amyloidosis, Fabry disease) and thyroid function tests for
hypothyroidism (POEMS {polyneuropathy, organomegaly,
endocrinopathy monoclonal gammopathy, skin changes,
mitochondrial myopathy) as hypothyroidism is seen in both
these conditions.
Brain natriuretic peptide (BNP) is a neurohormone
secreted in response to myocardial stretch. Plasma BNP
levels are increased in RCM and are useful for differentiating
it from constrictive pericarditis (especially idiopathic) in
which they remain normal. It is also a useful prognostic
marker as it increases with right heart failure.9
713
Figure 2: Electrocardiogram showing sinus rhythm, biventricular hypertrophy, prolonged QTc, biphasic T wave in chest leads
Figure 3A and B: Transthoracic echocardiography with color Doppler shows left ventricular hypertrophy secondary to amyloidosis in a 2-yearold child. Aortic valve is normal; B. Parasternal long-axis in 5 years old restrictive cardiomyopathy patient shows large pericardial effusion
Echocardiography
Echocardiographic examination includes M-mode assessment,
2D echo examination, pulse Doppler assessment of mitral,
tricuspid, pulmonary venous and hepatic flows, tissue
Doppler imaging and color M-mode examination. The
findings depend upon the involvement of left/right or both
ventricles and associated pericardial effusion (Figures 3A
and B).
M-mode Echo
Various abnormalities of septal motion, left ventricular
(LV) posterior wall and right ventricular (RV) anterior
wall have been described. Exaggerated movement of the
interventricular septum (IVS) with sharp sudden cessation
of the movement in early diastole, exaggerated thickening
of the posterior wall in late diastole have been described.
The compromise of diastolic filling is manifested by a larger
amplitude of the mitral opening at the beginning of diastole
which then remains flat during the rest of diastole. Right
ventricular endomyocardial fibrosis has been associated with
paradoxical septal motion, exaggerated RV anterior wall
motion as well as increased dimensions of the right ventricle
and right ventricular outflow tract.
2D Echo
714
Systolic function is normal till late stages of the disease.

Ventricular volumes are normal. There may be increased
wall thickness and a characteristic speckled appearance is
seen in certain infiltrative disorders. Biatrial enlargement is
ubiquitous in this disease state (Figure 4), along with dilated
non-collapsing inferior vena cava (Figure 5), hepatic veins
and pulmonary veins.
Figure 4: Apical four-chamber view showing biatrial enlargement
Doppler
Mitral and tricuspid regurgitation (TR) is often seen
(Figure 6A). This may be due to affliction of the valves by the
disease process itself as well as there may be secondary TR due to
pulmonary hypertension (Figure 6B). The flow through the mitral
and tricuspid valves, depending on which ventricle is damaged,
presents as practically forming one peak in protodiastole (the
E wave) with an acute reduction in declaration time (DT < 160
ms) and a short isovolumic relaxation time (IVRT < 70 ms)
(Figure 7), followed by a greatly reduced A wave (E/A ratio of
mitral inflow > 2.0) (Figure 8). This indicates a pattern of rapid
inflow immediately after valve opening followed by an abrupt
cessation due to reduction in distensibility.
50
Doppler Tissue Imaging

Doppler Tissue imaging of the mitral annulus or proximal
septum reveals abnormally low diastolic Doppler annular
velocities. E is usually less than 8 cm/s (Figure 10) and E/E
ratio is more than 15.
Figure 5: Dilated inferior vena cava (IVC) with no respiratory

variation (IVC Plethora)
Figure 7: Modified apical four-chamber view showing calculation of

isovolumic relaxation time (IVRT), from closure of aortic valve to opening
of mitral valve (Patient has a junctional rhythm, and sweep velocity of
tissue Doppler is 50 mm/sec
There is no respiratory variation in the filling patterns.

Concurrent with abnormalities of mitral valve inflow,
pulmonary vein flow may reveal blunted systolic forward flow.
The systolic/diastolic (S/D) ratio of pulmonary venous flow is
less than 1 (Figure 9) and the atrial reversal in accentuated.
Mid-diastolic reversal of flow across mitral and/or tricuspid
valves, diastolic MR, is more common with RCM.
Tissue Doppler and color M-mode imaging are less
preload dependent echocardiographic measures of diastolic
dysfunction.
Figure 8: Pulse wave Doppler at mitral valve level showing tall E

wave, E/A ratio is > 2:1, DT < 150 msec
Figures 6A and B: A. Transthoracic echocardiography in an 11-year-old girl of restrictive cardiomyopathy in apical four-chamber view shows
small ventricles (RV and LV) large atria (RA and LA), color Doppler shows severe tricuspid regurgitation; B. Color Doppler showing the presence
of tricuspid regurgitation and continuous wave Doppler at tricuspid valve demonstrating pulmonary hypertension. LA = Left atrium; LV = Left
ventricle; RA = Right atrium; RV = Right ventricle.
715
716
Figure 9: Pulse wave Doppler at pulmonary vein

showing systolic (S), diastolic (D) waves (D > S)
Figure 11: Color M-mode: Doppler flow propagation velocity (Vp)

is decreased (Vp < 45 cm/s)
Figure 10: Tissue Doppler: Mitral annular E velocity < 10 cm/sec
Figure 12: (1) Dip and plateau, Square-Root Sign; Elevated left
ventricular end diastolic pressure (LVEDP) and right ventricular
end diastolic pressure (RVEDP), LVEDP > 8 mm Hg (2) RVEDP <
1/3rd of right ventricular systolic pressure.
Color M-mode is also useful in RCM. 2 slopes can be

measured. One is the slope of transition from color to no
color as measured from tip of mitral leaflets to apex of LV and
second is the slope of the first aliasing velocity from the tip of
the mitral leaflets to a position 4 cm distal into the LV(Vp). In
RCM, Vp is less than 4 cm/s (Figure 11).
Restrictive cardiomyopathy is often a global process
and similar pathology can be noted in the right ventricle,
including varying degrees of hypertrophy and infiltration and
abnormalities of tricuspid inflow and hepatic vein flow as seen
on the left side.10
less than 1/3rd of the RV systolic pressure (Figure 12). The

early dip, rapid rise, and abrupt plateau gives rise to a square
root sign, similar to constrictive pericarditis. The ventricular
diastolic pressure rise may be followed by a more sustained
rise, a mid-diastolic ventricular pressure rather than a true
plateau. This dip and plateau in the diastolic pressure waveform
is represented by a rapid Y descent followed by a rapid rise and
plateau in the atrial pressure tracing (Figure 13). The descent
of V wave becomes more prominent in inspiration. A higher
LV than RV filling pressure (> 6 mm Hg) strongly favors the
diagnosis of restrictive cardiomyopathy.1,11
The cardiac index is often decreased. The early portion of left

and right ventricular pressure tracing in diastole is characterized
by a sharp dip (deep and rapid early decline in ventricular
pressure) and then a precipitous rise in the rapid filling phase.
The right ventricular end diastolic pressure (RVEDP) is usually
For a definitive diagnosis of RCM, Endomyocardial biopsy

(EMBx) is needed in many cases to establish the diagnosis
as well as to differentiate from constrictive pericarditis.
In RCM due to amyloidosis, myocardial biopsy shows
interstitial amyloid deposits. Immunohistochemical staining
determines the type of amyloid. In idiopathic RCM,

endomyocardial biopsy demonstrates interstitial fibrosis.
Immunofluorescent straining, immunohistochemical studies
and electron-microscopy may be needed for the diagnosis.
In storage disorders like Gaucher and Fabry disease, EMBx
can be diagnostic. Although not required for diagnosis in
hemochromatosis, it may be required to monitor the response
to therapy.12
Specific Cardiomyopathies
Treatment Strategies
Hypereosinophilic Syndromes
Diuretics
Angiotensin converting enzyme (ACE) inhibitors or other
vasodilators
Calcium channel blockers
Beta-blockers
Anticoagulation
Surgery
Implantable cardioverter defibrillator
Transplantation.
Endomyocardial fibrosis (EMF) is an endemic heart disease

in several tropical countries. It is characterized by deposition
of fibrotic tissue covering the endocardium initially at the
apex and then proceeding towards the atrioventricular plane.
The outflow tract is mostly free of the fibrotic tissue. The
involvement of chordae tendinae is frequent and causes
mitral and tricuspid regurgitation. The endocardial thickening
and myocardial involvement leads to decrease ventricular
distensibility and impairment of filling. Symptoms are mainly
of diastolic impairment depending upon which ventricle is
involved.
Treatment of Specific RCM

Amyloidosis: Immunosuppression (minor benefits).
Sarcoidosis: Steroids.
Loeffler Hypereosinophilic syndrome: Steroids, interferon
alpha, Anticoagulants.
Hemochromatosis: Chelation therapy.
Fabry disease: Recombinant human alpha-galactosidase
replacement.
Gaucher disease: Enzyme replacement therapy.
Treatment of restrictive cardiomyopathy is difficult because
the underlying processes usually do not respond to interventions.
Diuretics are often useful in relieving the congestive
symptoms. Their dose needs to be monitored carefully as they
may cause a decline in the preload and lead to hypotension.
Arteriolar and balanced vasodilators are not useful because
excessive afterload is not a problem. Venous vasodilators may
decrease congestive symptoms, but can provoke significant
50
Figure 13: Right atrial pressure tracing showing a rapid Y descent
hypotension. Patients of cardiac amyloidosis may be very

sensitive to cardiac glycoside. These are also not useful in the
early stages when systolic function is normal. Calcium channel
blockers are used by some because of their potential benefit,
but improvement in ventricular compliance has not been seen.
Beta-blockers are useful in the early stages. They control the
ventricular response in atrial fibrillation. As they increase
the diastolic filling period and hence the stroke volume.
ACE inhibitors and AT1 receptor blockers (angiotensinogen
II blockers) decrease LV mass in hypertension and have
been shown to be useful in experimental studies. They may
also induce hypotension and renal failure. AT1 receptor
blockers can improve exercise performance in patients with
diastolic dysfunction and a hypertensive response to exercise.
Anticoagulation should be considered because of significant
risk of thromboembolic complications. Therapies directed
at specific forms of this condition include chelation therapy,
phlebotomy, bone marrow transplantation, salt restriction and
implantable cardioverter defibrillator placement. In children,
RCM is primarily idiopathic and transplantation is the
treatment of choice. This is often required within 4 years of
diagnosis.
Diagnostic Studies
Hypereosinophilia may be present. Chest X-ray shows varying
degrees of cardiomegaly. Right atrial enlargement is seen in
right sided EMF, left atrial enlargement is seen in patient with
left-sided involvement and biatrial enlargement in biatrial
EMF. Pulmonary venous congestion is seen with left-sided
involvement. Occasionally myocardial calcification is seen.
2D echo shows the characteristic findings of apical
obliteration of the involved ventricle with gross enlargement
of the atrium. Pericardial effusion may be present.
Hemodynamics
A dip and plateau curve with high diastolic pressure is seen in
the corresponding ventricle.
717
Angiography
Cardiac Amyloidosis
Characteristic obliteration of the apex of the involved

ventricle with varying degrees of atrioventricular valve
regurgitation is seen in all patients with left or biventricular
EMF. Endomyocardial biopsy showed fibrous thickening
of the endocardium made up of collagen without classic
fibers.
Treatment: Endarterectomy with atrioventricular valve
replacement of the diseased ventricle has been done with
mixed outcome. Cavopulmonary connection has been done in
some patients.13
This is the prototype of infiltrative heart disease with

increased wall thickness. Amyloidosis is a systemic disorder
characterized by interstitial deposition of linear, rigid, nonbranching, amyloid protein fibrils in multiple organs (e.g.
heart, liver, kidney, nerve). However, absence of extracardiac
amyloid does not exclude the presence of amyloid heart disease
Currently, 5 subtypes of amyloidosis have been recognized.
Cardiac involvement is common in all types of amyloidosis
and is the most frequent cause of morbidity and mortality.
Idiopathic Hypereosinophilic Syndrome

Idiopathic hypereosinophilic syndrome is characterized by
prolonged overproduction of eosinophils of unknown cause
in addition to specific organ damage due to eosinophil derived
protein toxicity. Its prognosis is correlated with development
of restrictive cardiomyopathy.
Usually a disease affecting men of temperate climate and
the diagnostic criteria for this disease are:
1. Blood eosinophila of 1,500/uL (1.5 10.9/L) or higher
lasting more than 6 months.
2. No parasitic, allergic or known cause of eosinophilia.
3. Signs or symptoms of cardiac, hematological, pulmonary,
neurologic and cutaneous involvement.
Cardiac involvement has 3 phases:
i. Endocardial damage and eosionophilic infiltration of
the myocardium.
ii. Thrombosis of damaged endocardium.
iii. Progressive fibrosis and scarring of the endocardium
leading to RCM.
Because this is an eosinophil mediated damage, aim is
to reduce peripheral blood eosinophila and reduce cardiac
infiltration. Corticosteroids and hydroxyurea are widely
used to reduce eosinophil count and have improved
survival in hypereosinophilic syndrome. In some patients
where a favorable response is not seen with these drugs,
interferon alpha has been used to reduce the eosinophil
count, but reduction of organ damage still remains
controversial. Case reports of high doses of interferonalpha causing a definite improvement in the disease are
present. 14
Churg-Strauss Syndrome
718
This is primarily a disease of young women with a history of

allergic rhinitis and bronchial asthma. The presence of four
of the following six criteria provides a diagnostic sensitivity
of 85 percent-asthma, eosinophilia greater than 10 percent
of white blood cells (WBC) differential count; mono or
polyneuropathy; non-fixed pulmonary infiltrate on chest
X-ray; paranasal sinus abnormality; biopsy containing a blood
vessel with extravascular eosinophils.15,16
Clinical Features
Amyloid deposits can be interstitial and widespread causing
RCM, or localized to:
i. Conduction tissues resulting in heart block or ventricular
arrhythmias.
ii. Cardiac valves causing valvular regurgitation.
iii. Pericardium producing constriction.
iv. Coronary arteries causing ischemia and
v. Pulmonary vasculature causing pulmonary hypertension.
Diagnostic studies: The cardiac silhouette can be normal
or enlarged on the chest X-ray.
Electrocardiography (ECG) typically shows decreased
voltage, a pseudoinfarction pattern and conduction disturbances predominate the clinical course.
M-mode echo reveals symmetrical wall thickness
involving the RV and LV, a small or normal LV cavity, variable
(often depressed) systolic function, left atrial enlargement
and small pericardial effusion. 2D Echo findings include
thickening of the ventricular myocardium with a speckled
appearance, the interatrial septum and the valves. LV wall
thickness is an important prognostic variable. In one study
patients with biopsy proven amyloidosis and wall thickness
of greater than 15 mm had a median survival of 0.4 years
whereas those with wall thickness less than 12 mm had a
survival of 2.4 years. Doppler characteristics of restrictive
physiology are DT less than 150 msec and an increased
E/A transmitral ratio, which are strong predictors of cardiac
death.17
The infiltrative pathology associated with amyloidosis
can be detected by tissue characterization using magnetic
resonance imaging (MRI). In a recent study, qualitative
global and subendocardial enhancement of the myocardium
associated with faster gadolinium clearance from the blood
pool was higher in patients with cardiac amyloidosis than
hypertensive controls. Treatment is often unrewarding.18
Immunosuppressive therapy with melphalan and prednisolone
is the established treatment regimen for primary amyloidosis.
Autologous stem cell infusion reduces the monoclonal
gammopathy, but has little effect on existing infiltrative
amyloid deposits. Orthotopic cardiac transplantation is
generally not recommended because of systemic nature of the
disease and possibility of recurrence in the transplant.19
Hemochromatosis
Sarcoidosis
Systemic granulomatous disease of unknown etiology. It
affects young adults between 10 to 40 years of age and presents
with bilateral hilar lymphadenopathy, reticular pulmonary
opacities, joints, eyes and skin involvement (erythema
nodosum). Cardiac involvement occurs in 5 percent and heart
failure can be due to restrictive or dilated cardiomyopathy and
has a progressive course.22
Restrictive cardiomyopathy in Children

Restrictive cardiomyopathy in children is far less common
(35%) than in adults. Median age of presentation is 9 years
(range 1 month16 years). The etiology tends to be different in
children than adults. While the latter often have RCM associated
with amyloidosis or varieties of endocardial fibroelastosis or
idiopathic or familial; in children, it is exposure to radiation
or anthracyclines. While in infants evaluation for congenital
metabolic syndromes like Gaucher or Hurler is required,
many pediatric cases remain idiopathic with upto a third being
50
It represents an iron overload disorder or iron storage disease

characterized by accumulation of excessive iron within the
cells of various internal organs. It may result from a genetic
defect (hereditary hemochromatosis) or from secondary causes
(e.g. multiple blood transfusions as in thalassemia major
(ineffective erythropoiesis). Iron accumulates in the heart,
pancreas, skin, liver, anterior pituitary, gonads. The myocardial
iron deposition usually produces dilated cardiomyopathy, but can
produce RCM, congestive heart failure, conduction abnormalities
like supraventricular and ventricular arrhythmias occur in onethird of patients. Bronze diabetes, hepatic dysfunction are
commonly associated. Echocardiography may show granular
sparkling, atrial enlargement, but these are not specific. Ultrasonic
analysis of integrated backscatter has been used experimentally
to detect changes in echocardiographic reflectivity of the
myocardium with iron deposits. Computed tomography (CT)
and MRI can demonstrate subclinical cardiac involvement and
tissue characterization can be possible with MRI. Liver biopsy is
the definitive test for iron overload. Endomyocardial biopsy can
be confirmatory and reveals stainable iron in the heart. It is more
useful to monitor the therapy.
Repeated phlebotomy is recommended for primary
hemochromatosis and chelating agent desferrioxamine is
beneficial in secondary hemochromatosis. Combinations
with oral active chelator deferiprone have been successful
in Europe. Deferasirox is a novel, orally active agent with
a single oral dosing. An extensive clinical trial has shown
its efficacy in adults and children and it has a safety profile,
which is manageable with regular clinical monitoring.20,21
Cardiac transplantation can be considered in selected cases.
familial. Familial phenotypes may include an associated skeletal

myopathy with or without conduction abnormalities. A proper
family history should be taken and a genetic screening should
be done. Children may present with reactive airway disease,
recurrent respiratory infections, breathlessness on exertion, or
more ominously with palpitations, syncope or sudden death.
Most of these are manifestations are of increased left-sided
filling pressures and decreased myocardial reserve. Exercise
stress testing, Holter monitoring and serial BNP measurements
may be useful to monitor the disease progression. Presence of
LVS3/LVS4 is a ubiquitous finding on physical examination.
ECG is universally abnormal with biatrial enlargement and
non-specific ST-T changes. Echocardiography will show
diagnostic features of RCM.23
Natural History
This is a progressive disease with a mortality rate of 50 percent
in 2 years from diagnosis.24,25 Children with RCM should be
followed closely for progression of pulmonary hypertension.
Those with elevated but reversible pulmonary hypertension are
at an urgent need for cardiac transplant, while those with mildly
elevated, pulmonary artery pressures may remain stable for
years and may not require urgent listing for transplant. Children
presenting with chest pain and syncope and ECG or Holter
evidence of ischemia are at risk of sudden cardiac death. The
use of beta blocker, implantable cardioverter defibrillator and
urgent listing of cardiac transplant is indicated for these patients.
Genetic cardiomyopathies in children

These can be classified into four categories, which are not
mutually exclusive.26
1. Inborn errors of metabolism.
2. Malformation syndromes.
3. Storage disease: Pompe disease, Gaucher disease, Fabry
disease.
4. Disorders of energy metabolism that produce suspected
cardiotoxic intermediary metabolites.
Diagnostic Approach
Patients with inborn errors of metabolism often have signs of
multiple organ dysfunction. The indications to screen for a
biochemical abnormality are onset of acute/chronic encephalopathy, hypotonia, growth retardation, failure to thrive, etc.
Patients with storage diseases who cannot degrade certain
structural components of cells typically develop coarse or
dysmorphic facial features, organomegaly, short stature or
chronic encephalopathy with a degenerative course. Skeletal
muscle weakness without encephalopathy is usually due to a
primary neuromuscular and rarely due to inborn error of metabolism. Here skeletal muscle weakness precedes the cardiac
involvement.
719
Metabolic Cardiomyopathies
Glycogen Storage Diseases
Pompe disease: An autosomal recessive disorder caused
by deficiency of lysosomal enzyme acid-alpha-glucosidase.
Classic infantile onset disease, characterized by cardiomegaly
and profound weakness, leads to death in the year of life
from cardiorespiratory failure. ECG is diagnostic with
short PR interval and gigantic QRS complexes. Reversal of
cardiomyopathy and improved motor function has been seen
in clinical trials of enzyme alpha-glucosidase replacement
therapy (ERT).27
Lysosomal Storage Disease

Gaucher disease: Most common inherited lysosomal
storage disorder caused by deficiency of glucocerebroside
in lysosomes of macrophages. Children present with
hepatosplenomegaly, anemia and thrombocytopenia. It is
divided into 3 types depending on the severity and onset of
neurological symptoms. Cardiac involvement includes RCM,
cardiomegaly, thickening and calcification of aortic and mitral
valves and annulus.
Fabry disease: X-linked recessive lysosomal storage
disease, hence a male predominant disease, usually mani
festing at 11 + 7 years.28,29 Rarely, female carriers are
affected, though the onset is in later age (average: 29 years)

and is milder. The disease causes severe renal, cardiac and
cerebrovascular disease. The onset is in childhood and
adolescence and includes intermittent pain in the extremities
(acroparesthesias), episodic Fabry crisis of acute pain lasting
for hours, characteristic skin lesions (angiokeratomas), corneal
opacities, hypohidrosis, mild proteinuria and gastrointestinal
manifestations. Cardiovascular manifestations include left
ventricular hypertrophy, mitral regurgitation (MR), ascending
aorta dilatation, coronary artery disease and secondary
conduction defects. By adulthood, end stage renal disease has
set in. Cerebrovascular manifestations include early stroke,
hemiparesis, diplopia, dysarthria, nystagmus, etc. Disease is
diagnosed by alpha-galactosidase A activity in plasma and
peripheral leukocytes.
Cardiac Troponin Mutations

Often found to be the causative factor in idiopathic RCM in
children. A strong family history is usually present.30
Differentiating Restrictive Cardiomyopathy

from Chronic Constrictive Pericarditis
The differentiation of restrictive and constrictive pericarditis
can be a difficult task at times and in the rare case has rarely
led to exploratory thoracotomies31-33 (Table 1).
Table 1
Difference between restrictive cardiomyopathy and constrictive pericarditis
720
Features
RCM31,32
CCP
Clinical history
Rare, familial Hx should be ruled out
Past Hx of tuberculosis, cardiac surgery, chest

trauma, mediastinal irradiation, epicardial
pacemaker implantation, purulent pericarditis
JVP
Raised, with prominent 'a' wave with sharp x and

y descents present in early stages and prominent
y descent only will persists in later stages due to
atrial dysfunction.
Raised there is prominent rapidly collapsing y

descent combined with a normally prominent x
descent results in M or W shaped pattern .
Kussmauls sign
Absent
Seen in 80%
Pulsus paradoxus
Absent
Present in 20%
Extra sounds in diastole
Loud diastolic filling sound S3 (late), rarely S4,

a low frequency sound
Pericardial knockhigh-frequency sound
Mitral or tricuspid
regurgitation
May have a murmur of mitral or tricuspid

insufficiency
Usually a quiet heart
Chest X-ray
Often have cardiomegaly with biatrial

enlargement, pulmonary vascular redistribution
Normal cardiac silhouette, presence of

pericardial calcification is pathognomonic
(2030%), tubercular infiltrates in the lung
fields
Contd...
50
Contd...
P waves reflect right/left atrial enlargement.
Atrioventricular or intraventricular conduction
defects are not unusual. LVH is more common,
e.g. LVH with T-wave inversion in an infant
with endocardial fibroelastosis
P waves reflect intra-atrial conduction delay.

Conduction defects are rare.
RVH and right axis deviation are more
common.
Features
RCM31,32
CCP
Brain natriuretic peptide levels
Increased
Normal
Interventricular septal
movement in diastole
Abrupt septal movement in early diastole seen

only occasionally
Abrupt septal movement (notch) in early

diastole in most cases. Double component of
septal dip in atrial systole-atrial systolic notch,
additional dip occurs in early to mid diastole
-early diastolic notch.
Atrial enlargement
Profound
Slight or moderate at the most
Respiratory variation in mitral

and tricuspid flow velocity
Occasional
Usually marked
Pulmonary vein flow
Blunted S/D ratio, prominent atrial reversal

No respiratory variation of D wave
S/D ratio = 1
Prominent inspiratory decrease of S and D
waves.
Tissue Doppler
Lateral and diastolic e velocities of < 8 cm/s

have been accepted as a cutoff for RCM.
W wave may also be reduced to < 5 cm/s
Usually normal (e' >8 cm/s) as myocardium is

not affected (mitral annular calcification may
reduce sensitivity)
Color M-mode
Slow flow propogation (< 45 cm/s)
Rapid flow propagation (> 100 cm/s)
Speckle tracking imaging
Endocardial dysfunction, hence abnormal

longitudinal mechanics
Pericardial constraint affects circumferential and

twist mechanics
Myocardial velocity gradients
Low due to uniform affection of myocardium
High due to preserved endocardial motion but

decreased epicardial motion
Ventricular diastolic pressure
Helpful if unequal diastolic pressures

(> 6 mm Hg)
Equalization of diastolic
pressures (< 5 mm Hg).
LV and RV diastolic pressure

gradient
The LV diastolic pressure will exceed RV

diastolic pressure by > 5 mm Hg if volume
infusion, leg elevation or exercise is done
Diastolic gradients rise equally or even

decrease with these stresses
Dip and plateau

waveform in the right
ventricular pressure waveform
End-diastolic pressure often less than onethird of the systolic pressure
End-diastolic pressure more than one-third of

the systolic pressure in most cases
Pulmonary hypertension
Often present
Usually not present
CT
Normal pericardium
Pericardial thickness > 4mm is abnormal (may

occur in the absence of constriction). Highly
sensitive to calcium
Cardiac MR
Late gadolium enhancement of myocardium

on MR is suggestive of myocardial infiltrative
disease.
May detect thickening, less sensitive to

calcium. Cine MR can detect septal bounce
and real-time Cine MR can detect respiratory
variation seen on echo
EM biopsy
Findings vary according to the etiology
Normal
Echocardiography
ECG
CCP = Constrictive pericarditis; CT = Computed tomography; ECG = Electrocardiography; EM = Electron microscopy; Hx = History; JVP = Jugular venous
pressure; LVH = Left ventricular hypertrophy; MR = Magnetic resonance; RCM = Restrictive cardiomyopathy; RVH = Right ventricular hypertrophy.
721
Conclusion
Restrictive cardiomyopathy is a relatively rare form of
cardiomyopathy in which diastolic function is abnormal
due to the stiff ventricles. The most common cause of RCM
in adults is amyloidosis, whereas in children, the cause is
unknown. At present, medical therapy remains supportive
and appears to be ineffective and the development of
pulmonary hypertension is common. The prognosis for
RCM in infants and children is very poor and cardiac
transplantation is recommended soon after the diagnosis is
made.
In this sick room, ten cents worth of human understanding
equals ten dollars worth of medical science.
Martin H Fischer
References
722
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C hapter
51
Hypertrophic Cardiomyopathy
Krishnan MN
Introduction
Hypertrophic cardiomyopathy (HCM), the most common of
genetically mediated heart muscle disorder, characterized by
thickened non-dilated left ventricle (in the absence of other
cardiac or systemic conditions) and myocyte disarray.1-5
In about two-thirds of the cases, dynamic left ventricular
(LV) obstruction of varying degrees exists. Although a
relatively benign condition, it can cause atrial and ventricular
arrhythmias, sudden cardiac death (SCD) or progressive LV
dilatation leading to congestive heart failure. It is characterized
by variable penetrance, heterogeneous clinical expression and
variable natural history. It is the commonest cause of sudden
cardiac death in the young.
Although the disease entity was reported by French
pathologists in 19th century, the first contemporary reports
came from Russell Brocks, a British cardiac surgeon in 1957
and Donald Teare, a pathologist from London in 1958.6 Teare
described the autopsy findings of nine young patients who died
suddenly in a paper entitled Asymmetrical Hypertrophy of the
Heart in Young Adults.7 In the 60s, Goodwin laid foundation
to clinical details of the condition and Braunwald elucidated
the concept of dynamic obstruction of the LV outflow tract
(LVOT). Many names have been ascribed to this condition;
since LV outflow obstruction is not a uniform feature,
restrictive names like idiopathic hypertrophic subaortic
stenosis (IHSS) and muscular subaortic stenosis (MSS) have
been largely abandoned. Hypertrophic cardiomyopathy is
now accepted as the all inclusive name, and hypertrophic
obstructive cardiomyopathy (HOCM) in cases with LV
outflow obstruction.
Epidemiological studies have estimated a prevalence of
the HCM phenotype at 0.2 percent or 1 in 500 live births;8
considering a much lower occurrence of the disease in
cardiology practice, it can be inferred that most affected
individuals are asymptomatic and do not come to clinical
attention. The overall annual mortality of HCM has been
estimated to be 1 percent although somewhat higher in
children (~2%).9 The deaths are almost exclusively sudden.

About 3 percent of patients with HCM progress to a dilated
phase called end-stage (ES) HCM associated with progressive
systolic dysfunction ((LVEF) < 0.5).9 These patients show
progressive cavity dilatation, LV wall thinning and diffuse
gadolinium enhancement on magnetic resonance imaging
indicating extensive fibrosis. They often present with atrial
fibrillation (AF) or congestive heart failure (HF). Progression
to intractable HF and sudden cardic death (SCD) are frequent
(10% per year). The most reliable risk marker of progression
to ES is family history of ES HCM.
Genetics10,11
Hypertrophic cardiomyopathy is a genetic disorder of
sarcomeric proteins of cardiomyocyte. It is transmitted as
Mendelian dominant pattern of inheritance with variable
penetrance. The seminal report of the R403Q mutation in
MYH7 in a family with HCM by Seidmans group in 1990
unraveled the genetic enigma of HCM.11 The discovery led
subsequently to identification of more than 150 mutations of
11 sarcomeric proteins as causing the disease (Box 1). About
80 percent of the cases are accounted by b-myosin heavy
chain and myosin-binding protein C.
Box 1: Genetic mutations in HCM

Disease of sarcomeric protein. Dominant inheritance with
variable penetrance:
1. Alpha and beta-myosin heavy chain.
2. Myosin-binding protein C.
3. Troponin I and T.
4. Alpha tropomyosin.
5. Myosin light chain (essential and regulatory).
6. Titin.
7. Alpha-cardiac actin.
8. Muscle LIM protein (MLP).
724
Non-sarcomere protein mutations like Fabry disease,

PRKAG2, lysosome-associated membrane protein 2 (LAMP2)
cardiomyopathies mimic HCM clinically.
Morphology
Left ventricular hypertrophy in HCM is diverse in pattern
including dissimilar phenotypes in relatives. Wall thickness
of LV can range from normal to massive. Any degree of
or pattern of hypertrophy is compatible with clinical and/
or genetic diagnosis of HCM. Typically the hypertrophy is
asymmetric and transition to normal abrupt. Non-contiguous
patterns of hypertrophy and extension to right ventricle
are common. Hypertrophy of LV is frequently diffuse with
involvement of septum and free wall; however in sizable
minority it may be confined to septum only (asymmetric septal
hypertrophy) or apical regions (apical HCM) characterized
by spade deformity of LV cavity and deep T inversions in
electrocardiogram. There is no evidence to suggest that any
specific pattern of hypertrophy correlates with outcome. The
hypertrophy commonly develops over time with dramatic
increase in thickness and distribution through adolescence.
Structural abnormalities of the mitral valve apparatus
represent a primary morphologic alteration in HCM; the valve
may be twice as much as normal due to elongation of both
leaflets. In a small subset of patients, anomalous insertion of
anterolateral papillary muscle to anterior mitral leaflet causes
midventricular obstruction.
In HCM the cardiomyocytes show abnormal shape and size
with grossly disorganized patterns of oblique and perpendicular
angles (myocyte disarray) and replacement fibrosis. Abnormal
intramural coronary arteries with thickening of walls and
narrowing of lumen are seen in 80 percent of cases, leading
to ischemia, necrosis and replacement fibrosis. These areas
of fibrosis act as a substrate for ventricular arrhythmias and
sudden death.
ventricular volume or decrease systolic arterial pressure

augment the gradient and vice versa. Accordingly, exercise,
isoproterenol or dobutamine infusion increases the gradient;
beta-blocking drugs reduce it. Valsalva maneuver, standing up
from squatting, blood loss or dehydration by reducing volume
of LV increases the gradient; isometric handgrip, squatting
or phenylephrine administration reduces the obstruction by
elevating systolic blood pressure.
Diastolic Dysfunction
Abnormal filling of LV due to impaired relaxation is present
in vast majority of patients with HCM and contributes to
effort dyspnea, although parameters of diastolic dysfunction
by echocardiography do not predict symptoms, prognosis or
therapeutic response. Diastolic dysfunction is not directly
related to severity of hypertrophy. The abnormal diastolic
properties are consequent to hypertrophy, replacement fibrosis
and myocellular disarray and is the fundamental mechanism
for HF symptoms in HCM.
Autonomic Dysfunction
During exercise, approximately 25 percent of patients with HCM
have an abnormal blood pressure response defined by either a
failure of systolic blood pressure to rise by 20 mm Hg or a fall in
systolic blood pressure. The presence of this finding is associated
with a poorer prognosis. The inability to augment and sustain
systolic blood pressure during exercise is caused by the dynamic
left ventricular outflow tract obstruction (LVOTO) in the wake
of systemic vasodilatation during exercise. It is speculated that
autonomic dysregulation is present in patients with HCM and that
the fall in BP associated with bradycardia may be an abnormal
reflex response to obstruction.
Clinical Features12,13
Pathophysiology
Symptoms
Left Ventricular Outflow Tract Obstruction
Symptoms of HCM include dyspnea on effort, fatigue, angina

and syncope/presyncope. Dyspnea is predominantly due to
diastolic dysfunction and may be compounded by LVOTO.
Severity of symptoms often varies day-by-day. Symptoms are
more after a large meal or alcohol ingestion, which increases
the gradient. Angina occurs due to myocardial ischemia on
exertion. Syncope usually occurs during exertion although it
may present itself on sudden standing from supine posture.
The syncope is explained by several mechanisms including
arrhythmias and increase in outflow obstruction. CHF is rarely
seen in HCM in normal sinus rhythm, but it may be seen with
severe obstruction to outflow, severe systolic or diastolic
dysfunction or advent of AF. History of palpitations may also
be there during tachyarrhythmia and may be associated with
syncope.
About 70 percent of hospital-based patients with HCM have

LV outflow tract obstruction (gradient 30mmHg). In most
patients the obstruction is due to systolic anterior movement
(SAM) of the mitral valve and midsystolic contact with
septum caused by drag effect on the anterior mitral leaflet. The
magnitude of the gradient is directly related to the duration of
the contact. Mitral regurgitation (MR) may occur secondary
to the SAM and is usually directed posteriorly. The outflow
gradient imposes increased wall stress and oxygen demand
and is a predictor of progression to HF. However, there is no
consistent relation between the magnitude of gradient and risk
of sudden death. Outflow gradient is dynamic with spontaneous
variability. Interventions that increase contractility, reduce
Physical Findings
Table 1
Clinical parameter HOCM
Valvar aortic stenosis
Carotid pulse
Jerky/bisferiens
Delayed low volume,

carotid shudder
JVP
Prominent a
wave, if RV
involvement
(Broadys effect)
Prominent a wave
may be present
(Bernheim effect)
Apex beat
Double or triple,
forceful
Heaving, S4 may be
palpable
Thrill
Rare
Common
S2
Single or reverse
Single or reverse
Ejection click
No
Commonly present
Outflow murmur
3rd left space; no

carotid radiation
2nd right space;

radiates to carotids
MR
Common
No
51
Left ventricular involvement is reflected by a variably displaced

and forceful LV impulse. Patients with non-obstructive HCM
have no murmur and manifest only as forceful apical impulse
and palpable and audible fourth heart sound.
In patients with significant obstruction, the carotid pulse is
usually flicking or jerky and at times bisferiens character may
be present. Apex is variably displaced and forceful. Sometimes
a double systolic impulse may be felt over the apex. A fourth
heart sound may also be palpable causing a triple ripple. The
first heart sound is usually normal. The second heart sound may
be normal, fused or paradoxically split with increasing severity
of obstruction. A fourth heart sound is usually audible over the
apex. The mid systolic murmur of LVOTO is usually 2/6 or
3/6, best audible over the 3rd left intercostal space; it is seldom
associated with a thrill. There may be, in addition, an apical
systolic murmur of mitral regurgitation. Patients with midventricular obstruction may also have an apical systolic murmur
although it is usually softer than with subaortic obstruction. There
may be at times a very distinctive long diastolic murmur caused
by mid-ventricular narrowing and asymmetric relaxation. A
mid systolic clicking sound of mitral leaflet septal contact may
be rarely heard. The murmur of subaortic obstruction varies
significantly with maneuvers. Valsalva maneuver, standing
from squatting position or amyl nitrite inhalation increases the
gradient and the intensity of murmur; squatting or isometric
handgrip decreases the gradient and murmur. Postectopic
beat causes an increase in the obstruction and murmur, while
being associated with a smaller pulse volume as a result of
increase in contractility due to postextrasystolic potentiation.
The differential physical findings in HCM versus valvar aortic
stenosis are depicted in Table 1.
Differences in the physical findings of HOCM and valve aortic

stenosis
HOCM = Hypertrophic obstructive cardiomyopathy; JVP = Jugular venous

pressure
DIAGNOSIS/INVESTIGATIONS
Electrocardiography14,15
The 12-lead electrocardiogram (ECG) is abnormal in 90
percent of patients of HCM (Figure 1). The most common
abnormalities include tall R waves, deep narrow Q waves, ST-T
abnormalities and left atrial enlargement. Sometimes the ECG
pattern is very bizarre. The deep Q waves may at times
mimic myocardial infarction. About 25 percent of cases have
left anterior hemiblock. Deep negative T in lateral leads is
Figure 1: 12 lead electrocardigram in a 7-year-old with hypertrophic cardiomyopathy with both left and right ventricular outflow tract
obstruction showing both left and right ventricular hypertrophy.
725
characteristic of apical form of HCM. Normal ECG is seen

in five percent of cases and predict a favorable cardiovascular
course, but is not predictive of SCD. The ECG does not
distinguish between obstructive and non-obstructive forms of
HCM.
Echocardiography16
Left Ventricular Hypertrophy
A characteristic feature of HCM is hypertrophy of LV
septum disproportionate to free wall hypertrophy. Septal
thickness to posterior wall thickness ratio of 1.5 is
characteristic (Figures 2A to C). Although asymmetric
septal hypertrophy (ASH) is very characteristic of HCM,
other patterns like diffuse hypertrophy, disproportionate
posterior wall hypertrophy and apical hypertrophy are not
uncommon. Anterior septal hypertrophy is seen in majority
of patients and in 40 percent cases more than one segment
is affected. The LV is not dilated and systolic cavity size
is markedly reduced. Characteristically the septum fails
to thicken during systole. Left ventricular hypertrophy
(LVH), even asymmetric is not specific for HCM and can
be found in several other conditions (Box 2 and Box 3).
Various indices for assessment of LVH have been developed
Box 2: Conditions causing left ventricular hypertrophy

or thickened interventricular septum
1.
2.
3.
4.
5.
6.
7.
Sigmoid septum.
Hypertensive hypertrophy.
Atheletes heart.
Aortic stenosis.
Infants of diabetic mothers.
Tumors of septum.
Layered clot over the septum.
Box 3: Genetic diseases associated

with left ventricular hypertrophy
1. Fabry disease.
2. Friedreichs ataxia.
3. Noonan syndrome.
4. Pompe disease.
5. PRKAG2 mutation.
6. Lysosome-associated membrane proteins-2 (LAMP2)
cardiomyopathy (Danon disease).
(Table 2). Presence of wall thickness 30 mm is seen in

about 10 percent of patients and correlated with higher risk
of SCD.
C
726
Figures 2A to C: Echocardiogram in parasternal long-axis view: A. Shows hypertrophy of left ventricular septum disproportionate to free wall
hypertrophy; B. Septal thickness to posterior wall thickness ratio of 1.5 is characteristic; C. Measurement of thickness of interventricular septum
and posterior wall in short-axis view. Ao = Aorta; LA = Left atrium; LV = Left ventricle; PW = Posterior wall; RV = Right ventricle; VS = Ventricular
septum.
Table 2
Indices for echocardiographic assessment of left ventricular hypertrophy by echocardiography

Description
Score
Thickness of basal septum in mm
1519 : 1
2024 : 2
2529 : 3
30 : 4
Spiritos score
Left ventricular hypertrophy extent
1 segmentmild
2 segmentsmoderate
3 or moresevere
Spirito-Maron index
Left ventricular hypertrophy

extent and severity
Sum of maximum thickness of all 4

segments between mitral leaflet tip and
papillary muscle in short-axis view
Maximal wall thickness
Maximum thickness of any wall segment
30 mm
The degree of LVH varies throughout life. Although the

gross phenotypic expression and clinical profile of HCM
may occasionally be identified in infants and young children,
marked LVH is rarely documented during the 1st year of
life. Rapid changes in LV morphology often occur during
adolescence, when LV wall thickness may increase rapidly.
Genetic studies among large families demonstrated that
morphological LVH reaches a plateau at the third decade of
life in myosin heavy-chain and in tropomyosin mutations,
whereas it increases continuously though life in cardiac
myosin-binding protein C mutations.
Left Ventricular Outflow Obstruction

A common accompaniment to hypertrophy in HCM is
dynamic obstruction of the LVOT. Up to one-third of patients
with HCM will have obstruction under basal (resting)
conditions (defined as gradients 30 mm Hg). Another onethird or more of patients will have labile, physiologically
provoked gradients (< 30 mm Hg at rest and 30 mm Hg
with physiologic provocation). The final one- third of patients
will have the non-obstructive form of HCM (gradients < 30
mm Hg at rest and with provocation). The echocardiographic
hallmark of obstruction is SAM of the mitral valve (Figure
3A). The anterior mitral leaflet moves anteriorly toward
the interventricular septum (IVS) shortly after the onset
of systole and returns to its normal position just before the
onset of diastole. The finding is best seen with M-mode
echocardiography. There is close correlation between the
severity of obstruction and the duration of mitral leaflet
septal contact. The gradient is given by the equation:
LVOT gradient = (Septal contact time/Time from onset of
SAM to septal contact) 25 + 25 mm Hg.
Systolic anterior motion of mitral valve and obstruction are
classically dynamic and may not be always present at rest, but
may appear on provocation such as Valsalva maneuver, amyl
nitrite inhalation or intravenous isoproterenol.
Index
Wigle
51
Systolic anterior motion of the mitral valve may also

occur in conditions other than HCM (pseudo SAM). Mitral
annulus is an integral part of LV; motion exhibited by mitral
valve may be related to motion of mitral annulus and/or left
ventricular wall. Any condition in which posterior LV wall
motion is exaggerated can lead to SAM. In true SAM the peak
leaflet anterior motion is complete before the peak posterior
wall movement; in pseudo SAM the peak of AML movement
occurs after the peak of PW movement. SAM may be produced
by various parts of the mitral valve apparatus like anterior
mitral leaflet alone, anterior and posterior leaflets or chordae
alone. SAM is thought to be produced by venturi effect of
blood flowing across the hypertrophied septum or malposition
of papillary muscles. The aortic valve motion may show a mid
systolic closure of the anterior leaflet indicating alteration in
aortic blood flow (Figure 3B).
Spectral Doppler echocardiography helps in determining
the presence and severity of LVOTO. The classic continuous
wave Doppler recording shows relatively slow increase in
velocity in early systole and peaks in late systole producing
a dagger-shaped velocity envelope (Figure 4). Color Doppler
helps to identify the location of the obstruction and also the
presence and severity of MR (Figure 5). The jet of MR is
directed laterally and posteriorly and predominates during mid
and late systole. An anteriorly directed jet should suggest an
intrinsic abnormality of the mitral valve. The mitral diastolic
filling pattern is usually indicative of impaired relaxation with
E/A reversal or restrictive filling pattern. In mid ventricular
obstruction blood may actually flow from apex to the body
of the ventricle during diastole producing a high velocity
diastolic flow.
Hemodynamic Evaluation and Ventriculography17

Pull-back tracings from left ventricle will show gradient at
the LVOT in those with resting obstruction. The aortic tracing
may show spike and dome pattern in those with significant
727
B
Figures 3A and B: M mode in echocardiogram showing: A. SAM (arrow); B. Aortic valve presystolic closure (arrow)
728
Figure 4: Doppler in left ventricular outflow tract showing dagger

shaped velocity profile
Figure 5: Color Doppler showing left ventricular outflow tract (LVOT)

turbulence (arrow) and mitral regurgitation (MR). Ao = Aorta; LA = Left
atrium; LV = Left ventricle.
gradients; this represents the rapid early systolic ejection

followed by slowing of the ejection beyond midsystole
in the wake of progressive obstruction in the mid systole
characteristic of HOCM (Figure 6). Postextrasystolic aortic
tracing shows decrease systolic pressure and pulse pressure
in the beat after the pause with an increase in the LV pressure
and the gradient. During the long diastole, although increase
in the LV volumes tend to reduce the obstruction, the
postextrasystolic increase in contractility (postextrasystolic
potentiation) over-rides this effect and causes greater obstruc
tion (Brockenbrough-Braunwald-Morrow sign) (Figure 7).18
The LV and right ventricular end diastolic pressures are
usually elevated, so also the left atrial (LA) mean pressure. Mild
elevation of PA pressure may be present. Tall V waves in the
pulmonary artery wedge pressure tracing represent significant
MR or elevated LA pressures. Left ventriculography will
show hypertrophied ventricle with near obliteration of cavity

in systole, SAM and MR.
Cardiac Magnetic Resonance Imaging19-21

In the last few years, cardiovascular magnetic resonance
(CMR) has emerged not only as a diagnostic tool, but also as
a study with prognostic valve, by characterizing myocardial
fibrosis with great accuracy in HCM patients. Additionally,
CMR identifies the type of hypertrophy, analyses the
ventricular function, estimates the intraventricular gradient
and allows the determination of differential diagnosis.
Magnetic resonance is more sensitive and accurate to assess
hypertrophy and LV mass than echocardiography. European
and American Societies of Cardiology recently accepted
CMR as the primary modality of imaging in suspected HCM.
51
Figure 6: Left ventricle (LV) and aortic tracing showing gradient and
spike and dome aortic tracing
respect any specific coronary territory and in the majority

of HCM subjects is found mostly at the junction between
the interventricular septum and right ventricular free wall
conforming to necropsy studies. Two patterns of LGE have
been described: a localized, homogeneous confluent pattern
denoting better prognosis and a more diffuse, patchy and
heterogeneous pattern, usually associated with more than 2
factors for SCD and a worse prognosis.
Differentiating HCM from athletes heart is important as
competitive sports in patients with HCM carries high risk of
SCD.22 HCM is the single most common disease causally
linked to athletic field deaths, accounting for about one-third
of cases.
In HCM the septal thickness in usually >15 mm; the range
between 13 to 15 mm represents a gray zone. Ventricular
septal thickness of 13 to 15 mm can be seen in about 2 percent
of highly trained male athletes. The major differentiating
points between HCM and athletes heart is given in Table 3.
A 24 hours Holter recording is recommended in HCM as
an initial evaluation or when the patient develops palpitation
or giddiness.23,24
Presence of non-sustained ventricular arrhythmias is a risk
factor for SCD and identifies patients who may be candidates
for implantable cardiac defibrillator (ICD). The test may be
repeated every year. Invasive electrophysiologic testing has
little value in assessing the risk of SCD.
Treadmill ECG may be useful for assessing risk as
abnormal blood pressure response like failure for SBP to rise
> 20 mm or drop in SBP by > 20 mm portends high risk of
SCD.25,26
Exercise test may be done in patients with HCM
1. To assess the functional capacity,
2. To assess the risk of SCD and
Table 3
Differential features between HCM and Athletes heart
Figure 7: Brockenbrough signshows increase in left ventricle (LV)

systolic pressure, a decrease in ascending aortic systolic pressure
and increase in the gradient between the LV and ascending aorta in
the post-ectopic beat. Ao = Aorta; LA = Left atrium; VPC = ventricular
premature complex.
One of the major contributions of CMR, besides the

anatomical and functional data and geometric indices, is the
delineation of myocardial fibrosis in HCM, which follows
specific patterns. The presence of myocardial fibrosis
increases the diagnostic accuracy and insight on the prognosis.
About 80 percent of patients with HCM have been detected
to have myocardial fibrosis by late gadolinium enhancement
(LGE). The myocardial hyperenhancement in HCM does not
Parameter
HCM
Athletes heart
Family history
May be present
Absent
Reversibilty once
stopping excercise
Not reversible
Reversible
LVIDD
< 45 mm
> 55 mm common
Involvement
Asymmetric septal
hypertrophy
Diffuse hypertrophy
Septal thickness
Thickness >13 mm
Almost never > 11

mm in females and
> 15 in males
SAM
Yes
Never
Abnormal LV filling
pattern
Yes
No
MRI
LGE
Normal
LGE = Late gadolinium enhancement; LVIDD = Left ventricular internal

dimension in diastole; MRI = Magnetic resonance imaging; SAM = Systolic
anterior motion.
729
3. To provoke gradients in those who have resting gradient

<30 mm Hg.
Invasive coronary angiography is indicated in patients
who complain of angina-like chest pain with intermediate
likelihood for coronary artery disease (CAD), prior to surgical
septal myectomy (SSM) or percutaneous transluminal septal
myocardial ablation (PTSMA). Assessment of coronary
anatomy with computed tomographic angiography is
reasonable for patients with HCM with chest discomfort and
a low likelihood of CAD to assess for possible concomitant
CAD. Assessment of ischemia or perfusion abnormalities
suggestive of CAD with single photon emission computed
tomography or positron emission tomography myocardial
perfusion imaging (because of excellent negative predictive
value), is reasonable in patients with HCM with chest
discomfort and a low likelihood of CAD to rule out
concomitant CAD.
Risk Stratification27,28
Assessment of risk of SCD is an integral part of the patients
with HCM. Table 4 outlines the major risk factors for SCD in
HCM.
Several studies investigated the risk of SCD with
combination of major risk factors. The combination of history
of syncope with family history is a significant risk factor for
SCD. Patients with 2 or more risk factors have an estimated
annual SCD risk of 4 to 5 percent.
A minority of HCM patients have increased risk for SCD
with a rate of above 1 percent per year. Other than cardiac arrest,
Table 4
Risk factors for sudden cardiac death in hypertrophic

cardiomyopathy
Parameter
Definition
1. A
borted sudden cardiac
arrest
Documented cardiac arrest

or VF
2. Spontaneous sustained VT
VT lasting for > 30 s or

requiring cardioversion
3. Family history of premature SCD is first degree relatives

SCD
less than 40 years
730
4. Unexplained syncope
Syncope without a known

causal factor, 2 episodes in
the previous year
5. Nonsustained VT on Holter
> 3 consecutive ventricular

complexes at a rate of > 120
beats per minute
6. Extreme LV wall thickness
Maximum LV wall thickness

more than or equal to 30 mm
7. A
bnormal exercise BP
response
Failure to increase by at least

20 mm or a drop of 20 mm
during effort
BP = Blood pressure; LV = Left ventricle; SCD = Sudden cardiac death; VF

= Ventricular fibrillation; VT = Ventricular tachycardia.
each of the HCM risk factors has a low positive predictive

values (approx 1020%) and modest negative predictive
value (approx 8595%). Multiple risk markers in individual
patients may not indicate higher risk; the vast majority of
patients with more than one risk marker will not experience
SCD.29 The number of risk factors did not correlate with the
rate of subsequent appropriate ICD discharges. Data suggest
that the presence of a single risk marker may be sufficient
to warrant ICD placement in most patients; however these
decisions have to be individualized with regard to age,
strength of the risk factor and the risk benefit of lifelong ICD
therapy.
The usefulness of the following potential SCD risk
modifiers is unclear but might be considered in selected
patients with HCM for whom risk remains borderline after
documentation of conventional risk factors:
a. CMR imaging with LGE.
b. Double and compound mutations (i.e. > 1).
c. Marked LVOT obstruction. Invasive electrophysiologic
testing as routine SCD risk stratification for patients with
HCM should not be performed.
Treatment
Treatment strategies in HCM are tailored along:
1. Control of symptoms.
2. Prevention of sudden cardiac death.
3. Prevention and management of atrial fibrillation.
4. Management of dilated phase of HCM.
A large proportion of patients presenting with HCM are
asymptomatic and can achieve a normal life expectancy. It
is essential to educate these patients and their families about
the disease process and to screen the first degree relatives.
They should be advised to avoid strenuous physical activity
or competitive athletics. Risk stratification of SCD should be
performed in all patients irrespective of symptoms. Hydration
and avoidance of situations where vasodilatation may occur
are important in patients with resting or provocable LVOT obstruction. High dose diuretics and vasodilators and
inotropes should be avoided.
Beta-blockers are the mainstay of pharmacologic therapy
and the first line agents because of their negative inotropic
effects and ability to attenuate adrenergic induced tachycardia.
They act by reducing LVOT obstruction and myocardial
ischemia and improving diastolic filling of LV.
In patients, who cannot tolerate beta blockers or
unresponsive to beta blockers, non-dihydropyridines calcium
channel blockers (CCB) may provide symptomatic relief by
their negative inotropic and rate lowering effects. Verapamil
or diltiazem should be cautiously given in patients with
severe obstruction, elevated LA pressure and low systemic
blood pressure because a drop in the blood pressure may
trigger severe outflow obstruction and precipitate pulmonary
edema. Dihydropyridine class of CCB should not be used in
obstructive HCM.
Septal Reduction Therapy

Septal reduction therapy (SRT) involves invasive methods of
reducing the septal thickness viz. SSM and PTSMA. Septal
reduction therapy is indicated in eligible (those with septal
hypertrophy and SAM) patients with LVOTO (gradient basal
> 30 mm Hg and/or provocable > 50 mm Hg) with drugrefractory symptoms.
Surgical Septal Myectomy30

The first choice of septal reduction therapy in HCM is SSM.
Surgical septal myectomy, when performed in experienced
centers, can be beneficial for the majority of eligible patients
with HCM with severe drug-refractory symptoms and LVOT
obstruction. In the hands of experienced operators the success
rate is around 95 percent, surgical mortality < 1 percent and
major complications 2 to 3 percent. A rectangular trough
of septum from below the aortic valve to the distal septum
beyond the septal contact (or up to the insertion of papillary
muscle in extended myectomy) is removed. Mitral valve
repair, in addition to myectomy, may be most appropriate for

selected patients with severe MR caused by primary valvular
disease. Septal myectomy is established as a proven approach
for reversing the consequences of HF by providing permanent
amelioration of obstruction (and relief of MR) and restoring
functional capacity and an acceptable quality of life at any
age. The procedure results in excellent long-term survival of
90 percent at 10 years, superior to non-operated patients, and
reduces the incidence of SCD.
Percutaneous Transluminal Septal

Myocardial Ablation31
Alcohol septal ablation is a catheter-based procedure in
which 96 percent alcohol is injected through a major septal
artery supplying the basal hypertrophied septum (Figures 8A
and B). The eligibility is same as SSM; however, at present
the procedure is reserved for those who are poor surgical
candidates or those who refuse surgery. Ideal PTSMA
candidate is subaortic SAM-related LVOT obstruction
SAM-related MR with basal septum thickness > 18 mm,
but < 30 mm; while those with marked elongation of AML,
severe MR due to MV abnormalities, markedly thick and
fibrotic septum, abnormal insertion of papillary muscles are
poor candidates for the procedure. After measurement of basal
gradient, the septal branch is wired; the distribution area of
the septal branch is ascertained using myocardial contrast
echocardiography using Levovist through an over the wire
balloon in the septal branch; the balloon is inflated and a small
quantity of contrast is injected to rule out back-leak; 1 to 2 mL
of alcohol is then slowly injected keeping the balloon inflation.
Echocardiographic control is extremely important as the septal
branches have highly variable area of supply; misplacement
of alcohol into wrong branch could not only be ineffective,
but could cause remote infarction with serious complications.
Figures 8A and B: Coronary angiogram before (A) and after (B) Percutaneous transluminal septal myocardial ablation (PTSMA)
51
Those who remain symptomatic despite use of beta

blockers and CCB alone or in combination may benefit from
disopyramide due to its negative inotropic effect. The use of
disopyramide alone without beta blockers or verapamil is
potentially harmful in the treatment of HCM with AF because
it may enhance atrioventricular conduction and increase the
ventricular rate. Oral diuretics in patients with non-obstructive
HCM may be administered when dyspnea persists despite the
use of beta blockers and/or verapamil.
The use of angiotensin converting enzyme inhibitors or
receptor blockers in HCM with preserved systolic function is
not well established and these drugs should be used cautiously
in patients with LVOT obstruction.
731
732
The area of myocardium undergoes chemical necrosis and

later scarring. A final angiography control excludes left
coronary artery damage and verifies septal branch occlusion
while hemodynamic measurements confirm the immediate
result of septal ablation. Contraindications include the failure
of myocardial contrast echocardiography to identify a target
septal branch, the echocardiographic contrast opacification of
any cardiac structure other than the target septal area, or insecure
balloon positioning that bears the risk of alcohol reflux during
injection. Furthermore, alcohol injection should be avoided
if there is any suspicion of collateral flow that could lead to
infarction far from the target septal area. About 90 percent of
patients will have significant reduction in the gradient, which
will continue to decrease over time. Symptomatic improvement
parallels the hemodynamic changes.
Complications of PTSMA include bundle branch block,
complete heart block (CHB) and reflux of alcohol into left
anterior descending artery. Right bundle branch block
occurs in about 50 percent of patients after septal ablation.
In approximately half of patients undergoing alcohol septal
ablation, temporary complete atrioventricular block occurs
during the procedure. The incidence of persistent CHB used to
be > 10 percent in the earlier series of PTSMA; however with
myocardial contrast echocardiographic control and limited
use of alcohol (< 2 mL), the incidence has come down to <
5 percent almost equaling that of SSM. The block usually
occurs within 48 hours of the procedure although it may be as
late as 10 days; patients with pre-existing left bundle branch
block are more prone to CHB. Approximately 5 percent of
patients have sustained ventricular tachyarrhythmia during
hospitalization. In-hospital mortality is now < 1.5 percent.
A most feared complication is iatrogenic reflux of alcohol
into the left anterior descending artery, causing vessel
occlusion and anterior wall myocardial infarction. This can be
avoided, however, by the routine use of a slightly oversized
balloon compared to the septal artery diameter, and by
keeping the balloon inflated for at least 10 minutes after the
last alcohol injection.
Long-term results of PTSMA are encouraging with
sustained abolition of gradient and persistent symptomatic
improvement. Recently published data from a larger cohort
of 347 patients has shown 94 percent survival after 5 years
and 87 percent after 10 years, which is comparable to the
results of large myectomy studies. Many studies have raised
the concern over the occurrence of ventricular tachyarrhythmia
and SCD among patients who have undergone PTSMA. The
presence of a scar in the septum may act as a substrate for
arrhythmias. In a selected subset of 42 patients with an ICD
or permanent pacemaker that enabled detection of devicestored electrograms, the annualized event rate (ventricular
tachycardia, ventricular fibrillation, and/or appropriate ICD
discharge) was 4.9 percent per year.32 Similarly, the multicenter
HCM ICD registry of 506 patients demonstrated that the rate of
appropriate ICD therapy among ablation patients with primary
prevention ICDs was 3 to 4 times more frequent than in other

patients in that registry (10.3% per year compared with 2.6%
per year).33 Alternatively, incidence of sustained ventricular
arrhythmias after surgical myectomy is extremely low (0.2
0.9% per year).
Dual Chamber Pacing34

A small number of patients with HOCM may draw symptomatic
benefit from dual chamber pacing. Pacing the right ventricular
apex with maintenance of atrioventricular synchrony results
in a decrease in the LVOT gradient and improvement of
symptoms in a subset of patients. The exact mechanism of
improvement with pacing remains unknown; the decrease in
gradient may be caused by alteration in the timing of septal
contraction. Although there was an initial enthusiasm for
dual-chamber pacing as a primary treatment for patients with
obstructive HCM, subsequent data demonstrated long-lasting
beneficial results in only a small minority of patients, whereas
most perceived improvement was judged to be placebo effect.
Prevention of Sudden Cardiac Death35,36

The only treatment modality, which has been proven to
reduce SCD in HCM is implantation of ICD. The decision
to place an ICD should include application of strength of
evidence, benefits, risks and individual clinical judgment. The
indications for ICD implantation is outlined in Table 5.
The usefulness of ICD is uncertain in HCM with isolated
non-sustained ventricular tachycardia (NSVT) or abnormal
blood pressure response with exercise. The complications
of ICD in HCM include inappropriate discharge (25%), lead
complications (613%), device infection (45%) and bleeding
and thrombotic complications (23%). Dual chamber ICDs are
reasonable for patients with elevated resting outflow gradient
(> 50 mm Hg) and significant heart failure symptoms.
Management of Atrial Fibrillation37

Atrial fibrillation in patients with HCM usually causes
hemodynamic deterioration due to fast ventricular rate and
withdrawal of atrial booster action. Ventricular rate control can be
achieved with high doses of beta blockers or non-dihydropyridine
CCB. Disopyramide and amiodarone can be given to prevent the
recurrences in paroxysmal AF. Radio frequency ablation may
be considered in those who have refractory symptoms or who
are unable to take antiarrythmic drugs. Maze procedure with
closure of LA appendage is reasonable either during SSM or as
an isolated procedure in selected patients.
Physical Activity38
It may be reasonable for patients with HCM to indulge in
low-intensity sports or recreational activities. They should
Table 5
Indications for implantable cardiac defibrillator in hypertrophic cardiomyopathy
1. P
rior documented cardiac arrest, ventricular fibrillation or
hemodynamically significant ventricular tachycardia
Probable:
1. S
udden death presumably caused by hypertrophic cardiomyopathy
in one or more first degree relatives
2. A maximum left ventricle wall thickness more than or equal to 30 mm
3. Unexplained syncope
One or more recent episodes
4. Selected patients with non-sustained ventricular tachycardia
Particularly those less than 30 years of age and in the

presence of other risk factors
5. Abnormal blood pressure response with exercise
In the presence of other sudden cardiac death risk factors
not participate in intense competitive sports regardless of age,

sex, race, presence or absence of LVOT obstruction, prior
septal reduction therapy, or implantation of ICD.
Pregnancy39
Women with HCM can safely undergo pregnancy and labor
with minimal documented risks. The maternal mortality rate
is exceedingly low and is limited to those with advanced
disease. However careful evaluation of the functional and
hemodynamic status is of paramount importance. Usually
special medical precautions are unnecessary; cesarean
delivery is dictated by obstetric indications. However women
with advanced disease, like marked LVOT obstruction,
progressive heart failure, ventricular arrhythmias and severe
diastolic dysfunction will require regular monitoring and
specialized care. Those who are well controlled with medical
therapy should continue to take the medications. It is of great
importance that genetic counseling be given to any woman of
child bearing age with HCM.
End-stage HCM40
Patients who develop systolic dysfunction with an EF less
than or equal to 50 percent should be treated with angiotensin
converting enzyme inhibitors, angiotensin receptor blockers,
beta blockers, and other indicated medications. Other
concomitant causes (such as CAD) should be looked for and
treated appropriately. An ICD may be considered in these
patients (with EF < 50%) even though it is not otherwise
indicated. Negative inotropic agents may be discontinued.
Digoxin may be used for control of ventricular rate in atrial
fibrillation. Patients with ES HCM who are not responsive
to any form of medical therapy should be considered for
heart transplantation. Symptomatic children with restrictive
physiology and unresponsive/inappropriate for other forms
of interventions also may be considered for transplantation.41
Definite:
51
Future
The last decades have seen major steps forward in the under
standing of natural history, clinical features, risk assessment
and medical management of HCM. Future efforts should
focus on precise risk assessment of SCD and indications for
ICD implantation.
Mechanistic studies suggest that cardiac hypertrophy
in HCM is secondary to activation of various hypertrophic
signaling molecules and hence is potentially reversible.42
The hypothesis is supported by the results of genetic and

pharmacological interventions in animal models. The results
have shown potential beneficial effects of angiotensin II
receptor blocker losartan, mineralocorticoid receptor blocker
spironolactone,
3-hydroxy-3-methyglutaryl-coenzyme-A
reductase inhibitors simvastatin and atorvastatin and most
recently, N-acetylcysteine (NAC) on reversal or prevention
of hypertrophy and fibrosis in HCM. The most promising
results have been obtained with NAC, which through multiple
thiol-responsive mechanisms completely reversed established
cardiac hypertrophy and fibrosis in three independent studies.
The results in animal models have firmly established the
reversibility of established cardiac hypertrophy and fibrosis
in HCM and have set the stage for advancing the findings
in the animal models to human patients with HCM through
conducting large-scale efficacy studies.
Conclusion
HCM is a fascinating disease entity that has intrigued
cardiologists for decades. It is a unique hereditary disease in
which there is an abnormal increase in the thickness of the
heart muscle. The cause of HCM is said to be due to a gene
mutation with Mendelian dominant pattern of inheritance
with variable penetrance. It is a highly heterogeneous disease,
with diverse pathology, pathophysiology, and clinical course.
The appropriate therapies can be given for improvement of
733
734
symptoms and to identify those patients who may be at risk for

SCD. In the future, genetic testing and identification of genes
will continue to help clarify the treatment and management of
patients with HCM.
Temperance and labor are the two real physicians of man.
Jean Jacques Rousseau
Acknowledgment
I wish to thank Professor Dr B Ramesh and Dr AC Nagamani,
Associate Professor of Cardiology at Sri Jayadeva Institute
of Cardiovascular Institute of Sciences and Research for their
contribution of the images in this chapter.
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12. Maron BJ, Bonow RO, Cannon RO, et al. Hypertrophic
cardiomyopathy: interrelations of clinical manifestations, patho
physiology, and therapy. N Engl J Med. 1987;316:780-9, 88452.
13. Wigle ED, Rakowski H, Kimball BP, et al. Hypertrophic

cardiomyopathy. Clinical spectrum and treatment. Circulation.
1995;92:1680-92.
14. Montgomery JV, Harris KM, Casey SA, et al. Relation of
electrocardiographic patterns to phenotypic expression and
clinical outcome in hypertrophic cardiomyopathy. Am J
Cardiol. 2005;96:270.
15. McLeod CJ, Ackerman MJ, Nishimura RA, et al. Outcome
of patients with hypertrophic cardiomyopathy and a normal
electrocardiogram. J Am Coll Cardiol. 2009;54:229.
16. Losi M, Nistri S, Galderisi M, et al. Echocardiography in
patients with hypertrophic cardiomyopathy: usefulness of old
and new techniques in the diagnosis and pathophysiological
assessment. Cardiovascular Ultrasound. 2010;8:7-26.
17. Grossman W. Profiles in dilated (congestive) and hypertrophic
cardiomyopathies. In: Grossman W, (Ed). Cardiac cath
eterization and angiography. Philadelphia: Lea and Febiger;
1986. pp. 420-21.
18. Brockenbrough EC,Braunwald E,Morrow AG. A hemo
dynamic technic for the detection of hypertrophic subaortic
stenosis.Circulation.1961;23:189-94.
19. Shiozaki AA, Kim RJ, Parga JR, et al. Cardiovascular magnetic
resonance in hypertrophic cardiomyopathy. Arq Bras Cardiol.
2007;88(2):243-48.
20. Moon JC, Fisher NG, McKenna WJ, et al. Detection of apical
hypertrophic cardiomyopathy by cardiovascular magnetic
resonance in patients with non-diagnostic echocardiography,
Heart. 2004;90:645-49.
21. Rickers C, Wilke NM, Jerosch-Herold M, et al. Utility of
cardiac magnetic resonance imaging in the diagnosis of
hypertrophic cardiomyopathy. Circulation. 2005;112:855-61.
22. Cheng TO. Hypertrophic cardiomyopathy vs athletes heart.
International Journal of Cardiology. 2009;131:151-5.
23. Maron BJ, Savage DD, Wolfson JK, et al. Prognostic
significance of 24 hours ambulatory electrocardiographic
monitoring in patients with hypertrophic cardiomyopathy: a
prospective study. Am J Cardiol. 1981;48:252-7.
24. Monserrat L, Elliott PM, Gimeno JR, et al. Non-sustained
ventricular tachycardia in hypertrophic cardiomyopathy: an
independent marker of sudden death risk in young patients, J
25. Sadoul N, Prasad K, Elliott PM, et al. Prospective prognostic
assessment of blood pressure response during exercise in
patients with hypertrophic cardiomyopathy, Circulation.
1997;96:2987-91.
26. Olivotto I, Maron BJ, Montereggi A, et al. Prognostic value
of systemic blood pressure response during exercise in a
community-based patient population with hypertrophic
cardiomyopathy. J Am Coll Cardiol. 1999;33:2044-51.
27. Elliott PM, Poloniecki J, Dickie S, et al. Sudden death in
hypertrophic cardiomyopathy: identification of high risk
patients. J Am Coll Cardiol. 2000;36:2212-8.
28. Maron BJ. Contemporary insights and strategies for risk
stratification and prevention of sudden death in hypertrophic
cardiomyopathy. Circulation. 2010;121:445-56.
29. Maron BJ, Spirito P, Shen WK, et al. Implantable cardioverter
defibrillator and prevention of sudden cardiac death in
hypertrophic cardiomyopathy. JAMA. 2007;298;405-12.
38. Pelliccia A, Fagard R, Bjornstad HH, et al. Recommendations

for competitive sports participation in athletes with cardio
vascular disease: a consensus document from the Study
Group of Sports Cardiology of the Working Group of
Cardiac Rehabilitation and Exercise Physiology and the
Working Group of Myocardial and Pericardial Diseases of
the European Society of Cardiology. Eur Heart J. 2005;26:
1422-45.
39. Autore C, Conte MR, Piccininno M, et al. Risk associated with
pregnancy in hypertrophic cardiomyopathy. J Am Coll Cardiol.
2002;40:1864-69.
40. Harris KM, Spirito P, Maron MS, et al. Prevalence, clinical
profile, and significance of left ventricular remodeling in the
end-stage phase of hypertrophic cardiomyopathy. Circulation.
2006;114:216-25.
41. Towbin JA. Cardiomyopathy and heart transplantation in
children. Curr Opin Cardiol. 2002;17:274-79.
42. Marian AJ. Experimental Therapies in Hypertrophic Cardiomyopathy. J Cardiovasc Transl Res. 2009;2(4):483-92.
51
30. Ommen SR, Olivotto I, Betocchi S, et al. The effect of

surgical myectomy on survival of patients with hypertrophic
cardiomyopathy. J Am Coll Cardiol. 2004;43(Suppl)A:215 A.
31. Rigopoulos AG, Panou F, Kremastinos DT, et al. Alcohol
Septal Ablation in Hypertrophic Obstructive Cardiomyopathy.
Hellenic J Cardiol. 2009;50:511-22.
32. Noseworthy PA, Rosenberg MA, Fifer MA, et al. Ventricular
arrhythmia following alcohol septal ablation for obstructive
hypertrophic cardiomyopathy. Am J Cardiol. 2009;104:128-32.
33. Maron BJ, Spirito P, Shen WK, et al. Implantable cardioverter
defibrillators and prevention of sudden cardiac death in
hypertrophic cardiomyopathy. JAMA. 2007;298:405-12.
34. Vatasescu R, Evertz R, Mont L, et al. Biventricular/Left Ventricular Pacing in Hypertrophic Obstructive Cardiomyopathy:
An Overview Indian Pacing and Electrophysiology Journal.
2012;12(3):114-23.
35. Maron BJ, Spirito P, Shen WK, et al. Implantable cardioverterdefibrillators and prevention of sudden cardiac death in
hypertrophic cardiomyopathy. JAMA. 2007;298:405-12.
36. Maron BJ, Spirito P. Implantable defibrillators and prevention
of sudden death in hypertrophic cardiomyopathy. J Cardiovasc
Electrophysiol. 2008;19:1118-26.
37. Olivotto I, Cecchi F, Casey SA, et al. Impact of atrial fibrillation
on the clinical course of hypertrophic cardiomyopathy.
Circulation. 2001;104:2517-24.
Other Suggested Reading

1. Braunwalds Heart Disease: A Textbook of Cardiovascular
Medicine. 9th Ed. pp. 1582-94.
2. Hurst. The Heart. 13th Ed. pp. 837-64.
735
C hapter
52
Endocardial Fibroelastosis
Mishra SS, Mishra BR
Introduction
Fulminating Type
Endocardial fibroelastosis (EFE) is a rare entity, encountered

in clinical practice. This rare congenital anomaly is seen in
infancy and early childhood. It is characterized by thickening
of the endocardium due to fibroelastotic proliferation, with a
pearly white appearance. It leads to progressive heart failure
and generally has a poor prognosis. In 1943, Weinberg and
Himmelfarb for the first time described the disease and
coined the term EFE.1 This condition should not be confused
with endomyocardial fibrosis, which is a distinctly separate
acquired heart disease.
When the presentation is sudden and severe, it is known as

fulminating type of EFE. It manifests as acute congestive
heart failure.
Classification
Endocardial fibroelastosis (EFE) is classified into two types:
Primary Endocardial Fibroelastosis

When there is no identifiable congenital anomaly, it is known
as primary EFE.2,3 Primary EFE is again divided into two
types depending upon the size of left ventricle (LV).
a. Dilated type: When the LV is dilated it is called the dilated
type.
b. Contracted type: When the LV size is normal or small, it is
called the contracted type.
Secondary Endocardial Fibroelastosis

When EFE is associated with other congenital anomalies, it is
known as secondary type of EFE. The common associations
are hypoplastic left heart syndrome,4 aortic stenosis,5
coarctation of aorta6 and anomalous left coronary artery from
pulmonary artery.7
Clinical Classification
There are two types of EFE according to the clinical presentation:3
Chronic Type
When the presentation is insidious and it runs a protracted
course, it is known as chronic type of EFE. It manifests with
slow and progressive chronic congestive heart failure.
Incidence
EFE is a rare disease, with occurrence of 1 to 2 percent in
the list of all congenital heart diseases.8 In recent years, the
incidence of EFE has decreased considerably,9 compared
to the earlier reported incidence of 1 in 5,000 live births,10
possibly due to better antenatal scanning and decreased
incidence of mumps.11 There is no sex predilection with
equal affection of both sexes. In 80 percent of cases, clinical
presentation is within the first 3 to 6 months of age. It is one of
the causes of non-immune hydrops fetalis.12 Survival beyond
2 years is unusual.2 This is extremely rare in adolescents
and adults. Although the disease is sporadic, familial cases
with an X-linked pattern are also seen in about 10 percent of
cases.13
etiology
The fibroelastic process is thought to be secondary to various
endocardial stimulation in fetal life.14 Histological and
molecular studies substantiated viral etiology particularly
Coxsackie B virus and mumps infection.11 This is also linked
to presence of maternal anti-Ro and anti-La antibodies.15
Autosomal recessive and X-linked recessive inheritance
pattern of EFE were also reported including mutation of
gene 4.5 (tafazzin).16 Other possible etiological factors are
Pathophysiology
Normal endocardium is thin and transparent. In EFE, endo
cardium is diffusely thicked upto 1 to 2 mm due to proliferation
of collagen and elastic tissue and deposition of extracellular
matrix. The characteristic appearance of endocardium in
EFE is described as pearly white or milky white, glistening
and opaque. In the dilated type of pimary EFE, both LV
and left atrium (LA) are dilated. LV assumes a spherical
shape. Endocardial thickening also affects mitral valve
and other cardiac chambers.18 LV dilatation along with
abnormal origin of papillary muscles; poor LV function leads
to mitral regurgitation (MR) of various grades. High origin of
papillary muscles together with short and thick chordae results
in improper coaptation of mitral leaflets in systole. Aortic
valve is also involved in 50 percent of cases. Myocardial
thickness remains normal. Aorta and coronary arteries are not
involved.8
In contracted type, the LV endocardium resembles the
dilated type, but the LV remains normal or hypoplastic
(Figure 1). Similar morphologic changes in endocardium occur
in secondary type of EFE, but they are more often patchy.9
In EFE, thickened endocardium limits the contraction

and relaxation of the LV myocardium producing a splinting
action causing both systolic and diastolic dysfunction.
Impaired contraction and relaxation together with MR leads to
increased left ventricular end-diastolic pressure (LVEDP) that
leads to increased mean LA pressure and pulmonary venous
hypertension (PVH), PVH is responsible for symptoms of
dyspnea and leads to development of pulmonary arterial
hypertension (PAH), which ultimately gives rise to right
heart failure. In fetal life, it may lead to development of nonimmune hydrops fetalis.12 In contracted type, PAH develops
early and is more severe. Abnormal endocardium with
global hypokinesia sets the stage for mural thrombosis with
consequent systemic embolization.19
52
impaired lymphatic drainage, systemic carnitine deficiency,

neonatal lupus and subendocardial ischemia.
In secondary type of EFE, increased wall tension, cardiac
hypertrophy leading to myocardial oxygen demand and
supply mismatch, resulting in subendocardial injury, which is
thought to be the trigger to produce EFE. EFE is also seen
after myocardial infarction.17
Clinical Features
Symptoms
Infants present with dyspnea, wheezes, tacyhpnea, feeding
difficulties and failure to thrive. In some neonates, presentation
is acute (acute LVF) and the condition of the infant rapidly
deteriorates. It is the fulminant presentation of EFE.20 It is
one of the causes of sudden death in infancy.21 In other cases,
presentation is more insidious. Sometimes the infant presents with
diaphoresis, abdominal pain or with recurrent chest infection.
Signs
Infants with EFE are tachypneic. There is no cyanosis, but
peripheral cyanosis may be seen in severe cases of heart
failure. Tachycardia is usually present with a normal to low
volume pulse. Jugular venous pressure is raised when there is
right heart failure. Apex is displaced down and out. Thrill is
uncommon in spite of significant MR due to LV hypokinesia.
In contracted type, apex is right ventricular type type due
to PAH. Hepatomegaly is commonly seen. On auscultation
S1 is diminished, S2 is closely split with loud P2. A loud S3
is commonly heard widely throughout the precordium.18
Although MR is common, presence of murmur is uncommon
as LV is unable to generate sufficient force. Absence of murmur
in presence of cardiomegaly and congestive heart failure
(CHF) is one of the important diagnostic feature of EFE.22
Investigation
Electrocardiography
Figure 1: Opened out left ventricular inflow tract shows small size of
the left ventricle (LV) with smoothened out trabeculae and pearly white
endocardium. The mitral valve (MV) is dysplastic. Note the presence of
patent foramen ovale (PFO) (arrow). Courtesy: Dr. Pradeep Vaideeshwar
Sinus tachycardia is usually seen. Rarely supraventricular and

ventricular tachycardia, atrial fibrillation and atrioventricular
blocks may be detected. EFE has been implicated in
congenital complete heart block.23 QRS axis is usually normal
unless PAH is seen producing a right axis. P wave indicate
LA enlargement or biatrial enlargement. In dilated type,
left ventricular hypertrophy is usually present with narrow
737
q in V5 and V6 due to volume overload secondary to MR.

Flattening and inversion of T waves in lateral leads are also
seen in majority of cases. In contracted type, features of right
ventricular hypertrophy is seen. Wide QRS due to bundle
branch block and pre-excitation (WPW) are also reported.
Rarely low voltage QRS may be seen in terminal cases.3
Myocardial infarction pattern suggest secondary EFE due
to anomalous left coronary artery from pulmonary artery
(ALCAPA). But q waves in right precordial leads are not
uncommon in primary EFE.22
Chest X-ray
Cardiomegaly is conspicuous in chest X-ray of EFE. In dilated
type, it is due to LV and LA enlargement and in contracted
type, it is due to right atrial and right ventricular enlargement
secondary to PAH. In both types, features of PVH are seen.23
EFE is one of the causes of massive cardiomegaly in newborns
and infants. Although there is marked cardiomegaly in dilated
type, the aorta and pulmonary trunk remains normal, which
helps in differentiating EFE from other congenital heart
diseases.
Echocardiography
In echocardiography, LV and LA are dilated, LV dilatation is
accompanied by increased wall thickness. The characteristic
A
738
Figure 2: Echocardiography in endocardial fibroelastosis (done in

1987 in a 4 months baby) showing bright echogenic endocardium of
left ventricle, mitral valve, papillary muscles seen in parasternal longaxis view. Right ventricle is dilated. The mother had mumps in the first
trimester
finding is bright echogenic thickened endocardium seen on

2D echocardiography and M-mode (Figures 2 and 3A).24
LV shows global hypokinesia and MR is detected by
color Doppler (Figure 3B) and its severity can be graded.
In presence of severe MR, the LA may be hugely dilated.
Figures 3A and B: A. M- mode at the papillary muscle level shows dilated and hypertrophied left ventricle with hyperechogenicity of the
papillary muscle and posterior wall; B. Transthoracic echocardiogram in apical four chamber view shows deformed dysplastic mitral valve with
hyperechogenicity of papillary muscle (arrow), posterior wall and color Doppler shows severe mitral regurgitation. LA = Left atrium; LV = Left
ventricle; MR = mitral regurgitation; RA = Right atrium; RV = Right ventricle. Courtesy: Dr. IB Vijayalakshmi
Infiltrating and Storage Disease
Other Imaging Modalities
Management
In some cases, echo findings may be equivocal or nondiagnostic. In such cases, newer imaging like magnetic
resonance imaging (MRI)26 and electron beam computed
tomography27 are helpful. MRI using perfusion and delayed
enhancement demonstrate endocardial surface as a rim of
hypointense signal in perfusion sequences and a rim of
hyperintense signal in the myocardial delayed enhancement
sequence.
Cardiac catheterization and angiocardiography does
not help much as they do not add further to non-invasive
modalities.
Treatment is supportive, there is no medical or surgical

cure as yet developed. Nutrition and hydration are to be
maintained. Concurrent infections particularly chest infection
and anemia should be treated promptly. Decongestive
therapy with conventional regimen with digoxin, diuretic
and ACE inhibitors are prescribed.33 Rapid digitalization
was prescribed earlier is seldom used now. Digoxin is useful
in atrial fibrillation. Beta blockers like carvedilol34 are of
particular help in reducing heart rate when sinus tachycardia
is marked. Some infants do respond to medical management.
But others remain refractory in spite of medical management.
Treatment should be continued indefinitely even after
symptomatic improvement and reduction of heart size.
Role of steroid remains controversial. Dexamethasone was
shown to prevent conduction delay in case of EFE associated
with maternal anti-Ro and anti-LA antibodies.35 Those with
mural thrombi or episode of thromboembolism, will require
anticoagulation initially with heparin and then with oral
vitamin K antagonist. Cardiac transplant is recommended in
refractory cases.36
Congenital anomalies giving rise to CHF in neonates and
infancy with cardiomegaly comes in the differential diagnosis
of EFE.28
Congenital Mitral Regurgitation

In congenital MR, LA and LV are dilated in the presence of
MR and CHF. In congenital MR, the murmur of MR is quite
prominent unlike EFE. Echo demonstration of abnormal mitral
apparatus with preserved contractility and absent endocardial
thickening differentiates it from EFE.29
Myocarditis and Dilated Cardiomyopathy

In myocarditis and dilated cardiomyopathy there is LV
dilatation, MR and CHF. But marked myocardial and
endocardial thickening is absent. Viral serological tests,
molecular tests, nuclear perfusion imaging and endocardial
biopsy help in establishing diagnosis.30
Anomalous Left Coronary Artery from Pulmonary Artery

ALCAPA is also responsible for cardiomegaly and CHF in
neonates. ECG evidence of myocardial infarction pattern
in left coronary artery territory, wall motion abnormality in
echo and demonstration of origin of left coronary artery from
pulmonary artery differentiates it from EFE.31
Infiltrative and storage disease like Pompe disease, glycogen

storage disease and mucopolysaccharidosis may present with
similar findings, but marked generalized thickening of the
cardiac structures including right ventricular free wall along
with other systemic findings help to differentiate it from
EFE.32
52
Echocardiography also helps in assessing pulmonary

arterial pressure. In contracted type, LV cavity is small
with hypertrophied myocardium and bright echogenic
endocardium. PAH is particularly common in contracted
type as determined from tricuspid regurgitation jet, which is
usually present. Intrauterine detection is also possible by fetal
echocardiography.25 Doppler echocardiography study is the
tool of choice for diagnosis and follow-up.
Prognosis
The overall prognosis in primary EFE is ominous. Dilated
EFE with fulminating presentation and contracted type
are generally fatal. Even in chronic type, the disease
progresses relentlessly with 30 to 40 percent mortality
rate. Survival beyond 2 years is rare. Sudden death may
occur. Severe the symptom and younger the patient, poorer
is the prognosis.37
Conclusion
Endocardial fibroelastosis is characterized by diffuse
thickening of the ventricular endocardium due to proliferation
of fibrous and elastic tissue and impaired cardiac function.
It is most commonly seen in young children and rarely in
adults. It is often associated with congenital heart anomalies,
infection or gene mutation. Treatment is supportive with
decongestive therapy and sustained refractory ventricular
tachycardia might be an end-stage disease that requires
739
mechanical support and heart transplantation. The overall

prognosis is gloomy; survival beyond two years of age is
rare.
The purpose of medicine is to prevent significant disease,
to decrease pain and to postpone death... Technology
has to support these goals-if not, it may even be
counterproductive.
Dr Joel J Nobel
13.
14.
Acknowledgment
15.

Thoracic Division), Seth GS Medical College, Mumbai,
India for the pathological image and Dr IB Vijayalakshmi,
Professor of Pediatric Cardiology for the echocardiographic
images.
16.
References
1. Weinberg T, Himelfarb AJ. Endocardial fibroelastosis. Bull.
Johns Hopkins Hosp. 1943;72:299-308.
2. Andersen DH, Kelly J. Congenital endocardial Fibroelastosis.
II, A clinical and pathologic investigation of those cases
without associated cardiac manifestations including report of
two familial instances. Pediatrics. 1956;18:539-55.
3. Moller JH, Lucas RV, Adams P, et al. Endocardial fibroelastosis.
Circulation. 1964;30:759-82.
4. Noonan JA, Nadas AS. The hypoplastic left heart syndrome.
Pediatr Clin North Am. 1958;5:1029-56.
5. DuShane JW, Edwards JE. Congenital aortic stenosis in
association with endocardial sclerosis of the left ventricle. Proc
Staff Meet Mayo Clin. 1954;29:102-8.
6. Oppenheimer EH. Association of adult type coarctation of
aorta with endocardial fibroelastosis in infancy. Bull Johns
Hopkins Hosp. 1953;93:309-19.
7. Noren GR, Raghib G, Moller JH, et al. Anomalous origin of
the left cornary artery from the pulmonary trunk with special
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8. Keith JD, Rose V, Manning JA. Endocardial fibroelastosis.
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9. Lurie PR. Changing concepts of endocardial fibroelastosis.
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Rafinski T, Folenia A, Wozneiwicz B, et al. Familial endocardial
fibroelastosis. J Pediatr. 1967;10:574-6.
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Nield LE, Silverman ED, Smallhorn JF, et al. Endocardial
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741
Sec t i on
10

in Adults
C hapter
53
Transitional Care in Congenital

Heart Disease
Mary M Canobbio, Reema Chugh
INTRODUCTION
As the survival of children born with congenital heart disease
(CHD) into adulthood continues to increase, the need for an
effective transition plan is becoming an important clinical
concern. In 2003, the American Academy of Pediatrics/
American College of Physicians presented a consensus statement
on health care transition for young adults with special heath care
needs.1 A similar report was published in the UK addressing
the needs for the emerging population of young adults.2 The
term transitional care is a multifaceted, dynamic process that
attends to the medical, psychosocial and educational/vocational
needs of adolescents as they move from a child-focused to
an adult-focused health care system.3 The overall goal is to
provide uninterrupted health care that is patient centered, age
and developmentally appropriate and comprehensive.4,5 The
structured plan should be introduced in the pediatric cardiology
setting, in order to allow an efficient and caring transfer to the
adult setting. The following highlights key elements that should
be included in a transitional plan of care in order to ensure an
effective transfer program from childhood into adulthood
(Box 1).
Box 1: Seven key elements of an effective transfer

program from childhood to adulthood
Timing of transfer to adult care in order to form a policy
based on the individuals maturity, chronological age and
social factors, that is carried on during a period of medical
stability
Educational programs coordinated by nurse specialists in
pediatric and adult teams to prepare patients and their
families to navigate the adult health care system
A coordinated transfer process with transfer summaries
from the pediatric to adult clinics
Health passport for the patient to carrya snapshot of
congenital heart defects, procedures, surgeries, medical
conditions, medications, allergies, pertinent diagnostic
test results and an outline of the plan of care
Selection of an appropriate Adult Congenital Heart
Disease Center or specialists that is geographically and
financially feasible for the patients and their families
Involvement of primary care providers and administrative
support to ensure continuous quality improvement process
Ongoing consultation with the pediatric team/referring
pediatric cardiologist after the transfer is complete
COMPREHENSIVE MEDICAL CARE

The overall goal of transitional care is the transfer of care from
the pediatric setting to an adult-focused model.6 Despite the
recent attention given to transitional care, the actual transfer is
often unsuccessful because of a number of identified barriers
beginning with who is best qualified provider to take care of
the adult with CHD.7,8
The first model is that pediatric cardiologists can provide
continuity of care well into adulthood, based on the virtue
that they are better informed on CHD and are more familycentered. The main problem with this model is that pediatric
providers lack the experience of handling acquired heart
diseases and addressing adult care issues. A second model
proposes adult cardiologists as primary providers since they

are well prepared to deal with acquired diseases and address
adult issues. However, the main problem here is that they lack
training in the area of CHD and the management of long-term
residua and sequelae after surgery. Adult-centered care is also
more patient-centered and disease oriented thus it takes for
granted that the patient has the necessary skills to self-manage
his/her care.
Additionally, regardless of the setting, it is important to
recognized that as adults, most CHD patients will at some point
require a number of non-cardiac health referrals.9,10 These
may vary from routine preventive health care to non-cardiac
surgery. Throughout childhood, the pediatric cardiologist
Congenital Heart Disease in Adults
10
has served, in most cases, not only as the cardiologist, but

as the primary care provider. As the child grows, parents
need to be encouraged to identify a primary care physician
(general physician) who assumes not only the responsibility
of coordinating the care, but is also willing to work closely
with cardiology and other subspecialities.9
Particular attention must be given when the patient requires
non-cardiac surgery.10,11 Perioperative safety can be assured
if the risks inherent in each individual case are anticipated.
The surgical team must be informed as to the relative risk
of operation, including risks of bleeding, hypotension,
hypovolemia and infective endocarditis. Relative risk is
dependent upon the type of defect and any residual effects
of CHD including rhythm disturbances, ventricular failure,
acquired medical problems or comorbidities such as diabetes
or hypertension. Cyanotic CHD with or without pulmonary
vascular disease presents with the highest risk and should be
carefully evaluated prior to any surgical procedure.
For females, gynecologic and reproductive issues are the
leading non-cardiac health issues that health care providers
must address. A number of gynecologic issues such as
menstrual complaints and contraception frequently present
in adolescents and require age appropriate counseling and
referral.12
EDUCATION AND CAREER COUNSELING
746
While early studies reported that CHD had a negative

impact on school progress, later studies have demonstrated
that with early surgical intervention and improved
medical management, patients have attained educational
milestones similar to those of healthy peers.13-15 Recent
studies focusing on neurodevelopmental outcomes have
reported that while the majority of the children have
normal intelligence, a subgroup have demonstrated slightly
lower scores on standardized tests of cognitive ability
and academic achievement than those for the general
population.16,17 Specifically, children with complex CHD
such as d-transposition of the great arteries, hypoplastic
left heart syndrome and other functional single-ventricle
lesions have a higher incidence of problems with academic
performance, behavioral abnormalities, hyperactivity and
the ability to perform executive functions such as visualmotor integration.16 Despite these findings, today the
majority of young adults with CHD achieve educational
goals similar to that of the general population and should be
encouraged to believe that they will grow up to be healthy
and able to work. Career counseling and vocational guidance
should be offered in middle and high schools so that based
upon their intellectual abilities and interests, adolescents are
encouraged to achieve higher education and skills necessary
for employment in occupations that are manageable based
on their work capacity.
EMPLOYABILITY
Adults with CHD have been able to find comparatively steady
employment, although the type of employment for some
is inferior compared to the general population. Obtaining
suitable employment has historically been a serious concern
for the young adult with CHD.17 While less so today, full-time
or part-time employment has been reported to occur in only
71 percent of adults with CHD as compared with 84 percent
of healthy people.15,18,19 The rate of employment tends to be
higher among those with milder and acyanotic forms of CHD.17
One possible explanation for this high unemployment rate is the
misunderstanding and the lack of knowledge or misperception
regarding CHD by employers with respect to the individuals
future health prospects. Over the years, legislation in many
parts of the world has been enacted to reduce employment
discrimination of individuals with preexisting disabilities. It
is therefore important for health care providers to give career
and vocational counseling that assists the patient in selecting a
career. This should combine not only personal interests, but is
in keeping with clinical limitations that the young person with
CHD might have.20,21 In this way, we may provide them with
skills that are appropriate for achieving occupational success.
FINANCIAL COSTS OF HEALTH CARE AND

INSURABILITY
Access to specialized care for the adult with CHD is not
uniformly available in all parts of the world. Even in developed
countries, patients and their families often have to travel longdistances for specialized care and follow-up. While most
countries have national health care systems that will provide
care to this special population, many of these centers are not
within the patients reach. In the United States (USA), access
to health care requires some form of insurance coverage and
insurability. Infants and children are either covered by their
parents insurance carrier or by a state health care coverage.
For adults with CHD, lack of insurance is one of the major
barriers to long-term follow-up and therefore discussions with
parents and adolescent must be introduced, while they are still
covered by the parents or before the childs state heath care
coverage is terminated, which is usually at 21 years or at 26
years for students.18,20,22 Patients with complex CHD, who are
often more at risk, should be directed to explore policies that
tend to have fewer restrictions such as group policies obtained
through their employment.
SEXUALITY AND REPRODUCTIVE ISSUES

Sexual maturity is a major developmental milestone of
adolescence. For many adolescents with CHD, discussion
surrounding issues of human sexuality and reproduction are
often avoided or postponed by the parent and provider.

Table 1
Informational needs for the young with congenital health disease

Learning need
Topic
Defect-specific
learning
Discussion of treatment:
Medical follow-up:
INFORMATIONAL NEEDS
The ability to assume responsibility for their own health
care is an important developmental task for adolescents with
CHD. However, there are continuing reports unveiling the
young adults lack of knowledge about their defect, treatment
and need for follow-up. Many enter adulthood believing that
they are cured.25 One study found that while the majority of
patients (80%), from 18 to 46 year-of-age, with CHD were
able to correctly identify treatment plans, only 50 percent
of this study group was able to identify the frequency of
recommended follow-up medical/dental care and knowledge
about pregnancy risks.26
Thus, as the children enter their teenage years, health care
providers must continuously assess their patients knowledge
of the condition and begin to provide age appropriate
education.26 The adolescent should be given time, without his
or her parents present, to ask questions not only about their
heart condition, but also to establish a trusting relationship
so that sensitive issues about sexuality, self-esteem may be
explored and addressed. The level of discussion should be
based on the patients physical, psychosocial development
and the information should be presented in a manner that is
culturally and age appropriate.27 Topics to be included in a
structured educational plan are listed in Table 1.
Surgical interventions
Invasive/interventional cardiac
procedures
Medications and allergies/intolerance
Exercise, sports and limitations
Diet/nutrition
Preventive
Health
Practices
Adult CHD specialist or Pediatric

Cardiologist
Primary care physician/health care
providers
Dental Health: Brushing, flossing, and

cleaning to prevent plaque formation,
gingivitis and bacteremia
Indications for endocarditis prevention/
prophylaxis:
Dental hygiene or procedures

Elective surgery/medical procedures
Tattooing/body piercing
53
Transitional Care in Congenital Heart Disease
As a result many patients enter adulthood with a series of

misconceptions and fears about their sexuality or their ability
to conceive and bear children. There is limited emerging data
indicating that the majority of patients with CHD engage in
sexual practices similar to the general population.23,24 For some,
however, there remains some hesitation in disclosing their
CHD for fear of rejection. It is important, therefore, to permit
frank and open discussion on sexuality, childbearing and
contraception for females. For males there may be concerns
regarding the emotional impact of intercourse on their heart
condition and the risk transmission of CHD to their offspring.
Introducing the topic early in the transition process sends the
message to both teenagers and their parents that these are safe
and welcome topics to discuss as part of their clinic visit.
Risk Behaviors:
Counseling
Tobacco use
Alcohol
Substance abuse: Marijuana, cocaine,
street drugs
Unprotected sex
Educational and career development

Employment counseling
Insurance coverage: Medical, dental and life
insurance
Reproduction:
Females: Contraception, pregnancy and

gynecological issues
Males: Childbearing and supporting a
family
Genetic transmission
Adapted from Canobbio MM. Health care issues facing adolescents with
congenital heart disease. J of Ped Nurs. 2001;16(5):363-70.
Endocarditis Risk and Prophylaxis

While most, but not all patients with CHD present with risk
for developing endocarditis, it is prudent for patients at risk to
understand the behaviors that can serve as portals for infection.
These include poor dental care, body piercing and tattooing.
Early studies reported that only 50 percent of their population
could name one situation considered at risk for acquiring
endocarditis.28 Thus discussions emphasizing the importance
of maintaining regular good dental health and indications for
antibiotic prophylaxis should be introduced early in childhood
to the parents and their children with CHD. These discussions
should be continued through adolescence. When the children
with CHD enter teenage years, they should be educated

about the risks of infection associated with body piercing and
tattooing. The patients should be made aware of questions
to ask with respect to needle sterilization before getting the
tattoos. While the standards of needle sterilization and safety
techniques have improved, the frequency of procedurerelated infections remains a concern.29 There is small risk of
bleeding and topical infections. Permanent tattooing should
be discouraged in patients with CHD at risk for developing
endocarditis due to episodes of transient bacteremia or in
those taking oral anticoagulants.
747
10
Exercise Counseling
While the majority of available information on exercise
supports the benefits of exercise for children and adolescent
CHD patients, it is important to counsel this growing
population on appropriate recreational activities. This topic
is discussed in more detail in the chapter on exercise and
sports in CHD. As adolescents enter high school and look
to participate in higher level or competitive sports, exercise
testing is helpful in gauging safety. Over the years, the
American Heart Association and others have published
recreational and sport recommendations for young persons
with heart disease.30-32 These guidelines have been the
basis for outlining activities allowances and recommended
workloads for a number of postoperative defects and can be
helpful to guide competitive and recreational activities that
are safe.
Contraception and Preconception Counseling

for Young Females
Discussion on reproductive issues should be available to
females as they enter menarche. It should be presented in a
sensitive and culturally appropriate manner that is in alignment
with their individual level of emotional maturity and the value
system of their society. The initial discussions can take place
in presence of the patients mother or a female family member
with whom she is comfortable with, but if there are family or
cultural barriers associated with premarital sexual activity,
the adolescent must be made aware that the provider is there
for her to seek confidential counsel. It is important for health
care providers to proactively address questions and concerns
regarding their sexuality, the ability to conceive/bear children,
the safety and availability of contraceptives based upon their
underlying defects.33 Once a young female becomes sexually
active she should be referred to a gynecologist, preferably
one who works with adolescents, to ensure appropriate use
of contraception and discussion and/or detection of sexually
transmitted diseases.
Contraceptives
748
The prevention of unplanned pregnancy in adolescent/young

adult requires a collaboration between providers, patients and
sometimes, their parents. Additionally, the adolescent health
care provider should be familiar with the relation between
oral contraception, particularly the estrogenic type and venous
thromboembolism that makes this form of contraception
hazardous for females who are cyanotic and/or in those with
conditions such as right-to-left shunts, pulmonary vascular
disease, prosthetic valves/conduits.
A number of contraceptive methods are available to
teens.33 It is important, however, to consider the level of
maturity of the teenager and her commitment to adhering to the

prescribed contraceptive choice. Although oral contraceptives
are effective when used by teenagers, it is estimated that 13
percent of teen users between ages of 15 to 17 years will miss an
average of three pills per month.34 Similar results are reported
for patches and vaginal rings.34 Long-term contraceptives,
such as, implantable devices or IUDs, are safe for use in
young patients and carry a higher level of compliance.
Injectables which are also safe still require regular return
visits thus placing a certain level of responsibility on the teen
to return to clinic. Additionally, depomedroxyprogesterone
acetate (PMPS), known as Depo Provera carries a risk of
osteoporosis associated with the amenorrhea that occurs in
long-term users.35 Therefore, teen use should be carefully
monitored especially in females who are extremely thin,
suffer from anorexia nervosa or have a comorbidity of
chronic renal disease36
THE HEALTH PASSPORT

The American College of Cardiology/American Heart
Association along with Adult Congenital Heart Association
(ACHA), which is a patient advocacy group in the United
States, have developed a booklet called The Heath
Passport which provides a comprehensive, summarized
account of patient information.37 The Health Passport can
be downloaded from the ACHA website at (http://www.
achaheart.org/Portals/0/pdf/ACHAPassport.pdf). Its goal
is to outline routine health care recommendations and
specific information on diagnoses, procedures, operations,
medications, allergies, endocarditis prophylaxis, exercise,
contraception and the recommended frequency of medical
and dental follow-up. Patients are asked to carry it with
them at all times so that this information is available during
emergency or unscheduled visits to hospitals or providers
who are not familiar with the patients condition. They
should also carry a list of their cardiologist/health providers
and personal emergency contacts.
Therefore, such a summary is referred to as a health
passport in that it is similar to a travel passport, because it
carries vital information to ensure safe health care when
one is away from his/her own providers. Patients are also
encouraged to carry scanned copies of their medical reports
on a password encrypted flash drive so that more detailed
medical records are readily available during unforeseen
circumstances.
On their respective websites, the ACHA (www.achaheart.
org), and the International Society of Congenital Heart Defects
(ISACHD-www.isachd.org) have a list of some of the adult
CHD programs in the United States and around the world.
Even though this list is not complete, through these contacts
more information can be sought at the local and regional levels
by the health care providers and then passed on to the patients.
CONCLUSION
Be sober and temperate, and you will be healthy. Be in

general virtuous, and you will be happy.
Benjamin Franklin
(1706-1790)
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overview of the transitional care issues that must be addressed
with the adolescent/young adult with CHD and his/her family.
These measures are to ensure a smooth transition into the
adult heath care system and avoid the complications resulting
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14. Kanoch MJ, Collins-Nakai RL, Medwid SM, et al. Adult
patients knowledge about their congenital heart disease.
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15. Simko LC, McGinnis KA, Schembri J. Educational needs
of adults with congenital heart disease. J Cardiovasc Nurs.
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16. Wernovsky G. Current insights regarding neurological and
developmental abnormalities in children and young adults with
complex congenital cardiac disease. Cardiol Young. 2006;16
(suppl 1):92-104.
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Transition to Adulthood for Adolescents With Congenital Heart
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19. Kamphuis M, Vogels T, Ottenkamp J, et al. Employment in
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20. Hellstedt LF. Transitional care issues influencing access to
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21. McGrath KA, Truesdell SC. Employability and career
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understanding in children and adolescents with heart disease.
Heart. 2000;84:395-7.
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with congenital heart disease know about their disease,
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27. Day MJ. Educational assessment of the adult with congenital
heart disease. The Nursing Clinics of North America.1994;29:
299-312.
28. Cetta F, Warnes CA. Adults with congenital heart disease:
Patient knowledge of endocarditis prophylaxis. Mayo Clinic
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30. Gutgesell HP, Gessner IH, Vetter VL, et al. Recreational and
occupational recommendations for young patients with heart
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Disease in the Young, American Heart Association. Circulation.
1986;74:1195A-8A.
31. Bar-Mor G, Bar-Tal Y, Krulik T, et al. Self-efficacy and physical
activity in adolescents with trivial, mild, or moderate congenital
cardiac malformations. Cardiol Young. 2000;10:561-6.
32. Mitchell JH, Haskell W, Snell P, et al. Task Force 8:
classification of sports. J Am Coll Cardiol. 2005;45:1364-7.
33. Canobbio MM. Contraception for the adolescent and young
adult with congenital heart disease. Nursing Clinics of North
America. 2004;39:769-85.
34. Balassone ML. Risk of contraceptive discontinuation among

adolescents. J Adolesc Health Care. 1989;10:527-33.
35. Cundy T, Evans M, Roberts H, et al. Bone density in women
receiving depot medroxyprogesterone acetate for contraception
BMJ. 1991;303:13-6.
36. Cromer BA, Blair JM, Mahan JD, et al. A prospective
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C hapter
54
Management Issues in Adults

with Congenital Heart Diseases
Reema Chugh
INTRODUCTION
The tale of how adult congenital heart disease (ACHD)
became as subspecialty of cardiology is fascinating, especially
when eloquently told by Dr Joseph Perloff (USA) and Dr Jane
Somerville (UK), the founders of this field in the western
hemisphere.
Only just over a 100 years ago, William Osler, often
honored as the Father of modern medicine in North America
wrote a book entitled The Principles and Practice of
Medicine: Designed for the Use of Practitioners and Students
of Medicine, first published in 1892. He devoted only a 5
page chapter (out of 1,079 pages) to Congenital Affections
of the Heart. In his times, congenital heart defects were
considered as hopeless futilities. Little did he know then that
two of his female disciples would generate a new wave in the
field of medicine.
Maude Abbott, initially barred from studying medicine
because she was a woman, with her undying persistence and
perseverance acquired medical knowledge from universities
around the world. She returned to Montreal, Canada where
she soon became the curator of the McGill Pathological
Museum in 1901. Her chapter on Congenital Heart Disease
in Dr Oslers text Modern Medicine in 1908 was very well
received. Ironically, she was awarded an honorary medical
degree in 1910. Categorizing in detail the various congenital
heart defects over the course of decades, she published
her work in the Atlas of Congenital Cardiac Disease
in 1936. Her contributions have served as a foundation for
understanding the pathology of congenital heart disease.
Oslers other student, who was barred from receiving her
medical degree alongside her classmates, since she was a
woman, was Helen Taussig. She led the pioneering blue baby
operation along with Vivien Thomas and Alfred Blalock in
1944. This surgery changed the future of cyanotic congenital
heart disease.
In 1953 Dr John Gibbons, a surgeon and inventor at the
Jefferson Medical College in Philadelphia, performed the first
successful intracardiac operation with the help of his newly

designed heart-lung machine Model II, for closure of an
atrial septal defect in an 18-year-old girl. This set the stage for
the advent of cardiac surgeries assisted by artificial circulation
(bypass machine).
In the same era, Dr Paul Wood, a dynamic cardiologist
with his passion for physical examination of the heart and
his deep interest in congenital heart disease (CHD) attracted
students from near and far to drink up the new medicine
as described by his disciple, Dr Jane Somerville. Born in
India and raised in Australia, Dr Wood became well-known
for describing the Eisenmenger syndrome and for writing the
first single author cardiology textbook, Diseases of the Heart
and Circulation. Deeply influenced by the chapters from this
book on Physical examination and Congenital affections
of the heart another disciple, Dr Joseph Perloff went on to
write individual textbooks on these two topics. Dr Paul Wood
did not know, what his two students would do in the future.
Dr Somerville collaborated Sir Magdi Yacoub, a world
reknown pioneering CHD surgeon and a dedicated team at
the Royal Brompton Hospital, London to establish, a new
subspecialty that will be known as grown-up congenital heart
disease (GUCH) in Europe.
Dr Joseph Perloff partnered with a brilliant cardiologist,
Dr John Child whose phenomenal clinical skills and talent
for mental 3D reconstruction led to his expertise in imaging
CHD and a niche in Echocardiography in CHD. Joined
by Dr Hillel Laks, a CHD surgeon par excellence, diligent
nurse specialists, Mary Canobbio, Pamela Miner and a
multidisciplinary team at UCLA Medical Center in Los
Angeles, they established the first center for ACHD in North
America.
Why Adult Congenital Heart Disease

should be a subspecialty of cardiology?
Advances in all aspects of medicine and surgery have allowed
the majority of the infants born with congenital heart defects,
Congenital Heart Disease in aDults
10
who have access to healthcare, to survive into adulthood.

While most individuals born with congenital heart defects are
diagnosed in infancy and childhood, some go undiagnosed
until adulthood. Other than the exceptional case of an early
surgically ligated, isolated patent ductus arteriosus with no left
ventricular enlargement or dysfunction, all adults with CHD
have postoperative residual and sequelae that need follow-up
throughout their lives.
There has been organized global effort to integrate
multidisciplinary services devoted to this special population.
Many clinics/centers for Adult Congenital Heart Association
(ACHD) GUCH have sprouted around the world. The
International Society for Adults Congenital Heart Disease
(ISACHD) has been instrumental in bringing together experts
from all over the world (www.isachd.org). Over the past decade,
the American College of Cardiology,1 European Society
of Cardiology2 and the Canadian Cardiovascular Society
Consensus Conferences,3-6 published guidelines to establish
standards of care for the adult with CHD. In the United States,
the ACHA provides patient support and advocacy (www.
achaheart.org). Currently there are several professional and
patient-centered organizations assisting in the universal goal to
improve quality of life and care of the adults with CHD.
While there is a detailed discussion of embryology,
pathology, genetics, natural history, clinical presentation,
diagnosis and management of individual defects in other
chapters of this book, the aim of this chapter is to provide
a concise overview regarding salient management issues
encountered while caring for an adult with CHD.
DEFECT SPECIFIC MANAGEMENT

ISSUES IN ADULTS WITH CHD
SHUNT LESIONS
Patent Foramen Ovale
752
One of the most common indications for performing a

transesophageal echocardiogram is to rule out cardiac source
of emboli in an adult patient with a cerebrovascular event
(stroke or transient ischemic attack). Besides looking for an
obvious intracavitary thrombus, clot in the left atrial appendage
or atheromas in the ascending limb of the aortic root or arch,
the cardiologist is expected to rule out the possibility of a
paradoxical embolus through an interatrial communication
with a right-to-left shunt, such as a patent foramen ovale (PFO)
or an atrial septal defect with a bidirectional shunt or shunt
reversal. An adequate Valsalva maneuver is essential, while
assessing the presence of a right-to-left shunt by an agitated
saline contrast study with transthoracic or transesophageal
echocardiogram.
It is the most common CHD, with an autopsyderived
incidence for a probe-patent PFO of around 27 percent. This
slit-shaped tunnel-like defect in the atrial septum, residual from

the fetal circulation, due to the failure of the primum and the
secundum atrial septum to fuse postnatally, is often associated
with another defect of atrial morphogenesis called atrial
septal aneurysm (ASA). An ASA may be associated with one
or multiple PFO in 50 to 85 percent of the cases. The ASA is
characterized by a redundant, undulating, interatrial membrane
in the region of the fossa ovalis, with the diameter of the base
exceeding 15 mm and the amplitude of the interatrial septum
excursion up to 10 to 15 mm.7 Presence of a concomitant ASA
increases the likelihood of thrombus formation on the left atrial
side of the aneurysm. Besides an ASA, the other proposed highrisk factors for cerebral embolic events associated with a PFO are
Eustachian valve anatomy favoring right-to-left shunt, presence
of venous thrombus or hypercoagulable states. Both PFO and
ASA are undetectable on physical examination (Table 1).
Over the past two decades, the PFO has caught clinical
interest for potentially contributing to paradoxical embolism,
especially in adults < 55 years old with cryptogenic stroke. In
most studies, the clinical diagnosis of paradoxical embolism
was presumptive and was based on the presence of a rightto left shunt in the absence of a left-sided thromboembolic
source. Its association with migraines is still open to question.
The question also arose, whether transcatheter device closure
of PFO really shut the door?8
In a multicenter European study with 581 patients who had
an ischemic stroke, an association of recurrent stroke rate for
patients with ASA and PFO was 15.2 percent compared with
4.2 percent in the absence of these 2 defects.9 A prospective
population-based study, Patent foramen ovale In Cryptogenic
Stroke Study (PICSS), suggested that after correction for age
and comorbidity, an isolated PFO was not an independent
risk factor for future cerebrovascular events in the general
population.10 Unfortunately, the patients in this study were
not truly representative of the PFO patient population with
ischemic stroke. The quest for an answer to whether to close
or not to close the PFO in adults with cryptogenic stroke
younger than 55 years by a percutaneous device is still on. A
recent randomized trial (Closure I) did not detect any benefit
of closure over medical treatment alone.11-13
With respect to selection of antiplatelet versus
anticoagulant therapy, the data continues to be controversial.
In the Warfarin-Aspirin Recurrent Stroke Study (WARSS),
2,206 patients were randomized to aspirin or warfarin (INR
1.4 to 2.8) with no significant benefit from either treatment
at 2 years.14 The present opinion based on observational and
randomized data from 9 studies that compared the medical
therapies is consistent and suggests that anticoagulants are
superior to antiplatelets for preventing stroke recurrence.11,15
While the search for the optimal management continues,
patients with large PFO, especially in the setting of an atrial
septal aneurysm, may receive low dose aspirin for primary
prevention of thromboembolic events.
54
table 1
Heart defect
Cardiac examination
Residual and sequelae
Associated defects
(common)
Patent foramen
ovale
None
Paradoxical embolus
stroke
Atrial septal aneurysm
Secundum atrial septal

defect
Prominent right ventricular

impulse
Wide fixed splitting of S2
Pulmonary ejection systolic
murmur at left upper sternal
edge
Accentuated P2
Atrial arrhythmias
Right heart failure
Left ventricular dysfunction
Paradoxical embolism/stroke
Anomalous pulmonary
venous return
Pansystolic murmur
Precordial thrill
Accentuated P2 (in
pulmonary hypertension)
Infective endocarditis
Conduction defects
(heart block)
Aortic insufficiency
Atrial septal defects (ASDs)

Aortic valve regurgitation
Aortic root dilatation
Patent ductus arteriosus
Continuous machinery
murmur at the left upper
sternal border with radiation
to the back
Infective endocarditis/
endarteritis
Left ventricular heart failure
Aneurysmal
Calcification
Rupture
Occurs in association with

several congenital heart
defects
Accounts for 10% of all
congenital heart defect
(CHD)
Adapted from Chugh, R Caring for the adult with congenital heart disease: management of common defects. Perm J. 2007 Spring;11(2):40-6.
Atrial Septal Defects

One in six individuals born with an atrial septal defects (ASDs)
is likely to be first diagnosed in adulthood. Palpitations due to
atrial arrhythmias and dyspnea are the most common presenting
symptoms. An ASD is a direct communication between the
cavities of the atrial chambers that permits shunting of blood.
Associated defects occur in nearly 30 percent of patients with
a secundum ASD (the most common form). Characteristic
physical findings are a prominent right ventricular parasternal
lift, persistent or wide fixed splitting of the second heart sound
and a pulmonary systolic ejection murmur, at the left upper
sternal edge due to increased pulmonary flow. Pulmonary
hypertension leads to an accentuation of the pulmonary
component of the second heart sound. Electrocardiogram (ECG)
may show sinus rhythm or atrial fibrillation, right axis deviation
(left axis deviation in primum ASD) and a bifid notch on the
ascending limb of the R wave in inferior leads (crochetage).16
Transthoracic echocardiography establishes the diagnosis in
most cases by demonstrating a discontinuity of the interatrial
septum on two-dimensional echocardiogram and an intracardiac
shunt at the atrial level with color Doppler. Long-standing
significant left-to-right shunt causes right heart enlargement
and elevated pulmonary artery pressures, which is an indication
for ASD closure. A sinus venosus defect with associated

anomalous pulmonary venous return is suspected, when there
is right heart enlargement in the absence of a clearly defined
interatrial shunt. Further evaluation with a transesophageal
echocardiogram is recommended in these cases and in all cases
prior to ASD closure to rule out concomitant congenital heart
defects. Possible reasons for clinical deterioration in adults with
unclosed ASD are listed in Box 1.
The consensus is to close defects in symptomatic patients
and in those with right heart enlargement. Percutaneous
transcatheter device closure is presently the method of choice
for defects within the fossa ovalis with an adequate rim
of at least 4 to 5 mm (in order to avoid distortion of these
surrounding structures), between the ASD and the aortic valve
annulus, atrioventricular (AV) valves, pulmonary and systemic
veins. In the presence of pulmonary hypertension, the defect
may be safely closed if pulmonary artery systolic pressure
is less than 50 percent of the systemic arterial pressure.
Right heart catheterization to assess the pulmonary vascular
resistance may be required for those with higher pulmonary
artery pressures. In general, all defects should be considered
for early closure unless there are specific contraindications.
Endocarditis/endarteritis prophylaxis is recommended for 6
months after device closure.1
ManageMent issues in aDults witH Congenital Heart Diseases
Shunt lesions
753
10
754
Box 1: Causes for clinical deterioration in adults

with unclosed asD
Age-related decrease in left ventricular compliance may
lead to augmentation of the left-to-right shunt
Heart failure may be precipitated by atrial arrhythmias
Persistence of left-to-right shunt may lead mild to
moderate pulmonary hypertension, consequent right
ventricular pressure and volume overload
Delayed closure has been shown to be associated with a
higher likelihood of long-term complications:
Atrial arrhythmias
Right heart failure
Paradoxical embolism and stroke
Victor Eisenmenger in 1897 described a bidirectional or

reversed (right-to-left) shunt through the large VSD leading
to severe pulmonary hypertension. It was later defined by
Dr Paul Wood in 1958 as Eisenmenger syndrome with its
distinctive clinical and physiologic characteristics.19
In patients with a supracristal (subpulmonic) VSD there
is progressive aortic regurgitation, due to prolapse of the
aortic valve leaflet into the defect resulting from the venturi
effect. Closure of the VSD along with aortic valve repair is
recommended to avoid progressive left ventricular dilatation and
dysfunction from worsening aortic regurgitation. Endocarditis/
endarteritis prophylaxis is recommended for 6 months after
surgical closure for an isolated VSD and should be continued
lifelong if there is concomitant valve surgery or residual shunt.1
While some small ventricular septal defects (VSDs) close

spontaneously in childhood (10%), others persist into adulthood
with a 25 percent likelihood of serious complications.17 The
VSD is a communication between the two ventricles resulting
from the failure of the components of the interventricular
septum to fuse, with the perimembranous VSD being the
most common form. Residual shunts are sometimes seen in
patients with larger VSDs, who have undergone surgery or
percutaneous closure. Although aware of a murmur all through
their lives, many asymptomatic individuals are only diagnosed
in adulthood. Physical examination is characteristic of a
pansystolic murmur (and sometimes precordial). The pulmonic
component of the second heart sound may be accentuated in the
presence of pulmonary hypertension. Late closure of a VSD
predisposes to long-term residua and sequelae in adulthood.16
Echocardiography defines its location, degree of shunt
and associated defects and most long-term issues depend on
these parameters. The most important clinical issue is the risk
of endocarditis seen in around 11 percent of the adult with
a VSD.17 Meticulous dental hygiene, skin care, antibiotic
prophylaxis before dental procedures and early treatment of
infection are strongly recommended.
Common long-term complications of persistent VSD are
heart failure, pulmonary hypertension and arrhythmias,17 that
depend on the volume and pressure load. The direction and
the volume of an interventricular shunt are dictated by the size
of the defect and the ratio of pulmonary vascular resistance
to the systemic vascular resistance. The left heart experiences
volume load and depending on the size of the defect, the right
heart may experience a pressure load. In a small, restrictive
VSD, right ventricular systolic pressure is less than half of
the left ventricular systolic pressure. In a large unrestrictive
ventricular septal defect there is equalization of right and left
ventricular pressures due to free communication between
the two chambers. This leads to near systemic pressures in
the pulmonary arteries that causes irreversible pulmonary
vascular disease and pulmonary hypertension.18
Adults with a small patent ductus arteriosus (PDA) are usually

asymptomatic, while those with a moderate to large PDA may
present with dyspnea or palpitations. Patent ductus arteriosus
is a residual fetal communication between the proximal left
pulmonary artery and the descending aorta distal to the left
subclavian artery. During fetal life, it allows the diversion of
blood from the right ventricle to the descending aorta, thus
bypassing the pulmonary circulation. Physical examination
is remarkable for a continuous machinery murmur at the left
upper sternal border with radiation to the back. In others, PDA
is only detectable on an echocardiogram. After several decades,
PDA may get calcified and become visible on a chest X-ray.16
The long-term residua, sequelae and the type of intervention
depend upon the size and shape of the PDA. The risk of
endarteritis is present in all patients, therefore antibiotic
prophylaxis and early closure are recommended. Heart failure
and pulmonary hypertension are likely to develop with a
moderately sized or larger PDA. Device closure is preferred
for the majority of the patients.20 Surgical closure is indicated,
when PDA is too large and not amenable to device closure
or in the presence of a ductal aneurysm. Patients, who have
increased pulmonary vascular resistance at the time of closure
may present with late pulmonary hypertension. Presence of
severe, irreversible pulmonary vascular disease is a contraindication for PDA closure, as it is for all shunt lesions.
Endocarditis/endarteritis prophylaxis is recommended for 6
months after device closure and lifelong for residual PDA.1
VALVULAR DEFECTS
CONGENITAL PULMONARy VALVE LESIONS
Pulmonary Stenosis
This is the most common form of a right sided obstruction,
resulting from fusion of valve leaflets that may occur as an
isolated heart defect in up to 10 percent of patients with CHD.
The physical examination in an adult with moderate to

severe PS is significant for a prominent right ventricular
impulse palpable at the left sternal border (with or without a
thrill), normal first and widely split second heart sound with
normal respiratory variation, a harsh crescendo-decrescendo
systolic murmur that becomes louder with inspiration and is
heard best at the left upper sternal border.16
Echocardiography confirms the diagnosis and assesses
the severity of the transvalvular gradient, right ventricular
systolic pressure, right ventricular size, function and associated
defects (Table 2). Based on the peak systolic gradient on
transvalvular Doppler, the severity of PS is graded as mild
table 2
Valvular defects
Heart defect
Salient findings on
cardiac examination
Residua and sequelae
Associated defects
(common)
Pulmonary stenosis
Widely split second heart sound

with normal respiratory variation
Harsh crescendo-decrescendo
systolic murmur radiating to the
back and louder with inspiration
best heart at the left upper sternal
border
Pulmonary artery dilatation/
aneurysm
Right ventricular hypertrophy
Right heart failure
Sudden cardiac death
Patent foramen ovale (PFO)

Atrial septal defect (ASD)
Ventricular septal defect (VSD)
Peripheral pulmonary stenosis
Right heart enlargement

Widely split second heart sound
(absent if rudimentary or absent
Right heart failure
valve tissue)
Crescendo-decrescendo, short
diastolic murmurbest heard in the
second or third intercostal space
Pulmonary valve abnormalityisolated

Tetralogy of fallot
Ebsteins anomaly
Widely split first heart sound, split

second heart sound, soft, early
systolic murmur that increases
with inspiration best heard at the
lower left sternal border
Atrial arrhythmias- fibrillation/

flutter2530%
Supraventricular tachycardia
Right heart failure
Left heart failure
Cyanosis
Paradoxical emboli
PFOvery common
ASDover 30%
Wolf-Parkinson-White
syndrome525%
Congenitally corrected
transposition of the great
arteries (CCTGA)
VSD
Patent ductus arteriosus (PDA)
Left heart abnormalities
including left ventricular noncompaction (LVNC)40%
Pulmonary stenosis or atresia
Tetralogy of Fallot
Systolic ejection click

Early peaking systolic flow murmur
Aortic dissection
Aortic stenosis
Aortic insufficiency
Sub and supra-aortic stenosis
VSD

(MVP)
Apical mid to late systolic clicks

Late systolic murmur with
radiation to the apex due to mitral
regurgitation
Mitral regurgitation
Atrial arrhythmias
Endocarditis
MVP syndrome
Heart failure
Syncope (related to orthostatic
hypotension)
Sudden cardiac deathrare
Secundum ASD
Holt-Oram syndrome
Ebsteins anomaly
Marfan syndrome
Osteogenesis imperfecta
54
Pulmonary stenosis (PS) has been associated with maternal

rubella, Noonans syndrome, Williams syndrome and Alagille
syndrome.
Most patients with mild PS are asymptomatic and at lowrisk of getting infective endocarditis. Patients with the domeshaped valve are likely to have fusion of the leaflets with
increasing stenosis and calcification in adulthood. There is a
higher likelihood of pulmonary artery dilatation and aneurysms
due to an associated connective tissue disorder.21 In contrast, the
dysplastic pulmonary valve with thickened leaflets is not usually
associated with pulmonary artery dilatation. Other forms are
unicuspid, bicuspid, tricuspid, quadricuspid or their variations.
755
10
756
(2549 mm Hg), moderate (5079 mm Hg) and severe (over 80

mm Hg). In order to avoid adverse effects from long-standing
significant PS, percutaneous balloon valvuloplasty should
be performed, when the peak transvalvular gradient is over
50 mm Hg, even when the patient is asymptomatic.22 Severe
PS can lead to marked right ventricular hypertrophy, right heart
failure and risk of sudden cardiac death. Surgical valvotomy
or pulmonary valve replacement is considered, when there is
significant calcification, a thickened stiff dysplastic valve and/
or concomitant pulmonary artery aneurysm. Pulmonary valve
replacement (transcatheter or surgical) is indicated for severe
pulmonary regurgitation before it affects the right ventricular
function.1
Pulmonary Regurgitation
Clinically insignificant trace to mild pulmonary regurgitation
(PR) is seen in individuals with structurally normal hearts.23
It rarely occurs as an isolated defect. Most adults present
with significant PR in association with tetralogy of Fallot and
rarely with other malformations. Significant PR may occur in
the presence of morphologically abnormal pulmonary valves
or when there is total absence of the pulmonary valve. While
most adults tolerate low pressure PR, a small group may
develop right heart enlargement and right heart failure due to
long-standing severe PR.24 Pulmonary hypertension (primary
or secondary) can contribute to progression of PR.
Isolated PR is incidentally diagnosed because of the murmur,
in association with a dilated pulmonary trunk noted on a chest
X-ray or as an incidental finding on an echocardiogram.
On clinical examination, patients with right heart failure
will have prominent A and V waves of the jugular venous
pulse. On palpation, in patients with severe PR, there is a
hyperdynamic pulse at the left sternal border and subxiphoid
area. Dilated pulmonary artery may generate prominent
pulsations in the second left intercostal space. On auscultation,
a normal first heart sound is usually followed by a widely
split second heart sound (usually associated with increase
capacitance of the pulmonary vascular bed and slow elastic
recoil) that decreases with inspiration in the absence of right
heart failure. The second heart sound is absent, when there
is rudimentary or absent valve tissue. Patients with moderate
to severe PR have a distinctive crescendo-decrescendo, short
diastolic murmur that is best heard in the second or third
intercostal space.16
Two-dimensional echocardiogram defines the anatomy of
the pulmonary valve, the size of the main pulmonary artery,
proximal right and left branches, size and contractility of the
right ventricle. Pulmonary regurgitation is primarily graded
by color Doppler. An important point to note is that the right
ventricular outflow tract may have pulsatile motion in the case
of low pressure severe pulmonary regurgitation, even when
the color Doppler is not too impressive. Significant right heart
enlargement occurs with long-standing severe pulmonary

regurgitation. The interventricular septum is dyskinetic due to
right heart volume overload and the left ventricle may appear
D-shaped on the parasternal short-axis view.
Pulmonary valve replacement is indicated in patients
with severe pulmonary regurgitation, who are symptomatic
or have early signs of right heart enlargement with impaired
ventricular function.1
CONGENITAL TRICUSPID VALVE DEFECTS

Ebsteins Anomaly
Ebsteins anomaly is an abnormality of the tricuspid valve
characterized by the tethering of the septal leaflet to the
ventricular septum that gives an impression of apical
displacement of the tricuspid valve. It is associated with
discontinuity of the central fibrous body, which lends itself to
creating a substrate for accessory pathways and type B WolfParkinson-White (WPW) syndrome in 5 to 25 percent of the
cases. These patients are therefore predisposed to having
supraventricular tachycardia.25
On physical examination, the characteristic signs are a
palpable impulse in the left third intercostal space (due to an
enlarged infundibulum). On auscultation, the first heart sound
is widely split due to a delayed loud tricuspid component
(caused by the increased excursion of the elongated anterior
leaflet of the tricuspid leaflet that delays closure of the
valve). In the presence of a right bundle branch block, the
second heart sound is also split due to delayed closure of the
pulmonary valve. A quadruple rhythm may be heard due to
third and fourth heart sounds. There is a soft, early systolic
murmur that increases with inspiration and is best heard at the
lower left sternal border.16
The characteristic finding on the electrocardiogram of the
tall, peaked Himalayan p waves (described by Dr Helen
Taussig) occur primarily due to prolonged aberrant conduction
through the markedly enlarged right atrium.26 PR interval may
be prolonged in 50 percent of the cases except, when there
is preexcitation (demonstrated by an intermittent delta wave)
due to type B WPW syndrome in nearly 25 percent of the
cases. Additionally, there is right bundle branch block pattern
and deep Q waves in the inferior leads, as well as in V1-4.25
Chest X-ray is notable for a narrow vascular pedicle due to
lack of pulmonary artery border and a narrow ascending aortic
shadow. A box-like appearance of the cardiac silhouette is
due to a very prominent right atrial border contributing to the
right heart convexity and a dilated infundibulum contributing
to left heart convexity.16
Echocardiogram defines the morphology of the tricuspid
valve and allows assessment of the right atrial size, biventricular
size, function and associated defects (Table 3). The tricuspid
valve is characterized by apical displacement due to tethering
54
table 3
Heart defect
Salient findings on
cardiac examination
Associated defects
(common)
Thrill in the suprasternal notch

Loud aortic closure sound
Hypertension
Infective endocarditis/endarteritis
Recoarctation
Aortic aneurysm
Premature coronary artery
disease

Aortic aneurysm
Intracranial aneurysms
Subaortic stenosis
Mitral stenosis
Tetralogy of Fallot post

repair
Right ventricular heave (due to

right ventricular hypertrophy)
Single S2 (aortic component
only)
PR -crescendo-decrescendo
harsh to-and-fro diastolic
murmur loudest at the second
intercostal space
AR - grade 1-2/4 soft diastolic
murmur heard best in the left
lower sternal border
TR
Residual ventricular septal
defectpansystolic murmur at
the left lower sternal border
Signs of right heart failure
elevated jugular venous
pulsations, pedal edema,
ascites
Impaired right and left ventricular

function,
Right ventricular outflow tract
(RVOT) obstruction obstruction/
aneurysm
Ventricular arrhythmiasmonomorphic VT-nonsustained
Residual ventricular septal defect
(VSD)
Conduit (Rastelli) obstruction
Patent foramen ovale (PFO)

Atrial septal defect (ASD)
Muscular VSD
Right aortic arch
Coronary artery abnormalitiescommonest is left anterior
descending (LAD) originating from
right coronary sinus crossing the
RVOT
Hypoplastic pulmonary arteries
Dextro-transposition of
the great arteries
(D TGA)
post atrial switch repair
Single and loud S2 (due to

anterior position of the aortic
valve)
Heart murmurs depending on
associated valvular disease
Systemic ventricular dysfunction

Baffle leak
Baffle obstruction
Tachyarrhythmias
Bradyarrhythmias
VSD
PFO/ASD
Patent ductus arteriosus (PDA)
AV septal defect
Coronary artery fibrosis18%

Sudden cardiac deathischemia/
sustained ventricular tachycardia
Neoaortic valve regurgitation
Mild aortic root dilatation
Pulmonary artery stenosis at the
valvar, supravalvar or peripheral
levels525%
Ventricular function may be
affected due to coronary ischemia
in a small number of patients
Arrhythmias-atrial,
supraventricular tachycardia
(SVT) and advanced heart block
Endocarditis
As noted above
D TGA
post arterial switch
repair
Diastolic murmur due to neoaortic valve regurgitation

Pulmonary ejection murmur if
conduit stenosis is present
Abnormal origin of the coronary

arteries coarctation of aorta
(COA)5%
Left ventricular outflow tract
(LVOT) obstruction (subpulmonic
stenosis)25%
RVOT obstruction(subaortic
narrowing)
757
Contd...
Complex congenital heart defects
10
Contd...
758
Heart defect
Salient findings on
cardiac examination
Associated defects
(common)
D TGA post-Rastelli
repair
Pulmonary ejection murmur if

conduit stenosis is present
Diastolic murmur if conduit
regurgitation is present
Reoperations for conduit

obstruction
Arrhythmias-atrial and ventricular
Heart block
25%
Right ventricular dysfunction
Endocarditis
As noted in the previous page
Congenitally corrected
transposition of the
great arteries
Loud usually single second

heart sound (A2), soft P2.
Systolic murmur at the left
sternal border or apex due to
systemic AV valve regurgitation,
other murmurs depending upon
the associated defects
Systemic ventricular dysfunction

Heart failure
Systemic AV valve (tricuspid)
regurgitation
Complete heart block
Emboli stroke
Endocarditis
Conduit stenosis (in Rastelli
repair)
Ventricular septal defect (6080%)

Pulmonary stenosis
Tricuspid valve abnormality
(Ebstein/Ebstein-like
abnormality or dysplastic)
Patent foramen ovale
LVOT obstruction-subaortic or
supravalvular stenosis
Coronary artery anomaly (inverted
due to ventricular inversion)
Tricuspid atresia post

Fontan operation
Usually, quiet heart sounds

Single second heart sound
Holosystolic murmur radiating
to the apex due to mitral
regurgitation.
Heart failure
Systemic (usually left) ventricular
dysfunction
Atrial arrhythmias
Thrombus in the right atrium
Protein losing enteropathy
Endocarditis
Pacemaker
Atrioventricular valve regurgitation
Conduit obstructionObstruction
of the Fontan connectionusually
right pulmonary vein compression
with enlarged right atrium or
conduit obstruction
Univentricular heart/single ventricle

physiology with a hypoplastic right
ventricle
of the septal leaflet, over 2 cm in adults, in relation to the

septal attachment of the mitral valve. In contrast, the anterior
leaflet appears elongated and large with sail-like motion. The
right atrial size appears larger due to atrialization of the right
ventricle, with relatively small right ventricle. Color Doppler
is used to assess the severity of tricuspid regurgitation and
rule out an interatrial communication such as a patent foramen
ovale or an atrial septal defect.
Clinical presentation in adults with Ebsteins anomaly
depends upon the severity of morphological tricuspid valve
abnormality, the functional status (degree of regurgitation)
of the tricuspid valve and the presence of associated defects.
Adults with mild abnormality of the tricuspid valve with no
associated defects may remain asymptomatic for most of
their lives. The most common clinical issues in adulthood
are atrial arrhythmias such as atrial fibrillation/flutter and
supraventricular tachycardia. Dyspnea and decreased exercise
tolerance occurs due to an inadequate increase in pulmonary
blood flow and a decrease in systemic arterial oxygen

Transposition of the great arteries
saturation with activity. Severe tricuspid regurgitation and

increased degree of apical displacement of the tricuspid valve
predisposes to right heart failure. Eventually, left heart failure
may develop due to prolonged cyanosis, interventricular
dependence and left heart fibrosis.
Cyanosis occurs, when high filling pressures of the volumeoverloaded right ventricle instigate right-to-left shunting at the
atrial level. These patients are at risk for paradoxical emboli
or cerebral abscess because of the interatrial communication
(PFO or ASD). Atypical chest pain, the etiology of which is
not clearly understood, but sometimes attributed to sternal
compression of the enlarged right heart, is also seen in some.
Uncontrolled arrhythmias cause hemodynamic deterioration,
progressive cyanosis and syncope. The risk of sudden
cardiac death may be increased by sustained tachycardias
such as atrial fibrillation/flutter with rapid ventricular rates.
Atrial arrhythmias should be managed with medications.
Radiofrequency ablation (RFA) should be considered when
there is an accessory pathway, even though it is associated
CONGENITAL AORTIC VALVE DEFECTS

Bicuspid Aortic Valve
Infective endocarditis is often the clinical scenario in which
undiagnosed adults with bicuspid valves present, whether
or not it may have led to severe aortic regurgitation due to
damaged valve tissue.
Bicuspid aortic valve is defined as an aortic valve with
(effectively) two instead of three valve leaflets, with many
variations in the pattern. It most commonly presents with
fusion of the right and left aortic valve cusps. On physical
examination, there may be a systolic ejection click and an
early peaking systolic flow murmur (Table 3).
The diagnosis is confirmed by an echocardiogram. In the
parasternal short axis view, a bicuspid aortic valve (BAV)
opens as an oval (American football) in contrast to the
triangle of a trileaflet valve that appears like the Mercedez
Benz sign when closed. A transesophageal echocardiogram
may be required when the aortic valve morphology cannot
be visualized clearly in the parasternal short axis view on
a transthoracic echocardiogram. Approximately 9 percent
patients with BAV will have an autosomal-dominant pattern
of inheritance with incomplete penetrance and variable
expression that may affect several family members. Therefore,
echocardiographic screening of first-degree relatives is
recommended to look for BAV.30
A complete echocardiographic examination should define the
morphology, degree of aortic stenosis and aortic regurgitation
and assessment of associated defects (seen in 2050% of the
patients).
Due to inherent aortic structural wall abnormalities, BAV
has an associated risk of aortic root dilatation and aortic
dissection.21 The risk is markedly increased, when BAV
is associated with coarctation of aorta. Progression of the
ascending aortic dimensions may be achieved by controlling
hypertension, avoiding heavy weights and isometric exercises.
Although aortic root dilatation is most commonly associated

with Marfans syndrome, in absolute numbers there are more
people, who have aortic dilation associated with BAV (since
BAV is a more common defect). The aortic root dimensions
should be followed on serial echocardiograms. Computerized
tomography (CT) scan or magnetic resonance imaging (MRI)
is required, when aneurysm of descending aorta is suspected
in patients with coexistent coarctation of aorta.
Calcification leads to stenosis of the BAV at an earlier age
in men than in women, with an average increase of 18 to 27
mm Hg in the aortic valve gradient for each decade of life.
Anatomy of the cusps and acquired risk factors affect the rate
of progression. In patients with left ventricular dysfunction, the
valve gradients may underestimate the degree of stenosis. Risk
factors for atherosclerosis such as hyperlipidemia, hypertension,
obesity and smoking may also contribute to the age-related
deterioration of the aortic valve. Intensive cardiovascular risk
reduction should be advised to all patients with BAV.
Aortic valve surgery (repair or replacement) is performed
in symptomatic adults with severe aortic stenosis or significant
regurgitation. Concomitant aortic root surgery is performed
with the aortic root dimensions are over 4 cm. Emergent surgery
is required in those presenting with infective endocarditis and
new onset severe aortic regurgitation or an aortic root abscess.1
Due to a very high incidence of endocarditis and its associated complications, antibiotic prophylaxis is recommended
in all patients, even in the absence of associated stenosis or
regurgitation.
54
with relatively low success rates.27 Right heart catheterization

should be avoided since stimulation of the atrialized right
ventricle may produce ventricular tachycardia or ventricular
fibrillation.
Surgical repair or replacement of the abnormal tricuspid
valve and concomitant defects should be performed in
adults, who have poor functional capacity despite medical
therapy28,29 and/or have right heart failure or progressive
cyanosis. Valve repair is preferred over replacement, but it
can be very challenging due to the severity of tricuspid valve
abnormality. A bioprosthetic valve is preferred when valve
replacement needs to be performed.
Although endocarditis is rare in isolated Ebsteins anomaly,
probably because of the low velocity tricuspid regurgitant jet,
it is prudent to offer endocarditis prophylaxis, especially in
the presence of concomitant defects.1
CONGENITAL MITRAL VALVE DEFECTS

Mitral valve prolapse (MVP) is a very common connective
tissue abnormality of the mitral valve frequently associated
with mitral regurgitation (MR) and endocarditis in adults
with otherwise structurally normal hearts. It often occurs in
association with other CHD and connective tissue disorders.
Clinical symptoms of increasing dyspnea and decreasing
exercise tolerance may be related to severe mitral regurgitation
with or without atrial fibrillation, heart failure and/or
pulmonary hypertension. Endocarditis prophylaxis should be
offered, especially to those with significantly myxomatous
mitral valves and associated regurgitation. Acute rupture of
chordae may occur in severe MVP leading to acute severe
mitral regurgtitation and heart failure. Stroke probably from
an embolic phenomenon may occur due to platelet aggregation
on markedly myxomatous disrupted endocardial surface.
Mitral valve prolapse syndrome may occur in some adults
(especially in women) with atypical chest pain/pressure,
palpitations, anxiety, orthostatic hypotension (probably due to
autononic dysfunction).31 Management of the MVP syndrome
is primarily supportive with increased hydration, reduced
caffeine intake, aerobic activity, beta blockers, adequate dietary
759
10
potassium and magnesium intake. Significant orthostatic

hypotension in the absence of heart failure, may respond to
volume expansion with good hydration, high sodium intake
and the use of fludrocortisone acetate (Florinef USP). It is
a synthetic adrenocortical steroid, which produces marked
sodium retention and increased urinary potassium excretion,
because of its mineralocorticoid effects. This leads to a rise in
blood pressure, because of the effects on electrolyte levels. It
is usually prescribed as a daily oral dose of 0.1 mg.
On physical examination, although apical mid to late
systolic clicks (due to sudden tension in the subvalvular
apparatus when the leaflets prolapse) have been reported, the
more frequent auscultatory findings are a late systolic murmur
with radiation to the apex due to mitral regurgitation. ECG may
demonstrate nonspecific ST and T wave abnormalities that can
cause false positive treadmill stress tests. Two-dimensional
or three-dimensional, transthoracic or transesophageal echocardiography are the most accurate diagnostic methods.32
Afterload reduction with angiotensin converting enzyme
(ACE) inhibitors or angiotensin receptor blockers is
recommended in hypertensive adults with mitral regurgitation.
Mitral valve repair should be considered early in symptomatic
patients with preserved left ventricular size and function.
Although mitral valve replacement is less desirable, it
may be the only option for those with very friable, heavily
myxomatous valves with severe prolapse.
Cleft Mitral Valve

Besides MVP, congenital MR may occur in association with
a cleft mitral valve, usually seen in association with Down
syndrome or rarely as an isolated defect. The management
in adults with mitral regurgitation is guided by the criteria
outlined for acquired mitral regurgitation.33
Congenital Mitral Stenosis
760
A diverse group of congenital mitral valve anomalies can

cause obstruction to left atrial flow and that leads to mitral
stenosis. Although rare in adults, the diagnosis is confirmed
by transthoracic or transesophageal echocardiogram.
Most adults have had mitral valve replacement, since the
severe cases are usually diagnosed in childhood. It is rare
for an adult to present with Shones complex, characterized
by a supravalvular membrane or ring, parachute mitral
valve, subaortic stenosis and coarctation of aorta.16 Usually
presenting as a stable lesion, the supravalvular mitral ring
may also be seen in association with a VSD, PDA, AV septal
defects or double outlet right ventricle (DORV).
Clinical presentation is similar to rheumatic mitral stenosis,
with the additive effect from associated defects. When
congenital MS occurs in association with an ASD, there may
be an increase in left atrial pressure and left-to-right shunt.
Hence, closure of ASD will help reduce pulmonary blood

flow and the risk of developing pulmonary hypertension.
Echocardiography defines the morphological defect, left
tip mobility, papillary muscle anatomy and examines for
presence of a supravalvular fibrous membrane. The severity
of mitral stenosis is assessed by pressure half-time based
calculation of valve area, mean gradient and estimated of
the right ventricular systolic pressure that is a surrogate
for pulmonary artery pressures. In double orifice valve or
supravalvular membrane with multiple orifices, the area of the
individual orifices is added to give a total orifice area. Medical
management includes diuretics, beta blockers and arrhythmia
control. In case of severe symptomatic stenosis, surgery is
performed.33
Coarctation of Aorta
While moderate to severe coarctation of aorta (COA) is
usually diagnosed in infancy or childhood, the diagnosis is
suspected in a person presenting with secondary hypertension
in adulthood. Severe left ventricular hypertrophy by voltage
criteria on an electrocardiogram or by echocardiographic
criteria in a young adult should raise an alarm.
Coarctation of aorta is congenital narrowing of the aorta at
the junction of the distal aortic arch and the descending aorta,
below the origin of the left subclavian artery. It comprises up to
8 percent of all CHD. The discrete coarctation is not just limited
to focal stenosis, but is one variant of a diffuse arteriopathy and
associated structural abnormalities of the great arterial walls.16
A brachial and femoral blood pressure recording demonstrates
upper-body arterial hypertension. There are decreased arterial
pulsations and blood pressure in the left upper extremity when
there is interrupted blood flow into the left subclavian artery
(with compensatory blood flow via collaterals). Accurate
blood pressure recordings are obtained from the right arm in
these individuals. Characteristic physical findings are weak,
delayed femoral pulses, prominent left ventricular impulse,
a loud aortic closure sound, thrill in the suprasternal notch
and vascular murmur between the shoulder blades beginning
in mid systole and persisting beyond the second heart sound.
Continuous murmurs due to collaterals may be present.
Echocardiography demonstrates the gradient across the
aortic arch and defines the commonly associated defects bicuspid aortic valve in 75 to 85 percent of the cases, aortic
root dilatation/aneurysm, VSD, mitral valve abnormalities
(Table 3) and allows assessment of left ventricular mass
and function. MRI is useful for delineating aneurysms in
postoperative cases and also shows site of the stenosis, the
extent and degree of narrowing, pressure gradient across the
stenosis, aortic arch anatomy, and aortopulmonary collaterals.
Patients with COA are at increased risk for aortic
aneurysms and dissection. Hypertension often persists after
surgery and ambulatory blood pressure monitoring may
Tetralogy of Fallot
This is the most common cyanotic CHD accounting for
nearly 10 percent of all CHDs with slightly higher male
preponderance. Most adults have undergone palliative
surgeries and intracardiac repair. Unoperated adults with
tetralogy of Fallot (TOF) have high morbidity. They may
present with progressive cyanosis, atrial arrhythmias, impaired
biventricular function causing heart failure, paradoxical
emboli through intracardiac shunts leading to thromboembolic
events and cerebral abscesses. They are considered inoperable
in adulthood if irreversible pulmonary vascular disease/severe
pulmonary hypertension have developed. Without definitive
surgery, a high mortality of 25 percent in the first year of life,
40 percent by the 3rd year, 70 percent by 10th year and 95
percent by 40 years of life has been reported.38
Palliative Procedures
Some adults have only had palliative procedures in the past
with the purpose of increasing blood flow to the lungs and to
normalize the growth of the pulmonary arteries restricted due
to varying degree of infundibular stenosis. The major problems
with long-standing shunts are pulmonary hypertension (most
commonly occurs with the Waterston shunt) and stenosis with
narrowing or kinking (most often occurs with Waterston or
Potts shunts). Although the surgical approach has evolved
over the years, the basic palliative procedures and intracardiac
repairs are discussed in the Box 2. The long-term residua and
sequelae after a palliated shunt are the following:
Progressive cyanosis and complications associated with
prolonged cyanosis
Persistent interatrial shunt
Progression of pulmonary vascular disease
Pulmonary arteriovenous fistulae
54
Box 2: surgeries for tetralogy of Fallot
Palliative surgical procedures
Blalock-Thomas-Taussig (BTT) shunt: Classic shuntsubclavian to pulmonary artery anastomosis (end to side)
Modified BTT shunt: subclavian to ipsilateral pulmonary
artery
Waterston shunt-ascending aorta to main or right
pulmonary artery
Potts shunt-descending aorta to left pulmonary artery
(side-to-side)
Brock procedure-closed pulmonary valvotomy
Intracardiac repair
Salient features of a complete intracardiac repair are the
following:
Ventricular septal defect (VSD) patch repairWhen
more than half of the aortic valve is connected to the
right ventricle, the surgery is more complex since a larger patch is required across the VSD in order to connect
the aorta to the left ventricle.
Right ventricular outflow tract (RVOT) surgeryDepending upon the anatomical variations, the following are the
more commonly performed surgeries for the RVOT.
Pulmonary valvotomyPreviously known as the
Brock procedure (closed pulmonary valvotomy), it is
now performed at the time of intracardiac repair for
pulmonary stenosis (PS).
RVOT obstruction
- Previous surgical approach was to relieve obstruction
by infundibular muscle resection and/or by using
a patch across the RVOT or a right ventriculotomy
incision followed by and transannular patch
- Current surgical approach is a transatrial/
transpulmonary incision involving closure of the
VSD, relief of RVOT obstruction through the right
atrium and pulmonary artery.
Extracardiac conduit from right ventricle to pulmonary
artery (RV to PA ) conduit is indicated in the following
cases:
- Pulmonary atresia/severe stenosis of RVOT
- Coronary artery abnormality with the left anterior
descending (LAD) from right coronary cusp crossing
the RVOT
Concomitant surgeries for associated defects include
the following:
- Atrial septal defects and patent foramen ovale
(ASD/PFO) closure
- Aortic regurgitation repair
- Dilated aortic root (wider than 4 cm)augmentation
with Goretex or Dacron
- Hypoplastic pulmonary arteriespatch augmentation
or angioplasty of the main or branch pulmonary
arteries.
Pulmonary or subpulmonary stenosis

Atrial or ventricular arrhythmias
detect uncontrolled hypertension in those, who appear to

be normotensive at rest during office visits. Adequate blood
pressure control decreases the incidence of common long-term
complications such as premature coronary artery disease and
heart failure that are unfortunately common in these patients
and the cause of early morbidity and mortality.34,35
Surprisingly, intracranial aneurysms occur even in
normotensive patients with COA, presenting as headaches
or even hemorrhage due to rupture.36 All patients with COA
must receive endocarditis prophylaxis, since they are at risk
for endarteritis and endocarditis involving associated lesions.
Resection of the COA with end-to-end anastomosis is the
procedure of choice in most adults. Early operation reduces
long-term complications. Angioplasty with/without stenting
is an option for coarctation, recoarctation or residual stenosis
in the absence of any paracoarctation aneurysms.1 Since
ambulatory hypertension, occurs, even after intervention or
surgery it should be treated aggressively to reduce long-term
morbidity and mortality.37
761
10
Endocarditis
Paradoxical thrombo-embolism through interatrial rightto-left shunt.
Intracardiac Repair
The main purpose of the surgery is to close the VSD
and correct the overriding of the aorta, relieve the right
ventricular outflow tract obstruction and the pulmonary valve
abnormality. Follow-up of operated adults with TOF depends
upon a host of factors including the nature of previous
procedures/surgeries.
The main issues with intracardiac repairs are usually related
to an older surgical approach with right ventriculotomy incision/
transannular patch that predisposes to progressive PR due to loss
of integrity of the pulmonary valve annulus. The hemodynamic
burden of wide open PR on the postventriculotomy scar/the
transannular patch, generates an electrical nidus for monomorphic ventricular tachycardia. In addition it leads to right
ventricular dilatation and impaired ventricular function.
Ideally, a redo intracardic repair with removal of the scar/
aneurysm at the site of the transannular patch followed by
pulmonary valve replacement (PVR) is recommended before
right heart enlargement and impairment of right ventricular
function occurs. Progressive tricuspid valve regurgitation
due to stretching of the annulus may also predispose to heart
failure and atrial arrhythmias. PVR is often delayed until early
adulthood, since the valve size cannot keep up with individual
growth during childhood and adolescence. Additionally,
since the bioprosthetic valves have a limited life span of
10 to 15 years, cardiologists often try to minimize the number

of surgeries required in a lifetime by appropriately timing and
sometimes delaying the redo surgeries.
Early repair ensures much better long-term outcomes
for individuals born with TOF. In adults with repaired TOF,
the main surgical issue is impaired exercise performance,
supraventricular or ventricular arrhythmias, increasing
tricuspid regurgitation, right ventricular dilatation and failure.
A timely reoperation may protect from these adverse outcomes
and therefore it is important to determine the appropriate
timing of pulmonary valve replacement.39
All patients need follow-up preferably twice a year for
early detection and management of common residua and
sequelae noted in Table 3. The more commonly reported
clinical symptoms are exertional dyspnea, palpitations
(atrial arrhythmias), pedal edema, ascites (due to passive
liver congestion in advanced right heart failure), presyncope
and syncope (may be due to ventricular arrhythmias).
Characteristic physical findings are related to multivalvular
disease (regurgitation of the pulmonary, tricuspid and aortic
valves). ECG and echocardiogram should be performed every
12 to 18 months unless indicated sooner due to any change in
clinical status. On a routine ECG the presence of right bundle
branch block (RBBB)) is a universal finding post repair in
an adult with tetralogy of Fallot (Figure 1). The key points
to review on serial electrocardiograms are QRS duration,
since QRS prolongation is associated with an increased risk
of ventricular arrhythmias.40 Other abnormalities are QT
prolongation, varying degree of heart blocks, atrial fibrillation
or flutter.
762
Figure 1: ECG in a 43-year-old man with tetralogy of Fallot showing right bundle branch block (RBBB).
The QRS duration should be followed-up on serial electrocardiograms
as seen with Marfan syndrome, bicuspid aortic valve and

coarctation of aorta. It is not uncommon to see patients remain
stable with aortic roots around 5 cm.
TRANSPOSITION OF THE GREAT ARTERIES

Dextro or d-Transposition of the Great Arteries
Most adults with d-Transposition of the great arteries (D TGA)
have had a previous atrial switch (Mustard or Senning) repair.
The younger adults who have undergone an arterial switch
(Jatene) repair are now presenting in the adult CHD clinics. In
D TGA, there is ventriculoarterial discordance with the aorta
arising from the right ventricle and the pulmonary artery arising
from the left ventricle. Instead of a normal circulation with a
single series circuit, the ventriculo-arterial discordance makes
the blood circulate in two separate parallel circuits, without
allowing oxygenation of the systemic blood. Infants born with
an isolated D TGA have a very poor survival with up to 90
percent mortality in infancy.46 Survival is only possible after
birth when there is mixing of the blood through an intracardiac
shunt (ASD, VSD or PDA). Other associated defects are listed
in Table 3.
In a normal heart, the ascending aorta is posterior and
runs crisscross in relation to the main pulmonary artery.
Characteristics findings on an echocardiogram in DTGA
are that the two great arteries are parallel to each other. The
ascending aorta is anterior and rightward in relation to the
main pulmonary artery. This finding is best appreciated in the
parasternal short axis view at the level of the great vessels or in
a modified long axis view.
54
Holter test and/or treadmill stress testing should be requested

in a patient presenting with palpitations or presyncope, since
these tests help determine exercise-induced tachyarrhythmias,
chronotropic insufficiency/bradyarrhythmias and very frequent
premature ventricular complexes (PVCs). More than 30 PVCs
per hour have a high correlation with nonsustained ventricular
tachycardia.
Routinely, a tranthoracic echocardiogram is performing to
follow-up long-term residual and sequelae, especially biventricular size, function, pulmonary and aortic valve regurgitation. Severe pulmonary regurgitation is also associated with
propensity for ventricular arrhythmias and timely pulmonary
valve replacement may reduce this risk.41 A stress echocardiogram may be performed to assess the impact of exercise on
the ventricular function, pulmonary artery pressures and valve
gradients.
Impaired left ventricular dysfunction develops partly
because of biventricular interdependence and progressive
aortic regurgitation from poor coaptation of the aortic leaflets in
patients with aortic root dilatation. Congestive heart failure and
sudden cardiac death due to arrhythmias are the main causes of
morbidity and mortality. The causes of congestive heart failure
on TOF post repair are multifactorial and include the following:
Long-standing shunts
Prolonged cyanosis in patients with late repair
Poor myocardial preservation during multiple surgeries
Right heart failure due to severe pulmonary regurgitation.
Although, larger longer-term studies are needed to
determine if ACE inhibitors are beneficial in improving
ventricular remodelling and clinical outcomes, a recent study
reported that ramipril improves biventricular function in
patients with operated TOF.42
Sudden cardiac death related to monomorphic ventricular
tachycardia originating from the postventriculotomy scar
has been documented in many cases. The predictors of high
mortality in TOF are late age at repair, right heart failure and
impaired biventricular function. Left ventricular longitudinal
dysfunction has also been associated with greater risk of
sudden cardiac death/life-threatening ventricular arrhythmias.
It may be considered as a useful adjunct to established
markers such as QRS duration in determining the prognosis in
operated TOF.43
Atrial fibrillation or flutter occurs in nearly 30 percent of
the cases, usually in adults with long-standing systemic to
pulmonary artery shunts, late intracardiac repair or severe
tricuspid regurgitation. Dual chamber pacemakers are indicated
in patients with advanced heart blocks (trifascicular or complete
heart block) due to discontinuity of the bundle of His by a large
VSD. Pulmonary artery dilatation and aneurysm formation
may occur due to intrinsic tissue abnormality.44 Aortic root
dilatation is primarily due to structural abnormalities of the
great arterial walls associated with TOF.45 However, the aortic
root in tetralogy of Fallot is not as vulnerable to dissection
Palliative Procedures
Balloon septostomy of the atrial septum performed soon after
birth allows adequate shunting between the two circuits, so
that there is an adequate supply of oxygenated blood to the
vital organs until a definitive arterial switch repair is performed
(usually after the first two weeks of life in the current era). In
the past atrial switch repair was performed after 6 months of
life. Meanwhile, the balloon septostomy allowed the infants
to survive on 50 to 80 percent oxygenation resulting from the
intermixing of blood.
Atrial Switch Repairs (Mustard or Senning Operations)

These definitive repairs were usually performed in the first
year of life. Dr A Senning described the atrial switch operation
in 195947 and Dr WT Mustard described another version of the
atrial switch operation in 1964 in Toronto.48 These operations
fundamentally involve directing the deoxygenated blood from
the superior and inferior vena cava through a baffle into the
left ventricle, that pumps the blood into the pulmonary artery.
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10
The oxygenated blood returning from the lungs passes through

the pulmonary veins, via another baffle into the right ventricle
that pumps the blood through the aorta into the systemic
circulation. Hence, the morphological right ventricle is the
systemic ventricle and the morphological left ventricle is the
subpulmonic ventricle.
The major difference between the Senning and the Mustard
operations is the material used for the baffle. In the Senning
operation, the baffle is created from the patients tissues
(right atrial wall and part of the atrial septum).47 The Mustard
operation uses pericardium and synthetic material to make the
baffle.48
The long-term residua and sequelae experienced by the
patients, who underwent an atrial switch operation are listed
in Table 4. Most common causes of morbidity and mortality in
this population are heart failure due to progressive impairment
of systemic right ventricular, not designed to withstand the
pressure load of lifelong pumping into the systemic circulation.
Most patients demonstrate decreasing systemic ventricular
function by the second to third decade of life. Bradyarrhythmias
due to chronotropic incompetence from sick sinus syndrome
and atrial arrhthymias related to atrial surgical incisions and
baffle construction affect many young adults.
Rastelli Repair
Dr Rastelli, at the Mayo Clinic described this surgery in
1969.49 In patients with D TGA and pulmonary outflow tract
obstruction who have a large, subaortic VSD, a Rastelli repair
is performed utilizing a conduit to direct the blood from the
right ventricle (via the VSD) to the aorta. The blood from the
left ventricle is directed to the aorta thereby making the left
ventricle the systemic ventricle. These patients are relieved
of the long-term issues related to atrial repair, but may need
further re-operations for the conduit.
While a Rastelli repair in early infancy protects from
prolonged cyanosis, the infant-sized conduit needs more reoperations for replacement over a lifetime. Biventricular
dysfunction may occur due to long-standing conduit obstruction
or volume overload. Long-term issues in the postsurgical
patient with D TGA and Rastelli repair are listed in Table 3.
Long-term Issues with Atrial Switch Repair

Systemic Ventricular Dysfunction and Heart Failure
The right ventricle is unable to keep up with the demands of
pumping into the systemic circulation long-term and begins to
deteriorate in the third decade of life. The degree of deterioration
is multifactorial, but primarily depends on the right ventricular
morphology and demand-supply mismatch from right
ventricular hypertrophy. The right coronary artery is unable
764
to keep up with the increasing blood supply requirements,

leading to perfusion defects. Progressive systemic AV
(tricuspid) valve regurgitation behaves in a similar way like
mitral regurgitation affects a structurally normal heart.50-52
Systemic AV Valve Regurgitation

(Tricuspid Regurgitation)
There is an increased predisposition for systemic AV valve

regurgitation, due to the altered geometry of the systemic right
ventricle in D TGA. The tricuspid annular dilatation, globular
shape of the enlarging right ventricle and displaced chordal
attachments of the systemic AV valve leads to progressive
regurgitation. The systemic AV valve regurgitation then
leads to further right ventricular enlargement and worsening
systemic RV function.
Baffle ProblemsObstruction or Leaks

Baffle leaks usually occur along suture lines and most
commonly along the superior limb of the systemic venous
baffle, in 25 percent of the individuals, who have undergone
atrial switch repair. Fortunately, not all leaks are clinically
significant. A left-to-right shunt through the baffle leak is
hemodyamically more significant, when it has the potential
for volume overloading of the systemic ventricle. Rightto-left shunts are clinically more significant if they are
contributing to worsening systemic arterial oxygenation and
cyanosis.
Obstruction of the superior limb of the systemic venous
Mustard baffle is more common (510%) than that of the
inferior limb (12%). Pulmonary venous baffle obstruction
may occur in around 2 percent of the cases. Transesophagealguided transcatheter intervention with stent implantation may
relieve the obstruction in most cases. In other cases of severe
obstruction, surgical correction may be needed.
Arrhythmias
BradyarrhythmiasResting sinus bradycardia with a slow
junctional escape rhythm is common with progressive
sinus node dysfunction occurring in 50 percent of patients
postoperatively over time. Many patients will need pacemakers
after their third decade of life.
TachyarrhythmiasIncisional atrial re-entry tachycardia
(atypical atrial flutter) occurs in 50 percent of the adults post
atrial switch repair (Figures 2A and B). Electrophysiological
studies and radio frequency ablation (RFA) may help 75
percent of the patients, but the incidence of high grade AV
block requiring a pacermaker is very high.53-55
Pulmonary Vascular Disease

Pulmonary hypertension is more common in patients who
have long-standing shunts and underwent late repairs.
54
B
Figures 2a and B: Serial electrocardiograms in a 35-year-old woman with d-transposition of the great arteries postatrial switch repair
(Mustard operation) showing atrial flutter. The hidden flutter waves are revealed as the rate slows down
Sudden Cardiac Death
Arterial Switch Operation
Although, sudden cardiac death is most often associated with

severe systemic ventricular dysfunction, it is likely to be
arrhythmogenic due to ventricular tachycardia or fibrillation.
The exact mechanisms are not clearly known.
Dr Antoine Jatene first described the arterial switch operation

in 1975.56 For optimal long-term results, this operation is
ideally performed between the ages of 2 weeks and 6 weeks.
765
10
Delay in performing this surgery may result in long-term

left ventricular failure, since there is disuse atrophy of the
subpulmonic left ventricle due to low pressure load. In this
operation, the aorta and the pulmonary artery are transected
at the level above the coronary sinus and the coronaries are
dissected from the aortic sinuses with a button of tissue around
them and sutured into the neo-aorta. The main pulmonary
artery is repositioned anterior to the neo-aorta and the two
great arteries are sutured into their anatomically corrected
positions. The most important feature of this operation is that
it allows the left ventricle to function as the systemic ventricle,
thereby reducing the risk of early morbidity or mortality from
systemic ventricular dysfunction and heart failure. Long-term
outcomes are reviewed in Table 3.57 Coronary arterial fibrosis
leading to potential ischemia appears to be the major longterm issue in this population.58
Congenitally Corrected Transposition of the

Great Arteries
766
Patients with congenitally corrected transposition of the

great arteries (CCTGA) with no associated defects may go
undiagnosed into adulthood. They most commonly present
with heart failure when the morphological right ventricle,
which is the systemic ventricle, begins to fail. Nearly 25 percent
patients develop heart failure by 45 years of age.59 Although
the atria are in the normal position, there is double discordance
with transposition of the great arteries, and ventricular
inversion. Although these two wrongs try to make a right by
attempting to establish a physiologically correct circulation,
the major caveat is that the morphologically right ventricle
functions as the systemic ventricle, and pumps into the aorta.
The blood from the superior and inferior vena cavae flows
into the right atrium that drains into the left ventricle through
the morphological mitral valve. The left ventricle pumps the
blood into the pulmonary artery. The oxygenated blood returns
from the lungs returns via the pulmonary veins into the left
atrium and then flows through the morphological tricuspid
valve into the morphological right ventricle which pumps into
the aorta. Associated defects lead to varying presentations
and diagnosis is usually made early in life. Cyanosis may be
seen in patients with significant left ventricular outflow tract
(LVOT) obstruction associated with a VSD. Other long-term
residua and sequelae are reviewed in Table 3.
On physical examination, there is usually a loud single
second heart sound (A2). Sometimes a soft P2 may be heard.
Patients with systemic AV valve regurgitation will have a systolic
murmur at the left sternal border or apex. Other murmurs may be
audible depending upon the associated defects. An adult with no
associated defects/signs of heart failure may go undiagnosed.
The ECG is often misinterpreted as showing a previous
myocardial infarction, because there are Q waves in the
anterior leads due to ventricular inversion60 (Figure 3).
Coronary artery anatomy is also inverted.61,62
Unfortunately on echocardiography, it is not too uncommon

for the systemic AV valve to be mistaken, as the mitral valve
in an undiagnosed case of CCTGA. At times, an embarrassing
situation may occur when a cardiac surgeon opens the chest
to operate on the mitral valve and is shocked to find the
morphological tricuspid valve on the left side of the heart. If
there is no CHD surgeon available to help out, he/she may
end up closing the chest without performing the surgery. The
patient in this situation is so emotionally traumatized for
having undergone an unfruitful open-heart surgery that he/
she may refuse to undergo another surgery to fix the severely
regurgitating AV valve.
While reading echocardiograms one must look carefully
at the morphology of the ventricles. The AV valves follow
their respective ventricle, hence the systemic AV valve
(morphologic tricuspid valve) that is more apically placed
than the mitral valve (Figure 4) is on the same side of the heart
as the right ventricle.
Standard heart failure management is recommended with
the use of carvedilol, ACE I/ARB and aldactone titrated to
maximum tolerated dose. Digoxin may be added if tolerated.
Exercise training has miraculous effects on cardiovascular
conditioning in disciplined individuals, who can persistently
perform at least 45 minutes of daily aerobic activities. Surgical
management and the role systemic AV valve surgery are
discussed in the chapter on congenitally corrected transposition
of the great arteries.
Univentricular Heart (Single Ventricle Physiology)

with Fontan Operation
In 1971, Dr Francois Fontan performed a new surgical
procedure in patients with tricuspid atresia that would be
later become known as the classic Fontan operation. The
goal of this surgery is to improve blood flow to the lungs
by connecting the right atrium to the pulmonary artery.63
Tricuspid atresia is the commonest form of atrioventricular
atresia with complete absence of the tricuspid valve or
imperforate tricuspid tissue. Majority of the cases have a
concordant ventriculoarterial connection, while in nearly onethird cases there is transposition of the great arteries. There
may be a restrictive VSD connecting the left ventricle to the
hypolastic right ventricle.
Some patients have to undergo palliative surgeries in
childhood, such as a bidirectional Glenn to improve pulmonary
blood flow (especially in the setting of severe pulmonary
stenosis) and then later have a conversion to the Fontan
operation to improve oxygenation.64 Although, cyanotic
patients become acyanotic and have improved quality of life
and longevity after the Fontan operation, there are long-term
issues such as progressive ventricular dysfunction, atrial
arrhythmias, recurrence of cyanosis, elevated pulmonary
vascular resistance and protein-losing enteropathy, which
can result in heart failure, thromboembolism and stroke. The
54
by the use of intracardiac or extracardiac conduits, directing

blood from the superior and inferior vena cavae directly to the
pulmonary artery.
The cardiovascular examination in a post Fontan patient
may be unimpressive with quiet heart sounds. Usually there
is a single second heart sound and a holosystolic murmur
radiating to the apex due to mitral regurgitation. Patients with
protein losing enteropathy may have a palpable liver, ascites
and peripheral edema. An ECG may commonly show atrial
fibrillation or flutter. Echocardiogram allows assessment of the
ventricular function, degree of mitral and aortic regurgitation,
patency of the Fontan conduit, and rules out right atrial
thrombi.
Long-term issues in the postsurgical patient after Fontan
are described below:
Figure 3: Electrocardiogram in a 55-year-old man with congenitally corrected transposition of the great arteries. The abnormal q waves in the
anterior leads and poor R wave progression due to ventricular (as well as His bundle) inversion make it falsely appear like an old anterolateral
myocardial infarction
Arrhythmias
Figure 4: Transthoracic echocardiogram in the apical four-chamber
view showing crux anatomy. Note that the tricuspid valve (apically
displaced) is on the left side along with the morphological right ventricle
(with the prominent moderator band). LA = Left atrium; LV = Left
ventricle; MV = Mitral valve; MB = Moderator band; RA = Right atrium;
RV = Right ventricle; TV = Tricuspid valve;
recurrence of cyanosis may be due to fenestrated atrial septum,

pulmonary arteriovenous fistulae and other causes. Many
patients may also need revision of the Fontan operation. Over
the years, the Fontan operation has undergone modifications
with the total cavopulmonary connection (TCPC) achieved
There is higher probability of atrial arrhythmias in patients

with a classic Fontan due to markedly enlarged right atrium
and higher atrial pressures. In addition, mitral/systemic
atrioventricular valve regurgitation predisposes to left atrial
enlargement and atrial fibrillation. Suture lines in the atria from
prior surgeries may be also trigger arrhythmias. Medications
such as beta blockers or calcium channel blockers, with
or without digoxin are used for rate control. Amiodarone is
the antiarrhythmic of choice, when atrial fibrillation/flutter
persists. The lowest dose should be used and it should be
carefully monitored for adverse pulmonary effects, thyroid and
liver function tests.
767
10
Sometime intractable arrhythmias are a sign of a failing

Fontan. In these cases a revision of the Fontan or relief of the
conduit obstruction is indicated. Electrophysiology assessment
is indicated, when poorly controlled arrhythmias cause further
deterioration of the hemodynamics. Unfortunately, lateral
and extracardiac conduits limit catheter access for ablating
arrhythmias even though the likelihood of arrhythmias in these
patients is expected to be lower than in the classic Fontan.
Intra-atrial re-entrant tachycardia (atypical atrial flutter) is
common and often difficult to treat.
Heart Failure
Management of ventricular dysfunction is challenging.
Afterload reduction/vasodilators may not be well-tolerated in
the Fontan patient.
Antiplatelet Versus Anticoagulation Therapy

Classic Fontan puts patients at a very high-risk for thrombus
formation (Figure 5). The role of antiplatelet versus
anticoagulation therapy remains controversial and needs to be
individualized.
Protein-losing Enteropathy
This is the most serious complication post Fontan characterized
by increasing ascites, edema, pleural effusions and malnutrition.
The diagnosis is confirmed by low serum albumin levels and
increased fetal alpha antitrypsin. Feldt et al. showed that
the cumulative risk for the development of protein-losing
enteropathy (PLE) by 10 years was 13.4 percent and 5-year

survival after the diagnosis was 46 percent. Hemodynamic
data showed an increased systemic venous pressure, decreased
cardiac index, increased pulmonary vascular resistance and
increased ventricular end-diastolic pressure. Factors related
to PLE were ventricular anatomy, increased preoperative
ventricular end-diastolic pressure, longer operative bypass time,
increased length of hospital stay and postoperative renal failure.
Patient selection and perioperative factors seem to predispose
to PLE.65 The management options are limited and primarily
supportive. These include a special diet, unfractionated
heparin, corticosteroids and somatostatin analogs. Some
patients benefit from decreased systemic venous pressure and
passive hepatic congestion by transcatheter fenestration of the
atrial septum. Fontan revision and heart transplantation have
sometimes showed temporary improvement of the protein
losing enteropathy.
Endocarditis Prophylaxis
Appropriate dose of antibiotics is advised for endocarditis
prophylaxis in all Fontan patients.
CONCLUSION
Long-term follow-up and appropriate management are essential
to ensure improved quality of life and longevity in adults with
CHD. Antibiotic prophylaxis for bacterial endocarditis should
be prescribed when indicated, especially in high-risk patients
with complex CHD, conduits, pacemakers, defibrillators,
previous history of endocarditis and most importantly in those
with a bicuspid aortic valve or a ventricular septal defect.66
Echocardiography is the primary imaging tool for follow-up of
these adults.67 In addition to echocardiography, CT/MRI may
be required for monitoring the aorta in adults with BAV, COA
and other conditions that lead to aortic aneurysm, according
to the guidelines for management of thoracic aortic disease.68
The threshold for follow-up and surgery is 5 mm lower than
in general population. All the American Heart Association
guidelines can be downloaded for free in the PDF format
from the internet for up-to-date reference. A multidisciplinary
approach is required to provide complete care for multiple
issues including exercise/sports, mental health, obstetric and
gynecological care discussed in other chapters of this book.
Every human being is the author of his own health or
disease.
Sivananda
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Figure 5: Transesophageal echocardiogram confirming a right atrial

thrombus in a 38-year-old woman with tricuspid atresia with history of a
classic Fontan operation (right atrium to pulmonary artery connection)

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C hapter
55
Caring for the Adults with Cyanotic

Reema Chugh
INTRODUCTION
Inspired by the impact of high altitude physiology on Peruvians
residing in the high Andes,1 Dr Joseph Perloff embarked on a
lifetime of research to study the effects of cyanosis in adults
with congenital heart disease (CHD). He began drawing
correlations between these two populations, exposed to a
lifetime of chronic low oxygen saturations and unraveled the
long-term impact of hypoxemia and erythrocytosis that makes
cyanotic congenital heart disease in adults a multisystem
disorder.2-4
CYANOTIC CONGENITAL HEART DISEASEA

MULTISYSTEM DISORDER
The term cyanosis comes from the color cyan, which is
derived from kyanos, the Greek word for blue. Individuals
born with cyanotic CHD appear blue, due to intermixing of
higher concentrations of venous deoxygenated blood (carrying
deoxyhemoglobin over 2.5 g/dL) with the arterial oxygenated
blood, resulting in persistent systemic arterial desaturation
(usually below 85%). Central cyanosis is usually visible in the
oral mucosa making the lips appear blue. The bluish discoloration
is also seen in the skin and the nail beds of the fingers and toes.
This intermixing of the blood may occur at the atrial,
ventricular or arterial level (atrial or ventricular septal defects
or a patent ductus arteriosus) through a right-to-left shunt or
a bidirectional shunt. It may also occur by intermixing of
the blood in univentricular hearts, in congenital/palliative
surgical connections or in patients with intrapulmonary
shunts. Palliative connections include surgically created
systemic arterial to pulmonary artery shunts for augmenting
the restricted pulmonary blood flow in order to improve
cyanosis. These aortopulmonary shunts may be complicated
by pulmonary vascular disease, if they are too large.5
The communications between the systemic and pulmonary
circulation may sometimes be associated with pulmonary
outflow tract obstruction. The pulmonary outflow tract

obstruction/pulmonary stenosis is actually a boon in patients
with large shunts, since it offers protection from excessive
blood flow going to the lungs, which could lead to severe
pulmonary vascular disease or Eisenmenger syndrome (severe
pulmonary hypertension with reversal of the shunt).6
Cyanotic CHD is a multisystem disorder that results
from long-term effects of the deoxygenated blood flow to
all organs of the body (Table 1). Cyanotic CHD accounts for
approximately 25 percent of all congenital heart defects, with
the most common one being tetralogy of Fallot. Before the
advent of early interventions and surgical operations, many
adults with the manifestations of cyanotic CHD were seen
in clinics all over the world. In the past 20 years, we have
thankfully noticed a diminishing population of cyanotic CHD
in the United States (US) due to timely palliative procedures
and surgical repairs. Unfortunately, some people will continue
to be cyanotic with CHD as long as there is limited access to
pediatric and surgical care. This may also happen when early
interventions/surgeries are denied by the patients or their
families because of their belief system or fears.
Hematologic Manifestations
In his teachings, Dr Perloff has made it very clear that there is
a difference between polycythemia and erythrocytosis, since
these two terms are often used incorrectly and interchangeably
by the medical community worldwide. Patients with cyanotic
CHD have secondary erythrocystosis as a physiological
adaptive response to chronic low systemic arterial oxygen
saturation. This involves an isolated increase in the red
blood cell (RBC) mass. The RBC production is stimulated
by erythropoietin that is released from the renal cortex in
response to hypoxemia.
The term polycythemia refers to an increase in more than
one (generally all) of the formed elements in blood (from the
10
Greek polys, many) and the designation is not appropriate
for the isolated increase in red cell mass that characterizes
the hematologic response in patients with cyanotic congenital
Joseph K Perloff7
heart disease.
Secondary erythrocystosis in cyanotic CHD is very

different from polycythemia rubra vera, which is a malignant
clonal stem cell disorder that involves all three cell lines
leading to an increase in RBC mass, along with an increase in
white blood cells (WBC) and platelets.4
The two major determinants of increased whole blood
viscosity that affect patients with cyanotic CHD are:
1. Secondary erythrocytosis: Since, the principal function
of the erythrocytes is to carry oxygen, in cyanotic CHD
the secondary erythrocytosis is an appropriate adaptive
response to decreased tissue oxygenation. Low tissue
oxygenation causes the renal release of erythropoietin
leading to an increase in RBC mass. The platelet counts
are in the low range of normal and the WBC counts are
normal. All the major clinical manifestations are a result

of exposure of multiple organs to prolonged chronic
hypoxemia and secondary erythrocytosis.4
2. Iron deficient rigid microspherocytes: The iron
balance is very important in adults with cyanotic CHD.
Iron deficiency decreases muscle strength and exercise
tolerance. Most of the patients with cyanotic CHD are
often iron deficient due to repeated phlebotomies or chronic
blood loss such as from menstrual bleeding that occurs
especially in premenopausal women. Iron deficiency is
often unrecognized in this population since hemoglobin
and hematocrit levels are not reflective of the true degree
of iron deficiency and therefore serum ferritin levels need
to be assessed. The serum ferritin concentration directly
correlates with the level of total body iron stores making
it a sensitive and specific indicator of the iron status. The
peripheral blood smear is also helpful in early detection of
microcytic, hypochromic RBC that are indicative of irondeficient erythropoiesis.
Table 1
Multiorgan manifestations of cyanotic congenital heart disease

Organ
Disorder
Pathogenesis
Hematologic
Hyperviscosity
Secondary erythrocytosis with hematocrit over

65%, thrombocytopenia, shortened platelet
lifespan, clotting factor deficiencies, abnormal
prothrombin time and congenital hematologic
disorders
Cardiovascular
Dilated, tortuous, aneurysmal

coronaries with paucity of
atherosclerosis
Structural abnormalities of the walls

Effect of erythrocytosis
Nitric oxide (NO)
Hyperbilirubinemia
Hypocholesterolemia
Thrombocytopenia
Pulmonary
Pulmonary hemorrhage
Extrapulmonary bleeding
Pulmonary embolism
Main or branch pulmonary thrombosis
Syncope
Vasodilation (hot showers) or dehydration
Cerebral arterial thrombosis
Microcytic spherocytes
Brain abscess
Focal ischemia due to sludging of microcytes

acting as nidus for bacteremia
Renal
Proteinuria
Elevated urate levels
Platelet derived growth factor and transforming

growth factor-beta
Metabolism of bilirubin and glucose
Bilirubin stones
Hyperbilirubinemia
Central nervous system
772
Gout
Hyperuricemia
False hypoglycemia on blood tests
Glycolysis by secondary erythrocytosis
Rheumatological digits and long

bones
Clubbing
Hypertrophic osteoarthropathy
Platelet-derived growth factor (PDGF) and

transforming growth factor-beta
Vascular endothelial growth factor
Gynecological
Menstrual disorders
Infertility
Abnormal hemostasis
Prolonged cyanosis
Hyperviscosity Syndrome
Exacerbated by dehydration, adults with cyanotic CHD
may present with symptoms of hyperviscosity syndrome
(Box 1). Severe secondary erythrocytosis causes increased
plasma viscosity and impairment of the microcirculation. This
compromises tissue delivery and usually occurs in the setting
of volume depletion or dehydration. When a patient presents
with symptoms suggestive of hyperviscosity syndrome, it
is also important to examine the differential diagnosis that
includes, but is not limited to, hypovolemia, hypothyroidism,
depression, brain abscess and gout.
Symptoms of hyperviscosity usually respond to hydration.
Once the hematocrit is less than 65 percent, the symptoms
resolve but persist if there is iron deficiency.
The management of hyperviscosity syndrome involves
mainly hydration and long-term iron repletion.9 Laboratory
tests should be performed after adequate hydration and
these include a complete blood count, serum ferritin levels
and transferrin saturation. Phlebotomy should be avoided, if
symptoms of hyperviscosity improve. Hydroxyurea has a very
limited role as discussed later in this chapter.
Hydration: All patients with cyanotic CHD are constantly
reminded to drink enough water and fluids to remain adequately
hydrated. However, due to excessive insensible losses during
55
Box 1: Symptoms of hyperviscosity syndrome
Neurological symptoms
Headaches
Lightheadedness or dizziness
Faint
Irritability
Impaired concentration
Numbnessperioral and digital
Tinnitis
Visual symptoms
Blurring or double vision
Scotoma
Bleeding disorders
Bruising
Bleeding gums
Nose bleeds
Coughing up or vomiting blood
Excessive bleeding after trauma or surgery
Musculoskeletal symptoms
Muscle pains and weakness
Long bones pain
Joint pains and swelling
Gynecological symptoms
Menorrhagia
General symptoms
Fatigue
Lethargy
hot weather spells or dehyration resulting from gastrointestinal

disorders, they may present with symptoms of hyperviscosity
when oral intake cannot match the physiological demands. In
these cases, the hyperviscosity syndrome promptly responds
to an intravenous infusion with 1 liter of isotonic saline.
Iron replacement therapy: Providers need to be cautious and
avoid over treatment.10 The indications for iron replacement
therapy are as follows:
Serum ferritin less than 30 microgram/mL
Serum ferritin less than 50 microgram/mL with transferrin
saturation less than 15 percent
No history of intolerance to oral iron.
One of the preferred protocol for oral therapy is to prescribe
an iron formulation containing 66 mg of elemental iron once
daily, with an incremental increase in the dose, as tolerated,
to three times daily over a course of 3 months. Follow-up
laboratory testing for iron stores should be performed monthly
and the complete profile should be checked in 3 months.
If there is history of intolerance to oral iron, one may
consider giving parenteral therapy with an infusion of
intravenous iron sucrose 200 mg at one time then reassess
serum ferritin levels and transferrin saturation in 1 month to
determine the need for future doses.10
The most common side effects of oral iron replacement
therapy are abdominal pain, constipation or diarrhea. If the
Caring for the Adults with Cyanotic Congenital Heart Diseases
Iron deficiency may lead to microcytic and hypochromic

erythrocytes with decreased oxygen carrying capacity of
the blood because of reduced mean corpuscular hemoglobin
concentration in the RBC. There is reduced deformability
of the iron deficient RBC and they become into rigid
microspherocytes. Unlike the biconcave, iron-replete
RBCs that are more flexible in their passage through the
microcapillaries, these iron-deficient, rigid microspherocytic
RBCs are prone to sludging in the microcapillaries and
aggregate readily thereby promoting hyperviscosity. Careful
iron repletion is needed to correct this problem as discussed
later in this chapter.
Firstly, is there compensated or decompensated
erythrocytosis? In compensated erythrocyosis, there is a
proportionate rise in the hematocrit levels in response to
elevated erythropoietin stimulated by tissue hypoxemia.
This is a physiologic adaptation to tissue hypoxemia.
Hyperviscosity symptoms are usually mild, if the hematocrit
is over 70 percent and resolve when hematocrit is less than 65
percent.8
In decompensated erythrocytosis, as described by Rosove
et al. there is pronounced rise in the hematocrit in response
to tissue hypoxemia. The hematocrit continues rise in an
exaggerated manner beyond the physiological needs even after
normalizing serum iron, serum ferritin levels and achieving
an appropriate RBC mass. Hyperviscosity symptoms are
moderate to severe and recurrent in these patients.8
773
10
774
therapy is well tolerated and the patient completes the course,

the benefits include a significant increase in iron stores, mean
corpuscular volume (MCV) and hemoglobin concentration
within 3 months. There is also an increase in exercise capacity
and an improvement in quality of life.
Phlebotomy: The age old practice of phlebotomy has a
very limited role now and can be detrimental in most cases.
The indications for therapeutic phlebotomy in patients
with polycythemia rubra vera cannot be applied to patients
with cyanotic CHD as these two disorders have completely
different pathophysiology. Unfortunately, this fundamental
misconception caused too many inappropriate and often
harmful phlebotomies in cyanotic CHD patients for several
years. Phlebotomies have sometimes been fatal and at other
times exacerbated hyperviscosity syndrome by causing
more sludging in the microcapillaries, by the iron deficient
microspherocytes.
Phlebotomy should only be considered in an iron replenished
patient, if the hematocrit continues to remain above 65 and
there are persistent symptoms of the hyperviscosity syndrome,
even after receiving adequate hydration.
Phlebotomy should be performed with utmost care
only when it is strongly indicated.4,5 In the absence of iron
deficiency or dehydration, the main indications are:
a.
Persistence hyperviscosity symptoms when the
hematocrit is above 65 percent despite adequate
hydration.
b. Preoperative phlebotomy if the hematocrit is above
65 percent despite adequate hydration, for reducing
perioperative bleeding complications and/or for saving
autologous blood for potential transfusions.
Phlebotomy is performed as an outpatient procedure,
with admission to an observation unit with cardiac and noninvasive hemodynamic monitoring. The following protocol is
recommended:
Continuous cardiac electrocardiographic monitoring
Blood pressure, pulse rate and pulse oximetry checks every
15 minutes
Remove no more than 1 pint of blood slowly and replete
with equal or more volume of isotonic saline
Observe for 4 hours and reassess symptoms
Observe for improvement in symptoms
Assess for orthostatic hypotension before discharging the
patient.
When performed appropriately and carefully, phlebotomy
should result in favorable clinical effects within 24 hours by
improving the stroke volume, the systemic blood flow and
the oxygen transport in these patients. The primary goal of
phlebotomy is to provide temporary relief from moderate to
severe symptoms of hyperviscosity syndrome.
Use of hydroxyurea in hyperviscosity syndrome: Hydroxyurea
(hydroxycarbamide) is an S-phase specific chemotherapeutic
agent that inhibits ribonucleotide reductase, and thus
interferes with the production of DNA precursors required

for cell replication and maturation. The treatment must be
guided by a hematologist and reserved for selected cases of
refractory hyperviscosity syndrome. In these cases, despite all
measures, including iron repletion, the symptomatic patients
continue to have high hematocrits and are at increased risk for
adverse events. Potential serious side effects associated with
hydroxyurea treatment are neutropenia and thrombocytopenia
that usually resolve when the treatment is stopped.11
Hemostatic Abnormalities
Cyanotic CHD patients are vulnerable to bleeding that may vary
from mild to serious and sometimes fatal bleeding. Epistaxis,
bruising, petechial and gingival bleeding are examples of mild
bleeding. Bleeding associated with trauma or surgery can
be serious. Hemoptysis can be minor to fatal. Many factors
associated with bleeding tendency include erythrocytosis with
hematocrit over 65 percent, thrombocytopenia, shortened
platelet lifespan, clotting factor deficiencies and abnormal
prothrombin time.12,13 Some patients may have congenital
hematologic disorders (such as in von Willebrand disease)
associated with CHD.12
During cardiac surgery many patients will have excessive
bleeding due to further reduction in platelet counts and
function. Coagulation factor deficiencies, heparin-induced
thrombocytopenia, disseminated intravascular coagulation,
excessive fibrinolysis may also be contributing factors.
Clinically, all patients with cyanotic CHD should avoid
taking antiplatelet agents such as clopidogrel, Aspirin and other
nonsteroidal anti-inflammatory drugs (NSAIDs). They should
also avoid anticoagulation with low molecular weight heparin or
warfarin as far as possible. When warfarin is strongly indicated
for persistent atrial fibrillation, the presence of a mechanical
prosthetic valve, deep vein thrombosis or pulmonary embolus,
careful monitoring should be done to maintain the International
Normalized Ratio (INR) between 2 and 2.5.
When bleeding occurs, fresh frozen plasma and vitamin
K (for patients taking warfarin) may help. Appropriate
management of the cause, platelet transfusion, repletion of
any deficient factors may also be required. Desmopressin may
help in some situations especially in raising von Willebrand
factor concentrations. Platelet transfusions, fresh frozen
plasma, vitamin K, cryoprecipitate and desmopressin can be
used to treat severe bleeding.12
Cardiovascular Issues
Hypoxemic erythrocytotic residents of high altitudes lack
coronary atherosclerosis and have low cholesterol levels.
It was postulated that hypoxemic erythrocytotic adults with
cyanotic congenital heart disease might be analogous.
Joseph K Perloff
shunt. Other situations with lower benefits from oxygen

supplementation in cyanotic CHD are fixed pulmonary
vascular resistance or fixed obstruction in the outflow tract of
the subpulmonic ventricle.
While intermittent use of oxygen may be helpful especially
in acute situations, chronic use may result in drying of the nasal
mucosa predisposing to epistaxis and potential pulmonary
toxicity.4
Pulmonary Thrombosis
Pulmonary embolus due to thrombosis poses a therapeutic
dilemma in cyanotic CHD. In Eisenmenger syndrome,
female patients and/or those with lower oxygen saturations
are at the highest risk of developing thrombosis.20 It can be
segmental or massive to occlusive disease causing death. The
proximal pulmonary artery thrombus can migrate to cause
an intrapulmonary embolus, which may lead to pulmonary
infarction. This in turn may cause intrapulmonary hemorrhage
as well as a hemorrhagic pleural effusion. In acute situations,
the benefits of the chosen therapy for thrombosis must outweigh
the hemorrhagic risks. Due to the increased bleeding tendency
in these patients, the role of anticoagulation treatment needs to
be determined. Intravenous heparin may be used cautiously. It
is short-acting and its anticoagulant effect wears off within an
hour when it needs to be turned off. Low molecular heparin
should be avoided due to its longer half life in case there are
hemorrhagic complications.
There is no proven role for using thrombolytics in patients
with chronic thrombi. Nonsteroidal anti-inflammatory drugs
(NSAIDs) are to be avoided as far as possible since they
put the patient at risk for catastrophic hemorrhage. Oral
anticoagulation is avoided as far as possible and when it is
mandated, careful monitoring is essential to maintain the INR
between 2 and 2.5.4,21
55
Prolonged cyanosis and erythocytosis may have an

unusual effect on the coronary circulation. While coronary
atherosclerosis is a ubiquitous phenomenon that plagues our
modern civilization, adults with cyanotic CHD appear to have
some protection from obstructive coronary artery disease.
We studied extramural coronary arteries by reviewing
angiograms in 59 adults with cyanotic CHD from two medical
centers (UCLA and Washington University in St Louis), and
coronary histopathology in 6 adults from one medical center
(UCLA). The mean systemic arterial oxygen saturations were
79 percent and the mean hematocrit measurement was 67, in
these 25 women and 34 men between the ages of 34 and 56
years. The coronaries were aneurysmal, dilated and tortuous
in 86 percent of the patients with paucity of atherosclerosis.14
On histopathology examination after special stainings, the
dilated ectatic tortuous coronary arteries demonstrated the
following features:
a. Loss of medial smooth muscle cells
b. Increased medial collagen
c. Duplication of internal elastic lamina and
d. Fibromuscular intimal hyperplasia.14
These findings have been attributed to persistent
erythrocytosis in cyanotic CHD that causes increased
laminar endothelial shear stress leading to upregulation of
nitric oxide (NO) synthase by a cascade of interactions that
result in vasodilatation.15 Prostaglandins that contribute to
vasodilatation are also believed to be released in response to
increased endothelial shear stress.
The paucity of atherosclerosis seen in cyanotic CHD
may be due to hypocholesterolemia that persists after
surgical elimination of the cyanosis.16 In addition to
hypocholesterolemia, other independent coexisting anti
atherogenic factors are hypoxemia, hyperbilirubinemia,
upregulated nitric oxide (NO) and low platelet counts.
The basal coronary flow is significantly increased and the
remodeling of the microcirculation is based upon coronary
arteriolar length, volume as well as surface densities, that
contribute to preservation of flow reserve.17-19
Pulmonary Hemorrhage
Since the hemorrhage due to cyanotic CHD is intrapulmonary,
there is limited role for bronchoscopy, which sometimes can
be dangerous in these patients. Hospitalization with supportive
care and volume repletion is recommended.4
Pulmonary issues
Oxygen Supplementation
Very commonly cyanotic CHD patients are offered oxygen
supplementation in response to low oxygen saturation (SaO2)
especially in emergency rooms/casualty wards. This comes
more from a physicians reflex action rather than for a medical
indication.
Oxygen supplementation has more psychological than
physiological benefits in cyanotic CHD. It may only help
marginally, since there is a larger volume of deoxygenated
blood that may not reach the alveolar circulation for
oxygenation due to intermixing through a large right to left
Cerebrovascular events
The neurological manifestations in cyanotic CHD include
headaches, syncope, strokes/transient ischemic attack and
cerebral hemorrhage.
Syncope
Besides the neurological symptoms such as headaches that are
commonly associated with hyperviscosity syndrome, cyanotic
775
10
CHD patients often experience presyncope or syncope due

to inappropriate vasodilatation of systemic vascular bed. It
probably occurs because of the increased nitric oxide levels
may play a central role in regulating vascular tone. In addition
to adequate hydration, these patients should avoid hot showers
or prolonged exposure to hot weather.
Stroke
The residents of high altitudes with secondary erythrocytosis
do not have a high incidence of stroke. However, strokes are a
major cause of morbidity in cyanotic CHD population even in
the absence of classical cardiovascular risk factors. In patients
with cyanotic CHD lesions, the prevalence of stroke is over
10-fold above the average.22
Most episodes appeared to be embolic and usually occur
in cyanotic CHD patients with or without Eisenmenger
syndrome. Cerebral hemorrhage may be precipitated by
problems with hemostasis or the use of anticoagulant therapy.
Cerebral Arterial Thrombosis
Cyanotic CHD predisposes to an increased risk of stroke that

may occur due to paradoxical emboli. Passage of thrombotic
or particulate matter can occur from the pulmonary to
systemic circulation (cerebral circulation), without allowing
the blood to filter through the lungs. This risk can be reduced
by implementing prophylactic measures against deep venous
thrombosis (DVT) and by introducing air filters in all
intravenous lines.
For many years, adults with cyanotic CHD were inappropriately

phlebotomized for elevated hematocrit levels because of an
assumed risk of cerebral arterial thrombotic stroke caused
by hyperviscosity/sludging. Although the cerebrovascular
accidents due to thromboses of the intracranial venous sinuses
and veins have been associated with iron deficient secondary
erythrocytosis in children,4 there is no established correlation
between secondary erythrocytosis and cerebral arterial
thrombotic stroke in adults.28
In other studies, the reported incidence of strokes
in cyanotic CHD was up to 14 percent.29,30 Microcytic
spherocytes caused by iron deficiency remains the strongest
independent predictor for cerebrovascular accidents, even
when patients with the two other strong independent risk
factors are excludedhypertension and atrial fibrillation.30
Therefore, inappropriate phlebotomies should be avoided
since they exacerbate iron deficiency, which then leads to
an increased risk of stroke in cyanotic patients.
Brain Abscess
Renal
Cyanotic CHD poses a risk of developing a brain abscess,

which has been reported in 2 percent of the cyanotic patients.23
However, in another study among 149 patients presenting
with a brain abscess, 69 percent had cyanotic CHD.24
A brain abscess is a focal, intracerebral infection that
develops into a collection of pus surrounded by a wellvascularized capsule. Although brain abscesses are commonly
known to originate from infection of contiguous structures
or following head trauma/surgery, in patients with cyanotic
CHD they are mostly associated with hematogenous spread
(bacteremia) that seeds a focal area of ischemia in the brain
(caused by sludging from the erythrocytotic blood). The most
common organisms isolated in cyanotic brain abscess include
Streptococcus viridans, microaerophilic streptococci and
anaerobic streptococci.25,26
Brain abscess may present with a new or different headache
or any neurological symptoms. Management should be guided
by the infectious disease specialists and neurology to include
appropriate intravenous antibiotics, with adjunctive therapies
such as corticosteroids when indicated (for impending cerebral
In cyanotic CHD, renal issues can present as proteinuria,

hyperuricemia or renal failure, which is an independent
predictor of mortality.21 Although hyperuricemia is common,
patients with cyanotic CHD rarely develop urate nephropathy
or uric acid stones.
The structural renal abnormalities noted in cyanotic
CHD are vascular changeshypercellular congestion and
dilatation of capillaries and hilar arteriolethat appear to
be due to nitric oxide. In addition, there are non-vascular
changesprominence of juxta glomerular apparatus and
mesangium- that are attributed to stimulation of tissue by
the platelet-derived growth factor and transforming growth
factor beta cytokines released by the fragmentation of
megakaryocytes that bypassed the pulmonary circulation due
to a shunt. These megakaryocytes are normally destined to
breakdown in the pulmonary circulation to form platelets.31
The hypercellular and congested glomeruli eventually
become sclerotic.32
Among the functional renal abnormalities, abnormal renal
clearance of urate results in elevated uric acid levels that may
Paradoxical Emboli
776
herniation) or intravenous mannitol (for severe brain edema).

Some patients may require interventions such as aspiration of
the abscess24 and placement of a ventriculostomy catheter for
cerebrospinal fluid drainage, to relieve intracranial pressure
and/or abscess excision.27 Seizures are a frequent complication
of brain abscess and anticonvulsants may be needed.27
Bacterial endocarditis prophylaxis and early detection
and treatment may prevent high morbidity and mortality
associated with brain abscesses.
Metabolic disorders
Hyperbilirubinemia
Cyanotic patients have been observed to have a higher
incidence of gallstones (over 20%) as compared with the
acyanotic patients with CHD and the general population,
where the incidence is around 10 percent.35 While most of
gallstones are cholesterol stones (80%), the cyanotic patients
have brown and black pigment stones made of calcium
bilirubinate.
Over time in long-standing chronic cyanotic CHD, an
increased breakdown of red blood cells from excessive
erythrocytosis results in the release of heme. Heme then
breaks down to release unconjugated bilirubin, which is water
insoluble at physiological pH. Therefore, chronic cyanotic
patients are increased risk of calcium bilirubinate gallstones,
which are detected by an abdominal ultrasound.
Clinically, they may remain asymptomatic or present
with chronic biliary colic. The most common non-cardiac
surgery in cyanotic CHD patients is cholecystectomy. They
rarely have acute cholecystitis, but the presence of calcium
bilirubinate stones can set a substrate for gram negative
bacteremia, which can then lead to infective endocarditis or
sepsis in these patients.
A recent study from the Chiba Cardiovascular Center
in Japan confirms that the prevalence of cholelithiasis and
asymptomatic gallstones is significantly high in cyanotic
CHD patients regardless of cardiac repairs. In addition
to prolonged cyanosis in these patients, exposure to
frequent cardiopulmonary bypass during surgeries and
thrombocytopenia might influence gallstone formation in
adults with CHD.35
Hyperuricemia
In cyanotic patients, hyperuricemia occurs due to an increased
production-breakdown of erythrocytes and decreased
clearance (abnormal urate reabsorption with inappropriately
low fractional uric acid excretion and not due to urate
overproduction).33 The prevalence of hyperuricemia correlates
with age and hematocrit as well as renal function in cyanotic
CHD.36-39
Clinically as always, adequate hydration helps. These
patients should not be treated prophylactically with
allopurinol for their absolute uric acid levels. Allopurinol
although commonly used in patients with a chronic history of
gout has potential for serious side effects including a rare, lifethreatening dermatological condition called toxic epidermal
necrolysis syndrome (TENS).
During an attack of acute gout that may occur infrequently,
colchicine is the preferred medication of choice, given with
plenty of food and water to reduce as well as overcome the
occurrence of gastrointestinal side effects (vomiting and
diarrhea). These patients may continue on a daily maintenance
dose of 0.6 mg. Following an episode, allopurinol may also be
prescribed for prevention. Others medications are probenecid
or sulfinpyrazone. Nonsteroidal anti-inflammatory drugs such
as ibuprofen and salicylates should be avoided even in low
doses in cyanotic patients because of the risk of bleeding.
However salsalate which is not an antiplatelet agent may help
in management of pain in these patients without potentiating
hemorrhagic risks.4
55
predispose to gout and proteinuria due to increased glomerular

hydraulic pressure from secondary erythrocytosis.33
The important clinical implications of these findings are that
they result in a reduction of the glomerular filtration rate and
increased creatinine level along with the proteinuria. Cyanotic
patients undergoing cardiac catheterization or radiological
procedures may encounter problems with radiopaque contrast
material, leading to contrast-induced nephropathy especially
in the setting of dehydration. Similarly, they are at a risk for
acute renal failure leading to uremia, oliguria and even anuria,
after cardiopulmonary bypass or any condition that may cause
hypoperfusion or hypotension.21,34
These patients should be well hydrated before procedures
that involve contrast media. Providers should be aware of the
preoperative diagnosis of glomerulopathy. Gentle diuresis
with monitoring is indicated when there is fluid overload.
Although not yet proven, there may be a role for long-term
use of angiotensin-converting enzyme (ACE) inhibitors for
reducing proteinuria.
Rheumatological manifestations
Clubbing
The most common clinically visible rheumatological
manifestation of cyanotic CHD is clubbing. It is characterized
by bulbous enlargement of the ends of fingers or toes, with
loss of the normal angle between the skin and nail plate along
with excessive sponginess of the nail base.
In cyanotic CHD, there is cell proliferation and tissue
formation in the digits because of the release of platelet derived
growth factor and the transforming growth factor beta from
the breakdown of the megakaryocytes in the end capillaries of
the digits rather than in the lungs (where the breakdown would
have normally occurred in the absence of a large shunt). The
platelet derived growth factor is known to cause increased
capillary permeability and connective tissue hypertrophy that
appears to be the mechanism for clubbing.40-42
Hypertrophic Osteoarthropathy
Cyanotic CHD patients may have joint pains of mild to
moderate intensity in the distal ends of their long bones of
777
10
the forearms and legs. They may also have pains in the distal
ends of the metacarpals and metatarsals. Joint aches may be
accompanied with local tenderness. These symptoms are due
to hypertrophic osteoarthropathy seen in more than 30 percent
of the patients with cyanotic CHD.
In hypertrophic osteoarthropathy, there appears to be a
chronic inflammatory process with active bone metabolism.
There is edema, round cell infiltration with lifting of the
periosteum and involvement of the structures in the joint
capsule with adjoining soft tissue. The vascular endothelial
growth factor appears to play a role in addition to other
circulating growth factors that are normally inactivated in the
lungs.43 Bisphosphonates are generally effective for relieving
pain related to hypertrophic osteoarthropathy, when the pain
is disabling and refractory to conventional analgesics.44
Scoliosis
Scoliosis occurs more frequently in patients with CHD.
The impact of cardiac surgery on possibility of developing
scoliosis was reviewed in 998 patients with congenital heart
defects who were below the age of 16 years. In this Mayo
clinic study, there was no correlation between scoliosis and
the presence of cyanosis probably because of early surgical
correction of cyanosis.45
Pregnancy, contraceptive and

gynecological issues
Cyanosis is a recognized high risk factor to fetal growth and
development and impacts outcomes in pregnancy. There is
increased maternal and fetal mortality that correlates with
the degree of cyanosis, impaired ventricular function and
pulmonary artery pressures.46 Adverse fetal outcomes include
fetal wastage (high incidence of miscarriages), preterm
delivery and intrauterine growth retardation.
The use of contraceptives is important in avoiding high
risk and unplanned pregnancies in these women. Appropriate
guidance regarding choice of contraceptives is important,
since estrogen increases the risk of thrombosis. Reproductive
issues including menstrual disorders and infertility challenge
most women with cyanotic CHD.47,48
Pregnancy, contraception and gynecological issues are
discussed in more detail in the chapter relating to this topic.
General considerations
Dental Care
778
Infective endocarditis is more likely to result from daily

activities, such as bacteremia caused by bleeding during
brushing and flossing teeth rather than from bacteremia at the
time of dental procedures. Cyanotic CHD are at higher risk for
bacterial endocarditis, since they have fragile spongy gums

that bleed readily predisposing to bacteremia. Reducing the
risk of gingivitis by taking excellent care of gums can reduce
this daily and ongoing risk.
Meticulous daily dental care and biannual dental hygiene
visits are strongly advocated in all individuals with cyanotic
CHD. In addition, bacterial endocarditis prophylaxis should
be prescribed in all cyanotic CHD patients, since endocarditis
is associated with the most detrimental outcomes in this
population.49 Dental procedures should be avoided for 6
months after an operation, since endothelialization of the
prosthetic structures (such as valves, conduits) or sutures
needs to be complete in order to reduce the risk of seeding the
surgical site with bacteria.
Skin and Nail Care

Skin is the largest and most vulnerable organ of the body. Cuts
and wounds are portals for bacteremia, if they are not cleansed
immediately with soap and water following an injury. Careful
follow-up and appropriate wound care are essential to avoid
cellulitis and abscess formation. Acne frequently affects the
young people with skin lesions on the face, neck and shoulders.
These patients are advised to avoid picking on the pimples
and follow good skin hygiene, hydration, reduced caffeine
intake, stress management, get adequate sleep and take
medications recommended by dermatology. Body piercing,
tattoos and intravenous drug use are strongly discouraged.
Nail biting or picking adjacent soft tissues is another
common habit that opens up portals for bacteremia, besides
being socially unappealing. I have always enjoyed Dr Perloff
advising nail-biters to dip their fingers in hydrogen peroxide
solution from time to time during the day, since it is not only
a potent disinfectant but also tastes terrible!
Health Passport and Medical Records

The health passport and carrying essential medical records is
even more essential in patients with cyanotic CHD, especially
when they are traveling outside the vicinity of their home
town. The details about the health passport are discussed in
the chapter on transitional care in congenital heart disease.
Travel Advice and Precautions

Besides preventive advice on deep venous thrombosis (DVT)
that happens with prolonged immobilization during road or
air travel, patients with cyanotic CHD should actively stay
hydrated, since they are prone to excessive insensible losses.
Thirst is a poor indicator of dehydration, especially during air
travel. The cabin pressure during pressurized commercial air
travel is usually well tolerated and permission to carry oxygen
in a compressor should be obtained well before embarking on
Hospitalizations and Non-cardiac Surgery

Cyanotic patients are at a higher risk for complications during
any hospitalization or operation. Preventive management
strategies include reducing the risk of paradoxical emboli related
to air and particulate matter through the intravenous lines by
using a filter that is commonly available in pediatric wards.
These patients are prone to bleeding due to increased tissue
vascularity (potential effect of NO and prostaglandins), friable
tissues (especially skin and gums) and thrombocytopenia
with short platelet life span. Right-to-left shunts may deliver
whole megakaryocytes into the system arterial circulation,
bypassing the lungs (where megakaryocytic cytoplasm is
normally fragmented into platelets) thus reducing the platelet
production. The perioperative bleeding risk may be reduced
by preoperative phlebotomy, as discussed previously in this
chapter, since it may improve hemostasis.
They are also more prone to thrombosis due to secondary
erythrocytosis and precautions against DVT should be
implemented. Renal function also needs to be monitored.4,34
Exercise
It has been reported that despite similar cyanosis, patients
with Eisemenger syndrome show less exercise performance,
more ventilation-perfusion mismatch and a worse quality of
life when compared to complex cyanotic CHD patients with
pulmonary stenosis who are protected from severe pulmonary
vascular disease (due to decreased blood flow to the lungs
because of the pulmonary stenosis). The oxygen saturation
at rest predicts exercise capacity and ventilatory efficiency in
these patients.51,52
People with cyanotic CHD should avoid dehydration and
exercising in extremes of weather conditions. Competitive
sports should be avoided in cyanotic patients. Regular
aerobic exercise with slow warm up and slow cool down is
encouraged.
Work Restrictions
Many people with CHD are only able to work for limited
work hours. In addition, the emotional and mental intensity
involved in completion of the tasks and physical limitations
due to scoliosis or reduced muscle strength may hinder.
The physicians should be supportive in providing letters or
documents to the employers that will allow these people to
work within acceptable limits. Inevitably some need to go on

disability due to the severity of their cardiac condition and
associated comorbidities.
Psychosocial Challenges and Psychiatric Issues

Depression, anxiety and emotional difficulties are not
uncommon in individuals with chronic medical conditions
including cyanotic CHD.34 Unfortunately, these may have
a major impact on the quality of life and affect education,
vocation and relationships. A recent study by Mller et al
reported that even minor depressive symptoms in patients
with CHD may have a stronger impact on their quality of life
than on limited exercise capacity.53
This topic is discussed in more detail in the chapter
on Psychosocial Challenges and Psychiatric issues while
Growing Up with Congenital Heart Disease.
Smoking Cessation
Both active and passive smoking are even more detrimental
in cyanotic CHD, since inhaled tobacco products stimulate
erythrocytosis (seen in chronic smokers) due to an increase in
carboxyhemoglobin. The resulting carboxyhemoglobinemia
impairs oxygen carrying capacity of the red blood cells and
thereby stimulates secondary erythrocytosis. Young patients
should be advised early on to refrain from smoking and those
who are smokers should be introduced to smoking cessation
programs and acceptable pharmacological options.4
55
a flight.34,50 Although oxygen supplementation is not clearly

indicated, it may help to reduce anxiety.
All precautions should be taken to reduce travel fatigue
with good planning, timely arrangements, and reduced
luggage. Medications and equipment for special needs should
be carried as hand luggage.4
Special precautions for laboratory testing

For accurate measurement of hematological parameters,
special precautions are taken with blood drawn from patients
with cyanotic CHD. The hematocrit level of their blood
samples should be calculated by an automated electronic
particle counter because the microhematocrit centrifugation
results in plasma trapping and falsely raised hematocrit.
Sodium fluoride should be added to the tube carrying
the blood sample to avoid the false reading of marked
hypoglycemia due to increased in vitro glycolysis.4
CONCLUSION
Adults with cyanotic CHD have multisystem involvement
with issues that need close follow-up and care by a
multidisciplinary team (Table 2). Fundamental preventive
strategies, early detection and timely care can improve longterm survival and quality of life in these special individuals.
Faith and knowledge lean largely upon each other in the
practice of medicine.
Peter Mere Latham
779
10
Table 2
Care of the adult with cyanotic congenital heart disease: general considerations
Issues
Risks
Care points
Hydration
Dehydration will worsen effects of

erythrocytosis
Remind patients to stay well hydrated

Hydrate well before considering phlebotomy and also
after phlebotomy
Monitored iron supplementation
Nutrition
Iron deficiency
Exercise
Low oxygenation and decreased muscle Daily aerobic and light resistance exercises as
strength decreases exercise capacity
tolerated
Smoking cessation
Pronounced erythrocytosis
Avoid active and passive smoking
Dental care
Bleeding from spongy and fragile

gumsincreased risk of infective
endocarditis
Daily dental carebrushing teeth properly twice daily

with soft toothbrush, biannual dental hygiene visits
Bacterial endocarditis prophylaxis
Skin and nail care
Bacteremia from wounds and cuts
Clean wounds and cuts immediately with soap and

water and follow-up care
Acne
Avoid picking on pimples
Infection from site of nail-biting or

plucking skin tags
Avoid nail biting
Tattoos and body piercing
Avoid risk of infection from needles or bacterial/fungal

entry at puncture sites
Endocarditis prophylaxis
Bacteremia from multiple sources
Prophylaxis before dental work and high risk

procedures
Over-the-counter medications
Bleeding risks
Avoid nonsteroidal anti-inflammatory drugs (NSAIDs)

like Aspirin, ibuprofen
Oxygen supplementation
Epistaxis
Avoid dry nasal mucosa by using saline nasal spray,

topical application of Vaseline to nares, room humidifier
Decreased respiratory drive
Minimize oxygen supplementation
Travel
Deep venous thrombosis (DVT) risk
Increase ambulation and hydration
Travel-related strain and stress

Access to medical care
Reasonable travel plans and minimize exertion

Research local medical options/facilities
Non-cardiac surgery
Pregnancy
Immunization
780
Dehydration
Adequate volume repletion and travel precautions
Bleeding risk
Hydration
Preoperative phlebotomy to reduced risk of bleeding in
patients with hyperviscosity despite hydration.
Save this blood for autologous transfusions
Risk of paradoxical emboli
Intravenous line filters to avoid particulate matter or

bubbles from escaping into the systemic circulation
through the shunts
High risk of miscarriage and preterm

delivery
Increased incidence of prematurity,
small for gestational age babies
Preconception counseling
Correction of the defect prior to pregnancy
Appropriate antenatal care with planned labor and
delivery at a specialized center
Postpartum risk of DVT
DVT precautions
Immunocompromized
Pneumovax
Higher risk for pulmonary infections
Influenza vaccination
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55
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19. Perloff JK. Cyanotic congenital heart disease the coronary

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Complex congenital cardiac lesions. Can J Cardiol.
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accidents in adult patients with congenital heart disease. Heart.
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25. De Louvois J. The bacteriology and chemotherapy of
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26. Saez-Llorens XJ, Umana MA, Odio CM, et al. Brain abscess
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27. Mathisen GE, Johnson JP. Brain abscess. Clinical Infectious
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28. Perloff JK, Marelli AJ, Miner PD. Risk of stroke in adults
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syndrome. Factors relating to deterioration and death. Eur
Heart J. 1998;19:1845-55.
30. Ammash N, Warnes CA. Cerebrovascular events in adult
patients with cyanotic congenital heart disease. J Am Coll
Cardiol. 1996;28:768-72.
31. Perloff JK, Latta H, Barsotti P. Pathogenesis of the glomerular
abnormality in cyanotic congenital heart disease. Am J Cardiol.
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32. Flanagan MF, Hourihan M, Keane JF. Incidence of renal
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C hapter
56
Pregnancy, Contraception and

Gynecological Issues in Women
with Congenital Heart Disease
Reema Chugh, Pamela D Miner, Mary M Canobbio
INTRODUCTION
As women born with congenital heart diseases (CHD) mature
into child bearing years, they are exposed to the risks of
pregnancy that can vary widely among the specific types
of CHD. All patients must be well informed of the risks of
pregnancy, associated with their condition and the available
options to avoid pregnancy when desired. Some women are
also faced with gynecological disorders that may be related
to the underlying CHD. In this chapter, we have three sections
addressing these major issuespregnancy, contraception and
gynecological issuesin women with CHD.
REGNANCY IN WOMEN WITH chd

P
By Reema Chugh, MD, FACC
In order to improve the outcomes in women with CHD, risk
stratification is recommended before pregnancy. Unfortunately,
not all women present for preconception counseling and often
the process of risk stratification have to take place in early
pregnancy. This is either due to lack of patient education or
resources, or when the patient is first diagnosed with CHD
during pregnancy.
According to the guidelines, pregnant women in the lowrisk group can usually be managed in a community hospital
setting, while those who are at intermediate to high risk for
complications should be managed in a high-risk perinatal
unit by a multidisciplinary team that includes an obstetrician,
perinatologist, cardiologist, high-risk anesthesiologist and
a pediatrician.1 The team should meet early in the patients
pregnancy to develop a management plan after understanding
the status of the cardiac lesion, potential issues during
pregnancy, labor and delivery. They should address specific
issues including the timing, mode of delivery, the type of
anesthesia, the level of monitoring before and after delivery.
Review of medications, discontinuation of teratogenic drugs,
genetic counseling, fetal screening and the use of antibiotic
prophylaxis are among the other major topics addressed at

that time.
Overall, women with unoperated complex or cyanotic CHD
have a reduced cardiac reserve and decreased ability to tolerate
the cardiovascular demands of pregnancy, labor and delivery.
They are also at high-risk for cardiovascular complications and
adverse fetal outcomes. As reported in most studies, maternal
outcomes are directly related to New York Heart Association
(NYHA) functional class.2
Fetal outcomes directly depend on maternal health and
exposure to teratogens. Women with complex CHD are more
likely to have fetal wastage, prematurity, low birth weight and
CHD in the offspring.3
PRECONCEPTION ASSESSMENT FOR PREGNANCY RISK

ASSESSMENT IN WOMEN WITH congenital heart
diseases
A comprehensive clinical assessment is critically important
for identifying maternal status and directing appropriate
management (Box 1). It is important to obtain a detailed
medical, surgical, social and family history. This should be
followed by a thorough cardiovascular examination looking
for status of the underlying defects, their residua and sequelae.
In all women contemplating pregnancy, one must review
the possibility of exposure to medications and potentially
teratogenic agents. The physician should prescribe an
alternative medication when necessary. Angiotensin-converting
enzyme inhibitors (ACE inhibitors) and angiotensin II receptor
antagonists, atenolol and amiodarone are commonly used
cardiac medications that should be stopped before pregnancy.
In women who need anticoagulation during pregnancy, an
alternative to warfarin should be offered to avoid fetal exposure
to warfarin, especially in the first trimester (discussed later in
this chapter). Naturopathic medications or over-the-counter
preparations should be avoided during pregnancy, unless
approved by the health care providers. Preconception intake of
10
BOX 1: Preconception clinical assessment in women

with congenital heart diseases
History
Assessment of symptoms suggestive of cardiac issues:
Dyspnea, chest pain/discomfort, palpitations, presyncope,
syncope, orthopnea, paroxysmal nocturnal dyspnea,
peripheral edema
Medical history with review of medical records relating to
CHD and obstetric history
Cardiac surgery and interventional proceduresreview
of operation notes
Substance use: Alcohol, tobacco and recreational drugs
Inheritable disorders/CHD, coronary artery disease,
diabetes, hypertension or stroke
Medications and allergies
Identify potentially teratogenic medications: Discontinue
them and replace with alternate ones when feasible
Allergies/intolerance to medications, foods and
environmental/seasonal substances
Recommend the use of prenatal vitamins: Folic acid
supplements should be started early and prior to
conception for maximal beneficial effect
Physical examination
Assessment of vitals: Weight, blood pressure, heart rate
and rhythm, oxygen saturation on room air
Jugular venous pulsations, carotid pulsations and
upstroke
Pulmonary: Position of the trachea and assessment of
breath sounds to rule out heart failure/asthma
Cardiac examination
Inspection of the chest wall: Scoliosis, kyphosis, pectus
excavatum, scars from previous surgeries
Palpation: Cardiac borders, apical impulse, thrill.
Percussion
Auscultation: Heart sounds, murmurs, rubs and gallops
Abdomen: Situs (position of the liver and gastric
sounds), abdominal jugular reflux (AJR), palpable
masses or pulsations, bowel sounds
Extremities: Pulses, edema, cyanosis, clubbing,
varicose veins
784
multivitamins including folic acid decreases the incidence of

CHD in the offspring.4
Women with CHD should have genetic consultation to
review the etiology, inheritance, risk of transmission and
methods of prenatal diagnosis in order to assess the risk
of CHD in the offspring. A higher recurrence risk is likely
when the mother is affected with CHD rather than the father.
The risk of transmission can range from 3 to 15 percent for
most CHD and up to 50 percent for autosomal dominant
defects. Examples of autosomal dominant defects are: Marfan
syndrome, Noonan syndrome and the Holt-Oram syndrome.
Appropriate cardiac diagnostic tests are requested for
assessment of the baseline exercise functional capacity,
determination of stress-induced arrhythmias and evaluation
of the systemic ventricular systolic function. The status of the
BOX 2: Cardiac diagnostic tests in pregnancy

Electrocardiogram
Rate, rhythm and intervals (PR interval, QRS duration,
and QT intervals), axis, R wave progression
Left ventricular hypertrophy (LVH) or right ventricular
hypertrophy (RVH)
Sinus node function and conduction defects: Atrio
ventricular (AV) heart block, conduction blocks (bundle
branch blocks)
Wolff-Parkinson-White (WPW) syndrome
Echocardiogram
Establish normal findings in pregnancy114,115
Second trimester
Increase in size of the left and right ventricles and the
left atrium
Increased left ventricular (LV) volumes during both
systole and diastole
Increased left ventricular mass and wall thickness
Increased cardiac globularity in the third trimester
Third trimester
Biventricular reduction in global and segmental longitudinal
deformation (compensatory change to accommodate the
increase in cardiac dimensions during pregnancy)
No change in ejection fraction
Study serial changes between the preconception echocardio
gram and those during pregnancy and postpartum
Confirmation of the anatomy, situs, chamber size and
position (rule out ventricular inversion), valve disease,
shunts
Systemic and pulmonic ventricular size and function
Assessment of residual or recurrent lesions
Assessment of pulmonary hypertension
Stress echocardiogram with treadmill stress test (precon
ception)
Baseline functional capacity: Exercise duration, workload
metabolic equivalents of taskMETs
Exercise induced symptoms, arrhythmias or ischemia
Imaging for assessment of:
Contractile reserve: Response of systemic and
pulmonic ventricle to exercise
Pulmonary hypertension: Changes in estimated right
ventricular systolic pressure (RVSP) pre and post
exercise
Stenotic valve gradients, left or right ventricular outflow
tract gradient pre and post exercise.
underlying defects, operated or unoperated with their residua

and sequelae, are assessed and managed accordingly in order
to reduce the risk of maternal and fetal complications during
pregnancy, labor and delivery (Box 2).
HEMATOLOGICAL AND HEMODYNAMIC CHANGES IN

PREGNANCY
During pregnancy hemodynamic changes occur to sustain
intrauterine life and maintain maternal homeostasis (Table 1).
Table 1
Systolic blood pressure
Mildly decreased
Diastolic blood pressure
Decreased
Pulse rate
Increased by 15 to20%
Cardiac output
Increased by 30 to 50%
Systemic vascular resistance
Decreased
Pulmonary vascular resistance
Decreased
Plasma volume
RBC mass
Hemoglobin/hematocrit
Decreased
The maternal plasma volume progressively expands during

pregnancy and rises by 40 to 50 percent of the pregestational
volume by the 32nd week of gestation. A greater increase in
volume is noted in multigravidas (as compared to primigravidas)
and in twin pregnancies (as compared to a singleton
pregnancy).5,6 Distension of the atrial tissue may increase the
risk of atrial arrhythmias during pregnancy. Overall, the cardiac
output increases by 30 to 50 percent and stroke volumes rises by
18 to 25 percent. Since the uteroplacental blood flow is directly
dependant on the cardiac output, a decrease in cardiac output is
associated with intrauterine growth restriction (IUGR) and an
increased likelihood of preterm delivery.7
The rise in red cell volume is around 20 to 40 percent of
the pre-gestational values, causing a relative reduction of the
maternal hemoglobin concentration, also known as dilutional
anemia or physiological anemia of pregnancy.8 Most women
may appear anemic with hemoglobin levels of 11 to 12 g/100
ml and hematocrit levels as low as 33 to 38 percent during the
second trimester.8,9 An increase in extravascular fluid is caused
by a rise in plasma aldosterone levels, which promotes sodium
retention that leads to an increase in body water.6 Women often
encounter peripheral and generalized edema in late pregnancy.
This is due to the additive effect of elevated venous pressure in
the lower extremities and the increase in extravascular fluid.
Pregnancy is a thrombogenic state as a consequence of
the changes in the coagulation cascade. This results from an
increase in clotting factors and decreased fibrinolysis. There is
an additive effect of increased venous stasis. During pregnancy/
postpartum period, women are at risk for developing deep
venous thrombosis, especially when they are inactive or on
bed rest. Those with intracardiac shunts are at risk of having
transient ischemic attacks or stroke, due to paradoxical emboli.
The heart rate progressively rises by 10 to 20 bpm or 17
percent over pregestational rates, with mean values ranging
from 78 to 89 beats per minute. Changes in body position
from supine to lateral may cause a decrease in heart rate.10
The cardiac output rises by 30 to 50 percent over nonpregnant
levels, since it is the product of an increase in stroke volume
and an increase in heart rate. It rapidly rises after 12 weeks

and peaks by the 20th to 24th weeks, remaining at that level,
until late in pregnancy.11
There is a modest decrease in systolic blood pressure
(1015 mm Hg) and a more significant drop in diastolic blood
pressure (2025 mm Hg) that occurs in the first trimester
resulting in widened pulse pressure by mid-pregnancy. Blood
pressure during pregnancy is affected by maternal age over 35
years and parity.12
The systemic vascular resistance (SVR) decreases during
the first two months of pregnancy due to hormonal influences
(estrogen, prolactin and progesterone), along with a decrease
in pulmonary vascular resistance (PVR). These changes
result in an associated increase in uterine and regional blood
flow.11,13 Regurgitant valve lesions are therefore well tolerated
during pregnancy, unless there is severe systemic ventricular
dysfunction. The mean pulmonary artery pressures remain
similar to pre-gestational values.
Maternal position exerts a profound mechanical effect on
cardiovascular hemodynamics, particularly towards the end
of gestation, causing positional fluctuations in cardiac output
by the 38th and 40th weeks. There may be compression of the
inferior vena cava by the gravid uterus in the supine position,
which can decrease venous return, stroke volume and cardiac
output.14 In the last trimester, approximately 8 percent of
women will experience light headedness and nausea. This
supine hypotensive syndrome, can be relieved by placing
the patient in the lateral recumbent position.15 This is also the
preferred position in late pregnancy, during labor and delivery.
No changes in cardiac output are observed in this position. Of
note, the blood pressure taken in the supine position will be
higher than that taken in the left lateral position.10,16,17 The
hemodynamic changes during pregnancy return to the baseline
values usually within 6 to 8 weeks postpartum.
ANTEPARTUM ASSESSMENT
From the cardiovascular standpoint, pregnancy is usually
well tolerated in the first trimester, since major hemodynamic
changes do not occur until the second and third trimester
of pregnancy. The most important change is an increase in
cardiac output by 20 to 24 weeks, due to an increase in blood
volume and heart rate. These changes pose a burden on the
systemic ventricle and residual heart defects, which should be
identified and repaired before pregnancy, if possible.
Physicians and nurse specialists should be familiar with the
physiologic findings on cardiovascular examination during
pregnancy. By the 12 to 20th week of gestation, there may be
tachycardia with pulse rates 10 to 20 beats per minute above
baseline, a widely split first heart sound due to early closure
of the mitral valve and a third heart sound. In addition, there
may be low intensity ejection systolic murmurs along the left
sternal border due to a hyperdynamic circulation.18 In the last
trimester, a systolic murmur originating from the branches of
56
Pregnancy, Contraception and Gynecological Issues in Women with Congenital Heart Disease
Normal major hemodynamic and hematological changes in

pregnancy
785
10
the internal thoracic (mammary) artery and a continuous bruit

originating in the veins of the breast may be heard.19 Women
often have varicose veins and peripheral edema.
Among the abnormal heart sounds during pregnancy are a
fixed splitting of the second heart sound, a fourth heart sound,
a loud systolic murmur (over grade 3/6) or the presence of any
diastolic heart murmurs.
Early on and when indicated in pregnancy, medications
need to be reviewed for their safety data, as well as for
potential teratogenic effects and prescribed only if necessary.
More current information on the medications and their effects
during pregnancy can be obtained from certain websites at no
charge or subscription (www.drugs.com).
Electrocardiograms and transthoracic echocardiograms
can be performed safely as and when indicated. Stress testing
should be avoided whenever possible during pregnancy. A
submaximal treadmill stress test (70% of the maximum age
predicted heart rate on Bruce protocol) is performed only if
strongly indicated. Exposure to radiation should be minimized
and avoided unless absolutely necessary. Abdominal shielding
should be provided when the procedure is necessary and the
risk versus benefit ratio is in favor of performing the procedure.
The risk of radiation exposure to the fetus should be discussed
with the patient. When possible, the procedures should be
postponed, until late second or third trimester of pregnancy.
One such case could be a woman with critical aortic stenosis or
severe mitral stenosis who may need emergent valvuloplasty,
if she is in heart failure due to progressive volume load during
pregnancy.
Screening for Congenital Heart Diseases in the Offspring
786
The incidence of CHD in offspring is estimated to be 0.8

percent in the general population. Irrespective of age, women
with CHD should be screened, since the risk of CHD in
their offspring could vary from 3 to 15 percent, although the
offspring may not have the same defect.20
The maternal serum markers, alpha-fetoprotein in
conjunction with pregnancy-associated plasma protein A
(PAPP-A), human chorionic gonadotropin, and unconjugated
estriol, have improved detection rates of Down syndrome
and trisomy 18. Fetal nuchal translucency, the measurement
of fluid collection size at the back of fetal neck between 11
and 14 weeks of gestation, helps identify a broad range of
chromosomal, genetic and structural abnormalities as long as
the measurements are accurate.21
Chorionic villus sampling or amniocentesis may be
useful after discussion of the potential risks and benefits.
Amniocentesis more specifically detects chromosomal
defects. In a prospective clinical trial, amniocentesis carried a
procedure-related fetal loss rate of 0.06 percent.22
Fetal echocardiography at 14 to 16 weeks gestation should
be performed on all women. This may be repeated at 18 to 22
weeks and closer to delivery. The sensitivity and specificity
are operator dependent.23 The presence of moderate-to-severe
fetal defects may require a planned delivery at a tertiary care

center, or in some cases, medical termination of pregnancy.
Counseling should be offered to the parents of the offspring
and the involvement of a clinical social worker helps the
family deal with the challenges.24
DETERMINING THE MATERNAL AND FETAL RISK

Pregnancies in women with CHD without potential risk
factors are likely to carry low maternal and fetal morbidity/
mortality. Pregnancy carries the highest risk in women with
Eisenmenger syndrome with the postnatal maternal mortality
as high as 50 percent. Another high-risk scenario is a woman
with Marfan syndrome and a dilated aortic root over 4 cm,
which can be at high risk for an aortic dissection. This may
occur due to the impact that hemodynamic and hormonal
changes of pregnancy have on the aneurysmal aorta.
Pregnancy is therefore contraindicated in these women.
Risk factors for maternal morbidity include poor maternal
functional class, poorly controlled arrhythmias, heart failure,
cyanosis, significant left heart obstruction and a history of
cerebral ischemia. The common maternal risk factors are
listed in Box 3. Maternal health status, especially cyanosis
and exposure to teratogenic drugs are the major risk factors
for fetal and neonatal complications. Box 4 addresses the
major fetal risk factors.
Siu et al described a risk index scoring system to predict
the risk of adverse maternal events.25 In order to calculate
the score, the risk index awards one point each for poor
functional status (New York Heart Association [NYHA] > II),
cyanosis (oxygen saturation < 90%), left ventricular systolic
box 3: Contraindications for pregnancy
Absolute contraindications
Eisenmenger syndrome
Dilated aortic root in Marfan (over 4 cm)
Cyanotic congenital heart disease with decompensation
due to unoperated defects
Relative contraindications
Severe obstructive lesions such as critical aortic stenosis
or left ventricular significant outflow tract obstruction,
severe mitral valve or pulmonary stenosis
Symptomatic heart failure/systemic ventricular function
with ejection fraction less than 40%
Uncontrolled arrhythmias
History of transient ischemic attacks or cerebrovascular
accidents
Box 4: Fetal risk factors
Maternal use of teratogenic drugs

Maternal cyanosis
Maternal systemic ventricular dysfunction
Maternal uncontrolled arrhythmias
Fetus with a significant or complex congenital heart disease
H
istory of prior cardiac events such as arrhythmias, heart
failure, transient ischemic attack/stroke
Prior arrhythmias such as symptomatic sustained
tachyarrhythmia or bradyarrhythmia requiring treatment
Poor functional class (New York Heart Association
[NYHA] class > 2)
Cyanosis with low oxygen saturation of < 90% on room
air
Significant valvular and outflow tract obstruction (aortic
valve area < 1.5 cm2, mitral valve area < 2 cm2, or left
ventricular outflow tract peak gradient > 30 mm Hg)
Systemic ventricular ejection fraction < 40%
The risk index score is the sum of the points (one point is
awarded for each risk factor listed above) that predicts the
percentage likelihood of adverse maternal events. Women
with risk index of < 1, 1 and > 1, have a 5%, 27%, and 75%
likelihood of pregnancy-related complications (Adapted from
Siu et al)25.
dysfunction, left heart obstruction and a history of cardiac

events prior to pregnancy including arrhythmias, stroke, or
pulmonary edema.25,26 A risk index score of 0 indicates an
approximate risk of 5 percent, a risk index of 1 correlates with
a 27 percent of adverse maternal events, whereas a woman
with a risk index greater than 1 has a 75 percent likelihood of
adverse events (Box 5).
On the basis of these risk factors and the available data,
women can be stratified into low, intermediate, or highrisk categories. Unfortunately, most of the current data on
outcomes of pregnancy for individual defects are based
on retrospective case series or case reports. Therefore
decisions are often based on clinical experience.27,28 A
referral to a regional adult congenital heart disease (ACHD)
clinic/tertiary care center is recommended for pregnant
women who are at intermediate to high risk for maternalfetal complications. Included among the women identified
as having a high risk score, are those with unoperated
or operated complex CHD, such as transposition of the
great arteries postatrial switch repairs (Mustard/Senning
procedure) or univentricular hearts post-Fontan procedures.
CONGENITAL HEART DISEASES AND PREGNANCY

A brief overview of the potential maternal and fetal
management issues associated with simple and complex
CHD, most often encountered at a regional ACHD center, are
discussed below.
Shunt Defects
Patent foramen ovale, although not always classified as a
CHD, is arguably the most common CHD with a right to
left interatrial shunt, with an increased risk of paradoxical

embolism and stroke, especially when it occurs along with an
atrial septal aneurysm.
Atrial septal defects (ASD), ventricular septal defects
(VSD) and patent ductus arteriosus (PDA) are common lesions
with a left to right shunts.29,30 Women with unoperated or
residual VSD or PDA are at high risk of developing infective
endocarditis.31 Long-standing large shunts may predispose
to pulmonary vascular disease and significant pulmonary
hypertension. Eventually the rising right heart pressures may
cause reversal of the shunt (right-to-left rather than left-toright shunt) leading to Eisenmenger physiology.
Even after patch closure of an atrial septal defect, women
may have supraventricular arrhythmias during pregnancy.
Postventriculotomy ventricular tachycardia or conduction
block may occur following patch repair of a VSD. An early
surgically ligated or divided PDA poses no additional hazard
to the mother or the fetus.
Atrial Septal Defects

In a study of pregnancies in women who have ASD and
no associated lesions, a higher risk of neonatal events was
noted in women with unrepaired ASDs. The risk of cardiac
and obstetrical complications were comparable between
the women with unrepaired and the repaired ASDs. Women
with unrepaired ASDs had an increased incidence of preeclampsia, small-for-gestational-age babies (less than the 10th
percentile) and a higher fetal mortality (intrauterine death at
or after 20 weeks of gestation). Cardiac arrhythmias, namely
nonsustained ventricular tachyarrhythmia and supraventricular
arrhythmias (atrial fibrillation or supraventricular tachycardia)
occurred in 4.3 percent of the pregnancies, more often in older
women and in those with previous history of arrhythmias.
One woman with an unrepaired ASD had a transient ischemic
attack in the postpartum period, probably due to paradoxical
embolism. Reduced exercise tolerance and mild heart failure
were noted in around 3 percent women during pregnancy.32
Ventricular Septal Defects

A recent study comparing outcomes of pregnancy in women
with unrepaired versus repaired VSDs showed a higher
incidence of pre-eclampsia (8.7%) in those with unrepaired
VSD, mostly occurring after 34 weeks of gestation. A higher
incidence of preterm labor was noted in women with repaired
VSDs, probably related to a greater background risk with
relatively larger VSDs having undergone surgical repair. The
mechanism of these observations is not clear. One woman with
an unrepaired VSD suffered Streptococcus viridans infective
endocarditis involving a right heart valve in the postpartum
period, despite receiving antibiotics during an uncomplicated
vaginal delivery. The incidence of recurrence of CHD was
2 percent.33 Other studies have shown a lower incidence of
56
BOX 5: Risk score for predicting pregnancy-related

complications
787
10
pre-eclampsia (1.8%) as reported in a literature review by

Drenthen et al.28

Depending on the size of the ductus and degree of shunt, there
is an increased risk for developing pulmonary hypertension,
congestive heart failure and bacterial endocarditis/endarteritis.
The maternal morbidity and mortality in unrepaired PDA is
low. Women with a ligated or divided isolated PDA carry no
risk in the presence of normal left ventricular function and
normal pulmonary arterial pressures.34
Atrioventricular Septal Defects

In atrioventricular septal defects (AVSD), the architecture
of the fibrous skeleton of the heart is structurally different
from other septal defects and therefore, the clinical outcomes,
surgical repair, residua and sequelae differ significantly. Due
to these complexities, pregnancy is not always well tolerated
in women with AVSD.
In a multicenter study with 29 women who had 62
pregnancies, including 12 miscarriages (19%) and two
elective abortions, cardiovascular complications occurred
in almost 40 percent of the term pregnancies. There was
deterioration in functional class (NYHA) seen in 23 percent
and worsening of pre-existing atrioventricular (AV) valvular
regurgitation in 17 percent. Cardiac arrhythmias occurred in
19 percent and symptomatic heart failure in 2 percent of the
women. Mortality was high among the children (6.3%), since
12 percent had complex CHD. Among the three children who
died, two children had left-sided hypoplasia.35
Obstructive Outflow Tract Defects

Pulmonary Stenosis
788
Pulmonary stenosis (PS), the most common form of a rightsided obstruction, may occur as an isolated heart defect.29,30
The clinical presentation depends upon the severity of the
obstruction and can vary from being asymptomatic with good
long-term outcomes as seen with mild stenosis, to the presence
of right ventricular hypertrophy, right heart failure and sudden
cardiac death in uncorrected cases of severe pulmonary
stenosis. Balloon valvuloplasty is therefore recommended
when the resting gradient across the right ventricular outflow
tract is over 50 mm Hg or when the patient is symptomatic prior
to conception. It need not be performed during pregnancy in
women who are asymptomatic or mildly symptomatic. Most
women will tolerate a vaginal delivery.36,37
Surprisingly, an excessive rate of noncardiac complications
was reported in one multicenter study with 51 women with
corrected pulmonary stenosis, who had 108 pregnancies,
including 21 (19%) miscarriages and 6 elective abortions.
The major maternal complications were hypertension-related

disorders noted in 15 percent of the women. Four pregnancies
were complicated by pre-eclampsia and two women had
eclamptic seizures. These observations are unusual, because
the incidence of hypertension-related disorders and eclampsia
were much higher than seen in the general population.
Thromboembolic events occurred in nearly 4 percent pregnant
women with pulmonary stenosis. Cardiac problems were
palpitations/arrhythmias in nine women and deterioration
in functional class in two women persisting for one year
postpartum. Fetal complications were premature deliveries in
17 percent, fetal mortality in 4.8 percent and occurrence of
CHD in offspring 3.7 percent.38
Although, there is no clear explanation for the higher
incidence of non-cardiac complications among these women
undergoing pregnancy, early detection and close attention to
risk factors for hypertension-related disorders and premature
birth are advocated to improve maternal and fetal outcomes.
Bicuspid Aortic Valve

Bicuspid aortic valve (BAV) is one of the most common
CHDs.29,30 Pregnancy with mild to moderate stenosis is well
tolerated. However, severe stenosis encroaches upon the
circulatory reserve (valve area less than 1 cm2) and valve
replacement/repair should be advised before pregnancy.
Women proceeding with severe aortic stenosis (AS) are at
risk for developing heart failure (44%),36 angina, syncope
and sudden cardiac death during pregnancy. The aortic root
should be monitored in women by echocardiography during
pregnancy for dilatation/dissection.
In a study with 39 women who had congenital aortic
stenosis (AS) and carried 49 pregnancies, Silversides et
al report that although more than one-half had severe AS,
most of them were asymptomatic before pregnancy. Early
cardiac complications, including pulmonary edema and atrial
arrhythmias, occurred in three pregnancies. One of those cases
was a woman with critical aortic stenosis who required urgent
percutaneous aortic valvuloplasty at 12 weeks gestation.
The severity of AS dictated cardiac complications (10%
occurred in severe AS, compared to none in mild or moderate
AS). Fetal complications included prematurity (8%), small
for gestational age (2%) and neonatal distress respiratory
syndrome (6%).39
In a follow-up study on late outcomes after pregnancy with
congenital AS, Tzemos and Silversides et al reported that
women with moderate or severe AS who were symptomatic
during pregnancy were at higher likelihood of requiring
cardiac interventions late after pregnancy. There were also at
risk of experiencing a higher frequency of late cardiac events
than those who had not been pregnant (31% vs. 0%).40
In another multicenter study, Yap et al followed-up
53 successful pregnancies in 35 women (from a total of
58 pregnancies resulting in three miscarriages and two
changes in pregnancy cause some women to suffer aortic

rupture and dissection during pregnancy or postpartum.
Women with CoA have been reported to have a higher risk
of hypertensive complications of pregnancy in many series.
The incidence of pre-existing hypertension complicating
pregnancy and pregnancy-induced hypertension are both
increased in this population.44,45 In a study by Krieger et al,
hypertension occurred in 24.1 percent of all women with CoA
during their pregnancies, and 13.9 percent of those who were
previously considered normotensive were diagnosed with
hypertensive disorders during pregnancy.45 Although the
guidelines for the care of ACHD recommend vaginal delivery
in most cases, except in the setting of an obstetric indication
for cesarean delivery, this study noted that women with CoA
have a higher rate of delivery by cesarean section and longer
hospitalizations, than seen in the general population.45
Beauchesne et al reported 118 pregnancies in 50 women
with CoA and found a 34 percent incidence of hypertensive
complications.46 Women with unoperated coarctation of aorta
often become hypertensive in the third trimester of pregnancy.
They may develop paracoarctation aortic aneurysm/dissection
and should have resection with end-to-end repair before
conception. Unfortunately, risks persist in some women even
after having the operation. These include hypertension (not
related to age at the time of repair), aortic root dissection and
rupture of berry aneurysms that occur even in normotensive
patients. The residual aortic gradient was associated with an
increased risk for hypertensive complications of pregnancy.46,47
All patients should have adequate blood pressure control and
aortic root monitoring. The goal is to maintain a systolic blood
pressure between 100 to 120 mm Hg and a diastolic blood
pressure between 60 to 80 mm Hg.
Hypertension in pregnancy has also been linked to adverse
fetal outcomes, including higher incidence of preterm
delivery, low birth weight for gestational age and admissions
to a neonatal intensive care unit.48
Coarctation of Aorta
Tetralogy of Fallot
Coarctation of aorta (CoA) is not just limited to focal

stenosis, but is a variant of diffuse arteriopathy and associated
structural abnormalities of the great arterial walls.43 The
narrowing of the aorta usually occurs at the junction of the
distal aortic arch and the descending aorta, below the origin
of the left subclavian artery.29,30 This defect is thought to
be intrinsically associated with a diffuse vasculopathy with
vascular and endothelial dysfunction. In addition, there are
histopathologic abnormalities in great arterial walls43 leading
to arterial stiffness, endothelial dysfunction and endotheliumindependent vascular dysfunction that predispose to
hypertension. These structural abnormalities of the aorta
hypertension, the added stress from hemodynamic, hormonal
Tetralogy of Fallot (TOF) is the most common cyanotic

congenital heart defect.29 Women with unoperated tetralogy
of Fallot may experience increased cyanosis as systemic
vascular resistance decreases during the pregnancy. In most
series, cardiac (4.5% to 18%), obstetric (11% to 20%) and
neonatal (16% to 27%) events occurred during completed
gestations. Unrepaired tetralogy as well as the presence
of pulmonary atresia have been reported as independently
predictive of fetal prematurity, dysmaturity, fetal wastage, and
low infant birth weight.49-53
While complete intracardiac repair improves maternal
and fetal outcomes depending on the prepartum functional
class and biventricular function, adverse maternal events
Cyanotic Congenital Heart Disease
56
abortions). The most serious cardiac complications (9.4%)

were heart failure (3.8%) and atrial arrhythmia (5.7%).
Interestingly, noncardiac complications were far more
common with obstetric issues occurring in 22.6 percent and
perinatal complications in 24.5 percent. Hypertension-related
disorders (including one case of eclampsia) were noted in
six pregnancies (11.3%). Fetal complications were mainly
premature births in 7 (13.2%) and small for gestational age
births in 7 (13.2%). They concluded that pregnancy in women
with severe AS was associated with an increased incidence
of heart failure, premature labor, and shorter duration of
pregnancy, with a higher likelihood of perinatal events in
women over the age of 30.41
Preconception counseling is very important in women
with AS. The risk of late cardiac outcomes after pregnancy
should be considered in those with moderate to severe aortic
stenosis. Balloon valvuloplasty or aortic valve replacement
(bioprosthetic) should be recommended before pregnancy.
During gestation, in severely symptomatic women who are
unresponsive to medical management (mainly diuretics),
early delivery should be considered once fetal lung maturity
is achieved (usually around 36 weeks of gestation), so that
the mother can then undergo intervention or aortic valve
surgery. Those who cannot deliver the baby may require early
termination of pregnancy or relief of stenosis by percutaneous
balloon valvuloplasty or surgery. Although percutaneous
balloon valvuloplasty carries a risk of fetal radiation (partially
reduced by abdominal shielding), it is preferred over surgery
for aortic valve replacement, since the later carries higher risk
of maternal morbidity and fetal loss.
High risk anesthesiologists should assist with hemodynamic
monitoring during labor and delivery in patients with moderate
and severe AS. Vaginal delivery with an assisted second stage
of labor is the preferred mode of delivery, with cautious use
of adequate regional anesthesia in order to avoid a decrease
in systemic vascular resistance that may be poorly tolerated.
General anesthesia is preferred in women with severe aortic
stenosis undergoing a cesarean delivery.42
789
10
790
may be associated with left ventricular dysfunction, severe

pulmonary hypertension and severe pulmonary regurgitation
with impaired right ventricular function.49
The postventriculotomy scar exacerbated by a mechanoelectrical disturbance caused by severe pulmonary regurgita
tion, can trigger monomorphic ventricular tachycardia.54 An
echocardiogram should be performed during every trimester
or when indicated, to measure aortic root dilatation since
dissection has been reported in individuals with markedly
enlarged aortic root.55,56 The occurrence of CHD in the
offspring is as high as 6 percent of livebirths. The 22q11
deletion is associated with DiGeorge syndrome and tetralogy
of Fallot.49
In a retrospective review of 40 deliveries in 25 patients
with repaired TOF, Kamiya et al reported that 17.5 percent
pregnancies were complicated by cardiac events (mainly due
to decline in functional class and arrhythmias). The main
predictors of adverse outcomes were history of ablation and the
increased baseline cardiothoracic ratio on chest radiography.
While left ventricular size and function did not change with
pregnancy, the right ventricle was enlarged at 6 months after
delivery and could potentially affect the long-term prognosis
of women with repaired TOF.57
In another large retrospective international multicenter
study of 157 pregnancies in 74 women with corrected
TOF, Balci et al reported 123 completed pregnancies with
associated maternal cardiac events in 8.1 percent and
obstetric complications in 58.9 percent. There were adverse
fetal outcomes in 33.9 percent. The mortality in the offspring
was 6.4 percent. The most important predictors of adverse
maternal outcomes were the use of cardiac medications before
pregnancy, prior surgery for pulmonary valve replacement
(PVR) and the occurrence of arrhythmias before pregnancy.
Previous history of PVR was associated with arrhythmias, and
in one pregnancy, there was pulmonary embolism along with
arrhythmias, while another pregnancy in the PVR group was
complicated by arrhythmias and heart failure.58
The use of cardiac medications before pregnancy was also
associated with birth of significantly small-for-gestationalage babies. The reason for the association between adverse
maternal/fetal events and the use of cardiac medications
before pregnancy, may reflect a need based on less favorable
baseline cardiac condition in terms of ventricular function and
history of arrhythmias. The use of cardiac medication before
pregnancy was noted in 71 percent of women with PVR and
right ventricular dysfunction, indicating late timing of PVR.
In these cases, the PVR was performed when long-standing
pulmonary regurgitation had already compromised the right
ventricular function, predisposing to arrhythmias post-PVR.58
A possible relation between severe pulmonary regurgitation
and symptomatic right heart failure has been noted in other
series.59
The threshold for performing cesarean delivery for
obstetric/offspring reasons appears to be lower than usual
in these studies, probably because of caution on the part of

obstetricians in these more vulnerable mothers and babies. The
rate of antenatal complications was reported as significantly
higher in a study by Gelson et al.60 They noted a more frequent
use of epidural anesthesia, shorter length of the second stage,
with both spontaneous and assisted deliveries, in the women
with repaired TOF. Women with moderate to severe pulmonary
regurgitation also had small-for-gestational-age offsprings.
Preconception counseling is very important in this
population in order to review the circulation with particular
attention to severe right ventricular outflow tract obstruction,
severe pulmonary regurgitation and right ventricular
dysfunction. Since pregnancy carries the risk of arrhythmias,
right ventricular failure and endocarditis, an elective-induced
delivery should be planned once fetal lung maturity is
attained. A plan for delivery should be agreed and documented
by the team taking care of the patient. Close follow-up and
management of heart failure and arrhythmias is important.
If right ventricular failure occurs, preterm delivery should
be considered. Vaginal delivery with low-dose combined
spinal-epidural analgesia and assisted second stage of labor
is recommended. When cesarean delivery is indicated for
obstetric reasons, a low-dose combined spinal with incremental
epidural anesthesia, or incremental spinal catheter anesthesia,
are both suitable. General anesthesia is usually reserved for
emergency situations.61 Invasive hemodynamic monitoring is
not recommended, since there is a higher risk of complications
and limited clinical benefits. Noninvasive hemodynamic
monitoring with periodic blood pressure readings, continuous
telemetry to check for arrhythmias and pulse oximetry for
oxygen saturations are recommended.
It is important to note that the radial pulse will not be
palpable on the same side as the Blalock-Taussig shunt.
All women should receive prophylaxis against bacterial
endocarditis and deep venous thrombosis.
Dextro or d-Transposition of the Great Arteries

In d-Transpostion of the great arteries (d-TGA), there
is ventriculoarterial discordance due to the transposed
pulmonary artery and the aorta.29 Most women with d-TGA
have previously undergone an atrial switch repair (Mustard
or Senning procedure) and their morphological right ventricle
is the systemic ventricle that pumps into the aorta. Currently,
more women with arterial switch repair (Jatene procedure)
are entering into their child-bearing years.
Atrial Switch Repair

In a multicenter study, Canobbio et al reported that in women
with atrial switch repair (Mustard or Senning procedure), there
were cardiac complications, primarily heart failure and atrial
arrhythmias, most often in the third trimester, in 36 percent
of the pregnancies. There were two maternal deaths after
Arterial Switch Repair

As the women with arterial repair for d-TGA plan to have
pregnancies, the potential long-term residual and sequelae of
this surgery have to be taken into account. Limited data are
available regarding pregnancy in this population.
Despite pulmonary artery banding before surgery to train
the left ventricle to take over as the systemic ventricle, left
ventricular function may still deteriorate gradually after
arterial switch operation in patients with d-TGA and an intact
ventricular septum. Right ventricular outflow obstruction
(subpulmonic stenosis/infundibular stenosis) is commonly
noted and may require intervention in 10 percent of the cases.
Coronary events may occur in 7 percent due to an abnormal
coronary anatomy or coronary ostial fibrosis at the site of the
reimplanted coronaries, or due to kinking, torsion or extrinsic
compressions that require immediate surgery.
Tobler et al retrospective studied the prevalence of adverse
maternal cardiac events during pregnancy in nine women
with arterial repair, who had 17 pregnancies. There were
four miscarriages. Five women had clinically important
valve lesions and one had left ventricular dysfunction prior
to pregnancy. Cardiac complications occurred in two women;
nonsustained ventricular tachycardia was noted in one
woman with impaired left ventricular systolic function and
postpartum valve thrombosis occurred in another woman
with a mechanical mitral (systemic atrioventricular) valve.
Although the left ventricular function deteriorated during
pregnancy in two women, no pulmonary edema or ischemic
events occurred during or after any pregnancy. Two women

with dilated aortic roots did not have progressive enlargement
in pregnancy or postpartum. No maternal mortality was
reported in this study nor were there any significant adverse
fetal outcomes other than one small-for-gestational-age baby
born to a mother who had multiple comorbidities.68
Congenitally Corrected Transposition

of the Great Arteries
In congenitally corrected transposition of the great arteries
(CCTGA) there is transposition of the great arteries
(ventriculoarterial discordance) and ventricular inversion (AV
discordance). Although the circulation is physiologically)
corrected, the morphologic right ventricle is the subaortic
sytemic ventricle. Commonly associated defects are
ventricular septal defect and pulmonary stenosis.29
Women with unoperated defects may have worsening
cyanosis, risk of stroke because of microcytosis, paradoxical
emboli and systemic emboli (with severe right ventricular
cardiomyopathy). Heart failure occurs due to systemic
ventricular dysfunction and severe tricuspid regurgitation
in both unoperated and operated cases.69,70 In those with
biventricular repair, the risk of heart failure depends upon
the pregestational biventricular function. Maternal functional
capacity and cyanosis are major risk factors for fetal wastage
(627%) and the occurrence of CHD in the offspring varies
from 2 to 18 percent.70
Management issues during pregnancy are usually related
to heart failure or atrial arrhythmias. Fluid retention is treated
with gentle diuresis. Rate control in atrial arrhythmias may be
achieved by using beta blockers (propranolol). Direct-current
(DC) cardioversion is safe when there is hemodynamic
instability. Ideally women with history of arrhythmias should
consider radiofrequency ablation (RFA) prior to carrying a
pregnancy. Women with unimpaired systemic ventricular
function who are tolerating the pregnancy well may carry it
to term and have an elective induced vaginal delivery with
assisted second stage of labor under epidural anesthesia.
Those who are markedly symptomatic may need to deliver
as soon as fetal lungs are mature. Hemodynamic monitoring
should be noninvasive with blood pressure checks, telemetry
to check for arrhythmia and pulse oximetry instead of invasive
monitoring.71
56
delivery. The fetal complications seen in 39 percent included a

high rate of fetal wastage, low birth weight and prematurity.62
Similar risks have been shown by other studies.63-66 The
systemic (morphologic right) ventricle is likely to become
further dilated with volume load of pregnancy. The success of
pregnancy is related to function of the systemic right ventricle
prior to pregnancy, as well as the degree of aortic and tricuspid
insufficiency.65
A more recent study by Metz et al prospectively followed
the right ventricular function through pregnancy and the
postpartum period.67 There was a fall in the systemic right
ventricular function in 89 percent women during pregnancy
and although there was an improvement in the postpartum
period, the baseline function was not regained completely.
The degree of tricuspid (left AV valve) regurgitation also
progressed, but improved after delivery. A unique observation
was the high rate of atrial baffle obstruction that occurred in
36 percent women during pregnancy, as compared with only
5 percent reported in the all patients after an atrial switch
procedure. In all women, the superior limb of the systemic
venous atrial baffle was obstructed significantly (and was
probably unmasked by the increased venous return that
occurs during pregnancy). The baffle obstructions required
intervention in the postpartum period.
Ebstein Anomaly
Women with unoperated Ebstein anomaly of the tricuspid
valve may develop increased cyanosis because of the rightto-left shunt through an interatrial shunt. Right heart failure
may develop from severe tricuspid regurgitation and right
ventricular dysfunction. Supraventricular tachycardia may
occur because of an accessory pathway associated with WolffParkinson-White (type B) syndrome.12
791
10
792
In women with operated Ebstein anomaly, the outcomes

during pregnancy depend on baseline functional NYHA class,
adequacy of tricuspid valve repair or replacement, arrhythmias
related to an accessory pathway.72
Women with an accessory pathway should be advised
to have RFA before planning a pregnancy, in order to
reduce the incidence arrhythmias or the use of medications
needed to control them during pregnancy. Adenosine or DC
cardioversion according to advanced cardiac life support
protocol can be used to terminate SVT during pregnancy.
Overall, in the absence of significant maternal cyanosis
or arrhythmia, pregnancy is usually well tolerated. Fetal
outcomes depend upon maternal cyanosis, since it contributes
to an increased risk of prematurity and dysmaturity.73
Univentricular Heart
The univentricular heart (single ventricle physiology) is characterized by a large dominant ventricle (more commonly the
left ventricle) and a small rudimentary ventricle. Associated
heart defects include atrioventricular (AV) valves defects,
transposition of the great arteries and intracardiac shunt
defects.29 Right ventricular hypoplasia with tricuspid atresia is
the commonest form. Majority of the women have had a prior
Fontan procedure (classic Fontan involving a right atrium to
pulmonary artery conduit, also called atriopulmonary connection)74 or one of its modifications, such as direct connection between the systemic venous return and the pulmonary
artery, also called the total cavopulmonary connection (TCPC).
Long-term issues in women with Fontan procedure are related
to low cardiac output, increased venous pressure and congestion. Exercise tolerance may be reduced due to impaired
ventricular function and difficulty in increasing preload.
Canobbio et al reported that the major maternal
complications related to pregnancy are heart failure, atrial
arrhythmias (atrial fibrillation and flutter) and thromboembolic
complications related to intracardiac thrombi formed despite
antiplatelet therapy or anticoagulation.75 Arrhythmias, usually
supraventricular, were reported in 26 percent of pregnancies
and most often associated with the classic Fontan.76
There is an increased risk of first trimester miscarriages
(33%) and occurrence of CHD in the offspring. Due to preterm
rupture of membranes, premature labor and delivery between
26 and 33 weeks, the fetal complications are prematurity and
low birth weight. There is a significant risk of postpartum
hemorrhage.75,76
These women should avoid dehydration during pregnancy
and especially during labor and delivery, because volume
depletion can lower the central venous pressure and blood
flowing through the cavopulmonary connection to the lungs.
In order to prevent aortocaval compression by the gravid
uterus, the left lateral position is very important when lying
down. General anesthesia should be avoided for a cesarean
delivery, since positive pressure ventilation will decrease the
pulmonary blood flow.61
Eisenmenger Syndrome
Eisenmenger syndrome (ES) is characterized by irreversible
pulmonary vascular disease and severe pulmonary
hypertension in the presence of reversal of a shunt (right to
left shunt).29 Interestingly, adults with ES have better survival
and more favorable hemodynamics than those with idiopathic
pulmonary arterial hypertension.
Maternal mortality rates of 30 to 52 percent in ES are
largely due to the inability of the relatively fixed pulmonary
vascular resistance to adjust to the cardiovascular demands
of pregnancy, delivery and puerperium. Death usually occurs
during delivery or most commonly in the 1st to 6th weeks
post partum. Spontaneous abortions may occur in 40 percent.
The level of pulmonary arterial pressure before or in the early
stage of pregnancy is an important predictor of pregnancy
outcome.77,78 Fetal outcomes are poor, with prematurity in 55
percent, low birth weight in 30 percent and perinatal mortality
in 28 percent.77
Despite medical advances, the prognosis of pregnancy
in women with ES remains dismal.78-82 Pregnancy is
contraindicated in women with Eisenmengers syndrome.
Contraception should be offered to all women with ES during
their child-bearing years. Combined oral contraceptives
carry an increased risk of thrombosis, while progesterone
only contraceptives have a high failure rate as noted in the
section on contraceptive issues. Laparoscopic sterilization
with general anesthesia carries risk. The best options in
these women are the intrauterine coil and subdermal devices.
Medical termination of pregnancy should be addressed very
early, since procedures in later pregnancy carry a higher risk.
In women who choose to carry on with pregnancy despite
having informed risks about high rates of mortality associated
with pregnancy and ES, a detailed group discussion between
the medical/obstetric/clinical social worker team and the
patient with her family should occur and be documented in
the medical records.
These women will require very close monitoring during
their pregnancy with coordination between a multidisciplinary
team for early detection and treatment of pregnancy-induced
complications. Heart failure during pregnancy is common
and should be treated promptly with gentle diuresis. If the
pregnancy lasts until the third trimester, hospitalization for bed
rest and supplemental oxygen is recommended and there is a
high likelihood of preterm delivery. Although these women are
at high risk for thrombosis as well as hemorrhage, there are no
specified guidelines regarding the use of anticoagulation and it
remains controversial. Adequate hydration and antithrombotic
pumps with support hose stockings should be used to reduce
the risk of deep venous thrombosis.
Pulmonary vasodilators may be considered, other than the
use of endothelin antagonists, which are contraindicated in
pregnancy. Inhaled nitric oxide may be useful, particularly
in the peripartum period, since it increases pulmonary blood
flow and improves systemic arterial oxygen saturations in
COMMON MANAGEMENT ISSUES IN PREGNANCY

The American College of Cardiology (ACC)/American Heart
Association (AHA) guidelines in 2007 advocate intravenous
antibiotic prophylaxis, at the onset of labor, in women with
moderate to high risk CHD.84 This comprises all CHD except
for an isolated or repaired atrial septal defect (6 months
after closure), repaired ventricular septal defect with no
residual shunt, surgically ligated patent ductus arteriosus and
extracardiac, cardiac pacemakers and defibrillators.
The standard dosage of antibiotics are ampicillin 2 gm
intravenous (IV)/intramuscular (IM) and gentamicin 1.5 mg/
Kg initially and second dose of ampicillin 1 gm IV/IM or
orally 6 hours later. Vancomycin (1 gm IV over 12 hours)
plus gentamicin are used if the patient is allergic to penicillin.
Due to the low risk of bacteremia, the guidelines do not advocate
prophylaxis for an uncomplicated vaginal or cesarean delivery.
Since it is not possible to predict obstetric complications, most
centers prefer to administer antibiotics at time of the rupture
of the membranes during a vaginal delivery, because of the
high morbidity or mortality associated with endocarditis. No
major toxicities have been reported with dosage for bacterial
endocarditis prophylaxis.85 Concerns about inappropriate
obstetrical use of antibiotics mainly apply to situations other
than for bacterial endocarditis prophylaxis.86
Deep Venous Thrombosis

All women are hypercoagulable during pregnancy and have an
increased risk of deep venous thrombosis (DVT), pulmonary
embolism, paradoxical embolism and stroke depending upon
the associated underlying cardiac defects. These women
should be educated about preventive measures such as regular
ambulation, adequate hydration and support stockings.
Anticoagulation especially in the postpartum period may be

prescribed to very high-risk patients.87
Anticoagulation
The biggest challenges in anticoagulation during pregnancy
are the mechanical prosthetic valves.88 In a study of 33 women
with 82 pregnancies, the risk factors for valve thrombosis
were based on type (mechanical), position (mitral), number
of prosthetic valves, arrhythmias, previous thrombosis
and adequacy of anticoagulation. All fetal complications,
stillbirths, spontaneous and therapeutic abortions, occurred
in women taking warfarin (5 mg or higher). Low-molecular
weight heparin use was associated with intrauterine growth
retardation in 22 percent of the offspring. No anticoagulation
regimen conferred complete protection from thromboembolic
phenomena in pregnancy.89
The protocols for anticoagulation during pregnancy should
be individualized and based upon patient preference and risk
profile. Some prefer warfarin, except, in the first trimester and
2 weeks before delivery, during which period unfractionated
heparin or enoxaparin is used. Others advocate subcutaneous
unfractionated heparin (UFH) or enoxaparin throughout
pregnancy followed by a switch to intravenous heparin two
days before elective delivery.90-94 For higher risk patients,
warfarin dose should be adjusted to keep International
Normalized Ratio (INR) 2.5 to 3.5 and they should receive
an aspirin 81 mg oral daily when UFH or enoxaparin is given
to maintain a trough anti-Xa levels more than or equal to 0.8
IU/ml and peak anti-Xa levels less than 1.5 IU/ml. The antiXa levels should be monitored every 2 weeks, since the body
surface area and the drug volume of distribution are constantly
changing in pregnancy.
Aortic Root in Pregnancy

Many CHDs are associated with structural abnormalities
of the great arterial walls that lead to dilatation of the aorta
and/or the pulmonary arteries.43 Progressive dilatation of the
aortic root can occur in women with a bicuspid aortic valve,
coarctation of aorta, large ventricular septal defect, tetralogy
of Fallot/pulmonary atresia with ventricular septal defect and
in truncus arteriosus.
The potential risk of forming an aneurysm or dissection
is the highest at the time of labor and delivery because of a
surge in the cardiac output. Due to estrogen withdrawal, the
risk may continue to be high in the postpartum period. An
elective cesarean delivery is recommended in women with a
dilated aortic root that is progressively increasing in size. The
risk of rupture/dissection rises when the diameter reaches 5 to
5.5 cm or if dilatation of the aortic root progresses at the rate
of 1 cm or greater per year.95 Asymptomatic women should
consider undergoing prophylactic aortic root repair prior to
conception, even though the surgical risk associated with
56
patients with pulmonary hypertension.82 Invasive pulmonary

artery monitoring can be very dangerous should therefore
be avoided. The intravenous administration of pulmonary
vasodilators carries a risk of clinical deterioration despite
theoretically improving the pulmonary hypertension, by
causing a fall in systemic vascular resistance, an increase in
right-to-left shunting, worsening hypoxemia, acidosis and
decreased coronary artery perfusion.83
An elective cesarean delivery is usually scheduled between
30 and 34 weeks of pregnancy, when the fetus is viable and
before the occurrence of maternal hemodynamic compromise.
General anesthesia should be avoided and low-dose sequential
combined spinal-epidural or incremental spinal anesthesia is
recommended, since both allow slow titration with minimal
effects on the peripheral circulation.61 Close monitoring is
carried into the postpartum, since there continues to be a very
high incidence of maternal mortality.
793
10
aortic root surgery averages around 2.5 percent.96 According

to the clinical practice guidelines for thoracic aortic disease,
operative repair is indicated in symptomatic patients with
aortic diameter over 4.4 to 5 cm and/or growth greater than
0.5 cm per year, in ascending aortic aneurysms associated with
Marfan syndrome, bicuspid aortic valve or other geneticallymedicated disorders that are at high risk for dissection. The
aortic root should be assessed annually if the diameter ranges
from 3.5 to 4.4 cm and semiannually if it is 4.5 to 5.5 cm.97
Prior to conception, women undergoing an intracardiac
surgery for another indication should be considered for a
concomitant aortic root repair, if the aortic root is over 4 cm.
It is recommended that preconception transthoracic
echocardiographic assessment of the aortic root dimensions30
be performed, along with serial echocardiograms to document
changes in aortic dimensions at 20 to 24 weeks of pregnancy
and monthly thereafter until 4 to 6 weeks postpartum.
Arrhythmias
The severity and frequency of arrhythmias increases with
hemodynamic changes in pregnancy. The relation between
symptoms and cardiac arrhythmias was studied in 110
consecutive pregnant patients without evidence of heart
disease referred for evaluation of palpitations, dizziness and
syncope. Holter monitoring showed an increased incidence
of mostly atrial and ventricular premature complexes (VPCs)
during pregnancy with a substantial reduction in the incidence
in the postpartum period. Although the number of simple
and multifocal VPCs was higher in symptomatic patients,
there was no significant correlation between the incidence of
arrhythmias and symptoms. Only 10 percent of symptomatic
documented episodes correlated with the presence of
arrhythmias.98
Women with CHD are at increased risk of presenting for the
first time with a symptomatic arrhythmia during pregnancy or
if previously diagnosed, are at the risk of recurrence of their
arrhythmias.99 In women with complex CHD, uncontrolled
maternal arrhythmias can cause hypotension and decreased
cardiac output, leading to poor perfusion of the placenta
and fetus with possible premature deliveries of small-forgestational-age babies.
After considering the risk/benefit ratio for the mother and
the fetus, antiarrhythmic therapy should be restricted for
use in management of intolerable symptoms or intractable
arrhythmias that may be potentially harmful to the fetus.
Based on the data from observational reports, most available
antiarrhythmic drugs are classified as in pregnancy risk
category C.
Tachyarrhythmias
794
Adenosine may be used safely to diagnose or terminate a

supraventricular tachycardia. Beta blockers and digoxin may
be used for rate control in the second and third trimesters. Antiarrhythmic agents should be avoided during the first trimester,
since there are limited data on the safety of their use in
pregnancy. Women with effective antitachycardia pacemakers
or implantable defibrillators, who take medications to reduce
the frequency of overdrive pacing or discharge, can stop
antiarrhythmics during the first trimester. The preferred and
safe method for terminating hemodynamically compromising
atrial arrhythmias during pregnancy is by DC cardioversion.100
Bradyarrhythmias
Women with pacemakers for sick sinus syndrome or
chronotropic incompetence should have the lower rate limit
of the pacemakers increased to match the physiological heart
rate increase during pregnancy. In women with re-entrant
type of arrhythmia potentially induced by premature atrial
beats, the lower rate limit of the pacemaker may be elevated
to overdrive suppression of premature beats and decrease the
frequency of tachycardia.100
The obstetric team should be aware that high doses of
magnesium when used for treating pre-eclampsia or eclampsia
can increase pacing thresholds and this may lead to pacemaker
failure to capture. This is especially important when there is
impaired renal function.
Heart Failure
Women with moderate or severely reduced systemic
ventricular function and/or NYHA functional class III and
IV are at high risk for maternal complications and should be
advised against pregnancy. There is cumulative effect of all
pregnancies, including miscarriages and abortions, on the
systemic ventricular function.101
In case of mild to moderate systemic ventricular
dysfunction, heart failure medications including angiotensinconverting enzyme (ACE) inhibitors and aldosterone
antagonists such as spironolactone, should be prescribed for
a year before considering pregnancy, with reassessment of
systemic ventricular function prior to conception. Since these
two medication classes are listed as pregnancy risk category
D, they should be stopped once the woman is planning
pregnancy. Other heart failure medications such as diuretics,
certain beta blockers (especially propranolol) and digoxin may
be continued during second and third trimester of pregnancy.
Acutely decompensated heart failure in pregnant women
requires admission to the cardiac care unit with 100 percent
oxygen, diuretics and vasopressor support as indicated.
Concerns regarding fetal safety should be set aside, while
trying to stabilize the mother. The patient should lie in the
left lateral position to improve her cardiac output. Invasive
monitoring is rarely indicated and should be avoided as far as
possible. Noninvasive methods of monitoring are preferred.
Once stabilized, a woman in her third trimester, should be
considered for an induced delivery as soon as fetal lung

maturity is achieved.
Since none of the cardiac medications are absolutely safe for

the fetus during pregnancy, their use should be limited and
considered carefully only after reviewing the indications,
safety data and pregnancy risk category classification
(Table 2). Nursing mothers are advised to avoid feeding their
infants when the expected plasma concentration of the drugs
is the highest, even if no major clinical effects on infants have
been reported for that particular medication.102
Some of the more commonly prescribed cardiac
medications are discussed in this chapter. More up-todate information on cardiac medications in pregnancy
can be obtained from the US. Department of Health and
Human Services, Office on Womens Health (http://www.
womenshealth.gov/publications/our-publications/fact-sheet/
pregnancy-medicines.pdf) and from another website: www.
drugs.com.
Warfarin
Warfarin is classified as pregnancy category X. It inhibits
vitamin K-dependent coagulation factors, proteins C and S.
Side Effects
Warfarin embryopathy is characterized by nasal hypoplasia
and chondrodysplasia punctata that can occur in 6.4 percent
live births.91 There is a potential effect on childhood growth
and development.103 In addition, there is an increased risk of
fetal hemorrhage and wastage.
Contraindications
Warfarin should be avoided in the first trimester and its use
should be restricted for anticoagulating mechanical valves in
second and third trimesters. An informed consent should be
obtained from the patient before prescribing it.
Low-molecular Weight Heparin
Standard Dosage
Dose is adjusted for the lowest INR required for adequate
anticoagulation for an indication. While a dose of 2 to 2.5
Enoxaparin is classified as pregnancy category B and is a

subcutaneously administered anticoagulant. It has a lower risk
of osteoporosis than unfractionated heparin.104,105
Table 2
Classification of medications in pregnancy

Pregnancy
category
Definition of the category
Some commonly used medications in this category
Controlled human studies showed no fetal risk
Folic acid
Controlled human studies have not shown fetal risk despite

adverse findings in animal studies
or
Inadequate data from human studies, but animal studies
showed no fetal risk.
Amoxicillin
Inadequate data in human and animal studies. More likely

to have beneficial effects when used cautiously
Most cardiac medications including low dose aspirin,

furosemide, digoxin, most beta blockers (except
atenolol), nitrates, hydralazine, adenosine, calcium
channel blockers and adenosine
Data from human studies or subsequent use in humans

demonstrates fetal risk
Drug may be rarely acceptable if needed in a life-
threatening situation or serious disease for which safer
drugs cannot be used
Atenolol
Angiotensin-converting-enzyme (ACE) inhibitors
Contraindicated in pregnancy
Human and animal studies data show a very high risk of
adverse effects to the fetus
Warfarin
Based on the FDA system of classification: www.fda.gov
56
Common Cardiac Medications in Pregnancy
may be adequate for anticoagulation in most cases, one may

require a higher dose of 2.5 to 3.0 for mechanical prosthetic
valve. Careful monitoring is required, since the volume
of distribution of the drug is constantly changing during
pregnancy. Since fetal adverse effects are dose-related, women
are advised to avoid dietary/supplemental intake of vitamin K,
so that daily dose of 5 mg oral or less may be required for
adequate anticoagulation.91 It should be discontinued 2 weeks
before an elective delivery and replaced by unfractionated
heparin.
795
10
Standard Dosage
The dose is adjusted according to weight, creatinine clearance
and depending upon the indication. It is usually injected
subcutaneously every 12 hours and held for at least 8 hours
(ideally for 24 hours) before an invasive procedure. In order
to ensure adequate anticoagulation, the antifactor Xa levels
should be checked biweekly, 4 to 6 hour after an injection
and maintained between 1.0 to 1.2 U/ml.89,91
Side Effects
Standard Dosage
Low dose aspirin, 75 to 162 mg oral daily.
Main Side Effects

Bleeding, low birth weight.
Bleeding and hematomas.
Contraindications
Contraindications
Allergic rhinitis/nasal polyps, salicylate hypersensitivity.
Bleeding, heparin-induced thrombocytopenia (HIT), uncontrolled hypertension. Avoid intramuscular injections and use
in labor/delivery, since hematoma and bleeding are major
complications.106
Unfractionated Heparin
Unfractionated heparin is in pregnancy class C. It mediates
antithrombotic properties through an interaction with
antithrombin III and does not cross the placenta.
Standard Dosage
Subcutaneously injected with an average dose of 5,000
to 10,000 U every 8 to 12 hours adjusted to body weight,
or may be given as continuous intravenous infusion that
is titrated to achieve an activated partial thromboplastin
level (APTT), which is 1.5 to 2.5 times the normal value.91
It should be stopped 2 hours before delivery (vaginal or
cesarean) and resumed 4 hours after, if it there are no contra
indications.
Contraindications
Thrombocytopenia, hemorrhage (except in disseminated
intravascular coagulation).
Side Effects
Bleeding, heparin-induced thrombocytopenia (HIT), maternal
osteoporosis.
Aspirin
796
for stroke prevention and as conjunctive therapy in high risk

mechanical valves. Its use should be stopped 2 weeks before
delivery to avoid bleeding, prolonged gestation/labor and
premature closure of fetal ductus arteriosus.
A low dose of aspirin belongs to pregnancy class C, while

a full dose of 325 mg dose is considered as pregnancy class
D in the third trimester. Aspirin is a potent inhibitor of
prostaglandin synthesis and platelet aggregation. It is used
Diuretics
Loop diuretics such as furosemide are in pregnancy category
C and are used to decrease fluid retention by increasing
urinary sodium excretion. They provide rapid symptomatic
relief in heart failure.
Standard Dose
The initial dose is 20 mg oral daily, which is titrated to
increase urine output and decrease weight by 0.5 to 1 kg daily.
Excessive diuresis should be avoided, since low cardiac output
decreases uterine perfusion and leads to fetal hypoperfusion.
Rare teratogenicity effects are oligohydramnios, intrauterine
growth restriction, hypospadias, and neonatal death from
renal failure.
Main Side Effects

Hypotension, electrolyte depletion (hypokalemia) and
azotemia. Serum electrolytes and creatinine should be
monitored regularly. Potassium should be replenished to
maintain serum potassium levels between 4 and 5 meq/L.
Beta Blockers
Most beta blockers are in pregnancy category C except
atenolol, which is listed in category D. They inhibit
adverse effects on the sympathetic nervous system in heart
failure. Most of the data comes from their use in gestational
hypertension. Although carvedilol (alpha-1, beta-1 and -2
adrenergic receptor blocker) is the most effective beta blocker
in stable heart failure, its use in pregnancy is limited. The
clinical responses may not be apparent, until after several
weeks of therapy.
Propranolol has a longer safety record, but its use is
primarily limited to heart rate control in pregnant women
Contraindications
Standard Dose
Standard Dose
Carvedilol
Initial dose is 25 mg orally, which can be titrated to 75 to 100

mg, three times daily along with nitrates, if tolerated.
Digoxin use is avoided in patients with obstructive left ventricular

outflow tract lesions, WPW syndrome, sinus node dysfunction,
conduction disease, and in the presence of renal impairment.
Hydralazine
Hydralazine is in pregnancy class C and acts by direct
arteriolar vasodilatation and may be used for management of
heart failure and hypertension.
Initiated at 3.125 mg orally twice daily, titrated at 2-week

intervals to a maximum dose of 25 mg orally twice daily.
Main Side Effects
Propranolol
Tachycardia, flushing, headache, or fluid retention.
Initiated at 10 mg oral twice daily and titrated to three times

daily for better rate control.
Contraindications
Lupus-like reaction may rarely occur.
Main Side Effects
Nitrates
Increasing fatigue, hypotension, bradycardia, and heart block

when used until delivery. Fetal heart rate and neonatal blood
sugar levels should be monitored.
Asthma or active bronchospasm, sinus node dysfunction,

conduction disease, and florid pulmonary edema.
Isosorbide dinitrate is in pregnancy class C. It acts by

relaxing the vascular smooth muscle through the endothelialindependent pathway. Prolonged use of nitrates often causes
tolerance and loss of the beneficial hemodynamic effects.
Limited data is available regarding its use during pregnancy.
Isosorbide dinitrate has been associated with fetal heart rate
decelerations in cases of maternal hypotension.
Digoxin
Standard Dose
Digoxin belongs to pregnancy category C and since it crosses

the placenta, it may cause prematurity and intrauterine growth
retardation. It acts by inhibiting sodium-potassium adenosine
triphosphate and increasing the cardiac contractility. Treatment
for 1 to 3 months can improve heart failure symptoms in
pregnancy.
Isosorbide dinitrate initiated at 10 mg, titrated to 30 to 40 mg,

three times daily along with hydralazine if tolerated.
Standard Dose
Contraindications
The average dose of digoxin is 0.125 to 0.25 mg daily when

the renal function is normal. A loading dose is not necessary,
even if maternal serum levels are low.
Hypotension, severe anemia or cerebral hemorrhage.
Main Side Effects
Adenosine belongs to pregnancy class C and is the most

rapidly acting endogenous modulator of smooth muscle tone
that is often used to treat supraventricular tachycardia. No
fetal adverse effects have been reported.
Contraindications
Digoxin toxicity usually occurs in those with renal impairment

and abnormal serum potassium levels.
Main Side Effects

Headache, postural hypotension.
56
with atrial arrhythmias, valvular stenosis, or significant left

or right outflow tract obstruction. Propranolol or labetalol
are used to reduce the hemodynamic stress on the dilated
aorta, even though the evidence of benefit is limited in those
without Marfan syndrome.
Since beta blockers cross the placenta, fetal bradycardia
and hypoglycemia may occur. Although teratogenicity is low,
preterm labor, prematurity and intrauterine grown retardation
may occur due to reduce uterine blood flow. Low birthweight babies have been reported, especially with the use of
atenolol.107
Adenosine
797
10
Standard Dose
A rapidly administered intravenous injection of 6 mg followed
by 12 mg twice, if the desired effect is not achieved. Each
injection should be promptly followed by a bolus of 10
ml of intravenous saline through the same site to flush the
medication rapidly through the circulation.
Main Side Effects

Bronchoconstriction may occur in asthmatics. Sinus
bradycardia or AV block are short-lasting and resolve
spontaneously.
Contraindications
Avoid in bypass tract-mediated narrow QRS supraventricular
tachycardia (may precipitate atrial fibrillation), high degree
AV block, sick sinus syndrome.
Flecainide
Flecainide is a class I C antiarrhythmic agent that belongs to
pregnancy class C and is prescribed only by cardiologists/
electrophysiologists after careful risk assessment followed
by close monitoring. While efficient placental transfer can
cause adverse fetus effects, it is sometimes used to treat fetal
arrhythmias.
Indications
Suppression of documented sustained ventricular tachycardia.
Standard Dose
100 mg every 12 hours, increase by 100 mg/day every 4 days
to a maximum of 400 mg/day with dose adjusted for renal or
hepatic impairment.
Main Side Effects

Maternal hypotension, potentially proarrhythmic in CHD.
Severe toxicity may easily occur with flecainides narrow
therapeutic index.
Contraindications
Pre-existing high degree AV blocks, chronic atrial fibrillation,
systemic ventricular dysfunction.
Calcium Channel Blockers

798
Calcium channel blockers are pregnancy class C and their

use has been limited to late pregnancy for preterm labor.
They have not been extensively studied for other indications

or in the first and second trimesters. Short-term use may be
indicated for heart rate control in late pregnancy.
Cardiac Procedures in Pregnancy

Cardiac Catheterization and Interventions
Due to the high likelihood of teratogenic effects, fetal demise
and increased risk of malignancy in late childhood, radiation
exposure with fluoroscopic diagnostic/interventional cardiac
procedures holds a major concern during the first trimester
of pregnancy and should be avoided. Abdominal shielding
is used for all procedures requiring fluoroscopy to minimize
fetal radiation exposure.
Valvuloplasty
If a woman has critical aortic or mitral stenoses, with recurrent
heart failure refractory to medical therapy, pregnancy may
not be well tolerated due to volume overload, especially
during the late second and third trimesters. Balloon dilatation
valvuloplasty may be performed after 24 weeks to allow her
to tolerate the remaining pregnancy. In case of critical aortic
stenosis, the valvuloplasty serves only as a bridge to surgery.
Electrical Cardioversion
Synchronized electrical cardioversion may be performed when
atrial tachyarrhythmias are not well tolerated and associated
with heart failure, syncope or suboptimal response to medical
therapy. There are potential risks of thromboembolism during,
anesthesia or conscious sedation. Although the likelihood of fetal
arrhythmias is rare, fetal electrocardiography monitoring should
be performed during the procedure and in early recovery. There is
a remote possibility of synchronized direct current shock falling
onto the vulnerable phase of the fetuss action potential leading to
potentially life-threatening arrhythmias.
Anticoagulation prior to cardioversion is not required
for supraventricular tachycardia or when atrial flutter is
documented to be of less than 24 hours in duration. A
transesophageal echocardiogram to exclude an intracardiac
thrombus can be performed just prior to the cardioversion, in
hemodynamically stable patients at high risk of having a clot.
Energy doses required for monophasic/biphasic synchronized
shock should be the same as those used for the general
population and according to the current Advanced Cardiac
Life Support (ACLS) guidelines. The transthoracic impedance
does not significantly change with pregnancy.100
Electrophysiological Procedures
Whenever possible, the need for radiofrequency ablation (RFA)
or device implantation should be assessed prior to pregnancy.
one may lose both if maternal blood flow is not promptly

restored.109,110
Pacemakers
LABOR AND DELIVERY
Women with CHD, especially those with congenitally

corrected transposition of the great arteries, d-transposition of
the great arteries, post-Fontan procedure, large atrioventricular
(AV) septal defect may have symptomatic bradyarrhythmias
during pregnancy. This may occur due to underlying sinus
node dysfunction, AV node dysfunction, high degree
conduction heart block such as second degree (Mobitz II) or
third degree heart block. These conduction abnormalities may
be unmasked by the higher heart rate demand and increased
cardiac output during pregnancy. Transvenous or epicardial
pacemaker implantation can be performed with relatively
low maternal and fetal risk. Abdominal shielding is used to
minimize fetal radiation exposure during fluoroscopy. Women
with complex cardiac lesions and/or arrhythmias resistant to
conventional therapies should be referred to regional centers
for consultation and management.100
Automatic Implantable Cardiac Defibrillators

Women with long QT syndrome with family history of sudden
cardiac death or palliated tetralogy of Fallot with monomorphic
ventricular tachycardia should have an automatic implantable
cardiac defibrillators (AICD) implanted before considering
pregnancy. No major maternal/fetal complications have been
reported with their use during pregnancy.108
Surgical Procedures
All nonobstetric surgical procedures, other than emergency
operations, are best avoided during pregnancy.
During labor, there is a surge of blood flow into the maternal

circulation, with 300 to 500 ml being released with each
uterine contraction. This leads to nearly a 25 percent increase
in cardiac output. In addition, pain and anxiety lead to a rise
in blood pressure and heart rate, which in turn leads to another
rise in cardiac output by 40 to 50 percent. The cardiac output
peaks an hour after delivery. Adequate analgesia and anesthesia
during the active labor and delivery is necessary to allay pain
or anxiety. Epidural anesthesia without epinephrine shows
hemodynamic stability throughout delivery with a small rise
in cardiac output.5 Women with residual intracardiac shunts
should have intravenous particle filters to reduce the risk of
paradoxical thromboembolic events.
The left lateral position is favored during labor and
delivery. While supine, the gravid uterus compresses the
inferior vena cavale impeding venous return and causing a
fall in cardiac output and stroke volume.5 Following delivery,
there is an increase in venous return due to relief of inferior
vena caval compression and a shift of blood from the uterus
to the systemic circulation. The maximum volume shifts
occur in the first 48 to 72 hours leading to highest incidence
of major cardiovascular complications including heart failure,
arrhythmias and maternal mortality. These women should be
monitored and discharged only when stable.
Mode of Delivery
Cardiopulmonary Resuscitation
Unfortunately, cardiac arrest occurs in 1:30,000 pregnancies.
Women with CHD have a higher risk of sudden death from
postventriculotomy scar causing ventricular tachycardia, or
from severe cardiomyopathy or aortic dissection. Other causes
include amniotic fluid embolism, eclampsia, drug toxicity,
massive pulmonary embolism and hemorrhage.
Cardiopulmonary resuscitation should be performed
according to the standard ACLS algorithms. The pregnant
woman should be moved to the left lateral decubitus position
to relieve inferior vena caval compression, improve venous
return, and increase her cardiac output. The chest compressions
are higher on the sternum to adjust for the elevated diaphragm
caused by the gravid uterus. Emergency hysterotomy should
be performed within 4 to 5 minutes of cardiac arrest if the
fetus is older than 25 weeks gestation, since delivering the
fetus may improve venous return and maternal-fetal survival.
Maternal resuscitation is the key to fetus resuscitation and
The preferred mode of delivery is vaginal, with a facilitated

second stage of labor.
An elective induced delivery is preferred in women with
complex CHD or high risk factors, usually after 37 to 38
weeks when fetal lung maturity is achieved. Nearly all women
with CHD should deliver at a center with high risk obstetrics,
neonatology, pediatric cardiology and adult CHD specialists.
All patients need hemodynamic noninvasive monitoring
of blood pressure, heart rate, pulse oximetry. Telemetry is
indicated if there is a likelihood of developing arrhythmias.
Cesarean delivery is mainly performed for obstetric
indications, or in women on anticoagulation therapy with
warfarin, in order to avoid the potential risk of fetal intracranial
hemorrhage, because of fetal head compression in the birth
canal during contractions.
Relative indications for a cesarean delivery include a
dilated aortic root (over 4 cm), severe valvular stenosis,
56
RFA may be performed for intractable arrhythmias such as

paroxysmal supraventricular tachycardia that are unresponsive
to pharmacological therapy and pose a significant maternalfetal risk. This procedure can be cautiously performed during
the late second or third trimesters, with maternal abdominal
shielding to minimize fetal radiation exposure.
799
10
severe left ventricular outflow tract obstruction and severe

pulmonary hypertension.
In the United States, there have been concerns about
the rising incidence of cesarean deliveries from 5.5 percent
in 1970 to 29.1 percent in 2004.111,112 There are significant
associated risks including increased blood loss, delayed
ambulation and prolonged recovery. In addition, there is a
potential risk of scar rupture during labor and delivery with
future pregnancies. After adjusting for possible confounding
factors, the postpartum mortality is 3.6 times higher after
a cesarean delivery than a vaginal delivery, mainly due to
complications associated with anesthesia, puerperal infection
and venous thromboembolism.113
Postpartum Care
Women should be advised to resume contraception after
delivery. They are often most receptive to procedures such
as permanent sterilization, if a future pregnancy is contraindicated. Supportive care and education are usually well
received by the mothers.
DIET AND EXERCISE

A well-balanced diet with adequate fluid (preferably water)
intake and minimized use of artificial sugar sweeteners is
advised in all women. Caffeine, alcohol intake and smoking
are to be avoided during pregnancy.
Prenatal vitamins should be started, while planning a
pregnancy and continued while nursing or 6 months postpartum
to replenish the iron and vitamin stores. Daily folic acid intake
of over 400 micrograms reduces the incidence of neural tube
defects.4 Athough the daily intake of calcium should be over
1,500 mg (dietary and supplemental), no more than 600 mg
should be taken at a time, to allow adequate absorption.
Regular isotonic exercises and aerobic activity such as
walking and swimming help with cardiovascular conditioning.
Jogging should be avoided during pregnancy.
CONCLUSIONs
As more women with complex congenital heart defects are
entering into their reproductive years, careful risk assessment
and preconception counseling are becoming even more
important. Close follow-up with the perinatologists and
collaboration with a multidisciplinary team are essential for
favorable maternal and fetal outcomes.
ONTRACEPTIVE OPTIONS FOR WOMEN WITH

C
CONGENITAL HEART Diseases By Pamela
Miner, RN, MN, NP
800
Most children growing up with congenital heart disease in the

21st century will live long enough to confront family planning.
Adult survival and advances in pregnancy risk stratification

of women with moderate to complex CHD have opened up
the door to procreation like no other generation living with
CHD. However, by eliminating the prohibition of pregnancy
for all, but a select few women with the most significant forms
cardio/pulmonary disease, equal emphasis should be placed
on the importance of planning a pregnancy, rather than
confronting an unplanned high risk pregnancy. Regrettably,
unplanned pregnancies are still the reality for almost half of
all pregnancies,1 signifying a mismatch in either contraceptive
counseling/access and/or contraceptive compliance. Kovacs
and colleagues found that only 51 percent of women with
CHD recalled receiving information about birth control from
their health care provider.2 This reality makes effective,
accessible, easy and safe contraception a mandate for this
complex population and prepregnancy counseling is the
responsibility of all ACHD providers.
Contraceptive options available today, provide women with
CHD with many alternatives to prevent or postpone pregnancy.
For women with complex congenital heart disease, they confront
the highest risks with pregnancy, and therefore, a planned
pregnancy should always be approached as collaboration
between the procreating couple, the fetus and the ACHD/high
risk obstetric team (comprising the cardiologist and nurse
specialists in ACHD, a high risk obstetrician/perinatologist).
Part of that collaborative process usually entails a period of
time in which contraception is a necessity. The three biggest
considerations in choosing optimal contraception are:
a. The womans risk of thrombosis
b. Contraceptive ease and efficacy
c. The degree of side effects. Choosing the lowest risk and
most effective contraception can be a challenge for women
with the highest complexity of CHD.
The heterogeneity of congenital heart disease makes risk
stratification challenging. Some women have simple cardiac
defects, which have little to no impact on their contraceptive
and pregnancy decisions. However, for those women with
moderate to complex congenital heart disease, choosing a
safe contraceptive requires careful consideration of what their
actual pregnancy risk is (moderate, high or prohibitive) and
what risks and benefits come with the preferred contraceptive
option. For example, women with a prohibitively high risk for
pregnancy (Eisenmenger), the contraceptive option with the
lowest possible failure rate (such as sterilization, intrauterine
devices [IUD], or contraceptive implants) might be
considered. On the other hand, a woman with complex CHD
(such as double outlet right ventricle/Rastelli or transposition
of the great arteries/Mustard) may have a low risk for
thrombogenesis, but could confront dysfunctional menstrual
bleeding or polycystic ovarian syndrome. The potential benefits
of a combined hormonal contraceptive such as a drospirenone
containing combined oral contraceptive (Yaz, Yasmin) might
be considered for both contraception and hormonal advantage.
As this demonstrates, the decisions regarding contraception
Contraceptive Options
1. Combined hormonal contraceptives.
2. Progestin-only contraceptives.
3. Barrier methods/emergency contraception.
4. Intrauterine devices.
5. Sterilization.
6. Rhythm method/abstinence/abortion.
Combined Hormonal Contraceptives

Combined hormonal contraceptives contain both estrogen
and progestin and are highly effective at preventing
pregnancy (99.4%), when used correctly. They also have noncontraceptive benefits, including reductions of menorrhagia,
dysmenorrhea, acne, hirsutism and ovarian cancers. The
evolution of these oral combined hormonal contraceptives
in recent years has resulted in lower estrogen levels (20 to
35 mcg) and new generations of progestin aimed at reducing
symptoms of menstrual syndromes. These changes have
resulted in fewer side effects and a reduction in thrombotic
complications.4,5 However, lower hormone levels in these
combined hormonal pills have resulted in higher susceptibility
to contraceptive failure if a single dose is missed in the first or
third week of hormones or the hormone free interval exceeds
7 days, making back-up contraception a necessity, when these
low estrogen oral preparations are used.6
According to the WHO,7 the contraindications for using
combined hormonal contraceptives include (Box 6): previous
thromboembolic event or stroke or an inherited thrombophilia,
coronary artery disease or cerebrovascular disease,
complicated valvular disease, women over age 35 who smoke,
liver disease, pregnancy, or a history of an estrogen dependent
tumor. In addition, special consideration of the thrombotic
risks of combined oral contraceptives should be individually
assessed in the setting of hypertension, migraine headaches
with aura, or in obese women over age 35. In women with
congenital heart disease, risk stratification is more challenging
due to lack of data regarding overall thrombogenicity and
ultimately rests on experiential inferences from those managing
adults with CHD8,9 and associations linked to acquired heart
Box 6: Contraindications for combined hormonal

contraceptive use
General
Previous thromboembolic event or stroke
Inherited thrombophilia
Smoking
Liver disease
Pregnancy
History of an estrogen-dependant tumor
Migraine headaches with aura
Obesity
Age over 35
Cardiovascular
Hypertension
Coronary artery disease
Cerebrovascular disease
Complicated valvular disease
Older-style mechanical valves (even on Coumadin)
Dilated cardiomyopathy with LVEF < 30%
Right-to-left shunting
History of Fontan procedureshighest risk with classic
Fontan (right atrium to pulmonary artery)/ or with a markedly
dilated right atrium.
disease data. Thorne8 developed guidelines for contraceptive

use in women with heart disease, including CHD. Their
group categorized the highest risk groups from a thrombotic
standpoint to be those with older-style mechanical valves
(even on Coumadin), pulmonary hypertension, and dilated
cardiomyopathy with left ventricular ejection fraction (LVEF)
less than 30 percent. For these, the use of combined hormonal
contraceptives was considered contraindicated. In addition,
patients with cyanosis (or right-to-left shunting) or Fontan
procedures were also considered to be at high risk for clot (or
at highest risk for complications related to clot) and cautioned
against the use of combined hormonal contraceptives. The
ACC/AHA guidelines for management of adults with CHD10
shared some of the above concerns related to the highest risk
group, also warned against the use of estrogen containing
contraceptives in Fontan patients, pointing out that the highest
risk Fontan patients appear to be those with older version, right
atrium to pulmonary artery (RA-PA), Fontans or massively
dilated right atriums. According to Thorne,8 treating the
thrombotic risk in these patients with anticoagulation did not
change the precautions against the use of combined hormonal
contraceptives. However, there are ACHD specialists who
would consider using low estrogen oral contraceptives in
women with newer version Fontans, total cavopulmonary
connection (TCPC), and no sustained atrial arrhythmias, or
those who are consistently protected with anticoagulation.
The risk of estrogen-provoked thrombus in women who are
adequately anticoagulated is not known, so practice standards
56
can be more complicated than simply pregnancy prevention

and deserve comprehensive individualized evaluation and
treatment. Complicating matters is the paucity of published
data about contraceptive safety in women with CHD, since
so much of our clinical decision making is based on data
regarding women with acquired cardiovascular disease and
perhaps more so by expert consensus. Even with the data
published on contraceptive safety in women with other forms
of heart disease, the World Health Organization (WHO) and
the Centers for Disease Control, both emphasize the need
to take individual clinical circumstances into consideration
rather than holding firmly to published clinical guidelines.3
801
10
in this regard are left to the treating physician. This is where

the experiential line is drawn, allowing for different practice
standards that each may hold merit, but make generalized
guidelines that fit all patients very difficult.
Although the majority of combined hormonal contra
ceptives are administered orally, this method of administration
is associated with highest failure rates due to missed
doses or discontinuation among users. This has led to the
development of other combined hormonal contraceptive
methods, including the vaginal ring and transdermal patch.
The vaginal ring (NuvaRing) is inserted by the women and
stays in for 21 days and then is removed for 7 days. The
advantage of this method is easier compliance, they do not
need to be fitted and can be inserted anywhere in the vagina,
and by avoiding gastrointestinal absorption, lower hormone
doses are needed. In fact, systemic exposure to estrogen with
the ring was half that of the 30 mcg low estrogen combined
hormonal contraceptive pill,11 however, a corresponding
decrease in thrombotic risk has not yet been demonstrated. In
fact, recent studies indicate a slightly higher thrombotic risk
in these non-oral hormonal contraceptives, specifically the
vaginal ring and the combined hormonal transdermal patch
(known as Ortho Evra in the United States).12,13 In addition,
failure rates for the patch are higher in heavier women
(> 90 kg).
Progestin-only Contraceptives
802
Progestin-only hormonal formulations are the best nonpermanent contraceptive choice for women at higher risk
for thromboembolism. These formulations include an oral
pill, injectable form, implantable form and local release from
an intrauterine device. Oral progestin pills (mini pills) are
prone to higher failure rates due to the need to take the pill
each day at the same time. Variation of only a few hours can
reduce efficacy, since the primary contraceptive function of
oral progestin is to reduce sperm penetration by changing the
consistency of cervical mucus. A more reliable formulation
of progestin is the injectable depot medroxyprogesterone
acetate (DMPA). This injection is administered by a health
care provider every 3 months and acts both on the cervical
mucus and on inhibiting ovulation. Implantable progestin is
available in the form of Implanon in the United States and
provides for 3 years of effective contraception via a single
rod implanted in the under surface of the upper arm. All of
these formulations of progestin are associated with higher
rate of breakthrough bleeding, but ultimately help to suppress
menstrual bleeding altogether. One last version of progestin
is available in an intrauterine device (IUD) called Mirena
and the advantage of this formulation is the highest efficacy
of an IUD combined with only local release of progestin in
the uterus, which has the advantage of reducing or stopping
menstrual bleeding altogether without any of the potential
systemic side effects of the other formulations of progestin

(fluid retention, osteoporosis, etc.).
Intrauterine Devices
Intrauterine devices are highly effective at preventing pregnancy
for upto 5 years. This is a safe long-term contraceptive option
for women at low risk for sexually transmitted diseases
(STDs). Historically, IUDs were associated with a higher
rate of pelvic inflammatory disease, particularly in women
exposed to Chlamydia or gonorrhea and therefore, carried a
slightly higher risk for endocarditis. However, this risk has
not been borne out in the newer generations of IUDs, as long
as their use is confined to women in mutually monogamous
relationships or those who also use condoms to prevent
STDs. The two types of IUDs commonly used are the copper
IUD (Paragard) and the progestin-releasing IUD (Mirena).
Although no study has proven a link between prophylactic
antibiotic use at the time of IUD insertion and a decrease in
the incidence of pelvic infections, it is reasonable to consider
prophylactic antibiotics in CHD patients at the highest risk for
endocarditis. Doxycycline or erythromycin are appropriate
agents for this preventative purpose. The Mirena IUD would
be an appropriate contraceptive choice for women with CHD
at higher risk for thromboembolism and those who are at high
risk if they were to become pregnant. This provides long-term
effective contraception with very few side effects and the added
benefit of controlling any heavy menstrual bleeding issues.
Barrier Contraceptives/Emergency Contraception

Barrier methods of birth control are associated with the highest
failure rates (1532%) due to inconsistent and imperfect
utilization. These methods include condoms, diaphragms
and cervical caps. Using a double barrier method approach
increases the efficacy considerably, which includes the use of
spermicide with any barrier method, or the combination of
a diaphragm and condom. For purposes of preventing STDs
alone, the male or female condom should be used, even when
other forms of contraception are employed. Any woman with
CHD can safely use a barrier method to prevent pregnancy,
but women confronting the highest maternal or fetal risk with
pregnancy should never rely on a single-barrier method alone.
When a barrier method fails (broken condom) or is not
used, emergency contraception is an option for women in the
first 72 hours after sexual intercourse. In the United States,
Plan B (levonorgestrel) is available over the counter for
women 18 years an older, or by prescription for those under
age 18. This is a progestin only drug and is taken in a single
1.5 mg dose orally within 72 hours of unprotected intercourse.
Side effects include heavier menstrual bleeding, headache,
lower abdominal pain and dizziness. This is a safe option
for most women with CHD, in that it contains no estrogen.
Sterilization
Sterilization provides for the most efficacious and permanent
form of contraception. Options include vasectomy, surgical
tubal ligation and intratubal occlusion (known as Essure in
the United States). It is reasonable to recommend this form of
contraception to women who would confront a prohibitively
high risk with pregnancy, such as women with pulmonary
hypertension (Eisenmenger syndrome). Laparoscopic
surgical tubal ligation presents a small perioperative risk,
particularly to women with pulmonary hypertension.
A cardiac anesthesiologist should be present during the
procedure in high-risk women. Intratubal occlusion (Essure)
is a less risky option for permanent contraception and can
be performed using local anesthesia. A coil-like device is
embedded in the fallopian tubes via a transvaginal procedure
and causes irritation and scarring in the surrounding tubes.
Complete tubal occlusion needs to be confirmed with imaging
studies 3 months postcoil occlusion, so intermediate forms
of contraception need to be used in those first 3 months.
Vasectomy is a reasonable option and avoids any potential
risk confronted by the woman with CHD. One could argue
that the male partner may outlive the female partner with
CHD and as such, may desire future procreation options,
but in this instance, vasectomy can be reversed. Therefore,
sterilization using vasectomy should not be easily dismissed
from consideration.
Rhythm Method/Abstinence/Abortion
Rhythm method/abstinence/abortion are the least desirable
options for family planning. In the first half of the 20th
century, prior to the era of birth control pills, the rhythm
method, withdrawal or abstinence were a womans only
choices for preventing pregnancy. The rhythm method is only
marginally effective if a woman has very regular menstrual
cycles and can precisely predict ovulation. Relying on this type
of modification of ones sexual relationship is unrealistic, as is
abstinence. Contraception is available to provide women with
choices that prevent pregnancy and provide more freedom in
their sexual relationships. Fear and misinformation are often
the reason why a woman with CHD avoids entering into a
sexual relationship and this reflects a failure by the health care
provider to provide comprehensive contraceptive counseling.
This is both unfair to the woman and perhaps equally as
unfortunate as an unplanned pregnancy. Providers owe their
patients accurate, understandable and accessible information
regarding their options for birth control. Abortion is not
considered contraception, but provides the highest risk in

women with CHD, as an option to terminate a pregnancy
that puts them or their fetus at unacceptable risk. The risks
of a therapeutic (surgical) abortion should be included in all
contraceptive counseling, so that the woman understands the
potential risk of anesthesia, blood loss, infection, damage to
the uterus or cervix and psychological injury imposed by a
surgical abortion, thereby emphasizing the importance of
preconception action to avoid pregnancy.
Risk Stratification for Contraceptive Use

Risk stratification can be divided into two main considerations,
the risk of thrombosis and the risk of maternal/fetal morbidity/
mortality with pregnancy (Table 3). Often, those at highest
clot risk are also those in whom pregnancy would be the
most hazardous. The majority if women with CHD are at low
thrombotic risk. This includes those with unoperated valve
disease, small VSD, postoperative coarctation with controlled
blood pressure, postoperative valve repair or bioprosthetic
valve replacements, tissue valved pulmonary artery conduits,
transvenous pacemakers without right-to-left shunts, atrial and
arterial switch repairs, Marfan syndrome and postoperative
shunt repairs in the absence of pulmonary hypertension. Those
at moderate thrombotic risk include women with a known
thrombotic potential protected with antiplatelet therapy or
anticoagulation as indicated. This includes patients with
mechanical valve prostheses, total cavopulmonary Fontan
repairs, sustained atrial arrhythmias, unrepaired atrial septal
defect, or dilated cardiomyopathy with class I-II symptoms.
The highest thrombotic risk group includes those women
with CHD whose potential for clot cannot be effectively
prevented, or in whom the consequences of a clot presents
significant morbidity or mortality. This includes women
with pulmonary hypertension (Eisenmenger syndrome),
cyanosis, atriopulmonary Fontan repairs, NYHA class IIIIV heart failure with dilated cardiomyopathy, uncontrolled
hypertension, inherited thrombophilia or documented past
thrombotic tendency, obesity, or women over 35 years of age
who smoke.
Women in the low thrombotic risk group are candidates
for any form of contraception, including combined hormonal
contraceptives. Consideration must be given to those women
whose thrombotic risk may be low, but their pregnancy risks
are high (such as severe aortic stenosis) and therefore, more
definitive contraception might be considered, such as an
IUD. For those with moderate thrombotic risk, nonestrogen
options for contraception should be considered first, but
with individualized consideration towards modification of
thrombotic risk, one could consider a low estrogen containing
combined hormonal contraceptive. This may be indicated if
a woman confronts considerable menstrual symptoms such
as heavy bleeding or polycystic ovaries. Clearly those at
56
However, emergency contraception should never be used as

the primary form of contraception and it should also not be
used if pregnancy is already suspected or if over 72 hours
have passed since intercourse.
803
10
Table 3
Risk stratification for contraceptive use

Thrombotic risk
Recommended form of contraception
Low thrombotic risk

Unoperated valve disease
Small ventricular septal defect (VSD)
Postoperative coarctation with controlled blood pressure
Postoperative valve repair
Postoperative bioprosthetic valve replacements
Tissue valved pulmonary artery conduits
Transvenous pacemakers without right-to-left shunts
Atrial and arterial switch repairs
Marfan syndrome
Postoperative shunt repairs in the absence of pulmonary hypertension
Usually any form of contraception, including combined

hormonal contraceptives
Moderate thrombotic risk

Thrombotic potental protected with antiplatelet therapy/anticoagulation
such as in women with:
Mechanical valve prostheses
Total cavopulmonary connection Fontan repairs
Sustained atrial arrhythmias
Unrepaired atrial septal defects
Dilated cardiomyopathy with class I-II symptoms.
High thrombotic risk
Pulmonary hypertension (Eisenmenger syndrome)
Classic Fontan repair (atriopulmonaryright atrium to pulmonary artery)
NYHA class III-IV heart failure with dilated cardiomyopathy
Uncontrolled hypertension
Inherited thrombophilia or documented past thrombotic tendency
Obese women over 35 years of age
Smokers over 35 years of age
the highest thrombotic risk are not candidates for combined

hormonal contraceptives and should be guided to progestin
only options, IUD, sterilization or combined barrier methods,
depending on their pregnancy risks and future procreation
potential.
Contraceptive Counseling
804
Contraceptive counseling is often the most difficult subject to

address for pediatric cardiologists, although the best time to
begin addressing this in young women with CHD is when they
are entering puberty. These discussions need to be reassessed
over time, accounting for all non-cardiac risk factors for
thrombosis and any changes in maternal cardiac status.14 The
only way contraceptive counseling can be deemed a failure
is when it never takes place. One study found that 43 percent
of women with CHD had not been counseled regarding
contraception, and 48 percent had not been informed about
pregnancy related risks by their treating physician.15 Many
large ACHD centers have skilled nurse specialists who are
experienced in providing this level of comprehensive patient
First line are the nonestrogen options for contraception

Low estrogen containing combined hormonal
contraceptive may be considered based on each
individual case
Combined barrier methods

Progestin-only options
Intrauterine device (IUD)
Sterilization
education regarding contraception. Young female patients

should be referred to such a specialist if available, if only
to begin the conversation and guide future questions when
appropriate to their level of interest or evolving sexuality.
When contraceptive choices are considered contraindicated
for certain patients, alternatives must be provided. As outlined
in this review, multiple options are available to young women
today, who desire sexual activity without the risk of pregnancy.
Clearly additional investigation is necessary to outline
the contraceptive risks confronted by women with complex
CHD.
YNECOLOGICAL ISSUES IN WOMEN WITH CHD By

G
Mary M Canobbio, RN, MN, FAAN
Medical and surgical advancements have allowed most females
with CHD to survive into and beyond their reproductive
years. As a result, gynecological and reproductive issues
have emerged as one of the most common noncardiac health
care issues, cardiologist and other health care providers must
address as part of their clinical management.
MENSTRUATION
Menarche occurs in the normal female population at a mean

age of 12.3 years. For females with acyanotic congenital heart
disease, menarche occurs a little later at 13 years and for
females with cyanotic CHD, it occurs at the average age of
13.9 years.1 While the menstrual patterns in acyanotic females
with CHD are similar to the general population, females
with cyanotic CHD often will have menstrual irregularities
including shorter or longer cycle lengths, a greater frequency
of menstrual irregularities, breakthrough bleeding, and/or
missed periods including amenorrhea.
Limited data is available on the postoperative menstrual
patterns in women with CHD. An early study reported that
Fontan operation performed before the age of 10 years was
associated with menarche at the same age as the normal female
population, while Fontan operation performed after menarche
was associated with resumption of normal menstrual patterns
within 6 months of surgery.2
A subset of patients who remained cyanotic beyond
menarche reported dysfunctional bleeding evidenced by
complaints of oligomenorrhea, metrorrhagia and amenorrhea
suggesting a possible relationship with the duration of
cyanosis after menarche, although the exact cause remains to
be elucidated.2
Dysfunctional Uterine Bleeding

Dysfunctional uterine bleeding (DUB) is defined as abnormal
uterine bleeding in the absence of organic disease and is
the most common cause of abnormal vaginal bleeding in
women of child-bearing age. It is a diagnosis of exclusion
and approximately 90 percent of dysfunctional uterine
bleeding cases result from anovulation while 10 percent of
cases occur with ovulatory cycles.3 Dysfunctional bleeding is
characterized by a variety of menstrual complaints including
irregular noncyclic bleeding, heavy bleeding (metrorrhagia,
oligomenorrhea or amenorrhea).
In the general population, amenorrhea occurs in 0.1 percent
to 2.5 percent of the women as primary or secondary cause.
The occurrence of secondary amenorrhea is higher in CHD
(10.3%), while only 0.7 to 3.0 percent of the women in the
general population report this menstrual cycle disturbance.4
Causes of amenorrhea are similar to general population and
include hypothalamic dysfunction, endocrine disorders and
uterine disease. Patients cyanotic prior to menarche appear
to be at greater risk of developing secondary amenorrhea.
Oligomenorrhea also appears to be common in women
with CHD and the number of surgical interventions prior
to menarche may be a potential predictor, even though the
comparative data of the general population is lacking.
Metrorrhagia has been mainly reported by patients with
MEDICAL TERMINATION OF PREGNANCY

In cases of unplanned pregnancy, in women with CHD who
are at high risk for maternal-fetal complications, medical
termination of pregnancy is often recommended. The decision
to medically terminate a pregnancy must be a collaborative one
involving not only the patient, her spouse or partner, family,
obstetric/gynecology service, ACHD specialist, and clinical
social worker to discuss the risks associated with pregnancy,
as well as ensure that the choice is made with consideration to
the patients personal beliefs.
Once a decision to terminate a pregnancy has been made, it
is important to act swiftly, because the choice of procedure is
determined by the stage of pregnancy. An ultrasound should be
performed if there is discrepancy between dates and uterine size.
During the first trimester termination of pregnancy (first
12 weeks of gestation), the methods are either medical or
56
Menarche
uncorrected CHD. The use of anticoagulation also appears to

increase the risk of metrorrhagia or menorrhagia, although no
significant causal relationship has been reported. In the general
population, the primary causes include systemic illness (e.g.
hypothyroidism) and intrauterine lesions (e.g. myomas) or
endometriosis. Chronic metrorrhagia and menorrhagia can
result in iron-deficient anemia. For females with cyanotic
CHD, who are usually erythrocytotic as result of an adaptive
response to systemic arterial hypoxemia, hematocrit must be
carefully monitored if oral iron replacement is required. This is
because an increase in circulation erythropoietin predisposes
to a rapid and excessive rise in hematocrit.5
Metrorrhagia can be managed in the short-term with highdose progestins or dilatation and curettage. For prolonged
menstrual suppression, Depo-Provera or the progestinsecreting intrauterine device may be considered. For women
in whom pregnancy is not desired or when the risks are
prohibitive, endometrial ablation or hysterectoscopy may be
considered.
Regardless of cause, females with DUB require a thorough
gynecologic evaluation, which includes a detailed menstrual
history supplemented by a pelvic examination and pap
smear. Medical treatment of DUB includes a combination
oral contraceptive pills, however, the use of estrogen is
contraindicated in women at risk for thromboembolism.
Progesterone alone can be used to stabilize an immature
endometrium and is usually successful in the treatment of
women with anovulatory dysfunctional uterine bleeding.
The concern for anovulatory patients is that if left untreated,
chronic unopposed estrogen production can result in
continuous endometrial stimulation and hyperplasia that
may be accompanied by a three-fold increase in the risk of
endometrial cancer.6,7 Additional therapies that have proven
to be effective in reduction of DUB include the use of antifibrinolytic tranexamic acid, nonsteroidal anti-inflammatory
drugs (NSAIDs).7-9
805
10
surgical. If performed within the first 7 weeks of gestation,

medical abortion utilizing oral antiprogesterone agents
such as RU486 (Mifepristone) and vaginally administered
misoprostol (prostaglandin E1 analog) are as effective as
suction curettage.10-12 Because expulsion and bleeding
occur at home, the process is not controlled, so the systemic
vasodilation afforded by the PGE could potentially be risky
for women with Eisenmenger syndrome/primary pulmonary
hypertension. Dilation and suction curettage under local
anesthesia (paracervical block) is the most common method
employed for first trimester termination. It carries a very
low complication rate when performed by an experienced
obstetrician in an operating room rather than in an outpatient
setting.
Dilatation and evacuation of fetus and placenta are
more frequently used for termination of second-trimester
pregnancies. With introduction of a small dilator, called
Laminaria, the cervix is slowly dilated. Most of this occurs in
the first 6 hours, with maximum dilation usually occurring in
12 to 24 hour followed by evacuation. The procedure carries a
low rate of complications.
Another method is the intrauterine instillation of
prostaglandin (E2 or F) and hypertonic urea that results in
uterine contractions and expulsion of the fetus. However, the
labor can take up to 20 hours, is painful and requires in-patient
care. There is the risk of retention of the placenta, hemorrhage
and infection.
MENOPAUSE
806
Menopause is defined as the absence of menses for 12

consecutive months. The number of women with CHD
who are currently reaching menopause is increasing. As the
population of adults continues to grow, the number of women
reaching menopause will also increase. Currently, there
are no studies evaluating the patterns of menopause in this
population, therefore most of our understanding of symptom
presentation and management is drawn on population-based
studies.
While women may begin menopausal transition at about
47 years, for most women the menopause occurs between 50
and 55 years with an average of 51.13 Symptoms commonly
associated with menopause may develop during this
transitional period. Nulliparous women tend to experience
menopause earlier than multiparous women.
Health providers need to be sensitive to the emotional and
physical effects of menopause and also assist in decisions
regarding hormone replacement therapy (HRT). Estrogen
production begins to decline over a period of several years
before complete cessation. The principal goal of HRT is to
deliver the lowest effective dose of estrogen/progestin to
relieve menopausal symptoms and to potentially reduce the
risk of osteoporosis.
While earlier reports emphasized the benefits of HRT for
prevention of coronary artery disease, later reports questioned
these beneficial effects of HRT. The Womens Health Initiative

(WHI) stopped the Heart and Estrogen/Progestin Replacement
Study (HERS) trial of combined hormones/estrogen/progestin
in women with an intact uterus, because of the increased risk
of breast cancer, stroke and pulmonary embolism. The current
recommendation is neither to begin nor continue HRT for
primary or secondary prevention of cardiovascular disease.
Rather HRT should be limited to the treatment of menopausal
symptoms at the lowest effective dosage over the shortest
duration possible and continued use should be reevaluated on
a periodic basis.14-16
Currently, hormone replacement regimens include unop
posed estrogen or combined estrogen/progestin therapies.15
Unopposed estrogen is not recommended for women who
have an intact uterus. A systemic estrogen is available in
oral or transdermal form with a starting dose of 0.625 mg
of conjugated estrogen or the equivalent recommended
dose. Lower doses of estrogen (0.45 mg of conjugated
estrogen) when combined with a progestin (1.5 mg hydroxyprogesterone acetate) have been found to relieve vasomotor
symptoms and prevent bone loss. The addition of cyclic or
of daily progestin administration is recommended for women
with an intact uterus to reduce risk of endometrial cancer.17
Progestin (medroxyprogesterone acetate or norethindrone
acetate) is usually prescribed in oral form, while progesterone
is available in other forms including oral (micronized), vaginal
or rectal suppositories.
The decision to prescribe HRT must consider the individual
needs of each patient weighing the benefits against the risks.
For the woman with CHD, the decision to prescribe HRT
must take into account her underlying cardiac defect, previous
history of surgeries and her present clinical status. Because
the standard estrogen replacement dose, is approximately
one quarter of the estrogenic potency of the 20 mg of ethinyl
estradiol in an oral contraceptive pill, the majority of women
with CHD can safely receive these agents.
However, WHI reports a 41 percent increase in stroke and
a two-fold greater rate of venous thromboembolism (VTE), in
women receiving estrogen plus progestin therapy. Therefore
HRT use in women at high risk for thrombolic episodes is
discouraged.18 HRT should not be prescribed in women with
a history of thrombosis, embolism or bleeding.
In the absence of clinical data, one should prescribe the
lowest dose of systemic HRT that will address the vasomotor
symptoms associated with estrogen deficiency. If there are
residual complaints of vaginal dryness or dyspareunia due
to vaginal atrophy, the symptoms can be treated with vaginal
estrogen in the form of cream, tablets or ring. Estrogen doses
lower than 0.625 mg of conjugated estrogen are probably
as effective in reducing bone loss if combined with a
progestin.19,20 For females with cyanotic CHD, or at risk for
thromboembolic events, HRT should be contraindicated. For
these women, over-the-counter phytoestrogens or selective
serotonin reuptake inhibitors (SSRI) may be an alternative
to alleviate menopausal symptoms such as hot flashes.
CONCLUSION
Gynecologic issues such as DUB, remains one of the
commonest reasons for women with CHD to seek medical
attention. As the population of women with CHD increases,
menopause will need to be addressed. Detailed work-up of
these patients along with counseling/education is needed
in order to establish a diagnosis and prescribe appropriate
management in the setting of their particular cardiac
physiology.
A wise man should consider that health is the greatest of
human blessings, and learn how by his thought to derive
benefit from his illnesses.
Hippocrates
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57
Exercise and Sports in

Adolescents and Adults with
Reema Chugh
INTRODUCTION
Aerobic exercise is important for improving the general health
and well-being of all people. Those born with congenital heart
defects (CHD) are often overprotected and restricted from
getting involved in any organized exercise, sports or training
programs. Patients with CHD may often have low exercise
ability due to a combination of the underlying heart defects and
physician or self-imposed reduction in daily physical activity.
Studies have shown that the exercise capacity is decreased
on objective assessment even in self-reported asymptomatic
adults with CHD and may be similar to that seen in patients
with chronic heart failure. Known contributing factors are
blunted heart rate response to exercise (due to sinus node or
conduction diseases), impaired ventricular function, pulmonary hypertension, cyanosis and the propensity for developing exercise-induced arrhythmias. Poor functional capacity
is associated with poor prognosis, risk for hospitalizations or
death.
Guidance to aspire towards achievable and obtainable
activities is extremely important for improving clinical
outcomes and the quality of life.
EXERCISE
Benefits of Exercise
Moderate physical activity is known to help us lose weight
and regulate our metabolism, thereby reducing the risk of
developing hypertension, lipid disorders and diabetes. As
the population of adults with CHD ages, coronary artery
disease and metabolic disorders are becoming more prevalent.
Cardiovascular risk reduction plays an important role in
improving long-term outcomes, with diet and exercise being
the foremost recommendations.
Regular exercise also improves the ability to tolerate
pregnancy in all women and this is even more so for women
with CHD. Functional status has been shown to be a reliable

predictor for perioperative and long-term cardiac events and can
be improved by regular organized exercise.1 Besides improving
exercise tolerance, daily aerobic physical exercise has a positive
effect on emotional, mental and psychosocial well-being.
Types of Exercise
Exercise is generally categorized into two forms and with some
overlap between the movements that are primarily of one type
or the other. The two types (Table 1) of exercise are:
1. Isotonic exercise or dynamic
2. Isometric or static.2
Isotonic Exercise
During isotonic exercise, a person uses a relatively small force
to achieve changes in muscle length by rhythmic muscular
contractions, mainly leading to volume load of the heart.
Examples of this type of exercise are walking, jogging,
cycling, swimming, water aerobics, yoga and Tai Chi. Cardiac
patients are recommended this form of exercise for up to 30
to 45 minutes daily with a slow, long warm up and a slow
cool down. This leads to an improved exercise tolerance
and incremental increase in exercise capacity. The volume
overload of the heart during isotonic exercise is caused by
an increase in stroke volume as well as in heart rate. These
changes then lead to an increase in cardiac output and oxygen
consumption. The diastolic blood pressure may fall from a
decrease in peripheral vascular resistance.2-4
Isometric Exercise
During isometric exercise, a person uses a large force with
minimal or no change in muscle length leading to pressure
load on the heart. The most common form of isometric
exercise is weight lifting. Isometric work involves lifting or
57
table 1
Types of exercise
Isotonic
Isometric
Effect on the heart
Volume load
Pressure load
Blood pressure
Increase in systolic and decrease in

diastolic pressure
Sudden increase is systolic blood

pressure
Heart rate
+++
Stroke volume
+++
Cardiac output
+++
Oxygen consumption
+++
Legend: +++ significant increase; + limited increase.
carrying weights. One lift of a weight or completion of an

exercise movement is called a repetition (or rep in short). A
series of repetitions is called a set (or a set of reps in short).
Light weights with more repetitions are preferred because
they help in maintaining muscle mass, tone and bone strength.
Heavy weight-lifting is discouraged when there is aortic
root dilatation, since it may cause strain and progression of
aneurysmal formation, especially in patients with connective
tissue disorders involving the great arterial walls.5 Other
forms of isometric exercise are wrestling and gymnastics.
Heavy isometric exercise should also be avoided in individuals with severe left ventricular outflow tract lesions such as
significant aortic stenosis, subvalvular stenosis, hypertrophic
obstructive cardiomyopathy or coarctation of aorta, because a
surge in blood pressure and an uncontrolled increase in pressure overload may occur during this form of exercise.2-4
Levels of Intensity and Duration of Exercise
table 2
Classification of recreational activity

Category
Level of exercise
Types of activity
No restrictions
Athletics, contact sports,

endurance training
II
Moderate exercise
Regular physical education

classes, tennis
III
Light exercise
Jogging, cycling, golf and

recreational swimming
IV
Moderate limitation
Attending school or college,

avoiding organized sports or
physical education classes
Extreme limitation
Homebound or activities of
daily living only
Adapted from Gutgesell et al. Circulation. 1986 Nov;74(5):1195A-1198A.
table 3
Low intensity exercise is preferred in adolescents and adults

with CHD who have ventricular volume overload at rest.
Depending upon the degree of volume overload, even isotonic
exercise of moderate to higher intensity may cause fatigue and
severe strain on the heart. Walking at a comfortable pace is
therefore preferred to running. By increasing both the pace
and the duration of the physical activity as tolerated, over
time there will be an incremental increase in endurance and
exercise tolerance.
Gutgesell et al.6 categorized the levels of recreational and
occupational activity in a special report from the American
Heart Association in 1986 as shown in Tables 2 and 3. This
report emphasizes that the risks of brief periods of dizziness
or syncope can be more hazardous than the impact of severity
of workload involved in a particular activity. Examples of
such cases are unsupervised swimming, construction work at
high buildings and structures or flying an aircraft because of
the dangers of drowning and falls.6
Classification of occupational activity

Category
Level of exercise
Type of activity
Very heavy work
Lifting objects over 45 kg and/

or frequent lifting/carrying
objects over 23 kg
II
Heavy work
Lifting objects up to 45 kg and/

objects up to 23 kg
III
Medium work
Lifting objects up to 23 kg and/

objects up to 11 kg
IV
Light work
Lifting objects up to 9 kg and/or

frequent lifting/carrying objects
up to 4.5 kg
Sedentary work
Lifting objects up to 4.5 kg

and/or occasionally lifting and
carrying small articles
ExErcisE and sports in adolEscEnts and adults with congEnital hEart disEasE
Type of exercise
Adapted from Gutgesell et al. Circulation. 1986 Nov;74(5):1195A-1198A.
813
congEnital hEart disEasE in adults
10
ATHLETIC AND COmpETITIvE SpORTS
Ambulatory Holter and Event Recording
The 36th Bethesda conference guidelines define the

competitive athlete as one who participates in an organized
team or individual sport that requires regular competition
against others as a central component, places a high premium
on excellence and achievement and requires some form of
systematic (and usually intense) training. These highly
intense organized competitive sports are likely to put heavy
emotional and physical pressures on the athlete. In a person
with CHD, commitment to competitive sports may not allow
him/her to determine when it is prudent to terminate the
physical exertion if cardiac-related symptoms or warning
signs occur.7
For arrhythmias that occur sporadically or are affected by

changes in the hemodynamic status, serial electrocardiographic
recordings may be required over time. Depending upon the
frequency and duration of these arrhythmias, an ambulatory
Holter monitor or transtelephonic event recorder may be
helpful.
A recent study by Rodriguez et al showed that 15 percent
of the adults with CHD had arrhythmias on Holter monitoring.
Repeat Holter monitoring detected a new arrhythmia in
34 percent of the patients. The majority of the patients with
arrhythmias were asymptomatic (76%). Among those with
normal ECGs, arrhythmias were frequently detected on Holter
monitoring (26%).16
SUDDEN CARDIAC DEATH IN ATHLETES

The most commonly reported congenital heart or geneticallylinked lesions associated with sudden cardiac death (SCD)
during sports participation are hypertrophic cardiomyopathy
(HCM), coronary artery anomalies, Marfan syndrome and
aortic valve disease.8-10
Sudden cardiac death is less frequently linked with the
underlying diagnosis of complex congenital heart defects such
as tetralogy of Fallot, D-transposition of the great arteries,
congenitally corrected transposition of the great arteries or
defects associated with significant pulmonary hypertension.
More often than not these individuals are prudent regarding
exercise prescriptions and restrictions.
CARDIAC DIAGNOSTIC TESTING FOR SCREENING

Besides a good history and physical examination that are of
utmost importance,11 the following cardiac tests may assist in
identifying individuals at higher risk for SCD.
Electrocardiogram
For population-based preparticipation screening of cardiovascular diseases in young athletes, the 12-lead ECG has been
advocated as a practical and cost-effective tool.12 Although, the
likelihood of ECG abnormality associated with HCM is high
(7595%), other findings such as a prolonged QT in individuals
with the long QT syndrome or ST and T wave abnormalities
suggestive of coronary artery anomalies in the young or other
specific findings associated with inherited syndromes, may
not be consistently present on serial ECGs.13,14 ECGs may
sometimes be helpful in identifying Brugada syndrome15 and
other inherited syndromes that may place the person at a risk
for a high risk for SCD secondary to ventricular tachycardia/
fibrillation, under adrenergic stimulation.
814
Implantable Loop Recorder

An implantable loop recorder is a small device to help identify
the causes of unexplained syncope. Under local anesthesia, it
is inserted under the skin below the clavicle, usually on the
left side with closer proximity to the heart. It continuously
records heart rhythm for up to 2 years. When syncope occurs,
the device is activated to save the recording before, during
and after the episode. These recordings are then examined to
determine if there are any tachy or bradyarrhythmias causing
syncope.17
Treadmill Stress Testing

Treadmill stress testing allows objective assessment of the
functional capacity, exercise-induced arrhythmias and impact
of exercise on the QT interval. In addition, it is most commonly
used to evaluate ischemia. Regular organized exercise over
several months, in children and adolescents with CHD, has
beneficial effects on physical fitness and improves objectively
assessed functional capacity.18
Patients with coarctation of aorta (CoA) should have blood
pressure measurements checked in the right arm and leg before
and after exercise. The resting systolic blood pressure readings
and resting systolic blood pressure difference between the
right arm and leg are not indicators for blood pressure response
during exercise. Exercise testing is very important in patients
with CoA to unmask the exercise-induced hypertension.19,20
Those with cyanotic CHD should have their oxygen
saturation checked at rest and after at treadmill stress test
or before and after a six-minute walk test. Few centers
have bicycle stress testing that may allow more convenient
measurements of ECG, blood pressure and workload in people
with back problems, but this form of testing may be limited
due to leg fatigue.
Stress Echocardiography
Transthoracic echocardiography (2-dimensional, color and

spectral Doppler) is the principal diagnostic imaging modality
for clinical identification of structural heart diseases and
serial follow-up of residua and sequelae in individuals with
unoperated or operated CHD.21,22
The most common cause of sudden cardiac death in the
young is hypertrophic cardiomyopathy (HCM). A heart
murmur or abnormalities on ECG may be suggestive of classic
hypertrophic cardiomyopathy or its variants (Figures 1 and 2).
The diagnosis is usually confirmed by echocardiography.
The presence of unexplained asymmetric left ventricular
(LV) wall thickening with a maximal LV end-diastolic wall
thickness of 15 mm or more in an adult (two or more standard
deviations from the mean relative to body surface area; z-score
of two or more in children) is considered diagnostic for
HCM.23,24 However, when an echocardiogram is performed
in a person who has a mutant HCM gene, but is younger than
14 years of age, the left ventricular wall thickness may not
meet the criteria for HCM because he or she is in the prehypertrophic phase of the disease process.23 Therefore,
throughout adolescence annual serial echocardiography is
recommended in HCM family members.23,25,26
The second most common cause of sudden cardiac death
in athletes is a coronary artery anomaly. On a good quality
transthoracic (2-dimensional and color) echocardiogram,
the origin and proximal courses of the anomalous coronary
arteries may be visualized in the parasternal short-axis views.
In addition to the assessment of symptomatic and functional

response to exercise, stress echocardiography provides
valuable information on exercise-induced changes in
hemodynamics, ventricular function and pulmonary artery
pressure in adolescents and adults with CHD.
Biventricular response to exercise, changes in pulmonary
pressure and hemodynamic severity of the underlying defect
before and after exercise offers an additional prognostic value
for clinical management.
Cardiopulmonary Exercise Testing

Where available and affordable, cardiopulmonary exercise
testing (CPET) may offer additional prognostic information by
comparing peak oxygen uptake (peak VO2) of the individual,
in relation to the defined normal values that are greater than 90
percent of the predicted peak VO2.26
Kempny et al. reviewed 23 publications, with 2286
patients from the Medline literature, describing exercise
capacity in adults with CHD using CPET. They then included
2129 patients who underwent CPET at the Royal Brompton
Hospital in London, U.K. They observed that 80 percent of
patients had reduced peak oxygen uptake compared with
normal values. There were significant differences in peak VO2
between subgroups of adults with CHD. Even adults with
simple CHDs, on an average, had significantly reduced peak
VO2 compared with normal values. Adults with Eisenmenger
57
Echocardiography
Figure 1: Electrocardiogram in a 55-year-old woman with severe hypertrophic cardiomyopathy
815
10
Figure 2: Electrocardiogram in a 31-year-old woman with a variant of hypertrophic cardiomyopathy
syndrome and complex CHD had the lowest values. This study
allowed comparisons in the exercise capacity of individual
and their peers. The data obtained from this study should be
helpful in interpreting CPET results, guiding therapy, and
advising patients on activities of daily living, participation in
sports and choice of occupation.27
Coronary Computed Tomography Angiography
816
Coronary computed angiography (CTA) is now a popular and

relatively inexpensive imaging tool for definitive identification
of congenital coronary artery anomalies. Due to the heavy
exposure to radiation in a young person and the possibility of
an allergic reaction to the iodine contrast agent, this diagnostic
test is used prudently.
CTA is usually recommended when congenital coronary
artery anomalies are suspected, as in the case of young
people presenting with exertional syncope or palpitations
due to ventricular arrhythmias. Unfortunately, this diagnosis
is often missed during life since many young people may be
asymptomatic with daily activities and have a normal resting
ECG.
More commonly, congenital coronary abnormalities present
with anomalous origins from the wrong sinuses. The more
common type is the anomalous right coronary artery arising
from the left coronary sinus (ARCA). The most dangerous
type is the anomalous left main coronary artery (ALMCA)
originating from the right (anterior) sinus of Valsalva. The
ALMCA takes an acute angled bend with a course between
the right ventricular outflow tract/pulmonary trunk and the
anterior aspect of the aorta, that can get compressed between
the pulsatile aorta and the pulmonary artery post-exercise and

prove fatal.28,29 These individuals may present with exertional
syncope, chest pain or palpitations and surgical correction is
primarily indicated in symptomatic patients or when ischemia
is demonstrated on imaging.
Another coronary anomaly associated with SCD is the
anomalous left coronary artery arising from the pulmonary
artery (ALCAPA). Long-term outcomes in undiagnosed or
unoperated cases depend on whether or not the degree of
collateralization adequately compensates for myocardial
ischemia, its impact on left ventricular function, the severity
of mitral regurgitation due ischemic papillary muscle and risk
of ventricular arrhythmias caused by myocardial scarring
due to ischemia. Surgery to correct this anomaly should be
performed by implantation of the origin of the left coronary
artery into the aortic root or a bypass operation. Following
revascularization, stress testing is performed periodically to
evaluate exercise tolerance, ischemia and exercise-induced
arrhythmias before recommending level of exercise.
A very rare form of anomalous coronaries are the
congenitally hypoplastic coronary arteries. The risk of
sudden death increases during the growth phase, as the
myocardial demands outstrip the coronary blood supply.
Unfortunately, an adolescent may suffer sudden cardiac
death in sleep or during routine activity, with or without any
premonitory symptoms such as palpitations and/or lightheadedness. Sometimes serial electrocardiograms may show
subtle nonspecific ST and T wave abnormalities (Figures 3A
and B). Although not stated in the guidelines, our personal
experience guides us to admit an individual for a complete
diagnostic work up and potential treatment, if there are
57
B
Figures 3a and B: Serial electrocardiograms showing ischemic changes in a 19-year-old man with hypoplastic coronaries. Echocardiogram
showed borderline to mild left ventricular dilatation and normal left ventricular systolic function. He suffered sudden cardiac death due to
ventricular arrhythmias during normal activities
sporadic symptoms accompanied by subtle ECG changes and/

or mild left ventricular dilatation even when the left (systemic)
ventricular systolic function is normal.
magnetic Resonance Imaging

Magnetic resonance imaging (MRI) does not expose a person
to ionizing radiation and provides a good contrast between
the soft tissues of the heart and blood vessels, making it a
desirable imaging tool for several pathologies. Where it is

available and when it is affordable, it may be used judiciously
for clarifying the diagnosis in suspected cases of HCM, by
demonstrating segmental areas of hypertrophy of the left
ventricle (such as in the anterolateral free wall or apex).30,31
Arrhythmogenic right ventricular cardiomyopathy or
dysplasia (ARVC/ARVD) is among the common causes of
SCD in the young, with an incidence that is actually higher
than previously reported.
817
10
Figure 4: 50-year-old man with Brugada syndrome (Type 1 pattern) presenting with a history of short episodes of presyncope
818
It is characterized by a progressive replacement of normal

right ventricular muscle cells by fibrous tissue and fat, starting
with involvement of specific segments of the right ventricle
(RV), leading to RV enlargement with wall motion abnormalities
and then progressing to global RV involvement. The most
common ECG abnormality seen in ARVC is T wave inversion
in leads V1 to V3. ECG may sometimes demonstrate epsilon
waves described as a terminal notch in the QRS complex due to
slowed intraventricular conduction. In suspected cases, MRI is
the test of choice in identification of adipose tissue replacement
within the wall of the RV and aneurysm formation of the RV
which are the hallmarks for diagnosing ARVC.
Despite increased awareness and better cardiac imaging,
the diagnosis of ARVC may be delayed, since echocardiogram
is not always able to detect right ventricular involvement and
the sensitivity or specificity of MRI for diagnoses of ARVC is
limited.32-34
Brugada syndrome is an autosomal dominant inheritable
cause of sudden cardiac death due to ion channelopathies.
Loss-of-function mutations of sodium channel (SCN5A)
account for nearly one in five cases. Classic ECG abnormalities
suggestive of Brugada syndrome may sometimes be seen
in a young person presenting with palpitations leading to
presyncope or syncope (Figure 4), while in others the diagnosis
is made during electrophysiological work up for ventricular
arrhythmias. Implantation of an automatic implantable cardiac
defibrillator (AICD) is the only treatment proven effective in
preventing sudden death due to ventricular tachycardia and
fibrillation in these patients.
Genetic Testing
While genetic testing may be helpful in identifying some
inheritable disorders, it is very expensive, not routinely
available in all parts of the world. It is also not comprehensive
for screening populations for most genetic heart disorders.35
Currently, its use is restricted to limited cases where there is
high suspicion due to involvement of a family history or when
characteristic findings suggestive of a genetic disorder are
detected on other diagnostic modalities.
Coronary angiography is indicated only when non-invasive
imaging fails to make a diagnosis or when definitive diagnosis
is required prior to interventions/cardiac surgery, especially
in people who have a higher likelihood of having coronary
artery disease.
GUIDELINES FOR EXERCISE IN pATIENTS WITH

CONGENITAL HEART DEFECTS
Guidelines for physical activity, strenuous exercise, sports
and athletics in people with cardiovascular abnormalities,
especially in those with CHD, were established by the
Bethesda Conferences.36,37 With the help of these guidelines,
physicians can make individualized recommendations
based on each persons clinical status, physical abilities and
interests. The following discussion provides defect-specific
recommendations based upon the available published data

and the experience in taking care of the adults with CHD.
Adolescents and adults receiving anticoagulation should not

participate in any type of contact sport. All sport activities and
exercise have to be avoided during active infection with fever
associated with subacute bacterial endocarditis.
The main determinants of exercise tolerance besides
the severity of the underlying CHD lesions are ventricular
function, pulmonary hypertension, cyanosis and arrhythmias.
ventricular Function
Cardiovascular conditioning has a positive benefit on the
ventricular function which in turn affects exercise tolerance.
An annual assessment of ventricular function should be
performed for risk stratification of all patients with CHD who
have complex defects, unoperated or operated. Less frequent
assessment (every other year) may be performed in those with
simple operated CHD and no significant residua or sequelae.
An ejection fraction (EF) over 50 percent allows full
participation in sports while an EF less than 40 percent limits
participation in competitive sports.
pulmonary Hypertension
In day-to-day practice, the peak pulmonary artery systolic
pressure (PASP), is assessed by echocardiography based on the
estimation of the right ventricular systolic pressure (RVSP).
In the presence of tricuspid regurgitation (TR) by color-flow
Doppler imaging, the RVSP is calculated from the peak velocity
(V) of the TR jet (4 V2 + estimated right atrial pressure). The
TR jet can be enhanced by injecting saline through a peripheral
intravenous catheter.38 Severe pulmonary hypertension poses a
risk of SCD during sports and heavy exertional activities.
While there are no restrictions for participation in sports
based on a PASP of less than 30 mm Hg, those with mild
(3045 mm Hg), moderate (4560 mm Hg) or severe (greater
than 60 mm Hg) pulmonary hypertension should be guided on
an individual basis regarding exercise.
Cyanosis
Unoperated patients with cyanotic CHD have self limited
exercise abilities since the cyanosis worsens with effort due to
increasing hypoxemia (decrease in oxygen saturations measured
by pulse oximetry). Even after palliative procedures that relieve
the cyanosis at rest, exercise tolerance may still be depressed
due to hypoxemia with moderate to heavy exercise. In the
absence of a moderate to severe decrease in ventricular function
or tachyarrhythmias associated with impaired consciousness,
these patients may perform low intensity exercise as long as the
oxygen saturations are maintained over 80 percent.
While arrhythmias can occur with genetic conditions and

ion channel diseases, they commonly occur with CHD
restricting participation in exercise and sports programs.
There is specific prognostic importance linked with the
arrhythmias and CHDs, because the main determinant for
assessing sports participation in patients with arrhythmias
is the presence of structural heart disease. The Study
Group on Sports Cardiology, of the European Association
for Cardiovascular Prevention and Rehabilitation, has
made comprehensive recommendations for participation
in leisure-time physical activity and competitive sports, in
patients with arrhythmias and potentially arrhythmogenic
conditions.39,40
DEFECT-SpECIFIC EXERCISE RECOmmENDATIONS

Shunt Lesions
Atrial Septal Defect (ASD)
No exercise restrictions
Unoperated patient with a small to moderate ASD,
with a left-to-right shunt, without significant right
heart enlargement and not more than mild pulmonary
hypertension with an estimated right ventricular
systolic pressure (RVSP) less than 45 mm Hg on
echocardiography.
Postsurgical or device closure of an ASD (over 6
months ago) without a residual shunt or significant right
heart enlargement and not more than mild pulmonary
hypertension (estimated RVSP less than 45 mm Hg).
Restriction for athletics
ASDoperated or unoperated with associated
Severe RV enlargement or decreased function
Moderate to severe pulmonary hypertension (estimated
RVSP is over 45 to 60 mm Hg)
Uncontrolled arrhythmias (atrial fibrillation/flutter)
Ventricular tachyarrhythmias
High degree (second- or third-degree) atrioventricular
(AV) heart block.
57
GENERAL CONSIDERATIONS
Arrhythmias
Ventricular Septal Defect (VSD)

Operated VSD (more than 6 months ago) with no residual
shunts
Unoperated small restrictive VSD, with normal ventricular
function and absence of pulmonary hypertension (estimated
RVSP is less than 25 mm Hg)
Absence of any atrial or ventricular arrhythmias or high
degree AV heart block.
819
10
Restriction for athletics

VSD with large left-to-right shunt
Isometric exercises should be avoided since it may lead to
increase in left ventricular pressure that potentiates the leftto-right shunt
Mild isotonic exercises are allowed as tolerated
Restriction for moderate exercise
Nonrestrictive, large VSD with associated moderate to
severe pulmonary hypertension (Eisenmenger physiology)
Only mild intensity isotonic activities such as walking
for a limited duration are allowed
Patent Ductus Arteriosus (PDA)

No restrictions
Surgical-ligation or device-closure of the PDA (over 3 months
ago) with no residual shunt, normal left ventricular size and
function and absence of pulmonary hypertension
Best prognosis among all adults with CHD
Restrictions for heavy exercise and athletics
Unoperated patients with a small left-to-right shunt
Significant left ventricular enlargement and decreased
function
Mild-to-moderate isotonic exercise as tolerated
Restrictions for moderate exercise
Long-standing PDA with reversal of the shunt leading to
moderate to severe pulmonary hypertension/ Eisenmenger
physiology
Only mild intensity isotonic activities such as walking for
a limited duration are allowed
valvular Diseases
820
cardiac death. A fall in blood pressure during exercise is

a poor prognostic sign. The risk of developing arrhythmias
should be assessed by an ECG or Holter study.
Patients with minimal or mild stenosis (peak gradient less
than 40 mm Hg, mean resting gradient less than 20 mm
Hg) at the aortic, subvalvular or supravalvular levels in the
absence of left ventricular hypertrophy or arrhythmias may
perform mild-to-moderate isotonic exercises.
Heavy isometric exercise should be avoided with
Bicuspid aortic valve due to associated aortopathy5
Progressive increase in the gradient across the lesion
Significant left ventricular outflow tract obstruction
(may cause an increase in left ventricular pressure with
isometric exercise)
Aortic Valve Regurgitation

No restrictions
Mild aortic valve regurgitation
Normal end diastolic left ventricular size and systolic
function
Mitral Stenosis
Most of the information on exercise recommendations in
patients with congenital mitral stenosis are extrapolated from
the guidelines for acquired valvular disease.41 Again it is
emphasized that those who need anticoagulation should avoid
contact sports or any sports associated with a high probability
of injury. Exercise limitations depend upon the following
factors:
Severity of the valve stenosis
Size of the left atrium
Atrial arrhythmias atrial fibrillation.
Aortic Stenosis (AS), Subvalvular or

Supravalvular Stenosis
Restrictions for heavy exercise and athletics: Mild mitral

stenosis in normal sinus rhythm.
Most of the sudden deaths in patients with severe AS have been

found to occur on during physical exertion.37 Adolescents and
adults should undergo cardiac testing before being approved
for sports or athletics. Periodic re-evaluation (annually) is
required since AS may progress. Extrapolation of the data
from valvular AS, allows similar criteria to be applied for
patients with discrete (membranous) subaortic stenosis and
supravalvular aortic stenosis.37
Those with moderate (peak gradient over 40 mm Hg, mean
resting gradient between 20 to 40 mm Hg) and severe stenosis
(peak gradient over 64 mm Hg, mean resting gradient over
40 mm Hg), left ventricular hypertrophy or arrhythmias are
restricted from getting involved in athletic training, contact
sports and isometric exercise like moderate to heavy weight
lifting. They are also at risk of having syncope or sudden
Restrictions for moderate exercise: Moderate to severe

mitral stenosis with sinus rhythm or atrial fibrillation.
Mitral Regurgitation
Mild to moderate mitral valve regurgitation
Arrhythmias
Pulmonary Stenosis (PS) and Pulmonary

Regurgitation (PR)
Congenital PS may be due to a domed-shaped or dysplastic
valve, the former being associated with pulmonary artery
No restrictions
Mild PS with normal RV function
Operated PS with less than mild residual PS or PR, normal
RV function and less than moderate pulmonary artery
dilatation.
Restriction for heavy exercise and athletics
Moderate or severe pulmonary stenosis
Severe pulmonary regurgitation with/without significant
RV enlargement.
Coarctation of the Aorta (CoA)

Exercise often causes a marked increase blood pressure in the
aorta (especially proximal to the coarctation) in unoperated and
operated patients with CoA. Multiple factors including altered
vascular biology and reduced precoarctation aortic distensibility
contribute to this phenomenon, despite resolution of the local
obstruction by surgery or implantation of an endovascular stent.
Ambulatory hypertension is common in this population
even in individuals who are normotensive at rest. Exercise
stress testing helps in risk stratification before exercise
counseling and directing appropriate medical management for
better blood pressure control.43
Mild isotonic exercise with slow warm up and slow cool
down is usually recommended
Moderate to heavy isometric exercise like weight lifting
should be avoided to prevent aortic dilatation/aneurysmal
formation because of the associated aortopathy.
Tetralogy of Fallot (TOF)
Ebsteins Anomaly
In Ebsteins anomaly, the tricuspid valve abnormality and
its associated regurgitation leads to right heart enlargement
that may vary in severity, affecting clinical presentation
and exercise tolerance.42 If a patent foramen ovale is also
present, there may be an increased right-to-left shunt due
to abnormal diastology, causing cyanosis and decrease
exercise tolerance. The presence of an accessory pathway
associated with Wolf-Parkinson-White (WPW) syndrome
may predispose to supraventricular tachycardia (SVT)
during exercise. The progressive right atrial enlargement
may contribute to atrial arrhythmias. Individuals at the
severe end of the spectra of this defect may be at risk for
SCD.
No restrictions
Mild form of Ebsteins anomaly with normal right
ventricular size and function
Absence of atrial or ventricular tachyarrhythmias
Acyanotic.
Moderate tricuspid regurgitation
No arrhythmias other than premature ventricular ectopy
Post-tricuspid valve surgery with less than mild residual
tricuspid regurgitation or right heart enlargement and no
symptomatic atrial/ventricular arrhythmias.
Severe form of Ebsteins anomaly with significant right heart
enlargement and regurgitation.
Exercise testing, baseline electrocardiogram and echocardiography are essential for risk stratification of patients
with TOF, since exercise-induced QRS widening, more than
3 premature ventricular complexes in a row and ventricular
arrhythmias, namely non-sustained ventricular tachycardia
are prognostic signs for SCD.44,45
No restrictions
Operated patients with good biventricular function, normal
right ventricular dimensions, mild pulmonary regurgitation,
no significant right ventricular outflow tract obstruction
(peak gradient less than 25 mm Hg), with absence of residual
or very small restrictive VSD on echocardiography, normal
QRS duration on electrocardiogram and are tolerating
isotonic exercises.
57
dilatation.5 Echocardiography allows grading of PS as mild

(less than 40 mm Hg), moderate (40-60 mm Hg) and severe
(greater than 60 mm Hg) by a Doppler peak instantaneous
gradients. Prior to getting involved with athletics, cardiac
intervention with balloon valvuloplasty, or cardiac surgery
are indicated in symptomatic patients with a gradient greater
than 50 mm Hg. Postoperatively, the individual should
resume sports after three months.7 Isolated congenital PR
may occur due to an absent pulmonary valve or in association
with PS.

Operated patients with late repair leading to long-standing
pressure overload of RV (but with RVSP less than half
of systemic pressure), significant RV hypertrophy, RV
diastolic dysfunction
History of right ventriculotomy with annular patch
repair (associated with risk of monomorphic ventricular
tachycardia originating from the RV scar).
Moderate PR
Residual large VSD.
Severe right outflow tract obstruction (risk of sudden
cardiac death is high when RVSP is between half to twothird of the systolic pressure)
821
10
Severe PR
Marked RV dilatation and decreased RV function
Inoperable severe PS or infundibular stenosis.
Transposition of the Great Arteries

The impact of the systemic RV function, systemic AV valve
regurgitation, aortic regurgitation, small baffle leaks or
obstructions may take a toll on exercise performance in
these individuals. In addition to sinus node dysfunction,
conduction defects and propensity for atrial arrhythmias
also compound issues relating to exercise performance
in some of these patients.46,47 Incremental increase in
exercise training over years can markedly improve exercise
performance and cardiovascular status. Exercise testing with
annual re-evaluation should be performed in all patients with
transposition complex before allowing involvement in sports.
D-Transposition of the Great Arteries (DTGA)

Atrial switch repair
Maximal exercise capacity is reduced in adult patient
after a Mustard or Senning procedure.46,48 According to a
study by Buys et al. impaired peak exercise performance
results mainly from the inability to increase stroke volume
and heart rate at higher exercise intensities. In this study,
Senning (rather than Mustard) repair and a well-preserved
right ventricular function were related to a better peak
oxygen consumption. An active lifestyle was noted to have
a positive effect on exercise capacity and perceived physical
functioning.49
Reduced systemic RV function
Limited oxygen uptake due to the atrial baffles limiting
ventricular filling at higher heart rates, thereby restricting
an increase in stroke volume to match the increased
myocardial oxygen demands during exercise
Uncontrolled atrial arrhythmias
Chronotropic incompetence (due to sinus node dysfunction)
before pacemaker implantation.
Severely decreased systemic RV function
Severe subaortic or subpulmonic obstruction.
822
Arterial switch repair

Individuals who underwent arterial switch operation now have
the left ventricle (LV) as their systemic ventricle and nearly
normal physiology. This procedure involves transection and
removal of the great arteries above the sinuses of Valsalva
followed by reimplantation of the coronaries into the neoaorta. There can be a few issues impacting exercise capacity
and functional status of these patients. The success of this
operation depends on left ventricular function, patency of the

coronary arteries and the pulmonary blood flow.50
Those with coronary ostial fibrosis or obstructive coronary
artery disease may have exercise-induced ischemia. Varying
degree of residual impaired left ventricular function may limit
exercise performance. Impaired baseline LV contractility and
reversible myocardial perfusion defects and mild wall motion
abnormalities may occur.51 Abnormal pulmonary blood flow
distribution related to branch pulmonary artery stenosis
or hypoplasia has been associated with a reduced exercise
capacity and increased ventilatory drive during exercise in
these patients.52
Obstructive coronary artery disease
Severely decreased postoperative LV function
Severe aortic regurgitation from the neo-aorta
Branch pulmonary artery stenosis or hypoplasia.
Congenitally Corrected Transposition of the Great

Arteries (CCTGA)
In CCTGA, where the two wrongsatrioventricular
discordance (ventricular inversion) and ventriculoarterial
discordance (transposition of the great arteries)try to
make it right by restoring the physiological circulation, but
result in a systemic morphological right ventricle. Impaired
systemic right ventricular function, decreased contractility of
the pulmonic ventricle, presence of associated CHDs such as
a VSD or PS and decreased chronotropic response to exercise
dictate the cardiovascular performance.53
Regular aerobic exercise markedly improves cardiovascular
conditioning with very promising long-term results.
No restrictions
Asymptomatic patients with CCTGA without other cardiac
abnormalities
No systemic RV enlargement or dysfunction
No evidence of resting or exercise induced atrial or
ventricular tachyarrhythmias (confirmed on ambulatory
ECG monitoring or exercise testing).
Severely decreased systemic RV function
Severe subaortic or subpulmonic obstruction
Atrial or ventricular arrhythmias
Univentricular Hearts (Single ventricle physiology)

In the univentricular heart, the burden of pumping falls on a
large dominant ventricle (usually the left ventricle) since the
other ventricle is small and rudimentary. Right ventricular
hypoplasia with tricuspid atresia is the commonest form
for which most patients undergo the Fontan procedure
Restriction for Heavy Exercise and Athletics

Patients with univentricular hearts who have had a Fontan
operation may have very good exercise tolerance and can
participate in low intensity sports if the:
Systemic ventricular function is normal
Oxygen saturation is normal.
Restrictions for Moderate Exercise

Moderate or severe ventricular dysfunction
Arrhythmias
Reduced pulmonary functional capacity due to thoracic
abnormalities (kyphoscoliosis).
Eisenmenger physiology
Restrictions for moderate to heavy exercise and athletics
Patients with Eisenmenger physiology have severe pulmonary
vascular disease characterized by severe pulmonary
hypertension, due to reversal of shunt associated with an ASD,
VSD or PDA. Systemic vascular resistance may fall with
exercise and reduce the pulmonary venous return, leading
to exercise-induced syncope or SCD. Exercise tolerance is
usually very restricted in this population.58
For risk stratification in the office, a six-minute walk test
is recommended with blood pressure, heart rhythm and pulse
oximetry measurements taken before and after exercise. For
most patients, only mild isotonic exercise such as walking at
a tolerable pace for short duration and very light weights (less
than one lb/500 mg) with more repetitions to maintain muscle
and bone strength are recommended.
Exercise capacity and quality of life improves significantly
in iron-deficient patients with Einsenmenger syndrome,
after receiving three months of monitored iron replacement
therapy.59 Chronic nifedipine therapy has shown an increase in
arterial oxygen saturation on exercise and improved maximal
exercise capacity in these patients.60 Bosentan, an endothelin
receptor antagonist, has also shown an improvement in
functional class and objectively measured exercise capacity,

when used appropriately and cautiously as indicated.61
Syndromes
Exercise recommendations for adolescents and adults with
specific syndromes such as Marfan or Down syndrome, are
discussed in their respective chapters.
YOGA AND TAI CHI CHUAN

The integrating mind-body relaxation techniques are
well known to have a positive effect on health outcomes,
especially in patients with chronic diseases. More recent
studies have noted beneficial cardiovascular effects and
overall improvement in quality of life.62 By the nature of the
movements involved, it is possible for all people to perform
certain Yoga and Tai Chi exercises despite the limitations
imposed by other co-morbidities or age. Therefore, these
forms of exercises allow diverse application to people of all
ages, cultures and infirmities.
Yoga combines physical and breathing exercises that
have benefited people with many chronic health conditions.
Improved exercise tolerance and positive effect on levels of
inflammatory markers have been noted in patients with heart
failure.63 Yoga respiratory training improves respiratory
function leading to an improvement of both the cardiac
autonomic modulation and the sympathovagal balance
evaluated by heart rate variability.64 Pranayama, a yogic
exercise related to breathing, significantly reduces the indices
of ventricular repolarization dispersion in patients with
arrhythmia. Further studies are needed to assess its impact
on reducing the risk of malignant ventricular arrhythmias.65
Melville et al showed that yogic postures or meditation
performed in the office can acutely improve several
physiological and psychological markers of stress.66
Tai Chi is a low-impact, weight-bearing form of exercises
characterized by gentle movements designed to dissipate
force throughout the body while the subject changes poses.
It involves well-coordinated sequences of both isometric
and isotonic segmental movements in the trunk and
all extremities.67 Several studies have shown multiple
cardiovascular benefits including improvements in blood
pressure, arrhythmias and psychosocial well being.68,69 Like
yoga it appears to be safe and enjoyable for all age groups. For
people with CHD, it could be a valuable alternative to both the
high and low intensity aerobic exercise regimens. Tai Chi is a
group activity requiring only one supervising instructor for a
large number of people and is therefore cost efficient.70
57
(classic right atrium to pulmonary artery conduit or one of

its modifications). Exercise tolerance may be reduced due
to impaired ventricular function, increased venous pressure
and congestion and difficulty in increasing preload that leads
to low cardiac output. In addition, atrial arrhythmias have a
negative impact on exercise tolerance.54,55
Skeletal muscle function in Fontan patients is abnormal,
which may have an impact in the reduced exercise tolerance
encountered in these patients.56 Exercise training has beneficial
impacts on the skeletal muscle function in this population.57
Exercise testing should be performed before allowing
involvement in sports. Oxygen saturation should be tested
before and after exercise since intracardiac or intrapulmonary
shunting may reduce exercise tolerance.
CONCLUSION
Exercise and sports recommendations are designed to provide
guidance to clinicians so that they can individualize medically
823
10
table 4
Congenital heart defects and genetic disorders commonly
associated with sudden cardiac death during sports
Coronary artery anomalies-abnormal origins
Arrhythmogenic right ventricular cardiomyopathy/dysplasia
Marfan syndrome
Severe/critical aortic stenosis
Hypoplastic coronaries
acceptable exercise programs allowing participation in sports

for adolescents/adults with CHD. Exercise training and
physical rehabilitation programs may be recommended when
indicated.71 Appropriate screening should be performed to
identify the CHD and genetic disorders commonly associated
with SCD during sports (Table 4). Yoga or Tai Chi complement
the benefits of routine aerobic exercise and enhance mindbody relaxation. The goals of exercise/sports in CHD are to
enhance physical, mental and psychosocial well being while
improving long-term clinical outcomes that are so strongly
linked with functional capacity.
Health is a state of complete harmony of the body, mind and
spirit. When one is free from physical disabilities and mental
distractions, the gates of the soul open.
B.K.S. Iyengar
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C hapter
58
Psychosocial Challenges and

Psychiatric Issues while Growing Up
with Congenital Heart Disease
Tracy Kustwan Livecchi*, Reema Chugh**, Nolan Thompson***, Syed T Rizvi****
PSYCHOSOCIAL CHALLENGES
Introduction
Due to the rapid advances in early diagnosis and cardiac interventions, todays estimated survival rate of infants born
with congenital heart disease (CHD) has improved tremendously. According to one study, infants diagnosed with CHD
today have over a 95 percent chance of reaching adulthood in
developed countries. This figure is in comparison to the much
reduced survival rate of 55 years ago, in which only 25 percent
of these infants made it through their first year of life.1
Medical professionals are now faced with caring for over
1,000,000 adults with CHD in the USA alone.2 With the task of
caring for this first generation of adult survivors, many in the
field are just beginning to consider the psychosocial aspects of
this rapidly growing patient population. We write this chapter
in hopes of increasing awareness in health care providers
regarding the unique and often complicated psychiatric and
psychosocial issues affecting this patient population. We also
challenge you to consider how some of these described needs
can be better addressed in the facility in which you practice.
In exchange for this promising survival rate, children and
adolescents with CHD are often subject to a variety of extreme
stress producing events. These life altering experiences often
include numerous invasive procedures, surgeries, coping
with life-threatening symptoms and overwhelming medical
information, repeated hospitalizations, interruptions in
education and limitations on extracurricular activities and
socialization.
Since there is almost no surgical cure for congenital heart
disease, many of these same individuals face a wide spectrum
of continued cardiac symptoms and ongoing treatment
requirements as adults.1 Cardiac arrhythmias, the adjustment
to cardiac devices such as automated implantable cardiac
defibrillators (AICD) or pacemakers, the threat of cardiac
surgeries, heart failure and risk of sudden cardiac death are

just some of the medical challenges faced by the adult patients.
The information presented here is not only taken from
published literature but is also from our own perspectives (as
a patient with complex congenital heart disease who has also
experienced being a counselor working with CHD patients*
and as physicians caring for ACHD** and psychiatric
issues***, ****). We believe that presenting a combination
of sources is essential because when ACHD patients share
experiences with each other, many of the issues and challenges
identified fall outside of the existing published literature.3
Growing up with Congenital Heart Disease

Since there are a wide variety of diagnoses with different
levels of complexity, the individual experiences of this patient
population varies greatly. Furthermore, when looking at
psychosocial effects, it is important to note that each individual
must be taken into consideration in terms of their specific
medical history, age, prognosis, personality, social support
systems, individual coping style and resources available to
them. Even when faced with two individuals with identical
diagnoses and treatment histories, their overall mental health
and quality of life can be astonishingly different.
For many CHD patients, their cardiac defect presents
them with great trauma beginning from the day they are born.
Not only do many of them have to learn to live with a life
threatening illness, but they have to cope with numerous
traumatic and painful medical procedures. Often patients
will describe multiple emergency trips to the hospital,
unanticipated, pervasive physical symptoms and withheld
medical information and/or uncertain diagnoses. For some
patients with CHD, their illness sometimes feels relentless.
Loss is often a theme in working with CHD patients.
Sometimes it means being forced to cope with facing
mortality at a very early age. It can also mean the loss of
independence, physical abilities or a change in physical
10
828
appearance. For the adolescent with CHD, loss may mean

never having the opportunity to participate in team sports or
other physical or social activities. For an adult woman with
CHD, it sometimes means not being able to have a child
of her own (biological and/or adopted). There is often an
enormous sense of grief for these along with other losses,
which must be worked through in order to move on and
carve out a meaningful life for oneself.
This grief is sometimes complicated by societys reaction to
these feelings. One example of this is the common belief that
the longer one lives with a loss, the easier it is to overcome, i.e.
Since I have lived with this my whole life, I should be over
it by now. Some patients actually have disclosed feelings of
guilt regarding their intermittent or delayed feelings of loss.
However, for many CHD patients, it is not developmentally
possible for them to realize the full extent of their illness until
they reach adulthood.
Struggles with body image and the perception of being
different were mentioned in one study as being significant
issues in this patient population.4 Scarring, cyanosis and
physical restrictions are just some of the issues many of
these patients must learn to cope with on a daily basis. For a
teen struggling to fit in with his/her peers, this can often be
extremely difficult as peer relationships are such an important
part of individuation process. For adults, this theme is often
revisited when deciding how and what to tell a romantic
partner or employer regarding their CHD and then dealing
with potential negative reactions.
Academic performance and employment choices are also
important issues facing by patients. For some, occupational
success is hampered by lapses in school or work due to their
CHD. Health insurance and the financial ability to support
oneself is a consideration for the young adult transitioning
from their parents care. Many of the studies suggest that
moving into a state of independence can be challenging for
some CHD patients. One study found that 83 percent of
their subjects chose to stay close to their family home and
medical care.5 Another study found that among patients with
congenital heart disease there were significantly more of those
who had developed a dependent life style, living with their
parents without a marital or quasi-marital relationship.6
Verstappen articulately describes how the early messages
some CHD patients are given can greatly affect their overall
perspective with regards to their illness and how they live
their lives.3 One message that was given to some was that they
would not live long. As one can imagine, medically centered
anxiety, fear of death and apprehension regarding important
decision making are all potential emotional consequences of
such a belief. Many of these same patients, now adults, are
alive and wondering how to play catch up in terms of their life
choices (or lack of). Some may still be living with their parents
while others may wish they had invested in certain academic or
career choices. Some may find themselves alone as they were
never able to build a long-term, intimate relationship.
On the opposite end of the spectrum, some patients were

told that they had corrective surgery and that they were
cured. I was one of those lucky miracle babies and I
remember hearing this repeatedly as a child and finally let
my emotional guard down (after hearing dont worry, you
worry too much from both physicians and family) only to
end up with multiple cardiac problems as a young adult*.
Unfortunately, many CHD patients, after years of clinical
stability experience deterioration in their health and ability to
function. These patients often feel angry and betrayed by their
hearts, health, physicians and families because no one told
them that they may have to face cardiac difficulties again.5 As
a result, shock, anger, denial and fright are different emotional
reactions that many of these patients can experience. Often
the return of cardiac symptoms can propel the individual to
recount previous hospitalizations which may only contribute
to their anxiety, fear and uncertainty about their future.
Another theme occasionally expressed by patients with
CHD is awareness that the human heart holds strong symbolic
meaning. For many it signifies emotion, the center of life, love
and the human spirit. For some, this resonates beyond their
physical cardiac lesion and symptomatology; when one has a
broken heart this in of itself can have tremendous impact on
ones psyche. This concept was expressed so well by Fischer
and Cleveland by producing a rhythm felt throughout the
body, the heart plays a fundamental role in the individuals
image of self.4
Quality of Life
Quality of life reflects a patients life satisfaction and ability to
function in a variety of life domains including physical, social,
emotional and work-related.7 A study conducted by Moons
and colleagues defined quality of life as the degree of overall
life satisfaction that is positively or negatively influenced by
individuals perception of certain aspects of life important to
them, including matters both related and unrelated to health.8
Despite the higher rates of psychological distress and the
psychosocial issues described above, some of the research
has shown that CHD patients are thriving in many ways and
actually report having a better quality of life than their nonCHD counterparts.9 Much of the research has shown that this
group of individuals perseveres. One study had found that in
terms of academic achievement and occupational status these
respondents seem clearly beyond what one would expect in a
normal adult population and that by various criteria, these
patients seemed successful.10
Role of the Provider Caring for Patients with

As a provider, the following measures have shown positive
outcomes in our practice**. First of all, communication is
the key. We need to stop, look and understand. One needs to
CHD especially in those with complex CHD and/or cyanotic

CHD. We have seen many young girls and boys express
distress over the teasing that goes on in schools because they
have kyphoscoliois, cyanosis, clubbing or visible scars.
It is important to encourage positive thinking and make
the patient and families aware of realistic expectations. The
door should be left open with regards to questions relating to
long-term outcomes and possibilities such as What does the
future hold for me? The fields of medicine and surgery are
constantly in evolution and therefore the recommendations
also change over time.
I have several patients who never got married or had
families because they were told several decades ago that it
would not be feasible for them to do so. However, the
outcomes are far more positive if the health care provider
informs them of their current abilities and limitations. They
should be given hope by encouraging them to follow-up and
stay up-to-date with the changing paradigms. Guiding people
as to how they can experience the best possible outcome in
every situation heals them from despair over time. Reminding
ourselves that we mentally, psychologically and spiritually
make our own choices is critical to our existence. The World
Health Organization (WHO) defines health as a state of
complete physical, mental, social well-being and not merely
the absence of disease or infirmity. For a complete sense of
well-being, all the aspects of health need to be addressed.
As providers, our task is to provide the best information in
order for the individuals with CHD and their families to make
the best decisions from time to time. Facilitating transition
through stages of life, especially from childhood to adulthood
is vital for the continuity of care. The chapter on Transitional
Care in Congenital Heart Disease (Chapter 53) deals with this
matter in more detail.
Counseling for personal needs, advice regarding intimacy,
pregnancy and contraception are often ignored aspects of
medical care. Both men and women often have fears of passing
their congenital heart condition to their children or having them
suffer like they did. They are also worried about living long
enough to raise a child. Patients are usually too embarrassed
to bring up this issue. Many general practitioners are reluctant
to prescribe oral contraceptives to women with underlying
heart disease.4 On the other side of the spectrum, women with
cyanotic congenital heart disease may face fertility issues and
are also at higher risk for carrying a pregnancy should they
conceive. For many women not being able to bear children
because of their cardiovascular condition, can be a devastating
blow to their sense of identity and self worth.5 The Clinical
Nurse Specialist and the Clinical Social Worker are often
most tactful in laying the groundwork by gently addressing
these issues in a one-to-one session with the patients who are
generally too shy or embarrassed to bring these matters up in
front of their families. These patients can then be directed to
their physicians to address the technical aspects in dealing with
these issues.
58
Psychosocial Challenges and Psychiatric Issues while Growing Up with Congenital Heart Disease
understand, acknowledge the special needs, then approach

the individuals with CHD as well as their families in a kind
and sensitive manner. Knowing their lifelong struggles, their
challenges and limitations should lead us to individualize
management for each person. The clinic and the hospital
environment should to be warm, friendly and resourceful.
When faced with a medical or surgical emergency, it is
common for the patient and their family to feel overwhelmed
even if they are health care professionals. At this time of need,
there should be an established support system to help them
navigate physically, emotionally, mentally and spiritually
through the medical system with their difficulties. The Clinical
Social Worker and the Clinical Nurse Specialist (Registered
Nurse or Advanced Nurse Practitioner) who are involved in
caring for people with chronic disabilities (especially CHD)
are most resourceful. The families should have their contact
information in order to reach them promptly.
For routine care, the physicians and the Clinical Nurse
Specialist should make sure that there is a sound system to
ensure follow-up appointments, discuss test results, answer
questions/concerns for the patients and their families.
Prescriptions should be filled in an efficient and timely fashion.
These measures can help reduce anxiety and lapses in care.
We need to have genuine respect for our patients and allow
them to be active participants in their health care. We need
to empower them with the knowledge and understanding
of the routine care relating to their condition. Knowledge is
powerful and sharing information is even more powerful.
Health education classes, handouts and online resources help
those who are more receptive and the most effective moment
for a health care provider to share the key information is at
the clinic visit or during the hospitalization. These measures
promote compliance with preventive care, follow-ups and
medical/surgical treatments.
Denial is noted in many individuals with CHD from early
in life. This may come from parents, the children themselves
or the health care providers (especially physicians). Denial
and minimization can be both adaptive and maladaptive.
Although, denial may help normalize functioning with
regards to survival (such as with education and employment),
it can camouflage serious emotional problems leading to
high rates of undiagnosed or untreated mood and anxiety
disorders seen in this population. It has been observed that
very rarely patients have requested referrals and been referred
to a psychiatrist/psychologist. Their happy appearance may
cover feelings of fears of decline, premature death, loneliness,
isolation, anxiety and depression. These feelings can be
disabling especially in those who are single, unemployed and
isolated.5
One of the most common phrases that I hear from my
patients is I want to be normal. The definition of normal is
relative. It depends on the person and on his or her cultural and
environmental expectations. Many studies have shown that
feeling different is a common experience among patients with
829
10
830
Informative discussions on these issues can help allay their

fears and concerns. Some of these guidelines are discussed
in more detail in the chapter on Pregnancy, Contraception
and Gynecological Issues in Women with Congenital Heart
Disease (Chapter 56) A significant number of women with
CHD are able to have pregnancies, some choose adoption,
while others may have accidental pregnancies that they choose
to terminate.
The families of the individuals with CHD also need a lot of
support since they too suffer from many psychosocial issues.
Many mothers feel responsible for their childs illness and project
onto the sick heart all their suffering and sorrow. This may lead
to activation of unconscious aggressive feelings in the parents
and overprotective behavior towards the child. The family
may first react to the diagnosis with shock, discouragement
and depression. This may be followed by a phase of struggle
against the medical illness or they may end up in denial of the
illness. Chronic diseases often lead to a reorganization of the
family system around the illness. Siblings may also be affected
and are at increased risk for psychopathological disorders such
as behavioral and/or psychosomatic issues. Group meetings
with parents allow involvement of the parents in the treatment
plans. They help them overcome these issues by discussing
their hopes, fears and anxieties.11 Not to be ignored are the
family stressors relating to an increased strain and drain on the
family financial situation, from health care expenses. In the
unfortunate event of a death of the child, adolescent or adult
with CHD, family support and bereavement services should be
made readily available.
Patient driven support groups, national and international
association programs play an important role for most of
our internet-savvy patients. The Adult Congenital Heart
Association is very active in its efforts with patient advocacy,
in spreading knowledge, promoting research, offering social
networks and peer support (www.achaheart.org). The National
Marfan Foundation and its local chapters also promote
patient education, support through their websites, regional
and national conferences as well as other forums (www.nmf.
org). The International Society for Adults with Congenital
Heart Defects (www.isachd.org) offers many resources to
professionals and the public. A listing of international adult
congenital heart disease (ACHD) groups is available at www.
worldcongenitalheart.org. Individual clinics/centers can
provide information regarding local resources, support groups
to the patients/families to meet their personal and cultural
needs more adequately. People with CHD have a unique
impact on their healthcare and policies when they speak
directly of their own experiences.3
Appropriately educating complex CHD survivors requires
honesty and humility on the part of the providers. Promoting
the connection between the BODY, MIND AND SPIRIT
ultimately helps them the most in their lifelong journey. Both
the patient and the provider need to acknowledge the power
of the Mind over Matter. For some, adversity can be a gift
when turned around. A positive mindset and optimism can

help immensely. Most limitations are the ones that we impose
on ourselves.
Work is usually highly valued among most people with
CHD and they usually show amazing resilience in continuing
to be productive despite their physical limitations. Most of
them display persistence, perseverance, a tremendous amount
of patience in achieving their lifetime dreams and goals. We
can see the proof of this in our day to day practice where
many of our patients grew up and followed their dreams to
become emotionally, socially and economically successful.
Some chose careers in the health care profession and are
very sensitive to the needs of others. Many rose above
their physical limitations to participate in exercise and
sports beyond expectations. Some were triumphant in the
Special Olympics and other physically challenging sports.
Most survivors with CHD are extraordinarily courageous,
usually determined to work, contribute to society and be as
normal as possible.1 Although, studies have shown that their
level of education exceeded the national average, there are
many who consider themselves disabled and do not pursue
higher education or vocational training to gain meaningful
employment. Career and vocational counseling should be an
integral part of any CHD program.12 The goal is to assist the
patients in selecting a career corresponding to their special
needs or clinical limitations, while serving their personal
interests and aspirations.
It is important to feel good deep inside and therefore the
spirit cannot be ignored. The most important goal is to have
love, peace, harmony and balance in life for that is what we all
strive towards. Encouraging empowerment, offering support
and encouraging realistic, yet positive thinking can assist
patients in having the courage to work towards their goals.
PSYCHIATRIC ISSUES
Introduction
It has been found in a number of studies that this patient
population tends to have a higher incidence of mental health
issues than the general public. Brandhagen found that the
General psychologic development in adults with congenital
heart disease differed from that in a normal population.10
To substantiate, one study found that among CHD patients
who had been assumed to be well-adjusted, 36.4 percent
were experiencing a diagnosable psychiatric disorder,
with anxiety or depressive symptoms being prominent.13
Another found that Fifty percent of interviewed patients met
diagnostic criteria for at least one lifetime mood or anxiety
disorder,14 Finally another study found that approximately
79 percent of the CHD patients interviewed presented either
with a diagnosable psychiatric disorder of major depression,
panic disorder or were found to be suffering from frequently
endorsed clusters of psychiatric symptoms not meeting criteria
of cardiac lesion and the degree of psychological distress10

but yet another found significant correlations.13 Finally,
yet another study found that a persons social adjustment
and patient-perceived health status are more predictive of
depression and anxiety than medical variables.14
Could this increase of psychiatric conditions be connected
to the entry to adulthood? All of the tasks that this transition
requires (choosing and maintaining employment, supporting
oneself financially, maintaining an intimate relationship) could
simply be a reminder of ones differences and limitations. This
would be especially true for those who were never prepared
for entering adulthood. One could also say that the experience
of living with a life threatening condition, especially during
ones formative years, is in of itself enough to contribute to
this increased prevalence. After living with repeated traumatic
events, the underlying fear of it happening again often stays
with the individual. The effect this has on a person can vary
greatly and can manifest on so many different emotional and
psychological levels.
Another possible explanation for this increased prevalence
of psychiatric presentation is that perhaps there is a more
biological involvement due to lower blood oxygen levels,
limitations in physical activity, and due to the effect of
their cardiac medications.13 There is also an association of
psychiatric conditions with other cardiovascular diseases such
as coronary artery disease and heart failure. A higher incidence
of clinical depression and anxiety is noted in patients after
myocardial infarction, coronary artery bypass surgery and
with chronic heart failure. It is believed to be due to lower
blood oxygen levels during a myocardial infarction and the
cardiac surgery. It is also related to the life style changes
people have to make after having a heart attack or following
a heart surgery. Psychiatric conditions worsen the prognosis
of heart disease and vice versa, heart diseases have a major
adverse impact on mental health and psychiatric issues.21
Regardless of what the reasons for the connection to CHD
and psychiatric prevalence are, as health care professionals
we must examine why CHD patients, for the most part, are
not receiving the mental health treatment that they need. This
brings light to the issue of stigma, which unfortunately prevails
in many cultures when it comes to the acknowledgement of
mental health conditions and the need for treatment.
Stigma
58
for full disorder (post-traumatic stress disorder, dysthymia,

adjustment disorder with depressed mood and/or anxious
mood, either currently or in the past).5
One psychiatric diagnosis which is not often mentioned
in the literature is post-traumatic stress disorder (PTSD).
This is despite the fact that childhood illness qualifies as a
traumatic stressor in the diagnosis of PTSD.15 In one study, it
was found that approximately 29 percent of adolescents who
had undergone cardiac surgery as children were diagnosed
with full post-traumatic stress disorder (PTSD) likely.16 It
is our recommendation that further research into this topic be
conducted as there is preliminary evidence that PTSD may
be associated with non-adherence with medication and an
increased risk of clinical adverse events.17
It has consistently been found that mental health treatment
for these patients is greatly lacking. Kovacs stated that
approximately, 70 percent of the patients who met diagnostic
criteria at the time of study participation were not engaged
in mental health treatment.14 Furthermore, none of the
patients with diagnosable psychiatric disorders or clusters of
psychiatric symptoms in both the Bromberg13 and Horner5
studies were in mental health treatment of any kind.
The need for improved identification and treatment of
psychological disorders in this patient population could not be
more clear or convincing. Yet, as illustrated above, this very
important aspect of their care is greatly lacking. This is despite
the recommendation of the 32nd Bethesda Conference (Care
of the Adult with Congenital Heart Disease) which stated in
the summary document: The emotional health of adults with
congenital heart disease should be a priority in the overall care
of this patient population. Appropriate screening and referral
sources for treatment should be available at all regional ACHD
centers.18 Additionally, the Task Force on the Management of
Grown Up Congenital Heart Disease of the European Society
of Cardiology for grown-ups with congenital heart disease
stated (Practitioners) must be prepared to help patients and
their families with numerous psychosocial issues and work on
a multidisciplinary basis to provide psychological support.19
There is some research on the connection between CHD
and psychiatric prevalence. One study began with a hypothesis
that improvements in medical care would result in more
favorable behavioral and emotional outcomes for children and
adolescents with CHD treated recently. Could the medical
care patients received in the infancy of CHD treatment have had
enough of an effect to cause an increased rate of psychological
symptomatology? This group compared patients operated on
before 1980 with a group of patients operated on 10 to 15
years later. They found that despite evident improvements in
diagnostic and surgical techniques and medical treatment of
CHD over the past decades, virtually no changes were found
in levels of problem behavior.20 Another potential contributor
that has been examined is the possible connection between
medical severity and degree of psychological stress. One study
found that there was no correlation found between the severity
What is Stigma?
Stigma can be defined as a sign of disgrace or discredit, which
sets a person apart from other. According to Goffman, the
difference between a normal and stigmatized person is a
question of perspective not reality. There is also a courtesy
stigma where family members feel embarrassed or ashamed
of the illness of their loved ones, whether it is an emotional or
a physical condition.22
831
10
How do We Deal with Stigma?

Education is the first and most important factor in fighting
stigma. It helps with the fear of the unknown and takes down
the walls that people create to psychologically and at times to
physically protect themselves. Education should be provided
to the young patients at a level that they can understand
clearly. As more understanding grows, patients become less
embarrassed about their condition and will hopefully begin to
feel less different. Providing psycho-education can also help
patients and family members spread pertinent information to
the people in their lives and circles. Eliminating the fear of
the unknown relating to a medical condition can be helpful.
The stigma attached to illnesses like HIV/AIDS has been
successfully challenged by educating people more about
the facts versus the myths. Educational programs, media,
and support groups for families can assist in promoting
such efforts. Many health conditions receive positive public
attention (therefore reducing stigma) when high profile people
or celebrities openly discuss their personal medical conditions.
Role of Mental Health Services
832
Mental Health Services can provide emotional support,

coping strategies and the opportunity to explore ones
thinking for distortions that may adversely affect life goals
and relationships. Coping strategies which may have
been appropriate in childhood may no longer serve well in
adulthood. Distortions of thinking may cause unwarranted
sensitivity to rejection, social isolation or deferral of fulfilling
activities.
An important issue in making a referral to mental health
services is the level of comfort and knowledge on the part
of the health care provider and the patient in addressing
psychiatric issues. Discussion of the physiologic processes
(the role of Serotonin, for example) involved in anxiety or
depression symptoms may help reduce stigma for the patient
in need of mental health services.
Our experience has shown that although many CHD
patients do want mental health treatment, denial, lack of
acknowledging the need, the stigmata and paucity of access
to care may make it challenging for people based upon their
demographics. This is substantiated by a study which found
that 51 percent of patients indicated a high interest in at
least one of the seven defined focus areas of psychological
treatment.23 Unfortunately, however, according to Horner,
CHD patients in adulthood, as in their childhood, often
suffered silently and worried alone.5 Denial has been cited as
a common psychological defense in this patient population.5
The fact that many CHD patients in need are not receiving
treatment is especially concerning since there is existing
evidence that social support and emotional expression may be
associated with better medical outcome (cancer patients).24
Although, many ACHD centers do offer some form of
mental health services, the findings above indicate that it is
not enough. There continue to be many obstacles to addressing

the psychological needs of these patients. A lack of funding
and a deficiency of psychosocial awareness on the part of
CHD faculty, as well as patients and families are two areas
of concern. Additionally, our experience shows that there is
a fear on the part of some patients of not being understood
by (mental health) treatment providers. Many patients have
described the frustration of having to explain their medical
history repeatedly to mental health care providers only
to receive a variety of unhelpful responses ranging from
astonishment to pity. Perhaps, this is why it was found that
only 35 percent of the CHD patients in one study were found
to be interested in receiving peer support.23
Management of Children Growing Up

with Chronic Disabilities
Rapprochement is a part of a phase of development in toddlers
postulated by Margaret Mahler.25,26 In this sub-phase, a toddler
practices being independent and wants to explore the world.
The child realizes that his physical mobility demonstrates
psychic separateness from his mother. The child has a fear of
mother (primary caregiver) not being there when she is needed.
This phase can be disturbed in children who are challenged
with medical illnesses such as CHD and who are undergoing
a medical or surgical procedure. His/her experience with
their CHD may cause a child to become clingy to the parents
and issues of separation anxiety can arise. It is believed that
adolescents go through the same phase when they want to
practice their independence. It is also a time in their life when
existential questions are raised in the mind. The questions
such as Who am I?, Why am I in this world? and Who
do I belong to (in the psychological sense)? These are some
of the things that make this phase of life so challenging. It is
when the normal developmental challenges of independence
are coupled with the added stressor of a childs heart disease
that significant psychological issues can arise.
This may be why it is common to see some children
become increasingly non-compliant with treatment during
adolescence. Other factors that may affect non-compliance
are the general attitude of invincibility (in adolescence) and
denial used as a way of coping with their illness. Parents
and providers can help by acknowledging and validating
the adolescents health situation, feelings or struggles. They
can offer psychological education, unconditional love and
acceptance. Partnering with them, instead of telling them what
to do has more chances of success.
Management of Depression and Anxiety disorders

The treatment for depression and anxiety should be three-fold:
biologic, psychotherapy and lifestyle changes.27 The biologic
treatments are discussed in the section Pharmacological
interventions in patients with cardiovascular disease.
Psychotherapy can help in understanding one's patterns of
An Approach to Post-traumatic Stress Disorder

The best approach to post-traumatic stress disorder (PTSD) is
to minimize the emotional trauma during the treatment. The
health care provider can help by preparing the patient with
education about their illness or the procedure that they are
about to have. When it is possible, and especially in the case of
children, being close to a loved one until it is time to go under
anesthesia is very supportive. Processing the traumatic events
as early as possible can aid in any situation, so the same would
be true when dealing with a patients medical trauma. After
the procedure, guiding the patient back to their normal life as
soon as possible also helps in faster recovery, both emotionally
and physically. Nature created human beings with the flight or
fight response, so that when a danger arises, initially certain
hormones get pumped into the blood to allow us to either
fight it or get out of it. After a short period of time, the bodys
response diminishes and everything goes back to the baseline.
The challenge in patients with chronic illnesses or stressrelated disorders is that their bodies and emotions are in that
state of flight or fight response all the time. This takes a toll
on them, unless they are able to seek help in order to recognize
these patterns and learn new healthy coping skills.
Pharmacological Interventions in Patients

with Cardiovascular Disease
Along with counseling, supportive care, the pharmacological
interventions play a major role in management of depression,
anxiety disorders and other mental conditions in patients with
CHD as well as in those with other cardiovascular diseases.
Among biologic therapies, the selective serotonin reuptake
inhibitors (SSRI) such as fluoxetine, sertraline, paroxetine,
citalopram, have shown to be very effective in treating both
depression and anxiety. There is a rising interest in the use
of SSRIs in cardiac patients, especially in those with heart
failure due to coronary artery disease.28-31 In addition, the

positive impact of exercise training in patients with depression
and heart failure due to coronary artery disease should be
extrapolated to other cardiac patients (including those with
congenital heart disease).32
Effexor (Venlafaxine) is an antidepressant and antianxiety medication that is considered to be a serotonin and
norepinephrine reuptake inhibitor (SNRI). It can cause an
elevation in blood pressure and should be used cautiously with
proper monitoring. Benzodiazepines such as lorazepam and
clonazepam are good medications in reducing acute anxiety.
Clinicians have to be very careful in using any psychotropic
medications that may increase the heart rate, blood pressure
or prolong the corrected QT interval (QTc). For example,
stimulant medications commonly used to treat attentiondeficit hyperactivity disorder (ADHD) or lethargy related to
depression, can increase heart rate and blood pressure. These
drugs have potential side-effects including cardiac arrhythmias.
Their use may be contraindicated in patients with CHD who
have significant electrophysiological issues. Therefore, a
baseline electrocardiogram and a cardiology consultation are
needed before prescribing these medications. Because the
benzodiazepines can be habit-forming and may cause memory
problems, their use should be for short-term only especially
during acute phases, until the long-term medications such as
SSRIs or SNRIs start working. Most antipsychotic medications
used to treat psychotic disorders such as schizophrenia or mood
disorders such as bipolar disorders can prolong the QTc interval
(Figure 1). The worst offenders are Ziprasodone (Geodon) and
Thioridazine (Mellaril). Weight gain, elevated triglycerides and
cholesterol are potential side-effects of this class of medication.
Close monitoring for potential side-effects should be provided.
The tricyclic antidepressants (TCAs) should be used
with caution. A baseline electrocardiogram should be
obtained before starting this class of medications. Follow-up
electrocardiograms should be checked annually or if there are
any cardiac symptoms. In children, Imipramine in low doses
can be effective for nocturnal bed wetting and desipramine
has shown efficacy in treating attention-deficit hyperactivity
disorder (ADHD).33,34
Unfortunately, there are case reports of sudden death
associated with the use of TCAs. Nortriptyline is used to treat
obsessive compulsive disorder (OCD) in both children and
adults. TCAs are also used for controlling severe neurological
pain and migraine. With the advent of newer antidepressants,
the use of TCAs is now becoming limited. These agents are
still used in treatment of refractory depression.
58
thinking, how a person copes with situations and how a chronic

medical condition has affected his/her social, occupational or
educational life. Cognitive behavior therapy techniques can
be used in helping patients focus on seeing the glass halffull rather than half-empty. Lifestyle changes relating to
Healthy Living by eating healthy and incorporating exercise
in their daily routine are advocated. Stress management with
meditation, activities that bring peace, harmony such as music,
dancing, gardening and yoga should be a part of everyones life.
Patients should also be encouraged to think about their
priorities in life and how to take control of the direction of
their lives in a realistic way. Finding the enjoyment in the
little things such as a walk in the park, a stroll by the beach
or enjoying a cup of tea over a conversation with a friend can
also help in feeling fulfilled in ones life. We think that it is also
important for CHD patients to define themselves not by their
illness but instead as individuals with ideas, interests, goals
and dreams.
Drug-drug Interactions
Selective serotonin reuptake inhibitors (SSRIs) are widely
used and since most patients are taking multiple medications,
it is very important to be aware of drug-drug interactions.
Like many other drugs, SSRI's are metabolized by
cytochrome P450 system. Many drugs may increase or
833
10
Figure 1: Electrocardiogram showing long corrected long QT interval (QTc). The QT interval
should be corrected to age, gender and heart rate
Table 1
Medications and agents that may increase levels or toxicity when used with selective serotonin reuptake inhibitors (SSRIs)
Class of medications
Examples
Antiarrhythmics
Flecainide, Propafenone
Beta blockers
Propranolol, Metoprolol
Highly protein bound medications
Warfarin, Digoxin
Tricyclic antidepressants
Amitryptyline
Triptans
Sumatriptan (Imitrex)
Alcohol and central nervous system suppressants

Diuretics
Sympathomimentic drugs
Pseudoephedrine
Pain medications
Tramadol, Pethidine, Meperidine
Theophylline
Sibutramine
834
decrease the activity of various cytochrome P450 isoenzymes

either by inducing the biosynthesis of an isoenzyme or
by directly inhibiting the activity of the cytochrome P450
isoenzymes. Special consideration should be applied when
using medications for cardiac conditions that are also
metabolized by this system or by specific isoenzymes such as
CYP2D6.
The SSRIs may increase blood levels and risk of toxicity
of certain medications such as warfarin (coumadin), digoxin
and beta blockers. Certain agents and medications such as
diuretics may increase the toxicity of SSRIs. Alcohol use is
not advised during treatment with SSRIs since it may increase
the toxicity of the SSRIs (Table 1).
Conclusion
Screening for early detection and management of psychosocial
challenges and psychiatric issues is vitally important. Timely
and appropriate referral should be made to the clinical social
worker, psychotherapist and psychiatrist. There is a need for
ongoing in-depth studies in this population.
An integrated approach as described in Box 1 may help
improve psychosocial care in people with CHD. A special
relationship develops over the years between the providers
and the patients. They rely heavily on their providers for
long-term emotional support. The quality of life while living
with CHD can be improved by identifying a purpose to make
Integrate mental health care providers into the CHD medical

team and also utilize them as a community referral resource.
Develop outreach strategies designed to identify mental health
care providers (clinical social workers and psychologists) and
ideally refer to those who are specially trained in working with
patients with CHD.
Establish a plan to develop and test tools for screening of
psychosocial problems in this population.18
Provide psychological education to the faculty (at the
ACHD and Pediatric Centers), patients and family members
regarding identification, treatment and recommendations for
psychosocial/psychiatric issues.
Pediatric Centers should offer transitional support to assist
adolescents with the move to adult care.
Offer patient support groups and peer to peer relationships
locally.
Provide crisis intervention and psychotherapy (talk therapy)
to patients when indicated.
Short-term psychotherapy administered through the ACHD
centers.
Long-term counseling referred out to appropriate affiliated
mental health programs and community resources.
Inpatient counseling provided following a cardiac episode or
prior to cardiac procedures and surgery.
life more meaningful. As providers, we should encourage

the patients to feel more empowered when dealing with their
health conditions.
To keep the body in good health is a duty, otherwise we shall
not be able to keep our mind strong and clear.
Gautama the Buddha, 563 BC
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2. What are Congenital Heart Defects? National Heart, Lung
and Blood Institute, Diseases and Conditions Index, US
Department of Health and Human Services, National Institutes
of Health, Revised July, 2011
3. Verstappen A, Pearson D, Kovacs AH. Adult congenital heart
disease: the patients perspective. Cardiol Clin. 2006;24:
515-29.
4. Gantt LT. Growing up heartsick: the experiences of young
women with congenital heart disease. Health Care Women Int.
1992;13:241-8.
5. Horner T, Liberthson R, Jellinek MS. Psychosocial profile of
adults with complex congenital heart disease. Mayo Clin Proc.
2000;75:31-6.
6. Kokkonen J, Paavilainen T. Social adaptation of young adults
7. Kovacs AH, Silversides C, Saidi A, et al. The role of the

psychologist in adult congenital heart disease. Cardiol Clin.
2006;24:607-18.
8. Moons P, Marquet K, Budts W, et al. Validity, reliability and
responsiveness of the Schedule for the Evaluation of Individual
Quality of Life-Direct Weighting (SEIQoL-DW) in congenital
heart disease. Health Qual Life Outcomes. 2004;2:27.
9. Moons P, Van Deyk K, De Bleser L, et al. Quality of life and
health status in adults with congenital heart disease: a direct
comparison with healthy counterparts. Eur J Cardiovasc Prev
Rehabil. 2006;13:407-13.

10. Brandhagen DJ, Feldt RH, Williams DE. Long-term
psychologic implications of congenital heart disease: a 25-year
follow-up. Mayo Clin Proc. 1991;66:474-9.
11. Masi G, Brovedani P. Adolescents with congenital heart
disease: psychopathological implications. Adolescence. 1999;
34(133):185-91.
12. Simko LC, McGinnis KA. Quality of life experienced by adults
with congenital heart disease. AACN Clin Issues. 2003;14: 4253.
13. Bromberg JI, Beasley PJ, DAngelo EJ, et al. Depression and
anxiety in adults with congenital heart disease: a pilot study.
Heart Lung. 2003;32:105-10.
14. Kovacs AH, Saidi AS, Kuhl EA, et al. Depression and anxiety
in adult congenital heart disease: predictors and prevalence. Int
J Cardiol. 2009;137:158-64. Epub 2008 Aug 15.
15. Manne S. Commentary: Adopting [corrected] a broad perspective on post traumatic stress disorders, childhood medical
illness and injury. J Pediatr Psychol. 2009;34:22-6. Epub 2008
Apr 25. Erratum in: J Pediatr Psychol. 2009;34:338.
16. Toren P, Horesh N. Psychiatric morbidity in adolescents
operated in childhood for congenital cyanotic heart disease. J
Paediatr Child Health. 2007;43:662-6.
17. Spindler H, Pedersen SS. Posttraumatic stress disorder in the
wake of heart disease: prevalence, risk factors, and future
research directions. Psychosom Med. 2005;67:715-23.
18. Foster E, Graham TP Jr, Driscoll DJ, et al. Task force 2: special
health care needs of adults with congenital heart disease. J Am
Coll Cardiol. 2001;37:1176-83.
19. Baumgartner H, Bonhoeffer P, De Groot NM, et al. Task Force
on the Management of Grown-up Congenital Heart Disease of
the European Society of Cardiology (ESC). ESC Guidelines
for the management of grown-up congenital heart disease
(new version 2010). Eur Heart J. 2010;31:2915-57. Epub 2010
Aug 27.
20. Spijkerboer AW, Utens EM, Bogers AJ, et al. A historical
comparison of long-term behavioral and emotional outcomes
in children and adolescents after invasive treatment for
congenital heart disease. J Pediatr Surg. 2008;43:534-39.
21. Meijer A, Conradi HJ, Bos EH, et al. Prognostic association of
depression following myocardial infarction with mortality and
cardiovascular events: a meta-analysis of 25 years of research.
Gen Hosp Psychiatry. 2011;33:203-16. Epub 2011 Mar 31.
22. Goffman E. In Stigma: Notes on the Management of Spoiled
Identity. New York, Simon and Schuster, Inc. 1963.
23. Kovacs AH, Bendell KL, Colman J, et al. Adults with
congenital heart disease: psychological needs and treatment
preferences. Congenit Heart Dis. 2009;4:139-46.
24. Spiegel D, Sephton SE, Terr AI, et al. Effects of psychosocial
treatment in prolonging cancer survival may be mediated by
neuroimmune pathways. Ann N Y Acad Sci. 1998;840:674-83.
58
Box 1: Recommendations for improved psychosocial

care in people with congenital heart disease
835
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25. Martin A, Volkmar FR (Editors). In Lewiss Child and

Adolescent Psychiatry: A comprehensive textbook, 4th edition.
Philadephia, Lippincott Williams and Wilkins. 2007. p. 389.
26. Mahler MS. Rapprochement subphase of the separation
individualization process. Phychoanal. Q. 1972;41:487-506.
27. Schotte CK, Van Den Bossche B, De Doncker D, et al. A
biopsychosocial model as a guide for psychoeducation
and treatment of depression. Depress Anxiety. 2006;23:
312-24.
28. OConnor CM, Jiang W, Kuchibhatla M, et al. SADHARTCHF Investigators.Safety and efficacy of sertraline for
depression in patients with heart failure: results of the
SADHART-CHF (Sertraline Against Depression and Heart
Disease in Chronic Heart Failure) trial. 25. J Am Coll Cardiol.
2010;56:692-9.
29. Goodlin SJ. Sadness in heart failure: what is a clinician to do?
30. Tousoulis D, Antonopoulos AS, Antoniades C, et al. Role of

depression in heart failurechoosing the right antidepressive
treatment. Int J Cardiol. 2010;140:12-8. Epub 2009 Jun 6.
31. Watson K, Summers KM. Depression in patients with heart
failure: clinical implications and management. Pharmacotherapy. 2009;29:49-63.
32. Milani RV, Lavie CJ, Mehra MR, et al. Impact of exercise
training and depression on survival in heart failure due to
coronary heart disease. Am J Cardiol. 2011;107:64-8.
33. Spencer T, Biederman J, Coffey B, et al. A double-blind comparison of desipramine and placebo in children and adolescents with chronic tic disorder and comorbid attention-deficit/
hyperactivity disorder. Arch Gen Psychiatry. 2002;59:649-56.
34. Swanson JR, Jones GR, Krass elt W, et al. Death of two subjects
due to imipramine and desipramine metabolite accumulation
during chronic therapy: a review of the literature and possible
mechanisms. J Forensic Sci. 1997;42:335-39.
Sec t i on
11
Electrophysiological Issues
in Children
C hapter
59
Congenital Heart Blocks

and Bradyarrhythmias
Abhilash SP, Dinesh Choudhary, Narayanan Namboodiri
IntroduCtIon
Cardiac rhythm disorders range from benign to life-threatening
and bradyarrhythmias are arbitrarily defined as a heart rate below
60 beats/minute. Children have higher heart rates than adults and
heart rate tends to decrease across childhood upto adolescence.
Newborns have heart rates that range from 100 to 160 beats per
minute. Children aged between 1 and 10 years have heart rates
that range from 60 to 140 bpm. This age-dependency of normal
heart rates should be considered while interpreting heart rates in
infants and young children. Though uncommon, the presence of
bradyarrhythmia in children requires special attention, related
to some special issues. First, a clear differentiation of transient,
functional abnormalities such as vagotonia from primary disease
of the conduction system is required. Second, a decision to pace
needs consideration of issues like selection of optimal pacemaker
system, limited venous access options at the younger age and the
anticipated problems in the long years of follow-up to come.
Third, the confounding factors related to associated structural
heart disease if any, both anatomical and hemodynamic, and at
acute and long-term, also need to be addressed.
A brief description of clinically relevant bradyarrhythmias
(common to all age groups) is given below as it would aid
in clear understanding of specific bradyarrhythmia-related
issues in children.
BradyarrHytHmIaS rElatEd to aBnormal SInuS

nodE FunCtIon
Sinus Bradycardia
Sinus bradycardia can result from excessive vagal and/
or decreased sympathetic tone. It can also be an effect of
medications, disorders like hypothyroidism or due to anatomical
changes in the sinus node (SN) itself. During sleep, the normal
heart rate can fall to 35 to 40 bpm, especially in adolescents

with marked sinus arrhythmia, sometimes producing pauses
of two seconds or longer. Increased intracranial pressure due
to intracranial space occupying lesions and infections like
meningitis can also cause sinus bradycardia. Treatment of
sinus bradycardia per se is not usually necessary, but a careful
evaluation to rule out any correctable cause is suggested.
Sinus arrhythmia
Sinus arrhythmia is characterized by a phasic variation in
sinus cycle length during which the maximum sinus cycle
length minus the minimum sinus cycle length exceeds 120
milliseconds. The sinus rate increases gradually during
inspiration and decreases with expiration. The variation
is attributed to changes in vagal tone as a result of reflex
mechanisms arising from the pulmonary and systemic vascular
systems during respiration. This respiratory sinus arrhythmia
is the most frequent form of sinus arrhythmia and is considered
to be a normal event. Nonrespiratory sinus arrhythmia is more
likely to be seen in elderly individuals in association with heart
disease. Symptoms produced by sinus arrhythmia are rare, but
if the pauses between beats are excessively long, palpitations
or dizziness may result. Generally, sinus arrhythmia does not
require any specific treatment.
Wandering Pacemaker
This variant of sinus arrhythmia involves shift of the dominant
pacemaker focus from the SN to latent pacemakers that have the
next highest degree of automaticity in atria or atrioventricular
(AV) junction. In contrast with AV dissociation, the change
occurs in a gradual fashion over the duration of several beats;
thus, only one pacemaker at a time controls the rhythm.
Treatment is usually unnecessary.
ElEctrophysiological issuEs in childrEn
11
BradyarrHytHmIa rElatEd to aBnormal

av nodE FunCtIon
An AV block exists when the atrial impulse is conducted with
delay or is not conducted at all to the ventricle when the AV
junction is not physiologically refractory. During AV block,
the block can occur in the AV node, His bundle or infrahisian
conduction system.
Figure 1: Sinus pause of 1.6 s. This pause could be due to abnormality
in automaticity of sinus node (sinus arrest) or conduction from the
node to atrium (sinus exit block)
Sinus Pause
Sinus pause or absence of an expected P wave for more
than 3 seconds, may be due to sinus arrest (failure of the SN
pacemaker cells to depolarize) or be the result of sinoatrial
(SA) exit block (depolarization of the SN but failure to conduct
to the atria). The main feature to look for in electrocardiogram
(ECG) is P-P interval delimiting the pause does not equal a
multiple of the basic P-P interval. In patients with sick sinus
syndrome, characterized by marked sinus bradycardia or
sinus arrest, especially if symptomatic, permanent pacing is
necessary (Figure 1).
Electrocardiogram in SA exit block shows a pause resulting
from absence of the normally expected P wave. The duration
of the pause is a multiple of the basic P-P interval. Sinoatrial
exit block is caused by a conduction disturbance during which
an impulse formed within the SN fails to depolarize the atria
or does so with delay. Excessive vagal stimulation, acute
myocarditis or fibrosis involving the atrium, as well as drugs
such as beta blockers or digitalis, can produce SA exit block.
Sinoatrial exit block can be of three types. A first-degree SA
block cannot be recognized on the surface ECG. Seconddegree SA blocks are recognized frequently because of their
effect on the atrial rhythm. Analogous to second-degree AV
block, there are two types of second-degree SA block: type I
(Wenckebach periodicity) and type II, manifested by dropped
P waves during sinus rhythm. Type I block is clinically more
prevalent than type II block. Sinoatrial exit blocks are usually
transient and usually do not require treatment.
Sick Sinus Syndrome
840
Sick sinus syndrome is a term applied to a syndrome

encompassing a number of primary sinus nodal abnormalities,
including sinus bradycardia, sinus arrest or exit block,
AV conduction disturbances and alternation of atrial
tachyarrhythmias especially atrial fibrillation and periods
of slow atrial and ventricular rates (tachy-brady syndrome).
Permanent pacing for the bradycardia, combined with drug
therapy to treat the tachycardia, is required in those with
symptomatic tachycardia-bradycardia syndrome.
First-degree av Block
During first-degree heart block, conduction time across
AV node is prolonged resulting in prolonged PR interval in
ECG; but all impulses are conducted. Clinically important
PR interval prolongation can result from a conduction delay
in the AV node (A-H interval), in the His-Purkinje system
(H-V interval) or at both sites. Occasionally, an intra-atrial
conduction delay can also result in PR prolongation. Increase
in atrial rate or vagal tone can cause first-degree AV nodal
block to progress to type I second-degree AV block. Isolated
first-degree AV block warrants no treatment.
Second-degree av Block (mobitz type I and type II)

Blocking of some atrial impulses conducted to the ventricle
at a time when physiological interference is not involved
constitutes second-degree AV block. Second-degree heart
block occurs in two forms, Mobitz type I (Wenckebach) and
type II (Figures 2 and 3). Type I heart block is characterized
by a progressive lengthening of the conduction time until
an impulse is not conducted. Electrocardiographically,
type I second-degree AV block is characterized by progressive
PR prolongation culminating in a non-conducted P wave.
During a type I block, the increment in conduction time is
greatest in the second beat of the Wenckebach group and the
absolute increase in conduction time decreases progressively
over subsequent beats. In type I second degree AV block,
the interval between successive beats progressively
decreases, although the conduction time increases (but by
a decreasing function). The duration of the pause produced
by the non-conducted impulse is less than twice the interval
preceding the blocked impulse and the cycle following the
non-conducted beat is longer than the cycle preceding the
blocked impulse.
Type II heart block denotes occasional or repetitive
sudden block of conduction of an impulse, without prior
measurable lengthening of conduction time. In ECG, the
PR interval remains constant prior to the blocked P wave.
Type II AV block indicates disease in the infra-Hisian
conduction system and often antedates the development of
Adams-Stokes syncope and complete AV block, whereas
type I AV block with a normal QRS complex is generally
benign and does not progress to advanced heart blocks (Refer
indications for pacing given below).1
59
congEnital hEart Blocks and Bradyarrhythmias
Figure 2: Mobitz type I second-degree AV block. Note: The progressive prolongation

of PR interval before a P wave fails to conduct to ventricle
Figure 3: Mobitz type II second-degree AV block. Intermittently P wave fails to conduct, but not preceded
by prolongation of PR interval, unlike in Figure 2
2:1 atrioventricular Block

The 2:1 AV block can be a form of type I or type II second
degree AV block (Figure 4). If the QRS complex is normal, the
block is more likely to be type I and located in the AV node. If a
bundle branch block is present, the block can be located in the
AV node or His-Purkinje system. An EP study may be required
to localize the exact location of block with certainty.
third-degree (Complete) av Block

Third-degree or complete AV block occurs, when no atrial
activity is conducted to the ventricles and the atria and ventricles
are controlled by independent pacemakers (Figure 5). The atrial
pacemaker can be sinus or ectopic atrial or from AV junction
occurring above the block with retrograde atrial conduction.

The ventricular focus is located below the region of the block,
which can be above, at or below the His bundle bifurcation.
Complete AV block can result from block at the level of the AV
node; also known as suprahisian (usually congenital), within
the bundle of His or intrahisian or distal to it in the Purkinje
system or infrahisian (usually acquired). The ventricular rate
in acquired complete heart block is generally less than 40 bpm,
but can be faster in congenital complete AV block. Ventricular
pacemaker activity that are in or closer to the His bundle result
in a faster escape rate than can those located more distally in
the ventricular conduction system. Escape rhythm resulting
from conduction block in infrahisian conduction system is
slower and much more unstable (See below for indications for
pacing).1
841
11
Figure 4: 2:1 AV block. Conducted PR interval and the QRS width often give clue to the likely site of AV block in these cases
Figure 5: Complete heart block. This condition is easily identified by PP association, RR association,
PR dissociation and atrial rate exceeding the ventricular rate
BradyarrHytHmIaS: SPECIal ConSIdEratIonS

In CHIldrEn
842
Children presenting with symptoms owing to primary

bradycardias are relatively uncommon. Symptoms associated
with sinus node dysfunction are caused by inadequate heart
rate response to stress or exertion. Overt symptoms are
relatively uncommon in children with first- and seconddegree AV block too. However, complete heart block, either
congenital or acquired, can have a fatal outcome in children
and may need more attention.
The fetus and infant with congenital complete AV block
and no associated heart disease usually are asymptomatic.
However, if the escape rate is inadequate, symptoms may
range from growth retardation to overt congestive heart failure,
including hydrops fetalis. Older patients with congenital AV
block may develop varying degrees of exercise limitation or

syncope. Sudden death is uncommon during the first decade,
but increases thereafter. Syncope or sudden cardiac death due
to complete AV block may result from bradycardia, per se or
bradycardia-dependent polymorphic ventricular tachycardia
with degeneration to ventricular fibrillation (Figure 6).
Clinical Scenarios
The common clinically significant bradyarrhythmias secondary
to conduction system disturbances and relevant in children can
be grouped into the following main categories:
1. Sinus node dysfunction, which is secondary to surgical
repair of congenital heart disease (CHD), often with
concomitant atrial tachyarrhythmias.
2. Postsurgical atrioventricular block.
3. Congenital atrioventricular block.
4. AV conduction disturbances in Long QT syndrome (LQTS).
59
Postsurgical Sinus Node Dysfunction with or without Atrial

Tachyarrhythmias
Surgery for CHD often involves large incisions in the right
atrium and in certain types of operations, the SN can be
damaged.2,3 The SN may be damaged directly by incision,
clamping or suturing. Interruption of the blood supply to
the SN during surgery can also cause SN dysfuncion. Both
the Mustard and the Senning procedure for atrial redirection
in d-transposition of the great vessels involve extensive
atrial suture lines and the incidence of SN abnormalities
progressively increases as these patients grow into adulthood.
These two classical surgeries are not regularly performed
nowadays, as transposition is now managed by the arterial
switch procedure. Still, thousands of children and adults are
alive today following the Mustard or Senning procedure and
most have some elements of SN abnormality.
Another operation that is commonly associated with
SN dysfunction is the Fontan procedure. The loss of sinus
rhythm with subsequent junctional escape rhythm leads to AV
asynchrony. This loss of AV synchrony certainly has adverse
consequences in a patient with Fontan circulation. In patient
with borderline hemodynamic function, it is advisable to
consider permanent pacemaker to restore AV synchrony, even
if a more obvious indication such as syncope or chronotropic
incompetence is not present. Due to the presence of extensive
atrial incisions and suture lines, such patients are also at risk for
the development of atrial tachyarrhythmias and in particular,
intra-atrial reentrant tachycardia.4 The coexistence of these
tachyarrhythmias with significant SN dysfunction is especially
important. Episodes of tachycardia leads to hemodynamic
instability and syncope and moreover, the sudden termination
of an episode of atrial tachycardia may be followed by a very

prolonged asystolic episode in patients with profound SN
dysfunction, leading to syncope. Drugs such as beta-blockers
and amiodarone generally have only negligible serious
adverse effects in the presence of a normal SN. But when they
are given to patients with pre-existing SN disease, profound
abnormalities of SN function can result.
Figure 6: Bradyarrhythmia-induced torsades. These tracings were recorded during Holter evaluation in a child
with congenital complete block. The long short RR interval sequences initiate re-entry
Postsurgical Atrioventricular Block

The surgical repair for CHD carries some risk of damage to
either AV node or the distal conduction system. For example,
in patients with perimembranous ventricular septal defect
(VSD), the bundle of His perforates the central fibrous body to
emerge on the margin of the defect, before branching into right
and left fascicles.5 Placement of the patch requires placing
deep sutures into myocardium and the conduction system
is at risk. Surgical repair of tetralogy of Fallot and truncus
arteriosus also may injure the AV node or distal conduction
system. For all surgery at all ages, this incidence is 1 percent
to 2 percent6 but may well be higher in patients operated
during the first year of life. Patients with endocardial cushion
defects (AV canal defects) are at even higher risk, as are those
who have enlargement of their VSD as part of certain complex
repairs.
Postoperative AV block may also be seen following repair
of simple defects in the atrium, such as secundum atrial septal
defects, but in these situations, it is likely that it is the compact
AV node which is damaged, rather than the distal conduction
system. Postoperative AV block often resolves spontaneously
within several days of surgery and such resolution may allow
one to avoid placing of the pacemaker,7 even though some
843
11
844
of them may require temporary pacing support. AV block

persisting beyond 14 days is a clear indication for permanent
pacing. This is related to the poor prognosis of such patients
and the potential for syncope and sudden death. It should
be noted here that the observation of a seemingly adequate
heart rate in the presence of postsurgical complete AV block
should not be seen as reassuring, as such escape rhythms
are notoriously unreliable, particularly those with a wide
QRS complex. Unlike SN dysfunction, advanced AV block,
especially with a wide QRS escape is potentially fatal.
Congenital Atrioventricular Block

Patients are considered to have congenital complete AV
block, if AV block is present at birth or develops during the
first year of life. Anatomical disruption between the atrial
musculature and peripheral parts of the conduction system and
nodoventricular discontinuity are two common histological
findings. Most cases of complete congenital AV block are
related to maternal mixed connective tissue disease and/or
systemic lupus erythematosus.8,9 Mothers of affected infants
have abnormally high titers of antibodies to the factors SS-A
and SS-B (anti-Ro and anti-La). A second group of infants
have congenital heart disease, especially l-transposition of the
great vessels (congenitally corrected transposition). Finally,
there is a large group in whom the disease is idiopathic, some
of whom may carry the NKX2.5 mutation.10
Mortality from congenital AV block is highest in the
neonatal period, is much lower during childhood and
adolescence, and increases slowly later in life. Stokes-Adams
attacks can occur in patients with congenital heart block at
any age. It is difficult to predict the prognosis in an individual
patient. A persistent heart rate at rest of 50 beats/minute or
less correlates with the incidence of syncope and extreme
bradycardia can contribute to the frequency of Stokes-Adams
attacks. The site of block may not distinguish symptomatic
children, who have congenital or surgically-induced complete
heart block from those without symptoms. Prolonged
recovery times of escape foci following rapid pacing and slow
heart rates on 24-hour ECG recordings and the occurrence of
paroxysmal tachycardias may be predisposing factors to the
development of symptoms.
Infants born to mothers with antinuclear antibody
positivity may progress from second degree to complete
AV block during infancy. Some infants with complete
congenital AV block will present in utero with hydrops
fetalis. If they are born alive, pacing is clearly indicated.
Others may present with symptoms related to low heart
rates, such as syncope, near-syncope or documented exercise
intolerance. Children with congenital complete heart block,
who are symptomatic should receive permanent pacemaker
implantation. Indications for pacing and recommendations of
timing of pacing are difficult for those children who are totally
asymptomatic. One school of thought is to implant permanent
pacemaker for all, but a consensus is not yet there and many
believe this is unnecessary. In real world scenario, large
prospective randomised studies in children with congenital
AV block to assess the unintervened natural history may
not be possible because of multitude of reasons. Hence, the
recommendations are often supported only by evidence from
retrospective observations. It is interesting to note that not a
single recommendation (Class IIII) in the current American
College of Cardiology (ACC)/American Heart Association
(AHA) guidelines for pacing in bradycardia is backed up by
level of evidence A.1 However, the older the patient, the more
reasonable this recommendation would be, due to the easier
and safer implant procedure in larger patients. Most (but not
all) clinicians agree that daytime rates > 50 bpm in children
older than 1 year or long ventricular pauses (defined recently
as at least twice the basic escape cycle length) are indications
for pacemaker implantation in asymptomatic individuals.
Atrioventricular Conduction Disturbances in LQTS

The congenital LQTS is a potentially lethal disease caused by
mutations in specific cardiac ion channels. LQTS is known to
cause 2 : 1 AV block in children when the refractory period
of the His-Purkinje system exceeds sinus cycle length. Rarely,
it can manifest as first-degree or second-degree AV blocks as
well (Figure 7). These episodes of transient AV dissociation
or pseudo-AV block are due to the oscillations in refractory
period of infrahisian conduction system that are often initiated
by atrial premature beat. A small subset of patients with LQTS
with 2 : 1 AV block clinically manifests in the fetal or neonatal
period and has been associated with a lethal prognosis. A
mortality rate greater than 50 percent in the first 6 months of life
and up to 67 percent by age 2 years has been reported in some
series of patients with LQTS and 2 : 1 AV blocks. Suspicion
for and detection of LQTS in children presenting with AV
conduction disturbances in the immediate neonatal period
allow for close monitoring of high-risk infants. Shortening and
homogenization of refractoriness of His-Purkinje system with
AAI (atrium paced, atrium sensed and pacemaker inhibited in
response to sensed beat)pacing, potassium supplementation and
beta blockers or other genotype-specific drugs like mexilitene
often would be sufficient to prevent life-threatening torsades in
majority. In our experience, by this therapeutic approach, we
could manage even refractory cases with excellent long-term
follow up. The renewed interest in left cardiac sympathetic
denervation, which can be performed with minimally invasive
surgery, is increasingly offered to patients with refractory
torsades de pointes (TdP). However, smaller devices and
novel defibrillator configurations allow for implantation in
the neonatal period in a rare case which would not respond to
the above mentioned measures. The technical feasibility of an
epicardial system without incorporation of a large, restricting,
epicardial defibrillation patch permits implantation in infants
as small as 3.5 kg.
59
IndICatIonS For PaCIng

Recommendations for Permanent Pacing in Children,
Adolescents and Patients With Congenital Heart Disease
ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy
of Cardiac Rhythm Abnormalities: Executive Summary: A
Report of the American College of Cardiology/American
Heart Association Task Force on Practice Guidelines.
Class I
1. Permanent pacemaker implantation is indicated for
advanced second- or third-degree AV block associated with
symptomatic bradycardia, ventricular dysfunction or low
cardiac output (Level of Evidence: C).
2. Permanent pacemaker implantation is indicated for sinus
node dysfunction (SND) with correlation of symptoms
during age-inappropriate bradycardia. The definition of
bradycardia varies with the patients age and expected
heart rate (Level of Evidence: B).
postoperative advanced second- or third-degree AV block
that is not expected to resolve or that persists at least 7 days
after cardiac surgery (Level of Evidence: B).
congenital third-degree AV block with a wide QRS
escape rhythm, complex ventricular ectopy or ventricular
dysfunction (Level of Evidence: B).
congenital third-degree AV block in the infant with a
Figure 7: Atrioventricular conduction disturbances in Long QT syndrome. P waves intermittently

fail to conduct to ventricle. This happens, when the recovery period of the His-Purkinje system
exceeds the PP interval. Only the P waves falling well after T wave conduct normally and this
gives a clue to the functional nature of the conduction. Note the prolonged QT at baseline and the
changes in T wave morphology. High rate AAI pacing and optimal beta-blocker therapy resulted in
shortening and homogenization of QT in this case
ventricular rate less than 55 bpm or with CHD and a

ventricular rate less than 70 bpm (Level of Evidence: C).
Class IIa
1. Permanent pacemaker implantation is reasonable for
patients with CHD and sinus bradycardia for the prevention
of recurrent episodes of intra-atrial re-entrant tachycardia;
SND may be intrinsic or secondary to antiarrhythmic
treatment (Level of Evidence: C).
congenital third-degree AV block beyond the first year of
life with an average heart rate less than 50 bpm, abrupt
pauses in ventricular rate that are 2 or 3 times the basic cycle
length or associated with symptoms due to chronotropic
incompetence (Level of Evidence: B).
3. Permanent pacemaker implantation is reasonable for sinus
bradycardia with complex CHD with a resting heart rate
less than 40 bpm or pauses in ventricular rate longer than 3
seconds (Level of Evidence: C).
patients with CHD and impaired hemodynamics due
to sinus bradycardia or loss of AV synchrony (Level of
Evidence: C).
unexplained syncope in the patient with prior congenital
heart surgery complicated by transient complete heart
block with residual fascicular block after a careful
evaluation to exclude other causes of syncope (Level of
Evidence: B).
845
11
Class IIb
1. Permanent pacemaker implantation may be considered for
transient postoperative third-degree AV block that reverts
to sinus rhythm with residual bifascicular block (Level of
Evidence: C).
2. Permanent pacemaker implantation may be considered for
congenital third-degree AV block in asymptomatic children or
adolescents with an acceptable rate, a narrow QRS complex
and normal ventricular function (Level of Evidence: B).
3. Permanent pacemaker implantation may be considered
for asymptomatic sinus bradycardia after biventricular
repair of CHD with a resting heart rate less than 40 bpm or
pauses in ventricular rate longer than 3 seconds (Level of
Evidence: C).
Class III
1. Permanent pacemaker implantation is not indicated for
transient postoperative AV block with return of normal AV
conduction in the otherwise asymptomatic patient (Level of
Evidence: B).
asymptomatic bifascicular block with or without firstdegree AV block after surgery for CHD in the absence of
prior transient complete AV block (Level of Evidence: C).
asymptomatic type I second-degree AV block (Level of
Evidence: C).
asymptomatic sinus bradycardia with the longest relative
risk interval less than 3 seconds and a minimum heart rate
more than 40 bpm (Level of Evidence: C).
ConCluSIon
The presence of bradyarrhythmia in children requires special
care as symptoms are minimal. The transient, functional
abnormalities has to be differentiated from primary disease
of the conduction system. The confounding factors related to
associated structural heart disease, also need to be addressed.
Decision to pace needs consideration of issues like selection of
846
optimal pacemaker, limited venous access, and the anticipated

problems in long-term follow-up.
Medicine knows no limits, especially not its own.
Kocher, Gerhard
rEFErEnCES
1. Epstein AE, Dimarco JP, Ellenbogen KA, et al. 2012 ACCF/
AHA/HRS Focused Update Incorporated Into the ACCF/
AHA/HRS 2008 Guidelines for Device-Based Therapy of
Cardiac Rhythm Abnormalities: A Report of the American
College of Cardiology Foundation/American Heart
Association Task Force on Practice Guidelines and the
Heart Rhythm Society. Circulation. 2013 Jan 22;127:e283352.
2. Lewis AB, Lindesmith GG, Takahashi M, et al. Cardiac rhythm
following the Mustard procedure for transposition of the great
vessels. J Thorac Cardiovasc Surgery. 1977;73:919-26.
3. Bharati S, Molthan ME, Veasy LG, et al. Conduction system
in two cases of sudden death two years after the Mustard
procedure. J Thorac Cardiovasc Surgery. 1979;77:101-8.
4. Kalman JM, VanHare GF, Olgin JE, et al. Ablation ofincisional
reentrant atrial tachycardia complicating surgery for congenital
heart disease. Use of entrainment to define a critical isthmus of
conduction. Circulation. 1996;93:502-12.
5. Anderson RH, Wilcox BR. The surgical anatomy of ventricular
septal defect. J Card Surgery. 1992;7:17-35.
6. Bonatti V, Agnetti A, Squarcia U. Early and late postoperative
complete heart block in pediatric patients submitted to openheart surgery for congenital heart disease. Pediatr Med Chir.
1998;20:181-86.
7. Vetter VL, Horowitz LN. Electrophysiologic residua and
sequelae of surgery for congenital heart defects. Am J Cardiol.
1982;50:588-604.
8. Chameides L, Truex RC, Vetter V, et al. Association of maternal
systemic lupus erythematosus with congenital complete heart
block. N Engl J Med. 1977;297:1204-7.
9. Litsey SE, Noonan JA, OConnor WN, et al. Maternal
connective tissue disease and congenital heart block.
Demonstration of immunoglobulin in cardiac tissue. N Engl J
Med. 1985;312:98-100.
10. Benson DW, Silberbach GM, Kavanaugh-McHugh A, et al.
Mutations in the cardiac transcription factor NKX2.5 affect
diverse cardiac developmental pathways. J Clin Invest.
1999;104:1567-73.
C hapter
60
Tachyarrhythmias
Sathish S
EpidEmiology
Arrhythmias occur less commonly in childhood, constituting
5 percent of the emergency admissions in the pediatric
population.1 Majority of these tend to be accessory pathway
mediated supraventricular tachyarrhythmias such as WolffParkinson-White (WPW) syndrome.2 The non-accessory
pathway mediated supraventricular tachyarrhythmias commonly
seen in children are atrioventricular nodal re-entry tachycardia
(AVNRT), junctional ectopic tachycardia (JET) and automatic
ectopic atrial tachycardia (AT). JET and AT occur mostly in
the postoperative period after intracardiac repair for a structural
heart defect. Ventricular tachycardia (VT) although uncommon,
occurs in the pediatric age group in association with hypertrophic
cardiomyopathy, long QT syndrome (LQTS) and Brugada
syndrome. Occasionally, VT can also present symptomatically
as incessant idiopathic infant VT, right ventricular outflow
tract (RVOT) tachycardia, catecholaminic VT, idiopathic left
ventricular tachycardia and in postcardiac surgical patient.
Supraventricular tachycardia (SVT) is the most common
rhythm disturbance in children. It is estimated to occur in as
many as 1 in 250 otherwise healthy children. Episodes are
often recurrent although rarely life threatening. Treatment of
this disorder has undergone a remarkable transformation in
the past quarter century with the advent of radiofrequency
ablation (RFA). Although, SVT accounts for a small proportion
of children treated in an outpatient setting, the prevalence is
high enough that most general pediatric practitioners will at
some point, care for a patient with this disorder.
In the normal heart, the atrial and ventricular myocardium
are electrically insulated from one another except at the
atrioventricular (AV) node and bundle of His. Impulse
generation typically originates in the sinus node and the
impulse is conducted through the atrial myocardium to the AV
node. The major role of this structure is to allow conduction
of the impulse to the ventricle; however, equally important is
the inherent delay in the AV node that slows conduction from
the atrium to the ventricle, allowing ventricular filling. From
the AV node, there is rapid conduction via the specialized HisPurkinje system with associated right and left bundle branches
that intercalate to the ventricular myocardium.
mEChanism of TaChyCardia
re-entry
Re-entry is a depolarizing wave traveling through a closed
path.
There are three prerequisites for re-entry:
1. At least two pathways: Slow and fast AV nodal pathways,
accessory pathway or the presence of barrier (anatomic:
tricuspid valve; pathologic: incisional scars, myocardial
infarction and functional scar).3
2. Unidirectional block: This block can be physiological,
caused by a premature complex or increased heart rate or
pathological, caused by changes in repolarization gradients.
3. Slow conduction to prevent collision of the head and the
tail of the depolarizing wave: Physiologic caused by AV
nodal slow pathway in AVNRT; cavotricuspid isthmus
in atrial flutter (AFL), slow conduction across the crista
terminalis in upper loop tachycardia; pathologicischemic
or remodeled cells in atrium and ventricle (ventricular
tachycardia, atrial flutter).
In functional re-entry, unidirectional block can be due to
dispersion of refractoriness (repolarization) or dispersion
of conduction velocity (anisotropic re-entry).The former
can be caused by repolarization gradients due to spatial
heterogenicity of repolarization (ischemia, drugs), discordant
repolarization alternans (T-wave alternans during ischemia,
autonomic abnormalities) and transmural gradients from cellto-cell uncoupling (drugs, heart failure).
Triggered activity
Triggered activities are caused by after depolarization
currents. They are classified as early after depolarisation
11
(EAD), occuring inside the action potential (phase 2 and 3)

and delayed after depolarisation (DAD) occuring in phase 4 of
the action potential.4 These currents can in turn be responsible
for both focal and reentrant arrhythmias. The former is caused
by eliciting an excitatory response exceeding the activation
threshold and the latter can develop when these currents
cause prolongation in action potential, which facilitates the
development of a unidirectional block due to dispersion of
refractoriness.
automaticity
Automaticity is driven by spontaneous phase 4 depolarization.
Automatic depolarizations in the atria and ventricles are not
manifested normally due to overdrive suppression by the faster
depolarization caused by the sinoatrial node. However, during
excess catecholaminergic states, phase 4 depolarization may
exceed sinus node depolarization, causing depolarization to be
driven by the abnormal tissue.Ventricular tachycardias during
the acute ischemic and reperfusion phases are good examples
of automaticity. They often originate from the border zone
between normal and ischemic cells.
supraventricular Tachycardia
Supraventricular tachycardia is broadly defined as a narrow,
complex tachycardia that requires atrial tissue or the AV
node as an integral part of the arrhythmia substrate, with the
exceptions of SVT in presence of existing or functional bundle
branch block, antidromic atrioventricular reentry tachycardia
(AVRT), atrial fibrillation (AF) with bystander pathway
conduction which are broad complex tachycardias. The
majority (90%) of the clinically important SVTs in otherwise
healthy children are caused by the presence of an additional
(or accessory) electrical connection between the atrium and
ventricle (i.e. the bundle of Kent) or within the AV node itself.
inCidEnCE
848
The true incidence of SVT in children is unknown, but

has been estimated to be 1 in 250 to 1 in 1000 children.5
Approximately, 50 percent of children with SVT will present
with their first episode in the first year of life. After infancy,
the incidence peaks in early childhood (ages 69 years) and
then again in adolescence.6 In infants, spontaneous resolution
occurs in more than 90 percent by 1 year of age. After a
period of quiescence, upto one-third will have recurrence of
SVT at a mean age of 8 years. Only a small minority (15%)
of patients who are diagnosed after 1 year of age will have
spontaneous resolution. Supraventricular tachycardia due
to concealed or manifest accessory pathways, predominates
throughout childhood and adolescence, whereas the relative
proportion of patients with AVNRT tends to increase with age.
Most individuals with SVT have a structurally normal heart.
However, the prevalence of structural congenital heart disease

in patients with SVT has been estimated at 9 to 32 percent,
which is substantially higher than in the general population.
The most common association is noted between WPW
syndrome and the Ebstein anomaly of the tricuspid valve, but
a number of defects have been found, including ventricular
septal defects (VSDs) or atrial septal defects (ASDs), among
others.
EValUaTion
history
The clinical presentation of SVT is age and duration dependent.
In infants with paroxysmal SVT, the heart rate is usually 220
to 320 beats/minute; in older children, it is 160 to 280 beats/
minute. In infants, symptoms are usually nonspecific and
include poor feeding, irritability, vomiting, cyanosis and pallid
spells. If the symptoms are unrecognized for hours to days, the
infant can present with significant hemodynamic compromise
or heart failure symptoms.7 It is rare for infants who have SVT
for less than 24 hours to develop signs of congestive heart
failure at the time of presentation; however, congestive heart
failure is present in 19 percent of infants who have SVT for
24 to 36 hours and in 50 percent who have SVT for more
than 48 hours.8 Approximately, 20 percent of infants receive
a diagnosis during routine. In verbal children with SVT,
palpitations and fluttering in the chest are the usual presenting
symptoms.9 Because re-entrant arrhythmias are a circuit, they
tend to be all or nothing and the onset is frequently described
as being abrupt, similar to a light switch being turned on.
The offset may be less dramatic because the catecholamine
level is typically elevated, with resultant sinus tachycardia
at the termination of SVT and subsequent gradual slowing.
Frequently, lightheadedness and dizziness due to transient
hypotension can occur at the onset, but syncope is rare in SVT
and its presence should raise suspicion of something other
than SVT. The frequency and duration of the episodes vary
greatly from a few minutes to a few hours and occur as often
as daily or as infrequently as once or twice per year. Although,
rare in verbal children, incessant SVT symptoms may go
unrecognized until cardiac dysfunction develops.
diagnosis
Recording a heart rhythm strip during symptoms remains the
key to correct diagnosis and management. Options for this
include 24-hour ambulatory monitoring, event recorders and
electrocardiograms (ECGs). Each of these means of obtaining
a recording have associated advantages and disadvantages.
The Holter monitor provides a continuous multichannel
recording that usually allows the interpreter to see the whole
episode, including onset and termination. Most patients,
however, do not have daily symptoms, making the Holter
management
Acute Management
Acute management of regular narrow QRS (<90 ms or
<0.09 s) nodal dependent (AVRT and AVNRT) tachycardias
depends on how well the tachycardia is tolerated, presence
of underlying heart disease and the response to therapy
previously. If hemodynamically unstable, synchronized
cardioversion is done at 1 to 2 Joules/kg with pediatric paddles,
if weight is less than 15 kg. Vagal maneuvers, including
carotid sinus message, Valsalva and Muller maneuvers,
gagging and in case of infants exposing the face to ice cold
water is helpful in hemodynamically stable patients. Acute
management of AVNRT and orthodromic atrioventricular
reentry tachycardia (OAVRT) is the same, except in case of
AF with accessory pathway conduction and in antidromic
AVRT; drugs which prolong refractory period of pathway
is given along with AV node blocking drugs. Digoxin and
calcium channel blockers (CCB), which shorten the refractory
period are to be avoided. If vagal maneuvers fail, adenosine
is the initial drug of choice given at 0.1 mg/kg, 0.2 mg/kg
and 0.3 mg/kg at 5 minutes intervals, if hemodynamically

stable and no response. Up to 90 to 95 percent of AVNRT
and AVRT respond and 30 to 35 percent of atrial tachycardias
respond to this therapy. In patients with AT, by blocking
AV node, AT is uncovered AT as the cause of tachycardia,
however automatic AT may terminate with adenosine
(Figure 1). Verapamil (0.10.3 mg/kg over 2 minutes,
may be repeated after 15 minutes with a maximum dose
5 mg first and 10 mg second dose) and diltiazem are effective
in terminating AV node-dependent tachycardias in 90 percent
of cases. Verapamil should not to be used in children < 1 year,
because it causes profound hypotension. Amiodarone (5 mg/
kg) and procainamide (15 mg/kg) can be infused slowly over
30 to 60 minutes with careful ECG and pressure monitoring
in stable patients not responding to above maneuvers.
60
tachyarrhythmias
monitor typically impractical in the evaluation of SVT. Event

recorders are often the optimal solution for patients who have
symptoms more than once per month. Patients can wear the
monitor (loop recorder) or carry it with them (event monitor).
In both cases, patients activate the recording device during
symptoms. The advantage of the loop recorder is that the
recording encompasses the time before, during and after the
monitor activation. Finally, for infrequent episodes lasting
longer than 10 minutes, patients can often be referred to the
local emergency department for acute monitoring.
Long-term Management
The management of SVT has many variables that need to
be considered, including the age of the patient, the duration
and frequency of the episodes and the presence of ventricular
dysfunction. For children with rare and mildly symptomatic
episodes in whom SVT is easily terminated, the SVT may
not merit treatment. For children with episodes that are
difficult to terminate, occur frequently or occur during athletic
participation, it may be advisable to offer medical therapy or
transcatheter ablation as therapeutic options. Infants with SVT
deserve special recognition in regard to treatment options.
Most infants will undergo spontaneous resolution of SVT.
When this is combined with the increased risk of transcatheter
ablation in this age group, medical management is preferred;
ablation is preferred in presence of tachycardiomyopathy, or
aborted sudden cardiac death (SCD).
Figure 1: Responses of narrow complex tachycardias to adenosine.10 AT = Atrial tachycardia; atrial tachycardia; AV =
Atrioventricular; AVNRT = Atrioventricular nodal reciprocating tachycardia; AVRT = Atrioventricular reciprocating tachycardia;
IV = Intravenous; QRS = Ventricular activation on ECG; VT = Ventricular tachycardia
849
11
850
medical Therapy
Optimal medical management (in terms of whom to treat, with
which medication and for how long) of SVT in infants and
children has not been well studied and most current clinical
practices are extrapolated from small studies of adults and
uncontrolled pediatric studies.11-13 The intended effect of antiarrhythmic medications is to slow conduction, preferentially
within one limb of the re-entrant circuit, thereby terminating
the tachycardia as the circulating wave front encounters
refractory tissue. Nearly, all classes of antiarrhythmic agents
have been used to treat SVT successfully. The approach to
antiarrhythmic therapy includes the daily prophylactic therapy
and the single-dose pill-in-the-pocket approach, whereby
medication is taken only during an acute episode. The pill-inthe-pocket approach requires an immediate-release medication
and is appropriate for patients who have infrequent episodes
that are prolonged, but well tolerated.14 In adults combination
of diltiazem (120 mg) and propronolol (80 mg) have had good
results compared to flecanaide. They need however to be
avoided in antidromic AVRT.
In most cases, first-line therapy is directed at modifying
the conduction properties of the AV node and includes
treatment with beta-blockers (propronolol 24 mg/kg, 24
doses, maximum 16 mg/kg, metoprolol 13 mg/kg), CCBs
(diltiazem 1.52 mg/kg/24 hours, maximum 3.5 mg/kg/24
hours, verapamil 48 mg/kg/24 hours, 3 divided doses) and
digoxin (810 mcg/kg in 2 divided doses, from birth to 10
years; greater than 10 years 125 mcg/d) except in WPW
syndrome, with antidromic tachycardia when use of CCBs
and digoxin should be avoided.15 With medical therapy, there
is a significant reduction in the number of episodes, although
complete suppression is rare.
Supraventricular tachycardia refractory to first-line
medications can often be controlled with more potent antiarrhythmic agents such as flecainide acetate (24 mg/kg,
tid), amiodarone (5 mg/kg/day), sotalol hydrochloride, procanamide (1550 mg/kg, qid) or drug combinations. Sodium
channel blockers such as flecainide are particularly effective
in controlling SVT, but these agents are generally avoided in
patients with structural or ischemic heart disease because of
the risk of proarrhythmia. Sotalol, an agent with betareceptor and potassium channel blocking properties, is
also quite effective, but can lead to QT prolongation and
proarrhythmia.16 Radiofrequency ablation is preferred in
children weighing more than 15 kgs, in view of good success
and similar complication incidents as in adults.17
In 2002, a position statement was published by members
of the Pediatric Electrophysiology Society and endorsed by
the North American Society of Pacing and Electrophysiology.
(Friedman RA NASPE). Class I indications, in which there
is clear and consistent agreement that RFA will benefit the
patient, included:
WPW following aborted sudden death
WPW and syncope with a shortest prexcited R-R lesser

than 250 ms
Chronic or recurrent SVT with ventricular dysfunction
Recurrent VT associated with hemodynamic compromise
and is amenable to RFA.
Class IIA indications, in which the majority are of the
opinion or data favors RFA, include
Recurrent and/or symptomatic SVT refractory to medical
therapy and age greater than 4 years
Impending congenital heart surgery when vascular or
chamber access may be limited following surgery
Chronic (greater than 6 months) or incessant tachycardia
with normal ventricular function
Chronic or frequent recurrences of intraatrial reentrant
tachycardia
Palpitations
with
inducible
SVT
during
an
electrophysiological study (EPS).
Class IIB indications, in which there is a clear divergence
of opinion regarding the need for RFA, include:
Asymptomatic WPW and age less than 5 years when the
risk/benefits of RFA have been explained to the family
SVT, age less than 5 years, as an alternative to chronic
medical therapy that has controlled the tachycardia
SVT, age less than 5 years,when medications, including
sotalol and amiodarone, have not controlled the tachycardia
or have resulted in intolerable side effects
Intra-atrial re-entrant tachycardia, 13 episodes per year
requiring medical intervention
AV node ablation for intra-atrial re-entrant tachycardia
One episode of VT with hemodynamic compromise and
amenable to RFA.
Class III indications, in which there is agreement that RFA
is not indicated, include:
Asymptomatic WPW, age less than 5 years
SVT, controlled with medication, age less than 5 years
Nonsustained and non incessant VT without ventricular
dysfunction
Nonsustained, asymptomatic SVT.
prognosis
In the absence of structural heart disease or cardiomyopathy, the
prognosis of SVT is believed to be excellent. WPW syndrome
deserves special consideration with respect to prognosis
owing to the small, but real risk of SCD associated with this
condition. The principal indicator of risk in adults with WPW
syndrome is the presence of symptoms (e.g. palpitations and
syncope). Symptomatic patients with WPW syndrome have
an estimated 3 to 4 percent lifetime risk (0.25% per year) of
SCD.18 In children and adolescents, however, asymptomatic
may be better termed as presymptomatic. It has been estimated
that 55 percent of asymptomatic children and adolescents will
become symptomatic by 40 years of age. For this reason, all the
60
tachyarrhythmias
children or adolescents in whom WPW syndrome is identified

on an ECG, regardless of the presence of symptoms, should
be referred to a pediatric electrophysiologist for evaluation.
Patients with WPW accessory pathways, who are defined
as low risk on the basis of EPS findings appear to be at no
increased risk of SCD compared with the general population.
aTrial arrhyThmias
Atrial arrhythmias include atrial tachycardia, atrial flutter and
atrial fibrillation. All have in common the feature that they do
not require participation of the AV node or the sinus node or the
ventricles for maintenance of tachycardia. Atrial tachycardia,
therefore is unaffected by AV block, either spontaneous or
adenosine induced. Atrial tachycardia definition also excludes
other types of atrial arrhythmia such as atrial fibrillation and
atrial flutter (macro re-entry).
The label focal AT has been used recently to describe atrial
arrhythmias that originate from a point source or localized
area of the atrium. Such arrhythmias have also been known
as atrial ectopic tachycardia and ectopic AT. The term focal
atrial tachycardia does not imply a mechanism, which may
be micro re-entry, automaticity or triggered activity, although
abnormal automaticity (as in atrial ectopic tachycardia) is the
most likely. The difference between AT and AFL is rate cutoff
of 240 to 250/minute and the presence of isoelectric baseline
in AT. This ECG classification has several limitations,
neither rate nor lack of isoelectric baseline is specific for
any tachycardia mechanism.19 Macro re-entry AT include AT
not using cavotricuspid isthmus as a part of circuit. Those
using cavotricuspid isthmus are called atrial flutter. Atrial
tachycardia is common at extremes of age constituting 15
percent of arrhythmias in pediatric population.
Atrial tachycardia can present in children as either
paroxysmal or incessant automatic AT. The anatomic
distribution is similar to adultsthe ostium of pulmonary
veins, crista from sinus node to coronary sinus, left and right
atrial appendage and less commonly along AV valve annuli.20
It is a common cause for tachycardiomyopathy in pediatric
age group.
Figure 2: Atrial tachycardia diagnosed after giving adenosine

revealing 2:1 conduction (arrows show P wave). Intially there was 1:1
conduction and there was difficulty in diagnosing the rhythm.
A negative P wave in lead I or aVL or a positive P wave in

lead V1, favors a left atrial origin, negative P waves in the
inferior leads are suggestive of a low atrial origin, whereas
a positive P wave in those leads suggest a high atrial origin.
Atrial tachycardia from the high crista terminalis or right
superior pulmonary vein may resemble sinus P wave, but for
the positive P wave in lead V1.
Electrocardiogram
management
In ATs, the P waves are in the second half of the tachycardia

cycle, hence obscured by the T wave of the preceding QRS
complex (Figure 2). The presence of AV block during tachycardia
excludes AVRT and makes AVNRT very unlikely. During ATs,
an isoelectric baseline is usually present between P waves and it
is used to distinguish AT from typical or atypical flutter (i.e. saw
toothed or sinusoidal P wave morphologies), however, it may not
hold true in congenital heart disease.The diagnosis of AT can be
established with certainty only by an electrophysiological study,
including mapping and entrainment.
P-wave morphology on the 12-lead surface ECG is useful
for the determination of the site of origin of the focal AT.21
Acute Treatment
Atrial tachycardias may rarely be terminated with vagal
maneuvers and a proportion of focal ATs will terminate with
administration of adenosine and the common response is AV
block, revealing atrial rate more than ventricular rate suggestive
of AT. Class Ia or class Ic drugs may suppress automaticity or
prolong action potential duration and hence, may be effective
for some patients with AT. Similarly, DC cardioversion
seldom terminates automatic ATs, but DC cardioversion may
be successful for those in whom the tachycardia mechanism
is micro re-entry or triggered automaticity and should be
851
11
considered for patients with drug-resistant arrhythmia.

The usual acute therapy for AT consists of intravenous beta
blockers or CCBs for either termination, which is rare or to
achieve rate control through AV block. Direct suppression of
the tachycardia focus may be achieved by use of class Ia and
Ic or class III (e.g. sotalol, amiodarone) agents. Intravenous
class Ia or Ic agents may be taken by patients without cardiac
failure, whereas intravenous amiodarone is preferred for those
with poor ventricular function.
Long-term Pharmacologic Therapy

The available studies pertaining to long-term pharmacologic
therapy are observational and there are problems in discerning
whether the tachycardias were carefully differentiated from
other mechanisms (i.e. AVRT or AVNRT) or from other forms
of ATs. Review of the available data supports a recommendation
for initial therapy with CCBs or beta blockers because these
agents may prove to be effective and have minimal side effects.
If these drugs are unsuccessful, then class Ia, class Ic (flecainide
and propafenone) in combination with an AV-nodal-blocking
agent or class III agents (sotalol and amiodarone) may be tried
because they may prove to be effective. The potential benefit
should be balanced by the potential risks of proarrhythmia and
toxicity.22,23 The infants less than three years are managed by
medical means in view of spontaneous resolution in around 70
percent after 3 years and limitations of RFA, in view of size of
child and complications.24 The preffered drug for arrhythmias
are amiodarone and sotalol. Children more than 3 years are
managed by RFA, in view of amenability to ablation and need
for long-term medical management.
Wolff-parkinson- WhiTE syndromE and

orThodromiC aVrT
852
By definition, WPW syndrome means pre-excitation on

ECG with tachycardia, either orthodromic, commonest of
the two where the pathway conducts retrogradely or antidromic tachycardia, the pathway conducts antegradely. The
presentation may be in fetal life with tachycardia, requiring
fetal auscultation or ultrasonography and confirmation of
the tachycardia rate by combination of M-mode, Doppler
and two dimensional echocardiography. These patients may
present with hydrops fetalis, requiring aggressive treatment.
Medications used include digoxin; beta-blockers; CCBs and
classes I and III antiarrhythmics, either alone or in combination.
Variations in transplacental transport of medications complicate
treatment of the fetus, coupled with side effects in the mother,
who must be monitored closely for proarrhythmic effects such
as those seen with the class I and III agents. If the fetus does
not respond to medications in a timely manner and hydrops
persists, premature delivery may be required.
Among neonates having WPW syndrome, approximately
25 to 35 percent will experience disappearance of delta wave,
often by one year of age. After neonatal presentation of

tachyarrhythmia, there is second peaking at 8 years of age.This
may be related to functional changes in conduction properties,
cardiac dimension changes, maturation of autonomic nervous
system and increased physical activity. Those having neonatal
presentation, have recurrence of arrhythmia in 1/3 of cases,
but those presenting late have less chance of spontaneous
resolution.
Natural history studies are limited. In a study of 184
asymptomatic children, 38 percent developed tachyarrhythmia
in next 2 years, 30 percent of them were life threatening.25 The
electrophysiological characterstics of these were antegrade
refractory period < 240 ms, presence of multiple pathways
and inducibility of tachyarrhythmia. The risk of catastrophic
events increased in presence of digoxin, caused by heightened
adrenergic status.It is recommended that those children more
than 5 years of age with asymptomatic pre-excitation required
to participate in competitive sport, needs the assessment
of antegrade refractory period of pathway by looking for
intermittent pre-excitation on ECG, Holter and disappearance
of pre-excitation with treadmill test indicating poor antegrade
conduction over pathway and low risk of SCD. If non-invasive
studies suggest good antegrade conduction over the pathway,
they may require invasive EPS for risk stratification and RFA,
if needed.25,26
mechanism of Tachycardia
The accessory pathway permits either only antegrade or
retrograde or bidirectional conduction from the atria to the
ventricle. An early atrial extrasystole is conducted slowly
down the AV node to the HisPurkinje system and ventricle; it
returns to the atrium over the accessory pathway and then into
ventricle if AV node has recovered and is no longer refractory,
then a circus movement tachycardia, also known as re-entry
tachycardia or reciprocating tachycardia, can be established,
termed as OAVRT and antidromic AVRT if circuit is other way
around. A ventricular extrasystole can also trigger tachycardia
in this situation, via retrograde conduction up the accessory
pathway into the atrium, with the retrograde P wave then
being conducted anterograde across the AV node. Following
ventricular depolarization, there is conduction back up of the
accessory pathway and the tachycardia is initiated.25
Electrocardiogram
The baseline ECG may show delta wave if antegrade conduction
occurs over the pathway, the degree of pre-excitation depends
on how fast the pathway or the node conducts, septal and
right-sided pathways show more pre-excitation as the sinus
conduction reaches this site fast. The presence of intermittent
pre-excitation suggests weak antegrade conduction across the
pathway and low risk of sudden death. The ECG showing
different patterns of pre-excitation may indicate presence
inferior leads suggest inferior location of pathway, if positive

suggesting anterior location), ST depression in lateral leads
and ST elevation in aVR.29
management
Neonates and infants with tachycardia are often very sick,
presenting with congestive heart failure, in view of the infants
inability to communicate and the familys lack of awareness
that the child could have a significant medical condition and
long lasting tachycardia. Parents may note that the infant was
acting somewhat different than normal, more irritable or not
eating well, often interpreted as colic or some other normal
childhood problem. At presentation, these babies often
are acidotic from decreased cardiac output and may need
aggressive resuscitation including artificial ventilation and
rapid termination of the tachycardia. Intravenous adenosine
is effective in the acute termination of SVT in this population,
but intravenous access is often difficult in a 3 to 4 kg baby
in congestive heart failure. Transesophageal overdrive pacing
has proven very helpful. Once the rhythm is restored to normal
and the cardiac function has begun to recover, intravenous
access becomes easier and intravenous medications can be
employed.
Digoxin, a first-line medication used in the treatment of
SVT in infants with decreased myocardial performance,
is contraindicated in patients with WPW syndrome; Other
medications used acutely to treat SVT include intravenous
Figure 3: Regular narrow QRS short RP tachycardia with significant ST depression in lateral leads and elevation
in lead aVR and a subtle P wave immediately after QRS suggestive of orthodromic AVRT
60
tachyarrhythmias
of multiple pathways.There are different algorithms for

localization of the pathway with varing sensitivity and
specificity, based on initial 20 to 60 ms of delta wave or the
morphology or polarity of entire QRS complex.27,28 All left
free wall pathways show positive delta in V1, with R greater
than S in V1 or V2 at the latest. A negative delta wave in lead
I, aVL or V6 is suggestive of left free wall pathway. As the
pathway moves from posterior to lateral and more anterior,
the delta waves in inferior leads III and aVF, change from
negative to isoelectric to positive. A positive delta wave in V1,
with R greater than S, suggests left-sided pathway and if R
lesser than S suggests either right free wall or minimally preexcited left-sided pathway. A negative delta in V1 suggests
septal pathway. Right-sided pathways are recognised by small
R in V1, late transition at V3 or more and a positive delta
wave in lead I and aVL. As the pathway moves from right
superior to lateral and inferior location, delta wave in III and
aVF changes from positive to isoelectric to negative. The
tachycardia ECG may show regular narrow QRS tachycardia
if antegrade conduction occurs over the AV node, orthodromic
AVRT (Figure 3) and regular broad complex tachycardia if
antegrade conduction occurs over the pathway, producing
antidromic AVRT. Irregular broad complex tachycardia
occurs in AF with antegrade conduction over the pathway.
The ECG signs to suggest OAVRT are the presence of distinct
P wave in short RP tachycardia (the morphology of retrograde
P depends on the site of pathway, positive in V1 or lead I
suggests right- sided pathway, negative P wave in all the three
853
11
beta-blockers such as intravenous esmolol, procainamide and

amiodarone. These medications must be used with caution
because of their negative inotropic effects, which can lead to
worsening of cardiac function. The use of intravenous CCBs is
contraindicated in infants as there have been reports of sudden
death.30 The long-term treatment of infants with AVRT includes
the use of oral preparations of the medications. In patients with
good antegrade conduction over the pathway and antidromic
tachycardia, drug therapy should include class III and Ic group
of drugs.31,32 However, beta blockers and CCB can be used
in case of orthodromic AVRT. Radiofrequency ablation to be
considered in patients with drug refractory arrhythmias, aborted
SCD, antegrade refractory period less than 220 ms. In view of
improving success of RFA and less complications in pediatric
patients more than 15 kg, RFA is used more liberally. Families
can assess their children for recurrent SVT without the need
for continuous monitoring. Most infants are treated with oral
medications for 10 to 12 months, with the dosage adjusted based
on their weight. At 10 months to 1 year of age, if there have been
no recurrences of the SVT, the patient will be weaned from the
medication unless WPW syndrome is still present on the ECG.33
Approximately, one-third of all patients who develop SVT in the
first 3 months of life will outgrow it by 1 year of age.
aTrioVEnTriCUlar nodal rE-EnTranT TaChyCardia

Atrioventricular nodal re-entrant tachycardia is uncommon
during infancy accounting only for 4 percent of the arrhythmias.
The incidence of this is about 23 percent in the 1 to 5 age group,
34 percent in the 6 to 10 age group and 20 percent in those over
10 years of age. Most of these do not resolve spontaneously and
will require RFA.
mechanism
Presence of two distinct group of AV nodal cells with
different refractory properties, forming the re-entry circuit
(dual AV nodal physiology).34 One of these pathways has a
long refractory period and fast conduction, while the second
pathway has a shorter refractory period with slow conduction.
The classic finding on an ECG is a tachycardia in which
there is very short R to P interval on the ECG or absence of
P-wave (P wave may be buried in QRS). This is secondary to
the fact that the retrograde limb of the pathway conducts very
rapidly from the ventricle to the atrium (Figure 4). AVNRT
is classified into two types, based on which of the two limbs
are used for antegrade and retrograde conduction. In the
common type called slow fast AVNRT, antegrade limb is the
slow pathway and retrograde limb is the fast pathway. In the
uncommon type, fast-slow AVNRT, it is vice versa.35
854
Figure 4: Explaining the mechanism of typical slow fast AVNRT. The

atrial premature contraction (APC) is blocked in the fast pathway, due
to the long refractory period, and conducts through the slow pathway.
Once the fast pathway recovers, the impulse from the slow pathway
conducts retrogradely through the fast pathway producing echo beat.
It this impulse continues through the slow pathway it produces slow
fast AVNRT.
procanamide and amiodarone are preferred. For long-term

management, beta-blockers, CCBs are preferred. With the
improvement in the success of RFA in drug refractory cases
and with the use of cryotherapy, with which the incidence of
AV block can be reduced, the proportion of pediatric patients
treated with RFA is increasing. The target for ablation is the
slow pathway area at the posterior part of Kochs triangle
(Figure 5).36
Three different arrhythmias require consideration in
pediatrics in view of common prevalence in this age grouppersistent junctional reciprocating tachycardia (PJRT), JET
and incessant ectopic atrial tachycardia.
pErsisTEnT JUnCTional rECiproCaTing

TaChyCardia
The PJRT is an accessory pathway at the posteroseptal location
with only retrograde conduction and showing properties
of AV node like decremental conduction, responding to AV
nodal blocking drugs unlike other pathways. The tachycardia
has slower heart rate, in view of slower and decremental
conduction properties. The tachycardia being incessant and
at slower heart rate may be asymptomatic and present with
tachycardiomyopathy.37
management
Electrocardiogram
In acute management intravenous adenosine or metoprolol

can be used. In drug refractory cases intravenous
The mechanism of the tachycardia accounts for the ECG

appearances. The QRS is normal for age and P waves are
management
tachyarrhythmias
Management of PJRT is influenced by the age and clinical

condition of the child at presentation. Antiarrhythmic drug
treatment is almost always used in infancy. If the function of
the left ventricle is significantly impaired, the drug of choice
is probably amiodarone. If ventricular function is satisfactory,
flecainide or propafenone will usually prove effective. Success
is also reported with oral verapamil, although beta-blockers
and digoxin are less effective. The aim of drug treatment is
suppression of the PJRT, although intermittent tachycardia at
low rates on Holter monitoring is acceptable. Once control or
suppression of tachycardia has been achieved, the ventricular
function will improve and usually return to normal. Spontaneous
resolution of PJRT is uncommon. In most, this is a long-term
problem requiring catheter ablation, with good results.38
60
JUnCTional ECTopiC TaChyCardia
Figure 5: Showing anatomy of Kochs triangle and location of fast and

slow pathway. Slow pathway is the target for radio frequency ablation
in AVNRT
clearly seen with a 1 : 1 AV relationship. The pathway conducts

slowly retrogradely hence, the P wave is much closer to the
following QRS, so this is a type of long RP tachycardia. The
P waves are characteristically deeply inverted in leads II, III,
and aVF and V4 to V6 because the atria are activated first in
the low right atrium (Figure 6).
Commonly seen in the postoperative setting and sometimes

congenital. It is caused by abnormal automaticity around
AV node.39,40 The two differ with respect to duration and
response to therapy.The postoperative form associated with
repair of VSD alone or in combination with complex heart
surgeries, is usually transient (14 days) and responds well to
intravenous amiodarone and cooling. In contrast, congenital
JET not associated with congenital heart diseases, is incessant,
associated with strong family history, may spontaneously
resolve over period of months to years. The propensity to
resolve spontaneously, response to amiodarone and the
risk of AV block in ablations around AV junction has led to
855
Figure 6: Long RP tachycardia with inverted P wave in inferior and lateral leads
11
medical management, being the first choice. If unsuccessful,

ablation of JET can be attempted in the region of fast pathway,
preferably with cryoablation.41
Electrocardiogram
The ECG findings in JET shows tachycardia with a ventricular
rate that is faster than the atrial rate or both equal, if there
is 1 : 1 VA conduction, with a narrow QRS complex similar
to that seen in the patients normal sinus rhythm with rate of
180 to 240/min (Figure 7). Rarely, patients with JET develop
rate related aberrancy and some postoperative patients have
a bundle branch block that will lead to a wide complex
tachycardia. If there is a wide complex tachycardia, VT
must be ruled out by comparison to the QRS in normal sinus
rhythm or by pacing the atrium faster than the ventricular rate
to demonstrate wide complex conduction through the HisPurkinje system.
Treatment
Treatment strategies for the familial form of JET include using
digoxin to slow the rhythm and provide inotropic support.
Digoxin alone may not be sufficient to manage this arrhythmia
and the addition of a class la, class lc or class III antiarrhythmic
agent is required. The amount of antiarrhythmic medication
needed to control the rate to prevent decompensation of
cardiac function may suppress the sinus node sufficiently
to require a pacemaker temporarily. Patients with JET have
been treated with RFA.42 Because of the proximity of the AV
node and His-bundle to the area of enhanced automaticity
responsible for JET, RFA in this setting carries a high risk of
causing complete heart block. It is possible that over time the
junctional rate will slow to a point that the patient may be
weaned from medications.
In the postoperative setting, treatment involves use of
combination of medications along with surface cooling.43
Paired ventricular pacing to decrease the ventricular rate

has been used. intravenous amiodarone has been effective
in the treatment of these patients. In using intravenous
antiarrhythmics, one must be aware of the potential negative
inotropic effect of these medicines on the postoperative
patients heart. If the patient can be stabilized for a period of 48
to 72 hours, the rhythm disturbance will often spontaneously
revert to a normal sinus rhythm.
VEnTriCUlar arrhyThmias
Ventricular arrhythmias include premature ventricular
contractions (PVCs), couplets non-sustained ventricular
tachycardia (NSVT), sustained VT and ventricular fibrillation
(VF). The PVCs may be seen in 15 percent of normal
newborns, one-third of normal adolescents and two-third of
adolescents and adults with repaired congenital heart disease,
with difference in prognosis between PVCs in children with
normal and abnormal hearts.44
Evaluation
The evaluation should include a standard ECG for QTc interval
and 24-hour ambulatory monitor for the burden and complexity
of the ectopy and also for QTc measurment. In normal heart, less
than 20 percent ectopy usually does not interfere with cardiac
function, more than 30 percent ectopy may result in ventricular dysfunction over time. An echocardiogram to look for any
structural abnormalities, such as hypertrophic cardiomyopathy
and abnormalities in cardiac function that might accompany
myocarditis or dilated cardiomyopathy. Rarely, cardiac tumors
such as rhabdomyomas are identified. Magnetic resonance
imaging may be indicated if right ventricular dysplasia is suspected, based on ventricular ectopy having left bundle branch
block pattern and superior axis, basal ECG showing features
of arrhythmogenic right ventricular dysplasia (ARVD) and in
presence of family history. Generally, suppression of PVCs during exercise is a positive finding, development of bidirectional/
polymorphic VT may be suggestive of catecholamine induced
VT (CPVT). Prolongation of the corrected QT interval, especially in the recovery phase, may be seen in patients with long
QT syndrome. The EPS would rarely be indicated unless symptoms of syncope suggesting more complex arrhythmias or the
PVCs are associated with conditions that might predispose the
patient to VT or VF.
prognosis
856
Figure 7: Congenital JET diagnosed in a child of 3 years after giving

amiodarone infusion, revealing the onset of tachycardia by a junctional
beat
The PVCs and VT disappear over time in 37 to 65 percent of

patients with normal hearts. Sudden death is rare in normal
children with PVCs but has been reported.45 In children
with abnormal hearts, PVCs may be precursors of more
serious arrhythmias, especially if they are complex-multiform,
coupled or associated with VT.
Clinical signs and symptoms
Treatment
The PVCs in structurally normal heart and lesser than 20
percent ectopy burden does not require any intervention,
unless they are frequent enough to interfere with the cardiac
output, are closely coupled or frequently fall on the T wave in
a patient judged to be vulnerable to such occurrences (LQTS).
The PVCs associated with heart disease such as myocarditis,
cardiomyopathy or congenital heart disease may require
further investigation and treatment, especially if they are
frequent or occur in runs resulting in hemodynamic instability.
VEnTriCUlar TaChyCardia
Ventricular arrhythmias are less common than supraventricular
arrhythmias, occurring in both acute and chronic situations
in children. There is an increase in VT in patients after
congenital heart surgery, involving scarring of ventricles and
survival after complex surgery. The etiology of VT being the
congenital LQTS, hypertrophic and dilated cardiomyopathies,
ARVD, myocarditis, abnormal foci or circuits in structurally
normal hearts or idiopathic etiologies.
Electrocardiographic manifestations
The electrocardiographic diagnosis of VT is made most easily
in the presence of a wide QRS tachycardia with AV dissociation.
Many children have ventriculoatrial (VA) conduction with
relatively rapid 1 : 1 retrograde VA conduction, and AV
dissociation may not occur. The differential diagnosis of broad
complex tachycardia is SVT in the presence of existing or
fuctional bundle branch block, antidromic AVRT, AFIB with
bystander pathway conduction which are broad complex
tachycardias. It must be remembered that the normal QRS
duration in infants and young children is 40 to 80 ms, so a
wide QRS in an infant might only be > 80 ms. The rates of
VT in pediatrics vary from 120 to 300 bpm. The presence of
PVCs during sinus rhythm with the same configuration as VT
is a suggestive sign. AV dissociation is suggestive of VT, but
1 : 1 VA conduction is common, especially in young children.
Fusion beats are commonly noted at the onset or termination
of the VT. VT may be sustained (greater than 30 consecutive
complexes) or nonsustained (330 consecutive complexes).
Further, differentiation is made according to the morphology,
with VT being described as monomorphic or polymorphic.The
monomorphic VT classified as LBB or RBB morphology based
on predominant polarity in lead V1. Two types of polymorphic
Clinical signs and symptoms

The type and degree of symptoms appear to be rate related
and the underlying cardiac function, with symptoms most
common in patients with rates greater than 150 bpm and
cardiac dysfunction. Patients with VT have symptoms similar
to those with SVT.
60
tachyarrhythmias
Children under 5 years of age with PVCs are frequently

asymptomatic and unaware of their arrhythmias. Older
children may complain of a skipped or hard beat or a fluttering
in their chest, while some perceive PVCs as painful.
VT have been described, torsades de pointes and bidirectional

VT. Bidirectional VT shows beat-to-beat variation in the
QRS axis and is associated with digoxin toxicity, familial
hyperkalemic paralysis or catecholamine sensitivity.46
long QT syndromE
The congenital LQTS is an inherited condition characterized
by syncope, seizures and sudden death, associated in most
individuals with a prolongation of the QT interval on the ECG.
In addition to the prolongation of the QTc, these patients often
have bizarre or notched T wave morphology with prominent
U waves or T wave alternans. They develop life-threatening
VT, known as torsades de pointes or VF. This syndrome
includes the Jervell and Lange-Nielson syndrome, associated
with congenital deafness and thought to demonstrate an
autosomal recessive inheritance and the Romano-Ward
syndrome demonstrating autosomal dominant inheritance,
without hearing deficit.47
prevalence and presentation

The data from the new born from Italy demonstrate that,
among whites, the prevalence of LQTS is at least 1 : 2534
apparently healthy live births.48 In 1993, statistics from a
group of 287 children, the initial presentation was cardiac
arrest (9%), syncope (26%), seizures (10%), presyncope or
palpitations (6%), with 88 percent having exercise-related
symptoms, 39 percent were identified because of family
history or the identification of other family members with
the syndrome and 39 percent were asymptomatic.49 Of those
asymptomatic, 4 percent experienced sudden death compared
to 8 percent overall. The strongest predictors of sudden
death were QTc greater than 0.60 and noncompliance with
recommended medication. Bradycardia is commonly seen in
these patients, and some may develop or present with seconddegree AV block.50 This is more common in neonates (Figure
8) who may have second- or third-degree AV block but it may
be seen in older children, especially with exercise.
The abnormal genes that encode for proteins modulate
potassium or sodium ion channels, causing the LQTS by
altering cardiac repolarization and increasing the risk for
ventricular arrhythmias. These genes include KVLQTI,
HERG, SCN5A, minK and MiRp1. Not all families with known
LQTS have shown linkage to these known loci, suggesting the
presence of additional genes yet to be discovered. Apart from
857
11
table 1
Schwartz/Moss score for long QT syndrome (LQTS)
diagnostic criteria
Variable
ECG findings
Figure 8: Neonate with LQT presenting with CHB
QTc mseca 480

460470
450 (in males)
Torsade de pointes
T-wave alternans (macroscopic)
Notched T wave in three leads
Low heart rate for ageb
3
2
1
2
1
1
0.5
Clinical history
repolarization abnormality, imbalance or oversensitivity of the

myocardium to sympathetic stimulation appears to play a role
in the development of ventricular arrhythmias. The trigger
for arrhythmia in the LQTS is believed to be spontaneous
secondary depolarizations that arise during or just following
the prolonged plateau phase of action potentials, early after
depolarizations, which is augmented by increased sympathetic
tone.
Clinical associations of genetic findings

The influence of genotype on clinical course is being
elucidated.51 The frequency of cardiac events is higher among
subjects with LQT1 (63%) or LQT2 (46%) than among LQT3
patients (18%). The likelihood of dying during a cardiac event
was higher among LQT3 patients (20%) than among LQT1 or
LQT2 (4%) patients. Cardiac events in LQT1 patients occur
frequently during exercise (62%), especially swimming, 3
percent occurred during sleep. LQT2 and LQT3 patients
were less likely to have events during exercise (13%) and
more likely to have events during rest/sleep (29% and 39%).
The percentage of patients who were free of recurrence with
beta-blocker therapy was higher and the death rate was lower
among LQT1 patients (81% and 4%, respectively) than
among LQT2 (59% and 4%) and LQT3 patients (50% and
17%). LQT3 patients have more cardiac events at rest or
during sleep, while LQT2 patients experience more events
during exercise or stress. LQT2 events are more likely to be
stimulated by loud noises.
Evaluation and diagnosis
858
Points
Diagnosis is made by a careful history, both of the individuals

episodes and a complete family history looking for sudden
unexplained death, syncopal episodes in family members,
unusual seizure disorders or hearing deficits. All patients
suspected of LQTS should have a standard ECG with careful
QTc measurement, 24-hour ambulatory monitoring and
exercise stress testing if age is appropriate and provocative
testing such as isoproterenol or epinephrine infusions.52 The
Syncopec
With stress
Without stress
Congenital deafness
Family historyd
Family members with definite LQTSe
Unexplained sudden cardiac death < age
30 years among immediate family members
2
1
0.5
1
0.5
aQTc
calculated using Bazetts formula (QTc = QT/square root of RR).

exclusive.
cResting heart rate below the second percentile for age.
dThe same family member cannot be counted in both.
eDefinite LQTS is defined by an LQTS score greater than or equal to 3.5.
bMutually
longest QT interval in any lead is divided by the square root

of the preceding RR interval, values greater than 0.45 in any
lead as abnormal on the resting or exercise ECG. In addition
to QT interval prolongation, the Holter may be helpful in
illustrating T wave abnormalities, R on T phenomenon, short
runs of nonsustained VT, sustained VT or torsades de pointes.
Diagnostic Evaluation
Schwartz et al proposed the first diagnostic criteria for LQTS
in 1985, which included QTc greater than 440 ms as one of
the criteria that has rendered this cutoff value of 440 ms a
major limitation of the original Schwartz criteria.53 A
modified Schwartz score (Table 1) containing new criteria
and a point system based upon a range of QTc values and
the clinical/family history was formulated in 1993.54 The
Schwartz score, recently modified for what concerns the
points necessary for a high clinical probability of LQTS,
ranges from 0 to 9 and contains three diagnostic probabilities:
1 point, low probability of LQTS; 2 or 3 points, intermediate
probability of LQTS; and greater than 3.5 points, high
probability of LQTS. The Schwartz criteria provide a very
useful guide for contemplating a clinical diagnosis of LQTS
with the positive predictive value of a modified Schwartz
score greater than 3.5 approaching 100 percent. Importantly,
however, the Schwartz criteria should be used only for the
diagnosis of clinically evident LQTS. By definition, these
Epinephrine Challenge Test
stimulation of the intact IKs channel and augmentation of a

late inward Na current. Thus, the epinephrine QT stress test
provides an in vivo physiological assessment of the integrity
of the IKs pathway.
The two major protocols developed for epinephrine infusion
include the bolus and brief infusion developed by Shimizu, and
the escalating-dose protocol (Mayo protocol).59,60 Infusion
of epinephrine is initiated at 0.025 g/kg/minute. After 10
minutes of the infusion, QT/QTc, repeated. The epinephrine
infusion was then increased sequentially every 5 min to 0.05,
0.1 and 0.2 g/kg/minute and the measurements were repeated
5 minutes after each dose increase. The epinephrine infusion
was then discontinued and measurements were obtained 5
and 10 minutes afterward. The total duration of epinephrine
infusion was 25 minutes. The change in the uncorrected
QT interval and the change in QTc were calculated by the
difference between the maximal and minimal QT and QTc,
respectively, at any time during the epinephrine infusion at a
dose of 0.1 g/kg/min. Established stopping criteria included
systolic blood pressure 200 mm Hg, NSVT or polymorphic
VT, ten PVCs per minute, T-wave alternans or patient
intolerance (Figure 9).
60
tachyarrhythmias
criteria cannot identify the patients or family members with

concealed LQTS.
Provocative testing should include exercise stress
testing in children able to exercise. Exercise will generally
obliterate sinus arrhythmia and a strip can be obtained in
which a reasonable QTc calculation, if a good tracing free
of disturbances be obtained. The recovery period with
heart rates around 120 to130 bpm seems to demonstrate
the greatest degree of QTc prolongation in many patients.
Exercise may uncover abnormal T waves, polymorphic
PVCs, or VT.55,56 If suspicion for LQTS is high and other
testing has not been definitive, isoproterenol or epinephrine
infusion may help to identify these patients. Efforts to identify
patients at high risk for syncope and sudden death continue.
High-risk electrocardiographic markers have included QTc
greater than 0.60, T wave alternans and QTc dispersion. QT
dispersion, which indicates heterogeneity of repolarization,
could predispose to the development of torsades de pointes,
patients not responding to beta-blocker had a significantly
higher dispersion of repolarization than responders.57,58 T
wave alternans is known to be a high risk factor.
Treatment
Physiological basis: In the normal heart, epinephrine increases

both inotropy and chronotropy. This is achieved in part by
G-protein/cAMP/protein kinase Amediated phosphorylation
of IKs (slowly activating delayed rectifier potassium
channel) and the Ca activated Cl channel. IKs is one of the
dominant potassium channels responsible for repolarization
(particularly phase 3), which allows potassium ions to exit the
cell and action potential duration to shorten. Activation of this
channel explains the observed attenuation of the QT interval
that occurs with epinephrine infusion in normal subjects.
LQT 1 with KCNQ1 mutations (LQT1) have compromised
IKs channels that are not as responsive to sympathetic
stimulation and phase 3 repolarization in these individuals
is retarded. Consequently, during epinephrine infusion, there
are relatively more unopposed depolarizing forces via the
L-type calcium channel and the sodium calcium exchanger
that prolong the action potential duration and hence the QT
interval. LQT2 with KCNH2 mutations have dysfunctional
rapidly activating delayed rectifier potassium (IKr) channels,
a smaller fraction of the potassium channels responsible
for phase 3 repolarization and are not as sympathetically
responsive as IKs channels. Therefore, in patients with LQT2,
there may be a transient prolongation of the action potential
duration during epinephrine infusion, followed by a normal
abbreviation of the action potential duration and the absolute
QT interval due to the presence of unimpaired IKs channels.
This transient prolongation of the QT interval followed by
shortening is a characteristic feature of the LQT2 phenotype.
The LQT3 phenotype is characterized by a constant reduction
of the action potential duration with epinephrine due to
Emergent treatment of these patients includes lidocaine and

cardioversion. Magnesium may be used to treat torsades de
pointes; intravenous propranolol and phenytoin have also
been successfully used in these patients.61 The class I agents,
which are known to prolong the QT interval in normal patients,
should be avoided in these LQTS patients. This is related to
QTc prolongation with associated bradycardia or ventricular
arrhythmias or both. Temporary pacing and removal of the
offending agent are effective therapies.62
The standard long-term treatment in this condition is
the use of beta-blockers. Those most commonly used are
propranolol and nadolol.63,64 Some have suggested longacting metaprolol or atenolol. A concern about once-daily
dosing relates to the lowest levels being present in early
morning hours, a particularly high-risk time for some patients.
The dose of beta-blocker required is variable and is usually
greater per kilogram in younger patients. The dose can be
titrated by the heart rate response to maximal exercise testing,
aiming for a blunted maximal heart rate response on therapy
of 150 to 160 bpm. Treatment with beta-blockers can lower
the mortality to less than 4 percent, with greatest benefit in
LQT1.65 Patients are followed with exercise stress tests and
Holter monitoring to look for adequacy of treatment or the
development of significant ventricular arrhythmias or both.
Patients who do not respond to beta-blockers may be treated
with mexiletine, phenytoin or pacing. Mexiletine is more useful
in LQT3 patients. Rarely, other antiarrhythmics may be used,
but those known to prolong the QT interval should be avoided.
Potassium supplementation especially in LQT2 therapy may
859
11
Figure 9: Adrenalin challenge test in a child with family history of sudden cardiac death in the sibling showing increasing QTc
from base line value of 426 ms to 659 ms. This patient was later confirmed to have LQT1 gene defect
860
be helpful. Left stellate ganglionectomy is a treatment which

should be offered to all patients.66 Permanent pacing has been
shown to be an effective adjunctive treatment in these patients,
especially those with severe bradycardia either from the
syndrome itself or from the beta-blocker therapy, tachycardias
which are triggered by pauses. The rate of the pacing should
be at least 10 to 20 percent higher than the sinus rate and in
severe cases should control the rhythm as much of the time
as possible.67 Pauses should be avoided. Using this treatment,
episodes of torsades de pointes may be reduced or eliminated.
In patients known to have had a cardiac arrest or frequent or
significant syncope associated with ventricular arrhythmias,
on beta blockers and left cardiac sympathetic denervation
(LCSD), implantation of an automatic internal cardioverter/
defibrillator device may be necessary. These devices can
recognize VT or VF according to programed criteria and
provide a series of shocks to convert the patient to sinus
rhythm. Some can provide backup pacing. Their size led to
limited use in smaller children, but improved technology now
allows even small children to benefit from this technology.
This is not a therapy to be undertaken lightly at this time,
as follow-up and possible false discharges can significantly
affect a childs life and lifestyle.
At present following group of patients merit implantable
cardioverter-defibrillator (ICD):
1. All those who have survived aborted cardiac arrest (ACA)
on therapy
2. Many of those who have survived an ACA off therapy,
except those with a reversible/preventable cause, but noting
that for most LQT1 grown-up patients, full-dose betablockers might be sufficient. On the basis of additional
considerations, e.g. duration of the QT interval, this may
lead to an open discussion with patients and family
3. Patients who continue to have syncope despite full-dose
beta-blockade whenever the option of LCSD either is not
available or is discarded after discussion with the patients
4. All patients with two mutations who continue to have
syncope despite beta-blockade
5. Exceptionally, the rare asymptomatic patients with a QTc
550 milliseconds who also manifests signs of high electric
instability (e.g. T-wave alternans) or other evidence of
being at very high risk (e.g. very long sinus pauses that
might favor early after depolarizations).
Implantable Cardioverter-Defibrillator Complications

The relatively high rate of inappropriate shocks and
complications after ICD implantation increases the morbidity
of this treatment modality in LQTS patients and worsens its
risk benefit ratio. Inappropriate shocks were caused mainly by
abnormal sensing resulting from either T-wave over sensing or
lead failure. The young age at implantation (76% of patients
lesser than 40 years of age, 12 percent lesser than 10 years of
age) supports the hypothesis that the high rate of lead failure
is attributable to the activity-dependent increased strain on
ICD leads. Another cause of inappropriate shocks was SVT.
Besides avoiding unnecessary shocks, prolonging the detection
time and increasing the threshold of tachycardia detection
CaTECholaminE-indUCEd VEnTriCUlar
TaChyCardia
Catecholamine-induced VT is a genetic disorder associated
with stress-induced, bidirectional VT that may degenerate
into VF and result in sudden death, in the absence of both
structural heart disease and a prolonged QT interval. The CPVT
phenotype most often shows an autosomal dominant pattern
of transmission, although sporadic cases seem to be rather
frequent and a familial history of juvenile sudden death and
stress-induced syncope is present in about 30 percent of cases.
This condition usually occurs in childhood, adolescence or
young adulthood. Reports of mutation in the ryanodine receptor
gene RyR1 mapped to 1q42-q43 have been found in families
with catecholamine-induced VT, a recessively inherited CPVT
phenotype and the disease locus to a 16-megabase interval
on chromosome 1p1321, calsequestrin 2 (CASQ2) gene
mutation gives rise to a pathological clinical phenotype only in
homozygous carriers, while heterozygous carriers are usually
silent.
pathophysiology
The hypothesis that arrhythmias in CPVT are initiated by
DADs and triggered activity had been advanced based on
the observation that the bidirectional VT observed in CPVT
patients closely resembles digitalis-induced arrhythmias.
Digitalis-induced intracellular Ca2 overload leads to the
activation of sodiumcalcium exchanger that, in turn,
generates a net inward current (the so-called transient inward
ITi current). ITi underlies diastolic membrane depolarizations,
DADs, that may reach threshold for sodium current activation
and trigger abnormal beats. This mechanism for arrhythmia
initiation is defined as triggered activity.
60
tachyarrhythmias
may reduce inappropriate shocks caused by supraventricular

or sinus tachycardia, especially in young patients. In 223
implants, there were 67 adverse events in 58 patients, the more
severe adverse events resulted directly from the implantation
surgery such as lead placement issues, infections and vascular
problems. Most of the minor complications were related to
lead issues, including conductor fractures, insulation defects,
and changes in electric characteristics.68 These findings
substantiate the concerns about the long-term impact of
implanting an ICD in young LQTS patients, likely to live
another 7 to 8 decades after initial device implantation and
who would be subject to multiple procedures for generator
replacements and lead revisions/extractions with probable
complications. This makes the implementation of loose and
non-data-based indications for ICD implantation in LQTS
patients no longer preferred.
It is generally recommended that competitive athletics be
avoided by patients with LQTS and especially in those with
documented LQTS symptoms or arrhythmias. However, as
more carriers or asymptomatic patients are being discovered,
who have only a prolonged QT interval and no family history
of sudden death or ventricular arrhythmias, individual exercise
and sports participation recommendations may be made.
The most important aspect of the care of these patients is
continued surveillance. This is true for young family members
who appear to have normal QT intervals on initial evaluation.
The QT interval changes with age with periodic ECGs,
hence appropriate 24 hours and exercise ECG should be done
in children and adolescent members of LQTS families in
whom the initial evaluation was negative, unless the genetic
testing has definitively ruled out LQTS. It is recommended
that patients with LQTS avoid caffeine, adrenergic stimulants
such as epinephrine and over-the-counter stimulants such
as decongestants. Medications that prolong the QT interval
should be avoided.
Syncope, triggered by exercise or emotional stress, is often
the first manifestation of CPVT.69 Approximately 30 percent
of patients present with a family history of stress-related
syncope, seizure, or sudden death. Most events occur in the
first or second decade of life. CPVT diagnosis is established
after an average delay of 2 years from the first syncope,
because these events are often attributed to vasovagal events
or to neurological factors.70 Increasing evidence shows that
SCD can be the first manifestation of the disease.
Electrocardiogram
The resting ECG of CPVT patients is usually normal
with the exception of prominent U waves and mild sinus
bradycardia in some patients, which is especially abnormal
for children of this age. There is normal QTc, normal AV
conduction and no evidence of a Brugada like pattern.
Exercise or acute emotional stress is the typical trigger
of CPVT-related arrhythmias, constantly at heart rate of
110 to 130 beats per minute.71 The complexity and frequency
of ventricular arrhythmia progressively worsen with an
increase in workload, from isolated premature beats to
bigeminy and to ventricular tachyarrhythmia (Figure 10).
When the exercise stops, arrhythmias gradually disappear.
The most typical VT observed in CPVT patients presents
an alternating QRS axis morphology with a rotation of 180
degrees on a beat-to-beat basis, the so-called bidirectional
VT. In view of the role of triggered activity as a mechanism
for arrhythmias in CPVT, it is interesting to note that fast
SVT may act as a trigger for the development of DADs and
triggered activity in the ventricle.
diagnosis
Exercise or emotion-induced syncope in a patient with a
normal ECG (normal QT interval) and without structural
abnormalities should always suggest the possibility of
CPVT. An exercise stress test is the most important tool for
diagnosis since the bidirectional or polymorphic VT may be
reproducibly elicited during physical activity in most of the
861
11
Figure 10: Ventricular ectopics of different morphology in a child at baseline, developed polymorphic
ventricular tachycardia during stress test
patients. Furthermore, even in patients showing polymorphic

(and not bidirectional) VT, the progressive worsening of
arrhythmias with exercise is to be considered as diagnostic for
CPVT. Invasive electrophysiological testing and isoprenaline
infusion are of not proven value.
Treatment
862
malformations, sufficient to explain the degree of hypertrophy.75

The discovery that many patients with hypertrophic
cardiomyopathy had familial disease led to a search for the
genetic basis of the disease. In 1989, the first mutation in the
gene encoding the cardiac -myosin heavy chain was identified.
Since then, more than 400 mutations have been identified in this
and other cardiac sarcomeric protein.
Acute intravenous administration of propranolol dose is the

treatment of choice for the acute termination of CPVT-related
arrhythmias. Chronic treatment with beta-blockers can prevent
recurrent syncope in some patients.72,73 Nadolol at a daily
dose of 1 to 2.5 mg/kg/day is the preferred drug in view of 24
hours action and can be titrated upto 3.5 to 4 mg/kg/day. Betablockers reduce the occurrence of cardiac events, postpone the
induction of VTs during exercise, stress testing and slow the
rate of VT; ICD should be considered for primary prevention
of cardiac arrest in CPVT patients in whom severe ventricular
arrhythmias (sustained VT or rapid VT) are still observed while
on beta-blocker therapy. The beta blockers can be titrated based
on Holter monitoring and stress test, looking for ventricular
ectopic/VT.
Catecholamine-induced VT mutant RyR2 proteins cause a
gain of function and uncontrolled calcium release from
sarcoplasmic reticulum. Verapamil by directly inhibiting the
function of the ryanodine receptor may theoretically be an
alternative option for treatment.74 The limited experience with
amiodarone, mexiletine and magnesium produced unfavorable
results.
Epidemiology
hypErTrophiC CardiomyopaThy
sudden death
Hypertrophic cardiomyopathy is defined as left ventricular

hypertrophy in the absence of abnormal loading conditions
such as valvar disease, hypertension or other congenital cardiac
Sudden death occurs most commonly in adolescents and

young adults. The initial descriptions of the natural history
reported annual rates of sudden death from 3 to 6 percent,
Unexplained left ventricular hypertrophy occurs in approximately 1 in every 500 adults. The frequency of left ventricular
hypertrophy in children is unknown, but population-based
studies from Australia and the United States report an
incidence between 0.3 and 0.5 cases per 100,000, including
cardiomyopathies associated with inborn errors of metabolism,
neuromuscular disease and malformation syndromes.76,77
natural history
Hypertrophic cardiomyopathy can present from infancy
to old age. Many patients follow a stable and benign
course, with a low risk of adverse events, but a large
number experience progressive symptoms, caused by
gradual deterioration in left ventricular systolic and
diastolic function and atrial arrhythmias. A proportion of
individuals die suddenly, whereas others may die from
progressive cardiac failure.Neonatal presentation had
severe symptomatic presentation.
used to prevent sudden death in patients considered at highrisk. The drug, however, does not prevent SCD in this group
at high-risk. Amiodarone does, nonetheless, remain useful
for the treatment of atrial fibrillation.
BrUgada syndromE
introduction
Brugada syndrome has increasingly been recognized worldwide
as an important cause of SCD at a young age, in the absence of
structural cardiac abnormalities. Patients affected with Brugada
syndrome are at risk for SCD from fast polymorphic VT/
VF, especially at rest. Brugada syndrome is characterized by
a typical ECG pattern consisting of ST segment elevation in
the right precordial leads and in leads positioned in the upper
intercostal spaces.82
It is endemic in East and Southeast Asia, where it underlies
the sudden unexplained nocturnal death syndrome (SUNDS),
and is also particularly prevalent in Japan, Philippines and
Thailand, being the leading cause of sudden death among
young men.83 Arrhythmic events in Brugada syndrome
can occur at all ages, from childhood to the elderly (range
277 years), with a peak around the fourth decade, with
higher disease prevalence in males (7080% of all affected
subjects), particularly in regions where this syndrome is
endemic, despite equal genetic transmission among both
genders. However, in pediatric age, no sex predilection
is seen. A role in gender disparity could be played by sex
hormones.84 It is estimated that Brugada syndrome causes 4
to 12 percent of all SCD and up to 20 percent among patients
without identifiable structural abnormalities.The clinical
presentation is heterogeneous and may include palpitations,
dizziness syncope and (aborted) sudden death, but many
subjects remain asymptomatic.85
The pathophysiological mechanism underlying this
syndrome and the typical ECG features and the genesis of the
arrhythmias:86
1. A repolarization disorder, i.e. unequal expression of the
transient outward potassium current Ito between the
epicardium and the other transmural layers87 or
2. A depolarization disorder, i.e. a delay in the onset of the
action potential in the region of the RVOT.88
Three repolarization patterns of ST segment elevation
with two different shapes were recognized as potential
manifestations of Brugada syndrome.89 The coved-type
morphology (type I) is characterized by a cove-shaped J wave
elevation 2 mm, followed by a negative T wave. A type I
ECG is required for the diagnosis, while a saddleback-shaped
ST elevation or a coved-type lesser than 1 mm (types IIIII)
are indeterminate forms that necessitate pharmacological
challenge (Table 2 and Figure 11).
The diagnosis is posed when a type I ECG, spontaneously
or after provocation with sodium channel blockers, is present
in more than one right precordial lead in the absence of
60
tachyarrhythmias
recent studies in adults revealed rates of 1 percent or less per

year. Similarly, early studies of highly selected populations
of children reported rates of sudden death ranging from 2
to 8 percent per year, but recent population-based reports
from Australia and the United States report an overall annual
rate of sudden death of 1 to 1.5 percent per year beyond
infancy. The mechanism of sudden death is thought to be
ventricular arrhythmia in the majority and several triggers
are recognised, including atrial arrhythmia, myocardial
ischemia and exercise.The most reliable predictor is a
history of previous cardiac arrest. In patients without such
a history, the most clinically useful markers of risk are a
family history of SCD, unexplained syncope unrelated to
neurocardiogenic mechanisms, a flat or hypotensive response
of blood pressure to upright exercise, NSVT on ambulatory
electrocardiographic monitoring or during exercise and
severe left ventricular hypertrophy on echocardiography
defined as a maximal left ventricular wall thickness of 30
mm or more.78 Importantly, these markers of increased risk
can all be identified non-invasively. Studies have shown that
patients with none of these features have a low risk of sudden
death, less than 1 percent per year, whereas those with two
or more risk factors are at substantially higher risk of dying
suddenly, with an estimated annual mortality rate of 3 percent
for those with two risk factors, rising to 6 percent in those
with three or more risk factors. The evaluation of risk in
these patients, therefore, has to be tailored to the individual,
taking into account the significance of the risk factor as well
as patient specific variables such as age. A particularly
malignant family history may be sufficient to trigger
primary preventative measures in the absence of a second
risk factor. Several studies have shown that obstruction of
the left ventricular outflow tract is associated with increased
cardiovascular mortality, including sudden death. The
absolute risk of sudden death associated with obstruction
in isolation is low, but it may represent an incremental risk
factor in combination with other conventional markers. The
extrapolation of data derived from adults may not always be
appropriate for children.79 Of the conventional markers of an
increased risk for sudden death, unexplained syncope, severe
left ventricular hypertrophy, and a family history of sudden
death have been reported as being particularly relevant to
young individuals.80,81
In patients who are considered to be at high risk, insertion
of an ICD should be regarded as the treatment of choice. In
children, appropriate discharge rates are higher at 71 percent
per year in those chosen for secondary prevention and 4
percent per year in those having primary prevention. Despite
the life-saving benefits of ICDs, an increased incidence of
complications has been reported in children compared with
adults, including a higher rate of inappropriate discharges
for supraventricular or sinus tachycardia, an increased risk
of infection, complications with leads related to growth and
the psychological sequels of appropriate and inappropriate
discharges. Prior to the advent of ICDs, amiodarone was
863
11
structural abnormalities and in association with one of the

following conditions:
1. Documented VF or polymorphic VT
2. A family history of SCD at a young age or a type I ECG in
family members
3. Otherwise unexplained syncope
4. Inducibility of VT/VF with programmed electrical
stimulation. Patients with spontaneous Type I ECG are at
increased risk for malignant arrhythmias.
Brugada syndrome is inherited as an autosomal dominant
trait, linked to mutations in the SCN5A gene,91 encoding the
table 2
Diagnostic criteria for Brugada syndrome90
ST-segment abnormalities in leads V1-V3
Type 1
Type 2
Type 3
J point
2 mm
2 mm
2 mm
T wave
Negative
Positive or
biphasic
Positive
ST-T
configuration
Coved type
Saddleback
Saddleback
ST segment
(terminal
portion)
Gradually
descending
Elevated
1 mm
Elevated
< 1 mm
subunit of the cardiac sodium channel protein and a linkage

to a second locus on chromosome 3 was demonstrated in a
large Brugada syndrome family and direct sequencing of
that region led very recently to the identification of a novel
mutation in the glycerol-3-phosphate dehydrogenase 1-like
gene (GPD1L).92
Sudden death results from fast polymorphic VT originating
from the RVOT, degenerating into VF. Ventricular arrhythmias
and aborted sudden death in Brugada syndrome, occurs at
rest when the vagal tone is augmented and often at night.
Self-terminating VT may provoke recurrent syncope and
may explain why patients experience agonal respiration at
night after which they wake up, 80 percent of patients with
documented VT/VF have a history of syncope.
A central characteristic of Brugada syndrome is the absence
of clear structural abnormalities. The ability to detect slight
structural abnormalities has become greater with electron
beam computed tomography (CT) scan and cardiac magnetic
resonance imaging (MRI).93,94 These methods have revealed
right ventricular (RV) wall motion abnormalities and RVOT
enlargement. These findings demonstrate a link between
functional and structural abnormalities and also support the
hypothesis that sodium channel mutations themselves may
induce subtle structural derangements and myocardial cell
death.95
864
Figure 11: Different degrees of electrocardiographic changes seen in the same patient
risk stratification
The conditions that are also accompanied by ST segment

elevation should be carefully ruled out before the
diagnosis of Brugada syndrome is made, which include
arrhythmogenic right ventricular cardiomyopathy (ARVC),
early repolarization syndrome, acute myocardial infarction,
isolated right ventricular infarction, Prinzmetals angina,
electrolyte disturbances such as hyperkalemia and
hypercalcemia, acute pericarditis/myocarditis and ECG
recorded after electrical cardioversion (Box 1).
Drugs and intoxications can lead to a Brugada-like ST
segment elevation such as CCBs or nitrates, tricyclic or
tetracyclic antidepressant medications as well as selective
serotonin reuptake inhibitors and cocaine.96
The prognosis of Brugada syndrome patients is still being

debated. While it is accepted that patients with aborted sudden
death or those who have had symptoms such as dizziness,
syncope or nocturnal agonal respiration should receive an
ICD, conflicting data exist regarding risk stratification and
therapeutic options in asymptomatic individuals.
Therapy
The most effective prevention of sudden death in patients
affected by Brugada syndrome who suffered from (aborted)
cardiac arrest or syncope or are considered at high risk for
ventricular arrhythmias are ICDs.97 Quinidine is the only oral
agent that has been proven to normalize the ST segment and to
be effective in suppressing arrhythmic events in patients with
Brugada syndrome (both spontaneous events and inducible
VT/VF during EPS);98 neither beta-blockers nor amiodarone
have proven to be effective.
Box 1: abnormalities associated with Brugada-like st

segment elevation
Conditions that can lead to ST segment elevation, mimicking
Brugada syndrome
Early repolarization syndrome
Cocaine intoxication
Acute myocardial infarction or isolated right ventricular
Infarction
Prinzmetals angina
Hyperkalemia and hypercalcemia
Acute pericarditis/myocarditis
RBBB or LBBB and left ventricular hypertrophy
Acute aortic dissection/acute pulmonary embolism
Arrhythmogenic right ventricular cardiomyopathy
Long QT syndrome type III
Hypothermia
Duchenne muscular dystrophy
Friedreichs ataxia
Various central and autonomic nervous system
abnormalities
Mechanical compression of the RVOT by a mediastinal
tumor
LBBB =Left bundle branch block; RBBB = Right bundle
branch block, RVOT = Right ventriclular outflow tract.
posTopEraTiVE TaChyCardia
60
tachyarrhythmias
The principal patient groups include patients having had

incisions over the atrium or ventricle. Atrial arrhythmias
are seen after incision over right atrium for simple cardiac
repairs such as ASDs, VSDs, tetralogy of Fallot (TOF),
atrioventricular canal defects and related defects or following
complex surgeries such as Mustard or the Senning procedure
or the Fontan procedure. Ventricular tachycardia is seen in
surgically corrected TOF and with related lesions such as
certain types of double outlet right ventricle.99
Ventricular Tachycardia in postoperative Tetralogy of fallot

Postoperatively, the most common congenital lesion associated
with VT is TOF, 10 to 15 percent have VT postoperatively.100
Sudden death occurs in 5 to 10 percent. The risk factors associated
with the development of VT and sudden death include older age
at repair, a longer postoperative period, RV systolic pressure
greater than 60 mm Hg at rest, RV end-diastolic pressure greater
than 10 mm Hg at rest, depressed RV systolic function and
moderate to severe pulmonary or tricuspid regurgitation and
abnormal signal-averaged electrograms with late potentials and
the development of VT. A wide QRS duration of greater than
180 ms has been associated with VT, correlated with severe
pulmonary insufficiency leading to RV dilation. QRS duration
and degree of pulmonary regurgitation seem to be the greatest
risk factors for VT and sudden death.101,102 Valve replacement
decreases the incidence of episodes of VT and atrial flutter.The
ventriculotomy, myocardial resection, and subsequent scarring
provide the electrophysiological substrate of slow conduction
and block that predisposes the patient to develop reentrant
arrhythmias. Ventricular arrhythmias occasionally occur despite
good hemodynamic results, although sudden death occurs most
commonly in VT associated with poor hemodynamics. Patients
repaired earlier in life seem to have a lower incidence of VT,
suggest that early repairs may decrease the incidence of VT in
these patients.
Evaluation
All postoperative patients, especially those noted earlier at
highest risk, should have periodic follow-up (usually yearly)
with standard ECGs. Holter monitoring should be performed
every 2 to 3 years in those without known arrhythmias and
865
11
every year in those in whom arrhythmias have been identified

and those treated for arrhythmias may need more frequent
monitoring. Those with complex arrhythmias (NSVT,
polymorphic PVCs or polymorphic VT) or monomorphic
VT should undergo further testing, requiring an EPS. These
studies have been used to evaluate the propensity of these
patients to develop VT, evaluate the efficacy of specific
pharmacologic therapies and locate the site of origin of the
arrhythmia in patients who are candidates for ablative therapy.
Electrophysiological studies may be helpful in determining
the need for implantation of an automatic cardioverter
defibrillator, negative study does not guarantee that VT/VF or
sudden death will not occur.
management and Treatment

The presence of frequent or complex ventricular ectopy
probably identifies a high-risk group, but at present our ability
to further identify those patients at highest risk is limited. It
appears that patients with QRS duration above 180 ms and
severe pulmonary regurgitation represent high-risk patients.
Because of the high incidence of ventricular arrhythmias in
postoperative patients, their precise role in the occurrence of
sudden death is unclear. It is known after tetralogy repair that
exercise stress testing or ambulatory monitoring will uncover
a 25 to 70 percent incidence of ventricular arrhythmias.
It appears that patients with QRS duration above 180 ms
and severe pulmonary regurgitation represent high-risk
patients. The ICD should definitely be considered in patients
with aborted SCD, sustained VT. The treatment should be
individualised with combination of drugs, RFA and ICD.103
atrial arrhythmias
The late postoperative arrhythmias contribute significantly
to morbidity and mortality. The treatment options included
medical therapy with antiarrhythmic agents, implantation of
antitachycardia pacemakers, catheter ablation and surgical
ablation. The ablative techniques, potentially offer a curative
treatment. Even in patients having surgical right atrial scar
for surgeries for ASD, VSD, TOF, the common arrhythmia is
atrial flutter rather than incisional AT.
ConClUsion
Arrhythmias are an important cause of morbidity and
mortality in children. It is necessary to determine which
pediatric ECG findings are normal, which are abnormal,
and which must be addressed. A systematic approach to
the diagnosis of arrhythmias is essential so that appropriate
treatment can be given. Medical management remains the
mainstay of treatment, RFAs is usually considered in cases of
866
drug refractory cases. The ICD and pacemakers are valuable

tools in the treatment of certain arrhythmias.
In nature there are neither rewards nor punishments - there
are only consequences.
Robert G. Ingersol
aCknoWlEdgmEnT
I wish to thank Dr Somasekhar for his help in preparing this
article.
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28. Arruda M, Wang X, McClennand J. ECG algorithm for
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29. Fitzgerald DM, Hawthorne HR, Crossley GH, et al. P wave
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30. Epstein MC, Kiel EA, Victoria BE. Cardiac decompensation
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52. Garson A Jr. How to measure the QT intervalwhat is normal?
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53. Schwartz PJ. Idiopathic long QT syndrome: progress and
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54. Schwartz PJ, Moss AJ, Vincent GM, Crampton RS. Diagnostic
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56. Swan H, Toivonen L, Viitasalo M. Rate daptation of QT
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60. Shimizu W, Noda T, Takaki H, et al. Epinephrine unmasks
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64. Moss AJ, Zareba W, Hall WJ, et al. Effectiveness and
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sympathetic denervation in the therapy of congenital long QT
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67. Moss AJ, Liu JE, Gottlieb S, et al. Efficacy of permanent
pacing in the management of high-risk patients with long QT
68. Schwartz PJ, Priori SG, Brink PA, et al. Who Are the Long-QT
Syndrome Patients Who Receive an Implantable CardioverterDefibrillator and What Happens to Them? Circulation.
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69. Leenhardt A, Lucte V, Denjoy I, et al. Catecholaminergic
polymorphic ventricular tachycardia in children. A 7-year
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70. Cerrone M, Colombi B, Bloise R, et al. Clinical and molecular
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69-74.
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polymorphic ventricular tachycardia: Successful emergency
treatment with intravenous propranolol. Pediatr Emerg Care.
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antagonism reduces exercise-induced ventricular arrhythmias
in catecholaminergic polymorphic ventricular tachycardia
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cardiomyopathies: A position statement from the European
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98. Mizusawa Y, Sakurada H, Nishizaki M, Hiraoka M. Effects
of low-dose quinidine on ventricular tachyarrhythmias
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103. Stevenson WG, Delacretaz E, Friedman PL, Ellison KE.
Identification and ablation of macrore entrant ventricular
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mechanisms of Brugada syndrome: depolarization disorder,
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367-78.
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R, Brugada P, et al. Proposed diagnostic criteria for the Brugada
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61
Invasive Electrophysiology Testing

and Devices in Children
Dinesh Choudhary, Abhilash SP, Narayanan Namboodiri
Introduction
Preprocedure Preparation
The invasive management of both bradyarrhythmias and

tachyarrhythmias is limited in children, because of technical
issues involved in performing safe procedures, lesser
evidence-based recommendations in this population, to
substantiate the use of devices and as a consequence, lack of
regulatory approval for performing the procedures. The safety
and feasibility concerns, especially in ablative procedures are
particularly related to the anatomical rather than physiological
reasons. Children do have smaller cardiac chambers, thinner
and perhaps more fragile tissues, smaller coronary arteries
and smaller distances between structures, such as the posterior
septum and the atrioventricular (AV) node or the AV ring and
the coronary arteries in comparison to adults.1-8 Due to these
facts, catheters and devices tailored for use in adults may not
be ideal for use in children. However, arrhythmia mechanisms
and their management options in children largely overlap
with that in adults and it makes the practice of invasive
electrophysiology unique in many aspects.
The planning of EP study should include choice of intracardiac

and/or transesophageal technique and requires some preprocedure studies (e.g. electrocardiography [ECG], Holter
monitoring, exercise testing, imaging studies). The child and
family should be well explained about the procedure and
technique including success rate of procedure and potential
complications. Age-related patient and family preparation
should begin with the pediatric electrophysiologist and
continued by nurses and other technical staff. General anesthesia
should be used for all pediatric and young adolescent patients
for procedural success and to reduce complications due to
catheter movements in non-cooperative children. Continuous
intravenous propofol acts as a deep sedative with low doses
and as a general anesthetic with higher doses. It causes less
postprocedural nausea and vomiting, patients recover faster.
However, the electrophysiologic effects of propofol in children
are no different from isoflurane-based anesthetics.9
Invasive Electrophysiology in children:

an overview
Invasive electrophysiology (EP) in pediatric population can
be divided into diagnostic studies and mapping and ablation
of specific arrhythmias.
Diagnostic Electrophysiology Studies

The purpose of a diagnostic EP study is to assess the dynamic
electrophysiologic properties of the different atrial, AV
node, His-Purkinje system (HPS) and ventricular cells and
eventually try to induce and analyze cardiac arrhythmias with
concomitant use of drugs, if necessary (e.g. isoproterenol,
adenosine, atropine, procainamide, epinephrine, etc).
Sheath and Catheter Placement

To avoid antiarrhythmic serum concentration,10 0.5 to 1
percent concentration lidocaine given in sufficient amounts
(but not in increased volume) to achieve local anesthesia is
recommended. The number, size and location of the sheaths
relates to the age and size of the patient, underlying arrhythmia
and objectives of the study. In most studies, the number of
sheaths varies between 1 to 5, with the maximum number
consisting of three in the femoral vein, one in the internal
jugular vein and one in the femoral artery. Sheath sizes
usually correlate directly with the size of the patient and vary
between 4 and 8 French (Fr). The 6 or 7 Fr sheaths are used
because when intravenous drug administration is required, a
side-arm sheath larger than the catheter within it, permits free,
unobstructed flow of fluid into the vein.
catheters used primarily for recording and mapping contain

between 6 and 12 electrodes. Short (12 mm) interelectrode
distances are important in attaining the goals of maximumquality electrograms and precise mapping. The number,
manipulation and placement of electrode catheters involves
several factors, including patient size and age, underlying
arrhythmia, objectives of the individual study, size and type
of catheters (e.g. steerable), and underlying cardiac and blood
vessel anatomy.
Mapping and Ablation of Arrhythmias in Children

Ventricular tachycardia (VT) is relatively rare in children
(< 5% of all tachycardias and 20% of wide-complex
tachycardias).11 Supraventricular tachycardia (SVT) accounts
for most arrhythmias in children.1 SVT is most likely due
to accessory AV pathway (AP) in this age group and easily
ablatable.1 In the absence of a history of surgery for structural
congenital heart disease (CHD), accessory pathways (APs)
probably underlie about 75 percent of all SVTs in children1
and 95 percent in neonates,12 compared with 30 to 40 percent
of SVTs in adults. Atrioventricular nodal reentrant tachycardia
(AVNRT) and primary atrial tachycardias (both reentrant
and automatic) each appear to account for about half of the
remaining SVTs.1
Some arrhythmias like ectopic atrial tachycardia (EAT),
junctional ectopic tachycardia (JET) and the permanent form
of junctional reciprocating tachycardia (PJRT) are unique to
pediatric patients.
Ectopic atrial tachycardia accounts for 5 to 20 percent
of SVTs in children (< 2% of SVTs in adult).13,14 It is
usually due to automatic single atrial focus outside the sinus
node. It is frequently incessant and presents usually with
tachycardiomyopathy in 50 to 75 percent of cases.15,16
EAT may resolve spontaneously, if patient is younger than
6 months, but in many cases it is resistant to drug therapy
and arrhythmia surgery. Ventricular function usually returns
to normal after control of arrhythmia.15 This has led to an
aggressive approach with catheter ablation. Radiofrequency
(RF) catheter ablation for EAT arising from a single focus
has been acutely successful in 90 to 100 percent of cases
without significant complications.13 Most incessant EATs can
be successfully mapped. Map signals that precede the surface
P wave by more than 20 ms are most likely to indicate a
successful location.16
Junctional ectopic tachycardia is seen in two settings in
children: postoperative and congenital.17,18 Both are caused
by abnormal automaticity, from either low in the AV node
or high in the HPS. Postoperative JET is strongly associated
with ventricular septal defect repair, is usually transient,
lasting between 1 to 4 days and responds well to cooling and
intravenous amiodarone or propafenone.19 These observations
suggest that the tachycardia may be due to trauma and
inflammation induced at the time of the repair. Congenital JET
61
Invasive Electrophysiology Testing and Devices in Children
Transesophageal route as an additional access has been

used traditionally in many situations. Limitations in terms
of cost, higher risk and application in small infants may
dominate in specific situations, making the transesophageal
technique the best choice for the individual patient. The
inability to effectively pace the ventricle and fixed site of
recording and stimulation are the major limitations to the
transesophageal technique. The inability to reach the effective
refractory period of the atrium is occasionally overcome by
increasing the energy output. This is a potential limitation to
the transesophageal technique, especially when attempting to
fully evaluate patients with pre-excitation when the accessory
pathway refractory period is limited by reaching the atrial
refractory period first.
The heparin dose varies among laboratories, but the
initial dose is usually 70 to 100 U/kg, to a maximum of
5,000 U. Ongoing heparin anticoagulation can be provided
by a continuous intravenous infusion (e.g. 1520 U/kg/hr)
or by boluses. For the optimal anticoagulation during long
procedures, the activated clotting time (ACT) is measured
one to three times per hour to achieve a desired value of 200
to 300 seconds except higher values of 300 to 400 seconds
when 3-D balloon array mapping systems are used within the
left atrium or ventricle. Other pharmacological agents may
be required for a complete study, depending on the goal of
the EP study, e.g. use of adenosine to block conduction in
the AV node, provocative arrhythmic drug like isoproterenol,
epinephrine, caffeine, atropine, procainamide or flecainide.
The doses of isoproterenol and epinephrine continuous drip
infusions are similar and range from 0.01 to 0.1 mg/kg/min.
Atropine (0.010.04 mg/kg) is infrequently used, because it
cannot be administered as a continuous drip and because of its
longer-lasting effects. Invasive pressure monitoring is done
during the procedure for safety reasons with radial or femoral
artery access in indicated cases.
A standard diagnostic EP study involves use of 4 catheter
electrodes in high right atrium (RA) at lateral wall, right
ventricular apex, coronary sinus and His bundle location. The
coronary sinus catheter (decapolar) allows recording of left
atrial and ventricular electrograms. The other catheters (Halo
catheter, Lasso catheter, basket catheter, etc.) are for specific
use.
The catheter sizes vary between 2 and 7 Fr. Formerly, the 4
Fr catheters were used virtually only for infants, whereas the
5 Fr catheters most often were used in young children and 6
and 7 Fr catheters were used for adolescents and adult-sized
patients. Smaller (23 Fr) catheters are used for intracardiac
recordings as well as for epicardial mapping (by advancing
the catheters from the coronary sinus into the very small
branches throughout the epicardial surface). These small
catheters can be used in any size patients with the advantage
of minimizing the venous puncture site and therefore skin,
muscle and vein trauma. Most catheters used for recording
and pacing are in a quadripolar configuration, whereas
871
Electrophysiological Issues in Children
11
872
is typically not associated with structural CHD; is incessant;

has a positive family history in 50 percent of cases; usually
does not respond to cooling; is associated with the maternal
lupus anti-SSA and anti-SSB antibodies in some cases20 and
may spontaneously resolve. Both JET types appear to be
exacerbated by adrenergic stimulation,17 and respond well
to intravenous amiodarone. JET may initially be best treated
medically by minimizing adrenergic stimulation and starting
amiodarone, particularly in infants because of potential risk
of AV block from either catheter21 or surgical17 ablation of
the JET focus (no clear site of ablation) in the AV junction.
Cryotherapy is the treatment of first choice for ablation.
Permanent form of junctional reciprocating tachycardia
is caused by an orthodromic reciprocating tachycardia
involving a slow and decremental retrogradely conducting
concealed AP. It may resolve spontaneously.22 Catheter
ablation is highly effective technique in difficult to control
patients with PJRT, with minimal risk for AV block.23,24 Most
common site of these APs is posteroseptal, but may occur in
any location along the AV groove. Electrogram characteristics,
electrophysiologic techniques and mapping techniques are
somewhat different for PJRT pathways than for typical nondecremental APs. It is often impossible to confirm an AP
as the retrograde conduction pathway using the standard
technique of His refractory ventricular premature beat
because the retrograde conduction decrements after premature
ventricular stimulation. The VA interval is usually long and
an AP potential may be present in as many as 75 percent of
cases.25 The pathways must usually be mapped and ablated in
tachycardia, because it is often not possible to achieve reliable
exclusive AP conduction during ventricular pacing, owing to
either AV node conduction or retrograde block at any cycle
length longer than that of the tachycardia. Success rate of
radiofrequency ablation (RFA) is more than 95 percent, but
recurrence rates are higher than for typical APs. AV block and
coronary damage are the potential complications.4
Dual AV node physiology in pediatric patients is seen
in only 60 percent of cases26,27 in comparison to adults
(90100%)28 with inducible AVNRT. The difference in the
baseline conduction properties of the two pathways does not
reach the threshold for dual physiology in about 40 percent of
children. Magnitude of the AH (atrium-His bundle) change at
the transition from the fast to the slow pathway is related to
heart size and therefore to age, because AH or the PR interval
increases with age. Younger children have faster conduction in
the slow pathway than older children and adults.27 In children,
the slope change of AH versus AA (atrium-atrium) is a more
reliable and specific measure of the transition between the fast
and slow pathways than the AH jump alone. For ablation of
AVNRT, smaller catheter should be used in smaller children
(< 20 kg), to minimize the lesion size. Success rate is more
than 95 percent.26 The risk for heart block is higher because
of relatively large lesion size compared with the size of the
heart and closeness of smaller AV node to the slow pathway
in smaller patients. The reported incidences of coronary

injury4,6 are 0.03 percent in children29 and 0.06 to 0.1 percent
in adults30 during AVNRT and APs ablation. Cryoablation is
a good alternative therapy in children with a 97 percent acute
success rate and 2 percent recurrence with cryoablation.31
There are no reports of permanent AV block with cryoablation.
Accessory pathway function may spontaneously disappear
by 1 year of age.32 Aggressive pharmacologic control should
be attempted first before ablation, because of known risks of
catheterization and ablation in this age group. Radiofrequency
ablation lesions may increase in size during development and
may lead to sudden cardiac death.3 Coronary artery damage is
also a heightened risk in infants due to close proximity of the
coronaries (RCA and LCX) to the ablation catheter.4-6 Despite
these, ablation is still needed in a small subset of infants with
AP-mediated tachycardia. Lesion size is related to catheter-tip
size, RF power, tip temperature and lesion duration. Therefore
ablation should be done on atrial side with low temperature
(55C60C) and of shorter duration burns with 5F catheter
tip. Cryotherapy is much less harmful to coronary arteries.
The pre-excitation syndromes are statistically increased
in patients with Ebstein malformation, l-transposition of
the great arteries or hypertrophic cardiomyopathy. Multiple
pathways are present in 30 to 80 percent of patients33-37
compared with 5 to 10 percent of patients without CHD.30,34,36
Accessory atrioventricular connections in Ebstein
anomaly pose special problems. Differentiation of atrial
and ventricular signals and precise localization of the AV
groove can be difficult in Ebstein anomaly, leading to a
lack of specificity for what appear to be excellent signals
in predicting a successful ablation site. The true AV groove
(site of AP potentials) is best identified by a right coronary
electrode wire. Catheter stabilization for free wall pathways in
the largest hearts is difficult and is not sufficiently improved
through the use of a long sheath or a variety of approaches.2
Coronary damage is common, probably because of the thin
right ventricular wall and often diminutive right coronary
artery. The success rate is 80 to 90 percent with infrequent
major complications such as permanent AV block.33-35
Recurrence rates have been reported to be as high as 40
percent, particularly, if multiple pathways are present.33-37
Ablation procedures in patients with heterotaxy or
AV discordance require detailed echocardiography and
angiography for defining the complex anatomy of the atria, the
AV ring and the coronary sinus. Careful attention must be given
to locate the normal conduction system thereafter. In most of
the patients with AV discordance, the AP has been associated
with the tricuspid valve, whereas the His bundle has been
associated more closely with the mitral valve. After locating
the normal and abnormal conduction, electrophysiologic study
and RFA of the APs can proceed with less risk for damage
to the normal conduction system. The AV node in corrected
transposition is typically situated superior and anterior in the
atrial wall. The penetrating bundle then runs in the fibrous
Safety vs Efficacy of RADIOFREQUENCY Ablation

Risk for vascular injury, secondary to thrombus or embolus
formation, exists with any catheterization and ablation in
smaller children. To minimize these, a tendency is not to use
the retrograde arterial approach in children. New or increased
valvular regurgitation also has been reported in pediatric
patients after use of the retrograde arterial approach. The
risk for acute coronary damage is also increased in smaller
children. Data on late coronary function are not available
in animals, children or adults. Isolated case reports of late

coronary stenosis have also been described, especially in
children who had extensive ablation of transannular pathways
in conditions like Ebstein anomaly. Virtually all pediatric
programs use general anesthesia for ablation cases and most
non-electrophysiologic catheter interventions.
Safety concerns dominate the decision to ablate in many
pediatric arrhythmias. Myocardial injury3 and potentially
severe coronary injury4-6 are more likely with RFA in this age
group with AP ablation. Radiofrequency abalation lesion may
grow with age and may lead to sudden cardiac death.3 About
40 percent of APs in infants spontaneously stop functioning
during the first year of life32 and an additional one-third of
patients are unlikely to have symptoms between infancy
and early childhood,41 so ablation should be planned when
safety and benefits edge over complications. In contrast to
the situation in infants, even asymptomatic Wolff-ParkinsonWhite (WPW) patients between the ages of 10 and 18 years
may be managed more aggressively than adults. Unlike
asymptomatic adults older than age 28 years, who are unlikely
to ever have symptoms, the older child with a high-risk
pathway is exactly the type of patient who may present with
sudden arrhythmic death as their initial symptom, leading to
the recommendation that such patients should undergo risk
stratification and RFA accordingly.
Safety of radiofrequency and potential

use of cryoablation
61
continuity between the right sided mitral valve and the anterior
cusp of the posterior great artery and continues as left bundle
branch on the right side of the ventricular septum. The right
bundle branch then penetrates the ventricular septum to emerge
in the inferior left-sided right ventricle. A second AV node is
often present more inferiorly (in the normal area of the triangle
of Koch).This can also link to the ventricular conduction fibers
posteriorly (inferior to a ventricular septal defect). Conduction
sling,38 which joins these posterior and anterior ventricular
bundle branches together, is known as Mnckeberg sling. These
anatomic findings provide the substrate for different types of
ventricular excitation or preexcitation and AV reciprocating
tachycardias.
Despite all these limitations, most APs in patients with CHD
can be safely and effectively ablated despite the difficulties of
unusual anatomy and abnormal course of conduction fibers.
In children, atrial re-entrant tachycardias are relatively
rare in the absence of either structural or functional heart
disease. Age presentation is bimodal. Most common is during
the third trimester of fetal life, when atrial flutter accounts for
up to 33 percent of fetal tachycardias.1 Neonatal atrial flutter
almost universally resolves without recurrence, if it can be
managed successfully during fetal and early neonatal life.39 So
ablation therapy for such infants is usually not necessary and
has never been reported. A second presentation peak occurs
during adolescence, when both atrial flutter and fibrillation
may occur in the absence of any identifiable structural,
hormonal or chemical cause. Initial management should be
conservative. But ablation is usually needed in this age group
because of high recurrence rate despite medical therapy.
Success rate is more than 90 percent for the flutter subgroup.40
Techniques for ablation of atrial flutter or fibrillation
in the larger child are not much different than in adults. The
timing (when to ablate) and technique chosen should be the
most conservative in terms of safety because complications
such as pulmonary vein stenosis and stroke can be devastating
to a child.
Radiofrequency ablation of atrial tachycardia in post
operative CHD patients has many unique challenges, because
of anatomic complexity, atypical tachycardia substrates and
abnormally thick atrial muscle, which is difficult to ablate.
Technologic advances in 3D mapping and the broader
availability of ablation catheters designed to make more
effective RF lesions have significantly improved outcomes.
Electrophysiologic procedures cause major complications

in 0.7 (diagnostic EP study) to 2.0 percent (if ablation
is included). Myocardial injury and potentially severe
coronary injury are more likely with RFA in the pediatric
population. Cryoablation has several potential advantages
over RFA, including reversible cryomapping before the
production of a permanent lesion, adherence of the catheter
tip to the endocardium on freezing, a well-defined edge of
the cryolesion, minimal effects on adjacent coronary arteries
and a lower incidence of thrombus. Only disadvantage of
cryoablation is that lesion size is less and data regarding this
therapy in pediatric population are less.
Pacemakers in Children
About one percent of all pacemakers are implanted in the
children.42 Though there is not much difference in surgical
technique in children and adults for pacemaker implanation,
still it requires an experienced and skilled surgeon to evaluate
the problems in the smaller babies regarding implantation and
life long consequences.
Indications
Indications for pacing in newborns and infants are divided
predominantly into three groups based on American College
873
11
874
of Cardiolgoy/American Heart Association (ACC/AHA)

guidelines:43
1. Congenital abnormalities of the conduction system.
2. Acquired heart blocks after cardiac surgery for correction
of congenital defects.
3. Sinus node diseases.
Rare indications include the therapy of tachyarrhythmias,
hypertrophic obstructive cardiomyopathy and of the longQT-syndrome.
Implantation
Implantation of a pacemaker in infants requires the individual
assessment of:
1. Access (endovenous versus epicardial).
2. Leads.
3. Implantation site (infraclavicular versus abdominal).
4. Selection between subcutaneous versus submuscular plane.
The expected growth of the child, lifelong dependency
on pacing therapy and multiple revisions in future have to be
taken into consideration during implantation.
Currently it is recommended to use the epicardial approach
in infants until the age of 3 to 4 years in order to prevent a
lesion of the subclavian vein. With advancement in technique
and hardwares, the trend from epicardial towards endovenous
leads is increasing.
Lead revision due to growth of children remains a potential
problem in pacing therapy until puberty. Fibrotic attachment
to the vessel wall (mostly at the junction of the subclavian
and brachiocephalic vein with the superior vena cava) can
compromise a later advancement of the lead. This results in
implantation of an additional new lead in a relatively short
period of time after the first implantation despite the normal
lead parameters. Keeping the large loop in the RA to reduce
this increases the chances of displacement (due to tension
of the floating loop on the tip of the endocardial electrode),
arrhythmias (if migrating to right ventricle) and significant
pulmonary valve insufficiency (if migrating to pulmonary
artery). Every year approximately 10 millimeters of lead length
is necessary to compensate body growth, thus 80 millimeter
right atrial lead loop allows 6 to 12 years (mean 8 years) of
growth without need of lead replacement.44 Redundant lead
loop within the inferior vena cava or sliding technique of lead
fixation at the site of venous entrance with slowly absorbable
sutures are of questionable value in view of lead adherence to
vascular wall.
The isodiametric construction of leads allows an easier and
safer elective extraction. Active fixation allows an anchorage
at every desired position, which is helpful in anatomic
variations or complex cardiac malformations. Continuous
release of steroid in the first phase after implantation ensures
stable low chronic stimulation thresholds. Severe tricuspid
regurgitation and atrial or ventricular perforation are the
potential complications after lead placement.
Vessel recanalisation with balloon dilatation should be

considered in case of severe obstruction or occlusion of the
subclavian vein or the superior vena cava combined with
surgical treatment before planning an epicardial or alternative
approach.
Epicardial pacing indications in newborns or infants are:
1. Too small baby.
2. Venous abnormalities or congenital malformations, which
make a venous lead implantation impossible: discordant
atrioventricular connection, tricuspid atresia or after
Fontan surgery.
3. If all upper venous vessels have thrombotic occlusions and
alternative approaches are not possible.
4. If a right-to-left shunt with the risk of systemic embolization
exists.
5. If one wants to prevent the endovenous problems regarding
growth. Epicardial leads (cork-screw mechanism or only
a suture fixed) should be steroid-eluting and bipolar.
Disadvantage of epicardial pacing leads are higher
threshold and slightly higher fracture rate because of the
higher mechanical stress compared to endovenous leads.
Another alternative for endocardial pacing is the transatrial
approach. Indications for this more invasive approach are
occluded, obstructed, hypoplastic central veins or disconnected
superior vena cava from the RA (either congenital or post
surgical). A transatrial approach can replace the epicardial
stimulation, which would normally be used in these situations
and prevents its potential complications.
Pulse generators are usually implanted subpectorally (sub
muscularly) to prevent pocket related problems in small
children. This requires bipolar leads to prevent pectoral muscle
stimulation. The cosmetic aspect is much more favorable
with this approach. It also prevents Twiddler syndrome. For
using epicardial systems (mostly in babies), pocket is created
abdominally behind the anterior sheet of the rectus muscle
(subxiphoidal approach).
In view of multiple lead implantations during lifetime,
pediatric pacing therapy should only be carried out by
experienced surgeons and in well equipped cath labs to prevent
or to minimize complications. Prior to every single lead
insertion, physician should judge the central venous access in
terms of stenosis or occlusion sonographically and then try to
plan the operation. If a new pacing lead has to be implanted
endovenously, the old screw-in lead should be extracted
during the same session. An additional endovenous lead
loop for further growth has to be considered preoperatively.
The latest rate adaptive pacemakers should be implanted to
provide most physiological pacing mode.
Left ventricular systolic or diastolic dysfunction can
result after long-term right ventricular apical pacing in
the young. This can be reduced by pacing at septal or
high right ventricular outflow tract. With these positions,
echocardiographic findings show markedly normalized
ventricular contraction patterns.
Conclusion
Arrhythmia mechanisms, ongoing myocardial development,
increased risk for vascular injury, AV node damage, smaller
cardiac size and presence of CHDs should be considered
prior to ablation in children. In a child, safety should be a
priority over efficacy. Therefore, variations of technique
should be applied to the decision to ablate the energy source
and its delivery, the catheter approach to the heart and the
AV ring and the follow-up. Still it seems clear that a variety
of techniques and approaches are necessary to successfully
ablate substrates in all locations of the heart, including the AV
groove in children.
Pacemaker implantation into children does not differ
substantially from operations in adults. As most of these
children remain pacemaker dependent for lifetime, it is of
tremendous importance to minimize all revisions regarding
the implanted systems and to enable small patients a nearly
normal quality of life. For ICD and CRT in pediatric patients
data regarding indications and outcomes are limited and are
continuously evolving.
Declare the past, diagnose the present, foretell the future.
Hippocrates
References
1. Ko JK, Deal BJ, Strasburger JF, et al. Supraventricular
tachycardia mechanisms and their age distribution in pediatric
patients. Am J Cardiol. 1992;69:1028-32.
2. Saul JP, Hulse JE, De W, et al. Catheter ablation of accessory
atrioventricular pathways in young patients: use of long vascular
sheaths, the transseptal approach and a retrograde left posterior
parallel approach. J Am Coll Cardiol. 1993;21:571-83.
3. Saul JP, Hulse JE, Papagiannis J, et al. Late enlargement of
radiofrequency lesions in infant lambs: Implications for ablation
procedures in small children.Circulation. 1994;90:492-9.
4. Blaufox AD, Saul JP. Acute coronary artery stenosis during

slow pathway ablation for atrioventricular nodal re-entrant
tachycardia in a child. J Cardiovasc Electrophysiol. 2004;15:
97-100.
5. Paul T, Kakavand B, Blaufox AD, et al. Complete occlusion
of the left circumflex coronary artery after radiofrequency
catheter ablation in an infant. J Cardiovasc Electrophysiol.
2003;14:1004-06.
6. Bertram H, Bokenkamp R, Peuster M, et al. Coronary
artery stenosis after radiofrequency catheter ablation of
accessory atrioventricular pathways in children with Ebsteins
malformation. Circulation. 2001;103:538-43.
7. Hope EJ, Haigney MC, Calkins H, et al. Left main coronary
thrombosis after radiofrequency ablation: Successful treatment
with percutaneous transluminal angioplasty. Am Heart J.
1995;129:1217-9.
8. Nakagawa H, Chandrasekaren K, Pitha J, et al. Early detection
of coronary artery injury produced by radiofrequency ablation
within the coronary sinus using intravascular ultrasound
imaging. Circulation. 1995;92:I-610.
9. Erb TO, Kanter RJ, Hall JM, et al. Comparison of
electrophysiologic effects of propofol and isoflurane-based
anesthetics in children undergoing radiofrequency catheter
ablation for supraventricular tachycardia. Anesthesiology.
2002;96:1386-94.
10. Pass RH, Walsh EP. Intracardiac electrophysiologic testing in
pediatric patients. In: Walsh EP, Saul JP, Triedman JK (Eds).
Cardiac Arrhythmias in Children and Young Adults with
Congenital Heart Disease. Philadelphia: Lippincott Williams
11. Benson DW, Smith WM, Dunnigan A. Mechanisms of regular
wide QRS tachycardia in infants and children. Am J Cardiol.
1982;49:1776-88.
12. Weindling SN, Walsh EP, Saul JP. Management of supra
ventricular tachycardia in infants. J Am Coll Cardiol. 2000;21:
294a.
13. Walsh EP, Saul JP, Hulse JE, et al. Transcatheter ablation
of ectopic atrial tachycardia in young patients using radiofrequency current [see comments]. Circulation. 1992;86:1138-46.
14. Weindling SN, Saul JP, Walsh EP. Efficacy and risks of medical
therapy for supraventricular tachycardia in neonates and
infants. Am Heart J. 1996;131:66-72.
15. Gillette PC, Smith RT, Garson A Jr, et al. Chronic
supraventricular tachycardia: a curable cause of congestive
cardiomyopathy. JAMA. 1985;253:391-2.
16. Walsh EP. Ablation of ectopic atrial tachycardia in children. In:
Huang SK (Ed). Radiofrequency Catheter Ablation of Cardiac
Arrhythmias: Basic Concepts and Clinical Applications. Mt.
Kisko, NY: Futura; 1994. pp. 421-43.
17. Villain E, Vetter VL, Garcia JM, et al. Evolving concepts in
the management of congenital junctional ectopic tachycardia:
a multicenter study [see comments][review]. Circulation.
1990;81:1544-9.
18. Walsh EP, Saul JP, Sholler GF, et al. Evaluation of a staged
treatment protocol for rapid automatic junctional tachycardia
after operation for congenital heart disease. J Am Coll Cardiol.
1997;29:1046-53.
19. Sholler GF, Walsh EP, Saul JP, et al. Evaluation of a staged
treatment protocol for postoperative rapid junctional ectopic
tachycardia. Circulation. 1988;78:II-597.
61
The implantable cardioverter-defibrillator (ICD) is now

established as safe and effective for preventing sudden cardiac
death (SCD) in children. The continued miniaturization of
devices and leads have allowed their use in smaller patients,
including children, infants and even neonates. However, the
proper indications, implantation methods, programing and
long-term follow-up issues continue to evolve. Individualized
implant techniques are necessary for the smallest children and
those with complex CHD.
Cardiac resynchronization therapy (CRT) has been
extensively studied in adult heart failure patients. There
are less trial of CRT in patients with CHD who make up a
substantially different population that is characterized by
unusual anatomy including univentricular heart, systemic right
ventricles and other anomalies. CRT has been demonstrated
to benefit certain CHD patients, but significantly varies by
substrate.
875
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876
20. Dubin AM, Cuneo B, Strasburger J, et al. Congenital junctional

tachycardia and congenital complete AV block: a shared
etiology? Heart Rhythm. 2005;2:313-5.
21. Gillette PC, Garson A Jr, Porter CJ, et al. Junctional automatic
ectopic tachycardia: New proposed treatment by transcatheter
His bundle ablation. Am Heart J. 1983;106:619-23.
22. Guarnieri T, German LD, Gallagher JJ. The long RP tachycardias [review]. Pacing Clin Electrophysiol. 1987;10: 103-17.
23. Ticho BS, Walsh EP, Saul JP. Ablation of permanent junctional
reciprocating tachycardia. In: Huang SK, (Ed). Radiofrequency
Catheter Ablation of Cardiac Arrhythmias: Basic Concepts and
Clinical Applications. Mt. Kisko, NY: Futura; 1994. pp. 397409.
24. Gaita F, Hassaguerre M, Giustetto C, et al. Catheter ablation
of permanent junctional reciprocating tachycardia with
radiofrequency current. J Am Coll Cardiol. 1995;25:648-54.
25. Hassaguerre M, Montserrat P, Warin JF, et al. Catheter
ablation of left posteroseptal accessory pathways and of long
RP tachycardias with a right endocardial approach. Eur Heart
J. 1991;12:845-59.
26. Van Hare GF, Chiesa NA, Campbell RM, et al. Pediatric
Electrophysiology Society. Atrioventricular nodal reentrant
tachycardia in children: effect of slow pathway ablation on fast
pathway function [comment]. J Cardiovasc Electrophysiol.
2002;13:203-9.
27. Blaufox AD, Rhodes JF, Fishberger SB. Age related changes
in dual AV nodal physiology. Pacing Clin Electrophysiol.
2000;23:477-80.
28. Rosen KM, Bauernfeind RA, Swiryn S, et al. Dual AV nodal
pathways and AV nodal reentrant paroxysmal tachycardia. Am
Heart J. 1981;101:691-5.
29. Kugler JD, Danford DA, Deal BJ, et al. Radiofrequency
catheter ablation for tachyarrhythmias in children and
adolescents. The Pediatric Electrophysiology Society. N Engl J
Med. 1994;330:1481-7.
30. Calkins H, Langberg J, Sousa J, et al. Radiofrequency catheter
ablation of accessory atrioventricular connections in 250
patients: abbreviated therapeutic approach to Wolff-ParkinsonWhite syndrome. Circulation. 1992;85:1337-46.
31. Avari JN, Jay KS, Rhee EK. Experience and results during
transition from radiofrequency ablation to cryoablation
for treatment of pediatric atrioventricular nodal reentrant
tachycardia. Pacing Clin Electrophysiol. 2008;31:454-60.
32. Deal BJ, Keane JF, Gillette PC, et al. Wolff-Parkinson-White
syndrome and supraventricular tachycardia during infancy:
management and follow-up. J Am Coll Cardiol. 1985;5:130-5.
33. Levine JC, Walsh EP, Saul JP. Radiofrequency ablation of

accessory pathways associated with congenital heart disease
including heterotaxy syndrome. Am J Cardiol. 1993;72:689-93.
34. Jackman WM, Wang XZ, Friday KJ, et al. Catheter ablation of
accessory atrioventricular pathways (Wolff-Parkinson-White
syndrome) by radiofrequency current [see comments]. N Engl
J Med. 1991;324:1605-11.
35. Van Hare GF, Lesh MD, Stanger P. Radiofrequency catheter
ablation of supraventricular arrhythmias in patients with
congenital heart disease: results and technical considerations. J
36. Smith WM, Gallagher JJ, Kerr CR, et al. The electrophysiologic
basis and management of symptomatic recurrent tachycardia in
patients with Ebsteins anomaly of the tricuspid valve. Am J
Cardiol. 1982;49:1223-34.
37. Twidale N, Wang X, Beckman KJ, et al. Factors associated
with recurrence of accessory pathway conduction after
radiofrequency catheter ablation. Pacing Clin Electrophysiol.
1991;14:2042-8.
38. Symons JC, Shinebourne EA, Joseph MC, et al. Criss-cross
heart with congenitally corrected transposition: Report of a
case with d-transposed aorta and ventricular preexcitation. Eur
J Cardiol. 1977;5:493.
39. Dunnigan A, Benson DW, Benditt DG. Atrial flutter in
infancy: diagnosis, clinical features and treatment. Pediatrics.
1985;75:725-9.
40. Kugler JD, Danford DA, Houston K, et al. Radiofrequency
catheter ablation for paroxysmal supraventricular tachycardia
in children and adolescents without structural heart disease.
Pediatric EP Society, Radiofrequency Catheter Ablation
Registry. Am J Cardiol. 1997;80:1438-43.
41. Perry JC, Garson A, Jr. Supraventricular tachycardia due
to Wolff-Parkinson-White syndrome in children: early
disappearance and late recurrence [see comments]. J Am Coll
Cardiol. 1990;16:1215-20.
42. Bink-Boelkens MTHE. Cardiac pacing in infants and children.
Neth J Cardiol 1992;5:199-202.
43. Recommendations for Permanent Pacing in Children,
Adolescents and Patients With Congenital Heart DiseaseACC/AHA/HRS 2008 Guidelines for Device-Based Therapy
of Cardiac Rhythm Abnormalities: Executive Summary: A
Report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines.
44. Gheissari A, Hordof AJ, Spotnitz HM. Transvenous pacemaker
in children: relation of lead length to anticipated growth. Ann
Thorac Surg. 1991;52:118-21.
Sec t i on
12
Miscellaneous
C hapter
62
Congenital Coronary Artery

Anomalies
Nick Hayes, Shakeel Qureshi
Congenital coronary artery anomalies encompass a constellation

of conditions where there is a variation in the origin, course,
intrinsic anatomy or termination of one or both the coronary
arteries. Although the prevalence of these conditions are low
compared to that of other congenital heart defects (CHD),
their pathophysiological effects can be of critical importance.
In this chapter we will focus on isolated congenital coronary
artery abnormalities (i.e. those occurring in the absence of
other structural cardiac defects), for whilst coronary anomalies can often be found in association with other CHD (e.g.
transposition of the great arteries or pulmonary atresia), these
conditions are addressed specifically elsewhere.
Normal Coronary Arteries

Before considering coronary anomalies it is important to
review the anatomical structure, physiological function
and embryogenesis of normal coronary arteries. Defining
normal coronary arrangement is not however as straight
forward as it may seem. It would be simple to take a
definition of normality as the pattern occurring in the majority
(i.e. > 50%) of the population and consequently any deviation
from this as an anomaly. However, certain variations in
coronary arrangements with no physiological significance
can occur in large proportions of the population. For
example, a separate origin of the conal artery direct from the
right sinus of Valsalva, resulting in three distinct coronary
ostia, is observed in close to 50 percent of the population.1
It seems incongruous to classify such benign normal
variations as anomalous, which has led to the proposal that
an anomaly be defined as occurring in less than 1 percent
of an unselected population.2 This of course assumes that
the true prevalence of each pattern is known and does not
incorporate pathophysiological significance, but does
provide a useful platform on which to base a definition, with
subsequent further classification.
Anatomy
The coronary arterial circulation has been extensively described3
and in essence is similar to any systemic arterial network,
consisting of large proximal epicardial conductive arteries
leading to an extensive distal myocardial arteriolar-capillary
bed.4 Typically there are two major coronary arteries: the right
coronary artery and the left main stem, which take origin from
the two correspondingly named right and left aortic sinuses of
Valsalva, adjacent to the pulmonary artery (Figure 1). These
sinuses are small bulbous out pouchings between the aortic
valve and sinotubular junction. There are usually three aortic
sinuses, with the third most distant from the pulmonary trunk
termed the non-coronary sinus as it is extremely unusual for a
major coronary artery to take origin from this sinus. Whilst the
coronary artery ostia are usually located fairly centrally within
the aortic sinus and just below the sinotubular junction, there is
considerable variation both in proximity to valvar commissures
and height of take off, with ostia up to 1 cm above the sinotubular
junction still considered within the normal variation.5,6
Left Coronary Artery

The left main stem arises from the left sinus of Valsalva
and courses laterally, posterior to the pulmonary artery and
anterior to the left atrial appendage, a short distance (12 cm
in adult) before dividing into the circumflex and left anterior
descending (also termed the anterior interventricular)7 arteries.
The diameter is usually larger than the right coronary artery
(RCA) as it typically supplies a larger area of myocardium
including the majority of the left ventricle. In around 1 percent
of the population there are separate origins of the circumflex
and left anterior descending arteries direct from the left aortic
sinus with no left main stem.6
The left circumflex (LCx) artery runs under the left
atrial appendage and then travels posterior-inferiorly in left
Miscellaneous
12
Figure 1: Aortic root angiogram and cardiac MRI demonstrating normal coronary arrangement
atrioventricular groove. A number of marginal branches, the

largest of which is termed the obtuse marginal, arise along
the course of the circumflex and supply the lateral wall of
the left ventricle and the anterolateral papillary muscle. The
sinus node artery arises from the circumflex in 50 percent of
individuals. Around 10 percent of the population display a
left-dominant pattern,3 where the posterior descending (also
termed the inferior interventricular)7 artery arises from the
circumflex and proceeds to supply the atrioventricular node
and inferior right ventricular surface. In these individuals, the
circumflex artery is considerably larger in diameter.
The left anterior descending (LAD) artery descends along
the anterior surface of the heart in the anterior interventricular
groove and can continue beyond the apex to anastamose with
the posterior descending artery. The left conal artery is the first
branch and may form the circle of Vieussens by anastomosing
with the right conal artery.8 Diagonal branches supply the
anterior surface of the left and right ventricles and around
four septal perforators enter the interventricular septum
and anastamose with septal branches from the posterior
descending artery.
Right Coronary Artery
880
Originates from the right sinus of Valsalva and initially courses

anteriorly between the pulmonary trunk and right atrial
appendage to the right atrioventricular groove. In around 50
percent of the population the right conal artery forms the first
branch of the right coronary artery, although as previously

mentioned, in the rest the conal artery takes origin directly from
the aortic root with a separate ostial orifice. The next branch
is usually the sinus node artery, although again in around 50
percent this originates from the circumflex. Several marginal
branches, the largest of which is termed the acute marginal,
supply the right ventricular free wall. Around 90 percent of the
population have a right-dominant pattern, with the posterior
descending artery originating from the right coronary artery.3
It is important to note that the term dominance is merely a
descriptive term reflecting this pattern and does not refer to
the coronary artery supplying the majority of the myocardium,
which is nearly always the left coronary artery, irrespective
of the origin of the posterior descending artery. The posterior
descending artery supplies the inferior surface of the left and
right ventricles, has posterior septal perforators that penetrate
the interventricular septum and also has a branch supplying
the atrioventricular node.
Physiology
The coronary arteries are responsible for the supply of oxygen
to the highly aerobic myocardium. This supply is determined
by the oxygen content of the blood (which is primarily
related to amount of saturated hemoglobin) and the amount
of coronary flow, which in turn is determined by coronary
perfusion pressure (the difference between the coronary artery
pressure and ventricular end diastolic pressure) and coronary
Embryogenesis
Initial theories regarding embryological coronary artery
development focused on a supposed fusion of a subepicardial
vascular network with endothelial buds that grew out from
the base of the truncus arteriosus.9 However, in 1989 Bogers
identified major coronary arteries in the aortic wall prior to
the emergence of coronary ostia, suggesting in-growth, rather
than out-growth of these vessels10,11 and definitive evidence of
this has been demonstrated in chick embryos.12,13 Whilst the
myocardium is formed from an endothelial and muscular tube
derived from lateral plate mesoderm, the cells that generate the
epicardium that appears crucial to coronary vessel development,
originate from a component of mesothelium that arises near
the liver primordium, termed the proepicardial organ (PEO).
This grows towards the heart and then gradually spreads out,
encasing the entire myocardium and pericardial cavity.11 These
epicardial cells then undergo tansformation under the control
of various growth and transcription factors and differentiate
to form vascular progenitor cells, which migrate deep into the
myocardium and coalesce to form channels.13
The vascular tubes undergo branching and fusion to form a
complex subepicardial vascular network, part of which forms a
peritruncal ring, from which capillary plexi penetrate the aortic
root to form the beginnings of the major coronary arteries.11 This
appears to occur at multiple sites (including the non-coronary
sinus), but subsequent fusion and apoptosis occurs14 leading
to a definitive coronary circulation around 45 days gestation.9
Ongoing vascular remodelling then takes place in the presence of
blood flow through the arterial tree. The molecular mechanisms
behind many of these processes are poorly understood and
currently under investigation, but an appreciation of the complex
nature of coronary angiogenesis in fact makes it remarkable that
congenital coronary anomalies are so rare.
Abnormalities
Classification
Earlier classification systems tended to group anomalies into
major and minor variations depending on clinical relevance,
but a more recent and comprehensive classification system
has categorized the various anomalies based on the underlying
morphology and is displayed in Box 1.15 As can be seen, the
range of possible coronary anomalies is vast and further
discussion will focus on the more important conditions.
Abnormalities of Origin and Course

Anomalous Left Coronary Artery from the
Pulmonary Artery
Anomalous origin of the left coronary artery from the
pulmonary artery (ALCAPA) is also known by the eponymous
name Bland-White-Garland syndrome following the original
clinical description by these authors in 1933.16 This is a
rare anomaly with an estimated incidence of 1:300,000 live
births,17,18 but is of critical clinical importance as it represents
one of the most common causes of myocardial ischemia in
infants and children.19
62
Congenital Coronary Artery Anomalies
arterial vascular resistance. During ventricular systole,

the myocardial compressive forces cause almost complete
obstruction of the arterioles, resulting in an extremely high
vascular resistance. Consequently, coronary blood flow,
particularly to the left ventricle, occurs virtually exclusively in
diastole. Usually, coronary blood flow far exceeds myocardial
oxygen demand and there is sufficient coronary flow reserve
even at peak exertion. However, reduced coronary perfusion
pressure (for example, from coronary stenosis and/or elevated
end diastolic pressure) results in absence of coronary flow
reserve and ensuing myocardial ischemia to which the
subendocardium is particularly susceptible. It is of no surprise
that transient periods of ischemia occur with more mild
stenosis only at times of high myocardial oxygen demand
(i.e. on exertion). As the stenosis progresses and the impact
on coronary perfusion increases, ischemia becomes more
apparent. Ultimately, critical lack of oxygen supply results in
myocardial cell infarction.
Morphology and Pathophysiology

Anomalous left coronary artery from the pulmonary artery
typically occurs in isolation, although can be associated
with other CHD such as ventricular septal defects, tetralogy
of Fallot and aortic coarctation.9 Usually the anomalous left
coronary artery originates from the right pulmonary sinus,
which is in closest proximity to the left aortic sinus, although
occasionally there is take off from the other pulmonary
sinuses or even more distal in the main or proximal branch
pulmonary arteries.20,21 The pathophysiology depends on the
status of the blood flow in the left coronary artery.22 In the
initial neonatal period, the pulmonary vascular resistance
(PVR) and pressures are high and there is antegrade perfusion
of the left coronary myocardial territory, albeit with slightly
desaturated blood from the pulmonary artery. This generally
allows adequate myocardial perfusion to meet oxygen demand
and there is no ischemia.
As the PVR begins to fall, coronary perfusion pressure falls
and myocardial oxygen delivery depends on collateral flow
from the right coronary artery. Occasionally there is extensive
intercoronary collateralization or persistent elevation in
the pulmonary artery pressures and myocardial perfusion is
maintained, but typically this is not the case and significant
LV myocardial ischemia ensues. With further reduction in
the PVR, flow in the left coronary artery becomes retrograde,
resulting in steal from the right coronary circulation as it is
881
Miscellaneous
12
Box 1: Classification of coronary anomalies from Angelini15

A. Anomalies of origination and course.
1. Absent left main trunk (split origination of LCA).
2. Anomalous location of coronary ostium within aortic root
or near:
High
Low
Commissural.
3. Anomalous location of coronary ostium outside normal
coronary:
Right posterior aortic sinus
Ascending aorta
Left ventricle
Right ventricle
Pulmonary artery
LCA that arises from posterior facing sinus
Cx that arises from posterior facing sinus
LAD that arises from posterior facing sinus
RCA that arises from anterior right facing sinus
Ectopic location (outside facing sinuses) of any
coronary
- From anterior left sinus
- From pulmonary trunk
- From pulmonary branch
Aortic arch
Innominate artery
Right carotid artery
Internal mammary artery
Bronchial artery
Subclavian artery
Descending thoracic aorta.
4. Anomalous location of coronary ostium at improper sinus
(which may involve joint origination or single coronary
pattern):
RCA that arises from left anterior sinus, with
anomalous course:
Posterior atrioventricular groove or retrocardiac

Retroaortic
Between aorta and pulmonary artery (intramural)

Intraseptal
Anterior to pulmonary outflow
Posteroanterior interventricular groove (wrap
around).
LAD that arises from right anterior sinus, with
anomalous course
Between aorta and pulmonary artery (intramural)
Contd...

Intraseptal
Posteroanterior interventricular groove (wrap
around).
Cx that arises from right anterior sinus, with
anomalous course
Posterior atrioventricular groove

Retroaortic.
LCA that arises from right anterior sinus, with
anomalous course
Posterior atrioventricular groove

Retroaortic
Between aorta and pulmonary artery

Intraseptal
Posteroanterior interventricular groove.
5. Single coronary artery (see A4)
B. Anomalies of intrinsic coronary arterial anatomy
1. Congenital ostial stenosis or atresia (LCA, LAD, RCA,
Cx).
2. Coronary ostial dimple.
3. Coronary ectasia or aneurysm.
4. Absent coronary artery.
5. Coronary hypoplasia.
6. Intramural coronary artery (muscular bridge).
7. Subendocardial coronary course.
8. Coronary crossing.
9. Anomalous origination of posterior descending artery
from the anterior.
10. Split RCA:
Proximal + distal PDs that both arise from RCA
Proximal PD that arises from RCA, distal PD that
arises from LAD
Parallel PDs 2 (arising from RCA, Cx) or
codominant.
11. Split LAD:
LAD + first large septal branch
LAD, double (parallel LADs).
12. Ectopic origination of first septal branch:
RCA
Right sinus
Diagonal
Ramus
Cx
C. Anomalies of coronary termination
1. Inadequate arteriolar/capillary ramifications.
2. Fistulas from RCA, LCA, or infundibular artery to:
Right ventricle
Right atrium
Coronary sinus
Superior vena cava
Pulmonary artery
Pulmonary vein
Left atrium
Left ventricle
Multiple, right + left ventricles.
D. Anomalous anastomotic vessels
Cx = Circumflex; LAD = Left descending coronary artery; LCA = Left coronary artery; RCA = Right coronary artery; PD = Posterior descending branch.
882
is around 30 years of age, although for patients surviving

beyond 50, the risk of sudden death appears to decline.17
Clinical Features
The main aim of investigation is to differentiate ALCAPA

from other causes of a dilated poorly functioning left ventricle,
such as dilated cardiomyopathy and a high index of suspicion
is required in such patients.
Patients predominantly present in early infancy with

symptoms of congestive heart failure, such as breathlessness,
failure to thrive, sweating and wheezing. The classic history
includes acute episodes of irritability with associated pallor
secondary to myocardial ischemia, typically during feeding
or distress, when infant myocardial oxygen demand is at its
highest. Clinically patients have signs of left heart failure,
with reduced perfusion, displaced apex beat, 3rd or 4th
heart sounds and possibly a murmur secondary to mitral
regurgitation (which can be secondary to left ventricular
dilation or papillary muscle ischemia/rupture). Without
treatment around 90 percent of infants die within the first
year of life.23 Around 10 percent of patients with extensive
collateralization present later in childhood or adulthood
with a continuous murmur, angina, ventricular arrhythmia
or sudden death. The average life expectancy in this group
Investigation
Chest X-ray
Chest X-ray is non-specific with cardiomegaly from an
enlarged left heart and evidence of pulmonary congestion.
ECG
Classical signs of ischemia include pathological Q waves
in the inferolateral leads with poor R wave progression, ST
elevation and T wave inversion (Figure 2). However, not all
patients with ALCAPA have classical patterns of ischemia
on 12 lead ECG and although non-specific ST and T wave
changes are virtually always observed, they are also often
Figure 2: Twelve-lead ECG in a 6-week-old patient with ALCAPA. Note the pathological Q waves
and T wave inversion in I, aVL and V4-6, along with ST elevation in V2-3
62
shunted into the pulmonary artery, further aggravating the

ischemia. Stenosis of the origin of the left coronary artery may
at this point reduce the degree of steal and confer a degree of
protection.
883
Miscellaneous
12
present in myocarditis and dilated cardiomyopathy. The

presence of a Q wave width > 30 milliseconds in lead I, Q
wave depth > 3 mm in aVL and QR pattern in aVL has been
shown to be significantly associated with ALCAPA, but does
not confer a definitive diagnosis.24
ECHO
The left ventricle is typically dilated with severely impaired
systolic and diastolic function, although left ventricular
function can remain normal in infants with persistent elevation
in the pulmonary artery pressures25 and up to 10 percent of
adult patients may have normal global left ventricular function,
but often abnormalities are detected on strain imaging or stress
echocardiography.17,26 In contrast to dilated cardiomyopathy,
the papillary muscles tend to be bright and echogenic as a
result of infarction and fibrosis, although this is non-specific
(Figure 3). There is often significant mitral regurgitation
(MR) (from annular dilation, papillary muscle shortening and
also possible papillary muscle rupture) and the left atrium
is dilated. Advances in echocardiographic technology and
resolution now means that it is technically feasible to confirm
the diagnosis with 2D imaging of the coronary arteries, with
the left coronary artery demonstrated originating from the
pulmonary artery (Figure 4), but as the left coronary artery often
takes a course very close to the left aortic sinus, the connection
can easily be misinterpreted as normal (in as many as 70% in
some reports).24 Doppler assessment with color flow mapping
of the coronary flow is therefore essential for both confirming
and excluding the diagnosis with abnormal retrograde flow
noted in the left coronary artery and a retrograde jet of flow
noted in the pulmonary artery.27 The right coronary artery
tends to be dilated (with an RCA: aortic ratio often 0.14)28
Figure 4: Echocardiogram in parasternal short axis clearly demonstrating the connection of the left coronary artery to the pulmonary
artery on 2D, with retrograde flow from the coronary artery into the
pulmonary artery, noted on color flow mapping
and occasionally collateral flow can be seen. In cases where

the diagnosis remains uncertain following echocardiography,
more definitive imaging is required.
CT/MRI
Improved spatial resolution of cardiac computed tomography
(CT) and magnetic resonance (MRI) imaging has led to their
increasing use in coronary assessment and a number of reports
confirm accurate diagnosis of ALCAPA particularly in the adult
population where acoustic windows for echocardiography
tend to be poor.17,29-31 The CT demonstrates better spatial
resolution, although MRI allows for functional assessment of
the left ventricle and myocardium (including late enhancement
to assess myocardial viability) and does not involve ionizing
radiation. The high heart rates and high spatial resolution
required to clearly identify the coronary arteries in infants
limits the usefulness of these techniques in younger patients,
although it is likely that improving technology will extend
their use into this population.
884
Figure 3: 2-D Echocardiogram from the apical four-chamber view

in a patient with ALCAPA. The left ventricle is dilated, with severely
impaired ventricular function and in particular note the highly echogenic
appearance of the papillary muscles secondary to ischemic fibrosis.
A left atrial line is also seen crossing the atrial septum
Remains the gold standard for diagnosis, although with

improved imaging techniques catheterization is no longer
routinely necessary20 and invasive assessment in small
and often critically ill patients carries inherent risk. On
hemodynamic assessment the left ventricular end diastolic
pressure tends to be severely elevated with a consequent
increase in the pulmonary artery and right ventricular
pressures. Left to right shunts at the level of the pulmonary
artery tend to be small and may not be identified on a
saturation run, but this is rarely required with diagnostic
angiography. Either root angiography or selective right
coronary angiography should clearly delineate the anomalous
62
Figures 5A and B: Selective injection into the right coronary artery during cardiac cathterization in AP (panel A) and lateral (panel B) projections
in a patient with ALCAPA. The right coronary artery is dilated with collateral flow filling the left coronary system and a puff of contrast is seen
filling the pulmonary artery at the left coronary origin
left coronary artery and degree of collateralization (Figures

5A and B).
Management
Supportive medical management including ventilation,
inotropes, afterload reduction and diuretics can be used to
stabilise a sick patient, but the key to management is urgent
surgical repair to improve myocardial perfusion. Early surgical
techniques prior to the introduction of cardiopulmonary bypass
aimed to reduce pulmonary artery steal by either increasing
proximal pulmonary artery pressures with pulmonary artery
banding32 or ligating the pulmonary origin of the anomalous
left coronary artery.33 Subsequently establishment of a twocoronary system was reported with saphenous vein grafting34
or direct anastomosis of the left subclavian artery to the left
coronary artery.35 Direct reimplantation of the left coronary
artery was first reported in 197436 and with growing expertise
in neonatal coronary surgery as a result of the arterial switch
operation, has become established as the procedure of choice
in the majority. It is technically feasible in most patients and
affords high long-term patency rates.37 If the position or length
of the left coronary artery makes direct transfer unfeasible,
creation of an intrapulmonary coronary baffle (Takeuchi
operation)38 is an alternative to direct coronary transfer, but
future interventions for complications such as suprapulmonary
stenosis, baffle leaks and aortic regurgitation are required
in up to 30 percent of patients.20 It has been suggested that
in adults, reduced vessel elasticity, increased friability and

excessive collateralization make direct reimplantation more
hazardous and internal mammary artery bypass grafting may
be safer,39,40 There is, however, little data on long-term patency
of internal mammary grafts in ALCAPA patients and direct
reimplantation is still advocated in the majority of patients.41
If bypass grafting is performed, it is recommended that the
left coronary origin is ligated to prevent graft thrombosis from
competitive flow.
Overall mortality rates have fallen from 75 percent to 80
percent in the early 1980s to 0 percent to 23 percent in the
current era,20 with most mortality in the immediate postoperative period. Risk factors identified for 30 day mortality
include young age at operation and reduced pre-operative left
ventricular function, with the degree of MR not consistently
found to influence early mortality.42-44 The degree of MR tends
to improve with time and there is generally a consensus that
concomitant mitral valve surgery at the time of ALCPA repair
is not necessary (unless there is papillary muscle rupture).
This also increases cardiopulmonary bypass time in an already
compromised and ischemic ventricle.20,42-44 Mechanical
circulatory support may be required in the immediate
postoperative period to bridge to recovery and it is mandatory
that this is available to units performing surgical repair.
Mid- to long-term results following repair are excellent
with steady improvement and often normalization in left
ventricular function within 1 to 2 years and low long-term
mortality.20,43-46 Medical therapy to help off-load the ventricle
885
Miscellaneous
12
is often required for a period of time following repair. As

previously mentioned, additional surgery to repair the mitral
valve is usually not necessary unless there has been rupture of
a papillary muscle as the degree of MR tends to improve as the
left ventricular function and dilation improves. Late coronary
stenosis or graft occlusion can occur and symptoms suggestive
of ischemia, subsequent reduction in left ventricular function
or worsening in the degree of MR warrants investigation to
assess coronary patency.
Anomalous Right Coronary Artery from the

Pulmonary Artery
Anomalous origin of the right coronary artery from the
pulmonary artery (ARCAPA) appears considerably rarer
than ALCAPA, although on the whole ARCAPA appears
to be less severe and it is likely that the true incidence is
underestimated. The natural history is less well-defined, but
infant myocardial ischemia is unusual and typically patients
present at an older age with an incidental murmur and nonspecific ECG findings. Nonetheless some patients do present
with myocardial ischemia and sudden death, particularly
if there is a right dominant coronary pattern. Interestingly
associated cardiac lesions appear to be more common than
with ALCAPA and are reported in up to 1/3 of cases,47
although again this may reflect identification bias. Clearly
surgical repair, usually with coronary artery reimplantation,
is indicated in patients with evidence of myocardial ischemia.
There remains uncertainty as to whether surgery is indicated
in asymptomatic patients without evidence of myocardial
ischemia, but with dramatically improved operative mortality,
surgical repair is generally advocated to reduce the risk of
future sudden cardiac death (SCD).
Isolated Circumflex or Left Anterior Descending Artery

from the Pulmonary Artery
Both these anomalies are extremely rare, but can present with
signs of myocardial ischemia and there is a high incidence of
associated CHD.48 Experience is lacking regarding surgical
repair, but seems advisable, especially if there is evidence of
ischemia.
Total Anomalous Coronary Circulation

from the Pulmonary Artery
Either with both coronary arteries or a single coronary
circulation originating from the pulmonary artery. Extremely
rare and generally lethal, although successful repair in an
infant has been reported.49
Left Coronary Artery from the Right Aortic Sinus

886
The true prevalence of this anomaly is unknown, but estimates

range from 0.1 to 0.3 percent of the general population,50
which if true, represents a significant number of individuals.
Figure 6: Echocardiogram in the parasternal short axis demonstrating

a retroaortic course of the left coronary artery, having originated from
the right aortic sinus
Following origin from the right aortic sinus, the left coronary
artery takes one of four possible routes back to the left side of
the heart:51
1. Anteriorly around the pulmonary artery.
2. Between the great arteries (intra-arterial).
3. Within the subpulmonary muscular infundibulum.
4. Posteriorly around the aorta (retroaortic)Figure 6.
There may also be an associated proximal intramural
course, slit like opening of the coronary ostium and/or kinking
of the coronary artery of with acute angle take off.
This lesion has been noted in up to 20 percent of cases of
SCD in young adults, typically occurring during exertion,52 with
an interarterial coronary course conveying a particularly high
risk.51-54 Sudden death can frequently be the first presentation
with only about 1/3 of patients reporting previous symptoms
attributable to ischemia.52,53 Proposed mechanisms for
myocardial ischemia include: flap closure of a slit like coronary
ostium, compression of the intramural segment, kinking of
the coronary artery with acute angle take-off and compression
of the coronary artery as it passes between the great arteries
aggravated by increased stroke volume and arterial distension
during exertion, just as myocardial oxygen demand is highest.55
Why comparatively few patients report preceding symptoms
of ischemia despite multiple previous episodes of exertion is
unclear. Even when patients report ischemic symptoms, such
as angina or syncope on exertion, the diagnosis still requires
a high index of suspicion. Resting ECG, exercise stress tests
and baseline ventricular function are often normal52 and the
anomaly may be missed on echocardiography.
If echocardiography cannot exclude the diagnosis, further
investigation should be undertaken. Traditionally this involved
cardiac catheterization, but the three dimensional nature of
cardiac CT and MRI have been shown to clearly identify
the proximal course of anomalous coronary arteries with
even more accuracy than invasive angiography.56,57 Surgery
is warranted in symptomatic patients and there is general
RCA from the Left Aortic Sinus

Less commonly reported in the literature than anomalous origin
of the left coronary artery from the right sinus, but this likely
reflects a lower incidence of SCD than true prevalence of the
anomaly. Analysis of 1950 angiograms by Angelini actually
demonstrated the prevalence of RCA origin from the left sinus
(0.92%) to be higher than left coronary artery origin from the
right sinus (0.15%).15 The right coronary can then follow any
of the previously mentioned routes for the left. In reports it is
common for the RCA to pass between the great arteries (Figure
7), although this again may reflect presentation bias. Although
mechanisms for myocardial ischemia are presumably the same
as for the left coronary artery, patients very rarely complain
of symptoms and presentation with SCD, whilst reported,
is extremely unusual.52,60 As with ARCAPA, right coronary

dominance may play a role in clinical presentation and risk. As
the risk of sudden death appears lower, surgical repair is generally
only undertaken in symptomatic patients or asymptomatic
patients with documented ischemia on stress testing.59
Left or Right Coronary Artery from Non-coronary Sinus

This pattern is extremely unusual with only a few reports.61
In general the risk of myocardial ischemia appears low and
surgical correction has not been performed, although patients
should be assessed for the associated higher risk features such
as ostial stenosis and intramural course.
Single Coronary Artery

Occurs in approximately 0.024 to 0.066 percent of the
population62 with around 40 percent associated with other
CHD.63 Many patients are asymptomatic although a subsection
with higher risk patterns (such as inter-arterial course) can
suffer with myocardial ischemia63 and may warrant surgery.
Clearly the consequences of atherosclerotic disease affecting
the single coronary artery can be catastrophic and early
intervention is advised for symptomatic patients.
62
consensus that asymptomatic patients with high risk lesions,

such as intra-arterial course, ostial narrowing or an intramural
segment should also undergo surgery to reduce the risk of
sudden death, although patients without these features can be
managed conservatively as the risk of coronary insufficiency
appears low.58 Surgical options depend on the underlying
morphology, but include coronary reimplantation into the
left aortic sinus, ostial enlargement, unroofing if there is an
intramural course or translocation of the pulmonary artery in
cases of interarterial course if reimplantation is not feasible
(for example, if there is a single coronary ostia).50,55,58 Bypass
grafting is generally reserved for patients with concomitant
atherosclerotic disease, as competitive flow from the coronary
artery can result in poor long-term graft patency.55,59 Short to
mid-term results are encouraging with no late postoperative
ventricular arrhythmias or sudden death reported, but aortic
regurgitation is a recognized complication and longer term
follow-up is required.50,55
Abnormalities of Intrinsic Coronary

Arterial Anatomy
Left Main Coronary Artery Atresia
A rare condition where the left coronary ostium and left
main coronary artery are absent (sometimes a remnant
fibrous cord is present) with the distal left coronary system
filling via collateral flow from the right coronary artery.
Figure 7: The right coronary artery is noted to take origin from a high position of the left aortic sinus on this cardiac MRI
887
Miscellaneous
12
As with ALCAPA, patients can present in infancy with critical

myocardial ischemia, although interestingly and perhaps due
to the lack of pulmonary artery steal a much larger proportion
of patients appear to present in later childhood or adulthood
with symptoms of myocardial ischemia or occasionally
sudden death.64 Surgical therapy generally consists of internal
mammary artery bypass grafting.
Congenital Ostial Stenosis of the Left Main

Coronary Artery
Left main stem ostial stenosis is usually associated with
atheromatous plaque formation or other forms of systemic or
vasculitic disease, however case reports exist where isolated
ostial stenosis does appear to be congenital in origin often
with hypoplasia of the left main coronary artery.65,66 Again,
these patients have generally undergone internal mammary
bypass grafting.
Myocardial Bridging
888
A myocardial bridge is formed when an area of myocardial

muscle overlies a major epicardial coronary artery (most com
monly the middle segment of the LAD), producing a tunnelled
intramyocardial segment of coronary artery. Prevalence varies
with lower rates noted in angiographic compared to autopsy
studies, but on average myocardial bridges are present in around
1/3 adults67 and are reported even more frequently in patients
with hypertrophic obstructive cardiomyopathy.68 The muscle
bridge contracts during ventricular systole causing coronary
compression. Although coronary flow predominantly occurs in
diastole, significant compression in a proximal segment of the
coronary system can still result in reduced overall mean flow
and reduced coronary flow reserve.69 The segment proximal
to the bridge also frequently shows atheromatous plaque
formation,70 possibly due to altered flow dynamics. Angina,
myocardial ischemia, exercise induced arrhythmia and sudden
death have all been reported as a result of myocardial bridging,
although it appears only an extremely small proportion of
these anomalies are functionally significant given the overall
prevalence in the population.67 Resting ECG is frequently
normal with non-specific signs of ischemia on stress testing.
The diagnosis was traditionally made by coronary
angiography with a lumen diameter reduction of 70 percent
in systole and 35 percent in diastole defined as significant,71
although newer imaging modalities such as intravascular
ultrasound (IVUS) and MRI may provide more functional
information. Medical therapy with beta-blockers or calcium
antagonists is used as the first line, although nitrates should
be avoided as they can increase the degree of angiographic
narrowing and worsen symptoms.69 Surgical myotomy is
reserved for patients with objective evidence of regional
ischemia refractive to medical therapy and has been shown
to improve symptoms. Restenosis or major periprocedural
complications have been reported in up to 50 percent patients
who have undergone coronary stenting.67
Abnormalities of Coronary Termination

Coronary Artery Fistulae
Coronary artery fistulae comprise of an abnormal direct
vascular communication between the coronary arteries and
cardiac chambers (coronary-cameral fistulae), major veins
(coronary-arteriovenous fistulae) or pulmonary arteries
(coronary-pulmonary fistulae). They can vary from short
direct communications to large tortuous vessels and represent
one of the more common congenital abnormalities of coronary
arteries with a reported prevalence of 0.13 to 0.22 percent of
adults undergoing coronary angiography.72
Morphology and Pathophysiology

The fistulae appear to represent persistence of intratrabecular
spaces73 and can arise from any part of the coronary system.
Earlier studies prior to echocardiography suggested that
origination from the right coronary artery was slightly more
common (in around 60%), although it appears that small,
clinically insignificant fistulae more commonly originate from
the left.72 A recent review concluded that overall around 55
percent originated form the left coronary artery, 37 percent
from the right and 8 percent had multiple origins from both.74
Most fistulae terminated in the right heart (65%), followed
by the pulmonary arteries (23%), the left heart (11%) and
rarely multiple sites. Associated cardiac anomalies have been
reported in around a quarter of cases, most frequently tetralogy
of Fallot or pulmonary atresia. The underlying pathophysiology
depends on the size of the shunt and site of drainage. Many
shunts are small and of little hemodynamic significance. Large
left to right shunts will result in pressure and volume loading of
the right heart and pulmonary circulation, while drainage to the
left atrium or ventricle will produce similar effects to mitral or
aortic regurgitation respectively. Significant flow through the
fistula also tends to result in dilation of the proximal coronary
artery and if the shunt is large, there is potential for coronary
artery steal and myocardial ischemia.
Clinical Features
As with the pathophysiology, the clinical symptoms depends
on the degree of shunting and site of drainage. Large shunts
may present in infancy with congestive cardiac failure
and improving ultrasound technology has even permitted
prenatal diagnosis, particularly when the shunt is large
enough to produce chamber enlargement.75 These cases
are relatively unusual however, and within the pediatric
population most patients are asymptomatic and present with
an incidental murmur, which is classically continuous and
louder in diastole.74,76,77 The exact location of the maximal
intensity of the murmur depends on the site of fistula
drainage. Interestingly symptoms (such as dyspnea, exercise
intolerance and chest pain) and complications (including
coronary ischemia, myocardial infarction, heart failure,
Investigation
Twelve lead ECG is nearly always normal in small fistulae,
although may show signs of chamber enlargement, hypertrophy
and occasionally ischemia with larger shunts. Stress testing
may show signs of reversible ischemia in adults. Even
small coronary fistulae are usually readily identifiable on
echocardiography, with color flow mapping demonstrating
flow through the fistula and into the heart at the point of
termination, although non-standard views often have to
be utilised to demonstrate significant length of the fistula
(Figure 8). With large shunts, proximal coronary artery
dilation and cardiac chamber enlargement can also be clearly
demonstrated and Doppler assessment allows some estimation
on the hemodynamic effects. Catheter angiography has
traditionally formed the gold standard technique of assessment
with selective coronary angiography clearly delineating the size
and course of the fistula as well as associated coronary artery
dilation or disease, although cross sectional imaging with CT or
MRI (Figure 9) has also been used with increasing frequency
more recently.79
intervention is best delayed until the patient is slightly larger in

order to minimise procedural risk and because some neonates
may become asymptomatic with a relative reduction in the size
of the fistula over time.80 Equally, fistulae in symptomatic older
children and adults warrant occlusion, but debate still exists as
to when to intervene in asymptomatic patients. Traditionally
closure has been advocated for all patients diagnosed with a
coronary artery fistula in order to prevent future complications.9
However, complications in children appear uncommon and as
already mentioned, small fistulae have been reported to close
spontaneously.72,74 Conservative follow-up has therefore been
proposed for small fistulae, although given complications are
62
arrhythmias, endocarditis, pulmonary hypertension and very

rarely rupture)78 appear increasingly common in adulthood
and have been reported in up to 2/3 of patients.76 It would
therefore appear that fistulae have the potential to dilate over
time with a progressive increase in the degree of shunting,
although the exact time-course of this is not well understood
and conversely small fistulae can also close spontaneously.74
Management
Treatment decisions depend on the age of the patient, size of
fistula and degree of symptoms. Clearly large fistulae resulting in
cardiac failure unresponsive to medical management in infancy
require intervention. However, symptoms of congestive cardiac
failure in infancy may respond to medical therapy in which case
Figure 9: Cardiac MRI in the same patient as Figure 8 confirming

the proximal right coronary artery dilation and fistula connecting to the
right atrium
889
Figure 8: Echocardiogram in an oblique plane demonstrating a dilated proximal right
coronary artery and large coronary fistula draining to the right atrium
Miscellaneous
12
890
increasingly apparent in adulthood, elective closure of medium

to large asymptomatic fistulas should be considered.72
Surgical closure of the fistula, either by external ligation
or intracardiac closure on cardiopulmonary bypass was
the mainstay of treatment until the first reported catheter
occlusion in 1983.81 Since then percutaneous interventional
occlusion has gradually become the procedure of choice in the
vast majority of patients. Reports exist with devices ranging
from detachable balloons, coils, vascular plugs, patent ductus
arteriosus, atrial septal defect and ventricular septal defect

devices.72,74 Whilst techniques vary according to the position
and drainage of the fistula the key principle is to ensure there
is no coronary supply to the myocardium distal to the point
of occlusion. If uncertain, this can be tested by observing
the ECG during temporary balloon occlusion of the fistula
(Figures 10A to D). Results following device occlusion have
been comparable to surgical results with an expected mortality
of < 1 percent. Complications such as device embolisation,
Figures 10A to D: Catheter occlusion of coronary artery fistula. In panel A the large fistula is delineated on angiography from the right coronary
artery connecting to the right atrium, with the normal coronary artery seen descending at 6 oclock. In Panel B the fistula has been occluded with
a wedge catheter and injection of contrast proximally further delineates the right coronary artery and confirms no important myocardial supply
distal to the occlusion. Lateral (Panel C) and AP (Panel D) projections following occlusion of the fistula with a Amplatzer muscular ventricular
septal defect occluder
Conclusion
As this chapter demonstrates, the range of possible coronary
artery anomalies is vast, but a thorough knowledge of the more
severe and frequently encountered abnormalities is vital. Not
only can the pathophysiological consequences be devastating,
but also definitive diagnosis may be difficult and a high level
of suspicion is required for appropriate further investigation.
With advances in both surgical and transcatheter therapies the
vast majority of these abnormalities can be successful treated
with low mortality and long term morbidity.
The diseases which destroy a man are no less natural than
the instincts which preserve him.
George Santayana
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62
ST changes and coronary occlusion have been reported,

but are uncommon and small residual shunts appear to be
present in around 10 percent of patients, which is similar to
that seen after surgical closure.72 Surgery may be necessary if
close proximity of normal coronary vessels prevent selective
occlusion. There is relatively limited information on longterm follow-up of this very heterogeneous patient population
and whilst most patients appear to do well, the proximal
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thrombotic occlusion. As a result, long-term antiplatelet
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12
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48. Alexi-Meskishvili V, Dahnert I, Hetzer R, et al. Origin of
the circumflex coronary artery from the pulmonary artery in
infants. Ann Thorac Surg. 1998;66(4):1406-9.
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50. Said SM, Dearani JA, Burkhart HM, Schaff HV. Surgical
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893
C hapter
63
Cardiac and Extracardiac Masses

Bhanu Duggal, Vijayalakshmi IB, Nirav Panchani
Cardiac masses have been classified as either secondary or

primary. Secondary or metastatic tumors of the heart are 20
to 40 times more common than primary tumors and should
be suspected, when a patient with an underlying malignancy
develops signs and symptoms of cardiovascular disease.1
Primary cardiac tumors are extremely rare. Autopsy incidence
is only 0.02 percent. They may be classified by location or by
histology.1-3
Clinical Features
Cardiac tumors produce no characteristic signs and symptoms
unless they interfere with cardiac function. Hence only 5 to
10 percent may be diagnosed clinically, while some may be
found incidentally during evaluation for a seemingly unrelated
problem or physical finding. Because symptoms mimic other
cardiac conditions, the clinical challenge is to consider the
possibility of a cardiac tumor so that the appropriate diagnostic
test(s) can be conducted.4
The symptoms depend on the anatomic location of the tumor
rather than the tissue characteristics of the tumor itself. The
clinical features will depend on whether the tumor is largely
within the cardiac chambers or involves the myocardium or
pericardium (Table 1). The clinical presentation is determined
by many factors including presence of the tumor on the left/
right side of the heart, size (mass effect), growth rate, friability,
mobility and degree of invasiveness.
Intracavitary tumors
Intracavitary tumors are most commonly located in the atria
and produce clinical manifestations by interfering with cardiac
filling or ejection (Table 2). Exertional dyspnea is common
and when cardiac failure develops it is intractable because of
the mechanical obstruction to the atrial or ventricular filling.
This obstruction may be progressive as the size of the tumor
increases or intermittent in pedunculated, mobile tumors.
Table 1
General manifestations of cardiac tumors

Pericardial involvement

Pericarditis
Pericardial effusion
Radiographic enlargement
Arrhythmia, predominantly atrial
Tamponade
Constriction and compression of various cardiac structures
Myocardial involvement

Arrhythmias, ventricular and atrial

Electrocardiographic changes
Radiographic enlargementgeneralized, localized
Conduction disturbances and heart block
Congestive heart failure
Coronary involvementangina, infarction
Intracavitary tumor
Cavity obliteration
Valve obstruction and valve damage
Embolic phenomenasystemic, neurologic, coronary
Occasionally, a large mobile tumor can completely obstruct

an inflow/outflow leading to transient syncope and even
sudden cardiac death (SCD). As the cardiac output is severely
reduced it may result in the development of angina. Systolic
blood pressure may be low. Fragmentation of the tumor may
cause embolization.
Left Atrial Tumors

Tumors arising in the left atrium (LA) tend to grow into the
atrial lumen and cause symptoms of mitral stenosis or mitral
regurgitation (damaged valve by tumor prolapse termed
wrecking ball phenomenon). Left atrial tumors thus may
simulate mitral valve disease and produce heart failure and/or
secondary pulmonary hypertension.
63
Table 2
Clinical features in intracavitary tumors

Clinical features
Symptoms
Examples
Left atrial
Left ventricular inflow

obstruction
Dyspnea, paroxysmal nocturnal dyspnea,

orthopnea, syncope, sudden cardiac death
(SCD) (may have postural variation)
especially myxomas
Embolismcentral nervous
system, coronary,
peripheral, retinal
Stroke, myocardial infarction (MI)
Myxoma
Fibroma
Undifferentiated
sarcoma
Osteosarcoma
Left ventricular outflow

obstruction
Angina, syncope, SCD,

murmur on examination
Systemic embolism
Stroke, SCD, MI
Papillary fibroelastoma
Intramuralarrhythmias
Ventricular tachycardia, ventricular fibrillation,

atrioventricular blocks
Fibroma
Benign superior vena cava

syndrome (obstruction)
Right heart failure, i.e. peripheral

edema, ascites
Myxoma
Tricuspid stenosis/regurgitation
Murmur increasing with respiration
Angiosarcoma
Left ventricle
Right atrium
Location
Cyanosis, R-L shunt through patent foramen

ovale
Right ventricle
Right ventricular inflow and

outflow obstruction
Dyspnea, appropriate murmurs,

syncope
Fibroma
Pulmonary embolism
Right heart failure
Rhabdomyoma
Hamartoma
Commonly observed symptoms and signs include dyspnea,

orthopnea, paroxysmal nocturnal dyspnea, pulmonary edema,
cough, hemoptysis, edema and fatigue. Symptoms may be
worse in certain body positions in mobile pedunculated
tumors as in the left atrial myxoma. Respiratory symptoms
due to pulmonary venous hypertension that worsen rather than
improve in the upright position are a clue to the diagnosis of
this tumor. The characteristics of the clinical findings vary
on repeat examinations. On physical examination along
with the diastolic murmur, a characteristic tumor plop
may be heard in early diastole (only in 15% of the cases). A
fixed tumor does not produce a positional alteration in signs
and symptoms. The patients along with clinical features of
pulmonary venous hypertension often have a history of atrial
arrhythmia. In addition to interfering with the circulation, left
atrial tumors may release tumor fragments or thrombi into the
systemic circulation. The most serious complications of such
embolization are neurologic.
angiosarcomas are the commonest malignant primary tumors

and have a predilection to arise in the RA. Tumors arising in
the RA grow into the atrial lumen and obstruct blood flow,
producing hemodynamic changes that are similar to those seen
with triscuspid stenosis/regurgitation. Typical cardiovascular
signs and symptoms are those of right heart failure (i.e. fatigue,
peripheral edema, hepatomegaly, ascites and prominent a
waves in the jugular veins). On physical examination, a
diastolic murmur along with the tumor plop may be heard.
Occasionally patients present with recurrent arrhythmias. In
addition to obstructing circulation through the right side of the
heart, tumor fragments may be released into the pulmonary
circulation, causing symptoms consistent with pulmonary
embolism. Right atrial hypertension can result in shunting of
venous blood into the systemic circulation if a patent foramen
ovale is present, resulting in hypoxemia or systemic emboli.
Right Atrial Tumors
Tumors arising in the right ventricle (RV) can be misdiagnosed as pulmonic stenosis, restrictive cardiomyopathy
or tricuspid regurgitation. Lesions arising in the RV may
result in right-sided heart failure or right ventricular outflow
Similar to left atrial tumors, myxomas are the most common

tumors of the right atrium (RA). Sarcomas and in particular,
Right Ventricular Tumors
895
Miscellaneous
12
obstruction leading to shortness of breath, syncope and sudden

death.
Left Ventricular Tumors
Table 3
Prevalence of primary cardiac tumors

Benign
Intracavitary left ventricular tumors often result in narrowing

of the left ventricular outflow tract and present as aortic
stenosis or hypertrophic obstructive cardiomyopathy.
Intramural tumors
Intramural tumors may remain completely asymptomatic
for a long-time and cause symptoms at a late stage due to
myocardial damage or compression of the cardiac conduction
system with tumor expansion. Small but strategically placed
tumors can cause an earlier development of symptoms.
Patients may present with Stokes-Adams syncope due
to complete heart block or palpitations due to ventricular
arrhythmias. Symptoms and signs of left and/or right ventricular
decompensation are together important clinical manifestations
of myocardial tumors. Clinical signs may be subtle and consist
only of gallop rhythm and sinus tachycardia. With more severe
degree of myocardial involvement cardiomegaly, pulmonary
congestion and peripheral edema may occur.
Malignant
Cysts
Myxoma
27%
Rhabdomyomas
20%
Lipoma
10%
Papillary fibroelastoma
8%
Hemangioma
5%
Mesothelioma of the atrioventricular

(AV) node/paragangliomas/
Pheochromocytoma
1%
Angiosarcoma
9%
Rhabdomyosarcoma
5%
Mesothelioma
4%
Fibrosarcoma
3%
Malignant lymphoma
2%
Extraskeletal osteosarcoma
1%
Pericardial
18%
Bronchogenic
2%
Pericardial Tumors
Benign pericardial tumors are rare and account for one-fourth
of the benign tumors of the heart. Among the reported cases
are teratomas, fibromas, lipomas, pericardial cysts, etc. Many
are discovered because of a chance X-ray demonstration of
an unusual heart contour. In others, sudden appearance of
symptoms is due to hemorrhagic pericardial effusion. This
occurs in both benign and malignant pericardial tumors.
However, the latter have a more rapid course, are more
often associated with chest pain or dry cough and are often
associated with pulmonary metastasis.
The histological classification of cardiac tumors and their
prevalence are enumerated in Table 3 with details of the more
common tumors in the paragraphs that follow:5
Benign cardiac Tumors

Cardiac Myxomas
896
Myxoma is the most common benign cardiac tumor and is

usually located in the LA (75%). Other sites include RA (18%),
left ventricle (LV) (4%) and the RV (4%). The involvement of
more than one site can occur in 5 percent cases.6
Histologically, these tumors are composed of scattered
cells within a mucopolysaccharide stroma (Figures 1A to C).
The cells originate from a multipotent mesenchyme that is
capable of neural and endothelial differentiation. Myxomas
produce vascular endothelial growth factor (VEGF) which
C
Figures 1A to C: A. Solid, polypoidal, smooth-surfaced mass lesion
attached to the inter-atrial septum on left atrial aspect; B. Cut surface
shows myxoid, greenish yellow appearance with foci of hemorrhage;
C. Stellate to spindle shaped cells in myxoid background. Note
perivascular arrangement of cells (H&E x 400). Courtesy: Dr Pradeep
Vaideeswar
Clinical Features
The patient is usually 30-60 years old and may be asymptomatic
(20%) or present with a clinical triad of embolic events,
cardiac symptoms and constitutional symptoms.7 In nearly
one-third of the cases the cardiac myxoma can present with
embolic symptoms of which the central nervous system is the
commonest (83%). The other embolic locations are the retinal
artery (3%), the upper and lower extremities (45%) and the
coronary arteries (12%). Ischemic stroke and acute myocardial
infarction are the dreaded complications of embolism.
Recurrent emboli to the central nervous system may lead to
formation of intracranial aneurysms as tumor emboli infiltrate
and weaken the vessel wall and 12 percent of the cases can have
intracerebral hemorrhage or subarachnoid hemorrhage (5%).
The myxoma is attached by a stalk to the interatrial septum
(IAS) and may be large enough to cause atrioventricular
(AV) valve obstruction (less often regurgitation) due to
prolapse of the tumor across the annulus during ventricular
filling in diastole. A highly mobile tumor in the LA can cause
intermittent obstruction and positional symptoms. Left atrial
myxomas can cause mitral valve obstruction with dyspnea
and orthopnea from pulmonary edema or heart failure. Right
atrial myxoma may obstruct the tricuspid valve and cause
symptoms of right heart failure. Constitutional symptoms
of fever, malaise with raised inflammatory markers may
occur due to the release of vasoactive substances including

interleukin-6. Hemolytic anemia is associated with calcified
myxomas in a right atrial location.
Familial myxomas constitute 4.5 to 10 percent of all
myxomas and a significant portion of them are related to
Carney complex, a familial autosomal dominant syndrome.
They are likely to have a earlier presentation (median 20
years), atypical location, multiple tumors and higher chances
of recurrence. They also have one or more of the following
features: cutaneous lentiginosis or unusual hyperpigmented
skin lesions (excessive freckling), neurofibromas or a rare
endocrine neoplasm. Patient with cardiac myxomas and
pigmentary abnormality has been described as NAME (naevi,
atrial myxoma, myxoid, neurofibroma, ephelids) and LAMB
(lentigines, atrial myxoma and blue naevi) syndrome.8
Investigations
63
probably contributes to the induction of angiogenesis and the

early stages of tumor growth.
Macroscopically, typical myxomas are pedunculated and
gelatinous in consistency; the surface may be smooth, villous,
or friable. Tumors vary widely in size, ranging from 1 to 15
cm (mean 5 cm) in diameter and weight between 15 and 180 g.
About 35 percent of myxomas are friable or villous and these
tend to present with emboli. Larger tumors are more likely to
have a smooth surface and are associated with cardiovascular
symptoms.
Two-dimensional echocardiography is the imaging modality

of choice, which is used to identify the tumor (Figures 2A
and B), its location, size, functional valvar obstruction
(Doppler gradient) and exclusion of multiple mass.9 The
myxoma is a polypoid, mobile structure with a heterogenous
echogenicity. Its attachment to the IAS helps to differentiate
it from a thrombus. A careful search for multiple cardiac
tumors should be made to differentiate sporadic from familial
myxomas. If transthoracic echocardiography (TTE) has poor
acoustics, transesophageal echocardiography (TEE) may be
used for the diagnosis. LA being a posterior structure, TEE
permits superior imaging of LA myxomas. Computerized
tomography (CT) (Figure 2C) and magnetic resonace imaging
(MRI) have no incremental value in the diagnostic workup
of a classical myxoma unless it has an unusual location or
attachment. Due to the autosomal dominant transmission of
Carney complex, identification of multiple cardiac myxomas
in a young individual should prompt echocardiographic
screening of first-degree relatives.
Figures 2A to C: A. Apical four-chamber view shows a large right atrial myxoma obstructing the tricuspid valve with a pedicle attached to
inter-atrial septum (IAS); B. Left atrial myoxma obstructing the mitral valve; C. Contrast enchanced computer tomography (CT) showing
moderate sized lobular soft tissue density mass lesion in the body of left atrium with epicenter at IASclassical appearance of myxoma. Ao
= Aorta; LA = Left atrium; LV = Left ventricle; M = Mass; RA = Right atrium; RV = Right ventricle. CT image courtesy: Dr Madhav Hegde Dr
Madhav Hegde
897
Miscellaneous
12
Treatment and Prognosis

Once a presumptive diagnosis of myxoma has been made on
imaging studies, prompt resection for complete removal of the
myxoma is required because of the risk of embolization or
cardiovascular complications, including sudden death. The atrial
septum to which the myxoma is attached should be excised and
if this is a substantial portion of the septum, a Dacron patch
is used for the repair. This leads to normalization of serum
interleukin-6 levels and resolution of constitutional symptoms
and the intracranial aneurysms may regress and resolve. Cardiac
transplantation has been reported for other tumors and might be
considered for multiple recurrent atrial myxomas.
Postoperative recovery is generally rapid. However, atrial
arrhythmias or AV conduction abnormalities were present
postoperatively in 26 percent of patients in one series. In
addition, patients are at risk for recurrence of the myxoma,
which may occur in 2 to 5 percent of cases (due to incomplete
resection, growth from second pretumor focus or intracardiac
implantation from the original tumor) or the development
of additional lesions. Resection of entire region of fossa
ovalis with repair of residual defect reduces recurrences.
Development of a second primary myxoma may be more
common in patients with a family history of myxoma.
Lipomas
898
Lipomas account for 2.4 percent of primary cardiac tumors,

50 percent of these arise from the epicardial adipose tissue,
25 percent from subendocardium and 25 percent from the
myocardium. Histologically, the tumors are encapsulated
masses of adipose tissue.10 They may occur at any age with an
equal frequency in both genders. The clinical manifestations of
cardiac lipoma depends on its location and the possible resultant
compression or obstruction. Most frequent intracavitary
location is the RA. Those that interfere with cardiac functions,
such as a valvular or outflow obstruction, may produce earlier
symptoms or audible murmurs. On the other hand, lipomas
that involve the epicardium or infiltrate the myocardium may
remain asymptomatic, and thus grow to larger dimensions.
Myocardial lipomas can give rise to arrhythmias or cardiac
failure. Parietal pericardial lipomas often resemble pericardial
cysts and visceral pericardial lipomas are frequently associated
with pericardial effusion. Rarely, a pericardial lipoma can
assume gigantic proportions and its appearance on a chest
radiograph may be mistaken for a huge pericardial effusion or
massive cardiomegaly. Echocardiography typically reveals a
homogeneous hyperechoic mass, especially when located in the
subendocardium, while those located in the subepicardium are
hypoechoic. As CT and MRI have a high degree of specificity
for fat, they are the diagnostic modalities of choice for these
tumors. Encasement of the coronary arteries may occur and
preoperative assessment of the relationship of the mass to
coronary arteries is mandatory.11 The homogeneously increased
signal intensity of lipomas on T1-weighed images on MRI

shows the superior diagnostic ability of this modality. For the
atrial arrhythmias, medical management with antiarrhythmics
should be given, but if the patient fails to respond , surgical
resection is indicated. Because of the symptoms they cause
and their progressive growth, myocardial lipomas usually
require resection.
Lipomatous hypertrophy of the IAS is an exaggerated
growth of non-encapsulated normal fat existing within the
septum at the level of fossa ovalis and is not a true tumor.12
The septal hypertrophy is greater than 2 cm in thickness
(normal < 1 cm) and is seen primarily in older patients and
in those who are obese. In the absence of symptoms of atrial
arrhythmias or heart block, they do not require resection. It is
often necessary to differentiate lipomatous hypertrophy of the
IAS from lipomas. This is often seen in obese elderly people
and a TEE is required to show the hour glass septum with fatty
infiltration of the proximal and distal IAS with sparing of the
fossa ovalis region.
Papillary Fibroelastomas
Small tumors (< 1 cm), with valvular origin in 84 percent
of the cases. They account for three-fourths of all cardiac
valvular tumors which affect men and women equally at a
mean age of 60 years.
Pathologically it has multiple frond-like structures. Its
microscopic features include dense elastin at the core of each
frond coated with collagen and lined by flat endocardial cells.
Size, Location and Number

Tumors varied from 2 to 70 mm in size with a mean of 9 mm.
They usually occur over the heart valves on the left side of
the heart, i.e. aortic 39 percent, mitral 29 percent, tricuspid 11
percent and pulmonic 7 percent, while the remaining lesions are
scattered throughout the atria and ventricles.13 Multiple tumors
were present in 9 percent of the patients. These are found on
the arterial side of semilunar valves and atrial side of the AV
valves. They do not interfere with the functioning of the valve
and are found on the downstream of the valvular surface, which
helps in distinguishing them from vegetations. This tumor
closely mimics infective endocarditis due to embolic events
and valve appearance. Pathologically papillary fibroelastoma
may be distinguished from Lambls excrescences, which are
acellular deposits of organized thrombus and connective tissue
covered by a single layer of epithelium that are found at the
site of endothelial damage of the valves particularly along the
closure margins of the aortic valves.
Clinical Features
Most of these tumors are found incidentally at the time of
autopsy, cardiac surgery or echocardiography. Symptoms
63
Treatment
Surgery is recommended for patients, who have had embolic
events or complications directly related to tumor mobility
(e.g. coronary ostial occlusion) and those with highly
mobile or large (> 1 cm) tumors. Careful observation is an
acceptable option for asymptomatic patients, as long as the
tumor remains small and immobile. Recurrence of cardiac
papillary fibroelastoma following surgical resection has not
been reported.
MURAL TUMORS
Tumors involving the heart wall or valves, such as
hemangiomas, hamartomas and nodular rhabdomyomas have
mostly been reported as incidental autopsy findings. A few can
present as arrhythmias, myocardial dysfunction and interfere
with coronary blood flow or cause sudden death.
Hemangiomas
In the heart, vascular tumors composed of blood vessels, are
most commonly found in the lateral wall of the LV, anterior wall
and septum. They mainly grow intracavitarily with a pedicle,
but can be intramural or arise from the epicardium. Usually a
tumor of children and adolescents, they can be found in all age
groups. Rarely there may be hemangiomas at other sites. For
example, liver or port wine stain on the face. The most helpful
echocardiographic feature is the recognition of the septated and
cystic nature of the mass. Contract enhanced echocardiography
can demonstrate the vascularity of the tumor and differentiate it
from relatively avascular structures such as myxomas, lipomas
and fibromas.The tumors may grow, regress or remain the
same14 and complete resection of the tumor is recommended,
which may be possible in only 52 percent of the cases. Followup echocardiography is required to detect recurrences.15
Pericardial Tumors
Pericardial tumors include cysts and solid tumors. The solid
tumors consist of lipomas, hemangiomas, lymphangiomas,
leiomyoma, neurofibroma, heterotopic tissue, benign and malignant teratomas, mesothelioma, thymoma and sarcoma.
Figure 3: A case of hydatid cyst with multiple daughter cysts

in the pericardium on transthoracic echocardiography (TTE). TTE
shows the extracardiac mass compressing the cardia.
usually are caused by embolization, either of the tumor itself or

thrombus. The most common clinical presentation are stroke
or transient ischemic attack followed by angina, myocardial
infarction, sudden death, heart failure, syncope or presyncope
or pulmonary embolic events.
Fibroelastomas are well visualized on echocardiography
(TEE) and also unlike vegetations a characteristic shimmer
or vibration is seen at the tumor-blood interface ascribed to
finger like projections of the tumor. They are usually not seen
on CT or MRI unless they are very large.
Hydatid cysts can present rarely as pericardial tumors (Figure 3).

Malignant pericardial tumors predominate with sarcomas being
most frequent.
Pericardial tumors arise from surface lining of the
visceral pericardium or cells displaced during embryonic
development.16
Pericardial Cyst
These cysts are most common at the right heart border. They
can range in size from 1 to 15 cm in diameter. They are
multilobulated and contain a clear yellow fluid.17 They are
usually successfully excised surgically.
Heterotopia
Islands of thymic tissue and thyroid rests have been reported
in the parietal pericardium.4
Malignant Cardiac Tumors

A quarter of all the cardiac tumors are malignant, the
majority of which are angiosarcomas or rhabdomyosarcomas.
Malignant primary cardiac tumors are rare and nearly
95 percent of these are sarcomas. Lymphomas account for the
remaining 5 percent of the primary malignant cardiac tumors.
Malignant tumors usually begin as intramural and expand
rapidly extending to the pericardium and/or cardiac chambers.
Primary cardiac malignancies present a clinical dilemma and
are often asymptomatic until they become large and even
then, they produce non-specific symptoms. Although TTE is
a reasonable initial screening tool, TEE may offer important
clues as to the malignant nature of the lesion by showing
intramyocardial and vena caval invasion. The superior soft
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Miscellaneous
12
900
tissue characterization possible with CT and especially MRI

also allows for the determination of the degree of tumor
infiltration.
Sarcomas
Sarcomas are rare malignant mesenchymal neoplasms,
which constitute majority of the primary malignant cardiac
neoplasms and are the second most common primary cardiac
tumor. Primary cardiac sarcomas are by definition confined
to the heart or pericardium at the time of diagnosis with
no evidence of extracardiac primary neoplasm. The most
common cell types affecting the heart are angiosarcoma
(37%), unclassified (24%), malignant fibrous histocytoma
(MFH) (1124%), leiomyosarcoma (89%) and osteosarcoma
(39%).18 Approximately, 10 percent of the surgically
resected cardiac tumors are primary sarcomas. Although
majority of the angiosarcomas occur in the RA, other cell
types more commonly affect the LA. Sarcomas are common
between the 3rd and 5th decades of life. Eighty percent of
the cardiac angiosarcomas occur in the RA and involve the
pericardium and symptoms from right-sided heart inflow
obstruction or cardiac tamponade are common. The location
and degree of invasiveness helps in differentiating it from
myxomas. Left-sided tumors may be difficult to distinguish
from left atrial myxomas. TEE is the initial imaging of choice,
but to demonstrate tumor infiltration and mediastinal and
extracardiac involvement, CT or cardiac magnetic resonance
imaging (CMR) is required. They appear as low attenuation,
irregular nodular masses with heterogenous enhancement on
contrast CT and heterogenous mass on CMR. CT is helpful in
evaluation of these tumors as it shows the broad-based nonseptal attachment, myocardial, pericardial and mediastinal
invasion, as well as extension into the great vessels and
pulmonary metastasis. Pericardial involvement leads to
hemorrhagic pericardial effusion. Biopsy of extracardiac
metastasis or pericardial fluid cytology assist in diagnosis.
Cardiac angiosarcomas are aggressive tumors with mean
survival of 9 to 10 months. Common sites of metastasis are
lung, liver and bone. Treatment includes a multidisciplinary
approach including surgery, irradiation and neoadjuvant
chemotherapy for advanced stage patients, palliative therapy
to improve right ventricular function and stent to relieve
superior vena cava obstruction. Transvenous biopsy provides
histological diagnosis with procedure associated risk.
Virtually all types of sarcomas have been reported in the
heart. Cardiac sarcomas are extremely rare and for most types,
only isolated case reports have been described. Histological
subtypes of sarcoma includes angiosarcoma, leiomyosarcoma,
rhabdomyosarcoma, malignant fibrous histiocytoma, undifferentiated sarcoma and malignant lymphoma. Sarcoma showing
high mitotic activity (> 5 mitotic figures/10 hpf), tumor necrosis and poor cellular differentiation have worse prognosis.
As with benign lesions, the clinical presentation is
largely determined by the location of the tumor, rather than
its histopathology. The diagnostic approach relies upon

echocardiography, MRI and CT to define the presence of a
tumor and its anatomic relationship to normal structures.
Fibrosarcomas: Fibrosarcomas and malignant fibrous
histiocytomas are white fleshy (fish flesh) tumors that are
composed of spindle cells and may have extensive areas of
necrosis and hemorrhage. These tumors tend to extensively
infiltrate the myocardium.
Leimyosarcomas: Leimyosarcomas are spindle-celled,
high-grade tumors, that arise more frequently in the LA.
Mean age is in 4th decade. They present with constitutional
symptoms, congestive cardiac failure, pericardial effusions,
chest pain. They are rapidly growing with poor prognosis
and with a mean survival of 6 months. These sarcomas have
both a high rate of local recurrence and systemic spread.
Cardiac transplant is not effective due to the high rate of
recurrence. Palliative surgery is the only current treatment
option.
An alternative treatment, cardiac autotransplantation,
has shown promise. In these cases, the heart is excised, the
tumor is resected ex vivo, and the heart is reconstructed before
being reimplanted back into the patient. The advantage of this
procedure is the increased ease with which major resection
and reconstruction can be performed, while at the same time
avoiding the need for antirejection treatment.19
Primary Cardiac Lymphoma

Lymphomas account for 5 percent of primary malignant
cardiac tumors. Overall however, they are extremely rare
and represent only 1 percent of all (benign and malignant)
primary cardiac tumors. Primary cardiac lymphoma is
defined as an extranodal non-Hodgkin lymphoma, involving
only the heart and pericardium at the time of diagnosis.20
Lymphomatous involvement of the heart and/or pericardium
usually occurs by dissemination, and cardiac involvement as
the initial presenting manifestation of malignant non-Hodgkin
lymphoma is extremely rare. Clinical presentation of primary
cardiac lymphoma varies, is non-specific and depends on
which cardiac structures are involved. Clinical presentations
are acute and include dyspnea, edema, arrhythmia and
pericardial effusion. The incidence is increasing. Diffuse
large B cell lymphoma is most common in immunocompetent
and Burkitts and immunoblastic are more common in
immunocompromised. CMR is diagnostic. Anthracycline
and rituximab along with radiation therapy is the treatment
of choice. Prognosis is poor. Post-transplant lymphoma have
good prognosis with reduction of immunosuppression as the
primary treatment.21
Mesothelioma
Mesothelioma arises from the visceral or parietal pericardium
and are the third most common primary malignant neoplasm.
Patients are in the age range of 17 to 83 years with a male
to female ratio of 2:1. Most of these tumors diffusely

cover parietal and visceral pericardium. Histologically, it
is characterized by cellular irregularities and variability.
The tumor may consist of tubules, solid cords of malignant
cells or spindle-shaped cells with a patternless arrangement
of the connective tissue. These tumors invade the heart
only superficially in contrast with primary sarcomas, which
has a significant myocardial or intracavitary component.
They spread to adjacent pleura and mediastinum but distal
metastasis is rare. Distinction from mesothelial hyperplasia
secondary to radiation therapy can be difficult.22
Mesotheliomas arising in the pericardium produce
tamponade and constriction. These tumors can be diagnosed
by echocardiography (Figure 4), CT scan, MRI and sometimes
by chest X-ray. Pericardiocentesis may yield a cytologic
diagnosis.
More rarely, mesotheliomas may arise as benign tumors of
the AV node, where they may produce heart block. Diagnosis
of the AV nodal tumors causing heart block can be confirmed
with echocardiography.
Resection is the treatment of choice for mesothelioma, but
the prognosis with malignant pericardial mesotheliomas is
very poor. The addition of radiation and/or chemotherapy has
been attempted, but has not been shown to be of value.
TUMORS WHICH MAY BE BENIGN OR MALIGNANT

Paragangliomas
Paragangliomas can be either benign or malignant and can
be hormonally active or inactive.23 In tumors not producing
catecholamines, symptoms are due to cardiac compression
or tamponade. In contrast, cardiac paragangliomas, which
are hormonally active primarily produce norepinephrine and
may cause symptoms (e.g. headache, sweating, tachycardia,
hypertension).
Paragangliomas do not occur commonly in the chest, but
when they do, the hormonally inactive tumors are more frequent
63
Figure 4: Mesothelioma in the atrioventricular groove with pericardial

effusion. LA = Left atrium; LV = Left ventricle; M = Mass; PE =
Pericardial effusion.
in the pericardium, while hormonally active tumors (pheochromocytomas) more frequently arise elsewhere in the thorax. Paragangliomas may be localized with echocardiography.
Their extreme vascularity creates a characteristic MRI appearance.
Both benign and malignant paragangliomas occurring
within the pericardium, parasitize the cardiac blood supply and
are as a consequence very difficult to excise. All intrapericardial
paragangliomas require resection. Complete resection
may be difficult, but is usually possible. Cardiopulmonary
bypass and even circulatory arrest may be required because
of the high degree of vascularity or to moderate the extreme
hypertension possible from tumor manipulation of the
hormonally active tumors. If complete resection is not
possible, cardiac transplantation may be required. As is
true of all pheochromocytoma resections, preoperative and
intraoperative adrenergic blockade must be employed.
Secondary Tumors
Secondary tumors are 20 to 40 times more common than
primary tumors and should be suspected if any signs and
symptoms of cardiovascular disease occur in a patient known
to have a malignant lesion involving other organ systems.
Particularly, if this occurs in conjunction with cardiomegaly,
a new or changing heart murmur, electrocardiographic
conduction delay or arrhythmia. Cardiac involvement may
arise from hematogenous metastasis, direct invasion from
the mediastinum or tumor growth into the vena cava and
extension into the RA. Cardiac metastasis rarely may be the
first manifestation of malignant disease.24
Carcinomas of lung, breast, esophagus, pancreas, kidney
and testicle are those, most prone to involve the heart by
metastasis. In autopsy series, cardiac involvement is present in
10 to 20 percent of malignancies, with the lung and the breast
being the sites of the primary tumor in more than half the
cases. Lymphoma associated with acquired immunodeficiency
syndrome (AIDS), have frequent and extensive cardiac
involvement. Melanoma has the highest rate of pericardial
metastasis, but as the malignancy itself is very rare, the number
of patients is relatively fewer.
Non-primary cardiac tumors can affect the heart in three
ways:
By invasion of the pericardium, epicardium, myocardium
and endocardium.
By production of biologically active substances.
By side effects of radiation/chemotherapy.
The pericardium is the most frequent site of metastatic
disease.25 Seventy five percent of metastatic cardiac disease
involves the pericardium with or without the myocardium.
Pericardial metastasis is suspected when patient develops
pedal edema, ascites with raised jugular venous pressure and
other clinical markers of pericardial effusion/tamponade.
Confirmation of the diagnosis requires a pericardial tap
with pericardial biopsy. The differential diagnosis of
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Miscellaneous
12
pericardial effusion in a patient with malignancy includes

pericardial metastasis, radiation pericarditis as well as
idiopathic pericarditis (which is common in patients with
malignancy).
Myocardial involvement by metastatic disease is less
common than pericardial involvement, but does occur in
lymphoma or melanoma. It can project into or compress
cardiac chambers and cause hemodynamic compromise.
Endocardial involvement is rare. A specific type of cardiac
involvement is seen in renal cell carcinoma, where finger
like projections are seen protruding from the inferior vena
cava into the RA. These can be followed retrogradely back
to the kidney. This can also be seen in uterine carcinoma. The
diagnostic evaluation is the same as that for primary cardiac
tumors and relies upon echocardiography, MRI and CT to
ascertain the extent of cardiac involvement. In very carefully
selected patients, resection of cardiac metastasis has been
used to provide symptom palliation and prolong life. Tumors
can affect the cardiac structures indirectly.
Metastatic carcinoid tissue in the liver can produce
biologically active substances including serotonin which
can cause thickening and rigidity of the right sided tricuspid
and pulmonary valves. The patient typically presents with
right heart failure due to severe tricuspid regurgitation or
less commonly tricuspid stenosis. Left sided valves are less
commonly involved because serotonin is metabolized in the
lungs.
DIAGNOSTIC EVALUATION
The goals of the initial evaluation are to ascertain whether or
not a cardiac tumor is present, the location of the lesion within
the heart and to the extent possible, whether a tumor is benign
or malignant. This information is vital in planning further
evaluation and management.
Chest X-ray
Radiologic evaluation usually begins with chest radiography,
which typically reveals abnormal findings including cardio
megaly, signs of heart failure, abnormalities of cardiac
contour and pleural effusions. Specific chamber enlargement
may result from various intracavitary tumors, whereas mural
lesions may produce abnormal contours, ectopic or peculiar
cardiac calcification or cardiac enlargement. Pericardial
neoplasms usually produce a rapidly developing pericardial
effusion.
Electrocardiogram
902
Nonspecific electrocardiogram (ECG) abnormalities occur in

many cardiac tumors depending on the extent and location of
the tumor. Decreased qRs voltage, electrical alternans, ST-T
changes occur in many patients with pericardial involvement.
ECG findings of myocardial infarction, bundle-branch block

and varying degrees of AV block are found in intramural
tumors. Intracavitary tumors can cause left ventricular
hypertrophy, right ventricular hypertrophy and enlargement
of the atria. Atrial or ventricular arrhythmias may occur in
patients with involvement of the endocardium/myocardium
or pericardium.
Echocardiography
Echocardiography is widely available and provides a simple,
non-invasive technique of choice for the initial evaluation.
Abnormal masses (tumor, thrombi, vegetations) must be
distinguished from normal cardiac structures, which can
mimic a mass. These includes the Eustachian valve, Chiari
network, crista terminalis, pectinate muscles, moderator
band, lipomatous hypertrophy of the IAS. Artifacts
produced by pacemaker electrodes and surgical sutures
can be excluded by taking careful history of the patient.
Ultrasound artifacts and reverberations can be confused
with pathology on two-dimensional echocardiography (e.g.
apical thrombi). The other entity, which needs to be ruled
out are the extracardiac masses, which include mediastinal
tumors, coronary aneurysm or hiatal hernias (Figures 5 to
8). Thrombus is the commonest intracardiac mass. It can
be distinguished from a tumor by the associated findings of
atrial fibrillation, smoke in the LA, a regional wall motion
abnormality in the LV. In case of doubt, CT scan can help in
differentiating the thrombus from other tissues on the basis
of density. Echocardiography is the primary modality for
imaging intracardiac masses whose quality has improved
with introduction of new imaging technique such as tissue
harmonics.
Echocardiography images both the myocardium and the
cardiac chambers and can usually identify the presence of
a mass, its mobility, location and attachment. In addition,
echocardiography may provide information about any
obstruction to the circulation, hemodynamic changes (by
continuous wave Doppler) as well as the likelihood that the
tumor could be a source of emboli. Contrast echocardiography
uses microbubbles that traverses pulmonary vascular bed and
opacify the left heart demonstrating filling defect caused by the
intracavitary tumor. Myocardial contract echocardiography
is used to demonstrate intracardiac mass perfusion thereby
distinguishing tumor from thrombus. Although TTE is simpler
and usually can identify a tumor, TEE may be more informative
due to its ability to detect masses not visualized by TTE. The
superior diagnostic utility of TEE is due to the proximity of the
esophagus to the heart, the lack of intervening lung and bone
and the ability to use high-frequency imaging transducers
that afford superior spatial resolution. TEE is frequently
used for intraoperative monitoring. 3D TEE provides three
dimensional reconstruction of image simulating intaoperative
visualization.
63
Figures 5A and B: A. A 8-year-old boy with frontal glioma presented with superior mediastinal syndrome;
B. Right ventricular pressure in high (96/6 mm Hg)
Figures 6A and B: A. Fluoroscopy shows mediastinal tumor with collapsed lung (arrows) due to pleural effusion (PLE); B. Right ventricular
(RV) angiogram illustrates diffuse narrowing of right pulmonary artery (RPA) and left pulmonary artery (LPA) by compression due to the large
mediastinal tumor. Pigtail catheter is in the pericardial space.
Cardiac Magnetic Resonance Imaging and

Computed Tomography
The spatial and temporal resolution is far lower than echo
cardiography. Soft tissue contrast is superior to that of
echocardiography and both modalities allow imaging of
entire mediastinum and extracardiac extent of the disease. In
malignant tumors of the heart they provide global anatomic
information. The classical chest radiographic finding of
a tooth or cartilage is uncommon in a teratoma but readily
detected on CT. CT features suggestive of malignancy include

wide attachment to the walls of the heart, destruction of
cardiac chamber wall, invasion of pericardium especially
hemorrhagic extension into the pulmonary arteries, veins or
vena cava, necrosis of the mass lesion, multiple lesions and
involvement beyond the pericardium.
Although both cardiac MRI and ultrafast CT provide
non-invasive, high resolution images of the heart, MRI
generally is preferred. In addition to furnishing detailed
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12
Miscellaneous
tumors, atrial myxoma or lipomatous septal hypertrophy.

Hypermetabolic state of tumor is detected by PET scan by
2-fluoro 2-deoxy D-glucose (FDG) metabolic tracer.
Angiography
Angiography is not required routinely as adequate information
is provided by non-invasive tests. However, when noninvasive tests are inadequate to define location or attachment
of tumor and when coronary or valvular heart disease coexist,
cardiac catheterization may provide supplemental information.
Contrast material is injected upstream to the tumor location,
and demonstrates the filling defect in the chamber of interest.
The major risk of angiography is peripheral embolization.
Figure 7: Extracardiac mass compressing the left ventricle causing
wall motion abnormality. LA = Left atrium; LV = Left ventricle; MV =
Mitral valve.
anatomic images, the T1- and T2-weighted sequences

reflect the chemical microenvironment within a tumor,
thereby offering clues as to the type of tumor that is
present. However, CT scanning is still useful when MRI is
not immediately available or is contraindicated.
The combination of echocardiography plus cardiac MRI or
CT may be useful in differentiating thrombus from tumor
in lesions appearing to arise on a heart valve.
Positron Emission Tomography Scan

Positron emission tomography (PET) has been useful in
identifying cardiac involvement in patients with metastatic
A
904
Transvenous Biopsy
Limited data are available on the risks and benefits of transvenous biopsy of suspected cardiac tumors. Because myxomas
may embolize, transvenous biopsy is not generally warranted
if the appearance is typical on non-invasive imaging. Biopsy
is considered reasonable for other cardiac tumors, if potential
benefits are deemed sufficient to outweigh potential risks.
Summary
The information obtained from echocardiography and cardiac
MRI or CT can confirm the presence of a cardiac tumor and its
location within the heart and may provide an initial indication
of the type of tumor. Transvenous biopsy may be helpful
in certain situations. In general, the information from noninvasive imaging is sufficient to make a decision regarding
B
Figures 8A and B: A. Extracardiac lung mass compressing the cardia; B. Dilated inferior vena cava
with spontaneous echocardiographic contrast (SEC)
the need for surgery, where a definitive histologic diagnosis

can be established.
Fibromas
Rhabdomyomas
Rhabdomyomas develop almost exclusively in children,
being the most common cardiac tumor of the infants and
children, mostly before the age of 1 year.27 These are actually
myocardial hamartomas or malformations that are composed
of myocytes that resemble fetal cardiac myocytes rather than
true neoplasm. Microscopic hallmark of rhabdomyoma is
spider cells (Figures 9A to C).
With the increasing use of ultrasound and improvements
in technique and MRI, these tumors are being detected
with increasing frequency, even in the prenatal period.
Rhabdomyomas are usually found in the ventricular
walls or on the AV valves or septal myocardium. On
echocardiography they are usually small, multiple, lobulated
homogenous hyperechoic intramural tumors ranging from
2 mm to 2 cm in size.
About 80 to 90 percent of rhabdomyoma are associated
with tuberous sclerosis (autosomal dominant) which is
characterized by hamartomas in multiple organs, epilepsy,
mental retardation and facial angiofibromas (adenoma
sebaceum) (Figure 10 A).
Most rhabdomyomas regress spontaneously, and resection
is usually not required unless a child is symptomatic.
Symptoms, if present, are caused by obstruction of blood flow
Fibromas are the second most common benign tumors in

children. They are usually found in the ventricular myocardium
and usually occur in the left ventricular free wall, anterior free
wall and the interventricular septum. Histologically, these
are similar to fibromas arising elsewhere in the body. They
may become quite large ranging between 3 to 10 cm. Unlike
rhabdomyomas, fibromas do not regress spontaneously. They
arise approximately 5 times more frequently in the LV than
the RV.28 Heart failure is the most common symptom, due
to obstruction of blood flow or interference with valvular
function. Myocardial dysfunction and conduction disturbances
also occur. Echocardiography, supplemented with CT scans
or MRI confirms the diagnosis. Calcification is seen in 25
percent of the cases. Hence a solitary, ventricular, calcific
tumor is a fibroma. Symptomatic tumors should be resected.29
Complete resection of very large tumors may require cardiac
transplantation.
Gorlin syndrome is autosomal dominant syndrome characterized by multiple nevoid basal cell carcinomas, medulloblastomas, cardiac fibroma and fibrous histiocytomas. Fibroma
is seen in fewer than 14 percent of the patients.
63
Pediatric Tumors26
through the heart or consist of rhythm disturbances, such as

heart block (most common), supraventricular or ventricular
tachycardia, interference with coronary blood flow and death.
Teratoma
Teratomas arise within the pericardium, but do not originate
from the cardiac structures. They are usually attached to the
root of the pulmonary artery and aorta and receive their blood
supply from the vasa vasorum of these vessels. Dyspnea and
cardiomegaly are the presenting symptom due to tamponade or
through direct pressure on the heart. Thus, there is a high risk of
death in utero or immediately after birth. Treatment therefore
requires either fetal tumor excision or cesarean section and
immediate operation on the newborn. Because teratomas
usually have a single supply and are not invasive, properly
timed tumor excision is straightforward and successful.28
Purkinje tumors/Hamartomas
Figures 9A to C: A. Serial cross-sections of the neonatal heart shows

obliteration of the ventricular cavities by glistening yellowish-white
masses, rhabdomyomas; B and C. The masses were composed
of ballooned out vacuolated cardiac myocytes with formation of
characteristic spider cells. Courtesy: Dr Pradeep Vaideeswar
These tumors consist of small, flat sheets of cells most

frequently located in the LV and on the endocardial and
epicardial surfaces.30 As such, they are undetectable by
echocardiographic or radiologic techniques. These are usually
tumors of young children and present with incessant ventricular
tachycardia. Electrocardiograms often demonstrate a bundle
branch pattern (right bundle branch block, when the tumor is
in the LV). Electrophysiologic studies can localize the tumors,
facilitating surgical excision. Imaging study typically reveal
heterogenous mass with solid and cystic areas.
905
Miscellaneous
12
Figure 10 A and B: A. Picture of a 25 years old tuberous sclerosis woman with classical facial angiofibromas. B. Fetal echocardiography
showing muliple echogenic masses, rhabdomyomas, in all four chambers of the heart in her 35 weeks gestation fetus.
Rhabdomyosarcomas
They constitute as many as 20 percent of all the primary
cardiac sarcomas commonly seen in children. Embryonal and
pleomorphic are seen as primary, whereas alveolar type is
usually due to metastasis from other sites. They usually present
in the second decade of life with constitutional symptoms,
congestive heart failure, arrhythmias, murmurs, occasionally
hypereosinophilic syndrome, hypertrophic osteoarthropathy
and polyarthritis.31 ECG and chest X-ray reveal non-specific
findings. TTE and TEE supported by CT and CMR are
needed.32,33 Multiple sites of myocardial involvement are
common and there is no predominant localization within any
area of the heart. They are aggressive tumors with metastasis
to lung and lymph nodes with poor prognosis. Complete
surgical resection is the treatment of choice. Both radiation
and chemotherapy are not very effective.
Tumors in Fetal Life

Rhabdomyomas are the most common tumors detected in
fetal life (Figure 10B). Sequential scans are indicated in high
risk mother, as these tumors may also be detected later in the
developing fetus. Also it is imperative to monitor their growth
for they can lead to significant outflow obstruction and fetal
hydrops or present with fetal arrhythmias and subsequent
intrauterine death.34
Conclusion
906
The tumors of the heart do not contribute significantly to

the overall tumor burden though they may cause a variety of
cardiac and systemic symptoms. The clinical features depends
on the size and to a significant extent, on the anatomic location.
If in a critical location, small, benign neoplasms may have
devastating clinical consequences. Progress in imaging and

cardiac surgery have considerably improved the prognosis.
Time is generally the best doctor.

Ovid
Acknowledgments
Thoracic Division), Seth GS Medical College, Mumbai, India
for the excellent pictures of the pathological specimens of
cardiac tumors and Dr Madhav Hegde, Consultant Radiologist,
Bengaluru, India for the CT image.
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1. Otto CM. Cardiac masses and potential cardiac Source of
embolus. In: Textbook of clinical echocardiography, 4th
edition. Otto CM. Saunders, Philadelphia; 2009.
2. Goldberg HP, Steinberg I. Primary tumors of the Heart.
Circulation. 1995;11:963-70.
3. Braunwald E. Heart disease: A textbook of cardiovascular
medicine. 6th edition Philadelphia PA: WB Saunden Co; 2001.
4. Bloor CM, ORourke RA. Cardiac tumors. Clinical presentation
and pathologic correlations.
5. Mc Allister HA, Feriogoio JJ. Tumors of the cardiovascular
system. Atlas of tumor pathology, series 2, Fascicle 15.
Washington DG: Armed Forces Institute of Pathology; 1978.
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6. Meng Q, Lai H, Lima J, et al. Echocardiographic and pathologic
characteristics of primary cardiac tumors: a study of 149 cases.
Int J cardiol. 2002;84:69-75.
7. Peters MN, Hall RJ, Cooley DA, The clinical syndrome of
atrial myxoma. Jama 1974;230:695-701.
8. Vidaillet Jr HJ, Seward JB, Fyke 3rd FE, et al. Syndrome
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lymphoma of the myocardium mimicking clinical Hypertrophic
cardiomyopathy. Circulation 2006;113:662-4.
22. Furman R, Bryant LR, Srivastava TN, et al. Right ventricular
mesothelioma with
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obstruction.
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23. Jimenez JF, Warren ET, Shroff RK, Stolz GA. Primary cardiac
paraganglioma. J Ark Med Soc. 2005;101:362-4
24. Kasai T, Kishi K, Kawabata M, et al. Cardiac metastases
from lung adenocarcinoma causing atrioventricular block
and left ventricular outflow obstruction. Chest. 2007;131:
1569-72.
25. Adenle AD, Edwards JE. Clinical and pathologic features of
metastatic neoplasms of the pericardium. Chest. 1982;81:16669.
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tumors in children: a 16-year experience Rev Port Cardiol.
2009;28:279-88.
27. Webb DW, Thomas RD, Osborne JP. Cardiac rhabdomyomas
and their association with tuberous sclerosis. Archives of
Disease in Childhood. 1993;68:367-70.
28. Grande AM, Ragni TR, Vigano M. Primary cardiac tumors. A
clinical experience of 12 years. Tex Heart Inst J. 1993;20:
223-30.
29. Geha AS, Weidman WH, Soule EH, et al. Intramural ventricular
cardiac fibroma: successful removal in 2 cases and review of
literature. Circulation. 1967;36:427-40.
30. Burke AP, Ribe JK, Bajaj AK, et al. Hamartoma of mature
cardiac myocytes. Hum Pathol. 1998;29:904-9.
31. OReilly M, Mc Donald RT, Fornasier VL. Clinical presentation
of a myocardial rhabdomyosarcoma. British Heart J. 1975;37:
672-75.
32. Tatli S, Lipton MJ. CT for intracardiac thrombi and tumors. Int
J Cardiovasc Imaging. 2005;21:115-31.
33. Araoz PA, Mulvagh SL, Tazelaar HD, et al. CT and MR imaging
of benign primary cardiac neoplasms with echocardiographic
correlation. Radiographics. 2000;20:1303-19.
34. Groves AMM, Fagg NKL, Cook AC, et al. Cardiac tumors
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1992;67:1189-92.
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with pigmented skin lesions and peripheral and endocrine

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Ragland MM, Tahir T. The role of echocardiography in
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Fine G. Neoplasms of the pericardium and heart. In: Gould
SE (Ed). Pathology of the heart and blood vessles. 3rd edition.
Springfield: Charles C. Thomas: 1968. p. 865.
Hayash H, Hidaka F, Kiriyama T, et al. A left ventricular lipoma
diagnosed on three-dimensional electrocardiogram gated
cardiac computed tomography. Heart Vessels. 2008;23:366-9.
Tatli S, Lipgton MJ. CT for intracardiac thrombi and tumors.
The International Journal of cardiovascular Imaging. 2005;21:
115-31.
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fibroelastoma diagnosed by echocardiography: a case report.
European Journal of Echocardiography. 2009;10:726-8.
Tse TS, Tsui KL, Ling LC, et al. Necrotic cardiac hemangioma
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coagulation. Hong Kong Med J. 2005;11:308-10.
Marrone G, Sciacca S, D Ancona G, et al. A rare case of
left ventricular In tramural Hemangioma Diagnosed using
15-T Cardiac MRI with histopathological correlation and
successfully treated by surgery. Cardiovasc. Intervent Radio L.
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of the pericardium presenting itself as a pericardial effusion
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45:393-94.
Komodromas T, Lieb D, Baraboutis J. Unusual presentation of
a pericardial cyst. Heart vessel. 2004;19:49-51.
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Redulescu D, Pripon S, Radulescu LJ, et al. A rare case
of primitive right atrium angio sarcoma with favourable
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2004;54:187.
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C hapter
64
Lutembacher Syndrome
Nagamani AC, Nagesh CM
Introduction
The earliest description of Lutembacher syndrome in medical
literature is found in a letter written by anatomist Johann
Friedrich Meckel to Albrecht von Haller in 1750.1 In 1811,
Corvisart described the association of atrial septal defect
(ASD) with mitral stenosis. (MS) 2 In 1916, Rene Lutembacher,
a French physician published the first comprehensive account
of these two defects.3 He described his first case of this
syndrome involving a 61-year-old woman and he attributed
the mitral valvular lesion to congenital MS. Because the MS
was, in fact, rheumatic in etiology, the syndrome was defined
eventually as a combination of congenital ASD and acquired
MS almost always rheumatic in etiology.
The definition of Lutembacher syndrome has undergone
many changes. Opinion differs regarding what lesions the
syndrome should include. Originally, Lutembacher syndrome
was defined as the combination of congenital defect in the
atrial septum and acquired rheumatic MS.4-6 Subsequently,
a few cases have been described with severe acquired
mitral stenosis with high left atrial pressures and presumed
stretching of a patent foramen ovale leading to left-to-right
shunting.5,7 In the typical Lutembacher syndrome, the ASD is
large, usually larger than 1.5 cm in diameter. The concept has
been further broadened to include different anatomic types of
congenital interatrial communications and different anatomic
types of acquired mitral valve disease. In the current era of
mitral valvuloplasty for acquired MS, residual iatrogenic
ASD secondary to trans-septal puncture is more common
than congenital ASD. This is sometimes labeled as iatrogenic
Lutembacher syndrome.
The first report of iatrogenic Lutembacher syndrome was
by Dr John Ross Jr and colleagues from the National Institutes
of Health.8 Their series included three patients, who had
acquired MS and developed a persistent ASD after trans-septal
catheterization. Although this syndrome is generally defined
as MS in combination with ASD, some have argued to define
the syndrome as a combination of ASD and any mitral valve

lesion, i.e. MS, mitral insufficiency or mixed lesion. In majority
of patients reported till now, the shunt at the atrial level is of
ostium secundum type, but in minority it could be ostium
primum type9 or partial anomalous pulmonary venous return
with intact atrial septum.10 Patent foramen ovale is not included
in the definition even though Lutembacher stated that the high
left atrial pressure of MS might stretch the margins of a valveincompetent foramen ovale and cause a left-to-right shunt.5,6
Currently any combination of ASD like congenital or
iatrogenic and MS, congenital or acquired, is referred to as
Lutembacher syndrome.
Pathophysiology
Mitral stenosis is invariably due to rheumatic mitral
valve disease. Acquired ASD is almost always iatrogenic,
either intentional or as a complication of a percutaneous
interventional procedure. The incidence of left to right
shunt following mitral valvuloplasty is estimated at 11 to
12 percent.11 Although most of these ASDs are small and
hemodynamically insignificant, some can be large enough to
have hemodynamic consequences, especially in patients who
develop restenosis of the mitral valve.
The hemodynamic effects of this syndrome are the result
of the interplay between the relative effects of ASD and
MS.5,8,9 In its initial description, the ASD was typically large
in Lutembacher syndrome, thus providing another route for
blood flow. Iatrogenic ASDs tend to be smaller but still may
be hemodynamically significant. The direction of blood flow
is determined largely by the compliance of the left and right
ventricles. The hemodynamic features and natural history of
the patients depends upon the size of the ASD, severity of the
MS, pulmonary vascular resistance and the compliance of the
right ventricle.9
The magnitude of the shunt across the ASD is exacerbated
by the increased left atrial pressure due to the MS than what
Epidemiology
Although the exact prevalence of Lutembacher syndrome is
not known, it is probably higher in areas, where rheumatic
heart disease is common. Mitral stenosis is encountered in
4 percent of patients with an ASD. Congenital MS itself is rare,
accounting for only 0.6 percent of congenital heart disease
cases at autopsy. The incidence of ASD in patients with MS
is 0.6 to 0.7 percent.12 In the US study, the combination was
Table 1
Hemodynamic and clinical expression of ASD and MS

Effects of MS on ASD
Effects of ASD on MS
1. Increase in the L to R shunt
1. Decreases symptoms
2. Pulmonary hypertension
occurs earlier
2. Decreases episodes of
paroxysmal nocturnal
dyspnea
3. Increased incidence of right

ventricular failure
3. Decreases mitral valve

gradient
4. Increased incidence of
bacterial endocarditis
4. Decreased incidence of
calcification
5. Increased incidence of
atrial fibrillation
ASD=Atrial septal defect; MS=Mitral stenosis
found in 5 of 25,000 autopsies. In another study the incidence

of Lutembachers syndrome was 0.001/10,00000.14
The syndrome was diagnosed more frequently in the past
for the following reasons:
1. Without echocardiography, the combination of mid
diastolic murmur, actually due to the increased blood flow
across the tricuspid valve and systolic murmur of ASD led
to a mistaken diagnosis of Lutembacher syndrome.
2. The prevalence of both rheumatic heart disease and MS was
high in the past before the antibiotic era.With the decline in
the frequency of rheumatic fever, the prevalence of MS has
decreased and so has the diagnosis of the syndrome
3. The combination of ASD and MS may not be evident on
physical examination and for this reason it is best confirmed
by echocardiography.
Assuming a relatively uniform incidence of the ASD,
the incidence of coexisting rheumatic MS depends on the
geographic prevalence of rheumatic fever. The incidence of
Lutembacher syndrome is more in developing countries like
South-East Asia than developed countries because of the
higher incidence of rheumatic heart disease in developing
countries. In underdeveloped countries, a history of rheumatic
fever has been reported in 40 percent of patients with
Lutembacher syndrome.9
The syndrome can present at any age. It usually presents in
young adults but may present in elderly patients. Cases have
been diagnosed in the seventh decade of life. As described
above, the first case report of Lutembacher syndrome was a
61-year-old female, who had been pregnant for 7 times. It is
more frequently seen in females than males. Part of the reason
is the higher incidence of both congenital ASD and rheumatic
MS in females.
As the number of patients having MS undergoing
transcatheter valvotomy is increasing, the chance of iatrogenic
Lutembacher syndrome is more. Small ASD with pulmonary
to systemic shunt ratios of less than 1.5 are common after
balloon mitral valvuloplasty using the transatrial septal
approach, especially if highly sensitive techniques such as
transesophageal color flow echocardiography are used for
detection. Yoshida et al15 used transesophageal color flow
echocardiography and detected an 87 percent incidence of
ASD immediately after balloon mitral valvuloplasty using
a single-balloon technique. Cequier et al16 used right heart
oximetry and indicator-dilution curves to detect a 62 percent
incidence within the first day after balloon valvuloplasty
using a one-septostomy two-balloon technique. These defects
and the associated left-to-right shunting usually decrease or
are eliminated with time. Some patients however, can have
persistent shunting, which might be because of the size of the
initial defect created or the unsuccessful relief of MS. Currently,
there do not seem to be any major clinical sequelae of these
defects even when they persist; however, longer follow-up
of more patients is necessary to clarify some of the potential
64
Lutembacher syndrome
otherwise would be in a similar size of ASD in the absence

of MS. This occurs at the cost of progressive dilatation and
ultimately failure of the right ventricle and the reciprocal
decrease in the left ventricular filling and stroke volume.
Congestive heart failure leads to increased incidence of atrial
fibrillation.
If the ASD is restrictive, the shunt across the defect
will be less and hence patient will follow the course of
isolated MS. On the contrary, if the ASD is nonrestrictive,
most of the blood entering the left atrium will be shunted
across the ASD leading to decompression of the left atrium
thereby ameliorating the symptoms and signs of pulmonary
congestion.Thus the features of ASD dominate the clinical
picture despite significant mitral stenosis. Development of
Eisenmengers syndrome is very uncommon in the presence
of large ASD and high left atrial pressure of MS.
Susceptibility to infective endocarditis is increased by the
presence of MS in contrast to the negligible susceptibility of
an uncomplicated ostium secundum ASD.12 Calcification of
the mitral valve is less common in MS with associated ASD as
the mitral valve is subjected to less pressure and less turbulent
flow as the left atrium is decompressed (Table 1).
The term reverse Lutembacher syndrome is sometimes
used to describe those rare cases, in which a predominant
right-to-left shunt develops owing to the development of
severe tricuspid stenosis.13
909
Miscellaneous
12
clinical consequences. There are few case reports in the

literature describing the residual hemodynamically significant
ASD after percutaneous mitral balloon valvuloplasty who
required ASD closure because of right-sided heart failure.17-19
Clinical presentation
the left atrial pressure pulse are transmitted to the right atrium
and into the internal jugular vein.20 Lutembacher syndrome
is therefore responsible for an elevated mean jugular venous
pressure in the absence of right ventricular failure and for an
elevated jugular venous A wave in the absence of pulmonary
hypertension.
History
Precordial Examination
Patients may or may not have a history of rheumatic fever.They

may remain asymptomatic for many years. Symptoms depend
on the severity as well as the predominance of the lesion.
In patients with large ASD, symptoms of pulmonary
congestion typical of isolated MS do not appear until late
in the course of the disease. This group mainly present with
symptoms due to right sided volume overload, low cardiac
output or congestive heart failure (Figure 1). They usually
have fatigue and reduced exercise tolerance as the prominent
symptoms. Once the right heart failure supervenes, the patient
may develop progressive ankle edema, weight gain, right
upper quadrant pain and ascites.
In patients with restrictive ASD, signs and symptoms of
pulmonary congestion will occur depending on the severity of
MS. In the presence of severe MS, patients may present with
paroxysmal nocturnal dyspnea, orthopnea and hemoptysis.
Palpitations, paroxysmal or exertional, occur frequently.
Because of the augmented shunting of blood from left to right
atrium along with high left atrial pressure, both the atria will
be dilated and thus predisposing the patient to arrhythmias,
especially atrial fibrillation.
Paroxysmal nocturnal dyspnea, orthopnea and hemoptysis
are signs of pulmonary congestion and are seen less frequently
in Lutembacher syndrome than in isolated MS. They are
more common in patients with small ASD and are probably
more common in patients who develop reverse Lutembacher
syndrome. In some patients with large pulmonary blood
flow due to a large left-to-right shunt, orthopnea can develop
because of the decreased compliance of the lungs.
Precordial examination may reveal prominent left parasternal

heave in patients with nonrestrictive ASD having associated
MS than with an uncomplicated ASD, because MS augments
left to right shunt. Left ventricular impulse is unimpressive
because of under filling of the left ventricle. A tapping apical
impulse due to the palpable, loud first heart sound may be
present. The apex may be diffuse if the dilated right ventricle
occupies the apex instead of the left ventricle. Diastolic thrill
at the apex is exceptional as the mitral valve flow velocity is
comparatively low. Systolic thrill may be felt at the left upper
parasternal area.
Physical examination reveals signs due to the ASD and MS,
which are modified because of the presence of both lesions in
the same patient.
The Arterial Pulse

Pulse may be of small volume because of low left ventricular
stroke volume. It may be regular or irregular, atrial fibrillation
being the most common arrhythmia.

910
The right and left atrium functions as a common chamber,

when the ASD is non-restrictive, so the height and contour of
Auscultation
On auscultation, signs of MS are attenuated in Lutembacher
syndrome due to two reasons.4,12 First, decompression of the
left atrium to the right atrium, across the nonrestrictive ASD,
causes reduced flow across the stenotic mitral valve.3 Second,
as the apex is formed by the volume overloaded right ventricle,
the signs of left ventricular inflow obstruction are less audible.12
Loud first heart sound (S1), opening snap (OS) and a mitral
early to-mid diastolic murmur are the classic auscultatory
findings of MS, but are attenuated as described above.
Development of pulmonary hypertension and consequently an
increase in the right and left atrial pressure may increase the
transmitral pressure gradient and bring out these auscultatory
findings, but this phenomenon is concealed by further dilatation
of the right ventricle, thus obscuring the left ventricular apex.
Second heart sound (S2) is widely split and fixed. S2 is
widely split for two reasons. Firstly, the increased right heart
flow due to the ASD can result in delayed closure of the
pulmonary component of the S2 and secondly, because of the
reduced left ventricular filling and hence reduced aortic flow,
the aortic component of the second heart sound occurs early.
Third and fourth heart sounds of right ventricular origin may be
audible in left parasternal area and are louder with inspiration.
Systolic murmurs are due to the following:
Ejection systolic flow murmur in the upper left parasternal
area is frequently heard, because of the increased flow
across the pulmonary valve.
Holosystolic murmur due to the tricuspid regurgitation
may be heard at the left parasternal area and may get
transmitted to the apex as the right ventricle is dilated.9
This invites the mistaken diagnosis of mitral regurgitation,
but the inspiratory augmentation of the systolic murmur
(Carvallos sign) should be able to differentiate it.
64
Figure 1: Algorithm showing the approach to the patient with Lutembacher syndrome
may be required for proper assessment of ASD.
*Doppler pressure half time is not used as it overestimates the MVOA.
ASD=Atrial septal defect; CXR=Chest X-ray; ECG=Electrocardiogram; LA = Left atrium; LAE=Left atrial enlargement; MDM=Mid
diastolic murmur; MS=Mitral stenosis; MVOA=Mitral valve orifice area; OMV=Open mitral valvotomy. PTMC=Percutaneous transseptal mitral commissurotomy; RA=Right atrium; RAE=Right atrial enlargement; RV=Right ventricle; TEE=Transesophageal
echocardiogram; TTE=Transthoracic echocardiogram.
TEE
Mid diastolic murmurs are due to the following:

Increased flow across the tricuspid valve due to the ASD
or accompanying tricuspid stenosis, best heard at the
left lower sternal border or at apex for reasons already
mentioned.
Mitral stenosis murmur best heard at apex after exercise
and with the patient in left lateral position.
Continuous murmur can be heard at lower right sternal
area due to the continuous shunting of blood across
the restrictive ASD in the presence of severe MS.5,21
The continuous murmur may increase with slow deep
inspiration because of the delayed inspiratory increase in
the left atrial pressure and volume.8 This is an unusual
finding on physical examination. During the strain phase
of the Valsalva maneuver, the interatrial gradient is reduced
or abolished and the continuous murmur diminishes.8
Abdominal examination may reveal ascites and hepatomegaly in the presence of right heart failure.
The Lutembacher syndrome should be differentiated
from:
1. Atrial septal defect.
2. Mitral stenosis
3. Patent foramen ovale

4. Primary pulmonary hypertension
5. Secondary pulmonary hypertension
6. Tricuspid stenosis.
Complications
Patient with Lutembacher syndrome can develop the following
complications:
1. Right sided heart failure
2. Atrial arrhythmias
3. Pulmonary congestion in case of restrictive ASD
4. Bacterial endocarditis especially if the patient is having
Investigations
Similar to any disease process, a comprehensive evaluation is
required for the diagnosis of Lutembacher syndrome.
Electrocardiogram
Electrocardiogram (ECG) gives clue to the predominance
of the lesion in Lutembacher syndrome. When the ASD is
restrictive, the electrocardiogram resembles that of MS in
911
Miscellaneous
12
Figure 2: Electrocardiogram showing sinus rhythm, right axis deviation, left atrial enlargement and rSR pattern in lead V1
the form of broad bifid configuration in lead II and a deep

prolonged P-terminal force in lead V1. When the ASD is
non-restrictive, it resembles that of ASD in the form of P
pulmonale with right ventricular hypertrophy. In the presence
of sinus rhythm, tall, broad or bifid P waves in lead II with
a deep negative force in V1, suggests enlargement of both
atria (Figure 2). QRS shows right axis deviation, right
ventricular hypertrophy, complete or incomplete right bundle
branch block. Right ventricular hypertrophy is more common
than with isolated ASD. There is increased propensity for
atrial fibrillation in Lutembacher syndrome compared to
uncomplicated ASD.9
Chest X-ray
Chest X-ray (Figure 3) may reveal pulmonary plethora
without much evidence of pulmonary venous congestion
due to the large left to right shunt across nonrestrictive ASD.
Right atrium, right ventricle, main pulmonary artery are
dilated more than expected for an uncomplicated ASD of the
same size. On the contrary, pulmonary vascular congestion
and marked left atrial enlargement may be present if severe
MS is associated with a restrictive ASD.4,9 Atrial fibrillation
increases left atrial size.9 Mitral valve calcification can occur
late in life.
912
Echocardiogram
Two-dimensional echocardiography (Figures 4A to C) with
colour flow imaging and Doppler interrogation establishes
Figure 3: Chest radiograph shows cardiomegaly, prominent main

pulmonary artery with right atrial and left atrial appendage enlargement
the diagnosis of Lutembacher syndrome. It may show dilated

right atrium, right ventricle and main pulmonary artery. Type
and size of the ASD can be assessed. Mitral valve orifice area
can be calculated by planimetry. Color flow and Doppler
interrogation confirms the presence of shunt across the ASD,
mitral valve stenotic gradient, presence of mitral and tricuspid
regurgitation.
64
However, Doppler pressure half-time usually overestimates

the mitral valve orifice area because the ASD decompresses
the left atrium thus decreasing the transmitral pressure
gradient. On the other hand, planimetry and the Doppler
continuity equation method gives an accurate assessment
of the mitral valve orifice area in Lutembacher syndrome.22
On the contrary, the presence of ASD provides an additional
method of calculating left atrial pressure, the most important
determinant of the symptoms in patients with MS. In such a
patient, left atrial pressure can be determined by subtracting
the right atrial pressure from the Doppler measurement of the
gradient across the ASD.23
The continuous murmur at the right lower sternal border in
the presence of a restrictive ASD coincides with Doppler flow
patterns recorded by transoesophageal echocardiography.21 This
is used especially for proper sizing of the ASD and assessing its
suitability for transcatheter device closure. It is also useful to
rule out left atrial clot in patients prior to percutaneous transseptal mitral commissurotomy (PTMC).
In the present era, cardiac catheterisation is rarely needed
for the diagnosis of Lutembacher syndrome. It can be used to
evaluate the ASD, detect reversible pulmonary hypertension,
measure the mitral valve orifice area and evaluate the coronary
artery disease in high risk patients. Rather, it is more useful as
a treatment modality in the form of PTMC and transcatheter
device closure of ASD as discussed later in detail.
Management
Management strategy of a patient with Lutembacher syndrome
includes symptomatic treatment and definitive treatment with
either percutaneous or surgical procedures.
Symptomatic Treatment
1. Diuretics for right sided heart failure or pulmonary
congestion if present.
2. Digoxin, beta blockers and calcium channel blockers are
used for rate control in atrial fibrillation, while amiodarone
or sotalol may be used for both rate control as well as for
conversion to sinus rhythm.
Compared to uncomplicated ASD, these patients especially
if associated with mitral regurgitation are at increased risk
for subacute bacterial endocarditis (SBE) and hence SBE
prophylaxis is warranted.
C
Percutaneous/Transcatheter Treatment
Lutembacher syndrome has traditionally been treated by open
heart surgery. In the present era, because of advancement of
the percutaneous interventional techniques, availability of
newer and better hardwares, more experience in the field of
intervention, there is a shift of treatment strategy from surgery
to transcatheter approach in majority of the patients.
Figures 4A to C: A. M-mode echocardiography shows dilated right

ventricle (RV), paradoxical interventricular septal motion, thickened
and echogenic mitral value with reduced EF slope of anterior mitral
leaflet. B. Transthoracic echocardiogram (TTE) in apical fourchamber view shows dilated right atrium (RA), RV and left atrium
but small left ventricle (LV) with thickened stenotic mitral valve and
large ostium secundum atrial septal defect (ASD). Color flow Doppler
showing left-to-right shunt through the ASD; C. TTE in short axis
shows dilated RV, small LV, thickened mitral valve with mitral valve
orifice area of 0.8 cm2
913
Miscellaneous
12
914
The experience with transcatheter treatment of the

Lutembacher syndrome is small.24-31 The use of percutaneous
treatment of Lutembacher syndrome was first described by
Ruiz et al in 1992.24 He did combined umbrella closure of
the ASD with Locks Clamshell occluder in conjunction with
mitral and aortic balloon valvotomies as a rescue procedure
in a 43-year-old female with ASD, severe aortic and mitral
stenosis and pulmonary hypertension. Unfortunately, that
patient died suddenly at 8 weeks before surgical procedure
could be undertaken. Subsequent reports demonstrated the
feasibility of percutaneous balloon valvuloplasty and ASD
device closure using a variety of balloon catheter techniques
and devices. Successful combined transcatheter therapy
was first described by Joseph et al in 1999.25 He used the
Amplatzer septal occluder for ASD and Joseph mitral
balloon catheter for MS. Since then, several successful
cases have been reported.26-30 Because of the available
data in large number of patients with excellent long-term
follow-up results along with the safety and ease of usage of
Inoue-balloon catheter,25 the Inoue-balloon technique has
become the procedure of choice for percutaneous balloon
mitral valvuloplasty.32 The Amplatzer ASD occluder, on the
other hand, is a self-centring device with a high complete
closure rate of 93 to 97 percent at 1 month of followup.33,34 The advantages of this device in comparison with
other septal occluders include simple delivery system
using smaller-sized sheaths, easy retrievability and absence
of sharp corners or spokes. Thus, with the advent of the
newer techniques, percutaneous procedure has become the
definitive treatment modality rather than just a palliative
measure.
The combination of device closure of secundum ASD

by Amplatzer ASD occluder and Joseph mitral balloon
valvuloplasty (JOMIVA) using single-balloon technique with
the Joseph mitral balloon catheter35 is considerably simpler
and quicker than the conventional double-balloon technique.
When compared to the Inoue-balloon technique, the Joseph
mitral balloon valvuloplasty has comparable efficacy, safety
and simplicity.35 However, the cost of the Joseph balloon
catheter is less than half that of the Inoue-balloon catheter,
making the procedure cheaper even if a second balloon of
larger diameter is required for further dilatation.
Nowadays, PTMC using Inoue-balloon technique (Figure
5A) and ASD device closure (Figure 5B) with Amplatzer
septal occluder has been considered as the treatment of
choice for Lutembacher syndrome.30,33,34 The successful
combined use of these two techniques was first described
by Chau et al.26 Other advantages of transcatheter treatment
over traditional surgical correction include the avoidance
of complications associated with open heart surgery and
general anesthesia, quicker recovery from the procedure and
short hospital stay. Even though there is a minimal risk for
restenosis, repeat PTMC can be done with good results.28 Of
course, the presence of Amplatzer septal occluder in situ may
make it undesirable to use the transseptal approach for repeat
PTMC. The retrograde non-transseptal approach32 may be a
better option in this situation.
One might presume that presence of ASD simplifies
balloon mitral valvuloplasty by precluding the need for a
crucial but sometimes difficult step: the atrial septal puncture.
On the contrary, the large defect in the septum makes the
Inoue-balloon catheter unstable, which provides excessive
B
Figures 5A and B: A. Balloon mitral-valvotomy with Inoue-balloon; B. Amplatzer duct occluder in place
Surgical Management
With the advent of newer techniques and improvised hardware,
the role of surgical management in Lutembacher syndrome
is limited to large ASD not amenable to percutaneous device
closure or to the MS which is not suitable for PTMC. In this
group of patients, open mitral valvotomy is done along with
ASD patch closure. Patients may need valve replacement
surgery if valve is not suitable for valvotomy.
Prognosis
No definite data of morbidity and mortality are available.
Prognosis is related to the relative severity of the individual
lesions. Patients with Lutembacher syndrome have fairly
good survival. Patients have lived into their ninth decade
without developing any cardiac symptoms. Women have had
multiple pregnancies without complications. In present era,
with the advent of newer transcatheter techniques, there is
further decline in the morbidity associated with this disease.
Key Points
1. Lutembacher syndrome is defined as a combination of MS
with a left to right shunt at the atrial septal level, which
typically is the ostium secundum type.
2. The term reverse Lutembacher syndrome is sometimes
used, where pure tricuspid stenosis is associated with right
to left shunt across the atrial septum.
3. The presence of the ASD alters the pathophysiology and
thus the clinical course of Lutembacher syndrome as
compared to isolated MS.
4. The pressure half time method underestimates the severity
of MS, and hence planimetry is the preferred method in
this situation.
5. Treatment of choice is percutaneous transcatheter device
closure of ASD and mitral valvotomy until and unless the
lesions are unsuitable for the procedures.
Conclusion
Lutembacher syndrome is an unusual clinical entity of
congenital secundum ASD in combination with rheumatic
MS. In the setting of percutaneous mitral valvuloplasty,
the iatrogenic form of Lutembacher syndrome can occur.
Early diagnosis and optimal treatment has a good prognosis
but late diagnosis and development of heart failure bears
bad prognosis. Most of the patients die subsequently due
to heart failure, cardiac arrhythmias and thromboembolic

cerebrovascular diseases. Early diagnosis and transcatheter or
surgical management can reduce morbidity and mortality.
He's the best physician that knows the worthlessness of the
most medicines.
Benjamin Franklin
Acknowledgement
We wish to thank Dr Bhupinder Singh for his assistance in
preparing the manuscript.
64
space for free floatation of the catheter, making its passage

into the left ventricle difficult by the Inoue technique. So to
obviate this difficulty, one may have to do a septal puncture
just below the ASD and try to cross the mitral valve as this
anchors the balloon catheter.31
References
1. Wiedemann HR. Earliest description by Johann Friedrich
Meckel, Senior (1750) of what is known today as Lutembacher
syndrome (1916).Am J Med Genet. 1994;53:59-64.
2. Corvisart, JN. Essaisur les Maladies et les Lesions Organiques
du Coeur et des GrosVaisseaux. 2nd edition; Paris. 1811.
3. Lutembacher R. Dela stenose mitrale avec communication
inter auriculare. Arch Mal Coaeur. 1916;9:237-50.
4. Espino-Vela J. Rheumatic heart disease associated with atrial
septal defect: Clinical and pathologic study of 12 cases of
Lutembacher syndrome. Am Heart J. 1959;57:185-202.
5. Goldfarb B,Wang Y. Mitral stenosis and left to right shunt
at the atrial level. A broadened concept of the Lutembacher
syndrome. Am J Cardiol.1966;17:319-26.
6. Gueron M, Gussarsky J. Lutembacher syndrome obsolete? A
new modified concept of mitral valve disease and left to right
shunt at atrial level. Am Heart J. 1976;91:535.
7. Marshall RJ, Warden HE. Mitral valve disease complicated by
left-to-right shunt at atrial level. Circulation. 1964;29:432-39.
8. Ross J Jr,Braunwald E, Mason DT,et al. Inter atrial
communication and left atrial hypertension: A cause of
continuous murmur. Circulation.1963;28:853-60.
9. Bashi W, Ravikumar E, Jairaj PS, et al. Coexistent mitral valve
disease with left-to-right shunt at the atrial level: Clinical
profile, hemodynamics, and surgical considerations in 67
consecutive patients. Am Heart J. 1987;114:1406-14.
10. Wassermil M, Hoffman MS. Partial anomalous pulmonary
venous drainage associated with mitral stenosis with an intact
atrial septum. Am J Cardiol. 1962;10:894-99.
11. Cheng TO. Percutaneous baIIoon vaIvuIopIasty. New
YorkIgakushion; 1992:269.
12. Perloff JK. The clinical recognition of congenital heart disease.
4th edition. Philadelphia: Saunders. 1994. pp. 323-28.
13. Fadel BM,Hiatt BL,Kerins DM. Isolated rheumatic
tricuspid stenosis with reverse Lutembachers physiology.
14. Ali SY, Rahman M, Islam M, et al. Lutembachers
SyndromeA Case report. Faridpur Med Coll J. 2011;6:59-60.
15. Yoshida K, Yoshikawa J, Akasaka T, et al. Assessment of
left-to-right atrial shunting following percutaneous mitral
valvuloplasty by transesophageal color Doppler flow mapping.
Circulation 1989; 80:1521-26.
16. Cequier A, Bonan R, Serra A, et al. Left-to-right atrial shunting
after percutaneous mitral valvuloplasty: Incidence and longterm hemodynamic follow-up. Circulation. 1990;81:1190-97.
915
Miscellaneous
12
916
17. Zanchetta M, Onorato E, Rigatelli G, et al. Use of Amplatzer

septal occluder in a case of residual atrial septal defect
causing bidirectional shunting after percutaneous
Inoue mitral balloon valvuloplasty. J Invasive Cardiol.
2001;13:223-26.
18. Sadaniantz A,Luttmann C,Shulman RS,et al. Acquired
Lutembacher syndrome or mitral stenosis and acquired atrial
septal defect after trans-septal mitral valvuloplasty. Cathet
Cardiovasc Diagn.1990;21:7-9.
19. Chen CR, Cheng TO, Chen JY, et al. Long-term results of
percutaneous balloon mitral valvuloplasty for mitral stenosis: a
follow-up study to 11 years in 202 patients. Cathet Cardiovasc
Diagn. 1998;453:132-39.
20. Dexter L. Atrial septal defect. Br Heart J. 1956;18:209-25.
21. Iga K,Tomonaga G,Hori K. Continuous murmur in
Lutembacher syndrome analyzed by Doppler echocardiography.
Chest.1992;101:565-66.
22. Vasan RS, Shrivastava S, Kumar MV. Value and limitations
of Doppler echocardiographic determination of mitral
valve area in Lutembacher syndrome.J Am Coll Cardiol.
1992;20:1362-70.
23. Budhwani N,Anis A,Nichols K,et al. Echocardiographic
assessment of left and right heart hemodynamics in a patient
with Lutembachers syndrome. Heart Lung.2004;33:50-54.
24. Ruiz CE, Gamra H, Mahrer P, et al. Percutaneous closure of a
secundum defect and double balloon valvotomies of a severe
mitral and aortic valve stenosis in a patient with Lutembachers
syndrome and severe pulmonary hypertension. Cathet
Cardiovasc Diagn. 1992;25:309-12.
25. Joseph G, Rajpal KA, Kumar KS. Definitive percutaneous
treatment of Lutembachers syndrome. Catheter Cardiovasc
Interv. 1999;48:199-204.
26. Chau EM, Lee CH, Chow WH. Transcatheter treatment of a

case of Lutembacher syndrome. Catheter Cardiovasc Interv.
2000;50:68-70.
27. Aroney C, Lapanum W, Scalia G, et al. Transcatheter treatment
of Lutembacher syndrome. Intern Med J. 2003;33: 259-60.
28. Ledesma M, Martinez P, Cazares MA, et al. Transcatheter
treatment of Lutembacher syndrome: combined balloon mitral
valvuloplasty and percutaneous atrial septal defect closure. J
29. Ahmed WH, Al-Shaibi KF, Chamsi-Pasha H, et al. Nonsurgical correction of Lutembacher syndrome. Saudi Med J.
2003;24:307-08.
30. Cheng TO, Holmes DR, Jr. Percutaneous balloon mitral
valvuloplasty by the Inoue balloon technique: the procedure
of choice for treatment of mitral stenosis. Am J Cardiol.
1998;81:624-28.
31. Bhambhani A, Somnath HS. Percutaneous treatment of
Lutembacher syndrome in a case with difficult mitral value
crossing. J Invasive cardiol. 2012;24:E54-6.
32. Stefanidis C, Stratos C, Pitsavos C, et al. Retrograde non
transseptal balloon mitral valvuloplasty: immediate results and
long-term follow-up. Circulation. 1992;85:1760-67.
33. Masura J, Gavora P, Formanek A, et al. Transcatheter closure
of secundum atrial septal defects using the new self centering
Amplatzer septal occluder: initial human experience. Cathet
Cardiovasc Diagn. 1997;42:388-93.
34. Thanopoulos B, Laskari CV, Tsaousis GS, et al. Closure of
atrial septal defects with the Amplatzer occlusion device:
preliminary results. J Am Coll Cardiol. 1998;31:1110-16.
35. Joseph G, Chandy ST, George PV, et al. A new over-the wire
single-balloon technique for percutaneous mitral valvuloplasty.
Am J Cardiol. 1998 (suppl);82:113S.
C hapter
65
Pulmonary Hypertension
Maddury Jyotsna, Madhavapeddi Aditya
INTRODUCTION
The lung has a unique double arterial blood supply from
the pulmonary and bronchial arteries, as well as double
venous drainage into the pulmonary and azygos veins.1 The
pulmonary circulation is characterized by high flow (the
entire right ventricular output) and by low pressure and low
resistance. Its wide and thin-walled vessels reflect these
hemodynamic features. The normal pulmonary vascular bed
offers less than one-tenth the resistance to flow offered by the
systemic bed. The calculated pulmonary vascular resistance
(PVR) in normal adults is 67 23 dynes-seccm5 or 1 Wood
unit. Although it has been called the 'lesser circulation'
the response of the pulmonary vascular bed to a variety of
conditions and disease states is the major determinant of
clinical outcome.
DEFINITION
Pulmonary hypertention is defined as a mean pulmonary artery
pressure (PAP) greater than 25 mm Hg at rest.2 A mean PAP of
8 to 20 mm Hg at rest is considered normal, while a mean PAP
of 21 to 24 mm Hg at rest has uncertain clinical implications.
Two definitions that were previously accepted are no longer
used. They include a mean PAP greater than 30 mm Hg with
exercise (measured by right heart catheterization)3and a

systolic PAP greater than 40 mm Hg (measured by Doppler
echocardiography).4
Pulmonary hypertension may be secondary to heart defects
or lung parenchymal or vascular disease or thromboembolism
or idiopathic or combination of these. Because the causes of
pulmonary hypertension are so diverse, it is essential that the
etiology underlying the pulmonary hypertension be clearly
determined before embarking on treatment.
CLASSIFICATION OF PULMONARY HYPERTENSION

In 1998, a classification for pulmonary hypertension
was developed at the World Symposium on Pulmonary
Hypertension, co-sponsored by the World Health Organization
(WHO) and later modifications to this classification have been
proposed5 (Figure 1).
A patient can have pulmonary hypertension from the
standpoint of an elevated PAP but with normal PVR. There
are patients whose resting hemodynamics are normal, but in
whom marked elevations in PAP occur with exercise. Hence, a
a functional classification patterned after the New York Heart
Association (NYHA) for heart disease has been developed
to allow comparisons of patients with respect to the clinical
severity of the disease process (Table 1).
Table 1
World Health Organization functional classification of pulmonary hypertension7

Functional class
Description
Class I
Patients with pulmonary hypertension, but without resulting limitation of physical activity. Ordinary physical
activity does not cause undue dyspnea or fatigue, chest pain or near syncope.
Class II
Patients with pulmonary hypertension resulting in slight limitation of physical activity. They are comfortable at
rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain or near syncope.
Class III
Patients with pulmonary hypertension resulting in marked limitation of physical activity. They are comfortable at
rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain or near syncope.
Class IV
Patients with pulmonary hypertension with inability to carry out any physical activity without symptoms. These
patients manifest signs of right heart failure. Dyspnea and/or fatigue may even be present at rest. Discomfort is
increased by any physical activity.
MISCELLANEOUS
12
Figure 1: Revised Clinical Classification of Pulmonary Hypertension. AH = Alveolar hypoventilation; APAH = Associated with pulmonary
arterial hypertension; COPD = Chronic obstructive pulmonary disease; CVD = Collagen vascular disease; CSTPS = Congenital systemic-topulmonary shunts; Devel. ABN = Developmental abnormalities; DISTAL PA = Distal pulmonary arteries; FPAH = Familial pulmonary arterial
hypertension; HA = High altitude; HIV = Human immunodeficiency virus infection; ILD = Interstitial lung disease; IPAH = Idiopathic pulmonary
arterial hypertension; LS = Left-sided; NT- PE = Non-thrombotic pulmonary embolism; OTHERS = Thyroid disorders, Glycogen storage disease,
Gaucher disease, Hereditary hemorrhagic telangiectasia, Hemoglobinopathies, Myeloproliferative disorders, Splenectomy; PCH = Pulmonary
capillary hemangiomatosis; PH = Portal hypertension; PROX PA = Proximal pulmonary arteries; PVOD = Pulmonary veno-occlusive disease;
SD = Sleep-disordered breathing; TEO = Thromboembolic obstruction; VEN. HD = ventricular heart disease; VHD = valvular heart disease.
918
Figure 2: Major role of endothelial injury in pulmonary arterial hypertension (PAH) pathophysiology
MECHANISM OF DEVELOPMENT OF
PULMONARY HYPERTENSION
65
Morphological abnormalities in each cell line of the

pulmonary vasculature have been described in cases of
idiopathic pulmonary arterial hypertension (IPAH).6 The
vascular changes from pulmonary arterial hypertension
(PAH) occur across a spectrum and are likely to be
influenced by genetic and environmental factors. The exact
cause is unknown, but it probably represents the clinical
expression of PAH as the final common pathway from
multiple biological abnormalities within the pulmonary
circulation.7-10 Causative factors for PAH development are
dysfunctional endothelium, change in local hemodynamics,
defects in ion channels, increased plasma levels of serotonin
and elastolytic enzymes and other vascular proteins.
Endothelial cell dysfunction plays major role in pathogenesis
of PAH11 (Figure 2).
Probable pathways leading to hypertensive pulmonary
endothelial and smooth muscle cell changes are represented
in Figure 3. Due to reduced expression of the endothelial

isoform of nitric oxide (NO) synthase and expression of
different growth factors by dysfunctional endothelial cell,
intimal hyperplasia and medial hypertrophy occurs, which in
turn causes PAH (Figure 4). Equally important factor for PAH
development is the in situ thrombosis formation in the small
pulmonary arteries due to imbalance between the thrombotic
and prothrombotic factors (Figure 5).
Increase in pulmonary flow and shear stress, as in the
case of congenital shunt lesions, cause changes in the local
hemodynamics, can influence the pulmonary vascular
remodeling. Increase in flow causes release of mediators
from endothelial cells for induction of vascular smooth
muscle cell growth. Increase shear stress induces apoptosis of
endothelial cells. Genetic or acquired defect in potassium and
L- type calcium channels, which are important in regulating
pulmonary vascular tone are reported in PAH patients.12
The abnormality in platelet serotonin and mutations in the
serotonin transporter and 5-hydroxytryptamine 2B (5-HT2B)
receptor have now been reported in patients with IPAH.13,14
Figure 3: Probable pathways causing changes in pulmonary endothelial and smooth muscle cells. PAEC = Pulmonary artery endothelial cell;
PBF = Pulmonary blood flow; SMC = Smooth muscle cell.
Figure 4: Mechanism of action of dysfunctional endothelial cell in production of pulmonary arterial hypertension (PAH). BFGF = Basic fibroblast
growth factor; ECM = Extracellular matrix; ICS = Intracellular signaling; IH = Intimal hyperplasia; MH = Medial hypertrophy;
919
MISCELLANEOUS
12
Figure 5: Factors predisposing for in situ thrombosis during the

development of pulmonary arterial hypertension. HIF-1 = Hypoxia
inducible factor-1; PAI = Plasminogen activator inhibitor; PDGF =
Platelet-derived growth factor; tPA = Tissue plasminogen activator;
VEGF = Vascular endothelial growth factor.
Figure 7: Role of elastolytic enzymes in progression of pulmonary

arterial hypertension (PAH). BFGF = Basic fibroblast growth factor;
SMC = Smooth muscle cell; TGF- = Transforming growth factor-beta.
gene. Impaired transforming growth factor beta signaling

is found in PAH.17,18 The bone morphogenetic protein
receptor type 2 gene (BMPR-2) codes for a receptor member
of the TGF-b family . BMPR-2 modulates vascular cell
growth by activating the intracellular pathways (Figure 9).
Other genetic abnormalities found in PAH patient are over
expression of serotonin transporter and defects in a common
vascular signaling pathway involving angiopoetin-1
(Figure 10).
PATHOLOGICAL FEATURES
Figure 6: Mechanism of pulmonary smooth muscle cell proliferation
by mutated seratonin receptors and transporters in IPAH. 5-HT =
5-hydroxytryptamine; 5-HTT = 5-hydroxytryptamine transporter;
GTPaseAP = Guanosine triphosphatase activating protein; SMC =
Smooth muscle cell; SR = Serotonin receptor
920
(Figure 6). There is degradation of elastin in small pulmonary

arteries from the increased activity of serine elastase
(Figure 7). Increased plasma levels of adrenomedullin and
vasoactive intestinal peptide occur in PAH and hypoxic
pulmonary hypertension.15,16
All these causative factors in the presence of susceptible
individual (underlying genetic predisposition) causes vicious
cycle of PAH development (Figure 8). The PAP response to
hypoxia is particularly high in individuals with blood group
A. Presumably, a genetic basis underlies these differences
in pulmonary vascular reactivity, just as there appears to be
a genetic basis for the increased reactivity of the systemic
vascular bed in essential systemic hypertension.
Using linkage analysis, the locus designated PPH-1
on chromosome 2q33 led to the discovery of the PPH-1
Endothelial cell proliferation, smooth muscle cell hypertrophy

and increased connective tissue and extracellular matrix
are found in the large muscular and elastic arteries. In the
subendothelial layer, increased thickness may be the result
of recruitment and/or proliferation of smooth muscle-like cells.
Heath and Edwards classified the pulmonary vascular
changes in PAH19 as given below:
1. Grade IMedial hypertrophy: reversible.
2. Grade IICellular intimal proliferation in an abnormal
muscular artery: reversible.
3. Grade IIIOcclusive changes: partially reversible.
4. Grade IVVessel dilatation: irreversible.
5. Grade VPlexiform lesion: irreversible.
6. Grade VIAcute necrotizing arteritis: irreversible.
Structural Features Quantified in

Congenital Heart Defects20
In their study, Haworth et al demonstrated and explained
differences in the appearance of the peripheral pulmonary
arteries in different types of CHD, which help to interpret the
findings of lung biopsies.
65
Figure 8: Pathological basis of development of pulmonary arterial hypertension (PAH) in susceptible individual. CSA = Cross sectional area;
FN = Fibrinoid necrosis; PL = Plexiform lesions; PVB = Pulmonary vascular bed; PVR = Pulmonary vascular resistance;
1. Decreased artery size in ventricular septal defect (VSD),

tetralogy of Fallot (TOF), pulmonary atresia. Normal
size in hypoplastic left heart, total anomalous pulmonary
venous connection (TAPVC).
2. Decreased artery number in VSD, pulmonary atresia..
Normal number in TAPVC, TOF. Increased number in
hypoplastic left heart, TOF.
3. Extension of the muscle into peripheral arteries is seen in
VSD, hypoplastic left heart, TAPVC.
4. Increased medial wall thickness.
The most common vascular changes in PAH can best be
characterized as a hypertensive pulmonary arteriopathy, which
is present in 85 percent of cases and in the rest it is thrombotic
pulmonary arteriopathy. Histopathologically hypertensive
pulmonary vascular disease may involve arteries, veins or
capillaries (arteriopathy, venopathy and microangiopathy
respectively).21 Arteriopathy may be isolated medial
hypertrophy, plexogenic pulmonary arteriopathy, thrombotic
pulmonary arteriopathy and isolated pulmonary arteritis.

Venopathy or pulmonary veno-occlusive disease occurs due
to eccentric intimal fibrosis and recanalized thrombi within
diseased pulmonary veins and venules. In microangiopathy
pulmonary capillaries throughout the pulmonary parenchyma
are infiltrated. In thrombotic pulmonary arteriopathy typical
features include medial hypertrophy of the arteries and
arterioles, with both eccentric and concentric non-laminar
intimal fibrosis and the presence of colander lesions, which
represent recanalized thrombi.
CLINICAL FEATURES IN PULMONARY

ARTERIAL HYPERTENSION
History
Detailed history of the patient is a paramount step for diagnosis,
for finding etiology and planning for the management of
921
MISCELLANEOUS
12
Figure 9: Transforming growth factor-beta signaling pathway in promotion of proliferation of cells. ALK = Activin receptor like kinase; BMP =
Bone morphogenetic protein; BMP R2 = Bone morphogenetic protein receptor type 2 gene; R-Smad = Receptor-regulated Smad; TGF- =
Transforming growth factor-beta
922
suspected pulmonary hypertension.22 In most patients, it is a

insidious presentation with exercise-induced dyspnea which
is progressive over few years. Angina is also a common
symptom, occurs late in the disease, may be due to right
ventricular ischemia in a hypertrophied right ventricle.
As the cardiac output becomes fixed patient may develop
syncope or near syncope. Once right ventricle fails, signs and
symptoms of systemic congestion manifests. Patients rarely
develop orthopnea and paroxysmal nocturnal dyspnea late
in the disease process secondary to left ventricular diastolic
dysfunction. Chronic cough may be predominant symptom
in patients with pulmonary hypertension secondary to lung
pathology. Hemoptysis is relatively uncommon in patients with
pulmonary hypertension and may be associated with underlying
thromboembolism and pulmonary infarction or in some patients
with advanced mitral stenosis. Occasionally hoarseness of
the voice may occur due to compression or paralysis of left
laryngeal nerve by the dilated pulmonary artery. The systemic
disorders which are likely to be associated with pulmonary
hypertension, should be detected. In most of the patients with
congenital heart disease, there is a known history, but patients
with atrial septal defects usually manifest latter. These patients
may have cyanosis which worsens with exercise.
Cardiovascular findings consistent with pulmonary hyper
tension and right ventricular pressure overload include a large
a wave in the jugular venous pulse, a low-volume carotid
arterial pulse with normal upstroke, a left parasternal (right
ventricular) heave, a systolic pulsation produced by a dilated,
tense pulmonary artery in the second left interspace, an vascular
ejection click and flow murmur in the same area, a closely
split second heart sound with a loud pulmonic component and
a fourth heart sound of right ventricular origin. Late in the
course, signs of right ventricular failure (e.g. hepatomegaly,
peripheral edema and ascites) may be present. Patients with
severe pulmonary hypertension may also have prominent
v waves in the jugular venous pulse as a result of tricuspid
regurgitation, a third heart sound of right ventricular origin, a
high-pitched early diastolic murmur of pulmonic regurgitation
and a holosystolic murmur of tricuspid regurgitation. Tricuspid
regurgitation is a reflection of right ventricular dilation.
Cyanosis is a late finding and usually attributable to a markedly
reduced cardiac output, with systemic vasoconstriction and
ventilation-perfusion mismatch in the lung and rarely due to
right to left shunting across the stretched patent foramen ovale.
65
Figure 10: Probable mechanism of action of genetic and environmental factors in generation of pulmonary arterial hypertension (PAH) at
different phase of PAH with probable therapy. AP-1 = Angiopoietin-1; ARSP = Apoptosis resistant surviving positive; BMP = Bone morphogenetic
protein; BMPR = Bone morphogenetic protein receptor; EST2R = Endothelial-specific tie-2 receptor; PA = Pulmonary artery; PAEC = Pulmonary
arterial endothelial cell; PDGF = Platelet-derived growth factor; ST = Serotonin transporter.
Investigations
A number of tests are available for the assessment of PAH.23
Laboratory Tests
of the peripherial arteries, dilatation of right atrium, with or

without lung parenchymal pathology or oligemia. Lateral
chest X-ray more specifically detects the right ventricular
enlargement. Enlargement of the central pulmonary arteries
reflects level of PAP and duration.
Hemogram may detect polycythemia secondary to chronic

hypoxia of lung pathology or right to left shunt in congenital
heart disease. Tests to detect hypercoagulable state, abnorma
lities of platelet function and or defects in fibrinolysis should
be done in appropriate patient. Abnormal liver function test
results can indicate right ventricular failure, with resultant
systemic venous hypertension. Brain natriuretic peptide (BNP)
levels are elevated in patients with pulmonary hypertension
and correlate positively with the PAP.23 Uric acid levels
are elevated in patients with pulmonary hypertension and
correlate with hemodynamics. There is an increased incidence
of thyroid disease in patients with PAH.24
Electrocardiography
Chest Radiography
Echocardiography
The anteriorposterior chest roentgenogram may show the main

and branch pulmonary artery dilatation with marked tapering
In PAH, echocardiography plays a major role in detection,

assessing the severity and follow-up of PAH. It is also important
Right atrial (RA) enlargement and right ventricular (RV)

hypertrophy may be present. Right axis deviation and
precordial T wave abnormalities are early signs. Left atrial
enlargement may be detected in secondary PAH due to left
heart disease. These electrocardiographic abnormalities are
usually less pronounced in patients with chronic obstructive
pulmonary disease (COPD) than in patients with other forms
of pulmonary hypertension because of the relatively modest
degree of pulmonary hypertension that occurs and because of
the effects of hyperinflation.
923
MISCELLANEOUS
12
924
in detecting the congenital and left heart diseases producing

pulmonary hypertension. In thromboembolic pulmonary
hypertensive patients, direct visualization of the thrombus in
the main and major pulmonary artery branches can be done.
The parameters to be performed and reported in PAH
should include a measure of the RV size, RA size, RV systolic
function, fractional area change (FAC), tissue Dopplerderived
tricuspid lateral annular systolic velocity (S) and longitudinal
strain and strain rate, tricuspid annular plane systolic excursion
(TAPSE); RV index of myocardial performance (RIMP),
systolic pulmonary artery pressure (SPAP), pulmonary artery
diastolic pressure (PADP), an assessment of RV diastolic
function and PVR estimation.25 In advanced cases of PAH
even left ventricular diastolic and systolic function should be
assessed. In PAH, RA and RV dilatation with hypertrophy
occurs. Diameter > 42 mm at the base and > 35 mm at the
mid level indicates RV dilatation. Similarly, longitudinal
dimension > 86 mm indicates RV enlargement. Thickness >
5 mm indicates RV hypertrophy (RVH). RA area > 18 cm2,
RA length (referred to as the major dimension) > 53 mm, and

RA diameter (otherwise known as the minor dimension) > 44
mm at end diastole indicates RA enlargement. RIMP > 0.40
by pulsed Doppler and > 0.55 by tissue Doppler indicates
RV dysfunction. TAPSE < 16 mm indicates RV systolic
dysfunction (Figure 11). Two-dimensional FAC < 35 percent
indicates RV systolic dysfunction. To grade the diastolic
dysfunction of RV, pulse wave and tissue Doppler interrogation
should be done. A tricuspid E/A ratio <0.8 suggests impaired
relaxation, a tricuspid E/A ratio of 0.8 to 2.1 with an E/e ratio >
6 or diastolic ow predominance in the hepatic veins suggests
pseudonormal lling and a tricuspid E/A ratio > 2.1 with
deceleration time < 120 ms suggests restrictive lling. With the
tricuspid regurgitation peak velocity, using Bernoulli equation
(4v2), we can calculate the RV systolic pressure, which in turn
reflects the SPAP in the absence of RV outflow tract (RVOT)
obstruction. Pulmonary artery diastolic and mean diastolic PAP
can be calculated from the end-diastolic and early pulmonary
regurgitant velocities. PADP = 4 x (end-diastolic pulmonary
Figure 11: Echocardiographic recording of a Eisenmenger large patent ductus arteriosus (PDA). Upper leftshort axis view showing large
PDA. Upper right demonstrating bidirectional color and Doppler flow. Lower leftlow radionuclide myocardial perlusion imaging due to right
ventricular dysfunction. Lower righttricuspid lateral annular tissue Doppler velocities demonstrating diastolic right ventricular dysfunction
Even though many echocardiographic parameters can be

assessed and estimated, Doppler studies are too unreliable for
following serial measurements to monitor therapy. Even TR
jet velocity in estimation PASP is not very accurate, whenever
there is doubt better to do cath to know the severity of PAH.
Radionuclide Ventriculography
Radionuclide ventriculography can provide useful information
regarding right ventricular function. Although PAP cannot be
estimated with this technique, there is an inverse relationship
between PAP and right ventricular ejection fraction.
Pulmonary Function Tests
65
regurgitant velocity)2 + RA pressure. The mean PAP can also be

estimated as 4 x (early PR velocity)2 + estimated RA pressure.
Once systolic and diastolic pressures are known, mean pressure
may also be estimated by the standard formula, mean PAP =
1/3(SPAP) + 2/3(PADP).
Other method to know the mean PAP is from pulmonary
acceleration time (AT). Mean PAP = 79 (0.45 AT), if in
patients with AT < 120 ms, then formula for mean PAP is
90 (0.62 AT) (Figure 12). PVR can be estimated using
a simple ratio of peak TR velocity (in meters per second) to
the RVOT velocity-time integral (in centimeters) (Figure 13).
The Doppler tissue velocities and time intervals obtained at
the lateral tricuspid valve annulus are: peak velocity during
atrial contraction (Aa), AT, peak velocity during early diastole
(Ea), ejection time (ET), myocardial acceleration during
isovolumic contraction (IVA) peak myocardial velocity during
isovolumic contraction (IVV), peak velocity during ejection
period of systole (Sa). Regional RV strain and strain rate can
be measured as research tools.
Although pulmonary function in patients with PAH is often

completely normal, reductions in lung volumes of 20 percent
are common. Elevated PAP causes restrictive physiology.
Mainly to diagnose and to detect the severity of obstructive
Figure 12: Echocardiographic recording of a large muscular ventricular septal defect (VSD) with severe PAH. Upper left Muscular VSD
with bidirectional shunt. Upper right M- mode of pulmonary valvulogram in PAH. Lower left pulmonary artery mean and diastolic pressure
estimation with pulmonary regurgitant velocity. Lower right Estimation of mean pulmonary artery pressure from acceleration time of pulmonary
jet velocity
925
12
Exercise Testing
MISCELLANEOUS
Routine treadmill test with Naughton protocol in less

symptomatic patient and 6 minute walk test in more severely
symptomatic patient, are used to assess the efficacy of therapy.
Severe exercise-induced hypoxemia should cause consideration
of a right-to-left shunt. Dyspnea during exercise in pulmonary
hypertension is attributable to worsening ventilation-perfusion
mismatch, lactic acidosis and arterial hypoxemia.
Figure 13: Echocardiographic recording of the same patient described

in Figure 11, showing high pulmonary vascular resistance (PVR)
and restrictive lung diseases pulmonary function tests are

performed along with diffusing lung capacity (DLCO).
Arterial blood gas (ABG) analysis will show the hypoxia,
hypercarbia and in a sick patient with RV failure, the severity
of the acidosis can also be detected.
Lung Scintigraphy
Patients with PAH may reveal a relatively normal perfusion
pattern or diffuse, patchy perfusion abnormalities. A perfusion
lung scan will reliably distinguish patients with PAH from
those who have pulmonary hypertension secondary to chronic
pulmonary thromboembolism.
Computed Tomography
926
Spiral chest computed tomography (CT) scans have been used

successfully in diagnosing chronic thromboembolic pulmonary
hypertension. In addition to visualization of thrombi in the
pulmonary vasculature with contrast enhancement (Figure 14),
a mosaic pattern of variable attenuation compatible with
irregular pulmonary perfusion can be determined on the nonenhanced CT scan. Marked variation in the size of segmental
vessels is also a specific feature of chronic thromboembolic
disease. High-resolution CT is the best test by which to
diagnose interstitial lung disease and emphysema.
Cardiac catheterization also establishes the severity of the

disease and allows an assessment of prognosis. By definition,
patients with PAH should have a low or normal pulmonary
capillary wedge pressure. It has been shown that left
ventricular diastolic compliance becomes impaired in patients
with PAH and parallels the severity of the disease; thus,
pulmonary capillary wedge pressure tends to rise slightly in
the late stages of PAH, although it rarely exceeds 16 mm Hg.
It can be extremely difficult to pass a catheter into the
pulmonary artery in patients with pulmonary hypertension,
because of the tricuspid regurgitation, and pulmonary
regurgitation. A specific flow-directed thermodilution balloon
catheter has been developed for patients with pulmonary
hypertension (American Edwards Laboratories, Irvine, CA);
it has an extra port for the placement of a 0.28-inch guide wire
to provide better stiffness to the catheter.
Response to Pulmonary Vasodilator Therapy

Many pulmonary vasodilators are studied to detect the
responders of chronic vasodilator therapy.26 Adenosine
is an intermediate product in the metabolism of adenosine
triphosphate that has potent vasodilator properties through
its action on specific vascular receptors. It is believed
to stimulate the endothelial cell and vascular smooth
muscle receptors of the A2 type, which induce vascular
smooth muscle relaxation by increasing cyclic adenosine
monophosphate. In patients with PAH, adenosine has been
shown to be a potent vasodilator and predictive of the chronic
effects of intravenous prostacyclin as well as the calcium
channel blockers. Adenosine has an extremely short half-life
(less than 1 to 6 seconds), which provides safety due to its
rapid dissolution, should any adverse side effects occur. It is
administered intravenously as an infusion in doses of 50 g/
kg/min and titrated upwards every 2 minutes until the patient
develops chest tightness or dyspnea
Epoprostenol has been used in vasoreactivity studies in
patients with PAH. Like adenosine, its short half-life allows
use of the drug to be discontinued if any acute adverse
effects result. Also similar to adenosine, it is administered
incrementally, at 2 ng/kg/min and increased every 15 to 30
minutes until systemic effects such as headache, flushing or
nausea occur, which limits the acute dose titration. Favorable
65
Figure 14 : Plain and contrast computed tomography scans of a 12 year old boy of nephritic syndrome presented with subaute pulmonary
thomboembolism. Upper left dilated RV () and RA ( ). Upper middle Arrow showing prominent pulmonary artery. Upper right showing
eccentric thrombus () in left pulmonary artery. Lower left Mediastinal window showing thrombus and normal lumen ( ) in left descending
pulmonary artery. Lower middle same scan in lung window. Lower right showing pulmonary oligemia () of left lower lobe
acute effects from epoprostenol are predictive of a favorable

response to calcium channel blockers.
Adenosine and epoprostenol possess potent inotropic
properties, in addition to their ability to vasodilate the
pulmonary vascular bed. When using these drugs for the acute
testing of patients, one needs to pay particular attention to
changes in cardiac output that occur in association with the
changes in PAP. An increase in cardiac output with no change
in PAP will result in a reduction in calculated PVR and may be
erroneously interpreted as a vasodilator response.
Nitric oxide is also a useful drug to test pulmonary
vasoreactivity. It binds very rapidly to hemoglobin with
high affinity and is thereby inactivated. Inhalation of NO
gas results in selective pulmonary vascular effects without
influencing the systemic circulation. It can also predict
the effectiveness of calcium channel blockers. NO differs
importantly from adenosine and epoprostenol in that it has
little effect on cardiac output. It is usually given via facemask

at 20 to 40 ppm.
It must be emphasized that hemodynamic assessment of
the entire circulatory system is essential when determining the
influence of drugs in these patients. Small changes in PAP are
usually caused by variability rather than direct drug influence.
Changes in PVR cannot be directly measured, but are computed
by the change in PAP and cardiac output simultaneously. The
commonly used thermodilution cardiac output method, can be
associated with large errors in reproducibility, hence particular
care should be taken in the methodology of thermodilution
used in these patients. In addition, when an underlying rightto-left shunt exists, the Ficks determination of cardiac output is
required.
Changes in pulmonary capillary wedge pressure can have
important influences on the determination of PVR. A rising
capillary wedge pressure secondary to increased cardiac
927
MISCELLANEOUS
12
output may be the first sign of impending left ventricular

failure and an adverse effect of a drug, whereas the calculated
PVR may become lower and suggest a beneficial effect.
Right atrial pressure also reflects the filling characteristics
of the RV. A RA pressure increase in the face of rising
cardiac output suggests RV diastolic dysfunction. Effective
vasodilator drugs can result in vasodilation of blood vessels
supplying poorly ventilated areas of the lung and can worsen
hypoxemia.
Pitfalls and Limitations in the Interpretation of the

Pulmonary Wedge Angiogram
Although pulmonary angiography carries an increased risk

in patients with pulmonary hypertension, it can be performed
safely if adequate precautions are taken. Maintenance of
adequate oxygenation by the administration of supplemental
oxygen and the avoidance of vasovagal reactions and rapid
treatment of those that occur with intravenous atropine, should
reduce the associated risk in this patient group. Continuous
arterial pressure monitoring is advised and non-ionic contrast
agents appear to be better tolerated.
1. Pulmonary stenosis or previous placement of pulmonary

artery band gives the impression of rapid tapering.
2. With very advanced vascular disease, there is sometimes
such extensive intimal hyperplasia that the vessel appears
narrowed all the way from hilum, so that abrupt tapering
is no longer apparent. In this, however background haze
is absent and the pulmonary circulation time is usually
prolonged.
3. If the injection of contrast fails to fill the vessels all the way
out to the pleura, the background will appear dark.
4. If the balloon doses not completely occlude the vessel, the
false impression of a dense background will be created
owing to the filling of capillaries and veins.
Pulmonary Wedge Angiogram
Lung Biopsy
Abnormal structural changes in pulmonary vascular bed

represented in wedge angiogram (Figure 15) are:27
1. Sparsity of arborization of the pulmonary tree.
2. Abrupt termination of arteriesthe rate of tapering of the
arteries is assessed by measuring the length of a segment
Even after catheterization if there is controversy regarding

operability, then lung biopsy may be indicated in this subgroup
of patients. Grading of severity of abnormality in growth and
development of pulmonary vascular bed are:28-30
1. Grade AMechanism: Precocious differentiation to
mature smooth muscle cells (the pericyte in nonmuscular
region of the artery and the intermediate cell in the partially
muscular region)probably stretch is the stimulus for
smooth muscle cell differentiation from precursor cells.
a. Abnormal extension of muscle into small peripheral
arteries.
b. And/or mild increase in wall thickness of muscular
arteries (< 1.5 times normal).
c. Hemodynamic correlationincreased pulmonary blood
flow, increased pulse pressure, normal mean PAP.
2. Grade BMechanism: Hypertrophy as well as hyperplasia
of preexisting smooth muscle cells and also increase in the
intercellular connective tissue proteins.
a. Mild Grade B
i. More severe medial hypertrophy of normal
muscular arteries.
ii. Medial thickness >1.5 - < 2 times normal.
iii. Hemodynamic correlation pulmonary hypertension
is usually present.
b. Severe Grade B

i. Medial wall thickness > 2 times normal.
ii. Hemodynamic correlation pulmonary pressure
value > half of the systemic level.
3. Grade CMechanism: Failure of new vessels to grow
normally, although some loss of arteries may also occur.
Pulmonary Angiography
928
over which the lumen diameter narrows between 2.5 mm

and 1.5 mm.
3. Tortuosity and narrowing of small arteries.
4. Reduced background capillary filling.
Figure 15: Pulmonary wedge angiogram in a young female with

idiopathic pulmonary arterial hypertension
Clinical Course
TYPES OF PULMONARY HYPERTENSION
Familial Pulmonary Arterial Hypertension
Idiopathic Pulmonary Hypertension
The prevalence of familial PAH (FPAH) is uncertain, but it

occurs in at least 6 percent of cases and the incidence is likely
higher.31 The age of onset is variable and the low penetrance
of the gene confers only about a 20 percent likelihood of
development of the disease. The observation that fewer males
are born in PAH families than in the population at large
suggests that the PAH gene might influence fertilization or
cause male fetal wastage. Patients with FPAH have a similar
female-to-male ratio age of onset and natural history of the
disease as those with IPAH. Vertical transmission has been
demonstrated in as many as five generations in one family and
is indicative of a single autosomal dominant gene for PAH.
Pathological Features
It has been proposed that somatic mutation rather than nonselective cell proliferation occuring in response to injury
accounts for the growth advantage of endothelial cells in
patients with IPAH. Heterogeneity in the smooth muscle and
fibroblast populations also contributes to discordance between
phenotype and function. Interconversion between cell types
(fibroblast to smooth muscle cell or endothelium to smooth
muscle cell), in addition to neovascularization may occur. As
already mentioned, in pathophysiology of PAH, classically
hypertensive and thromboembolic pulmonary arteriopathy
changes are seen.
The clinical features and investigations in IPAH are as
those mentioned for PAH. The most extensive study on the
natural history of IPAH was reported from the National
Institutes of Health (NIH) Registry on Primary Pulmonary
Hypertension from 1981 to 1987. The study included the longterm follow-up of 194 patients in whom IPAH was diagnosed
by established clinical and hemodynamic criteria. Sixty three
percent of the patients were female and the mean age was 36
15 years (range, 1 to 81 years) at the time of diagnosis. The
mean interval from the onset of symptoms to diagnosis was 2
years, and the most common initial symptoms were dyspnea
(80 percent), fatigue (19%), syncope or near syncope (13%),
and Raynauds phenomenon (10%). No ethnic differentiation
was observed, with 12.3 percent of patients being black and
2.3 percent being Hispanic.
Univariate analysis from the NIH Registry has pointed
to the mean RA pressure, mean PAP, and cardiac index, as
well as the DLCO, as being significantly related to mortality.
The NYHA functional classification was also strongly related
to survival. A reduced left ventricular ejection fraction in
PAH is related to interventricular dependence or extrinsic
compression of the left main coronary artery by the pulmonary
artery.
With the onset of overt right ventricular failure manifested by

worsening symptoms and systemic venous congestion, patient
survival is generally limited to approximately 6 months. The
most common cause of death in patients with IPAH in the NIH
Registry was progressive right-sided heart failure (47 percent).
Sudden cardiac death was limited to patients who were in
NYHA functional Class IV. The remainder of the patients
died of other medical complications, such as pneumonia
or bleeding, which suggests that patients with IPAH do not
tolerate coexistent medical conditions well.
65
a. Mild Grade C

i. Arterial concentration is reduced.
ii. Arterial size is reduced.
iii. Hemodynamic correlation PVR > 3.5 U/m2
b. Severe Grade C

i. Artery number is < half of normal.
ii. Hemodynamic correlation PVR > 6 U/m2
Quantitative techniques have been applied to the analysis
of lung biopsy tissue prepared by frozen section to decide
between a palliative or corrective procedure when preoperative
hemodynamic data are borderline or difficult to interpret more
in Fontan procedure.
Secondary Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension Associated with
Increased pulmonary blood flow from hyperthyroidism
and beriberi have been reported to be associated with the
development of unexplained pulmonary hypertension, which
suggests that high pulmonary blood flow, rather than being
mere coincidence is the basis for the development of pulmonary
hypertension in patients with pretricuspid shunts, such as
atrial septal defect or anomalous pulmonary venous drainage.
The clinical features and investigations in PAH asssociated
with congenital heart diseases are as those mentioned
for PAH.

Connective Tissue Diseases
One-third of CREST (calcinosis, Raynaud syndrome,
esophageal dysmotility, sclerodactyly, telangiectasia)
syndrome patients, two-thirds of mixed connective disorder
patients and nearly one-fourth of systemic lupus erythematosus
patients develop PAH. Pulmonary hypertension has also been
described in patients with polymyositis, dermatomyositis and
929
MISCELLANEOUS
12
rheumatoid arthritis. Most of the time PAH is insidious in

onset with a slowly progressive course and early recognition
becomes difficult. Arterial hypoxemia is characteristic and
should also prompt an evaluation of possible pulmonary
hypertension in these patients. The clinical features and
investigations in PAH asssociated with connective tissue
diseases are as those mentioned for PAH. Because hypoxemia
is so common, patients should be tested with pulse oximetry
during exercise and supplemental oxygen should be
used whenever indicated. The prognosis of patients with
connective tissue disease in whom pulmonary hypertension
develops is poor.

Portal Hypertension
A large postmortem study from the Johns Hopkins Hospital
has shown that the prevalence of unexplained or pulmonary
hypertension in patients with cirrhosis is 5.6 times higher than
that of IPAH alone. Although the mechanisms are uncertain,
several possibilities are consistent. Portal hypertension itself
induces numerous modifications in the vascular media that may
trigger a cascade of intracellular signals and/or cause activation
or repression of various genes in endothelial and smooth
muscle cells. Increased levels of several vasoactive mediators,
cytokines and growth factors have been demonstrated in patients
with portal hypertension, including serotonin and interleukin-1.
Other angiogenic factors such as hepatocyte growth factor
or vascular endothelial growth factor may be involved in
pulmonary artery remodeling. Severe pulmonary hypertension
is considered a contraindication to liver transplantation because
of the risk of irreversible right-sided heart failure.

Human Immunodeficiency Virus Infection
A large case-control study of HIV-associated PAH conducted in
the Swiss HIV Cohort study reported the cumulative incidence
to be 0.6 percent in the entire HIV-infected population. PAH
was diagnosed in patients in all stages of HIV infection and
without an obvious relationship to immune deficiency, because
it was unrelated to the CD4 cell counts. Possible mechanism of
production of PAH is unknown and may be mediated by release
of inflammatory mediators or by autoimmune mechanisms.
Pulmonary Arterial Hypertension Related to Anorexigens
930
Fenfluramine and aminorex can produce pulmonary hypertension.32 These drugs can cause pulmonary vasoconstriction
by inhibiting voltage-gated potassium channels in the smooth
muscle cells of the resistance level pulmonary arteries.
Although the degree of pulmonary vasoconstriction noted was
small, it increased dramatically when NO synthase was inhibited.
Pulmonary Hypertension Related to Sickle Cell Disease

Cardiopulmonary complications are common in sickle cell
disease. The cause of pulmonary hypertension, which has been
reported in 20 to 32 percent of sickle cell disease patients is
multifactorial with contributing factors including hemolysis,
impaired NO bioavailability, chronic hypoxemia, high cardiac
output, thromboembolism and parenchymal and vascular
injury caused by sequestration of sickle erythrocytes, chronic
liver disease and asplenia.33 In a recent study by Florence Parent
in adults with sickle cell disease, the prevalence of pulmonary
hypertension as confirmed on right heart catheterization was
6 percent. Echocardiographic evaluation alone had a low
positive predictive value for pulmonary hypertension.34
Persistent Pulmonary Hypertension of the Newborn

Although persistent pulmonary hypertension of the newborn
can vary in severity, severe cases are usually life-threatening.
Mechanism of development of PAH in newborn is mentioned
in Figure 16. It is usually associated with severe hypoxemia
and the need for mechanical ventilation. Echocardiographic
findings of severe pulmonary hypertension and right-to-left
shunting at the level of the ductus arteriosus or foramen ovale
are common. Inhaled NO, intravenous epoprostenol and
extracorporeal membrane oxygenation has also been used.
Pulmonary Veno-occlusive Disease

Pulmonary venoocclusive disease (PVOD) is a rare form of
PAH (Table 2).35
Pulmonary Capillary Hemangiomatosis

Pulmonary capillary hemangiomatosis is a very rare cause
of pulmonary hypertension.36 Histological findings often are
also common. Most patients appear to be young adults. It is
difficult to distinguish pulmonary capillary hemangiomatosis
from IPAH clinically.
The clinical course of patients with this condition is usually
one of progressive deterioration leading to severe pulmonary
hypertension, right-sided heart failure and death (Table 3).
Pulmonary Venous Hypertension

Considerable variability in pulmonary arterial vasoconstriction
occurs in response to pulmonary venous hypertension.
Marked reactive pulmonary hypertension with SPAP in excess
of 80 mm Hg occurs in less than one-third of patients whose
pulmonary venous pressures are elevated more than 25 mm
Hg. Chronic elevation of pulmonary venous pressures as
a result of other disorders, such as left ventricular diastolic
dysfunction, also results in a disproportionate elevation in
PAP in a subset of patients.
65
Figure 16: Diagrammatic representation of types, causes and pathophysiology of persistent pulmonary hypertension. MH = Medial hypertrophy;
MT = Muscular tissue; PA = Pulmonary arteries; PAP = Pulmonary arterial pressure; PBF = Pulmonary blood flow; PVB = Pulmonary vascular bed
Table 2
Diagnosis, pathology and management of pulmonary venooclusive disease

Features
Information
Histopathological
diagnosis
Presence of obstructive eccentric

fibrous intimal pads in the pulmonary
veins and venules. Arterialization of the
pulmonary veins medial hypertrophy
and muscularization of the arterioles
with eccentric intimal fibrosis.
Pulmonary capillary
wedge pressure
Normal, in late stages.
Chest radiograph
Increase in basilar bronchovascular

markings.
Perfusion lung scan
Diffuse, patchy non-segmental

abnormalities.
Chest computed
tomographic scan
Smooth interlobular septal thickening,

ground-glass opacities and a mosaic
attention pattern.
Treatment
Unsatisfactory. Any therapy needs

close supervision and early referral
of the patient for lung transplantation
should be considered.
The mechanisms involved in elevating PVR are unclear.

In addition to hypertrophy of the media of the vasculature, a
neural component may be present. An elevation in pulmonary
venous pressure may also narrow or close airways, which may
diminish ventilation and lead to hypoxia and vasoconstriction,
and interstitial pulmonary edema secondary to pulmonary

venous hypertension. Some patients may also have a genetic
predisposition.
Pathology
Structural changes in the pulmonary vascular bed develop
in association with chronic pulmonary venous hypertension,
irrespective of its origin. At the ultrastuctural level, these
changes include swelling of the pulmonary capillary
endothelial cells, thickening of their basal lamina, and wide
separation of groups of connective tissue fibrils, indicative of
interstitial edema. With persistence of the edema, reticular and
elastic fibrils proliferate and the alveolar capillaries become
embedded in dense connective tissue. The permeability of
interendothelial junctions depends on pulmonary capillary
pressure, with leakage of large molecules (40,000 to 60,000
Da) occurring at capillary pressures in excess of approximately
30 mm Hg. Pathophysiology of development of PAH in
pulmonary venous hypertension is mentioned in Figure 17.
Light microscopic examination of the lungs of patients
with pulmonary venous hypertension shows distention
of pulmonary capillaries, thickening and rupture of the
basement membranes of endothelial cells and transudation
of erythrocytes through these ruptured membranes into the
alveolar spaces, which contain fragments of disintegrating
erythrocytes. Pulmonary hemosiderosis is commonly observed
and may progress to extensive fibrosis. In the late stages of
pulmonary venous hypertension, areas of hemorrhage may be
scattered throughout the lungs, edema fluid and coagulum may
931
MISCELLANEOUS
12
932
Table 3
Features of pulmonary capillary hemangiomatosis

Features
Information
Age group
Young adults
Presentation
Dyspnea and/or hemoptysis
Inheritance
Sporadic with a hereditary form with probable autosomal recessive transmission.
Chest radiograph
Diffuse bilateral reticular nodular pattern associated with enlarged central pulmonary arteries
Ventilation-perfusion scans
Often abnormal and may show matched or unmatched defects.
High-resolution computed
tomographic scan
Diffuse bilateral thickening of the interlobular septa and small centrilobular, poorly circumscribed,
nodular opacities. Diffuse ground-glass opacities.
Histological findings
Include irregular small nodular foci of thin-walled capillary-sized vessels that diffusely invade the
lung parenchyma, bronchiolar walls and adventitia of large vessels. These nodular lesions are
often associated with alveolar hemorrhage. Changes of hypertensive arteriopathy manifest by
intimal fibrosis and medial hypertrophy.
Treatment
Intravenous epoprostenol has been used, but it has been reported with the associated
development of severe pulmonary edema. The only definitive treatment for these patients is
bilateral lung transplantation.
Figure 17: Pathophysiology of pulmonary venous hypertension. AV = Aortic valve; CSV = Compliant small vessels; CT = Cor triatriatum; IPAH
= Idiopathic pulmonary arterial hypertension; LAM = Left atrial myxoma; LAP = Left atrial pressure; LV = Left ventricle; MV = Mitral valve; PA =
Pulmonary artery; PAP = Pulmonary arterial pressure; PBF = Pulmonary blood flow; PVD = Pulmonary venous drainage; PV = Pulmonary vein;
PVP = Pulmonary venous pressure; PVR = Pulmonary vascular resistance; RV = Right ventricle; VC = Vascular channels

Disorders of the Respiratory System
Different causes of respiratory disorders which can produce
PAH are mentioned in Figure 1. The possible mechanisms of
PAH development in these patients are depicted in Figure 18.
Chronic Obstructive Pulmonary Diseases

Structural change rather than hypoxic vasoconstriction,
is required for the development of sustained pulmonary
hypertension in patients with COPD. A genetic predisposition
to pulmonary hypertension in COPD patients as a result of
a 5-hydroxytryptamine transporter (5-HTT) polymorphism
has been described, which may predispose to more severe
pulmonary hypertension in hypoxemic patients with COPD.37
More recently, the cardiopulmonary hemodynamics of
a retrospective series of 998 patients with COPD has been
published.38 Twenty seven patients had severe pulmonary
hypertension, defined as a mean PAP higher than 40 mm
Hg. Interestingly, 16 of these 27 had another possible cause
of pulmonary hypertension, such as anorexigen exposure,
connective tissue disease, thromboembolic disease, or left

ventricular disease. In only 11 patients or 1.1 percent was COPD,
the only potential cause of the pulmonary hypertension. The
median mean PAP in these 11 patients was 48 mm Hg. They had
an unusual pattern of cardiopulmonary abnormalities with mild
to moderate airway obstruction, severe hypoxemia, hypocapnia
and a very low diffusing capacity for carbon monoxide.
We found that hypoxia-induced pulmonary vascular
medial hypertrophy and intimal endothelial cells migration
and angiogenesis, which were mediated by 15-hydroxyeicosatetraenoic acid (15-HETE). Moreover, 15-HETE
regulated the cell cycle progression and made more smooth
muscle cells from the G0/G1phase to the G2/M + S phase
and enhanced the microtubule formation in cell nucleus. In
addition, we found that the Rho-kinase pathway was involved
in 15-HETE-induced endothelial cells tube formation and
migration and smooth muscle cell proliferation. Together,
these results show that 15-HETE mediates hypoxia-induced
pulmonary vascular remodeling and stimulates angiogenesis
via the Rho-kinase pathway.39
Given the inaccuracy of the echocardiogram in patients
with pulmonary disease, an elevated estimated SPAP obtained
by echocardiography must be interpreted with caution,
because approximately half of the time it will represent a
false-positive finding.
65
collect in the alveolar spaces and widespread organization and

fibrosis of pulmonary alveoli may be present. Occasionally,
the alveolar spaces become ossified. Pulmonary lymphatics
may become markedly distended and give the appearance
of lymphangiectasis, particularly when pulmonary venous
pressure chronically exceeds 30 mm Hg. Structural alterations
in the small pulmonary arteries, arterioles and venules include
medial hypertrophy, intimal fibrosis and rarely necrotizing
arteritis. In Table 4 the distinguishing features of pulmonary
venous hypertension from PAH are mentioned.
Cystic Fibrosis
Cystic fibrosis is the most common lethal genetic disease
in whites and occurs in approximately 1 of every 2,000 live
births. As the disease progresses, patients develop disabling
lung disease and eventually respiratory failure, pulmonary
hypertension and cor pulmonale. The pathophysiology of
Table 4
Distinguishing features between pulmonary venous hypertension and idiopathic pulmonary arterial hypertension
Features
Pulmonary venous hypertension
Idiopathic pulmonary
arterial hypertension
History
1.
Paroxysmal nocturnal dyspnea
Yes
No
2.
Orthopnea
Yes
No
Atrial fibrillation
Yes
Uncommon
Electrocardiogram
1.
Right axis deviation
Uncommon
Common
2.
Left atrial enlargement
Common
No
Detects the underlying conditions
Severity of pulmonary
arterial hypertention can be
assesed
Echocardiogram
1.
Pulmonary capillary wedge pressure (PCWP)
>15 mm Hg
< 15 mm Hg
Left ventricular end-diastolic pressure
>15 mm Hg
< 15 mm Hg
3.
Fluid challenge, in certain cases (in a patient in whom

the index of suspicion for diastolic dysfunction is high)
basal PCWP may be

< 15 mm Hg, but with fluid challenge
Same as basal pressures
933
MISCELLANEOUS
12
Figure 18: Possible mechanism of PAH development in respiratory disorders. AP = Airway pressure; BA = Bronchial artery; CH = Chronic
hypoxia; CSA = Cross sectional area; IF = Interstitial fibrosis; LH = Left heart; LVF = Left ventricular failure; PA = Pulmonary artery; PAI =
Peripheral airway inflammation; PAT = Pulmonary arterial thrombosis; PBF = Pulmonary blood flow; PRV = Pulmonary resistance vessels; PV =
Pulmonary vein; PVOD = Pulmonary venoocclusive disease; SC = Secondary polycythemia; VC = Vasoconstriction.
pulmonary hypertension in cystic fibrosis is believed to be

related to progressive destruction of the lung parenchyma and
the pulmonary vasculature and to pulmonary vasoconstriction
secondary to hypoxemia. The development of pulmonary
hypertension in patients with cystic fibrosis carries a grave
prognosis. The mean survival time from onset has been
reported to be as short as 8 months. The severity of the
pulmonary hypertension appeared to correlate significantly
with declining pulmonary function, as well as with the degree
of oxygen desaturation with exercise.
Sleep-Disordered Breathing, Pulmonary Hypertension

and Alveolar Hypoventilation Disorders
Observational studies have demonstrated a wide variation (17
to 52.6 percent) in the incidence of pulmonary hypertension
as a complication of sleep apnea with a wide range of severity.
Proved therapy is continuous positive airway pressure.
Pulmonary hypertension frequently occurs in patients with
thoracic-vertebral deformities. Pulmonary hypertension
is related to the reduction of the vascular bed, because of
hypoventilation and hypoxia. The development of rightsided heart failure is an unusual manifestation of respiratory
failure solely caused by respiratory muscle weakness.
Bilateral diaphragmatic paralysis is an uncommon and rarely
recognized cause of pulmonary hypertension.
Pulmonary Hypertension Caused by Chronic Thrombotic

or Embolic Obstruction of the Pulmonary Arteries
934
Using high-resolution non-enhanced CT, areas of increased

attenuation that do not obscure the vessels and that have a
ground-glass appearance have been characterized as a mosaic
pattern corresponding to hypoperfusion of the lung. Although

this pattern is consistent with chronic thromboembolic
pulmonary hypertension, it may also be seen in patients
with cystic fibrosis, bronchiectasis and lung transplant
recipients, but it is virtually never seen in patients with IPAH.
The contrast-enhanced CT features suggestive of chronic
thromboembolic pulmonary hypertension include evidence
of organized thrombus lining the pulmonary vessels in an
eccentric or concentric fashion, enlargement of the right
ventricle and central pulmonary arteries, variation in size of
segmental arteries (relatively smaller in the affected segments
compared with uninvolved segments), bronchial artery
collaterals and parenchymal changes to pulmonary infarcts.
Marked variation in the size of the segmental vessels is more
specific for chronic thromboembolic pulmonary hypertension
and is believed to represent involvement of the segmental
vessels caused by thromboemboli.
It is a true endarterectomy, requiring establishment of
a dissection plane at the level of the media. An operative
classification of thromboembolic disease has been established
and may be useful in terms of prognostication.40 Among 202
patients who underwent pulmonary thromboendarterectomy,
intraoperative classification of thromboembolism was defined
as follows:
Type 1 (37.6 percent), thrombus in the main lobar
pulmonary arteries.
Type 2 (40 percent), intimal thickening and fibrosis
proximal to the segmental arteries.
Type 3 (18.8 percent), disease within distal segmental
arteries only.
Type 4 (3.4 percent), distal arteriolar vasculopathy without
visible thromboembolic disease. Although all four patient
groups were similar with respect to age, preoperative PAP and
Pulmonary Hypertension Caused by Disorders Directly

Affecting the Pulmonary Vasculature
Schistosomiasis
The development of pulmonary hypertension almost always
occurs in the setting of hepatosplenic disease and portal
hypertension. Clinical features appear when ova embolize
to the lungs, where they induce formation of delayed
hypersensitivity granulomas. In addition, deposition of
fibrous tissue causes narrowing, thickening and occlusion of
the pulmonary arterioles. Histologically, focal changes related
directly to the presence of schistosome ova may be located in
the alveolar tissue or in the pulmonary arteries and plexiform
or angiomatoid lesions may be found. Fibrosis surrounds most
focal lesions. The clinical symptoms and radiographic findings
in these patients who develop pulmonary hypertension are
not distinctive. The diagnosis of schistosomiasis-induced
pulmonary hypertension is confirmed by finding the parasite
ova in the urine or stools of persons with symptoms. However,
the insidious onset of pulmonary vascular disease years after
infection makes finding these parasite ova difficult.
Eisenmenger Syndrome
Eisenmenger syndrome (ES) is defined as CHD with an initial
large systemic-to-pulmonary shunt that induces progressive
pulmonary vascular disease and PAH, with resultant reversal
of the shunt and central cyanosis. Eisenmenger syndrome
represents the most advanced form of PAH associated with
CHD.5
Hemodynamically ES is defined as an elevation of the PVR
to 12 Wood units or to a pulmonary-to-systemic resistance
ratio equal to or greater than 1.0. Thus, ES is caused by
any large congenital cardiac defect, no matter where it is
located, permitting increased pulmonary blood flow and
transmission of the elevated pressure to the pulmonary
circulation, causing a balanced or predominant right-to-left
shunt secondary to a fixed and markedly elevated PVR. The
clinical classification of congenital systemic-to-pulmonary
shunts associated to PAH is given in Table 5.5
Eisenmenger syndrome represents a severe form of PAH
associated with CHD. The prevalence of this condition, is on
the decline with advances in cardiac imaging and surgery.
Patients survive up to the 3rd or 4th decade with this condition
but overall life expectancy continues to be poor.41 The
actuarial survival rate is 80 percent at 10 years, 77 percent at
15 years, 42 percent at 25 years. Most Eisenmenger patients
die from sudden cardiac death, congestive heart failure,
hemoptysis, cerebral abscesses, thromboembolic events, from
complications during pregnancy or due to non-cardiac surgery.
Sudden cardiac death being a frequent cause of mortality in
this condition.42-44
Pulmonary arterial hypertension and pulmonary vascular
disease are caused by uncorrected congenital cardiac anomalies
with a left-to-right shunt. In due course vascular changes and
a decrease of the overall cross-sectional area develop in the
65
PVR, patients with proximal thromboembolic disease (groups

1 and 2) had a significantly greater improvement in SPAP
and PVR. There was also a greater increase in postoperative
cardiac index and decrease in RV systolic pressure in these
patients as compared with those who had disease in the
segmental or distal branches (groups 3 and 4). Although in
previous series, the operative mortality rate has been reported
to be fairly high, 1 month survival rates in patients who fell
into groups 1 and 2 were 98.7 and 97.5 percent, respectively,
whereas the 1 month survival rates in patients in groups 3 and
4 were 86.8 and 85.7 percent, respectively.
Table 5
Clinical classication of congenital systemic-to-pulmonary shunts associated to pulmonary arterial hypertension5

1.
Eisenmengers syndrome
Includes all systemic-to-pulmonary shunts resulting from large defects and

leading to a severe increase in PVR and a reversed (pulmonary-to-systemic)
or bidirectional shunt; cyanosis, erythrocytosis, and multiple organ involvement
are present
2.
PAH associated with systemic-to-pulmonary

shunts
Includes moderate to large defects; PVR is mild to moderately increased,

systemic-to-pulmonary shunt is still largely prevalent, and no cyanosis is
present at rest
3.
PAH with small defects
Small defects (usually ventricular septal defects < 1 cm and atrial septal defects
< 2 cm of effective diameter assessed by echocardiography) clinical picture is
very similar to idiopathic PAH
4.
PAH after corrective cardiac surgery
Congenital heart disease has been corrected, but PAH is still present
immediately after surgery or recurs several months or years after surgery in the
absence of signicant postoperative residual lesions or defects that originate
as a sequela to previous surgery.
PAH = Pulmonary arterial hypertension; PVR = Pulmonary vascular resistance
935
MISCELLANEOUS
12
pulmonary bed. When two-thirds of the pulmonary vascular

bed is compromised, pulmonary resistance and pressure
increases.
Secondary to the elevated PAP, the left-to-right shunt
converts into a right-to-left shunt, resulting in desaturation of
systemic arterial blood and cyanosis.
The effect of the shunt depends on the exact location and its
size. Shunts may cause different loading conditions and exert
strain on the pulmonary vascular tree and the subpulmonary
ventricle and thus modify morbidity and mortality.
Shunt at Atrial Level

Atrial septal defects, anomalous pulmonary venous drainage
and common atrium deliver mainly large blood volumes
without an increase of pressure and without shear stress to the
pulmonary endothelium.
In the case of anamolous veins, the shunt is fixed and
obligatory due to the abnormal connection. In atrial septal
defects, the shunt volume can be large and causing right
heart dilatation. The amount of left-to right shunt depends
on RV compliance and will decrease with increasing RV
stiffness. Pulmonary vascular resistance usually increases in
the 3rd and 4th decade, an additional pressure load develops,
and RV myocardium fails. Cyanosis worsens as a result of
increased right-to-left shunt due to increased RV filling
pressure.
Shunt at Ventricular Level

Ventricular septal defects, atrioventricular canal defects
deliver volume and pressure to pulmonary vascular bed during
ventricular systole. The quantum of shunt depends on the size
of defect, ratio of systemic to pulmonary vascular resistance.
There may be a different shunt direction and volume in early
and late diastole, which depends on the ventricular compliance.
This explains the angiographic and hemodynamic findings of
left-to-right shunting during systole and right-to-left shunting
in diastole in the presence of a hypertrophied and stiff right
ventricle. The atrioventricular canal defect adds the atrial
shunt physiology to this.
Shunt at Arterial Level

Patent ductus arteriosus, aortopulmonary window, and
truncus arteriosus deliver increased blood flow and systemic
pressure to the pulmonary vascular tree continuously during
both systole and diastole and are therefore associated with an
early and rapidly progressive rise of PVR.
Size of Shunt
936
The size of the defect determines the quantum of flow and

transmission of pressure . The threshold is 2 to 3 cm at atrial
level and 1 to 1.5 cm at ventricular level and 0.5 to 0.7 cm

at arterial level. On the contrary, if the entire septum is
almost absent (e.g. in common atrium, single ventricle), then
complete mixing of the venous and arterialized blood occurs
and the resulting saturation is a function of the Qp:Qs ratio.45
Eisenmenger physiology may occur not only in unoperated
patients, but also postoperatively if communications between
the systemic and pulmonary circulation persist. Surgically
created systemic arterial to pulmonary shunts (Waterston and
Pott-shunts, rarely Blalock-Taussig anastomosis) improve
oxygen saturation, but at the expense of volume loading of the
systemic ventricle. Blood flow through these non-restrictive
shunts are frequently difficult to control and may result in
raised PVR.
Three Scenarios of Pulmonary Artery Hypertension

In post tricuspid shunts, congestive cardiac failure (CCF) occurs
in infancy and cyanosis can occur later in the second decade.
The CCF occurs due to the increased pulmonary blood flow
due to the establishment of the shunt after the physiological
decrease in PVR post-natally. This leads to pulmonary venous
congestion, pulmonary reactive hypertension and increased
PVR. This eventually causes a decrease in the shunt with
improvement in the symptoms. Subsequently, the obliterative
changes causes a fixed PVR and a right to left shunt.
There may be a role of genetic disposition in the
development of PAH. There are minimal symptoms in
childhood PAH. They can have mild symtoms like fatigue
etc. There is enlargement of the right sided chambers with
increased PVR.
In complex cyanotic CHD (single ventricle, Truncus etc),
the cyanosis is progressive throughout life. The development
of the pulmonary vascular obstructive disease occurs earlier
in these patients due to the increased pulmonary blood
flow and the pulmonary vasoconstriction caused due to the
hypoxemia.
Pathophysiology
In patients with a left-toright shunt, the physiologic decrease
of PVR early after birth results in increased left-to-right. It
is likely that in patients with a large communication high
flow causes mechanical stretch and intimal tears. Moreover,
it produces progressive structural abnormalities and
histological changes in the pulmonary vasculature, which
are accompanied by an increased production of intrinsic
elastase and vascular endothelial growth factors. Endothelial
and medial hypertrophy and pulmonary occlusive lesions can
progress further. Furthermore, endothelin concentrations and
serum thromboxane levels increase and induce endothelial
dysfunction and platelet activation. Complex pathobiological
processes cause pulmonary obstructive lesions and pulmonary
hypertension can develop, which results in decreased
Dyspnea, cyanosis, fatigue, dizziness and syncope are the
common presenting symptoms with the added burden of
arrhythmias. Eisenmenger syndrome is a multisystem disorder
affecting almost all systems.48-50
a. HematologyHyperviscosity syndrome (Hypoxia
erythrocytosis hematocrit), thrombotic (viscosity,
dilated cardiac chambers, atrial fibrillation) as well as
bleeding (thrombocytopenia, coagulation factors) risk
b. CNSParadoxical embolism, hyperviscosity leads to
stroke risk. Brain abscess risk increased.
c. Vascular system SVR secondary to vasodilatation,
risk of syncope.
d. Coronary circulationVasodilation leads to dilated,
tortuous and aneurysmal coronaries. There is higher basal
coronary blood flow due to low saturation. Coronary flow
reserve is decreased.
e. Bilirubin metabolismErythrocytosis impacts formation
of unconjugated bilirubin leading to gall stone formation.
f. Renal/rheumatologic-hyperuricemia (erythrocyte metabolism), glomerular dysfunction can lead to urate stones,
renal dysfunction
g. SkeletalHypertrophic osteoarthropathy, clubbing, etc.48-50
Exercise Physiology in Pulmonary Artery Hypertension

In patients with pulmonary vascular disease, the physiological
decrease in PVR does not occur. In patients with ES, the
bidirectional shunt prevents suprasystemic right ventricular
pressure and enables left ventricular filling. A right-to-left
shunt at atrial level even augments left ventricular filling and
may prevent heart failure during exercise, however, it is at the
expense of cyanosis during exercise. In Eisenmenger patients,
systemic vascular resistance decreases substantially during
exercise, whereas PVR decreases inadequately. The ratio of
pulmonary to systemic vascular resistance, which might be
less than 1 at rest, increases to more than 1 during exercise.
In addition to the findings in patients with pulmonary
hypertension without shunt, the right-to-left shunting in
Eisenmenger patients provokes a further increase in the VE/
VCO2 slope (minute ventilation to CO2 production), a further
increase in end-tidal partial pressure of O2, a further decrease
in end-tidal CO2, an increase in the respiratory exchange ratio
(VCO2/VO2), and a decline of the oxygen pulse.51,52
NATURAL HISTORY AND CLINICAL COURSE

Patients with PAH, however, do have a very poor prognosis.
The idiopathic patients in many studies have a survival that
can be measured at 50 to 60 percent at 5 years. The patients

with connective tissue disease do much, much worse (Figure
19).53 French registry gives information about the survival of
combined PAH vs predicted population (Figure 20).54
Lowe BS et al in their retrospective longitudinal cohort
study conducted in acyanotic congenital heart disease
(ACHD) patients >18 years, found that the prevalence of
pulmonary hypertension in the ACHD population was
5.8 percent.55 Of the pulmonary hypertension patients,
59 percent were women, and the median patient age was
67 years. All-cause mortality rate of ACHD patients was
increased, if a diagnosis of pulmonary hypertension was
present (hazard ratio [HR] - 2.69; 95% confidence interval
[CI] - 2.41-2.99). Heart failure and arrhythmia were also
more common in ACHD patients with a diagnosis of
pulmonary hypertension (HR - 3.01; 95% CI - 2.80-3.22).
Health services utilization, including cardiac catheterization
and coronary and intensive care hospitalizations were
increased in ACHD patients with pulmonary hypertension
(rate ratio- 5.04; 95% CI - 4.27-5.93 and rate ratio - 5.03;
95% CI - 4.86-5.20, respectively).55
Survival of patients with ES has been reported to be 80
percent at 10 years, 77 percent at 15 years, and 42 percent
at 25 years.42,43 Survival is typically related to mean RA
pressure and PVR.53 The prevalence of PAH in a survey
of adult CHD patients with septal defects was 6.1 and
58 percent of these patients had ES.56 Central cyanosis,
dyspnea, fatigue, hemoptysis, syncope and right heart
failure constitute the clinical findings. Reduced arterial
oxygen saturation can lead to abnormal hemostasis and risk
for both bleeding and thrombosis. Survival subjects may
reach the third or fourth decade, exceptionally the seventh
decade.
Figure 19: Survival in pulmonary arterial hypertension (PAH) due to

HIV, connective tissue disorders, portopulmonary hypertension and
congenital heart disease.53 CTD = Connective tissue disorders; HIV =
human immunodeficiency virus; IPAH = Idiopathic pulmonary arterial
hypertension.
65
pulmonary blood flow in turn.46,47 As long as PVR is lower

than the systemic vascular resistance, a predominant left-toright shunt is present.
937
MISCELLANEOUS
12
Figure 20: French registry: Survival in pulmonary arterial hypertension (PAH)
MANAGEMENT
Screening Guidelines
Early detection of PAH is important in the proper management
and prevention of complications. PAH risk patients defined as
those patients in whom the prevalence of PAH is more than
the general population. Such patients should be screened.
Patients with known PAH risk are known BMPR2 mutation
(20% prevalence), systemic scelerosis (8% prevalence), HIV
(0.5%), portal hypertention (4%) and CHD patients with leftto-right shunt.43
Lifestyle Changes
Exercise may elevate the pulmonary arterial pressures. So,
graded exercise activities, such as bike riding or swimming,
in which patients can gradually increase their workload and
easily limit the extent of their work, are thought to be safer
than isometric activities. Sometimes, isometric activities
may produce syncope so, better to avoid them. Algorithm for
treatment of PAH is mentioned in Figure 21.
Pregnancy Issues
938
The subject of pregnancy should also be discussed with women

of childbearing age. The physiological changes that occur
during pregnancy may be detrimental to mother and fetus.
In addition to the increased circulating blood volume and
oxygen consumption that will increase RV work, circulating
procoagulant factors and the risk of pulmonary embolism from
deep vein thrombosis and amniotic fluid are serious concerns.
Syncope and cardiac arrest have also been reported to occur

during active labor and delivery and a syndrome of postpartum
circulatory collapse has been described.
Medical Therapies
Mainly the therapy concentrates on inhibition of the three
pathways, endothelin, NO and prostacyclin, for generation of
PAH.
Digoxin
Digoxin causes an increase in resting cardiac output of
approximately 10 percent and causes a significant reduction
in circulating norepinephrine. Its role is limited to right or left
ventricular systolic failure states.
Diuretics
In addition to systemic congestive state, diuretics are
helpful in patients with advanced IPAH with increased left
ventricular filling pressures and also serve to reduce RV wall
stress in patients with concomitant tricuspid regurgitation and
volume overload. The fear that diuretics will induce systemic
hypotension is unfounded, because the main factor limiting
cardiac output is PVR and not pulmonary blood volume.
Supplemental Oxygen
Hypoxia is a potent vasoconstrictor, which if untreated
further increases the pulmonary hypertension. Supplemental
low-flow oxygen alleviates arterial hypoxemia. Patients with
65
Figure 21: Algorithm for treatment of pulmonary arterial hypertension. WHO-FC = World Health Organization-functional class
severe right-sided heart failure with resting hypoxemia and

primary lung disorder patients with hypoxemia are going to
be benefitted by supplemental oxygen.
Anticoagulants
Oral anticoagulant therapy is widely recommended for
patients with PAH. A retrospective review of patients with
PPH monitored over a 15-year period at the Mayo Clinic has
suggested that patients who received warfarin had improved
survival over those who did not.57 The current recommendation
is to use Warfarin in relatively low doses, as has been
recommended for prophylaxis of venous thromboembolism
with the international normalized ratio (INR) maintained at
2.0 to 3.0 times that of controls.
Vasodilator Therapy
Subset of IPAH patients are going to benefited by vasodilator
therapy. The final common cellular pathway by which
vasodilators work is through a reduction of intracellular
calcium in the vascular smooth muscle cell and cellular growth
inhibition. The doses of various pulmonary vasodilators are
given in Table 6.
Calcium Channel Blockers

It has been reported that 10 to 20 percent of patients with IPAH
who are challenged with very high doses of calcium channel
blockers may manifest a dramatic reduction in PAP and PVR,
which on serial catheterization has been maintained for more

than 15 years.58 It appears essential that high doses (e.g.
amlodipine, 20 to 30 mg/day; nifedipine, 180 to 240 mg/day;
diltiazem, 720 to 960 mg/day) be used to realize full benefit.
When patients respond favorably, quality of life is restored
with improved functional class and survival (94 percent rate
at 5 years) is improved when compared with non-responders
and historical control subjects (36% rate).
Prostacyclins
Continuous intravenous infusion of epoprostenol has been
shown in randomized clinical trials to improve quality of
life and symptoms related to IPAH, exercise tolerance,
hemodynamics and short-term survival.59 The long-term
effects of epoprostenol in IPAH include its vasodilator and
antithrombotic effects, but its effects may also be importantly
related to its ability to normalize cardiac output. Patients
may have a reduction in PVR of more than 50 percent, even
if no acute hemodynamic effects are noted. Epoprostenol
is administered through a central venous catheter that is
surgically implanted and delivered by an ambulatory infusion
system. The delivery system is complex and requires patients
to learn the techniques of sterile drug preparation, operation
of the pump and care of the intravenous catheter. Most serious
complications that have occurred with epoprostenol therapy
have been attributable to the delivery system and include
catheter-related infections and temporary interruption of the
infusion because of pump malfunction. Side effects related to
epoprostenol include flushing, headache, nausea, diarrhea, a
939
MISCELLANEOUS
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Table 6
The various pulmonary vasodilators and their dosage

Mode of administration
Starting dose
Maximal dose
Nifedipine
Oral
90-180 mg/day
240
Diltiazem
Oral
240-720 mg/day
960
Epoprostenol
Intravenous
2-4 ng/kg/min
25 - 40 ng/kg/min
Treprostinil
Intravenous/Subcutaneous
1-2 ng/kg/min
75 -150 ng/kg/min
Beraprost
Oral
20-100 g BID to QID
Iloprost
Nebulizer system
6-9 times/day (2.55 g/inhalation)
Bosentan
Oral
62.5 mg BID
125 mg BID
Sildenafil
Oral
20 mg TID
80 mg TID
Tadalafil
Oral
10 mg OD
40 OD
OD = Once a day; BID = Twice a day; TID = Three times a day; QID = Four times a day.
940
unique type of jaw discomfort that occurs with eating, chronic

foot pain and a poorly defined gastropathy. The optimal dose
ranges between 25 and 40 ng/kg/min. A high cardiac output
state has been reported with chronic infusion therapy. The
experience with epoprostenol in patients with IPAH for more
than 10 years has been reported by two large centers.60,61 The
usual starting dose of epoprostenol in children is the same as
in adults: 2 ng/kg/min with up titration until the maximum
tolerated dose is reached. In children, the maintenance dose
is generally higher than adults, and there is considerable
interpatient variability for optimum dose.62
Treprostinil is a stable prostacyclin analogue that has
pharmacological actions similar to those of epoprostenol,
but differs in that it is chemically stable at room temperature
and neutral pH and has a longer half-life (4 hours). Its
pharmacological properties allow it to be administered
through continuous subcutaneous infusion and infusion site
pain is common. In a large randomized clinical trial in patients
with PAH, treprostinil was effective in increasing the distance
walked in 6 minutes, symptoms of dyspnea associated
with exercise and hemodynamics.63 The optimal dose of
treprostinil has never been determined, but doses of 50 to 80
ng/kg/min are typical. Patients who deteriorate after a long
period of stability usually do not respond to further increased
dose.The high rate of infusion site reactions and pain with
subcutaneous treprostinil precludes this treatment option for
many children.62
Iloprost, an analogue of prostacyclin, has been approved for
use via inhalation. In randomized clinical trials, inhaled iloprost
was shown to have an acute effect on hemodynamics similar
to those of inhaled NO. When iloprost was given chronically,
patients reported an improvement in exercise, manifested by
a post inhalation 6-minute walk test and in hemodynamics.64

Because of the short half-life of iloprost however, it requires
frequent (up to 12/day) inhalations. Iloprost is given by 2.5
or 5.0 mg ampules via dedicated nebulizer. The small and
very sick children may not be able to manage the mask and
nebuliser device, nor the frequency of nebulisations.62
Beraprost is an orally active prostacyclin analogue that
has been evaluated in randomized double-blind placebocontrolled multicenter trials in patients with PAH. In
one large European trial (ALPHABET study), beraprost
improved exercise capacity and symptoms over a 12 week
period, but had no significant effect on cardiopulmonary
hemodynamics or functional class.65 Adequate data
concerning the clinical effect of beraprost in children with
PAH are not available.62
Endothelin Receptor Blockers

Bosentan is a non-selective endothelin receptor blocker that
is approved as a treatment of PAH. In a large randomized
clinical trial, bosentan showed a significant improvement
in 6 minute walk distance after 16 weeks as compared with
placebo. Importantly, there was a dose-dependent increase in
hepatic transaminase levels noted from the medication, with
significant elevations in 14 percent of the patients randomized
to the higher dosage (250 mg twice daily). The approved
dosage of bosentan is 125 mg twice daily.66,67 Bosentan is
being used in infants and children with severe disease and
clinical improvement has been observed in patients as young
as 9 months.62 In children, an initial dose of 1-2 mg/kg twice
daily appears appropriate. The dose may be increased to 2-4
mg/kg twice daily after 4 weeks.68
INVASIVE TECHNIQUES
Sildenafil is a phosphodiesterase type 5 (PDE5) inhibitor. It

produces pulmonary vasodilation by promoting an enhanced
and sustained level of cGMP, an identical effect to that
of inhaled NO. Sildenafil has a preferential effect on the
pulmonary circulation because of the high expression of
this isoform in the lung. A large, randomized, clinical trial
demonstrated that sildenafil caused significant improvements
in 6-minute walk distance and hemodynamics in patients with
PAH.69 The recommended dosage is 20 mg three times daily,
but dosages as high as 80 mg three times daily have been used
safely. Sildenafil is given in a dose range of 15 mg/kg per day
in 4 divided doses in children.70
In ES syndrome, there are recommendations for treatment
(Table 7).45 Oral anticoagulation and antiplatelet agents are
controversial: oral anticoagulation is indicated in subjects
with atrial fibrillation and with pulmonary artery thrombosis,
but with low bleeding risk. No data are available on calcium
channel-blocking drugs. Prostanoids, endothelin receptor
antagonists (ERAs) and PDE5 inhibitors demonstrated
efficacy and safety in PAH associated with CHD and in ES in
uncontrolled studies and in small trials for bosentan, sildenafil
and tadalafil. The final option is lung transplantation with repair
of the cardiac defect or combined heartlung transplantation.
The timing of the procedure is still challenging.
Atrial Septostomy
Table 7
Recommendations for treatment in Eisenmenger syndrome
Recommendations
Classa
Levelb
Targeted PAH therapy in CHD should only

be performed in specialized centers
The ERA bosentan should be initiated in

WHO-FC IIIc patients with Eisenmenger
Other ERAs, phosphodiesterase type5 inhibitors and prostanoids should be

considered in WHO-FC IIIc patients with
IIa
Combination therapy may be considered

in WHO-FC IIIc patients with Eisenmenger
syndrome
IIb
The use of calcium channel blockers

should be avoided in patients with
Eisenmerger syndrome.
III
Class of recommendation.
Level of evidence.
c Although recent data support the use of ERAs such as bosentan also
in WHO-FC II in patients with idopathic PAH and PAH associated with
connective tissue diseases, such data are currently not availble for
Eisenmenger patients. Because of marked differences in the natural history
betwwen these groups, the results cannot simpy be applied to congenital
patients, and further studies are required before recommendations.
CHD = congenital heart disease; ERA = endothelin receptor antagonist;
PAH = pulmonary arterial hypertension; WHO-FC = World Health
Organization-functional class
b
Atrial septostomy should not be performed in a patient

with impending death and severe RV failure or a patient
receiving maximum cardiorespiratory support. Predictors
of procedure-related failure or death have been identified
and include a mean RA pressure higher than
20 mm Hg, a PVR index higher than 55 units/m2 or a predicted
1 year survival rate of less than 40 percent.71 The mechanisms
responsible for the beneficial effects of atrial septostomy
remain unclear. Possibilities include increased oxygen delivery
at rest and/or with exercise, reduced RV end-diastolic pressure
or wall stress, improvement in RV function as by the FrankStarling curve or relief of ischemia.
65
Phosphodiesterase Type 5 Inhibitors
Heart-Lung and Lung Transplantation

Heart-lung transplantation has been performed successfully in
patients with PAH since 1981.72 The operative mortality rate
ranges between 16 and 29 percent and is somewhat higher
for recipients of a single-lung transplant. The 1-year survival
rate is between 70 and 75 percent, the 2-year survival rate
is between 55 and 60 percent, and the 5-year survival rate is
between 40 and 45 percent.73 Although their postoperative
mortality is higher than patients with lung disease, their longterm survival is comparable.
CONCLUSION
The morbidity and mortality in PAH was very high before
the era of vasodilator therapy and palliative atrial septostomy.
The inhaled NO is promising. Ultimately heart-lung or lung
transplant is literally life saving.
Yet, there is already plenty of evidence to show that we are in
much danger of losing our clinical heritage and of pinning
too much faith and figures thrown up by machines. Medicine
must suffer if this tendency is not checked.
Paul Wood (1907-1962)
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66
Congenital Pericardial Diseases

Prasanna Simha Mohan Rao
Congenital Absence of pericardium

The spectrum of pericardial diseases include congenital
defects, cysts, pericarditis, chylopericardium and neoplasms.
Pericardial defects are rare and are commonly related to
structural anomalies of the lung and diaphragm. They are also
associated with other congenital anomalies of the heart. The
most common congenital abnormalities of the pericardium are
pericardial celomic cysts and the rarest are pericardial bands
that obstruct the superior vena cava. Congenital absence of the
pericardium and pericardial cysts are the two major congenital
abnormalities of the pericardium.
History
Columbus first described congenital absence of the
pericardium in 1559.
Demography
The Male:Female ratio is 3:1. It is usually detected in the
second decade of life and detection may be incidental
during imaging, cardiac surgery or postmortem. Most are
asymptomatic and only a few present with symptoms related to
it directly. The prevelance varies from 0.002 to 0.004 percent
and the difference is based on the incidence of detection by
imaging, cardiac surgery, and autopsy.
Types
Partial absence is more common than complete absence. Seven
percent of the cases involve absence of the left pericardium
and most are partial absence. Right sided absence is less
common and bilateral absence is still rare.
A foraminal absence is seen in one-third of cases and
complete left sided absence is seen in another third. A
diaphragmatic defect may be seen in 17 percent of cases. Total
bilateral absence is seen in 9 percent and complete right sided

absence is seen in only 4 percent of cases.
Embryological basis
Congenital absence of pericardium is related to defects in
the development of the pleuropericardial membrane and
persistence of the pleuropericardialchannel due to premature
atrophy of the left common cardinalvein. The size of the defect
is determined by the timing of its degeneration. Others have
suggested that herniation of alung bud or enlargement of the
developing heart may impair closureof the pleuropericardial
foramen. Some defects may result from a traction-induced
tear inthe pleuropericardial membrane during embryogenesis
rather thanfailure of the foramen to close. Early atrophy of
the right duct of Cuvier can cause right sided defects, whereas
early atrophy of the left duct of Cuvier could give rise to left
sided defects and also bronchogenic cysts.
Clinical Features
Most cases are asymptomatic and are incidentally detected.
Some patients may present wth symptoms like tachycardia,
palpitation, positional discomfort elicited by a particular
position, and sharp stabbing chest pain.
Electrocardiography
This may show bradycardia due to a high vagal tone and
incomplete right bundle branch block. In left-sided complete
absencethere may be poor progression of R waves due to
cardiac rotation.
Chest X-ray
The basic findings of absent left pericardium are related to the
marked levoposition of the heart. An absent right heart border
Echocardiography may show hypermobility of the heart,

unusual echocardiographic windows, abnormal septal motion
and swinging of the heart. There may be laterally displaced
parasternal windows.
Mostpericardial cysts are asymptomatic and are an

incidental findingon roentgenograms or at surgery. Symptoms
may be due to local compression, torsion or hemorrhage into
the cysts. Rarely a ruptured giant cyst can cause tamponade.
Radiologically they can present as a round homogeneous
radiodenselesion at the cardiophrenic angle. More than
two-thirds being found on the right. These findings are
usually diagnostic, but confirmationof the diagnosis may be
obtained by two-dimensional echocardiographyor computed
tomography. Contrast CT is recommended for diagnosis and
follow up of these cysts.
Management of these cysts include observation, percuta
neous drainage and excision. If percutaneous drainage is done,
the injection of a sclerosing agent can reduce the incidence
of recurrence. Excision is recommended for symptomatic
cysts. This can be done by open surgery or preferably by
thoracoscopy.
Conclusion
Magnetic resonance imaging provides excellent delineation

of the pericardium and its defects. Interpostion of the lung
between the aorta and the pulmonary artery, and the heart and
the diaphragm may be seen.
Congenital absence of pericardium and cysts are rare

malformations, mostly asymptomatic. They are discovered
accidentally at cardiac surgery, on routine chest imaging, or
while investigating unrelated problems.The echocardiography
is the primary imaging modality used to examine the
pericardium, CT and MR imaging provide various advantages.
A few cases symptomatic cases may need surgical correction.
Any associated disease may have to be concomitantly corrected.
Echocardiography
Management
The asymptomatic patients are not in danger and hence require
only observation. Symptomatic small defects may need
treatment due to the possibility of herniation and strangulation
of the left atrial appendage or left ventricle. Surgery involves
enlarging restrictive defects or patching the defects with a
prosthetic material. Atrial appendectomy may be required for
herniation of left atrial appendage.
Associated cardiac malformations, which may be present
in up to 30 percent of symptomatic patients (like tetralogy of
Fallot, ventricular septal defects and patent ductus arteriosus)
may need treatment on their own merits. Associated
diaphragmatic hernia, bronchogenic cysts and pulmonary
sequestration should also be treated.
Pericardial Cysts
Pericardial cysts are caused by a failure of coalescence offetal
lacunae forming the pericardium. The estimated incidenceof
pericardial cysts is 1:100,000. They are typically unilocular
true cysts, which are lined by endothelium or mesothelium.
They contain clear serousfluid unless there is hemorrhage in
them. They do not communicate with the pericardial space.
66
congenital pericardial diseases
is seen as the cardiac border becomes retrosternal. In a partial

defect there may be a focal bulge in the area of the pulmonary
artery or left atrial appendage. There may be a tongue of
lung tissue interposing between the main pulmonary artery
and aorta.There may be an increased distance between the
sternum and the heart in a lateral chest X-ray due to absence
of the sternopericardial ligament.
Right-sided absence may be more difficult to diagnose
on chest X-ray but herniation of the heart may produce
prominent right heart border.
A cheerful heart is good medicine.

Bible, Proverbs 17:22
bibliography
1. Columbus MR. De re anatomica. Vol 15. Beurlaque N, (ed).
Venice; 1559. pp. 265-9.
2. Gatzoulis, Michael A, Munk, Marc-David, Merchant, et
al. Isolated congenital absence of the pericardium: clinical
presentation, diagnosis, and management Ann Thorac Surg.
2000;69:1209-15.
3. Le Roux BT. Pericardial coelomic cysts. Thorax. 1959;14:2734.
4. Noyes BE, Weber T, Vogler C. Pericardial cysts in children:
surgical or conservative approach? J Pediat Surg. 2003;38:
1263-5.
5. Satur CM, Hsin MK, Dussek JE. Giant pericardial cysts. Ann
Thorac Surg. 1996;61:208-10.
6. Van Son JA, Danielson GK, Schaff HV, et al. Congenital
partial and complete absence of the pericardium. Mayo Clin
Proc. 1993;68:743-7.
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67
Marfan Syndrome
INTRODUCTION
Marfan syndrome is an autosomal dominant connective tissue
disorder, which occurs in about one in 5,000 individuals in
the United States. It was first described in 1896 by a French
pediatrician, Dr Antoine Marfan.
Marfan syndrome is the result of a defect in the FBN1
gene on chromosome 15 that codes for a glycoprotein called
fibrillin 1. Fibrillin is essential for the formation of the elastic
fibers found in connective tissue. Fibrillin is secreted into
the extracellular matrix by fibroblasts and is incorporated
into insoluble microfibrils, which provide a scaffold for
deposition of elastin, another connective tissue protein that
allows many tissues in the body to resume their normal shape
after stretching or contracting. The ocular, cardiovascular and
musculoskeletal systems are primarily involved in Marfan
syndrome.1 It also affects the respiratory system, the central
nervous system and the skin. The entire aorta is abnormal and
remains at risk for dissection and aneurysm even after repair.
In this chapter, we provide an overview of Marfan
syndrome with a focus on the cardiovascular system.
GENETICS AND DIFFERENTIAL DIAGNOSIS

OF MARFAN SYNDROME
Since transmission is through autosomal dominant inheritance,
an individual with Marfan syndrome has a 50 percent chance
for transmitting a mutation to each of his or her children. About
25 percent of cases represent a new FBN1 gene mutation, not
infrequently in the offspring of an older father, defined as over
age 40.
The differential diagnosis of Marfan syndrome includes
autosomal dominant familial thoracic aortic aneurysms
and aortic dissections (TAAD), Loeys-Dietz syndrome,
homocystinuria and the vascular type of Ehlers-Danlos
syndrome (also known as EDS type IV or EDS4) (Table 1).
Cardiovascular manifestations of familial thoracic aortic

aneurysms and aortic dissections (TAAD) are:
1. Dilation of the aorta at the level of the ascending aorta or
the sinuses of Valsalva.
2. Aneurysms and dissections of the thoracic aorta involving
either the ascending or descending aorta. Cardiovascular
involvement is usually the only finding. Affected
individuals typically experience progressive enlargement
of the ascending aorta, leading to either aortic dissection
involving the ascending aorta (type A dissection) or
consequent tear or rupture. The onset and rate of progression
of aortic dilatation is highly variable. Mutations in one of
seven genes FBN1, TGFBR1, TGFBR2, MYH11, ACTA2
MYLK7 and SMAD3are responsible for TAAD.2
Loeys-Dietz syndrome3 is another connective-tissue
disorder with features that overlap Marfan syndrome and
the vascular type of Ehlers-Danlos syndrome. Loeys-Dietz
syndrome is inherited as an autosomal dominant condition.
Mutations in two genes that encode transforming growth factor
(TGF) receptors 1 and 2 (TGFBR1 and TGFBR2) have been
found in association with a continuum of clinical features. On
the mild end, the mutations result in a presentation similar to
that of Marfan syndrome (sometimes referred to as Marfan
syndrome type 2) or with TAAD. On the severe end, mutations
are associated with a complex phenotype, in which aortic
dissection or rupture commonly occurs in childhood. This
latter phenotype is characterized by a triad of hypertelorism,
a bifid uvula, cleft palate, or both, and generalized arterial
tortuosity with widespread vascular aneurysm and dissection.
Since transmission is through autosomal dominant
inheritance, an individual with Loeys-Dietz syndrome has a
50 percent chance for transmitting a mutation to each of his or
her children.
Marfan syndrome is clinically similar in its ocular
manifestations and physical proportions to autosomal recessive
homocystinuria, a disorder of methionine metabolism. Unlike
67
Table 1
Differential diagnosis of Marfan syndrome

Clinical features
Special comments
Familial thoracic aortic

aneurysms and aortic
dissections (TAAD)
Progressive aortic root dilatation and

dissection of the thoracic and abdominal
aorta. Risk of cerebral aneurysm.
Autosomal dominant inheritance with reduced penetrance

Variable age of presentation with aortic dilatation
Non-cardiovascular features of Marfan syndrome are
lacking
Loeys-Dietz syndrome
Aortic aneurysms
Aortic dissection
Arterial tortuosity
Hypertelorism without ectopic lentis
Broad, bifid uvula
Cleft palate
Velvety tongue
Clubfeet
Autosomal dominant
Dissections may occur in aorta and smaller arteries
Homocystinuria

Ocular manifestations similar to Marfan
syndrome
Developmental delay
Thrombophilia and increased risk of
thromboembolism
Higher risk for coronary artery disease
Osteoporosis.
Autosomal recessive
Elevated total plasma homocysteine and urinary
homocysteine levels
Aortic dilation, aneurysm or dissection is unusual
No joint laxity
vascular type, formerly
called EDS type 4
Aortic and arterial dilation, spontaneous

vascular dissection or rupture
Translucent skin with visible veins
Skin laxity and scars
Easy bruising
Acrogeria
Gastrointestinal perforation
Organ rupture
Autosomal dominant
Arterial, intestinal and/or uterine fragility leads to very
high-risk pregnancies
Clubfoot and/or congenital dislocation of the hips in
neonates
Inguinal hernia, pneumothorax and recurrent joint
subluxations/dislocations in childhood
Bicuspid aortic valve with

associated aortopathy
Aortic root dilatation occurs at the sinotubular region despite having a normal
functioning valve
Autosomal dominant with reduced penetrance

Follow-up echocardiograms since aortic root dilatation
may occur at variable ages
Screen family members with echocardiograms for valve
disease, but may have aortic root involvement without
valve disease
MASS phenotype
Aortic dilatation-mild and nonprogressive

Autosomal dominant
Non-specific skin and skeletal features that may be similar
to Marfan syndrome
Stickler syndrome
Pierre Robin syndrome with cleft palate

and micrognathia
Flat facial profile
Sensorineural hearing loss
High myopia and retinal detachment.
Autosomal dominant
No ectopia lentis
Beals syndrome
(congenital contractural
arachnodactyly)
Joint contractures
Scoliosis
Crumpled ears
Autosomal dominant
Marfanoid appearance
Joint contractures improve or resolve as child gets older
FBN2 gene mutations
Marfan syndrome, however, homocystinuria is associated with

developmental delay and osteoporosis in many cases, has no
joint laxity, and untreated patients are at risk for thrombophilia,
but not for aortic dilation, aneurysm or dissection.4
The Ehlers-Danlos syndrome vascular type (EDS4)
is a rare autosomal dominant disorder with an estimated
prevalence of one in 200,000. EDS4 is due to mutations in
the COL3A1 gene that encodes collagen type III. The disorder
is characterized by thin, translucent skin with visible veins;
easy bruising; and a characteristic facial appearance in some
individuals consisting of thin lips and philtrum, small chin,
thin nose and large eyes; an aged appearance to the hands
(acrogeria); and arterial, intestinal and/or uterine fragility.
Vascular dissection or rupture, gastrointestinal perforation, or
Marfan syndrome
Genetic disorder
947
Miscellaneous
12
organ rupture are the presenting signs in the majority of adults

identified with EDS4. Arterial rupture may be preceded by
aneurysm, arteriovenous fistulae, or dissection, but also may
occur spontaneously. Neonates may present with clubfoot
and/or congenital dislocation of the hips. In childhood,
inguinal hernia, pneumothorax and recurrent joint subluxation
or dislocation can occur. Pregnancy for women with EDS4
poses up to a 12 percent risk for death from peripartum
arterial rupture or uterine rupture. One-fourth of individuals
with EDS4 who have undergone molecular analysis of the
COL3A1 gene to confirm their diagnosis have experienced a
significant medical problem by age 20 years and more than 80
percent by age 40 years. The median age of death is 48 years.5
Four additional conditions, all of which fit an autosomal
dominant mode of inheritance, are associated with FBN1
gene alterations. Closest clinically to Marfan syndrome is the
MASS phenotype (mitral-valve prolapse, borderline and nonprogressive aortic enlargement, striae and Marfanoid skeletal
features). The others areisolated ectopia lentis, isolated
familial mitral-valve prolapse and the Shprintzen-Goldberg
syndrome (craniosynostosis, microcephaly, developmental
delay, mitral valve prolapse and Marfanoid body habitus).1
However, in only some cases can the Shprintzen-Goldberg
syndrome be attributed to an FBN1 gene mutation.
myopic, which may be rapidly progressive during childhood

and may lead to retinal detachment. About 50 percent exhibit
dislocation of the ocular lens, generally in an upward direction
(Figure 3). Glaucoma is also more common in Marfan
syndrome. Lung septation in Marfan syndrome is abnormal,
which helps explain an increased risk of spontaneous
pneumothorax. Lumbosacral dural ectasia and hepatic and
renal cysts, as well as cholelithiasis, arise more commonly in
Marfan syndrome subjects than in the general population.1
Of greatest concern with Marfan syndrome is an increased
risk for cardiovascular complications, such as dissecting
aneurysm of the ascending aorta, aortic insufficiency, mitralvalve prolapse and dilation of the main pulmonary artery.
However, not all individuals with Marfan syndrome will
experience such complications.
CLINICAL FEATURES OF MARFAN SYNDROME

Skeletal manifestations of Marfan syndrome include
kyphoscoliosis, pectus carinatum or excavatum, joint laxity,
pes planus and relatively tall stature, with a decreased upperto-lower body segment ratio and a disproportionate increase
in the length of the arms, legs, fingers and toes (Figures 1
and 2). Individuals with Marfan syndrome are often highly
948
Figure 1: Patient with Marfan syndrome. Note: The long, narrow face,
thick glasses and arachnodactyly. Courtesy: wikispaces.com
Figure 2: Steinberg thumb sign on left and Murdoch-Walker wrist sign

on right. Normally, the thumb should not extend beyond the edge of the
palm, nor should it reach the distal interphalangeal joint of the 5th finger
when wrapped around the wrist. Courtesy: primehealthchannel.com
Figure 3: Superomedial dislocation of the ocular lens in a patient

with Marfan syndrome. Courtesy: Jonathan Trobe, MD University of
Michigan Kellogg Eye Center, Ann Arbor

Table 2
2010 Ghent criteria for a clinical diagnosis of Marfan syndrome7

Wrist and thumb sign, 3 points (wrist or thumb sign, 1 point)
Pectus carinatum deformity, 2 points (pectus excavatum or
chest asymmetry, 1 point)
Hindfoot deformity with pes planus, 2 points (pes planus
alone, 1 point)
Pneumothorax, 2 points
Dural ectasia, 2 points
Medial acetabular protrusion, 2 points
Reduced upper body segment/lower body segment and
increased arm span/height, 1 point
Scoliosis or thoracolumbar kyphosis, 1 point
Reduced elbow extension, 1 point
Facial features (3/5) (dolichocephaly, enophthalmos, downslanting palpebral fissures, malar hypoplasia, retrognathia),
1 point
Skin striae, 1 point
Myopia > 3 diopters, 1 point
Mitral-valve prolapse (all types), 1 point
* Maximum total: 20 points; score of 7 or greater meets systemic criteria
Marfan syndrome in a given individual, even within the

same family.1
CARDIOVASCULAR ASSESSMENT
IN MARFAN SYNDROME
Cardiovascular diseases are a predominant feature of Marfan
syndrome. Aortic dissection is still the primary cause of
mortality and morbidity. The Stanford system and the DeBakey
system are widely used for classification of aortic dissection.
The Stanford type A dissection involves the ascending aorta,
while the Stanford type B dissection extends from the distal
part of the aortic arch.9
67
Marfan syndrome
In the absence of a family history of Marfan syndrome, the

diagnosis may be made in one of four ways:
1. The presence of aortic root dilation, aneurysm or dissection
with ectopic lentis allows unequivocal diagnosis of Marfan
syndrome regardless of systemic findings.
2. The presence of aortic root dilation or dissection and an
FBN1 gene mutation.
3. In the presence of ectopia lentis, but in the absence of
aortic root dilation or dissection, detection of an FBN1
gene mutation.
4. When aortic root dilation or dissection is present, ectopic
lentis is absent and the mutation status of FBN1 is negative
or unknown, Marfan syndrome can be diagnosed clinically
in accordance with criteria codified in 1986, revised at a
conference in Ghent, Belgium in 1996 and further revised
in 2010 (Table 2).6,7
The rarest form of Marfan syndrome is an often sporadic,
neonatal form, characterized by severe arachnodactyly, joint
contractures, congenital emphysema, aortic dilation and severe
tricuspid and mitral regurgitation. Approximately 50 percent
of patients with the neonatal form die of cardiac failure within
the first year of life. Both the neonatal and classical forms of
Marfan syndrome are associated with FBN1 mutations, which
primarily involve exons 24 to 32.8
FBN1 gene sequencing and deletion/duplication analysis
is clinically available. Preimplantation, prenatal or presymptomatic diagnosis of family members is possible when an
FBN1 mutation has been identified. However, the presence
of an FBN1 mutation cannot be used to predict the course of
History and Physical Examination

A detailed clinical assessment should be performed on the
initial visit and during annual follow-up (Table 3).
Most individuals with a dilated aorta are asymptomatic.
Hypertension and smoking are medical risk factors for
reoperation.10 During the clinic visit the blood pressure is
reviewed with the patient. Records of home blood pressure
monitoring using an automated digital sphygmomanometer,
or frequent checks at a local clinic/pharmacy are strongly
encouraged. Blood pressure goals are to be reviewed at each
visit. The goal is to keep the systolic blood pressure between
100 and 120 mm Hg and the diastolic blood pressure between
60 and 80 mm Hg. Smoking or second hand exposure to
smoking are discouraged and aids for smoking cessation
should be offered. Information about daily skin and dental care
is provided along with a prescription for bacterial endocarditis
prophylaxis, when indicated. Since sleep apnea is a major
risk factor for blood pressure elevation, aortic dilatation and
adverse cardiovascular events, it is essential to screen and test
for sleep apnea when necessary.
Individuals with Marfan syndrome should be informed to
present to the emergency room with sudden onset of chest pain.
Chest pains made worse by taking a deep breath, shortness
of breath and/or dry cough may be due to a spontaneous
pneumothorax that needs medical attention, but is not usually
life-threatening. However, when a person with Marfan
syndrome arrives in an emergency setting with symptoms, it
is important to determine whether there is an aortic dissection.
Symptoms of a type A dissection with the initial tear in the
ascending aorta can be variable. The classic presentation is
acute onset of severe chest pain going through to the back.
Approximately 10 percent of acute dissections in Marfan
syndrome are Type B and typically present with the initial
tear in the proximal descending thoracic aorta. Symptoms of
heart failure due to left ventricular overload may occur if there
is acute aortic regurgitation due to dissection or mitral-valve
prolapse with severe regurgitation.
The cardiovascular examination may help to determine the
degree of valvular involvement. A mid-systolic click is usually
949
Miscellaneous
12
Table 3
Cardiovascular assessment in Marfan syndrome

Clinical history:
Review for history of chest pains/pressure and give advice regarding symptoms that require the patient to seek emergency care
Blood pressuregoal is less than 120/80 mm Hg with the use of beta-blockers and angiotensin II receptor blockers
Exercise counseling to avoid contact/competitive sports, isometric or strenuous exercises or weights. Recommend daily low to
moderate intensity aerobic activity as tolerated for 30 minute
Smoking cessation
Screen for obstructive sleep apnea
Advice regarding dental and skin care to reduce the risk of endocarditis. Provide bacterial endocarditis prophylaxis
Review history for:
Cardiac and aortic involvement: Aortic dilatation, aneurysm, dissection, valve disease, heart failure, prior surgeries
Central nervous system manifestations: dural ectasia causing back pain, headache, or meningocele-related signs and symptoms
Pulmonary involvement: Spontaneous pneumothorax, apical bullae, interstial parenchymal disease, bronchiectasis
Ocular problems: displacement of the lens (ectopia lentis), retinal detachment, high myopia
Musculoskeletal issues: History of recurrent or incisional hernias, pectus deformity requiring surgery, kyphoscoliosis
General physical examination:
Weight and height for calculation of body surface area
Blood pressure
Skin involvement: Stretch marks, recurrent incisional hernia
Skeletal features: Pectus deformities, scoliosis, pes planus, acetabular protrusion, arachnodactyly, joint laxity
Cardiovascular examination:
Ejection click may be heard when aortic root is dilated
Mid-systolic click heard with mitral valve prolapse
Murmurs associated with valve regurgitation: mitral regurgitation, aortic regurgitation, pulmonary regurgitation or tricuspid
regurgitation
Electrocardiogram and Holter:
12-lead surface electrocardiogram
Holter if there is a history of palpitation or presyncope/syncope
Imaging
Chest X-ray: On initial visit and then when there is chest pain/dyspnea
Rule out widened mediastinum
Pneumothorax
Apical blebs
Echocardiogram: Every 612 month in childhood and adulthood
Aortic root diameter:
Measured at the 4 points (indexed to body surface area and also to age in younger patients)
Yearly follow-up if maximum diameter less than 4.5 cm, every 6 month if over 4.5 cm
Measurements of the ascending aorta, arch, proximal descending aorta, abdominal aorta and rule-out dissection
Left ventricular dimensions, systolic and diastolic function
Mitral valve prolapse and degree of mitral regurgitation
Transesophageal echocardiogram: For bedside assessment of aortic dissection in a critically ill patient
Magnetic resonance imaging or computerized tomography: Performed for initial assessment, periodically and in emergency
situations to rule out aortic dissection
Provides visualization and assessment of the entire thoracic aorta and abdominal aorta
950
High sensitivity and specificity in diagnosis of aortic dissection

Assessment of the lower spine for dural ectasia, particularly if patient has neurologic symptoms

Table 4
Cardiovascular manifestations of Marfan syndrome (Nolen and

Mulder)
Dilatation of the ascending aorta at the level of the aortic
sinuses60 to 80%
Aortic aneurysm
Electrocardiogram and Ambulatory Electrocardiography
Dilatation and dissection of the descending thoracic or

abdominal aorta below the age of 50 year
People with Marfan syndrome may present with palpitations,

and there are reports of cardiac arrhythmias, delayed
atrioventricular conduction and a prolonged QT interval
on ambulatory electrocardiography (Holter monitoring).11
However, arrhythmias are not a feature of Marfan syndrome
per se. Cardiac arrhythmias associated with mitral valve
prolapse, mitral regurgitation, aortic dissection leading to
myocardial ischemia/infarction, or ventricular dysfunction
may occur in patients with Marfan syndrome.12
An increased number of premature ventricular complexes and
non-sustained ventricular tachycardia has been reported in
association with left ventricular dilation and abnormalities of
repolarization.13
An electrocardiogram should be checked on a yearly
basis. Additional electrocardiograms and ambulatory electrocardiography should be requested when clinically indicated in
people presenting with palpitations, chest pain, presyncope or
syncope.
Aortic annular enlargement with aortic valve regurgitation

Mitral valve prolapse with or without mitral valve
regurgitation66%
67
Marfan syndrome
heard with mitral valve prolapse. A holosystolic murmur

heard loudest in the apical area signifies mitral regurgitation.
An ejection click may be heard when the aortic root is dilated.
A diastolic murmur is best appreciated along the left sternal
border with aortic regurgitation.
Pulmonary artery dilatation without pulmonary valve or

peripheral pulmonic stenosis below the age of 40 year
74%
Premature mitral annular calcification (below the age of 40
year)
Tricuspid valve prolapse
Coronary artery dissection
Interatrial septal aneurysm
Left ventricular dilatation and dysfunction
Diastolic dysfunction
Pericardial effusion due to extension of the aortic root
dissection
Imaging in Marfan Syndrome

According to the guidelines, the aortic root and the entire aorta
should be regularly evaluated with an annual echocardiogram.
Magnetic resonance imaging (MRI) or computerized
tomography (CT) should be performed initially and then every
3 years. Annual MRI/CT of the entire aorta is indicated when
there is dilatation of a segment of the aorta approaching an
indication for surgery, or postoperatively one year after aortic
surgery, or during yearly follow-up for 2 to 3 years after an
aortic dissection to monitor stability of the residual dissected
aorta.12
Echocardiography
Echocardiography is the most widely used imaging method
for early diagnosis and follow-up of children and adults with
Marfan syndrome. The cardiovascular manifestations of
Marfan syndrome are presented in Table 4.
Serial aortic root assessment is of utmost importance in
Marfan syndrome, as there can be rapid progression without
symptoms. It should be recorded in the parasternal long axis
view at the four pointsannulus, mid-sinus level, sinotubular junction and proximal ascending aorta (Figure 4). The
annulus is an imaginary line at the aortico-ventricular junction,
along the plane of attachment of the leaflets of the aortic valve.
The sinuses of Valsalva are an anatomically dilated segment
Figure 4: Echocardiographic assessment of the aortic root in

Marfan syndrome in the parasternal long-axis view at the four
pointsannulus, mid-sinus level, sinotubular junction and proximal
ascending aorta
of the aortic root above the aortic valve. The sinuses of

Valsalva taper at a point called the sinotubular junction before
becoming the tubular ascending aorta. Measurements should
be made perpendicular to the long-axis of the aorta using the
leading edge-to-leading edge technique in views where the
largest diameters can be demonstrated.
Height and weight are recorded before each echocardiogram
to calculate the body surface area, so that the cross-sectional
951
Miscellaneous
12
952
aortic root dimensions can be indexed to body surface area.

Body surface area strongly influences aortic root size at all
the levels in children and also in adults. In general, women
have aortic roots 5 mm smaller than men. As compared with
the M-mode measurements, two-dimensional measurements
offer more information clinically and technically since there
is full visualization of the entire aortic root throughout the
cardiac cycle.14 In a study from the Netherlands, Rozendaal et
al noted that the Marfan population differs from the standard
reference population in body surface area and aortic root size
variability. They proposed that an adjusted nomogram be used
for accurate diagnosis of an enlarged aortic root in the Marfan
population due to their deviant body surface areas.15
The aortic root should also be measured at the level of
the aortic valve leaflets in the parasternal short-axis view.
Additional measurements should be made at the arch and the
descending thoracic aorta in the suprasternal notch view. The
subcostal view may allow for measurement of the abdominal
aorta in most patients.
In aortic dissection, an intimal tear allows blood to enter
the medial layer of the aorta, creating a false lumen that
can be demonstrated by color Doppler. The transthoracic
echocardiogram has a lower sensitivity of 55.5 percent and
is not as useful as other imaging modalities for assessing the
arch and the descending thoracic aorta for dissection.
Aortic valve regurgitation results from dilation of the
sinuses of Valsalva that extends to the sinotubular junction
and into the aortic annulus in Marfan syndrome (Figure 5).
The degree of aortic regurgitation can be assessed by
comparing the height and the width of the jet in relation to
the left ventricular outflow tract (LVOT) in M-mode with
color Doppler, in the parasternal long axis view. A broader jet
signifies increased severity of aortic regurgitation. Continuous
wave Doppler is used to assess the pressure half-time of the
regurgitant jet. It may cause fluttering of the mitral valve
leaflets in diastole. Diastolic flow reversal in the ascending or
the descending aorta (seen in the suprasternal notch view) is
noted in severe aortic regurgitation.
Mitral valve prolapse is common in Marfan syndrome and
defined as the displacement of one or both mitral leaflets by
more than 2 mm above the high points of the mitral annulus
recorded in either the parasternal long axis view or the apical
two-chamber view. Studies have shown that displacements
of less than 2 mm are not associated with increased leaflet
thickness, mitral regurgitation, or valve related complications.
When the leaflet displacement is greater than 2 mm, prolapse
is further subdivided into classic (> 5 mm) and nonclassic (<
5 mm) forms based on leaflet thickness. Complications such
as endocarditis and severe mitral regurgitation occur mostly
with classic prolapse. Severe mitral regurgitation, the most
common complication of mitral valve prolapse, occurs due
to progressive degeneration of the valve and chordae, with
myxomatous infiltration (thickening of the mitral layers due to
glycosaminoglycan accumulation), fibroelastic and collagen
Figure 5: Diagram showing aortic root dilatation at the sinuses of

Valsalva in Marfan syndrome
alterations. Sudden deterioration occurs in 75 percent of the

cases due to chordae rupture. Transforming growth factor
(TGF) beta-dysregulation in the connective tissue plays an
important role in the development of mitral valve prolapse in
Marfan syndrome.16
Individuals with Marfan syndrome may have prolapse
due to leaflet billowing, which is usually caused by valve
enlargement with abnormal chordal structures or annular
distensibility.17 The degree of mitral regurgitation should
be accurately assessed since it is an important prognostic
indicator. Color Doppler allows assessment of the origin,
width, direction and size of the regurgitant jet. Eccentric
jets can be more difficult to assess and their severity can be
assessed by looking for pulmonary venous flow reversal. The
shape and density of the Doppler signal should be assessed
with continuous-valve Doppler to assess the severity of mitral
regurgitation. A holosystolic signal usually signifies severe
The impact of aortic or mitral regurgitation on the left
ventricle is assessed by serially recording the left ventricular
dimensions, systolic and diastolic function. Initially, there
is an increased hypercontractility, which is followed by left
ventricular enlargement resulting from volume overload over
time.
In cases with tricuspid valve prolapse, the degree of
regurgitation can be assessed by color Doppler in the
apical four-chamber view. Pulmonary artery dilatation and
pulmonary valve regurgitation are best seen in the parasternal
short axis view at the level of the aortic valve. Measurements
should be made to assess the diameter of the right ventricular
outflow tract (normal range 1.83.4 cm), pulmonary valve
annulus (normal range 12.2 cm), main pulmonary artery
(normal range 0.92.9 cm), and right (normal range 0.71.7
cm) and left pulmonary branches (normal range 0.61.4 cm).
Transesophageal Echocardiography
There are limited indications for cardiac catheterization/
coronary arteriography in Marfan syndrome because of the
specific risks of catheter manipulation in patients with a fragile
aorta. This procedure is primarily indicated to delineate the
coronary arteries for coronary artery disease when an elective
cardiac surgery (for aortic or valvular disease) is planned, in
patients older than 50 years of age or in younger individuals
who are at increased risk for coronary artery disease.
67
Marfan syndrome
In the majority of cases, the dilatation is at the root of the main

pulmonary artery, just distal to the pulmonary valve.17 The
main pulmonary artery is considered to be dilated when it is
over 3.48 cm, but this is rarely of clinical consequence.18,19
Abdominal ultrasound has its limitations, especially in
obese people, since the descending thoracic aorta cannot be
visualized very well. Ultrasound can be used for screening
and alternately in conjunction with another imaging modality
such as MRI/CT.
Medical Management
Transesophageal echocardiography is a very sensitive

imaging method (100% sensitivity) for detecting a dissection
of the thoracic aorta, but has a lower specificity (68.2%) and
accuracy (86.8%) than an MRI, primarily due to false-positive
findings in the ascending aorta.20 The specificity may have
improved over the past two decades with multiplanar and
three-dimensional transesophageal echocardiography. Trans
esophageal echocardiography has the advantage of bedside
evaluation in a critically ill patient. The site of the entry of the
dissection, the degree of aortic regurgitation and pericardial
effusion can be accurately assessed by this semi-invasive
procedure.
A dissection can be confirmed by the presence of two
vascular lumina separated by an intimal flap. The central
displacement of intimal calcifications is considered a positive
finding of dissection when the false lumen is completely
thrombosed. The site of entry is identified by color Doppler
flow between two vascular lumina or by disruption of the
dissected membrane with fluttering of the ruptured intimal
borders on two-dimensional echocardiography. An acute
aortic dissection may extend into the coronaries and cause
pericardial effusion, which manifests as an echo-free space
between the pericardium and epicardium, since fresh blood is
echolucent.
Magnetic Resonance Imaging and

Computerized Tomography
Magnetic Resonance Imaging (MRI) scanning can be safely
performed even in severely ill with aortic dissection. It is also
an excellent tool for serial measurements of the entire aorta
and its branches and for the assessment of lumbosacral dural
ectasia. When MRI is not available or cannot be performed
due to pacemaker/defibrillator issues or claustrophobia,
computerized tomography (CT) is a suitable alternative.
The sensitivity and the specificity of MRI is 100 percent for
detecting a dissection of the thoracic aorta irrespective of
location.20 In addition, MRI is the most sensitive imaging
modality for detecting thrombus formation in the false lumen
of both the aortic arch and the descending segment of the aorta.
It can accurately determine the site of entry to a dissection,
aortic regurgitation and pericardial effusion.
Aortic dilatation leading to dissection is the main cause of

mortality in Marfan syndrome. For those with aortic-root dilation,
the beta-adrenergic-1 receptor antagonist atenolol is generally
prescribed, although the angiotensin II receptor antagonist
losartan currently under study has shown promise in slowing
the rate of dilation and keeping the aortic root from reaching a
dimension, at which elective surgery might be required.21
Other drug therapies that have shown some promise
are angiotensin-converting enzyme inhibitors (ACEIs)
in prevention of aortic dilatation in patients with Marfan
syndrome.22 The ACEIs can raise the serum concentration
of bradykinin leading to vasodilatation and reduced aortic
wall rigidity or act by reducing vascular smooth muscle cell
apoptosis that is mediated by AT2 receptor activation.
Similarly, matrix metalloproteinase inhibitors (MMPI)
such as doxycycline have shown greater efficacy than atenolol
in the Marfan population by preventing aneurysm formation
and preserving the integrity of the elastic fibers, normalizing
vasoactive function and eliminating TGF-beta activation in
small studies.23, 24
To aid pediatricians and other clinicians who care for
children with Marfan syndrome, a monograph entitled,
Health Supervision for Children with Marfan Syndrome,
which contains clinical guidelines and growth charts, was
published by the American Academy of Pediatrics in 1996 and
reaffirmed in 2007.25
Beta-blockers
In 1971, beta-blockers were found to reduce the risk of aortic
dissection, leading to their extensive use for prophylactic
therapy. They are still widely used for this purpose, despite
more recent meta-analyses not clearly demonstrating longterm benefits.26 The aorta in Marfan syndrome is stiff and
dilates progressively with age. Independent predictors of
progressive aortic dilatation are aortic diameter and aortic
distensibility.27 Significant predictors of aortic dilatation
are increased systolic blood pressure, increased aortic
stiffness index, decreased maximum aortic wall expansion
(distensibility), velocity, and strain. Tissue Doppler imaging
(TDI) using transesopahageal echocardiography demonstrates
953
Miscellaneous
12
that the predictors of aortic root dissection are decreased

aortic strain, maximal wall expansion velocity, and increased
stiffness index.28 Beta-blockers lower the heart rate and blood
pressure, reduce the force of left ventricular ejection, increase
aortic distensibility, and reduce aortic stiffness.19
Aortic diameter > 5 cm
Aortic root dilatation progressively extending beyond the

sinuses of Valsalva
Angiotensin II Receptor Blockers
Rate of aortic dilatation more than 5% per year or more than

2 mm per year in adults
In 1991, Dietz et al found a correlation between Marfan

syndrome and mutations of the FBN1 gene, which encodes
the fibrillin-1 protein of the extracellular matrix.29 In 2003,
Neptune et al showed that TGF-beta signaling plays a
role in Marfan syndrome. Increased TGF-beta signaling
is believed to be associated with excessive proteolysis
of the extracellular matrix by promoting production of
several matrix metalloproteinases (MMP).30 The imbalance
between the MMP and their tissue inhibitors (TIMP) leads to
development of thoracic and abdominal aneurysms. This has
lead to further research in the use of losartan, an angiotensin II
type 1 receptor blocker (AT1 antagonist), that acts as a TGFbeta-blocker in reducing the risk of progression of aortopathy
in Marfan syndrome with promising preliminary results.21, 31
Presently, the COzaar in Marfan Patients Reduces Aortic
Enlargement (COMPARE) study, an open-label, randomized,
controlled trial is in progress to prospectively determine the
efficacy of losartan in the Marfan population.32 Treatment
with losartan will be compared with no additional treatment
after three years of follow-up, before evidence-based
recommendations are made. Patients taking beta-blockers will
continue to use this standard treatment.
Family history of aortic dissection
Baseline diameter of the arch and descending aorta
Surgery
954
Table 5
Risk factors for aortic dissection in Marfan syndrome
Elective aortic root replacement is recommended in Marfan

syndrome in individuals with an aortic root of 4.5 to 5 cm, or
when there is rapid aortic growth (more than 5% per year or
more than 2 mm per year in adults), or there is a family history
of aortic dissection, as well as in those with a relatively small
body surface area since that is associated with an increased
risk of aortic dissection (Table 5).12 Elective surgery is
also preferred since there is high mortality associated with
emergency surgery at the time of aortic dissection. Gott et
al reviewed outcomes in 675 Marfan syndrome patients who
underwent surgery at 10 expert centers. The early mortality
was 1.5 percent for elective surgery and 11.7 percent for an
emergency operation. The overall five-year survival was 91
percent and 10 percent of those needed reoperation for the
distal aorta.33
The well-known original operation called the Bentall
procedure has been advocated since 1968 when it was
first described by Hugh Bentall and Anthony DeBono.34
In this operation, a composite valve graft is used with
concomitant aortic root and aortic valve replacement along
with reimplantation of the coronaries. This operation has
dramatically changed outcomes in the Marfan population,

especially when it is performed electively.35 Before the
introduction of this operation, surgery was usually performed
primarily during an aortic catastrophe, with an early mortality
as high 60 percent even in leading centers.
Over the years, the modified Bentall procedure using a
mechanical, bioprosthetic or homograft aortic valve prosthesis
has been performed with promising results. This continues
to remain the standard of care with promising results at
experienced centers. However, there is a responsibility
to follow up with life long anticoagulation and bacterial
endocarditis prevention/prophylaxis, since there is an
increased risk of thromboembolism and endocarditis. Due
to shorter durability of the bioprosthetic valves, mechanical
valves are preferred in most patients.
In patients with primarily normal valves, in whom aortic
insufficiency is due to the dilated annulus or dissection, valvesparing operations have become popular. One involves aortic
root replacement by a Dacron prosthesis and reimplantation of
the coronary arteries into the prosthesis (David operation),36
and the other involves remodeling of the aortic root (Yacoub
operation).37 If necessary, all other parts of the aorta can be
replaced. Patient selection is critical, and 10 to 20 percent of
patients may not qualify since valve-sparing surgery should
not be performed in severely stretched, thinned out aortic
leaflets or in those with multiple fenestrations.
Overall, the advantages of the valve-sparing operations
are a lower risk of thromboembolism and avoidance of anticoagulation. The limitations of the valve-sparing aortic root
operations are limited long-term data, development of aortic
regurgitation over 10 years in up to 25 percent of the patients,
and the need for careful patient selection since 10 to 20 percent
of patients are not candidates for valve-sparing operations.18
Although the valve-sparing operation has gained popularity,
it appears to have limited durability, with 17 percent patients
needing re-operation by 10 years.38
In a landmark study, Cameron et al. retrospectively
reviewed the evolution of aortic root replacement surgery
in Marfan syndrome and its late results in 372 patients over
30 years (1976 to 2006), at the Johns Hopkins Medical
Institutions (Baltimore, Maryland, USA)39 Interestingly, in
the first 24 years, 85 percent received a Bentall homograft,
Thoracic Aneurysms and Chronic Dissections

Expansion of a chronic thoracic dissection (Type B dissection)
in patient with Marfan syndrome may require surgery even
though the surgical mortality is three times higher than with
medical management. Preoperative risk factors for increased
surgical mortality according to the International Registry
of Acute Aortic Dissection are listed in Table 6 with two
independent predictors of surgical mortality being:
1. Age over 70 years.
2. Preoperative shock and hypotension.40
Elective replacement of the descending aorta should
be considered when the diameter of the chronic dissection
exceeds 5 to 6 cm.19
Table 6
Preoperative clinical conditions associated with increased surgical

mortality in patients with Marfan syndrome and Type B aortic
dissection
Preoperative altered consciousness
Partial thrombosis of the false lumen
Periaortic hematoma on diagnostic imaging
Descending aortic diameter > 6 cm
Right ventricular dysfunction at surgery
67
Marfan syndrome
while in the last eight years, 61 percent had valve-sparing

surgery. There was no operative or early mortality (within 30
days of the surgery) among the 327 patients who underwent
an elective repair. Emergent or urgent operative repair carried
an early mortality risk of 4.4 percent.
The most common late complication in this study was
thromboembolism (with thrombosis of the mechanical valve).
Actuarial freedom from thromboembolism in patients with a
composite graft was 96.3 percent, 93.3 percent, 91 percent
and 89.8 percent at 5, 10, 15 and 20 years. The incidence of
late coronary anastomotic dehiscence was reduced after 1990,
when the coronary button technique with felt reinforcement of
the anastomosis was adopted.
The impact of dissection at the time of the original operation
had a profound effect on late survival and freedom from
reoperation on the distal aorta. Survival at 10 and 20 years
among those with a dissection was 65 percent and 53 percent,
respectively, as compared with 87 percent and 76 percent in
those without dissection. Freedom from reoperation on the
arch and descending aorta among those with a dissection was
67 percent and 43 percent, respectively, at 10 and 20 years,
as compared with 92 percent and 77 percent in those without
dissection.
The late deaths were due to dissection or rupture of the
residual distal aorta and arrhythmia followed by prosthetic
valve endocarditis. Freedom from endocarditis was 97.2
percent, 95.1 percent, 94.2 percent and 91.7 percent at 1, 5, 10
and 20 years, respectively. Seven of the 40 patients undergoing
valve-sparing surgery (David II remodeling procedure) had
severe aortic insufficiency. The late mortality was 26 percent
among those who needed concomitant mitral valve surgery.
Actuarial survival among the 372 patients with Marfan
syndrome after aortic root replacement was 91.9 percent,
85.5 percent, 81 percent and 75.5 percent at 5,10, 15, and 20
years. Age and mitral valve surgery were the most significant
independent risk factors for mortality.
Shorter time from onset of symptoms to surgery

Age over 70 year
Preoperative shock/hypotension
Role of Endovascular Stents in Marfan Syndrome

Endovascular stents are of limited value in this population due
to the underlying connective tissue disorder that may lead to
further complications.41 Despite several reports of short-term
success after endovascular stent grafting of the descending
thoracic aorta in Marfan syndrome, it is not recommended
unless the risk of conventional surgical repair is prohibitive.12
From time-to-time, the American Heart Association revises
its guidelines for antibiotic treatment in conjunction with
dental procedures and other situations, in which there is a high
likelihood of bacteremia (invasive otorhinolaryngological,
gastrointestinal and genitourinary procedures). According to
the most recent guidelines in 2007, oral antibiotic prophylaxis
is no longer required in patients with mitral valve prolapse
or other valve disorders, but is still recommended for those
patients who have an artificial heart valve.42 This decision
was not based on any evidence from clinical trials. It was
based on a hypothesis that the risk of endocarditis is not only
present at the time of such procedures, but it is a cumulative
risk present in association with such routine activities of daily
living as the normal brushing, flossing of the teeth and the
chewing of food. It is therefore considered that the cumulative
risk of endocarditis during daily activities is higher than that
associated with a specific dental or other invasive procedure.42
Since individuals with Marfan syndrome or other inherited
connective tissue disorders are neither specifically included
nor excluded from this list, the National Marfan Foundation
(NMF) Professional Advisory Board issued a statement on
their website (www.nmf.org) recognizing the importance of
good oral health and regular dental evaluations for people
with Marfan syndrome and related disorders. The NMF
recommended that all patients who have had a composite graft
955
Miscellaneous
12
repair, placement of an artificial valve, or a history of infective

endocarditis receive antibiotics, before dental work or other
procedures expected to cause bacteremia.
Although additional studies are needed to address this issue,
the NMF also finds a compelling argument for the continued
use of antibiotics in people with Marfan syndrome who are
unoperated, have classic myxomatous mitral valve changes,
or have multivalvular involvement, other cardiovascular
disease, systemic illness that can predispose to infection or
hamper recovery from endocarditis. The rationale for this
recommendation is that the risks associated with endocarditis
are higher than the risk associated with the use of antibiotics
for endocarditis prophylaxis.
Endocarditis prophylaxis is not clearly indicated in
individuals with Marfan syndrome without valvular
abnormalities or with mild mitral-valve prolapse without an
obvious leak, as such individuals are at low risk of endocarditis.
Pregnancy in Women with Marfan Syndrome
956
Major cardiovascular changes occur during pregnancy, with

an increase in cardiac output due to expansion of the blood
volume and increase in heart rate. Histological changes such
as fragmentation of the reticulum fibers, decreased acid
mucopolysaccharides and loss of normal structure of the
collagen in the aortic wall occur in women due to hormonal
changes during pregnancy. The combination of hemodynamic
stress and hormonal changes leads to an increased
predisposition towards aortic dissection, especially during the
third trimester of pregnancy, labor/delivery and for up to six
months postpartum.12
Since pregnancy carries a very high risk of aortic dissection in
women with Marfan syndrome, it is absolutely contraindicated
when the aortic root diameter exceeds 4 cm. The multiple risk
factors among women with Marfan syndrome for morbidity
and mortality during pregnancy, labor and delivery and the
postpartum period are noted in Table 7.43
Both men and women with Marfan syndrome should
receive genetic counseling, as there is a 50 percent chance of
transmitting this disorder to their offspring due to its autosomal
dominant inheritance. The use of beta-blockers carries
potential side-effects and fetal risks, such as low birth weight,
bradycardia, neonatal hypoglycemia, hyperbilirubinemia, and
apnea. There is a higher rate of obstetric complications (40%),
such as premature rupture of the membranes and an increased
fetal mortality.44
Before pregnancy, the ascending as well as the descending
aorta should be evaluated by MRI or CT. If there is an
indication for elective surgery, it should be carried out before
pregnancy. If a woman needs aortic valve replacement,
she should be apprised of the complexities and fetal risks
with anticoagulation during pregnancy in women who have
mechanical prosthetic valves. She should also be made aware
Table 7
Risk factors for morbidity and mortality during pregnancy in

women with Marfan syndrome
Volume overload due to hyperdynamic circulation during

pregnancy with the maternal intravascular plasma volume
rising to 150% of prepregnancy volume
Hormonal changes in pregnancy with progesterone

causing inhibition of collagen and deposition of elastin
Pre-existing vascular disease with aortic diameter > 4 cm
Rapid dilatation of the aorta on serial echocardiograms

during pregnancy
Increased risk of endocarditis
Increased risk of obstetric complications: preterm delivery

due to premature rupture of membranes or cervical
incompetence, postpartum uterine hemorrhage
Increased incidence of neonatal complications: fetal and

neonatal mortality.
of the limited durability of the bioprosthetic valve or valvesparing operations. Women with an aortic diameter more than
4 cm should be warned about a 10 percent risk of dissection
during pregnancy.45 There is an increased incidence of fetal
death and morbidity if a woman develops aortic dissection
during pregnancy and/or undergoes aortic surgery. Emergency
cesarean delivery should be performed just prior to the urgent
aortic surgery, to reduce adverse fetal outcomes, especially if
fetal lung maturity has been attained.
The reported safety of pregnancy in Marfan women with
aortic diameters between 2.5 cm and 4.5 cm in some studies
is questionable. These studies had major limitations including
the inherent absence of randomization, no strict control groups,
and a bias towards electing pregnancy by those counseled as
being at a lower risk.44,46 A new prospective study by Donnelly
et al in women with Marfan syndrome assessed the impact of
pregnancy on the rate of aortic growth as well as on shortand long-term clinical outcomes.47 Although no acute aortic
dissections were observed during all the pregnancies, there
was a significantly higher rate of aortic growth noted during
pregnancy as compared with each woman's baseline aortic
growth rate before pregnancy. Adverse outcomes and elective
aortic surgeries during long-term follow-up were higher in
women who had a prior pregnancy as compared with those
without previous pregnancies.
In women with Marfan syndrome, aortic dissection has been
reported even with a normal-sized aorta during pregnancy.
Hence, an event-free pregnancy cannot be guaranteed to any
patient with Marfan syndrome. Surgical replacement of the
aortic root does not completely normalize the risk, since a
dissection may occur elsewhere.
If a woman with Marfan syndrome chooses become
pregnant, she should be closely monitored with a multidisciplinary team comprised of specialists in obstetrics,
Physical Activity and Exercise

People with Marfan syndrome are at increased risk for
sudden aortic dissection because of underlying weakness
of the blood vessels. They also face problems with their
heart valves, eyes, lungs and musculoskeletal system. Highimpact, competitive and collision/contact sports are therefore
potentially dangerous.
Exercise counseling should be provided during each visit.
Exercise and activity recommendations in patients with
Marfan syndrome should be individualized according to the
underlying severity of aortic root dilation and/or a family
history of aortic dissection. People with Marfan syndrome
may have been inappropriately encouraged to compete in
sports without knowing the dangers involved often because of
their tall stature and agility arising from joint hypermobility.
Physical activities should be safe, regular, of low to
moderate intensity and individualized for each person to
improve physical conditioning, lower the blood pressure, and
reduce the risk of coronary artery disease. Protective eyewear
is recommended whenever appropriate. Some examples of
recommended exercise (low static /low dynamic) are walking,
cricket, golf, bowling and billiards.48
The following activities should be avoided in the Marfan

population:
1. Heavy isometric exercise, such as weight-lifting, which
can markedly increase peripheral vascular resistance and
proximal aortic wall stress.
2. Competitive aerobic sports, which can markedly increase
cardiac output and raise aortic pressure over prolonged
periods of time.
3. Activities that involve a risk of bodily collisions.
4. Marked changes in ambient air pressure (as in scuba-diving
or sudden changes in altitude in a non-pressurized aircraft)
because they can predispose to pneumothorax.
67
Marfan syndrome
perinatology, cardiology and genetics. She should have

monthly follow-up with her cardiologist. Beta-blockers should
be continued, but their dose should be titrated to reduce the
heart rate by at least 20 percent. Serial echocardiograms to
assess the aortic dimensions should be performed during each
trimester and prior to delivery if the aortic root size remains
less than 4 cm. Serial echocardiograms should be performed
more frequently, every four to six weeks, if the aortic root is
dilated more than 4 cm, when there is progressive dilatation
during pregnancy, or if there is a previous history of aortic
dilatation or dissection.
Although there is no consensus about the safest mode of
delivery, the preferred mode of delivery at most centers is an
elective cesarean operation, as soon as fetal lung maturity is
achieved. Epidural anesthesia should be offered to minimize
pain and anxiety and reduce the stress of labor. The presence
of dural ectasia may complicate epidural anesthesia and the
anesthesiologist needs to determine the best alternative. Shortacting beta-blockers such as esmolol can be used to reduce blood
pressure and an increased heart rate during uterine contractions.
Postpartum follow-up of the aorta is continued for up to six
months. The newborn should be evaluated by a neonatologist
and geneticist. If the mother or father harbors a known FBN1
gene mutation and prenatal diagnosis had not be performed
to determine the fetal mutation status, an umbilical cord or
peripheral blood sample should be obtained from the newborn
to look for the parental mutation.
CONCLUSION
Despite advances in genetics, medicine and surgery, the Marfan
syndrome continues to be intriguing with its complexities
and humbling with its potential for catastrophic aortic
complications and sequelae. Aortic aneurysms in Marfan
syndrome tend to occur in younger people, in whom the aorta
may enlarge quite rapidly. Sudden death can occur from aortic
dilatation leading to dissection, or from spontaneous atlantoaxial subluxation.
A multidisciplinary approach is essential for the complete
care of a person with Marfan syndrome. Besides the primarycare physician, the individual should receive routine care
from specialists in genetics, cardiology and ophthalmology.
In addition, referrals should be made to specialists in rheu
matology, obstetrics and gynecology, clinical social work,
and cardiothoracic surgery/anesthesiology when indicated.
Lifelong follow-up is indicated in all operated and unoperated
patients.
Early intervention appears to hold the key for better
outcomes since surgery needs to be performed, before aortic
dissection occurs, not only because of the high incidence of
early mortality, but also a reduction in long-term survival
after 20 years by over 30 percent and the doubled risk of
re-operation. The presence of mitral-valve regurgitation has
a deleterious effect on the left ventricular myocardium and
the existence of mitral-valve disease may be a marker of the
severity of cardiac involvement in Marfan syndrome. Valvesparing operations should be avoided in unsuitable candidates,
since the long-term morbidity associated with progressive
aortic insufficiency continues to be high. The timing of the
operation based upon aortic root diameter still continues to be
a moving target and better ways to identify people at risk are
needed.
We should always presume the disease to be curable, until its
own nature prove it otherwise.
Peter Mere Latham
957
Miscellaneous
12
958
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15. Rozendaal L, Groenink M, Naeff MS, et al. Marfan syndrome
in children and adolescents: an adjusted nomogram for
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16. Weyman AE, Scherrer-Crosbie M. Marfan syndrome and
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17. Stout M. The Marfan syndrome: implications for athletes
and their echocardiographic assessment. Echocardiography.
2009;26:1075-81.
18. Nollen GJ, Mulder BJ. What is new in the Marfan syndrome?
Int J Cardiol. 2004;97 (Suppl 1):103-8.
19. Ammash NM, Sundt TM, Connolly HN. Marfan syndromediagnosis and management. Curr Probl Cardiol. 2008;33:7-39.
20. Nienaber CA, Spielmann RP, von Kodolitsch Y, et al. Diagnosis
of thoracic aortic dissection. Magnetic resonance imaging
versus transesophageal echocardiography. Circulation. 1992;85:
434-47.
21. Brooke BS, Habashi JP, Judge DP, et al. Angiotensin II blockade
and aortic-root dilation in Marfan's syndrome. N Engl J Med.
2008;358:2787-95.
22. Yetman AT, Bornemeier RA, McCrindle BW. Usefulness of
enalapril versus propanolol or atenolol for prevention of aortic
dilatation in patients with the Marfan syndrome. Am J Cardiol.
2005;95:1125-7.
23. Chung AW, Yang HH, RadoMGski MW, et al. Long-term
doxycycline is more effective than atenolol to prevent
thoracic aortic aneurysm in Marfan syndrome through
inhibition of matrix metalloproteinase -2 and -9. Circ Res.
2008;102:e73-85.
24. Lebreiro A, Martins E, Cruz C, et al. Marfan syndrome:
clinical manifestations, pathophysiology and new outlook on
drug therapy. Rev Port Cardiol. 2010;29:1021-36.
25. American Academy of Pediatrics Committee on Genetics.
Health supervision for children with Marfan syndrome.
[Internet] Available from: http://aappolicy.aappublications.org/
cgi/reprint/pediatrics;98/5/978.pdf [1996 Nov, reaffirmed 2007
May] [cited 27 May 2011].
26. Gersony DR, McClaughlin MA, Jin Z, et al. The effect of betablocker therapy on clinical outcomes in patients with Marfan
syndrome: a meta-analysis. Int J Cardiol. 2007:114:303-08.
27. Nollen GJ, Groenink M, Tijssen JG, et al. Aortic stiffness and
diameter predict progressive aortic dilatation in patients with
Marfan syndrome. Eur Heart J. 2004;25:1146-52.
28. Vitarelli A, Conde Y, Cimino E, et al. Aortic wall mechanics
in the Marfan syndrome assessed by transesophageal tissue
Doppler echocardiography. Am J Cardiol. 2006;97:571-7.
29. Dietz HC, Loeys B, Carta L, et al. Recent progress towards
a molecular understanding of Marfan syndrome. Am J Med
Genet C Semin Med Genet. 2005;139C:4-9.
30. Neptune ER, Frischmeyer PA, Arking DE, et al. Dysregulation
of TGF-beta activation contributes to pathogenesis in Marfan
syndrome. Nat Genet. 2003;33:407-11.
31. Habashi JP, Judge DP, Holm TM, et al. Losartan, an AT1
antagonist, prevents aortic aneurysm in a mouse model of
Marfan syndrome. Science. 2006;312:117-21.
32. Radonic T, de Witte P, Baars MJ, et al. Losartan therapy in
adults with Marfan syndrome: study protocol of the multi-center
randomized controlled COMPARE trial. Trials. 2010;11:3.
33. Gott VL, Cameron DE, Alejo DE, et al. Aortic root replacement
in 271 Marfan patients: a 24-year experience. Ann Thorac
Surg. 2002;73:438-43.
34. Bentall HH, DeBono A. A technique for complete replacement
of the ascending aorta. Thorax. 1968;23:338-9.
35. Aomi S, Nakajima M, Nonoyama M, et al. Aortic root
replacement using composite valve graft in patients with aortic
valve disease and aneurysm of the ascending aorta: twenty
years experience of late results. Artif Organs. 2002;26:467-73.
36. Sarsam MA, Yacoub M. Remodelling of the aortic valve
annulus. J Thorac Cardiovasc Surg. 1993;105:435-8.
37. David TE, Feindel CM. An aortic valve-sparing operation
for patients with aortic incompetence and aneurysm of the
ascending aorta. J Thorac Cardiovasc Surg. 1992;103:617-21;
discussion 622.
38. Birks EJ, Webb C, Child A, et al. Early and long-term results
of a valve-sparing operation for Marfan syndrome. Circulation.
1999;100:1129-35.
43. Rossiter JP, Repke JT, Morales AJ, et al. A prospective

longitudinal evaluation of pregnancy in the Marfan syndrome.
Am J Obstet Gynecol. 1995;173:1599-606.
44. Meijboom LJ, Drenthen W, Pieper PG, et al. Obstetric
complications in Marfan syndrome. Int J Cardiol. 2006;110:
53-9.
45. Task Force on the Management of Cardiovascular Diseases
During Pregnancy of the European Society of Cardiology.
Expert consensus document on management of cardiovascular
diseases during pregnancy. Eur Heart J. 2003;24:761-81.
46. Meijboom LJ, Vos FE, Timmermans J, et al. Pregnancy and
aortic root growth in the Marfan syndrome: a prospective
study. Eur Heart J. 2005;26:914-20.
47. Donnelly RT, Pinto NM, Kocolas I, Yetman AT. The immediate
and long-term impact of pregnancy on aortic growth rate and
mortality in women with Marfan syndrome, J Am Coll Cardiol
2012;60:224-9.
48. Braverman AC. Exercise and the Marfan syndrome. Med Sci
Sports Exerc. 1998;30:S387-95.
67
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39. Cameron DE, Alejo DE, Patel ND, et al. Aortic root replacement
in 372 Marfan patients: evolution of operative repair over 30
years. Ann Thorac Surg. 2009;87:1344-9;discussion 1349-50.
40. Trimarchi S, Nienaber CA, Rampoldi V, et al. Role and results
of surgery in acute type B aortic dissection: insights from the
International Registry of Acute Aortic Dissection (IRAD).
Circulation. 2006;114:1357-64.
41. Akin I, Kische S, Rehders TC, et al. Current role of endovascular
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a guideline from the American Heart Association Rheumatic
Fever, Endocarditis, and Kawasaki Disease Committee, Council
on Cardiovascular Disease in the Young, and the Council on
Clinical Cardiology, Council on Cardiovascular Surgery and
Anesthesia, and the Quality of Care and Outcomes Research
Interdisciplinary Working Group. Circulation 2007;116:173654. Erratum in: Circulation. 2007;116:e376-7.
959
C hapter
68
Down Syndrome
Introduction
Genetics
Prior to the advent of amniocentesis, chorionic villus sampling

and maternal serum biochemical marker screening, or noninvasive prenatal testing by means of cell-free fetal DNA
analysis, in combination with measurement of the nuchal
translucency, a trisomy 21 karyotype occurred in approximately
one in 800 live births, making it the most common aneuploid
condition compatible with survival to term. The phenotype
produced by trisomy 21 was described by a British physician,
Dr John Langdon Down, in 1866 (Figure 1). In 1959, Dr Jerome
Lejeune of Paris, established trisomy 21 as the cause of Down
syndrome.1,2 Prior to this, the earliest representation of Down
syndrome dates back to a 16th century Flemish Nativity painting.
Clinical descriptions were made by two artists: Jean Etienne
Dominique Esquirol in 1838 and Edouard Seguin in 1844.3
In this chapter, we present an overview of the diagnosis
and management of individuals with Down syndrome, with
special attention to cardiac defects.
About 95 percent of people with Down syndrome have a

full trisomy 21 chromosome complement, written out as 47,
XX, + 21 or 47, XY, + 21 (Figure 2) and which is due to
nondisjunction during meiosis I in 77 percent or meiosis II in
23 percent (Figure 3).2,3 Eighty-eight percent of nondisjunction
takes place in the maternal gamete, with 8 percent arising from
nondisjunction in the paternal gamete (The Down syndrome
critical region, which is responsible for the phenotype,
Figure 1: Girls with Down syndrome

http://www.worlddownsyndromeday.org
Figure 2: Female karyotype showing 47 chromosomes with an

additional number 21, written out as 47, XX, +21
68
Down Syndrome
Figure 3: Illustration of nondisjunction in meiosis I and meiosis II. An error in maternal meiosis I accounts for 77% of trisomy 21 conceptions.
Embryos fertilized by a monsomic gamete (n-1) do not survive, whereas fertilization with a gamete containing an additional chromosome (n+1) will
result in trisomy. Courtesy of Pearson Education Inc., publishing as Benjamin Cummings.
encompasses chromosome bands 21q22.1 to q22.3.)3 It

has long been known that there exists a direct relationship
between the mothers age and the incidence of trisomy 21 due
to maternal nondisjunction.1,3
Rarely, trisomy 21 in the offspring may be the result of
gonadal mosaicism for an additional number 21 chromosome in
the ovaries of a woman whose karyotype is otherwise normal.4
In 2 to 3 percent of individuals with trisomy 21, the
additional amount of chromosome 21 material arises from an
unbalanced Robertsonian translocation involving chromosome
21 and another acrocentric chromosome, usually a number
14. In two-thirds of translocation cases, the translocation is
non-hereditary (i.e., neither parent carries the translocation
in a balanced form). When one parent of a fetus or infant
with Down syndrome is discovered to harbor a balanced
Robertsonian translocation, it is usually the mother. That is
because in such cases, the risk of a maternal translocation
carrier giving birth to a child with Down syndrome is 10
percent, whereas a paternal carrier has only a 2.5 percent risk.
The parental carrier of a balanced 21/21 translocation, on the
other hand, whether male or female, faces a 100 percent risk
of Down syndrome in his or her offspring.5
A mosaic pattern of trisomy 21 and a normal chromosome
complement, which is the result of mitotic nondisjunction
after fertilization, is seen in 2 to 4 percent of patients with
features of Down syndrome.1
About two-thirds of trisomy 21 conceptuses are spontaneously
aborted, generally during the first trimester. Confined placental
mosaicism, in which cytogenetically normal cells coexist with
trisomic cells in the placenta, has been proposed to explain fetal

survival in trisomies 13, 18, and 21.5,6
Prenatal Screening
In the United States, Canada, Great Britain, Israel and several
other countries, women are offered noninvasive prenatal
screening for fetal trisomy 21, incorporating ultrasound
measurement of the nuchal translucency at between 11 and
14 weeks of pregnancy (Figure 4) with analysis of maternal
serum biochemical markers in the first and second trimesters.
(First-trimester biochemical marker screening is performed at
10 to 14 gestational weeks, while second-trimester screening
is performed at 15 to 20 weeks). Sequential integrated
screening, as this methodology is known, will detect 95
percent of Down syndrome fetuses at a false-positive rate of
5 percent.3,7 Women, who screen positive for trisomy 21 can
then opt either for chorionic villus sampling at 10 to 14 weeks
of gestation or amniocentesis at 15 weeks or later. Screening
of cell-free fetal DNA in the maternal circulation for trisomies
21, 18 and 13, which can be performed as early as 10 weeks
gestation, may eventually replace first- and second-trimester
sequential integrated screening.
Clinical Features
The typical features of Down syndrome consist of
brachycephaly, flat facial profile, upslanted palpebral fissures,
epicanthal folds, Brushfield spots in the iris, small ears,
961
12
Miscellaneous
are infertile, and the cognitive and neuropathologic changes

of Alzheimer disease are commonly observed in patients with
Down syndrome who are past age 50.3
The most common congenital anomalies seen in this
population are the congenital heart defects diagnosed in
45 to 50 percent, with atrioventricular (AV) septal defect (also
referred to as endocardial cushion defect) and ventricular
septal defect (VSD) being the most frequently encountered
cardiovascular malformations (Table 1).3
These are discussed in greater detail in the section on
cardiac issues in children and adults with Down syndrome.
Down Syndrome and Leukemia
Figure 4: First-trimester sonogram of an increased nuchal

translucency (arrow)
small nose, fifth-finger clinodactyly, single transverse palmar

crease, sandal-gap deformity between the first and second
toes, ligamentous laxity and infantile hypotonia.
Growth and development in Down syndrome progress at
a different rate than in other children. Patients are likely to be
of shorter stature. There is an increased risk for ear infections,
conductive hearing loss, upper and lower respiratory infections
and sleep apnea during infancy and early childhood, but
patients generally outgrow these tendencies in later childhood.
Individuals with Down syndrome also face an increased risk
for refractive errors of the eye such as myopia and astigmatism,
autoimmune thyroid abnormalities, celiac disease, Hirschprung
disease and for atlantoaxial joint instability (present in 15%,
but symptomatic in only 12%).8 Adult males with trisomy 21
Childhood leukemia, with the same increased ratio of acute

lymphocytic leukemia to acute myelogenous leukemia, is
14 times more frequent in Down syndrome, however. In
addition, approximately 10 percent of neonates with trisomy
21 develop a transient leukemia or myeloproliferative
syndrome. Among Down syndrome, infants with transient
leukemia or myeloproliferative syndrome, 20 to 30 percent
will later develop acute megakaryocytic leukemia in
conjunction with somatic GATA1 transcription factor gene
mutations at a mean age of 16 months.9
Patients with Down syndrome who develop leukemia
have unique clinical features and significant differences in
treatment response and toxicity profiles compared to patients
without Down syndrome.
In children with Down syndrome and acute myeloid
leukemia, especially in the acute megakaryocytic leukemia
subtype, the cure rates are high with event-free survival rates
ranging from 80 to 100 percent. Conversely, the outcomes of
children with Down syndrome and acute lymphocytic leukemia
(ALL) are worse than among individuals without Down
Table 1
Phenotypic features of Down syndrome3
962
Characteristic
Percentage
Characteristic
Percentage
Mental retardation
100%
Small teeth
60%
Short stature
100%
Small, flattened nose
60%
Atypical fingerprints (dermatoglyphics)
90%
Clinodactyly of 5th finger
52%
Diastasis of rectus abdominis muscle
80%
Umbilical hernia
51%
Ligamentous laxity
80%
Short neck
50%
Infantile hypotonia
80%
Shortened hands
50%
Brachycephaly
75%
Congenital heart disease
45%
Smaller genitalia
75%
Single transverse palmar crease
45%
Eyelid crease
75%
Macroglossia
43%
Shortened extremities
70%
Epicanthal folds
42%
Oval palate
69%
Strabismus
40%
Low-set, small, rounded ears
60%
Brushfield spots of iris
35%
Cognitive Impairment and Alzheimer Disease

All people with Down syndrome exhibit cognitive impairment,
but one cannot predict in the newborn period how mildly or
severely affected the person might ultimately be. The average
intelligence quotient in Down syndrome is 50. Individuals
with mosaicism for trisomy 21 and a normal chromosome
complement may exhibit a more typical physical appearance
and intelligence. Early intervention, such as infant stimulation
programs and special education beginning at age 3, may
enhance development.11
Learning and Development

While children and adults with Down syndrome experience
developmental delays, they should be encouraged and given
an opportunity to develop their talents and gifts.
Although most children with Down syndrome have mild to
moderate impairments, they are emotionally more like other
children rather than being different. Early intervention services
that should be provided shortly after birth include physical,
speech and developmental therapies. Early on, depending
upon their cognitive level, they may attend their neighborhood
schools, in regular classes or in special education classes. The
children with more significant needs should be enrolled in a
more specialized program.
There are some high school graduates with Down syndrome
who participate in postsecondary education. Many adults
with Down syndrome are capable of working as packers or
assemblers in the community, while others may require a
more structured environment.
Alzheimer Disease
Nearly all persons of Down syndrome are prone to the
neuropathological pattern of Alzheimer disease by the age of 40
years and clinically manifest symptoms in their early 50s. The
clinical dementia of Alzheimer disease may be more difficult
to document, because of the underlying mental retardation and
wide variation in baseline cognitive functioning in individuals
with Down syndrome. The early stages of Alzheimer disease
may be masked depending upon the level of mental retardation.
Higher functioning patients may present with memory
impairment, temporal disorientation and reduced verbal output.
In most cases, the first symptoms are personality changes,

such as irritability or emotional lability. Individuals with more
profound mental retardation may exhibit a need for greater
assistance in activities of daily living (such as eating, dressing
and using the toilet).12
Recent studies indicate that gamma-aminobutyric acid
(GABA)A receptors are potential targets for the treatment
of both cognitive deficits and seizure activity in Alzheimer
disease and Down syndrome. There is a need for validation
of potential GABAA therapeutics to be tested and validated
in currently available Alzheimer disease and Down syndrome
mouse models and in banked postmortem human tissues.
Thus far, studies on GABAA receptors in aging, Alzheimer
disease and Down syndrome provide documentation of the
alterations of inhibitory circuitry, but also exemplify the
dynamic plasticity intrinsic to the adult brain even during
neurodegenerative disease progression.13
68
Down Syndrome
syndrome who have ALL. Children with Down syndrome and

leukemia are more prone to suffer from significant toxicity to
chemotherapy, particularly with methotrexate. The reasons for
these remarkable differences are not completely understood.
The hypothesis is that they are either due to the unique
biological characteristics of the Down syndrome leukemia
blast cell or are related to a gene dosage effect for chromosome
21-localized genes, which are overexpressed secondary to the
presence of an extra copy of chromosome 21.10
Thyroid Disorders
There is a higher prevalence of acquired hypothyroidism
in individuals with Down syndrome, which is mainly due
to autoimmunity.14 Although not so commonly seen, some
reports also indicate a slightly higher risk of hyperthyroidism
in this population as well.15
Autoimmune thyroid disease is infrequent among young
children with Down syndrome, but is common after 8 years
of age. The reported incidence of hypothyroidism in adults
varies between 3 and 54 percent, with one-third of patients with
Down syndrome developing hypothyroidism before age 25.15
Deceleration in growth associated with weight gain is a sensitive
clinical indicator of hypothyroidism. Yearly monitoring of
thyroid function and height and weight should allow for detection
of overt hypothyroidism. Looking for subtle symptoms and
signs of hypothyroidism is very important. The ultrasensitive
thyroid assays are helpful in population screening and also in
confirming the diagnosis, but are not adequate without clinical
correlation before administering medical treatment.
Hypothyroidism should be diagnosed on the basis of a
combination of the following:
1. Low thyroid stimulating hormone (TSH), with either
2. Low serum concentration of free T4
3. Marginally low concentration of free T4 combined with
symptoms (such as dry skin, constipation, weight gain
and decreased growth velocity relative to a specific Down
syndrome growth chart).
The nonspecific nature of the symptoms of mild hypo
thyroidism, the effectiveness of thyroxine administration to
children with Down syndrome and the subtle abnormalities
of thyroid function make this a more complex issue
that needs to be studied further in randomized, doubleblind controlled studies. Although prompt diagnosis and
treatment are important for the physical well-being and
mental development of these individuals, clinicians should
963
Miscellaneous
12
refrain from treating only on the basis of subtle biochemical

abnormalities, since this could lead to overmedicating these
patients.16
Cardiac Issues in Children and Adults with

Down Syndrome
Congenital heart defects are usually diagnosed early in infancy
by an echocardiogram following a physical examination. The
most common cardiac defects are: atrioventricular septal
defect, cleft mitral valve, common AV valve, left AV valve or
common AV valve regurgitation.
Cardiac catheterization is indicated when there is an
intention to repair the defects, especially an AV septal defect,
before the onset of progressive pulmonary hypertension and
irreversible pulmonary vascular disease.
There are different types of AV septal defects resulting
from morphologic variations in the five-leaflet valve seated
in the common AV orifice and based also on the relationship
of the bridging leaflets to contiguous structures.17 Usually, the
two AV valves, namely the tricuspid and the mitral valves,
have two separate annuli (fibrous rings) and lie at different
levels, with the tricuspid valve being more apical than the
mitral valve in relation to the ventricular septum. However,
when there is an AV septal defect, the five-leaflet AV valve
has a single annulus (fibrous ring) that lies at the same level
in relation to the ventricular septum (Figure 5). This valve is
seated in the common AV orifice or on separate right and left

AV orifices. This is a key finding in the diagnosis of AV septal
defect on echocardiography.
Although often described as the ostium primum type of
atrial septal defect, the interatrial communication actually
represents absence of the AV septum and is not truly an atrial
septal defect.18
The cleft in the anterior mitral valve is actually a commissure
between the left anterior and left posterior bridging leaflets,
whose margins are supported by chordae tendineae that attach
to the ventricular septum in these cases. The shunt occurs at the
atrial level when the bridging leaflets attach to the crest of the
ventricular septum. In cases where the bridging leaflets attach
to the distal end of the atrial septum, the shunt occurs at the
ventricular level. In cases where the bridging leaflets are not
attached to either septum and are free-floating, the shunts occur at
both the atrial and the ventricular levels. Hence, the relationship
of the bridging leaflets to the adjoining ventricular septum
determines the level of shunting through the AV septal defect.19
Physical Examination of the

Heart and Circulation
Inspection
The jugular venous pulsations (JVP) may exhibit a large
V-wave due to the high right atrial volume resulting from a
shunt from the left atrium, as well as volume from the left
ventricle through the AV septal defect. In patients with heart
failure, both A and V waves are elevated and so, are the mean
JVP. A right ventricular heave may be appreciated in those
with right heart volume and pressure overload.20
Palpation
The arterial pulse is usually small, with a water hammer-like
character in those with severe AV valve regurgitation due to
rapid ejection of a large stroke volume from the left ventricle.
The left ventricular impulse is prominent with an apical thrill,
when there is a large nonrestrictive atrial septal defect and
severe left AV valve regurgitation.
The right ventricular impulse is easily palpable when there
is volume and pressure overload to the right heart in those
with a complete AV septal defect.
A prominent impulse can be palpated in the second
intercostal space when the main pulmonary artery is dilated
and in the third intercostal space when the right ventricular
outflow tract is significantly dilated.
964
Figure 5: Diagrammatic representation of the apical four-chamber view

on a transthoracic echocardiogram showing the horizontal position of
the atrioventricular (AV) valves in an individual with AV septal defect.
(2 white arrows). LA= left atrium, LV= left ventricle; MV = Mitral valve;
PV = Pulmonary vein; RA= Right atrium, RV= Right ventricle; TV =
Tricuspid valve.
Percussion
Percussion may aid in delineating the cardiac borders and in
assessment of lung pathologies such as pleural effusion.
Auscultation
Electrocardiogram
The electrocardiographic features associated with AV septal
defects are often present. Frequently, there is PR prolongation
and progressive AV block that may even proceed to complete
AV block due to conduction disease. Increased length of
the right bundle branch leads to a delay in right ventricular
activation. Right ventricular hypertrophy is seen in those with
pulmonary hypertension. Atrial fibrillation and flutter may
occur more frequently with advancing age. Extreme left axis
deviation is common with Down syndrome.
Chest X-ray
The twelfth rib is usually absent or underdeveloped. On the
lateral films, a double manubrial ossification center may be
noted in the sternum.
A prominent main pulmonary artery and increased
pulmonary vascularity may be seen when there is significant
pulmonary hypertension. The right atrium is often enlarged
and the left cardiac border may be straightened, because of the
enlarged right ventricular outflow tract.
The pulmonary findings will depend upon the nature of
upper airway or alveolar disease. In patients with heart failure,
there may be pulmonary congestion and pleural effusions.
Echocardiography
68
Down Syndrome
In patients with a common AV valve, the first heart sound is

single. In unoperated patients with an ostium primum atrial
septal defect (ASD), there is fixed, wide splitting of the second
heart sound, with a pulmonary midsystolic flow murmur.
In patients with significant left AV valve regurgitation, an
apical holosystolic murmur radiating to the sternum can be
heard. The ventricular septal defect (VSD) usually generates
a systolic murmur best heard at the mid to lower left sternal
border.
between the left anterior and left posterior bridging leaflets.

The size of the ostium primum defect and the functional
status of the mitral valve (the left AV valve) or the common
AV valve, determines the hemodynamic consequences of
the atrial septal defect.21 When the ostium primum defect is
nonrestrictive, the left atrium decompresses as it receives the
flow of a mitral regurgitant jet. When the ASD is small and
restrictive, it behaves as isolated mitral regurgitation.21
Severe regurgitation is a risk factor for early development
of heart failure and increased mortality and especially occurs in
infants with complete AV canal defects. Atrial arrhythmias (atrial
fibrillation or atrial flutter) accelerate clinical deterioration.22
Chamber dimensions should be accurately recorded and
followed up on subsequent echocardiography to assess the
hemodynamic effects of the shunt, as well as the degree of
Generally, the degree of pulmonary vascular disease
depends upon the size of the ventricular septal defect and
whether it is restrictive or nonrestrictive. Patients with a
nonrestrictive VSD are at risk for early development of
pulmonary hypertension. Down syndrome per se is an
independent risk factor for pulmonary vascular disease. Some
of the contributing factors are hypoventilation induced by
upper airway abnormalities with short nasal passages, small
oral cavity and oropharynx, retrodisplacement of an enlarged
tongue (macroglossia), enlarged tonsils/adenoids, mandibular
and maxillary hypoplasia. The number of alveoli as well as
the internal surface area of the lungs are reduced and there is
a higher incidence of sleep apnea.23, 24
An incorrect estimation of the right ventricular systolic
pressure (a surrogate for pulmonary artery pressures) may be
obtained when there is contamination of blood flow from the
jet across the VSD due to a left-to-right shunt.
The gooseneck deformity classically described on cardiac
catheterization can be seen on a parasternal long-axis view. It
results from the combination of an elongated left ventricular
outflow tract, anterosuperior position of the aortic valve and
apical position of the inlet ventricular septum with the VSD.
Surgery for Heart Defects
The best diagnostic view on a transthoracic echocardiogram is

the apical four-chamber view that shows the AV septal defect,
characterized by the complete absence of the AV septum. It
also shows the position of the mitral and tricuspid annuli in
relation to the crux anatomy (at the same horizontal level as
shown in Figure 5).
Color Doppler shows the presence of an interatrial
communication (often described as an ostium primum atrial
septal defect) and a perimembranous ventricular septal defect.
The cleft mitral valve is best demonstrated in the parasternal
short-axis view at the level of the mitral valve. The cleft is
demonstrated on 2D echocardiography and the regurgitant
jet is best seen with a color Doppler jet in the commissure
A VSD will rarely close spontaneously in patients with Down

syndrome. In selected cases, the tricuspid tissue is responsible
for this phenomenon. Early surgery affords the most favorable
results. While cardiac surgery has been questioned in children
with Down syndrome based upon past surgical results or the
long-term natural history and survival of this population, more
recent data demonstrate that complete biventricular repair
yields substantial benefits.25,26 The perioperative risk factors
include higher pulmonary vascular resistance, pulmonary
edema, atelectasis, abnormal airways and lung parenchyma
requiring a longer duration of mechanical ventilation,
intensive care and hospital stay.27,28
965
Miscellaneous
12
966
Interestingly, left-sided obstruction and right ventricular

predominance, left AV valve abnormalities such as double
orifice valve and a single papillary muscle are more prevalent
in children with a normal karyotype.
In a retrospective study of 206 consecutive patients, who
underwent cardiac surgery for a complete AV septal defect over
a 10-year period, data were compared between the patients
with Down syndrome and those with a normal karyotype.
Overall mortality was 7.7 percent. Actuarial survival was 94
percent among the patients with Down syndrome versus 86
percent in the group with a normal karyotype. The presence
of unbalanced ventricles was the only independent risk factor
affecting survival in a multivariate analysis (p < 0.0001).
The need for Norwood-type surgery (12% versus 1.5%) and
pulmonary banding (22.9% versus 9.3%) was more frequent
among the patients with a normal karyotype. Cumulative
mortality was also higher (44% versus 2.9%, p = 0.0001) and
freedom from reoperation was lower (81.4% versus 94.6%,
p = 0.04) in those with a normal karyotype. The explanation
for these findings appears to be due to the higher prevalence
of abnormalities of the mitral valve (4.9% versus 1.8%) and
left ventricular outflow tract (7.3% versus 0%) in those with
complete AV septal defects and a normal karyotype.25
Subsequently, other studies have confirmed that the
presence of Down syndrome in patients with complete AV
septal defect is not a risk factor for surgical repair. Primary
repair should be performed within the first 6 months, because
of the early development of pulmonary vascular disease in
unoperated patients with Down syndrome.26 This conclusion
was based upon a retrospective analysis in 476 patients
with complete AV septal defects, who underwent surgery, of
whom 71.6 percent had Down syndrome. The significant risk
factors for 30 day mortality using multiple logistic regression
analysis were: young age at repair (less than 6 months) and
associated left AV valve anomalies. Causes of late mortality
were mainly heart failure and late pulmonary infections. In
this study, reoperation was defined as a second operation after
complete AV septal repair requiring cardiopulmonary bypass.
Over a course of 30 years, 11.1 percent of patients with Down
syndrome and 22.7 percent of those with a normal karyotype
required reoperation 7 days to 8 years after primary repair. The
main indication for reoperation was significant left AV valve
incompetence (82%). Repair of left AV valve was possible in
most cases, but 27 cases required valve replacement. Other
indications for reoperation were subaortic stenosis, recurrent
VSD and tricuspid regurgitation. Postoperative AV block led
to pacemaker implantation in 6 percent of the patients.
The safety and outcome data of cardiac surgery in adults
with Down syndrome was recently reviewed at the Mayo
Clinic (Rochester, Minnesota, USA). In this retrospective
study, 50 patients who were over the age of 18 years underwent
57 surgeries between 1969 and 2008, at a mean age of 33
years. This study showed that at an experienced center, adults
with Down syndrome can undergo cardiac surgery with a

low risk of early mortality (2%) and an acceptable morbidity,
with atrial arrhythmias occurring in 25 percent and early
postoperative pulmonary infections in 11 percent.29
Dental and Surgical Procedures

Most procedures in this population, including dental work,
often need to be performed under general anesthesia,
especially when patient cooperation is unattainable. The risk
of endocarditis is linked to the degree of left AV valve (mitral)
regurgitation. With a common AV valve, the risk is lower due
to a low-flow state.
Pulmonary artery thrombosis and emboli can occur in those
with enlarged pulmonary arteries. Deep venous thrombi are
less likely to cause paradoxical emboli, because the inferior
vena caval flow is directed to the midportion of the inter-atrial
septum (rather than the lower end, where the ostium primum
defect resides).
Transition from Childhood to Adulthood

Resources for families along the challenging path from
childhood to adulthood may aid in easing much of the stress
and anxiety that arises while caring for an individual with
Down syndrome. Information regarding local support groups
and organizations should be provided. A licensed clinical
social worker can help the family navigate through the
medical system and can furnish information regarding schools
and training programs for these children. Such programs help
provide growing children with the skills required to deal
with activities of daily living, as well as to direct them to
vocations that offer community involvement, reimbursement
and a sense of accomplishment which promotes self-esteem.
Support programs also provide an opportunity for parents
and grandparents to interact with other families in similar
circumstances.
There are several national and international organizations
which are driven by families of individuals born with Down
syndrome. Major organizations in the United States include
the National Association for Down syndrome (www.nads.org),
National Down Syndrome Congress (www.ndsccenter.org) and
the National Down Syndrome Society (www.ndss.org). These
organizations offer clinical resources and support through
networking. Additional programs offer parental workshops,
medical in-service, psychosocial services, mentoring, public
awareness, internet-based discussion forums and newsletters.
Regional and national organizations in other countries can
establish programs based on this model to offer resources
appropriate for the needs of their local population.
There are several books on the subject of Down syndrome
available online or can be obtained at a local book store or
library. One relatively recent publication which has received
Ethical Dilemmas
Pregnancy and contraception are important issues that need to
be discussed in light of the belief systems, local cultural values
and expectations of family members. There are concerns that
females with Down syndrome, based on their intellectual
development, may be challenged to care for their offspring.
The incidence of congenital heart defects is also higher in the
offspring of those born with an AV septal defect (up to nearly
15%). Pregnancy on its own can pose hemodynamic strain in
females born with congenital heart defects and, in particular,
carries a higher risk in those with pulmonary vascular disease.
Limited longevity and other co-morbidities such as early onset
of Alzheimer disease may also limit the ability of women with
Down syndrome to care for their offspring, thus adding to the
list of ethical dilemmas in allowing them to procreate.
Paradoxically, the life expectancy of those with Down
syndrome without congenital heart defects (CHD) is
significantly shorter than in those born with CHD.30
Conclusion
Advances in pediatric, medical and surgical care, along with
deinstitutionalization, have improved the survival of patients
with Down syndrome.
Most children with Down syndrome have health com
plications beyond the usual childhood illnesses (Box 1).
Box 1: Risk-factors for morbidity and mortality
in Down syndrome
Congenital heart defects
Respiratory tract infections
Gastrointestinal tract congenital defects
Hepatitis B virus
Hematological issues: leukemia
Endocrine disorders: hypothyroidism
Immunological disorders
Around 45 to 50 percent have congenital heart defects. It

is imperative that an echocardiogram be performed on all
newborns with Down syndrome in order to identify any serious
cardiac problems that might be present. Some of the heart
conditions require surgery, while others only require careful
monitoring. These patients also have a higher incidence of
comorbidities such as upper and lower respiratory infections,
impaired vision, hearing problems and thyroid disorders,
among other medical conditions.
Recommendations for the care of the infant and child
with Down syndrome include an echocardiogram in the
immediate newborn period; referral to an ophthalmologist
and audiologist by age 6 months and free T4 (thyroxine) as
well as TSH (thyrotropin) for hypothyroidism at birth, at age 1
year and every other year thereafter. The American Academy
of Pediatrics no longer advises routine lateral cervical spine
X-rays in flexion and extension at the ages of 3 to 5 years,
12 years, and 18 years for the diagnosis of atlantoaxial
instability.10
Additional information for clinicians about the manage
ment of infants and children with Down syndrome is available
in an American Academy of Pediatrics publication, Clinical
ReportHealth Supervision for Children with Down
Syndrome.11
In adults, routine follow-up with an internist or family
practitioner and a cardiologist should be performed
annually in stable patients. In medically stable individuals,
aside from a history and clinical examination, annual tests
should include laboratory studies to assess the complete
blood count (to follow the white blood count), thyroid
function, electrolytes and creatinine (since individuals
with AV valve regurgitation may be taking angiotensinconverting-enzyme inhibitors). They should be reminded
about maintaining adequate hydration, eating a balanced
diet and performing regular exercise. Information should
be provided about routine dental/skin care and bacterial
endocarditis prophylaxis before dental cleaning. In patients
over 35 years of age, screening for Alzheimer disease should
be performed.
Unoperated adults who develop pulmonary hypertension
with or without cyanotic congenital heart defects need
additional medical management.
Appropriate medical and surgical care can lead to an
improved quality of life in most children and adults with
Down syndrome. Currently, the average life expectancy
of individuals with Down syndrome is 55 years, but may
increase with early surgical intervention and medical
care.
Happiness is nothing more than good health and a bad
memory.
Albert Schweitzer
Premature Alzheimer disease
68
Down Syndrome
good press is The Down Syndrome Transition Handbook:

Charting Your Childs Course to Adulthood, by Jo Ann
Simons, published by Woodbine House (www.woodbinehouse.
com) in 2010.
In the clinics, transition should be made from pediatrics to
adult services by the age of 21 years, since there are acquired
medical conditions that require management by an internist
or a family practitioner. For females with Down syndrome,
the transition may start earlier, since there is a need to discuss
contraception and sterilization with the patient and her family
at menarche and implement these actions following informed
consent from the parents or guardians.
967
Miscellaneous
12
968
REFERENCES
1. Jorde LB, Carey JC, Bamshad MJ. Medical genetics. 4th
edition. Philadelphia: Mosby; 2010.
2. Antonarakis SE, Petersen MB, McInnis MG, et al. The meiotic
stage of nondisjunction in trisomy 21: determination by using
DNA polymorphisms. Am J Hum Genet. 1992;50:544-50.
3. Wikipedia. Down syndrome. [Internet] [2011 July 23] [cited
23 July 2011]. Available from: http://en.wikipedia.org/wiki/
Down_syndrome.
4. Strauss JF, Barbieri RL. Yen and Jaffes reproductive
endocrinology. 6th edition. Philadelphia: Saunders; 2009.
5. Hulten MA, Jonasson, Nordgren A, et al. Germinal and
somatic trisomy 21 mosaicism: how common is it, what are
the implications for individual carriers and how does it come
about? Curr Genomics. 2010;11:409-19.
6. Kalousek DK, Barrett IJ, McGillivray BC. Placental mosaicism
and intrauterine survival of trisomies 13 and 18. Am J Hum
Genet. 1989;44:338-43.
7. MacRae AR, Chodirker BN, Davies GA, et al. Second
and first trimester estimation of risk for Down syndrome:
implementation and performance in the SAFER study. Prenat
Diagn. 2010;30:459-66.
8. Pueschel SM, Scola FH. Atlantoaxial instability in individuals
with Down syndrome: epidemiologic, radiographic, and
clinical studies. Pediatrics. 1987;80:555-60.
9. Xavier AC, Ge Y, Taub J. Unique clinical and biological
features of leukemia in Down syndrome children. Expert Rev
Hematol. 2010;3:175-86.
10. Xavier AC, Taub JW. Acute leukemia in children with Down
syndrome. Haematologica. 2010;95:1043-5.
11. American Academy of Pediatrics Committee on Genetics.
Clinical reporthealth supervision for children with Down
syndrome. [Internet] [2011 July 21] [cited 29 July 2011].
Available from: http://pediatrics.aappublications.org/content/
early/2011/07/21/peds.2011-1605.full.pdf.
12. Lai F, Williams F. A prospective study of Alzheimers disease
in Down syndrome. Arch Neurol. 1989;46:849-53.
13. Rissman RA, Mobley WC. Implications for treatment: GABAA
receptors in aging, Down syndrome and Alzheimers disease. J
Neurochem. 2011;117:613-22.
14. Kennedy RL, Jones TH, Cuckle HS. Downs syndrome and the
thyroid. Clin Endocrin. 1992;37:471-6.
15. Karlsson B, Gustafsson J, Hedov G, et al. Thyroid dysfunction

in Down syndrome: relation to age and thyroid autoimmunity.
Arch Dis Child. 1998;79:242-5.
16. Van Vliet G. How often should we screen children with Downs
syndrome for hypothyroidism? Arch Dis Child. 2005;90:557-58.
17. Anderson RH. New light on morphogenesis of atrioventricular
septal defects. Int J Cardiol. 1988;18:79.
18. Gutgesell HP, Huhta JC. Cardiac septation in atrioventricular
canal defect. J Am Coll Cardiol. 1986;8:1421-4.
19. Edwards JE. The problem of mitral insufficiency caused
by accessory chordae tendinae in persistent common
atrioventricular canal. Mayo Clin Proc. 1960;35:299-305.
20. Brandenberg RO, DuShane JW. Clinical features of persistent
common atrioventricular canal. Mayo Clin Proc. 1956;31:50913.
21. Perloff JK. The Clinical Recognition of Congenital Heart Disease.
6th edition. Philadelphia: WB Saunders Co; 2012. p.256.
22. Somerville J. Ostium primum defect: factors causing
deterioration in the natural history. Br Heart J. 1965;27:413-9.
23. Clapp S, Perry BL, Farooki ZQ, et al. Downs syndrome,
complete atrioventricular canal, and pulmonary vascular
obstructive disease. J Thorac Cardiovasc Surg. 1990;100:115-21.
24. Suzuki K, Yamaki S, Mimori S, et al. Pulmonary vascular
disease in Downs syndrome with complete atrioventricular
septal defect. Am J Cardiol. 2000;86:434-7.
25. Formigari R, Di Donato RM, Gargiulo G, et al. Better surgical
prognosis for patients with complete atrioventricular septal
defect and Downs syndrome. Ann Thorac Surg. 2004;78:
666-72.
26. Lange R, Guenther T, Busch R, et al. The presence of Down
syndrome is not a risk factor in complete atrioventricular septal
defect repair. J Thorac Cardiovasc Surg. 2007;134:304-10.
27. Morray JP, MacGillivray R, Duker G. Increased perioperative
risk following repair of congenital heart disease in Downs
syndrome. Anesthesiology. 1986;65:221-4.
28. Rizzoli G, Mazzucco A, Maizza F, et al. Does Down syndrome
affect prognosis of surgically managed atrioventricular canal
defects? J Thorac Cardiovasc Surg. 1992;104:945-53.
29. Majdalany DS, Burkhart HM, Connolly HM, et al. Adults with
Down syndrome: safety and long-term outcome of cardiac
operation. Congenit Heart Dis. 2010;5:38-43.
30. Baird, PA, Sadovnick AD. Life expectancy in Down syndrome.
J Pediatr. 1987;110:849-54.
Sec t i on
13
General Issues
C hapter
69
Prevention of
Sunitha Maheshwari, Kiran VS
One constant question faced by a Pediatric Cardiologist, while

counseling parents of a child with congenital heart disease
(CHD) is Will this happen again? Is a similar condition going
to affect my next child? What can I do to prevent it? A simple
question with no easy answers. In this chapter, our objective
would be to learn the answers for this pertinent question to the
best of current knowledge.
The difficulty in answering this question is largely because
of lacunae in identifying the actual etiology. The possible
cause of the defect may lie anywhere from genes to drugs or
diseases affecting the embryogenesis. The diagnostic advances
achieved to date still fall short of unearthing the precise cause
of congenital heart diseases in all cases. Some of the tests
are so sophisticated that they are yet to come out of research
laboratories! Added to the woes are lack of trustworthy
regional epidemiological data to understand the interaction
between various possible causes and how they work in tandem
or independently. Hence, the progress made thus far has not
achieved primordial or primary prevention. Yet, secondary
prevention has progressed to noteworthy levels.
Modes of prevention
The broad categorization of prevention can be summarized as:
1. Primary prevention: Modification/abolishment of risk
factors, e.g. vaccines or health promotion via exercise,
vitamins.
2. Secondary prevention: Recognition of subclinical disease
and early treatment of initial clinical manifestations to
prevent progression of disease.
3. Tertiary prevention: Limiting the disability to the least
possible and aiding the recovery from complications, e.g.
rehabilitation efforts.
Some of the known causes of CHD are listed below:1
1. Diabetes.
2. Rubella.
3. Febrile illnesses, such as influenza.
4. Maternal phenylketonuria (PKU).

5. Obesity.
6. Seizure disorders and seizure medications.
7. Human immunodeficiency virus (HIV).
8. Retinoic acid and vitamin A congeners.
9. Thalidomide and sulfa drugs.
10. Caffeine and analogues.
11. Alcohol.
12. Smoking.
13. Race/ethnicity.
Some of the preventable causes of CHD will be discussed in
more detail below.
Maternal Diabetes Mellitus2,3,4

Preexisting and gestational diabetes, either type 1 or 2, has
established its teratogenic role. Among the cardiac problems
associated with diabetes are:
1. Conotruncal anomalies: Outflow defects with normally
related great arteries.
2. Complex d-transposition of great arteries.
3. Complex heterotaxy: Laterality defects and situs inversus/
ambiguous.
4. Hypertrophic cardiomyopathy associated with diabetes in
mother is usually non-obstructive. Even the obstructive
variants rarely persist.
The relative risk for cardiac defects is estimated to be 4
to 5 times. However, the relative risk would vary for specific
heart defects. It would be different, if the heart defects are
associated with extracardiac anomalies.5,6
Prevention
Gestational diabetes is a challenge for both diagnosis and
management, as the presentation of patient can be anytime
during pregnancy. Early diagnosis and treatment is the best
available option at present. Strict glycemic control before
General Issues
13
conception and during the course of pregnancy has been

shown to reduce the risk of diabetic embryopathy significantly.
Meticulous use of fetal echocardiography can detect the highrisk newborns and a predelivery management plan can be
enumerated for better overall outcome.1,7
In developing countries, it is not uncommon to uncover
the diabetic status of mother after the delivery of baby with
typical features of an infant of diabetic mother. Rehabilitative
measures for such children include a tertiary level neonatal
intensive care unit (NICU), early recognition of features of
diabetic embryopathy and appropriate management. The
diabetic status of the mother needs to be reevaluated and the
risk for subsequent progeny needs to be informed to both the
parents and caretakers.
Congenital Rubella Syndrome

The credit for the immunization drive in prepubescent girls
against rubella and the subsequent success in large-scale
control of rubella embryopathy in the developed countries
should go to the studies published in 1941 by Gregg et al.8,9
The risk of rubella embryopathy can be virtually eliminated
by ensuring that women of childbearing age are immunized
against rubella.10
Despite the vaccination success in the west, developing
countries still come across rubella mediated teratogenicity
(Figures 1A and B). The most common cardiac associations
of congenital rubella syndrome are pulmonic stenosis (PS)
972
(subvalvar, valvar and supravalvar variants) and patent ductus

arteriosus (PDA). Uncommonly, tetralogy of Fallot (TOF) is
included in this list by some studies.11
Prevention
Rubella confers a very good opportunity to provide primordial
prevention. It is one case, wherein immunizing the mother can
protect the baby completely, eliminating the root cause of the
problem.
Irrespective of the immunization status, every pregnant
woman should be advised to maintain good hygiene and to
avoid contact with possible viral infections if possible.
Rubella has subtle features. The rash may be extremely
difficult to identify in dark-skinned people. The fever can
be so mild that it may go unnoticed. Whenever the antenatal
ultrasound scans pick up any findings suggestive of possible
rubella infection, high alert should be sounded. Since PDA
is normal and PS cannot be picked up well in the fetal
echocardiography, the primary source of confirming the
cardiac findings is the early postdelivery echocardiography.
Since congenital rubella syndrome has multiorgan
involvement, teamwork becomes essential with the pedia
trician or geneticist sheet-anchoring the management. After
the diagnosis and correction of problems, rehabilitation is
required mainly for non-cardiac issues.
The rubella vaccine is freely available and the target age
group can be identified easily. It is time to create awareness on
B
Figures 1A and B: Rubella syndrome baby: A. With bilateral congenital cataract with microphthalmia;
B. With bilateral absent eyelids
Maternal Phenylketonuria
Maternal Phenylketonuria (PKU) is relatively lesser known
in developing countries, largely due to our own inability to
diagnose this condition and the lack of interdepartmental
coordination among the superspecialists. However, the
problem is well recognized and studied in the Western
literature.
The main organ involved is the brain. Pregnant women with
high levels of circulating phenylalanine in blood are likely
to have children with microcephaly and mental retardation.
Cardiac lesions associated with maternal PKU are; left heart
obstructive lesions, septal defects and TOF. One report adds
patent arterial duct and single ventricle to the list. The relative
risk is estimated to be at least 6 to 15 fold high. Levy et al
in 2001 estimated that the absolute risk for cardiac defects is
about 14 percent for uncontrolled maternal PKU.14
Prevention
Since most of the prospective mothers are already diagnosed,
there are chances of primordial prevention. If the biochemical
control is poor, pregnancy can be hazardous and counseling
can be attempted on this issue. Avoiding pregnancy if the
medications are suboptimal or the compliance to therapy is
less than adequate may prevent future catastrophe.15
The biochemical variation in the level of phenylalanine
with pregnancy is well known. However, studies have proved
that with rigid diet control and maintenance of near normal
levels before conception and during the course of pregnancy,
the additional risk involved can be nullified.16
Obesity
Obesity is one condition where the holistic approach to
health by prevention comes into play. Whether the underlying
problem caused obesity or vice versa is a matter of pure
theoretical interest. The more important issue is the prevention
of risk factors causing obesity and obesity-related problems.
At least 2 fold to 6.5 fold risk of cardiac defects has been
documented in offsprings of obese women in different ethnic
populations.17,18
control. The non-obese members in the family with the risk

of obesity should take adequate measures and appropriate
medical advice to avoid becoming obese.
Achieving a healthy lifestyle with disciplined diet and
exercise in tandem with appropriate medical advice will
help in ensuring the health of offspring. Early diagnosis can
be offered to the pregnant with screening for causes like
gestational diabetes.
The period of pregnancy can be utilized to educate the
future mother on the overall advantages of healthy lifestyles.
Epilepsy and Antiepileptic Medications

Increased risk of congenital heart defects and congenital
anomalies in general has been noticed in the offsprings of
women with epilepsy. However, differentiating the effects of
epilepsy per se from the teratogenic effects of the antiepileptic
drugs is a difficult task. Some of the drugs are known to
cause direct teratogenicity, whereas others act through
folate metabolism to cause indirect teratogenic effects. The
well defined fetal hydantoin syndrome has cardiac defects.
Ventricular septal defect (VSD) and atrial septal defects
(ASD), coarctation of the aorta and PDA are the most
frequent.19
69
Prevention of Congenital Heart Diseases
elimination of this condition and it is essential for all medical

personel to be a part of the global drive for eradication of
rubella program.12,13
Prevention
Optimal medication and good control of seizure activity is
the cornerstone of prevention. Women with epilepsy in childbearing age should have a clear discussion with the neurologist
and pharmacist on the correct choice of medication. Newer
generation antiepileptics gabapentin, topiramate, lamotrigine
have proven to be much safer and more effective.20
Human Immunodeficiency Virus Infection

Vertical transmission of human immunodeficiency virus (HIV)
infection from mothers to their offspring is well established.
Studies have demonstrated that children infected with HIV-1
in utero end up with increased risk of dilated cardiomyopathy
and disproportionate left ventricular hypertrophy. This is
associated with a lower ejection fraction by inadequate left
ventricular (LV) fractional shortening. However, no risk for
structural cardiac malformations has been found with maternal
HIV infection.21
Prevention
Prevention
Obesity gives ample chances to the preventive medicine
specialist to drive the important need of maintaining a healthy
life style.
Families prone for obesity should undergo a detailed
evaluation to determine the secondary causes. The problem
should be tackled with clear understanding of the benefits of
There is equivocal evidence on maternal HIV viral load and

fetal cardiac abnormalities. Nevertheless, it is prudent to
advice every pregnant woman to take proper care of overall
well being and to strictly adhere to the standards of care and
medication with correct execution of peripartum protocols of
management. The treating HIV team can be of great help in
early recognition of problems in the newborn.22
973
General Issues
13
Exposure to Drugs and Chemicals

Any detailed analysis of this vast subject is out of purview in
this chapter. Only those drugs which are commonly used or
those having a definite association with cardiac teratogenicity
or those with controversy surrounding it are discussed. The
interested reader can access standard textbooks in this subject
or the references quoted for more detailed descriptions.
Retinoic Acid and Vitamin A Congeners

Cardiac defects are among the plethora of congenital defects
that are associated with maternal exposure of retinoic acid
and vitamin A congeners. Conotruncal anomalies have been
consistently associated. Some molecules of this class are
known to be retained by the body for extremely long durations.
One report on etretinate demonstrated its teratogenic potential
even 45 months after stopping the drug prior to conception.23
However, barring these long acting congeners, most of
the regular vitamin A preparations do not appear to possess
teratogenic potential once discontinued before conception. 24
Although claimed to be safe in usual doses, data on teratogenicity of topical preparations with tretinoin is insufficient
to make any definite statement.
Prevention
Women in the childbearing age group are ideally kept away

from any congeners of vitamin A. It may be prudent to avoid
topical applications also. All women in the childbearing age
or those planning pregnancy, should be questioned on their
routine use of common medicinal preparations, including
vitamin supplements. Family physicians and obstetricians
should take charge of putting these questions and data into
their list.
In view of conflicting results in large studies, metronidazole

is still not cleared of its stigma in causation of congenital
heart defects. Hence, it may be prudent to avoid the systemic
use of this agent during periconceptional period and
early pregnancy. The risk of antifolate related congenital
anomalies reduce with the supplementation of folic acid in
the periconceptional period. Hence, apart from education,
the general physicians and obstetricians should avoid using
trimethoprim-sulfamethoxazole in the periconceptional period.
Also, this is an opportunity to promote the universal use
of periconceptional folate supplementation in women of
childbearing age group.
Antibiotics and Antibacterials
Antifungals
Although the 1979 study by Rothman et al25 speculated about

the association between maternal ampicillin treatment (in
authors own words, about the time pregnancy began) and
transposition of great arteries in the newborns, subsequent
studies with similar design did not prove the association.26 This
led to the design of a separate case-control study, which also
failed to show any association.27 Finally, a team of Hungarian
researchers decided to put an end to the turmoil with a large
population based case-control study with maternal use of
ampicillin in the first trimester. A total of 4,468 cardiovascular
malformations were analysed and no association was found
with maternal ampicillin use.28
The ampicillin fiasco led to another systematic study:
This time with penicillin. Although no association was
found between the use of penicillin and congenital cardiac
Studies have centerd on the most commonly used antifungal

agent: Fluconazole. Side effects of this medicine show dose
dependence as does the teratogenicity. Single oral dose
and median doses of 200 mg in the first trimester have not
shown any increase in the frequency of congenital anomalies.
However, high dose fluconazole used in first trimester for the
treatment of fungal meningitis have shown to have resulted
in congenital anomalies including heart defects in the
offspring.34,35
Prevention
974
malformations even in large studies, a few Danish researchers

decided to do a systematic population-based record linkage
study. They evaluated the frequency of congenital heart
diseases with maternal use of penicillin during the first
trimester in 1886 and found that the association was not
significantly different from the non-users.29
Another drug of frequent use is maternal vaginal
metronidazole. Meta-analysis done on the use of this agent in
early pregnancy did not reveal any increase in the incidence
of congenital heart defects.30 However, the BaltimoreWashington Infant Study showed association between the
maternal use of metronidazole during pregnancy and increased
risk of outflow tract anomalies with normally related great
arteries and an increased risk of membranous VSDs.31
Agents interfering with folate metabolism are known
teratogens. A large case-control study showed association
between maternal use of trimethoprim-sulfamethoxazole
during the first trimester and congenital heart defects.32
Similar findings were seen in a case-control surveillance of
congenital abnormalities study from Hungarian researchers.33
Prevention
Although the evidence has not been very strong, a potential
dose-related teratogenicity exists with the maternal use of
fluconazole in the first trimester. Hence, the use of medication
Antiviral Agents
With increase in the spread of HIV, teratogenicity related
to antiretroviral drugs has been debatable. In one study, a
surprising association of increased incidence of congenital
heart defects was seen in pregnant women receiving
zidovudine in second and third trimesters in contrast to those
receiving in the first trimester. This was against the general
acceptance of teratogenic mechanisms. This findings led to
development of the Antiretroviral Pregnancy Registry. The
registry has shown no increase in teratogenicity among the
women receiving zidovudine in the second and third trimester
of pregnancy.36
Non-Steroidal Anti-Inflammatory Drugs

A study by Ericson and Kallen in 2001 showed the association
between the maternal use of non-steroidal anti-inflammatory
drugs (NSAIDs) in the first trimester and cardiac defects.
These defects ranged from simple bicuspid aortic valves to
membranous VSDs to lesions as complex as d-transposition
of the great arteries.37
The use of NSAIDs 48 to 72 hours prior to delivery has
been associated with persistent pulmonary hypertension and
premature closure of arterial duct in newborns.38,39
Prevention
childbearing age. If inadvertently exposed, they should be

offered fetal echocardiography and complete evaluation of
the newborn for early recognition and management of
problems.
Lithium
For a long time, the association of maternal ingestion of oral
lithium carbonate during pregnancy and congenital heart
defects (especially, Ebsteins anomaly) was made popular.41,42
However, in 1993, a large case-control study by Hungarian
researchers involving 10,698 children with congenital
anomalies did not show any association of maternal lithium
ingestion and Ebsteins anomaly.43
This speculation led to the designing of more systematic
studies including metaanalysis which finally ruled out the
cardiac teratogenic nature of lithium. As of now, the concept
of maternal lithium ingestion as a cause of Ebsteins anomaly
in offspring has no validation.44
Maternal Alcohol Ingestion

The first ever description of fetal alcohol syndrome was by
Jones and Smith in 1973. This led to the documentation of
cardiac teratogenicity by alcohol in several studies.45
A Finnish study published in 1991 demonstrated the
association of maternal alcohol ingestion and increased
incidence of VSDs in the offspring.46 This was also noticed
in the Baltimore-Washington Infant Study31 and another
Spanish study, but only with heavy consumption of alcohol
in both.47
Other than paracetamol, none of the agents are free from

teratogenic blame in the literature. Hence, whenever possible,
it is advisable to limit the choice of analgesia to paracetamol.
If any other agent is used inadvertently, then follow-up for
its teratogenicity is to be advocated for early diagnosis and
appropriate management.
Prevention
Thalidomide
Maternal Cocaine and Marijuana Ingestion
It was to the credit of Helen Taussig that thalidomide was

identified as a teratogen. Cardiac embryopathy caused by
thalidomide can range from simple septal defects to complex
conotruncal anomalies. It is absolutely contraindicated during
pregnancy, with one report showing its teratogenic potential
even with a single dose of 50 mg capsule during the critical
period of gestation.40
The can of worms on the maternal use of cocaine and cardiac

teratogenicity was brought up by Shepard et al in 1991.
The author contemplated coronary thrombosis in the fetal
coronaries as the possible cause of single ventricle.48
In a study done via neonatal toxicology screening data,
Lipshultz and coworkers found a higher incidence of peripheral
pulmonic stenosis associated with maternal cocaine abuse.49
Heterotaxy syndromes have also been associated with cocaine
consumption during pregnancy.50
Maternal marijuana use has been linked to an increased
risk of membranous VSD, Ebsteins anomaly and conotruncal
defects in various studies.31,51,52
Prevention
Avoiding the drug is the only prevention that can be offered.
It is advisable to avoid this drug totally by all women of
69
should be tailored to the risk-benefit ratio of individual patient.

It may be advisable to avoid the medicine, if possible during
pregnancy.
Cardiac teratogenicity is a part of the maternal alcohol

ingestion complex. A team effort involving medical personnel
and professional counsellors should be stressed to tackle this
multifaceted problem in the periconceptional period.
975
General Issues
13
Prevention
Maternal cocaine abuse needs wider attention and introspection
than evaluation of congenital heart defects alone. However,
explanation of fetal implications would form a good impetus
for those who are addicted and have willingness to quit, but are
unable to for various reasons. A combined approach centerd
on a professional counsellor and deaddiction team would be
of great help.
Maternal Tobacco Consumption

Studies analysing the association of tobacco and cardiac terato
genicity started in the early 70s. However, systematization
of such studies occurred only in the late 90s. Atrial septal
defects, atrioventricular septal defects and TOF have been
noticed with maternal smoking.53 L-transposition of great
arteries and single ventricle have also been suspected to have
an increased incidence.54,55
Prevention
Maternal tobacco use forms a significant cohort. Due to
plethora of brands and forms, it is difficult to trace the
nicotine based denominator accurately. Yet, it should not be a
deterrent for prevention. There is no safety zone in this issue.
Campaigns should be offered for the entire population at risk,
irrespective of the quantum of tobacco consumed. This also
involves avoiding passive smoking and a combined approach
involving all family members.
Social and Epidemiological Issues

Maternal Age
Elderly primigravida aged more than 30 years has been linked
to various congenital cardiac defects in large epidemiological
studies. The Baltimore-Washington Infant study31 showed
increased risk for transposition of great arteries, Ebsteins
anomaly, bicuspid aortic valve and ASD. Also, young maternal
age (< 20 years) has been associated with increased risk of
tricuspid atresia. Similar findings were noted in Metropolitan
Atlanta Congenital Defects Program from 1968 to 2000 which
studied non-chromosomal birth defects.56
Paternal Age
976
Murdoch et al57 in 1972 had shown the association of paternal

age with Marfan syndrome and thereby, cardiac defects. In
1975, Vogel58 had shown an association between parental age
with achondroplasia and Apert syndrome. In 1986, Lian et al59
showed that the new dominant mutations were more common
in older fathers. Olshan et al60 evaluated the association
between increased paternal age and cardiac defects in the

offspring and found an increased risk for ASD, VSD and PDA.
Similarly, for paternal age of less than 20 years, increased risk
was found for VSD and possibly for ASD.
PRINCIPLES AND PRACTICAL ASPECTS OF PREVENTION

Prevention should aim at minimizing the exposure to potential
teratogenic agents right from the prenatal period. In developing
economies with care towards birth control, it becomes essential
to educate the prospective parents towards any issue capable
of affecting the pregnancy and outcome. The topics to be
covered include lifestyle, habits, occupation, physical activity,
nutrition, family history, prevailing medical condition and
drug exposure and so on. A questionnaire based approach may
be helpful for both prospective parents and to the physician for
research purpose.
The prospective mother would require detailed interview
and evaluation. It would be ideal to get screened for diabetes,
phenylketonuria and discuss past rubella exposure/ vaccination.
Appropriate management of phenylketonuria and diabetes
mellitus in expert guidance cannot be overemphasized. It might
be advantageous to avoid contact with people having influenza
or rubella-like symptoms. Occupational or casual exposure to
potentially toxic organic solvents should be avoided. Use of
folic acid should be encouraged in periconceptional period.
Use of any medication including over-the-counter drugs
should be enquired and discussed.
Preconceptual use of folic acid, i.e. 400 micrograms per day
3 months before pregnancy has been demonstrated to reduce the
incidence of congenital heart disease. Meticulous use of fetal
echocardiography at 16 to 18 weeks of gestation can be very
useful in decision making and secondary prevention. Although
there are specific indications for fetal echocardiography put
forward by American Society of Echocardiography, experts
are in consensus that the indications can be custom made
for specific situation. Hence, when in doubt or when the
teratogenic potential of some exposed agent is not specified, it
may be worthwhile getting fetal echocardiography.
FUTURE
With all said and done, there is lot said than done. Our
understanding of issues capable of being teratogenic is still
primitive. Research in this regard is highly limited. There are
methodological issues interfering with research. Till date, no
reliable evidence based studies are done. Hence, there is lack
of adequate database to enumerate preventive strategies as of
now.
However, with improvement in technology, better methods
of acquiring and compiling data and large multicenter
involvement, the future appears much brighter. Large casecontrol studies have been designed and evaluated for learning
The superior doctor prevents sickness; The mediocre doctor

attends to impending sickness; The inferior doctor treats
actual sickness.
Chinese Proverb
Acknowledgment
We wish to thank Dr I B Vijayalakshmi, Professor of Pediatric
Cardiology, for providing all the images.
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69
more about birth defects. Such studies will help us in

understanding the potential risk factors and teratogens along
with the risk involved in particular subgroups of population.61
A few large studies have been designed specifically to
study the contribution from genetic and environmental
factors along with gene-environment interactions. Such large
prospective studies will provide adequate opportunities for
evaluating the impact of teratogens on common heart defects,
their developmental outcomes, associated anomalies and their
impact on adulthood and subsequent progeny.62
To end, it may be prudent to list the preventive strategies63
for now. Any woman of childbearing age and a prospective
mother should follow the following six-point agenda:
1. Take 400 mcg folic acid every day for 3 months before
pregnancy.
2. Consult a qualified medical specialist for pericon
ceptional care, including screening and management of
phenylketonuria and diabetes mellitus.
3. Get immunized against rubella.
4. Discuss the use of any medication, including over-thecounter drugs with their doctor for possible known
teratogenicity and fetal echocardiography.
5. Avoid contact with people with flu or any febrile illness
and avoid exposure to organic solvents.
6. If in doubt, get a fetal echocardiogram at 16 to 18 weeks of
gestation
977
General Issues
13
978
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maternal use of Bendectin and other drugs in early pregnancy.
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zidovudine use and congenital anomalies in a medicaid
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37. Ericson A, Kallen BA. Nonsteroidal anti-inflammatory drugs
in early pregnancy. Reprod Toxicol. 2001;15:371-5.
38. Premature closure of the fetal ductus arteriosus after maternal
use of non-steroidal anti-inflammatory drugs: Adverse
Drug Reactions Advisory Committee. Med J Aust. 1998;169:
270-1.
39. Zenker M, Klinge J, Kruger C, et al. Severe pulmonary
hypertension in a neonate caused by premature closure of the
ductus arteriosus following maternal treatment with diclofenac:
a case report. J Perinat Med. 1998;26:231-4.
40. Smithells RW, Newman CG. Recognition of thalidomide
defects. J Med Genet. 1992;29:76-23.
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593-7.
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43.
Czeizel AE. Epidemiological studies of congenital
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44. Warner JP. Evidence-based psychopharmacology, 3: assessing
evidence of harm: what are the teratogenic effects of lithium
carbonate? J Psychopharmacol. 2000;14:77-80.
45. Clarren SK, Smith DW. The fetal alcohol syndrome. N Engl J
Med. 1978;298:1063-7.
46. Tikkanen J, Heinonen OP. Risk factors for ventricular septal
defect in Finland. Public Health. 1991;105:99-112.
47. Martinez-Frias ML, Bermejo E, Rodriguez-Pinilla E, et al. Risk

for congenital anomalies associated with different sporadic
and daily doses of alcohol consumption during pregnancy:
a case-control study. Birth Defects Res A Clin Mol Teratol.
2004;70:194-200.
48. Shepard TH, Fantel AG, Kapur RP. Fetal coronary thrombosis as
a cause of single ventricular heart. Teratology. 1991;43:113-7.
49. Lipshultz SE, Frassica JJ, Orav EJ. Cardiovascular abnormalities in infants prenatally exposed to cocaine. J Pediatr.
1991;118:44-51.
50. Shaw GM, Malcoe LH, Lammer EJ, et al. Maternal use of
cocaine during pregnancy and congenital cardiac anomalies. J
Pediatr. 1991;118:167-8.
51. Williams LJ, Correa A, Rasmussen S. Maternal lifestyle factors
and risk for ventricular septal defects. Birth Defects Res A Clin
Mol Teratol. 2004;70:59-64.
52. Adams MM, Mulinare J, Dooley K. Risk factors for conotruncal
cardiac defects in Atlanta. J Am Coll Cardiol. 1989;14:432-42.
53. Torfs CP, Christianson RE. Maternal risk factors and
major associated defects in infants with Down syndrome.
Epidemiology. 1999;10:264-70.

54. Kuehl KS, Loffredo CA. Population-based study of
l-transposition of the great arteries: possible associations with
environmental factors. Birth Defects Res A Clin Mol Teratol.
2003;67:162-7.
55. Steinberger EK, Ferencz C, Loffredo CA. Infants with single
ventricle: a population-based epidemiological study. Teratology. 2002;65:106-15.
56. Reefhuis J, Honein MA. Maternal age and non-chromosomal
birth defects, Atlanta19682000: teenager or thirtysomething, who is at risk? Birth Defects Res A Clin Mol
Teratol. 2004;70:572-9.
57. Murdoch JL, Walker BA, McKusick VA. Parental age effects
on the occurrence of new mutations for the Marfan syndrome.
Ann Hum Genet. 1972;35:331-6.
58. Vogel F, Rathenberg R. Spontaneous mutation in man. Adv
Hum Genet. 1975;5:223-318.
59. Lian ZH, Zack MM, Erickson JD. Paternal age and the
occurrence of birth defects. Am J Hum Genet. 1986;39:648-60.
60. Olshan AF, Schnitzer PG, Baird PA. Paternal age and the risk
of congenital heart defects. Teratology. 1994;50:80-4.
61. Yoon PW, Rasmussen SA, Lynberg MC, et al. The National
Birth Defects Prevention Study. Public Health Rep.
2001;116(suppl 1):32- 40.
62. Branum AM, Collman GW, Correa A, et al. for the National
Childrens Study Interagency Coordinating Committee, Centers
for Disease Control and Prevention; National Childrens Study
Interagency Coordinating Committee, National Institute
of Environmental Health Sciences; National Childrens
Study Interagency Coordinating Committee, National
Institute of Child Health and Human Development; National
Childrens Study Interagency Coordinating Committee, US
Environmental Protection Agency. The National Childrens
Study of environmental effects on child health and development.
Environ Health Perspect. 2003;111:642-6.
factors and congenital heart defects: current knowledge: a
scientific statement from the American Heart Association
Council on Cardiovascular Disease in the Young. Circulation.
2007;115:2995-3014.
C hapter
70
Oral Health Care in Children and

Adolescents with Congenital
Heart Diseases
Sphoorthi Anup Belludi
Introduction
Congenital cardiac disease is one of the most common
developmental anomalies in children and affects
approximately 8:1,000 live births. Children with complex
anomalies constitute approximately one-third of all children
with congenital heart disease (CHD).1,2 Pediatric cardiology
has undergone extensive evolution during recent decades.
Increased detection, diagnosis and the introduction of
new surgical and anesthetic techniques together with the
development of special pediatric intensive care units have
improved the treatment and care of patients with CHD.3
Hence, many children who previously would have died,
either because of an undiagnosed anomaly or because of
technical inability to deal with the problem, now survive into
adulthood.4 The increasing survival rate of children with CHD
makes them a significant proportion of those attending for a
dental treatment and it is an essential challenge for dentistry to
provide care for the pediatric patients, whose medical health
can be hazardous as a result of poor dental health.5
Early dental health problems are common in children
with severe CHD and there are complicated background
factors often associated with nutrition, medication and the
demanding situation of their families.3,6-9 Lower frequencies
of regular dental care have been displayed in children with
CHD than in those without this medical problem.8,10-13
Therefore, early preventive dental care should be adjusted
to the special needs of children with CHD in their first years
of life.1,3 Hence, a detailed knowledge of the dental and oral
conditions of such children is essential if preventive care
is to be directed effectively. Though there have been many
studies14-16 concerning bacteremias associated with various
dental procedures, there is little available information in the
literature on the dental health of these children17 and none
on the quality of their dental treatment, despite the fact that
the dentist encounter these patients on a day-to-day basis.
Hence, this chapter attempts to enlighten the pediatricians
and dentists on the epidemiology of oral diseases in children

with CHD, highlight the importance of good oral hygiene
and prophylactic measures in these children (who may be
susceptible to infective endocarditis (IE) and emphasize the
role of pediatricians, pedodontists and parents in maintaining
oral health and preventive dental care in this set of population.
Infective endocarditis, an infection of the endocardium,
typically affects the heart valves and can occur on septal
defects or mural endocardium. For the past half century it has
been considered that IE occurs in patients with predisposing
heart lesions, especially in high-risk and moderate risk
patients. However the recent guidelines emphasize on
high-risk patients and accordingly recommends antibiotic
prophylaxis for the same to prevent the dreaded disease
(Box 1).18,19 The disease, however, can also occur in an
uncompromised host. Despite the relatively low number of
cases, the disease must be regarded as very serious because
if untreated, it results in death. IE has a mortality rate as high
as 15 to 50 percent, even with the best medical treatment.20-22
Choudhury20 studied clinical data from 186 patients with
infective endocarditis retrospectively and found that CHD was
the second most underlying heart lesion next to rheumatic heart
disease. In the Western world, CHD is present in approximately
80 percent of children, who develop IE.21-23 Several guidelines
have existed, which have identified specific underlying
cardiac conditions that placed children at increased risk of
IE.24,25 Evidence suggests that there is a rise in the incidence
of IE in the pediatric age group.21 Advances in neonatal
care, pediatrics and cardiovascular surgery over the past
three decades have resulted in the survival of infants with
previously fatal CHD.21,26 The number of children susceptible
to IE has therefore increased; this trend is likely to continue.
Infective endocarditis can affect children at any age, but
approximately one-half of children with IE are 10 years of
General Issues
13
980
Box 1: Endocarditis prophylaxis recommended18,19

2007 Guidelines
1997 Guidelines
Prosthetic cardiac valve or prosthetic material used for

cardiac valve repair
Prosthetic cardiac valves including bioprosthetic and

homograft valves
Previous bacterial endocarditis
Previous bacterial endocarditis
Cardiac transplantation recipients who develop cardiac

valvulopathy
Congenital heart disease (CHD)
Unrepaired cyanotic CHD, including palliative shunts and
conduits
Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by
catheter intervention, during the first 6 months after the
procedure
Repaired CHD with residual defects at the site or adjacent
to the site of a prosthetic patch or prosthetic device (which
inhibit endothelialization)
High-risk category
Complex cyanotic CHD (e.g. single ventricle states,
transposition of the great arteries, tetralogy of Fallot)
Surgically constructed systemic-pulmonary shunts or
conduits
Not required
Moderate risk category

Acquired valvular dysfunction (e.g. rheumatic heart
disease)
Mitral valve prolapse with valvular regurgitation and/or
thickened leaflets
age or older.27 The average age of children with IE is rising.

From 1930 to 1950, the mean age for children with IE was 5
years of age28; this increased in the 1970s to l3 years of age.27
Infective endocarditis is unusual below the age of 2 years,
but neonatal IE is being reported with increasing frequency
and is related to the routine use of indwelling intravascular
catheters in intensive care units.28-30 Data for mortality rates
vary and are influenced by the causative microorganisms, the
rapidity of diagnosis and treatment. Infective endocarditis was
usually fatal until the advent of antibiotic therapy in 1944.31
In the period 1960 to 1980, when surgical intervention was
not widely practiced, the mortality rate was thought to be
about 3040%; today the mortality rate is approximately 20
percent.21,32 Delay or failure to diagnose IE and failure to
intervene surgically if there is a deteriorating hemodynamic
state, are common reasons for the continuing high mortality
rate.
The microbial etiology of IE spans the whole spectrum
of microorganisms; however, the majority of infections are
bacterial.21 The relationship between oral microorganisms and
the development of IE is well-known. Previous studies have
shown that more than 4060 percent of the pediatric patients
with positive hemoculture can be attributed to streptococci21,22
and among those, most frequently encountered are viridans
streptococci presenting 50 percent of this group.33,34 Among
the viridans Streptococci, Streptococcus sanguis and aureus are

most often found in the blood stream in IE patients. In 1995, Fiehn
et al35 gave a final proof of a possible oral origin of infecting
bacteria in IE after ribotyping between blood isolates and dental
plaque isolates. These isolates were identified as Streptococcus
(S) mutans, S. oralis/S. mitis and S. mitior. These are an essential
part of the normal flora of the oral cavity. These bacteria
are located in dental plaque and associated with gingivitis,
which may lead, to periodontitis.36 Periodontal pathogens
(i.e. Actinobacillus actinomycetemcomitans (recently renamed as Aggregatibacter actinomycetemcomitans), Eikenella
corrodens, Fusobacterium nucleatum, and Bacteroides
Forsythus) and HACEK organisms (i.e. Haemophilus
aphrophilus, Haemophilus parainfluenzae, Actinobacillus
actinomycetemcomitans, Cardiobacterium hominis, Eikenella
corrodens and Kingella kingae) have also been revealed in
blood samples from IE patients.37 The initial event in the
pathogenesis of IE is the invasion of the blood stream by the
bacteria, resulting in bacteremias. Oral bacteria may gain
access to the circulation not only as a result of lost mucosal
integrity or dental therapy (e.g. oral surgery, periodontal,
therapy, endodontic treatment and dental implant placement),
but also after mastication and oral hygiene procedures.
The circulating bacteria may adhere to the endothelium of
the heart, when there is a previous damage or when there
Dental Procedures that may Precipitate

The importance of dental treatment as a cause of IE has
historically been overstated in relation to oral health conditions.
Nevertheless, dentistry remains the greatest identifiable risk for
patients who are susceptible to IE, though IE of dental origin
has dropped to 515 percent of cases.9 Hence, the maintenance
of optimum dental health with precise dental treatment is
important for the prevention of IE in children and adolescents
known to be susceptible to this disease.26 It is generally
agreed that procedures that reliably cause a bacteremia
such as scaling, extractions and endodontic instrumentation
require local and systemic prophylaxis. It can be seen from
Table 126 that bacteremias may result from many operative oral
procedures and even from non-invasive activities, including
tooth brushing or mastication and thus place a patient at
risk from IE.26 It is, therefore, of fundamental importance to
assess and manage patients susceptible to IE with great care.
The dentist is often concerned about treatments such as crown
preparation or placement of subgingival restorations that may
occasionally give rise to bacteremias. It is unrealistic and
undesirable to give systemic prophylaxis for the majority
of such procedures. Simple preoperative mouth rinsing
and gingival irrigation with chlorhexidine should suffice.
However, the necessity for systemic chemoprophylaxis for
Table 1
Occurrence of bacteremias (positive blood cultures) associated

with various dental procedures and oral activities26
Procedure
Bacteremia (% of cases)
Extractions:
Single
51
Multiple
68100
Subgingival scaling
5183
Gingivectomy
83
Full periosteal flap
3383
Root canal therapy:

Intracanal instrumentation
Extracanal instrumentation
31
Flossing
2058
Chewing
1750
Tooth brushing
750
root canal therapy is controversial. Infective endocarditis as

a consequence of root canal therapy has only been reported
infrequently.40 There is no consensus of opinion for such grey
areas and thus the clinician must assess each case individually.
If possible, it may be prudent to carry out such contentious
procedures at the same visit, when prophylaxis is required for
other procedures.26 Antibiotic cover would not be required at
further visits for biomechanical preparation and obturation, if
instrumentation is confined within the canal. However, pulp
treatment of primary teeth is contraindicated in children with
cardiac defects.41 The recent amendments published by the
British Society of Antimicrobial Chemotherapy (BSAC)42
also warned against the use of intraligamentary anesthesia in
patients at risk for IE. This practice is liable to carry a risk
of severe bacteremia and should not be used in susceptible
patients.
Antimicrobial Prophylaxis Against Dentally Induced

Prophylaxis in patients at risk from IE is sometimes
erroneously interpreted as solely meaning antibiotic
prophylaxis. Prophylaxis against IE should primarily be
concerned with the maintenance of good oral hygiene and
prevention of oral disease to reduce the magnitude and
frequency of spontaneous bacteraemias. This is probably far
more important than antibiotic prophylaxis in reducing the
incidence of streptococcal endocarditis.43,44
The key principles of antibiotic prophylaxis against
endocarditis include identification of patients at risk,
identification of procedures that pose a risk and the use of
antibiotics with a spectrum of activity appropriate for the
organisms known to cause bacteremias and endocarditis.
The 1997 guidelines from the American Heart
Association18 (AHA) had identified patients at risk
and stratified them into high-, moderate-, and lowrisk groups based upon the cardiac defect involved
(Box 1),18,19 In 2007, the AHA revised the guidelines on
appropriate antibiotic prophylaxis (Table 2),19 risk groups
(Box 1)18,19 and the dental procedures for which antibiotic
prophylaxis is recommended and those for which it is not
necessary (Box 2).18,19
American Heart Association19 has included suture removal
in the list of procedures that require antibiotic prophylaxis.
There are also various procedures for which antibiotic
prophylaxis is not recommended, although recent research
shows that they cause significant bacteremia. These include
the use of a matrix band and wedge and the placement of a
rubber dam.45
The AHA guidelines (Table 2)19 and recommendations
of the BSAC42 and National Institute of Health and Clincal
Excellence (NICE) guidelines are somewhat similar with some
important distinctions.46 Although the most recent (2007) AHA
guidelines18,19 are by far the simplest, yet many physicians and
dentists still do not comply with AHA recommendations.46
70
Oral Health Care in children and adolescents with Congenital Heart Diseases
is (by accident) a microscopic lesion of the endothelium

that has resulted in a so-called non-bacterial thrombotic
endocarditis, which is sterile.38 The bacterial adhesion to
the non-bacterial thrombotic endocarditis is favored and a
multiplication of bacteria subsequently follows and initiates
a focus of intravascular infection.39 This emphasizes the role
of dental diseases and dental procedures as a risk factor to IE.
981
General Issues
13
Box 2: Dental procedures and endocarditis prophylaxis18,19

Dental Procedures Requiring Antibiotic Coverage
2007 Guidelines
1997 Guidelines
All dental procedures that involve manipulation of gingival

tissue or the periapical region of teeth or perforation of the
oral mucosa
All dental procedures that involve manipulation of gingival

tissue or the periapical region of teeth or perforation of the
oral mucosa
Suture removal
Extractions
Extractions
Periodontal procedures (scaling, root planing, probing,

surgery, recall maintenance)
Periodontal procedures (scaling, root planning, probing,

surgery, recall maintenance)
Implant placement and remimplantation of avulsed teeth
Implant placement and reimplantation of avulsed teeth
Endodontic instrumentation or surgery when beyond the apex
Endodontic instrumentation or surgery when beyond the apex
Subgingival placement of antibiotic fibers or strips
Subgingival placement of antibiotic fibers or strips
Intraligamentary local anesthetic injections
Intraligamentary local anesthetic injections
Prophylactic cleaning of teeth or implants
Prophylactic cleaning of teeth or implants
Biopsies
Biopsies
Placement of orthodontic bands
Placement of orthodontic bands

Dental Procedures not Requiring Antibiotic Coverage
2007 Guidelines
1997 Guidelines
Suture removal
982
Restorative dentistry without retraction cord (unless

bleeding is anticipated)
Restorative dentistry without retraction cord (unless bleeding is

anticipated)
Local anesthetic injections through non-infected tissue

(non-intraligamentary)
Local anesthetic injections through non-infected tissue (nonintraligamentary)
Intracanal endodontic treatment
Intracanal endodontic treatment
Post placement and buildup
Post placement and buildup
Rubber dam placement
Rubber dam placement
Making of oral impressions
Making of oral impressions
Fluoride treatments
Fluoride treatments
Taking radiographs
Taking radiographs
Placement or removal of orthodontic or prosthetic

appliances
Placement or removal of orthodontic or prosthetic appliances
Placement of orthodontic brackets
Placement of orthodontic brackets
Adjustment of orthodontic appliances
Adjustment of orthodontic appliances
Shedding of deciduous teeth
Bleeding from trauma to the lips or oral mucosa
Bleeding from trauma to the lips or oral mucosa
70
Table 2
Antibiotic prophylactic regimens as recommended by American Heart
Unable to take oral

medications
Allergic to penicillins or
ampicillinoral
Allergic to Penicillin or
ampicillinUnable to
take oral regimen
Agent
2007 AHA Guidelines
1997 AHA Guidelines
Amoxicillin
Adults: 2 g
Children: 50 mg/kg
Adults: 2 g
Children: 50 mg/kg
Orally 3060 minutes prior to dental

procedure

procedure
Ampicillin
or
Adults: 2 g
Children: 50 mg/kg
Adults: 2 g
Children: 50 mg/kg
Cefazolin or
Ceftriaxone
Adults: 1 g
Children: 50 mg/kg
IM/IV 3060 minutes prior to dental
procedure

procedure
Cephalexin or
Cefadroxil
or
Adults: 2 g
Children: 50 mg/kg
Adults: 2 g
Children: 50 mg/kg
Clindamycin
or
Adults: 600 mg
Children: 20 mg/kg
Adults: 600 mg
Children: 20 mg/kg
Azithromycin or
Clarithromycin
Adults: 500 mg
Children: 15 mg/kg
Adults: 500 mg
Children: 15 mg/kg

procedure

procedure
Cefazolin or
Adults: 1 gm
Children: 50 mg/kg
Adults: 1 g
Children: 25 mg/kg
Ceftriaxone
or
Adults: 1 gm
Children: 50 mg/kg
Clindamycin
Adults: 600 mg
Children: 20 mg/kg
Adults: 600 mg
Children: 20 mg/kg

procedure

procedure
Examples of non-compliance include overprescribing or

underprescribing antibiotics, errors in dosage and timing,
improper choice of antibiotics, prescribing antibiotics for
low-risk patients or procedures and not prescribing antibiotics
for at-risk patients or procedures. Hence, Wahl46 addressed
the mounting issues about the dental-induced endocarditis and
associated aspects and concluded with the following facts:
1. Most physicians and dentists do not comply with AHA
recommendations for prevention of IE. All clinicians
should study the AHA recommendations. Physicians
should communicate to their patients in clear and
concise oral and written language.
2. Most cases of bacterial endocarditis of oral origin are
not caused by dental procedures, but rather by poor
oral hygiene, including poor home care. Patients at

risk for endocarditis should be encouraged to maintain
a high-level of oral health.
3. The AHA antibiotic regimens are not a panacea for
prevention of IE. They have been known to fail to
protect against endocarditis after dental procedures.
Until more studies on protective efficacy are done,
clinicians should continue to follow AHA guidelines.
4. The AHA antibiotic regimens should not be
administered for injections of local anesthetic (except
intraligamentary injections) in the absence of other
dental procedures that cause bleeding.
5. If an at-risk patient is receiving recent antibiotic
therapy before the dental procedure, then the antibiotic
Standard oral
prophylaxis
Association18,19
983
General Issues
13
(and probably its dose) should be changed before the

dental procedure.
6. The risk of antibiotic toxic effects, including death, is
sometimes greater than the risk of endocarditis. The
AHA guidelines address this and recommend against
chemoprophylaxis for certain low-risk conditions.
7. Oral antibiotic regimens are preferable for most
patients with high-risk conditions (e.g. prosthetic heart
valves and history of endocarditis).
8. Patients with mitral valve prolapse (MVP) should
receive antibiotic prophylaxis before dental procedures
only if they have valvular regurgitation.
9. Clinicians, who err on the positive side of antibiotic
prophylaxis may put their patients at greater physical
risk and themselves at greater legal risk than they
would by following AHA guidelines.
10. Finally, the AHA should call for a placebo-controlled
human study on antibiotic prophylaxis for IE. Such a
study would surely resolve much of the controversy
surrounding this issue.46
Dental Treatment During Infective Endocarditis

Dental treatment should ideally be carried out during
the first week of treatment for IE. If this is not possible,
it should be deferred until 4 weeks after completion of
treatment. Patients, who have had one episode of IE are
especially susceptible to developing this condition again
and they should be treated as special risk patients.42 It
is imperative that the oral health of special risk patients
is monitored regularly and maintained to the highest
levels possible. Prophylactic measures are not infallible;
IE can occur despite antibiotic prophylaxis after dental
treatment. Therefore, all patients susceptible to IE
should be told that they should inform their doctor in the
event of any unexplained pyrexia or illness during the
4 weeks immediately after dental treatment. If possible such
patients should be referred immediately to a cardiologist or
pediatrician before antibiotic therapy is commenced.21
Dental Disease in Children and Adolescents
localized dissolution and destruction of the calcified tissues

(Figures 1A and B). It is a multifactorial disease in which
there is an interaction between three principle factors:
1. Susceptible host tissue.
2. Microflora with cariogenic potential.
3. A suitable local substrate.48,49
In children with complex heart disease, other problems
often appear that may jeopardize dental health compared with
their control group counter parts due to following reasons:
1. Chronic intake of sugared medicines.
2. Increased tooth susceptibility from developmental enamel
defects.
3. Greater consumption of sweets in compensation to the
problems related to cardiac disease.
4. Negligence of oral hygiene as a result of a greater concern
with cardiac disease.8,6,16,50
The other reasons could be attributed to difficulties with
nutrition during their first years of life with vomiting and
nausea posing as a common problem.3 A study by Rai et al51
observed an incidence of anorexia (21.8%), vomiting (12.4%)
and nausea (11.2%) in these children. To compensate for
this, feeds are frequent and night meals are often necessary
to maintain energy intake at an acceptable level. In addition,
some of the medicines for heart disease contain diuretics
that can cause xerostomia.52 Infections often last for longer
periods than in normal children with an increased need for
drinking, sometimes at night, when salivary protection is
low.6,8,9
Dental disease is today the most common human disease

worldwide. Dental caries and periodontal diseases are
the two most common chronic diseases of the oral cavity.
Experimental and epidemiological studies have demonstrated
that dental caries and periodontal diseases are caused by the
microorganisms present in dental plaque.
Dental Caries
984
Dental caries are virtually ubiquitous; they begin soon after

the teeth erupt and increase in prevalence with age.47 It is an
infectious microbiologic disease of the teeth that results in
B
Figures 1A and B: Dental caries of maxillary and mandibular arches
Periodontal Disease
Periodontal diseases are the most prevalent chronic diseases
affecting children, adolescents, adults and the elderly. It is
postulated that periodontal disease in adults is, at least in
part, precipitated by gingival inflammation in the formative
years of childhood and early adolescence. The nondestructive gingival inflammation (Figure 2) of childhood,
without appropriate intervention, may progress to significant
periodontal diseases (Box 3) seen in the adult population.57 In
70
Figure 2: Calculus and gingivitis (gingival inflammation)
addition, recent research indicates a high correlation between

periodontal disease and cardiovascular disease, myocardial
infarction, stroke and low-birth weight babies.60
Hobson et al17 in their study of 69 medically compromised
children found that one-third of the children had wellestablished periodontal disease and over half of them had
untreated decay.
In a study conducted by Rai et al,51 out of 170 children with
CHD, there were 76 (44.7%) cyanotic and 94 (55.3%) with
acyanotic heart diseases. Relevant oral findings and systemic
findings are shown in the (Tables 3 and 4).51
There were no relevant extraoral findings except for one
cyanotic case with allergic pruritis. It has been observed
that 29.41 percent of the patients showed healthy gingiva
with no inflammation, while 26 to 47 percent had mild, 34.1
percent moderate and l0 percent showed severe gingival
inflammation.20 Das et al61 noted that children with CHD had
more severe gingivitis and increased plaque accumulation
as compared to normal children. Plaque accumulation was
found in 41.8 percent while 35.3 percent showed presence
of calculus (Figure 3). Presence of halitosis (1.16%) and
tongue coating (50.6%) were presumed to be because of
the poor oral hygiene. Presence of glossitis (25.3%) and
bald tongue (17.1%) could be attributed to the underlying
nutritional problems. Conjunctival petechiae were observed
in 30.6 percent and minor percentage (1.8%) of children
had petechiae of the extremities. Auluck et al 62 reveals that
excessive bleeding can occur in patients with congenital heart
patients for reasons other than the use of acetyl salicylic acid
and anticoagulant therapy. Perloff 63 reports that hematologic
abnormalities can be thrombocytopenia accelerated
fibrinolysis or decreased production of coagulation factors
leading to increased prothrombin time and thromboplastin
time.
Interestingly, there was a significant correlation between

the number of months on digoxin and the dmfs-value (decayed,
missing and filled teeth index score). Digoxin is administered
in a sucrose containing syrup (LanoxinTM). Today sucrose is
avoided as a sweetener in most medicines, because it is widely
accepted that sugar containing medicines are a cause of dental
caries in chronically sick children.53,54 At present, there are
no alternatives available for children, who need digoxin. For
these patients the development of sugar-free digoxin syrup is
a priority.3
In a study of children with cyanotic heart disease,
acyanotic heart disease and healthy controls, Berger50 found
that cyanotic children had more actively carious teeth and the
lowest levels of treatment. Furthermore, there was a much
higher prevalence of premature loss of primary teeth among
children with CHD.9
Similarly, Stecksen-Blicks et al3 found higher levels of oral
disease in children, whose cardiac condition was defined as
complex compared to healthy controls.
Hallett et al 6 also found 15 percent of teeth with carious
lesions in children with CHD. Caries poses a significant risk
in the children with CHD as it can result in pulpal infection,
which may in turn lead to spontaneous bacteremias that require
dental procedures of risk in order to establish satisfactory oral
health. Another serious factor is that the presence of an open
cavity may lead to a high accumulation of dental plaque and
thereby resulting in gingival inflammation. This may create
an appropriate environment for the development of viridans
Streptococci in the mouth.8
Rai et al51 followed World Health Organization criteria to
assess enamel hypoplasia55 and observed that 56.5 percent
children were reported normal. Dental caries was found in
47.4 percent children, which is quite alarming. Hayes et al7
concluded that untreated caries can be a contraindication for
heart surgery. Previous studies have reported variable results,
when comparing oral health in children with CHD against
healthy controls,3,6-9,12,50,56-59 although a number do report
higher incidence of untreated oral diseases.3,6,9,50,59
Although the prevalence of dental caries has declined in the
general population, there is no evidence to suggest a similar
reduction in this at-risk group. This lack of data prevents
targeting of resources to deal with them.9
985
13
General Issues
Box 3: Gingival and periodontal diseases in children and adolescents
Table 3
Table 4
Oral findings51
Clinical features
Systemic findings51
Number of
patients
Percentage
Incompetent lips
15
8.8%
Mouth breathing habit
19
11.2%
Cyanosis of tongue and lip
67
39.4%
Glossitis
43
25.3%
Bald tongue
29
17.1%
Tongue coating
86
50.6%
Candidiasis like lesion
17
10.0%
Dental plaque
71
41.8%
Dental calculus
60
35.3%
Extrinsic stains on the teeth
39
22.9%
Dental caries
72
42.4%
Malocclusion
50
29.4%
Dental care and prevention
986
The consequences of dental disease and certain dental

procedures are potentially, so serious that these children
require priority dental care. A continuing comprehensive
preventive care regimen is needed from as early an age as is
possible and if restorative treatment is required, it should be
of the highest quality.26
Clinical features
Number of patients
Percentage
37
21.8%
Vomiting
21
12.4%
Nausea
19
11.2%
Dyspnea
29
17.1%
Weakness
102
60%
Fatigue on exertion
132
77.6%
Pallor
38
22.4%
Headache
57
33.5%
Cyanosis
71
41.8%
Clubbing
57
34%
Epistaxis
19
11.2%
Anorexia
Oral Hygiene Aids

Tooth Brushes
Tooth brush remains the most effective and most widely used
device to remove dental plaque. The different varieties of
tooth brushes include:
Dental Floss
Combined with a toothbrush, dental flossis the most effective
method of removing plaque. It reaches parts of the oral cavity
that tooth brush bristles are unable to reach (interdental areas).
Dental floss must be used with care and is not recommended
for children under 10 years of age.
Foam Cleaning Sponges

These can be used as a temporary measure or combined with
a tooth brush to remove debris and cleanse the mouth, when
a child is unable to brush his/her teeth effectively. Foam
cleaning sponges are ineffective at removing plaque. Foam
cleaning sponges should be disposed once opened. They are
useful in the following situations:
1. When a child has no teeth.
2. Whenachildhas a platelet count below 20,000 with
associated bleeding.
70
Figure 3: Finger cap brush for infants
Figure 4: Powered tooth brush
3. Whena childhas severe mucositis that prevents them from

brushing their teeth, foam sponges can be moistened with
water or diluted chlorhexidine.
4. For palliative care situations when comfort is the only
intended outcome.64
1. Manual tooth brushes.

2. Powered tooth brushes.
3. Sonic and ultrasonic tooth brushes.
4. Ionic tooth brushes.
Manual tooth brushes are designed to reach and efficiently
clean most areas of the oral cavity. Conventional tooth
brushes may be modified in order to achieve enhanced plaque
removal.47,48 A small headed, soft, nylon bristled tooth brush
with round ended filaments should be used to brush or clean
teeth. In infants, a finger cap type of tooth brush can be used for
effective cleaning (Figure 3). Tooth brush should be changed
every 3 months or sooner if the bristles become frayed. It
should also be changed in cases of debilitating diseases,
oral infection, exposure to foreign substances or if child is
undergoing any kind of transplantation. The tooth brush
should be for the sole use of the child. Most of the researchers
have observed that the tooth brush may act as a vehicle in
breeding and transmitting various organisms in the oral
cavity. Experts thus advise cleaning the tooth brushes daily in
antiseptic mouthwashes such as phenolic derivatives. Storing
tooth brush in a dry, open air area and out of proximity from
other brushes is necessary to prevent bacterial proliferation
and cross-contamination.47
Powered tooth brushes: These brushes mimic the action of
manual tooth brushes and also make tooth brushing faster
and efficient (Figure 4). These have rotating, oscillating and
vibratory actions, which are effective against short and longterm decay. Brushes that work with a rotatory oscillating action
remove more plaque and reduce gingivitis more effectively
than a manual tooth brush. As the bristles are hard,they are
not advisable for children with a fragile mucosa. Powered
tooth brush is useful in young children, who find it difficult to
use a manual tooth brush or lack the manual dexterity and in
institutionalized patients.48
Fluoride Toothpaste
The overall increased vulnerability of the cardiac child to
stressful treatment procedures is one major reason to focus on
caries prevention.3 The benefits of fluoride in the reduction of
dental caries have been known for years. The mechanisms by
which fluorides increase caries resistance are as follows:
1. Increased enamel resistance/reduction in enamel solubility
2. Increased rate of posteruptive maturation.
3. Remineralization of incipient lesions.
4. Interference with plaque microorganisms.
5. Modification in tooth morphology.
Fluorides can be delivered either as topical fluorides or as
systemic fluorides. They can be professionally applied or selfapplied (Figure 5).65
987
General Issues
13
Figure 5: Fluoride delivery methods
988
For children likely to develop dental caries, the use of

1,350 to 1,500 ppm fluoride toothpaste may be recommended
by a dentist. If the risk of fluorosis is a concern, a tooth paste
containing less than 1,000 ppm may be recommended.49
Pit and Fissure Sealants

Caries potential is directly related to the shape and depth of
the pits and fissures. While the fluorides successfully prevent
caries on the smooth tooth surfaces; the narrow isolated
70
crevices and grooves that harbor food and microorganisms are

the most important anatomical features leading to development
of occlusal caries. The cariostatic properties of sealants are
attributed to the physical obstruction of pits and fissures
(Figure 6). This prevents the penetration of fermentable
carbohydrates and production of acid in cariogenic con
centrations. Dental sealants are cost-effective treatment
modalities, when placed on teeth of children at high-risk
for dental caries. Materials used as sealants range from
Cyanoacrylates, Polyurethanes, dimethacrylates to glass
ionomers. The fact that pit and fissure sealants are safe and
effective should justify their routine use as a preventive
measure.66
Chlorhexidine Mouthwash (0.2% Solution)

Chlorhexidine gluconate is a cationic bisbiguanide, which is
effective against an array of microorganisms, including grampositive, gram-negative organisms, fungi, yeasts and viruses.
Chlorhexidine exhibits both antiplaque and broad antibacterial
properties (Figure 7).48 It shows different effects at different
concentrations, i.e. bacteriostatic at low concentration and
bactericidal at high concentration. The superior antiplaque
activity is due to its property of sustained availability
substantivity. This involves a reservoir of chlorhexidine,
slowly dissolving from all oral surfaces, resulting in the
bacteriostatic milieu in the oral cavity. Its mode of action
prevents dental plaque formation, but does not remove plaque
efficiently. Hence, it is used as an adjunct to mechanical
oral hygiene methods and should not be considered as a
substitutefor effective tooth brushing.47 Chlorhexidine
can be used as a mouthwash, spray or gel for prevention of
secondary infection in mucosal ulceration and for control
of gingivitis, as an adjunct to other oral hygiene measures.
Chlorhexidine should not be used before or immediately after
using a tooth paste as the interaction with anionic surfactants
found within the formulations will reduce its efficiency. At
least 30 minutes should be allowed between using mouthwash
and tooth paste. Chlorhexidine can be targeted at children who
Figure 7: Chlorhexidine mouthwash
are institutionalized, medically compromised, physically or

mentally handicapped with compromised oral hygiene. It is
indicated:
1. In high caries risk patients, as chlorhexidine appears to
offer synergistic effects to fluoride in caries prevention.
2. To reduce the bacterial load in saliva and oral cavity
thereby limiting the operatory contamination.
3. As a substitute to tooth brushing in painful oral conditions,
e.g. primary herpetic stomatitis, minor recurrent aphthous
ulceration and in children with hemorrhagic disorders.
However, prolonged use of chlorhexidine causes reversible
brown staining of the teeth and oral mucosa.47,48
Tooth Brushing Techniques

A number of tooth brushing techniques have achieved
acceptance by the dental profession. Each technique has been
designed to achieve a definite goal. However, fones or circular
method and scrub method are best indicated in young children,
physically or emotionally handicapped and children who lack
manual dexterity. As the name suggests, in circular technique,
the child is asked to brush in a circular fashion on the teeth
(Figure 8). The scrub method of brushing requires vigorous
horizontal, vertical and circular motions. It is the virtual free
style of brushing scene. However, in adolescents Modified
Bass technique can be incorporated as a routine oral hygiene
measure (Figures 9A to C). It allows the patient to achieve
good gingival stimulation and excellent interproximal,
gingival and sulcular cleaning. The technique combines the
vibratory, circular and sweeping movements. The tooth brush
is held in such a way that the bristles are at 45 to the gingiva.
Bristles are gently vibrated by moving the brush handle in a
back and forth motion. The bristles are then swept over the
sides of the teeth towards their occlusal surfaces in a single
motion.48
Figure 6: Pit and fissure sealants
989
General Issues
13
Figure 8: Fones (Circular) technique
Role of parents/guardians
Prevention of dental diseases begins early with the involvement
of parents or guardians, who should be encouraged to bring
their children to the dentist as early as possible. This will
allow the child to acclimatize to the dental environment in the
absence of dental pain and active treatment. Patient education
requires constant reinforcement. The recognition of the
importance of their (young patients susceptible to IE) dental
health and their compliance with a preventive philosophy
bodes well for their dentition throughout life.67
Considering the foresaid aspects, the importance of
evaluating the practice and oral health conditions of children
A
990
at risk is recognized and there is a need to discover the

degree of their parents awareness.
Parental awareness on the importance of maintaining good
oral hygiene, its systemic effect and about preventive dentistry
has been evaluated and found to be very poor. Majority of
the patients were unaware of the knowledge about medicinal
caries and the importance of maintaining a good oral hygiene
(85.3%).51
Similar results (413% of awareness) were noted by da
Silva et al.57 In their study, 98 percent of the patients presented
visible plaque and 99 percent presented spontaneous or
provoked gingival bleeding. Similarly, studies in patients with
risk of IE have also shown that they present with worse oral
health than healthy children.6,8 Hallett et al6 found that 31
percent of the responses about this knowledge were affirmative,
while other studies found results varying from 21-4 percent
and 66 percent.67,68 In the study conducted by Lesley et al,26
parental attitudes to reception in the dental service differed
and parents of healthy children scored in the reception at
the dental clinic better than parents of children with CHD.
Despite adults performing tooth brushing more frequently
in 2 to 6 years old children than in the other age groups, the
numbers were below expectations. Numerous studies have
shown that being aware of the importance of good oral health
measures does not alone lead to appropriate daily oral care.
Figures 9A to C: A. Modified Bass technique (Facial aspect); B. Modified Bass technique (Occlusal aspect);
C. Modified Bass technique (Palatal aspect)
suggested that a competent dentist should be included in the

team at the cardiology department, to overcome difficulties
with early dental contacts. A practical way to provide such
early contacts could be in conjunction with the out-patient
cardiology visit, but in the dental clinic.3
Possible barriers to care are lack of training, philosophical
and economical constraints. This reluctance to treat dental
disease may be compounded in children, who are medically
compromised and for whom primary care practitioners may
feel inadequately trained. Certainly children, who have had
multiple medical interventions may become sensitized to
treatment, making it more difficult for them to have dental
interventions.70 Therefore, the role of both the pediatrician
and the pedodontist is equally important as that of the parent
or guardian.
Role of pediatricians and pedodontists

Oral health is an integral part of the overall health of children.
Pediatricians and pedodontists must be competent in issues
of oral health and disease if they are to fulfill their role as
professionals dedicated to the health of children.
Oral disease has implications beyond the mouth and can
cause significant problems for children with other chronic
diseases. Pediatricians receive very little education on oral
health during their medical training and numerous barriers
exist in incorporating oral health into practice. Despite these
facts, opportunities exist to both, to increase knowledge, to
overcome the barriers and to incorporate oral health into
daily practice. Collaboration with pedodontists to improve
childrens oral health will make the job of the pediatrician
easier and vice-versa.71
Studies considered the results disappointing as a high
percentage (19% and 28.8%) of children with CHD had never
visited a dentist.8,57 As a consequence, these children are not
receiving primary dental care or operative treatment, when
this is needed. Such negligence may put the general health
of these patients at risk, as oral infections can be a source
of frequent bacteremias in routine home care and activities
such as tooth brushing and chewing. The great concern of
doctors and dentists about the use of antibiotics can act as an
additional obstacle.
Among dentists, several studies have shown that compliance
with AHA guidelines on antibiotic prophylaxis has been very
low.72-74 The compliance rate among physicians has been
shown to be even lower. A 1989 survey73 of practicing dentists
and physicians found an overall compliance rate of only 39
percent for responding dentists and 27 percent for responding
physicians.46
Even the patients could avoid dental appointments in order
to avoid an antibiotic cover. It is well-known that prophylactic
antibiotics do not guarantee total protection against IE, the
promotion of oral health being much more effective.3 Despite
these children being at risk from dental disease, many
70
da Silva et al 57 also showed that there was no correlation

between knowledge and attitudes. Consequently, the absence
of a relationship between knowledge and oral status might
be anticipated. This parental negligence of oral hygiene may
be due to an absence of motivation and a greater concern
towards the systemic condition. The parents of children aged
between 1 and 5 years must be instructed to carry out oral
hygiene procedures for their children, who do not have the
manual dexterity and/or are not well motivated for good oral
hygiene. Good oral hygiene habits, when established early in
childhood, follow the individual until adult age. The results of
this study may suggest that knowledge about the importance
of good oral health may encourage visits to the dentist. On
the other hand, this does not imply that these children will
have good oral health. Hence, these children with cardiac
lesions susceptible to IE have special needs and they should
be regarded as medically compromised. The recall interval of
these patients should be individually assessed for each child,
but should not exceed 6 months.
Apart from consistent monitoring of childrens periodontal
status, it is also important to educate parents and children
in the prevention of dental caries. Despite the reduction in
caries prevalence over the past 20 years, a large proportion of
children still have active untreated decay.69 Adolescents need
regular screening in order that early stages of dental disease
may be diagnosed and preventive measures initiated.26
Hence, the motivation of parents and children is the biggest
difficulty for the treatment of periodontal disease, particularly
among special patients, where the systemic problem is often
the main concern of the guardian. Professional persistence
and certainty are necessary to educate such patients as to
the importance of good oral hygiene in ensuring periodontal
health and the health of the patient as a whole.
It is apparent that the recommendation that susceptible
patients should maintain a high standard of oral health has not
been properly followed.
Stecksen-blicks et al3 has shown that children with
severe CHD in Swedish communities mainly received their
dental health information from a physician or a dentist and
healthy children mainly received information from a dental
hygienist, indicating that children with severe CHD are given
priority in the dental care system. Dental health information
is provided to parents of these children, as young as oneyear-old. Information from such communities could help in
planning dental care for the increasing number of children
with complex heart anomalies, who are being successfully
treated with surgical interventions.3
Children with CHD have received sedation before operative
dental treatment significantly more often than healthy children.
It is suggested that children with severe CHD should receive
dental care in clinics for pediatric dentistry, particularly at
early ages.
Many parents stressed the importance of early information
on how to prevent poor oral health in their comments and
991
General Issues
13
are apparently not given oral hygiene instructions, dietary

counseling or advice on the use of fluoride supplements.10,11,17
Consequently, this information should be emphasized by
doctors. A systematic integration of medical and specialized
dental care should be established for all children with CHD
before they are 1 year old and the goal should be to maintain
oral health.3 Some dental practitioners seem unwilling to treat
children with heart defects and there is a lack of specially
trained personnel to whom they may be referred.9 The key to
protection of susceptible patients is improved dental health
education, effective preventive care and sensible treatment
planning, so that episodes of significant bacteremias are
reduced to a minimum. A similar suggestion was made by
Pogrel et al75 who, in a retrospective study of 83 patients
who had suffered from endocarditis, found that oral sepsis
alone was the cause in 12 percent of the patients.9 If dental
treatment is necessary, painful and stressful situations should
be avoided. Local anesthesia should be used and sedations
should be considered. In some vulnerable children, treatment
using sedation has to be performed in cooperation with the
childs cardiologist.7
Of major significance is the fact that untreated caries can
be a contraindication for heart surgery.7 As patients with more
complex anomalies often require several surgical interventions,
it is particularly important that scheduled surgery does not
have to be postponed, because of dental disease.3
Rai et al51 proposed that a dental appointment be scheduled
as part of the medical re-evaluation protocol for children in
this category. Such a system would provide immediate access
to information pertaining to medical and dental treatment
needs and facilitate pediatric medical professionals and the
public to know when and how to seek specialist care.51
Hence, closer cooperation between pediatricians, pediatric
cardiologists and pediatric dentists and an understanding of
the demanding situation for the parents and families of the
patients with cardiac disease could help improve dental care
for these children.3,51
Conclusion
Given the small numbers and the degree of risk, it would
seem sensible to recommend that these children receive
complete dental care in a specialized setting or at the very
least have a specialized pediatric dentist over seeing their
care. More research is required to clarify further the disease
level and the barriers to care in this particular population.
The rarity of the condition and decrease in the morbidity rate
of this group due to advances in interventions and surgical
techniques suggest that any further research would need to
be multi-centered.
992
He who cures a disease may be the skillfullest but he who

prevents it is the wisest.
Thomas Fuller
Acknowledgments
Dedicated to my beloved parents Dr Suresh Harve and
Dr Vijayalakshmi Suresh, who have peen dutiful parents and
a guiding force throughout my life. I sincerely acknowledge
Dr Simran Parwani MDS Senior Lecturer and Dr Ruchi
Banthia MDS Professor in department of Periodontics,
Modern Dental College and Research Centre, Indore. Without
their pensive suggestions and critical evaluation, this chapter
would not have seen the light of the day. I am indebted to
Dr. Naveen Reddy Banda, MDS, Reader in Department of
Pedodontics for helping me with some of the images.
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1989;118:169-73.
75. Pogrel MA, Welsby PD. The dentist and prevention of infective
endocarditis. Brit Dent J. 1975;139:12-16.
C hapter
71
Infective Endocarditis in
Anita Shet
INTRODUCTION
Infective endocarditis (IE) continues to loom as a dreaded
complication of congenital heart disease (CHD). Despite the
availability of newer diagnostic and imaging techniques and
early management with antibiotics and surgery, the incidence
of IE among children and adults has not decreased.1,2 Part of
the reason can be attributed to the tremendous advances made
in the field of cardiology. CHD currently reigns supreme as
the leading risk factor for pediatric IE, having usurped this
position from rheumatic heart disease. The reported incidence
of IE in CHD is up to 140 times higher than the incidence in
the general population.2,3 With advances in modern medicine
and improved surgical techniques, children with CHD are
remaining healthy and living well into adulthood. There are
increased instances of use of prosthetic devices in CHD,
which subsequently add another layer of risk for IE.4
EPIDEMIOLOGY
The demographic features of IE among CHD are constantly
changing due to medical advances and the dynamic nature of
the infective organisms. The mean age of IE developing in
individuals with CHD has been found to range between 13
to 33 years; longitudinal studies have seen increasing mean
age at diagnosis with each passing decade due to the greater
proportion of adults in more recent decades.2,4,5 There are 1.5
males for every female, who develops this disease and this
gender ratio has remained constant over the past 4 decades.4
PATHOGENESIS AND RISK FACTORS

The pathogenesis of IE in CHD is similar to the occurrence
of IE in other structural heart disease or de novo occurrence
(Figure 1). A series of complex interactions between valvular
and mural endothelium, blood components, circulating
pathogens and host responses can culminate in IE. The

presence of foreign or prosthetic material can worsen risk and
outcomes in children with CHD and IE. Fibrinogen is a highly
hydrated macromolecule that adheres to the prosthetic device
easily.
The risk of developing IE depends on the type of cardiac
defect and also on the infecting pathogens (Table 1 and
Box 1). The risk factors may be categorized into the following:
1. Cardiac factors: type of heart malformation causing
valvular, mural, or vascular damage.
2. Pathogen and host factors: particularly the source of
bacteremia and host characteristics
Cardiac Risk Factors for Infective Endocarditis

The exact type of congenital cardiac lesion, its severity,
location and status of surgical repair can influence the risk
of developing IE. Factors which can increase risk are the
presence of unrepaired complex cyanotic CHD and use of
prosthetic material such as conduits or shunts during repair.4
Cardiac Risk Factors among those with Unrepaired CHD

The presence of cyanosis in CHD adds tremendously to the
overall risk of developing IE. Among unrepaired cardiac
defects, the lifetime risk for IE in cyanotic CHD is up to 8.2
cases per 1,000 patients per year, while the lifetime risk for
IE in acyanotic CHD is 1.7 to 2.4 cases per 1,000 patients
per year.6,7 Unrepaired ventricular septal defect (VSD) is the
most frequent CHD associated with IE especially if associated
with aortic insufficiency or with left ventricle to right atrial
shunt. The second CHD most frequently associated with IE
are the outflow tract obstructions such as aortic and pulmonic
valve stenosis. IE is less frequent in other conditions such as
patent ductus arteriosus (PDA), atrioventricular septal defect
and atrial septal defect.1
General Issues
13
Figure 1: Pathogenesis of infective endocarditis in congenital heart disease
Table 1
Infective endocarditis among those with and without congenital heart disease
IE in CHD child (< 18 years)
IE in CHD adult
IE not associated with CHD
Lifetime risk of IE
Cyanotic: 8.2/1,000 patients/ year

Non-cyanotic: 1.72.4/1,000
patients/year
Tetralogy of Fallot (25%)
Overall risk is 513%

Ventricular septal defect at
30 year of age (10%)
Bicuspid aortic valve (20%)
Rheumatic heart disease (6%)

Mitral valve prolapse (30%)
Degenerative valvular disease
(20%)
(5%)
Prosthetic valve (5%10%)
Microbiology
Streptococcus species (42%)

Staphylococcus species (26%)
Others (Enterococcus species,
fungi, HACEK) (16%)
Culture negative (14%)

fungi, HACEK) (16%)

fungi, HACEK) (15%)
Location of
lesions
Left-sided: mitral valve (26%)

> aortic valve (16%)
Right-sided: tricuspid valve (15%),
pulmonary valve (9%)
Left-sided (60%): mitral

valve > aortic valve
Right-sided (40%)
Left-sided: mitral valve (40%)

> aortic valve (25%)
Right-sided: tricuspid valve
(<10%), pulmonary valve
(< 5%)
Complications
Cardiac: CCF (30%), valvular

damage (30%), valvular abscess
(< 5%), arrhythmia (5%)
Extracardiac: emboli (20%);
cerebral (15%), renal (10%)

abscess (510%), arrhythmia (5%)

abscess (35%)
Outcome
Overall mortality (10%)

Surgical mortality (14%)
Overall mortality (10%)
Overall mortality (10%30%)

Surgical mortality (20%)
Modified from Knirsch, Eur J Pediatr 2011

IE = Infective endocarditis; CHD = Congenital heart disease; HACEK = Haemophilus species (Haemophilus parainfluenzae, Haemophilus aphrophilus,
Haemophilus paraphrophilus), Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella species.
CCF = Congestive cardiac failure
996
Box 1: Risk factors for infective endocarditis among

Risk factors for infective endocarditis among those with
congenital heart disease
I. Cardiac factors:
Any unrepaired complex cyanotic congenital heart disease
Ventricular septal defect with left-to-right shunt or aortic
insufficiency
Tetralogy of Fallot
Aortic valvular stenosis
Pulmonary valvular stenosis
Primum atrial septal defect
Any cardiac prosthetic device surgically implanted
II. Pathogen factors:
Source of bacteremia: highest risk associated with medical
procedures:
Dental procedures
Cardiac surgery
Catheter-related procedures
Animal bites
III. Host factors:
Intravenous drug abuse
Body piercing and tattooing procedures
Habits such as nail biting
Chronic eczema
Poor skin hygiene and recurrent minor skin infections
Cardiac Risk Factors among those with

Reparative Heart Surgery
Surgical repair of CHD can decrease overall risk for IE,
although, the implantation of prosthetic material may increase
risk for post-interventional IE. Following surgical repair,
IE risk was highest in valvular aortic stenosis (cumulative
incidence of IE in a 25-year longitudinal US-based study
was 13.3%) and seen among those with coarctation of the
aorta (3.5%), primum atrial septal defect and isolated VSD
(2.7%2.8%) and tetralogy of Fallot, (1.3%).8 Children with
secundum atrial septal defect, PDA arteriosus or pulmonic
stenosis did not seem to develop IE after surgery.
The type of prosthetic material used can also influence
the degree of risk. Material such as Dacron polyethylene
terephthalate, which have a high critical surface tension, can
exhibit higher binding capacity for fibrinogen and platelets
and can thus have a higher disposition to initiate devicerelated infections.9 Prosthetic material such as Teflon and
other fluorocarbon polymers have lower surface tension and
are associated with lower risk for IE.
The source of bacteremia is a critical factor in determining

the risk in IE. The highest risk is associated with medical
procedures such as dental procedures, cardiac surgery, catheterrelated procedures and other non-cardiac invasive procedures,
that can all predispose to bacteremia. Body piercing, tattooing
and nail biting are risk factors for bacteremia. Other events
such as animal bites and intravenous drug abuse are also
potential sources for bacteremia. Minor skin lesions such
as small abscesses and eczema can also predispose to IE,
especially Staphylococcus-related IE.4,10
Can one predict the occurrence of IE in patients with CHD?
A recently developed model included patient characteristics
such as age, gender; type of congenital defects, complications
and interventions in childhood; a score was assigned using
these characteristics and the model was able to accurately
predict patients at relatively low or high-risk of IE.11 Highrisk factors were male gender, presence of multiple defects,
specific CHD such as VSD, tetralogy of Fallot, aortic or
pulmonary stenosis; and complications in childhood such
as IE and cerebrovascular accident. Some congenital heart
defects such as PDA, after repair appear to pose no increased
risk for IE.11,8 This study also found no difference in risk of IE
between patients with corrective and palliative interventions.11
71
Infective Endocarditis in Congenital Heart Diseases
those with congenital heart disease
Pathogen and Host Factors for Infective Endocarditis
Location of Infective Endocarditis

in Congenital Heart Disease
The striking difference in the anatomic location of IE in CHD
compared to non-CHD structural heart disease lies in the
cardiac location of CHD-related IE (Table 1). In general, rightsided IE is more frequent in CHD than in acquired cardiac
disease. Right-sided IE lesions constitute about 30 percent of
such lesions in CHD, while only 5 percent or less right-sided
lesions occur in structural heart disease.4,12 In CHD, the right
side of the heart is more likely to face conditions such as lower
oxygen saturation or low pressure states, which predispose its
tissues to IE and cardiovascular device-related infections to a
larger extent than left-sided heart areas.
CLINICAL MANIFESTATIONS
The clinical course usually begins with bacteremia and is
superimposed on the underlying risk factor of CHD. Two
patterns of clinical progression have been described previously,
based on the presentation and rate of disease progression.
In acute IE, a sudden onset with a fulminant course is seen
and is associated with a high rate of complications and poor
outcome. Subacute IE is characterized by an insidious onset,
more subtle course and is usually responsive to antibiotics.13
This type of classification is less useful in the current era,
where a high-index of suspicion of IE, rapid diagnosis and
prompt institution of management is encouraged.14
997
General Issues
13
Box 2: Modified Duke Criteria for diagnosis of infective endocarditis

Major criteria
1. Positive blood culture (BC)
Two separate positive BCs with typical microorganisms consistent with IE (Viridans Streptococci, Streptococcus bovis, HACEK
group, Staphylococcus aureus and enterococci) in the absence of a primary focus
2 positive BCs drawn >12 hour apart or all of 3 or a majority of 4 separate BCs (with first and last sample drawn at least 1 h apart)
One positive BC for Coxiella burnetii or antiphase-I immunoglobulin G antibody titer >1:800
2. Evidence of endocardial involvement
Positive echocardiogram (TEE recommended in prosthetic valves or complicated IE; TTE as the first test in other patients):
Vegetation on valve or supporting structure
Abscess
New partial dehiscence of prosthetic valve
New valvular regurgitation
Minor criteria
1. Predisposition and presence of risk factors for IE
2. Fever
3. Vascular phenomena (major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial or conjunctival
hemorrhage or Janeways lesions)
4. Immunologic phenomena (glomerulonephritis, Oslers nodes, Roths spots or rheumatoid factor)
5. Microbiological evidence: positive BC that does not meet major criteria or serological evidence of infection
6. Echocardiographic minor criteria eliminated
Definite IE: Clinical criteria - 2 major criteria or 1 major + 3 minor criteria or 5 minor criteria
Possible IE: 1 major + 1 minor criterion or 3 minor criteria
BC = Blood culture; HACEK group = Haemophilus species, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, and Kingella species;
TEE = Transesophageal echocardiogram; TTE= Transthoracic echocardiogram
998
Fever is almost universally present, with over 95 percent

presenting with low grade intermittent rise in body temperature,
with associated features of malaise and fatigue. Other clinical
features are failure to thrive, nausea and vomiting, headache
and arthralgia. Other typical clinical features of IE are similar
to those seen in cases of non-CHD-related IE and include
splenomegaly, changing heart murmur, eye conditions such
as Roth spots and skin manifestations such as Osler nodes,
Janeway lesions and splinter hemorrhages. The modified
Dukes criteria, which include many of these manifestations,
are shown in Box 2.
The causative organism also plays a role in the clinical
profile and outcome of patients with CHD and IE.
Staphylococcal species were more common among the
younger children, especially among infants, Streptococcus
species were typical among older children <16 years.5 The
same study found that Staphylococcus species occurred
more frequently in patients with cyanotic CHD (47%), while
Streptococcus species was more closely associated with
acyanotic CHD (68%). Certain bacteria such as Haemophilus
species demonstrated a decreased predilection for causing
vegetations and therefore were less likely to cause embolic
phenomena.5 Higher mortality was seen when S. aureus was
the causative pathogen (19% mortality) compared to the other
common species like Streptococcus species (5% mortality).
Other pathogens associated with high mortality (> 40%) were
Candida and Pseudomonas species.5
Complications of Congenital Heart Disease Related

The most common complication, which can occur in up to
50 percent of the cases is congestive cardiac failure (CCF).
CCF usually occurs secondary to hemodynamic compromise
following the destruction of affected valves. Other rarer
causes of CCF can be myocarditis, perivalvular or myocardial
abscess, arrhythmias and emboli in coronary arteries.
Complications caused by embolic episodes are more frequent
in large single vegetations and in left-sided compared to rightsided vegetations. Common embolic complications lead to
cerebral infarct (stroke) and pulmonary infarcts; less common
episodes lead to renal, splenic and peripheral vascular
infarcts.2,15
An uncommon complication of endocarditis is an acquired
ventriculoatrial or Gerbode defect. Though majority of
Gerbode defects are congenital, acquired left ventricular
to right atrial (LV-RA) communications are rare and are
reported following ventricular septal perforation as a result
of endocarditis, trauma, myocardial infarction, valve
replacement and following closure of VSD.16-21 The acquired
Gerbode shunt due to the patient developing endocarditis,
three months after surgical closure of atrial septal defect is
shown in Figure 2. Sometimes IE can occur after transcatheter
interventions like balloon valvuloplasty. The transthoracic
echocardiography in a 6-year-old girl, who presented with
71
Box 3: When to suspect infective endocarditis

in congenital heart disease
Figure 3: Transthoracic echocardiogram in a 6-year-old girl shows

aortic root abscess after aortic balloon valvuloplasty. AO = Aorta; LA =
Left atrium; LV = Left ventricle; RV = Right ventricle; VEG = Vegetation.
intermittent high fever spikes within 2 weeks after aortic

balloon valvuloplasty shows root abscess (Figure 3).
DIAGNOSIS
The diagnosis of IE is usually made after consideration
of a number of factors, including a thorough history and
physical examination, inflammation parameter determination,
repeated blood cultures from different peripheral sites,
echocardiography and tests to rule out other potential causes
of fever and CCF. In general, any patient with CHD presenting
with persistent fever or new onset cardiac failure should be
investigated for IE (Box 3). The diagnosis can be made on the
basis of the modified Dukes criteria, which has also shown to
be useful in children.22,23
Figure 2: Transthoracic echocardiogram in post surgical atrial septal defect closure in a 4-year-old girl shows, Gerbode defect with vegetation
on all four valves with blood culture growing methicillin resistant staphylococcus. LA = Left atrium; LV = Left ventricle; RA = Right atrium; RV =
Right ventricle.
New regurgitant murmur

Embolic events of unknown origin
Sepsis of unknown origin (especially if associated with
IE-related organism)
Prolonged fever that is associated with:
Intracardiac prosthetic material
Previous history of IE
Cardiac failure
Recent intervention likely to produce bacteremia
Vascular or immunological phenomena
Peripheral abscesses (renal, splenic, cerebral,
vertebral)
New stroke
New conduction disturbance
Blood Culture
One of the mainstays of diagnosis in IE is the positive
blood culture. The use of modern automated blood culture
systems, which include the presence of resins to bind to
antibiotics existing in the blood of patients, who were treated
previously with antibiotics, will help to increase sensitivity
of the yield of positive blood cultures. Usually 3 sets of
blood cultures (aerobic blood cultures) are drawn during the
diagnostic investigation period, with each sample being 12
hours apart. In very acutely ill patients, 3 blood cultures
should be obtained over a 1 hour time span before beginning
empiric therapy.24 Anaerobic cultures are not routinely done
in children. The recommended volume of blood for culture
is as follows: 1 to 3 mL for infants, 3 to 5 mL for children 2
to 6 years and 10 mL for school-aged children > 6 years.25
999
General Issues
13
A positive blood culture that defines IE consists of recovery of a microorganism consistent with IE, from two
separate blood culture sets drawn more than 12 hours apart,
all three sets or a majority of four or more separate blood
culture sets, with first and last drawn at least 1 hour apart.
Microorganisms consistent with IE are: Viridans streptococci,
Streptococcus bovis, HACEK group; commonly-acquired
Staphylococcus aureus or enterococci in absence of primary focus.22 Negative blood cultures can occur in 3 to
30 percent of all cases of echocardiographic or postmortem
confirmed IE.26
Echocardiography
A key diagnostic indicator of IE is echocardiography which
can visualize several important aspects of cardiac involvement
during IE.27 Vegetations as small as 2 to 3 mm can be seen by
traditional two-dimensional transthoracic echocardiography
(TTE). Valvular regurgitation can be seen with color Doppler,
and should be used if IE is suspected. A transesophageal
echocardiography (TEE) allows more precise visualization
of vegetations and improved sensitivity for diagnosis of
IE (Figure 4 A and B). These advantages of TEE have also
been demonstrated in children.28 The recently revised 2012
British guidelines state that TTE can be used as the first-line
imaging modality, when IE is suspected.24 A TEE can be
used in patients with high clinical suspicion of IE and a nondiagnostic TTE. If the echocardiography result is negative and
the clinical suspicion of IE remains high, a TTE or TEE may
be repeated after 7 to 10 days. It is important to note that a
negative study does not exclude the diagnosis.
MANAGEMENT
Antimicrobial therapy and surgery are the two cornerstones of
management of IE in CHD.
Figures 4A and B: Transthoracic echocardiogram in apical fivechamber view in a 2-year-old girl with Gerbode defect (GVSD) with
large vegetation in right atrium (RA). LA = Left atrium; LV = Left
ventricle; RA = Right atrium; RV = Right ventricle; VEG = Vegetation.
1000
Medical Management
Antimicrobial Therapy
Vegetations tend to be avascular environments, hence, the
hosts normal defences are limited resulting in impaired ability
to eradicate infection.29 Pathogenic bacteria tend to exist in
a state of reduced metabolic activity inside densely packed
vegetations. These bacteria need to be eliminated completely
and the vegetations need to be sterile in order to achieve
cure of IE. Thus for optimal management, bactericidal rather
than bacteriostatic agents are preferred and must be used in
relatively high dosages for a prolonged period of time.29
Factors to be taken into account, while deciding the choice
of antibiotics and duration of therapy are the underlying
risk factors, causative microorganism and involved valve.
Antibiotic therapy should be initiated promptly. Three sets of
blood cultures should be drawn at 30 minutes intervals before
initiation of antibiotics.30 An empiric combination of a betalactam and an aminoglycoside is usually used together for their
synergistic bactericidal effect and broad spectrum activity.31
The intravenous route is preferable to oral therapy in order to
achieve higher serum drug levels. The duration of treatment
should last for at least 2 weeks in some situations, but 6 weeks
or longer is the minimum requirement for cardiovascular
device-related IE.
For specific doses and duration of antibiotic regimens
in different etiological situations, the reader is referred to
current guidelines for antibiotic treatment of CHD-associated
IE that have been published by several authorities including
the American Heart Association (AHA),32 the European
Society of Cardiology (ESC)30 and the British Society for
Antimicrobial Chemotherapy.24
Surgical Management
Surgery contributes by removing infected material and draining
abscesses. The aims of surgical intervention are to avoid
progressive cardiac failure and irreversible structural damage
caused by severe infection. The three main indications for
early surgery in IE are refractory cardiac failure, uncontrolled
infection and for prevention of embolic events.30 The various
echocardiographic features which suggest the potential need
for surgery in IE are given in Box 4.32 Surgery performed early
during IE using reconstructive techniques on the native valves
without foreign material can minimize pre- and postoperative
complications and mortality.33 Recommendations for timeoptimized cardiovascular surgery for patients with CHDassociated are yet to be defined.34 Surgery involves total
removal of infected tissues and reconstruction of cardiac
morphology, including repair or replacement of the affected
valve or valves.
Box 4: Echocardiographic features that suggest potential

Vegetation
Persistent vegetation after systemic embolization
Anterior mitral leaflet vegetation, particularly with size 10 mm*
One or more embolic events during first 2 weeks of
antimicrobial therapy*
Increase in vegetation size despite appropriate antimicrobial
therapy*
Valvular dysfunction
Acute aortic or mitral insufficiency with signs of ventricular
failure
Heart failure unresponsive to medical therapy
Valve perforation or rupture
Perivalvular extension
Valvular dehiscence, rupture, or fistula
New heart block
Large abscess or extension of abscess despite appropriate
antimicrobial therapy
* Surgery may be required because of risk of embolization.
Surgery
therapy.
may be required because of heart failure or failure of medical
Echocardiography
should not be the primary modality used to detect or

monitor heart block.
Common postsurgical complications include severe

coagulo
pathy, acute renal failure, pneumonia and
atrioventricular block. Development of IE after cardiac surgery
is a potentially life-threatening complication, which often
requires surgical reintervention with removal of contaminated
foreign material as antimicrobial treatment alone is often
insufficient.35
OUTCOME
Infective endocarditis in CHD carries a mortality of 4 to
10 percent, which is much less than that seen in the general
population that gets affected by IE.1,36 IE in adults with
structural heart disease carries a higher mortality, which
can be as high as 30 percent.37 A poor outcome for IE in
children with CHD can be predicted by delay of hospital

admission and antibiotic initiated, age < 3 years and a
vegetation size >10 mm detected by echocardiography.38
Overall outcomes in CHD-associated IE have improved in
the last few decades. The decrease in mortality is attributable
to earlier repair of CHD, improvement in diagnosis of IE and
antimicrobial treatment and early cardiac surgery for IE as
necessary.2,5,39,40
PREVENTION
Primary prevention of endocarditis is central to minimizing
morbidity and mortality among those with CHD. There are
several extensively reviewed guidelines for the prevention of
IE.30,41-43 These guidelines are evidence-based and focus on
the underlying cardiac conditions associated with the highest
risk of adverse outcome. Antibiotic prophylaxis is indicated
only in certain high-risk groups. Table 2 outlines the revised
recommendations for antibiotic prophylaxis.30
Antibiotic prophylaxis is given for those patients at
highest risk for IE, such as those with cyanotic CHD without
surgical repair or with residual defects. Prophylaxis is not
recommended for any other form of native valve disease
(including the most commonly identified conditions, bicuspid
aortic valve, mitral valve prolapse and calcific aortic stenosis).
Patients with prosthetic material used for cardiac repair are
also at increased risk for IE. Dental procedures that involve
the manipulation of the gingival mucosa or perforation of
the oral mucosa are associated with high-risk for IE and thus
recommended for prophylaxis. Other procedures such as
respiratory, gastrointestinal or genitourinary manipulations
are not associated with increased risk of IE and hence are
not listed under procedures for antibiotic prophylaxis. The
antibiotics used can be ampicillin or amoxicillin (single dose
3060 minutes before the procedure). Alternative drugs are
cephalexin or ceftriaxone or in the case of penicillin allergy,
clindamycin.30
The importance of good oral, dental and skin hygiene are
of particular importance for the prevention of IE.44 Nutritional
guidance, attention to immunization and proper attention
71
need for surgical
intervention32
Table 2
Recommendations for antibiotic prophylaxis for prevention of infective endocarditis in CHD

Antibiotics are no longer recommended for prophylaxis in all forms of CHD other than those mentioned in the revised guidelines.
Antibiotic prophylaxis is recommended for those patients at higher risk for IE:
1. Patients with a prosthetic valve or those with prosthetic material used in cardiac repair
2. Patients with previous history of infective endocarditis
3. Patients with specific types of congenital heart disease such as cyanotic congenital heart disease without surgical repair, or with
residual defects, shunts or conduits.
Procedures associated with high risk of infective endocarditis are advised antibiotic prophylaxis:
1. Dental procedures involving manipulation of the gingival or peri-apical region of teeth or perforation of the oral mucosa.
No prophylaxis is recommended for respiratory tract procedures, gastrointestinal or genitorurinary procedures, dermatological or
musculoskeletal procedures.
1001
General Issues
13
to common illnesses can go a long way in prevention of

complications in these children.45 Patient education forms a
critical art of the IE prevention strategy.46
CONCLUSION
Adults with CHD form a relatively new population that
is steadily growing in number and age due to improved
survival.47 With the advent of more daring surgical
corrections of CHD performed at earlier ages, the prevalence
of unrepaired CHD decreases, alongside the numerical
increase of patients with repaired or palliated CHD. The
risk of IE in this population is still omnipresent and strict
guidelines for prevention, early diagnosis and management
of IE in this population remains key to nurturing this
population to remain in good health.
Soap and water and common sense are the best disinfectants.
William Osler
Acknowledgment
Thanks to Dr IB Vijayalakshmi, Professor of Pediatric
Cardiology, for providing all the illustrative images for this
chapter.
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1002
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24. Gould FK, Denning DW, Elliott TS, et al. Guidelines for the
diagnosis and antibiotic treatment of endocarditis in adults: a
report of the Working Party of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother. 67:269-89.
25. Connell TG, Rele M, Cowley D, et al. How reliable is a
negative blood culture result? Volume of blood submitted for
culture in routine practice in a childrens hospital. Pediatrics.
2007;119:891-6.
26. Prendergast BD. Diagnostic criteria and problems in infective
endocarditis. Heart. 2004;90:611-3.
27. Habib G, Badano L, Tribouilloy C, et al. Recommendations for
the practice of echocardiography in infective endocarditis. Eur
J Echocardiogr. 11:202-19.
28. Humpl T, McCrindle BW, Smallhorn JF. The relative roles of
transthoracic compared with transesophageal echocardiography
in children with suspected infective endocarditis. J Am Coll
Cardiol. 2003;41:2068-71.
29. Kubak BM, Nimmagadda AP, Holt CD. Advances in medical
and antibiotic management of infective endocarditis. Cardiol
Clin. 1996;14:405-36.
39. Sadiq M, Nazir M, Sheikh SA. Infective endocarditis in

children--incidence, pattern, diagnosis and management in a
developing country. Int J Cardiol. 2001;78:175-82.
40. Knirsch W, Haas NA, Uhlemann F, et al. Clinical course and
complications of infective endocarditis in patients growing
up with congenital heart disease. Int J Cardiol. 2005;101:
285-91.
a guideline from the American Heart Association Rheumatic
Fever, Endocarditis, and Kawasaki Disease Committee,
Council on Cardiovascular Disease in the Young, and the
Council on Clinical Cardiology, Council on Cardiovascular
Surgery and Anesthesia, and the Quality of Care and Outcomes
Research Interdisciplinary Working Group. Circulation.
2007;116: 1736-54.
42. Danchin N, Duval X, Leport C. Prophylaxis of infective
endocarditis: French recommendations 2002. Heart. 2005;
91:715-8.
43. Gould FK, Elliott TS, Foweraker J, et al. Guidelines for the
prevention of endocarditis: report of the Working Party of the
British Society for Antimicrobial Chemotherapy. J Antimicrob
Chemother. 2006;57:1035-42.
44. Duval X, Leport C. Prophylaxis of infective endocarditis:
current tendencies, continuing controversies. Lancet Infect
Dis. 2008;8:225-32.
45. Woodward CS. Keeping children with congenital heart disease
healthy. J Pediatr Health Care. 25:373-8.
46. Moons P, De Volder E, Budts W, et al. What do adult patients
with congenital heart disease know about their disease,
treatment, and prevention of complications? A call for
structured patient education. Heart. 2001;86:74-80.
47. van der Bom T, Luijendijk P, Bouma BJ, Koolbergen DR, de
Groot JR, Mulder BJ. Treatment of congenital heart disease:
risk-reducing measures in young adults. Future Cardiol.
2011;7:227-40.
71
30. Habib G, Hoen B, Tornos P, et al. Guidelines on the prevention,

diagnosis, and treatment of infective endocarditis (new version
2009): the Task Force on the Prevention, Diagnosis, and
Treatment of Infective Endocarditis of the European Society
of Cardiology (ESC). Endorsed by the European Society of
Clinical Microbiology and Infectious Diseases (ESCMID) and
the International Society of Chemotherapy (ISC) for Infection
and Cancer. Eur Heart J. 2009;30:2369-413.
31. Malacoff RF, Frank E, Andriole VT. Streptococcal endocarditis
(nonenterococcal, non-group A): single vs combination
therapy. Jama. 1979;241:1807-10.
32. Baddour LM, Wilson WR, Bayer AS, et al. Infective
endocarditis: diagnosis, antimicrobial therapy, and management
of complications: a statement for healthcare professionals
from the Committee on Rheumatic Fever, Endocarditis, and
Kawasaki Disease, Council on Cardiovascular Disease in
the Young, and the Councils on Clinical Cardiology, Stroke,
and Cardiovascular Surgery and Anesthesia, American Heart
Association: endorsed by the Infectious Diseases Society of
America. Circulation. 2005;111:e394-434.
33. Hickey EJ, Jung G, Manlhiot C, et al. Infective endocarditis in
children: native valve preservation is frequently possible despite
advanced clinical disease. Eur J Cardiothorac Surg. 2009;35:130-5.
34. Ferrieri P, Gewitz MH, Gerber MA, et al. Unique features of
infective endocarditis in childhood. Circulation. 2002;105: 2115-26.
35. Kaiser SP, Melby SJ, Zierer A, et al. Long-term outcomes
in valve replacement surgery for infective endocarditis. Ann
Thorac Surg. 2007;83:30-5.
36. Yoshinaga M, Niwa K, Niwa A, et al. Risk factors for inhospital mortality during infective endocarditis in patients
with congenital heart disease. Am J Cardiol. 2008;101:114-8.
37. Hasbun R, Vikram HR, Barakat LA, et al. Complicated leftsided native valve endocarditis in adults: risk classification for
mortality. Jama. 2003;289:1933-40.
38. Hansen D, Schmiegelow K, Jacobsen JR. Bacterial endocarditis
in children: trends in its diagnosis, course, and prognosis.
1003
C hapter
72
Noncardiac Surgery in
Ramesh Santhanakrishnan, Chandrika YR, Narendra Babu M, Gowrishankar
Introduction
Major advancements in the diagnostic/interventional
cardiology and surgical techniques, apart from the tremendous
improvement in the post-operative intensive care have resulted
in better survival of patients with congenital heart diseases
(CHD).
With far widespread availability of cardiac services in our
country and the easier access to advanced cardiac care for
the common man, we have witnessed a quantum leap in the
quality of life of children and even adults with CHD.
Consequent to the dramatically altered natural history of
CHD, increasing number of patients with CHD present to us
for various non-cardiac conditions (NCC) requiring surgical
intervention. It is essential for the concerned clinicians
to be well conversant with the implications of CHD in the
management of such conditions in order to avoid preventable
morbidity. The surgical intervention for NCC may be in the
form of:
1. Congenital anomalies associated with CHD, e.g. esophageal atresia/tracheo-esophageal fistula, exompholos
major, anorectal malformation, etc. In these cases, there is
a definite scope for prediction and evaluation and to prioritise the procedures based on the severity of the CHD.
2. Elective surgery for patients with CHD, which may be
minor procedures like hernia, undescended testis, etc.
or major procedures like pyeloplasty, major laparotomy
etc. In these situations, there is adequate time for those
involved in the management to suitably prepare for the
patient as well as the operation theatre (OT) personnel for
the intervention.
3. Emergency surgery like acute appendicitis, acute abdominal
conditions or for trauma, etc. There may not be sufficient
time for thorough evaluation and ideal preparation for the
operative intervention.
The general implications of CHD even if the surgical
intervention is for non-cardiac lesions are:
1. The parents are generally more anxious and concerned in

view of the childs existing cardiac anomaly.
2. The child/patient is also that much more anxious due to the
earlier multiple hospital visits and interventions.
3. Inappropriate anesthetice management can be disastrous to
the child.
4. Similarly, inappropriate surgical approach may also
complicate the childs problem.
5. Inadequate antibiotic prophylaxis can lead to subacute
bacterial endocarditis (SBE).
Hence, it is very essential for those handling a patient with
CHD to be aware of the implications of CHD during surgical
interventions for NCC. This chapter will outline the essential
knowledge in the assessment and management in these
situations.
Etiology
Congenital heart defects may be inherited or can result
from environmental factors, such as maternal infection or
exposure to radiation or noxious substances during pregnancy.
Congenital anomalies of the heart and blood vessels arise
during the first 10 weeks of embryonic development. The
same factors, which lead to the development of CHD may
also result in the maldevelopment of the other organs, which
develop in the same time frame.
About 5 percent of patients have chromosomal
abnormalities (e.g., trisomy 13, 18 or 21; Turners syndrome);
other anomalies may be part of a genetic syndromes (e.g.,
Holt-Oram, Noonans, Williams, 22q11 deletion).
Other possible causes are maternal illnesses (eg,
diabetes mellitus, systemic lupus erythematosus, rubella),
environmental exposures (e.g., to thalidomide or alcohol or a
combination).
Most defects are probably caused by an interaction between
inherited and environmental factors that results in arrested
embryonic development. Usually, no specific cause is identified.
Preoperative Assessment
Preoperative assessment is very essential as most of the
patients with CHD will have associated comorbidities and
other congenital anomalies. A thorough history should include
the feeding habits, the extent of physical activities, exercise
tolerance and the degree of failure to thrive. This is needed
to assess the severity of the disease. The detailed history of
the current medications the child is taking, the therapeutic
interventions the child has undergone is very essential to
formulate anesthetic plan.
Laboratory Data and Ancillary Tests

Laboratory data and ancillary tests will provide further
information regarding the diagnosis and the severity of
the disease. This will aid in preoperative optimization of

the patient and reduce the peri-operative morbidity and
mortality.
The investigations required are as follows:
Complete blood count (CBC)to rule out anemia,
polycythemia and thrombocytopenia
Prothrombin time (PT), partial thrombo plastin time (PTT)
and international normalised ratio (INR)especially if the
patient is on oral anticoagulants
Serum electrolytesespecially for patients on diuretics
and digoxin
Blood grouping and cross matchingfor patients
undergoing major surgery
ECG, ECHO, cardiac catheterization reports
Chest X-ray, where indicated.
Preoperative Preparation
1. Starvation: These children should not be starved for a
longer period especially those with cyanotic CHD as this
will lead to dehydration and thus increase the chances of
thromboembolism. They have to be taken as the first case
in the list or else a maintenance fluid has to be started in the
ward, in the preoperative waiting period.
2. SBE prophylaxis: It was long believed that antibiotics
need to be administered for children with cardiac ailments,
undergoing invasive procedures like dental, cystoscopic
or open surgery involving genitourinary/gastrointestinal/
respiratory systems to prevent infective endocarditis.
American Heart Association (AHA) had even given
guidelines which was in vogue for long.
However, recently published guidelines have begun
to focus on restricting infective endocarditis prophylaxis
for only those patients with the greatest risk of adverse
outcome undergoing specific procedures, and limiting
duration of therapy. This has helped to clear up a great deal
of ambiguity regarding who needs treatment.
The task-force of AHA critically evaluated the
effectiveness of antibiotics in preventing SBE and came
up with the following recommendation: Administration
of antibiotics solely to prevent endocarditis is not
recommended for patients who undergo a genitourinary
or gastrointestinal tract procedure. These changes are
intended to define more clearly when infective endocarditis
prophylaxis is or is not recommended and to provide
more uniform and consistent global recommendations.
These guidelines were endorsed by American Academy
of Pediatrics, Infectious Diseases Society of America, the
International Society of Chemotherapy for Infection and
Cancer, and the Pediatric Infectious Diseases Society.
Patient specific indications are outlined in Table 1.
3. Medications which the patient is taking need to continued
on the day of surgery.
72
Noncardiac Surgery in Congenital Heart Diseases
Cardiac and other anomalies can also occur as a part of a

genetic association or genetic syndrome. Genetic association
(e.g. VACTERL association - vertebral, anorectal, cardiac,
tracheoesophageal, renal and limb) can occur more often than
can be readily explained by chance of two or more traits in a
population of individuals, of which at least one trait is known
to be genetic.
The CHARGE syndrome (formerly known as CHARGE
association), is a genetic disorder leading to a set of unusual
congenital features seen in a number of newborns and
comprises coloboma of the eye, heart defects, atresia of the
nasal choanae, retardation of growth and/or development,
genital and/or urinary abnormalities, ear abnormalities and
deafness.
These associations entail a thorough clinical evaluation
of the cardia and echocardiography (ECHO) in all cases of
other congenital malformations. The implications of CHD in
these congenital NCC also involve determining the timing of
surgery for each of these conditions.
The most common CHD in these cases are atrial septal
defect (ASD)/ventricular septal defect (VSD)/patent ductus
arteriosus (PDA), which do not require too elaborate manage
ment during anesthesia or surgery and hence the congenital anomaly which is more life-threatening like esophageal
atresia/tracheoesophageal fistula, anorectal malformation, etc.
need to be addressed.
However, in some cases, there may be more complex
anomalies and hence, would require specialised care and it is
safer to shift the child to higher centre specialized in neonatal
intensive care and neonatal surgery/anesthesia.
With the advent of percutaneous device closures of ASD/
VSD/PDA, the management of these cases have become
much more easier. It is very essential that the treatment for
each child is individualized based on the condition by the
entire team comprising the cardiologist, pediatric surgeon and
the pediatric anesthetist.
1005
General Issues
13
4. Premedication: These children require a good

premedication to reduce the anxiety of parenteral separation
and to reduce the stress response. The drug used depends
upon the general condition of the patient and the severity
of the disease. Every institution has its own institutional
protocol which has to be followed. The drugs generally
used are benzodiazepines, opiates and anti-cholinergics.
5. Adequate blood and blood products should be available as
these children will have coagulopathies.
Anesthesia for Children with Congenital Heart Disease

for Non-cardiac Surgeries
Anesthesiologists will encounter children with CHD for either
elective or emergency non-cardiac surgeries at one of the
three stages:
Unpalliated CHD
Partially palliated CHD
Completely palliated CHD
Table 1
Guidelines for subacute bacterial endocarditis prophylaxis American Heart Association (AHA)
Patient: Specific Indications
As per the 2007 AHA guidelines, endocarditis prophylaxis prior to dental procedures is considered reasonable for the following highrisk patients:
Patients with prosthetic heart valves or prosthetic material used for cardiac valve repair
Patients with a history of previous infective endocarditis
Patients who have congenital heart disease (CHD) in the following categories only:
Unrepaired cyanotic CHD, including palliative shunts and conduits
Completely repaired CHD with prosthetic material/device (surgical or catheter intervention) during first 6 months following the
procedure
Repaired CHD with residual defects at or near the site of a prosthetic patch or device (thus preventing endothelialization)
Recipients of cardiac transplantation with valve regurgitation due to a structural abnormality of the valve
Procedure: Specific Indications
The procedures for which endocarditis prophylaxis is considered reasonable in high-risk patients (see above) are:
All dental procedures involving manipulation of gingival tissue or the periapical region of the teeth, or perforation of the oral
mucosa
Respiratory tract procedures involving incision or biopsy of the respiratory mucosa
Respiratory tract procedures to treat an established infection, e.g. abscess or empyema drainage
Procedures involving infected skin, skin structures, or musculoskeletal tissue
Prophylaxis prior to procedures is not recommended for:
Routine anesthetic injections through noninfected tissue
Dental radiographs
Placement or adjustment of removable prosthodontic or orthodontic appliances or brackets
Bleeding from trauma to the lips or oral mucosal
Bronchoscopy without mucosal incision
Gastrointestinal (GI) or genitourinary (GU)
Management for High Risk Patients
Give the following 30-60 min prior to procedure:
1006
If able to take oral medicines
Amoxicillin 2 grams PO
If penicillin allergic: cephalexin 2 grams or clindamycin 600 mg or azithromycin 500 mg
or clarithromycin 500 mg.*
If unable to take oral medicines
Ampicillin 2 grams IM/IV or Cefazolin 1 gram IM/IV or Ceftriaxone 1 gram IM/IV

If penicillin allergic: Cefazolin 1 gram IM/IV or Ceftriaxone 1 gram IV/IM or Clindamycin
600mg IV/IM
* Other first- or second-generation oral cephalosporin in equivalent dose may be used alternatively
Cephalosporins should not be used in an individual with a history of anaphylaxis, angioedema, or urticaria with penicillins
or ampicillin.
Pediatric dosage: Amoxicillin, Ampicillin, Cefazolin, Ceftriaxone, Cephalexin 50 mg/kg

Azithromycin, Clarithromycin 15 mgs/kg

Clindamycin 20 mgs/kg
Contd...
72
Contd...
The procedures for which endocarditis prophylaxis is considered reasonable in high-risk patients (see above) are:
If the dosage of antibiotic is inadvertently not administered before the procedure, the dosage may be administered up to 2 hours
after the procedure
For respiratory tract procedures involving incision or biopsy of the respiratory mucosa, antibiotic prophylaxis with the above
regimens is reasonable for high-risk patients. In high-risk patients with an established respiratory infection requiring procedure,
cover with a regimen against Streptococci viridans. If Staphylococcus aureus is suspected, then antistaphylococcal coverage with
penicillin or cephalosporin, or vancomycin is necessary.
For procedures on high-risk patients with infected skin, skin structure or musculoskeletal tissue, it may be reasonable to treat with
an agent active against staphylococci and hemolytic streptococci, such as an antistaphylococcal penicillin or a cephalosporin
(or vancomycin or clindamycin)
While IE prophylaxis is not recommended in general for GI/GU procedures, patients at high risk for endocarditis with ongoing
infections of the GI or GU tract should be considered for antibiotics against enterococcus. Penicillin, ampicillin, piperacillin
or vancomycin are reasonable choices. No published studies demonstrate that such therapy would prevent enterococcal IE,
however.
The objective will be a focus on preoperative assessment,

including consultation with a pediatric cardiologist, preoperative optimization, intra-operative management and postoperative care so as to minimize the peri-operative morbidity
and mortality.
Anesthetic Management
The anesthetic management regarding the induction technique,
air way management and the anesthetic maintenance are
based on the patients functional status, the pathophysiology
of the underlying defect, the proposed operative procedure
and the anticipated hemodynamic response to the anesthetic
agent. The cardiac grid (Table 2) will be useful to formulate
anesthetic plan.
Essential Monitoring during Surgery
hemodynamics. In addition, certain critical CHDs may

preclude the child to be placed in the prone position for
prolonged periods. Infundibular spasms is a very real risk
in children with Fallots tetralogy and would necessitate
expert use of beta blockers and other medications to
salvage the baby.
Coagulation issues: If the patient has a prosthetic valve,
he is likely to be on oral anticoagulants and hence will
have a prolonged prothrombin time and consequent
bleeding tendency. If the surgery is elective, the oral anticoagulants may be temporarily stopped and surgery can
be done once the PT is normalized. In the event of an
emergency surgery, it would be needed to administer fresh
It is crucial that the patient is constantly monitored during the

surgery to detect any deviation from the normal at the earliest
and responding promptly:
Precordial stethescope
ECG
Non-invasive blood pressure measurement
Oxygen saturation
End tidal carbon dioxide
Temperature
Invasive monitoring (in cases with complex CHD).
Surgical Considerations
The surgical procedures and steps are essentially the same in
these patients with CHD as those without. However, special
precautions need to be taken in the following areas:
Patient position: In general, extremes of positioning
have to be avoided as these may tend to alter the
frozen plasma to normalise the PT on an urgent basis. It

is also necessary to monitor the coagulation profile and
to restart the anti-coagulants once the surgical problem is
handled.
Blood loss/replacement will be dictated by the amount and
rapidity of the blood loss and the childs hemodynamic
status. Massive transfusions (exceeding the childs
blood volume) over a short period is likely to complicate
the issues by triggering disseminated intravascular
coagulation.
Precise and quick surgery is very much essential to
reduce the operative time and to avoid other unnecessary
morbidity. So, it is very necessary that the surgery should
be done by experienced team of surgeons with adequate
surgical alternatives if the condition so arises.
Laparoscopic and thoracoscopic surgery: Special emphasis
is placed in keeping the intra-abdominal/intrathoracic
pressures low during these procedures by keeping the carbon
dioxide flow and pressure low, as a very high pressure or a
very rapid flow rate may further strain the cardiac status.
Team approach: The importance of a team approach
with extensive preoperative planning about the possible
alternatives and preparedness for any emergencies
Noncardiac Surgery in Congenital Heart Diseases
Special Management Considerations:
1007
General Issues
13
Table 2
Cardiac grid for common congenital heart diseases (CHD) (desired hemodynamic changes)
Lesion
Preload
PVR
SVR
HR
Contractility
ASD
VSD (L-R)
TOF
IHSS
PDA
PS
AS
MS
AR
MR
AR = Aortic regurgitation; AS = Aortic stenosis; ASD = Atrial septal defect; HR = Heart rate; IHSS = Idiopathic hypertrophic subaortic stenosis; MR = Mitral
regurgitation; MS = Mitral stenosis; PDA = Patent ductus arteriosus; PS = Pulmonary stenosis; PVR = Pulmonary vascular resistance; SVR = Systemic
vascular resistance; TOF = Tetralogy of Fallot; VSD = Ventricular septal defect.
cannot be over-emphasised. Every team member

the caridologist, the pediatrician/physician, the
anesthesiologist, the surgical team, the assistants, the staff
nurses, the OT technicians and the intensive care unit
(ICU) staff is important and it is very necessary to clarify
the role of each one of them to increase efficiency and
reduce avoidable errors.
Postoperative Care
Perioperative Pain Management
Pain relief is very essential in these patients as pain causes
sympathetic stimulation with rise in blood pressure and
tachycardia, which will be detrimental in these patients as it
will increase the oxygen demand by an already compromised
heart. Pain relief can be multimodal as follows:
IV opiates like morphine, fentanyl or ramifentanyl
Regional anesthesia like caudal/lumbar epidural anesthesia
Local infiltration of the wound/local nerve blocks
Rectal paracetamol suppositories.
Postoperative Period
1008
Postoperatively, these patients are prone for hypoxia and hence

have to be monitored in the ICU. Oxygen supplementation
is needed. Ventilatory support depends on the patients
condition. Adequate postoperative analgesia is dictated by
the extent of the surgery and the patient requirement. The
careful and titrated administration of medications is very
important.
Conclusion
Surgery for non-cardiac conditions in patients with CHD is
being done increasingly, and may need to be done either on
an elective or emergency basis. Whether minor or major,
the anesthetic and surgical management is that much more
challenging due to various complicating issues. Adequate
knowledge of the pathophysiology, thorough evaluation of
the patient along with meticulous management is necessary
for handling these patients well. The cornerstone of a
successful outcome is a team work of pediatric cardiologist,
anesthesiologist and surgeon alongside the other support staff.
Life is not merely being alive, but being well.
Martial, 66 AD, Epigrams
Suggested reading
1. Bertoso SE. Anaesthesia for non-cardiac surgeries in children
with CHD. University of Philippines.
2. Cotc CJ. A practice of anaesthesia for infants and children.
3. Engelhardts T. CHD and non-cardiac surgeries. 2008.
4. Motoyama, Davis, Smith's, Text book of anaesthesia for infants
end children.
5. Nishimura RA, Carabello BA, Faxan DP, et al. ACC/AHA 2008
Guideline update on valvular heart disease: Focused update on
infective endocarditis. J An Coll Cardiol. 2008;52:676-85.
6. Ullah S. Anaesthesia for non-cardiac surgeries in patients with
CHD. 2005.
7. Wilson W, Tubert KA, Gewitz M, et al. Prevention of infective
endocarditis: Guidelines from the American Heart Association.
Circulation. 2007;115:1736-54.
C hapter
73
Anesthesia in the
Catheterisation Laboratory
Introduction
Every 15 minutes, a neonate with congenital heart disease
(CHD) is born in the US, with a reported incidence of CHD
of between 0.24 and 0.8 percent. In India, the incidence is
supposed to be more and a crude estimate suggests that about
180,000 children are born with an abnormal heart every year.
Of these, nearly 60,000 to 90,000 suffer from critical CHD
requiring early intervention. Today, the realization has come to
manage these challenging children under a specialized super
specialty called the department of pediatric cardiology and the
day is not very far in the development of a subspecialty as
pediatric cardiac anesthesia.
Role of an anesthesiologist in the present day dynamic field
of interventional pediatric cardiac catheterisation laboratory
under the department of pediatric cardiology is destined
to change fast with the recent advances in percutaneous
interventional cardiac catheterisation techniques. This is well
complimented by high quality sophisticated three-dimensional
echocardiography, as well as the cardiac magnetic resonance
imaging (CMRI). These two advanced non-invasive
diagnostic modalities can delineate the structure and function
of the heart, as well as quantify the flows and gradients across
various structures. Further cardiac catheterisation also plays
a major role in the early diagnosis of ambiguous situation in
the postoperative period. Thus, there is a significant change
from the operative to non-operative approach of a child with
a congenital heart defect. Nowadays, rarely a child with CHD
is posted exclusively for diagnostic angiography and shunt
fraction calculations. The focus has been shifted towards:
1. Assessment of physiologic parameters such as pressure
and resistance data.
2. Anatomic definition when other diagnostic modalities are
inadequate.
3. Electrophysiologic testing or treatment.
4. When therapeutic transcatheter interventions are required
on younger children with more complex CHD. Thus, in
the current era, more and more complex and prolonged
interventional cardiac procedures are ventured under

anesthesia. Further, many of these children with multiple
cardiac defects have poor operative risks. Pre-surgical
innovative interventional procedures improve the
vascular anatomy, reduce pressure loads on ventricles and
decrease the repetitive operative risks. For example, in
case of Fallot with hypoplastic pulmonary arteries (PAs),
balloon angioplasty and vascular stenting procedures
create favorable PA anatomy and reduce proximal PA
pressure and right ventricular end-diastolic pressure
(RVEDP). It has become a routine to anesthetize these
children in the pediatric catheterisation laboratory for nonoperative common interventional techniques that would
avoid surgical intervention requiring cardiopulmonary
bypass (CPB). The list of the common interventional
catheterisations at present starts from endomyocardial
biopsies, angioplasties and stenting of stenotic vessels,
dilatation of valves and conduits, occlusion techniques
for both native defects such as: device closure of atrial
septal defect (ASD), ventricular septal defect (VSD),
patent ductus arteriosus (PDA), patent foramen ovale
(PFO); coil embolization in case of decompressing veins,
aortopulmonary collaterals, surgical shunts, coronary
atrioventricular fistulas. Under the complex interventions,
one would include angioplasty for PA stenosis, dilatation or
thrombectomy for shunt thrombosis, balloon septostomy
for restrictive ASD; severe pulmonary hypertension and
extracorporeal membrane oxygenation (ECMO) left heart
decompression, angioplasty for aortic arch obstruction,
stenosis of pulmonary or systemic veins; coil embolization
for aortopulmonary collaterals and decompressing veins.
As it stands today, the latest addition to this long list of
interventions happens to be the placement of aortic
and pulmonary valve, hybrid techniques and in utero
interventions. These techniques are particularly beneficial
to children with coarctation and muscular or apical VSDs,
who are at a higher risk of operative intervention. Other
advantages include:
General Issues
13
1. Less invasive procedures compared to surgical intervention.

2. Avoidance of surgical trauma and related perioperative
morbidity.
3. All the harmful effects of CPB are avoided, including
systemic inflammatory response syndrome (SIRS).
4. Less blood loss and less trauma to various blood cells.
5. Reduced intensive care unit (ICU)/ventilator time as well
as the duration of the hospital stay.
However, the pediatric cardiac intervention procedures
are associated with certain adverse effects and complications
like:
i. Cost
ii. Dislodgement or malposition of the device or coil
resulting in embolization or obstruction or regurgitation.
iii. Unnoticed blood loss
iv. Hypothermia.
v. Vascular injury.
vi. Air embolism.
vii. Pericardial effusion.

viii. Rhythm disturbances ST segment changes,
arrhythmias, complete heart block, atrial fibrillation.
ix. Failure of the procedure and need for urgent surgical
intervention.
Physiological Considerations and Challenges

Any attempt to develop an unified approach to the anesthetic
management of the pediatric patient with CHD for cardiac
intervention is fraught with problems. The spectrum of
children who will be anesthetized will include different age
group, cardiac disease and comorbid or associated congenital
anomalies under different syndrome profile.
Cardiovascular System
1010
The CHD children have the same complex cardiac physiology

and in some cases, greater physiologic complex and less
cardiovascular reserve, and hence have high operative
mortality and morbidity. Generally, CHD is comprised of
either intracardiac or exracardiac shunting of blood and
the obstruction or regurgitation of blood flow. Alteration in
pulmonary blood flow is the major consequence of shunting
of blood flow into or away from the pulmonary circuit. This
is dependent on the presence of a communication between
systemic and pulmonary circulations, the pressure gradient
across the communication and the resistance to flow on
either side of the communication. The major consequences
of lesions that obstruct blood flow are an increase in cardiac
work to overcome the obstruction and a reduction of blood
flow distal to the obstruction. Thus, these children will be
thriving under a delicate balance and any physiological or
mechanical intervention during intracardiac intervention may
tilt the balance with an unfavorable outcome.
Noncardiac anomalies of most importance to the anesthe

siologist involve the trachea, bronchi and lungs. Tracheal
shortening or stenosis may remain unrecognized, until the
time of general anesthesia in the cardiac catheterisation
laboratory; this is especially true in children with a history
of prolonged intubation in the neonatal ICU. Respiratory,
myocardial and metabolic issues must be considered during
cardiac catheterisation and while conducting the therapeutic
interventions in a child with CHD. Neonates have limited
respiratory reserve and are prone for respiratory failure.
The diaphragm is the main muscle used for respiration and
any abdominal distension interferes with ventilation. In
infants, the high ratio of minute volume (MV) to functional
residual capacity (FRC) will lead to rapid development
of desaturation if hypoventilation or airway obstruction
occurs.
The myocardium of the newborn demonstrates diminished
contractility, reduced myocardial muscle mass with diastolic
dysfunction and reduced fiber shortening. Cardiac output is
heart rate (HR) dependent, so, bradycardia due to any cause is
not tolerated. Interventional procedures can impose pressure
load (transient valvular stenosis) and cause acute valvular
regurgitation during balloon dilatation.
Preoperative Evaluation
Each child with CHD presenting for interventional cardiac
procedure deserves an in-depth preoperative evaluation.
Important decisions will be formulated during the preoperative
visit based upon the history, physical examination, laboratory
findings and the information from the cardiac grid or road
map provided by the pediatric cardiologist.
It is worth spending some time with the child and its
parents so as to:
1. Develop a detailed understanding of the childs cardiac
anatomy and its physiologic consequences after going
through the records available and the history provided by
the parents.
2. Ascertaining anesthetic problems pertaining to the childs
cardiac condition and or concomitant congenital syndrome.
3. Counseling and educating parents would reduce the anxiety
and fear relating to the procedure and anesthetic approach
by thorough psychological preparation of the family. The
child who belongs to school-going age may be allowed to
take part during counseling.
4. Finalizing the anesthetic plan, consent, preoperative
preparation, starvation period, premedication, time of the
schedule and any extra pre or postoperative considerations
that may be necessary.
Medical History
Apart from the routine inquiries into allergies, medications,
past medical history and previous anesthetic experiences, the
The examination of children with CHD should focus on
the cardiorespiratory system and any abnormalities that
pertain to the interventional procedure. A frequent finding
in children with CHD is failure to thrive. A comparison of
the childs height, weight and head circumference against
age-standardized norms will quickly uncover children with
failure to thrive. The vital signs should also be noted with
particular attention paid to the HR, blood pressure (BP) and
room air pulse oximetry oxygen saturation (SpO2) in all four
extremities. Children with CHD are at increased risk for an
abnormal origination of the arterial supply to the extremities
and for unsuspected stenosis of peripheral vessels. In addition,
children who have undergone palliative surgical shunt
procedures, may have had the subclavian arterial supply to the
arm sacrificed on the shunted side. Neonates and infants with
preoperative bradycardia require immediate attention because
of their dependence on HR for maintenance of cardiac output.
It is mandatory to document other associated congenital
deformities that the child may be having.
Laboratory Studies
Hemoglobin
The absolute hemoglobin level must be evaluated in the light
of the patients age and disease process. Cyanotic infants,
normally do not develop the typical physiologic anemia of
infancy, because there are with a high erythropoietin levels
throughout the newborn period. In fact, the relative hypoxemia
in these children can lead to development of hemoglobin levels
more than 20 g/dL. The increase in red blood cell (RBC) mass
leads to a relative hypervolemia, increase in viscosity of the
blood, peripheral sludging, which in turn will lead to acidosis
due to poor peripheral oxygen delivery. Hence, consideration
should be given to preoperative starvation period to prevent
the risk of organ thrombosis and infarction (renal and
cerebral) specially when the child is placed on a regimen of
limited preoperative hydration or is exposed to cold ambient
operating room temperatures.
Coagulation
The finding of hemostatic abnormalities during the preoperative
laboratory evaluation is common. The erythrocytosis (older
terminology = polycythemic) child is particularly at risk
for decrease in number of functional platelets, increased
fibrinolysis and a decrease in clotting factors. All children with
CHD undergoing a major interventional procedure deserve a
preoperative hemostatic evaluation.
73
Anesthesia in the Catheterisation Laboratory
history taking portion of the childs preoperative interview

should be directed to how well the child has been coping with
the CHD. Cyanosis and congestive heart failure (CHF) are
two clinical states that can produce adverse pathophysiologic
consequences.
Parents should be questioned about the general health and
activity of their child in order to obtain some information
about cardiorespiratory reserve. This can be accomplished
by exploring the childs exercise tolerance in comparison
to siblings. A history of physical limitation with increasing
fatigability, decreasing activity, more cyanotic episodes
and increasing shortness of breath indicates that the child is
not coping well with the cardiac disease. In case of infants,
questioning the mother regarding the infants ability to feed
and to gain weight provides the required information. The
presence of dyspnea, diaphoresis, or irritability during feeding
all serve as a warning signal. For children with cyanotic
lesions, questions should be directed at determining if the
cyanosis is static, progressive, intermittent, or continuous. If
the child has hypercyanotic spells, determination should be
made of the situation with which they are associated. The
finding of a compromised cardiorespiratory reserve in any
child scheduled for a planned cardiac intervention should alert
the anesthesiologist, to have a detailed discussion with the
pediatric cardiologist and finalize the anesthesia approach and
postoperative management in an ICU. In addition, the history
or presence of neurologic impairment should be documented
preoperatively. Recent data suggest that, any child presenting
with a history of prematurity, low Apgar score and low birth
weight should alert the anesthesiologist to spend extra time to
ascertain the nature and extent of birth defects, its implication,
duration and depth of the cardiorespiratory support received
in the neonatal ICU.
Laboratory tests
Preoperative evaluation of electrolytes, particularly potassium
is recommended for all children receiving digitalis or
diuretics. In addition, infants under stress are prone to
develop hypoglycemia, hypocalcemia and metabolic acidosis.
Evaluation of arterial blood gas (ABG) along with serum
lactate level should be reserved for the children with, suspected
respiratory compromise or severe cyanosis. The existence of
partial pressure of oxygen (PaO2) in the range of 30 to 40 mm
Hg or SpO2 of less than 70 percent indicates a child at risk
for the development of metabolic acidosis. Identification and
treatment of these disturbances preoperatively is suggested,
followed by serial intraprocedural evaluations to prevent the
adverse neurologic and hemodynamic sequelae that result
from these abnormalities. Suspicion should be high in those
children who exhibit restlessness, tachycardia and tachypnea
during emergence from anesthesia.
Preoperative Fasting Recommendations

The avoidance of preoperative dehydration, hypoglycemia and
patient discomfort are especially important in children with
cyanotic CHD and erythrocytosis (polycythemia). It seems
that one can allow clear liquids up to 2 hours prior to induction
of anesthesia. Patients are more likely to be euvolemic without
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General Issues
13
hypoglycemia, and preoperative intravenous (IV) cannulation

can be avoided.
Preanesthetic Medication
Ideally a premedicant, should produce a sedate and
cooperative child at the time of separation from the parents.
Premedicants are also administered to block the unwanted
airway reflexes, decrease airway secretions, decrease gastric
volume and facilitate a smooth induction of anesthesia with
easy mask acceptance. However, some anesthesiologists
fear that even minimal respiratory depression caused by
the premedicant may result in significant oxyhemoglobin
desaturation in children with cyanotic CHD. Consensus
of several investigators is that, there will be no significant
decrease in SpO2 at 60 and 90 minutes following the oral
premedication. In this respect, oral midazolam has proved to
be a safe and efficacious premedicant. Children on blockers
drops are prone to develop bradycardia.
Preparations in the Cath Lab

For every procedure, the minimal preoperative preparation
includes checking for the presence of a functional suction
apparatus, an operational anesthesia workstation with
an appropriate pediatric circuit to reach the child, vital
monitors, a selection of airway and intubation equipment
and immediate availability of a variety of pharmacologic
agents, cardioresuscitative drugs, pacemaker with a external
pacing pads and a defibrillator with the appropriate sized
pediatric defibrillation paddles. It is a usual practice to draw
an individual anesthesia protocol beforehand. This chart will
enumerate the calculated dosage, volume and the infusion rate
of the anesthetic drugs, resuscitative drugs, vasoactive agents,
as well as the maintenance fluid in a closed system using
several programmable syringe pumps.
Venous Access
1012
Consideration should be given to the elective placement of

an IV cannula for all procedures in unstable children with
CHD, since prompt administration of parenteral medication
may be required at any given time. In case of children with
stable haemodymamic presentation, the establishment
of a functioning IV access can usually be deferred, until
after the induction of anesthesia. Availability of eutectic
mixture of lidocaine and prilocaine cream for pain free IV
cannulation may alter the approach. Special precautions are
necessary, whenever an IV cannula is placed in presence of an
intracardiac shunt to prevent inadvertent introduction of air
into the venous system. Children with right-to-left shunt, are
at risk for systemic embolization with the introduction of air
into a vein (paradoxical air embolism). Precautions to prevent
the inadvertent introduction of venous air include:
1. Meticulous preoperative deairing of all the IV tubing and

intravascular monitoring lines.
2. Use of closed system of infusion system (computer-based
syringe pumps) and the use of pressure tubing to deliver
the anesthetic drugs, as well as maintenance fluid and
electrolytes instead of routine extension tubings, which
take a larger volume to charge it.
3. Prior ejection of air from the syringe and needle before an
IV injection.
4. Keeping the syringes in the vertical position to enable air to
rise away from the outlet.
5. Avoiding injection of the last milliliter of fluid from the
syringe.
6. Using air traps whenever possible.
7. Avoiding nitrous oxide, if possible.
Monitoring
Standard monitoring for the children with CHD undergoing
interventional procedure includes: Electrocardiogram (ECG),
non-invasive blood pressure (NIBP), SpO2, capnography
(ETCO2), fraction of inspired oxygen (FIO2). temperature,
airway pressure, etc. Additional monitoring, invasive
blood pressure (IBP) and central venous pressure (CVP),
transesophageal echocardiography (TEE) and urinary catheter,
may be warranted on an individual basis when either the
childs haemodynamic presentation or proposed intervention
or anesthetic management predicts the likelihood of circulatory
instability. Both pulse oximetry and transcutaneous oxygen
and carbon dioxide evaluation have proven themselves to be
more reliable than physical observation in promptly identifying
intraoperative desaturation. Under the said conditions, in spite
of their value, the information provided by the peripheral
oxygen evaluation can be misleading and must be interpreted on
the basis of the specific clinical situation. If the pulse oximeter
is placed on an extremity with reduced blood flow, as a result
of either a previous shunting procedure, a vascular anomaly, or
direct vessel compression during the interventional procedure,
the information provided from the probe may not reflect the
childs systemic oxygenation. Although pulse oximeters have
limited accuracy of oxyhemoglobin saturation below 70
percent, they reliably predict oxyhemoglobin saturation in the
range that is normally encountered in children with cyanotic
CHD (70 to 90%). It is intuitive that acute desaturation below
70 percent, regardless of the accuracy of the pulse oximeter,
should be considered to indicate deleterious hypoxemia and
corrective measures are instituted promptly. Another limitation
of pulse oximetry is its inability to ascertain hyperoxemia,
which in neonates may contribute to the development of
retinopathy of prematurity (ROP).
Information provided by the capnography must also be
evaluated in light of the childs CHD. In the presence of rightto-left shunts, ETCO2 consistently underestimates partial
pressure of carbon dioxide (PaCO2). Another misinterpretation
Thermal Stabilization
Thermal homeostasis is a concern whenever a small child is
brought to the interventional cardiac catheterisation laboratory,
which is super cooled to keep the cardiac resynchronization
therapy (CRT) tubes and the transformer functioning. Not
only do infants exposed to cold undergo constriction of the
cutaneous vascular beds, which are directly exposed to the

cold, but reflex sympathetic activation can lead to change in
blood flow throughout the body. A reduction in temperature will
also produce a significant increase in blood viscosity, metabolic
acidosis, oxygen consumption and cardiorespiratory depression
apart from an increased overall stress and stress response. The
younger the child, the greater the risk for development of
hypothermia. There is a range of ambient temperatures called
the neutral thermal environment in which infants can exist
with the least metabolic stress. Increasing or decreasing the
ambient temperature out of this thermal range, induces increased
metabolic stress on the infant, who might already be critically
ill. However, care should be exercised, while taking measures
to keep the child warm by appropriate means like draping the
entire child with transparent self- adhesive surgical drape.
However, the practice of keeping bags or bottles containing
warm water is not recommended, since severe thermal injury
can easily occur when the cold skin comes in contact with a
warm surface. Thus, there should never be a direct skin contact
with any warm surface or a heating system.
Fluid Management
73
of ETCO2 occurs in children weighing less than 8 kg, when

continuous-flow, time-cycled ventilation is used. In this
situation, ETCO2 is diluted, leading to an underestimation of
an actual PaCO2. ETCO2 monitoring is also indicated during
balloon dilatation of valvular aortic stenosis.
If arterial cannulation is required for direct measurement of
BP and multiple sampling for ABG, the use of percutaneous
radial cannulation is recommended. In a newborn with PDA,
who is at risk for ROP, blood samples taken from arteries
arising from the aorta distal to the PDA will underestimate the
true PaO2 that is reaching the retina, because of bidirectional
shunting of blood through the PDA. This could lead to the
inadvertent use of higher than required inspired FIO2 and
increased risk of development of ROP. For this reason, one
should use right radial, brachial or axillary arterial sites for
ABG monitoring. Soon after the interventional procedure,
decision on withdrawal of the sheath is taken depending on
the status of the child at the end of the intervention. In case of
unstable children or in case of those children who may need
a surgical intervention within a short period, it is advisable
to retain the central vascular access for the postprocedural
monitoring. However, it must be recognized that in small
children retrograde embolization of air to the brain can occur
with vigorous flushing of upper extremity arterial lines.
In a very sick child with unstable cardiovascular profile,
the internal jugular veins (IJV) or external jugular veins (EJV)
are most commonly used for placement of a CVP catheter.
However, femoral and axillary veins and very rarely umbilical
veins have also been used. Although cannulation of EJV has a
low complication rate, significant percentage of these catheters
will follow an abnormal path, curving back up in the neck
and curtailing the flow and formation of venous thrombosis,
which can result in systemic embolization in patients with
intravascular shunts. The major complication with IJV is the
possibility of carotid artery puncture. This can be reduced by
using ultrasound guidance to visualize prior to cannulation.
The position of any central catheter should be confirmed with
a chest radiograph to ensure that the tip is proximal to the
superior vena cavaright atrium junction.
The use of TEE during interventional procedures has been
reserved for certain specific conditions and in which the child
is placed at risk for air embolization. As this monitoring
modality continues to gain acceptance, the number of
indications for its intraoperative use will continue to grow.
However, use of inappropriate sized TEE probes in children is
associated several problems and complications.
Fluid management must be individualized for each child

based on the patients cardiac physiology, age-specific fluid
needs, preoperative deficit and expected third-space fluid
and blood losses associated with the planned interventional
procedures. The liberalization of preoperative fasting
regimens to allow ingestion of clear liquids up to 2 hours prior
to induction of anesthesia results in most children having a
minimal deficit at the time of induction. Although most
children with CHD benefit from higher preloads, care must
be taken not to overload a child with a borderline myocardial
dysfunction. The ultimate goal of fluid management is to
produce a hemodynamically stable child during anesthesia
and the procedure, while maintaining a urine output of 0.5 to
1 ml/kg/h. Parenteral fluid must be selected, which will avoid
hypoglycaemia.
Anesthetic Management
Under the said circumstances, now-a-days the anesthesiologist
role is becoming more important, as well as challenging to
manage these children with CHD while undergoing ever new
time consuming and complicated intracardiac interventions.
For a novice, it may look like any other general anesthesia
with endotracheal intubation in a child that is blue! In fact,
the anesthetic management of interventional or diagnostic
procedures in the catheterisation laboratory must include
the same level of preparation that applies in caring for these
patients in the operating room. Managing a small and sick
cyanotic child with complex cardiac physiology for hours in an
alien dark and cold environment that is away from the regular
operation theater demands a complete and comprehensive
1013
General Issues
13
knowledge of the problems, as well as the preparedness to

face any complication that would arise out of the blue. The
set standard protocols for the interventions have been drawn
and it includes:
1. Sedation, followed by general anesthesia with endotracheal
intubation.
2. Heparinization.
3. Antibiotics.
4. TEE.
5. Preventive measures against hypoglycemia, dehydration
and hypothermia.
6. Pre- and postprocedural ECG and transthroracic echocardiography
7. Measurement of Qp:Qs and PA measurement at the time of
cardiac catheterisation.
8. Postprocedural medication includes: Aspirin 75 to 100 mg/
day for 6 months: clopidogrel 75 mg once daily for 4 weeks
and endocarditis prophylaxis for 1 year. The anesthetic
plan must consider the specific cardiology objectives of
the procedure. In general, there are three distinct periods
involved in an interventional catheterisation:
i. The data acquisition period.
ii. The interventional period.
iii. The postprocedural evaluation period.
Data Acquisition Period
1014
The pediatric cardiologist performs a hemodynamic

catheterisation to evaluate the need for and extent of the planned
intervention. In most children, access to the central circulation
is accomplished percutaneously via the femoral approach.
Those with difficult femoral access or with cavopulmonary
connections may require venous access through an internal
jugular vein. In neonates, umbilical vessels are the preferred
site for vascular access using 5 Fr catheter, specially while
performing balloon atrial septoplasty. Care should be taken to
see that the catheter is not placed in the hepatic veins.
In general, most examinations involve hemodynamic
evaluation with recording of pressure data through catheters
positioned at various sites of interest. Oxygen saturation
data are obtained by reflectance oximetry or blood gas measurement from various cardiac chambers and vessels. It is
important to recognize that, in contrast to the oxygen saturation calculations derived from a blood gas analysis, reflectance oximetry assessments are actually measured values.
This allows for the determination of oxygen content (total
amount of hemoglobin in the blood) and when combined with
values of oxygen consumption, for the assessment of blood
flows and other calculations (i.e. shunts). Additional data may
be obtained, which include pressure gradients, cardiac output
measurements, and parameters to derive vascular resistance
and valve areas. Catheterisation data obtained under normal
physiologic conditions; that is at room air: physiologic PaCO2
and spontaneous ventilation are preferred, since an increased
FIO2 or changes in PaCO2 may obscure physiologic data. To

facilitate these sampling, the child is sedated along with local
or regional (caudal) anaesthetic supplementation.
During the Procedural Period

The child is more often intubated and mechanically ventilated.
A secured airway allows the anesthesiologist to concentrate
on hemodynamic issues. Intermittent positive pressure
ventilation (IPPV) also reduces the risk of air embolism.
During the spontaneous ventilation, a large reduction in
intrathoracic pressure can entrain air into vascular sheaths and
result in moderate to large pulmonary or systemic air emboli.
Precise device placement is also facilitated with muscle
relaxants that eliminate patient movements and controlled
ventilation, thereby reducing the respiratory shifting of cardiac
structures. Substantial blood loss and change in ventricular
function occur commonly during intervention. Blood volume
replacement and inotropic support may be necessary during or
immediately after the interventional procedure. During balloon
inflation, the circulation is blocked and severe hypotension
may result, because of the critical condition of the patient and
in addition, valvular insufficiency may develop. The resulted
hypotension may not resolve immediately on deflation of the
balloon. Inotropic, antiarrhythmic therapy may be necessary
and preload may need to be optimized with intravenous fluid
administration. Other complications of the procedure are
similar to those of cardiac catheterisation.
During the Postprocedural Period

The success and the physiologic impact of the intervention
are evaluated. Continuous BP, mixed venous saturation,
ventricular end-diastolic pressure and cardiac output are used
to assess the impact of the intervention. Persistent severe
hemodynamic derangement indicates the need for monitoring
and cardiorespiratory support. support. An understanding of
the childs preoperative physiology, coupled with the impact
of anesthesia and interventional procedure on the physiology,
is helpful in predicting those patients who can be extubated in
the catheterisation laboratory on completion of the procedure
and those who should be ventilated. If the child is successfully
extubated, adequacy of oxygenation and ventilation should
be closely monitored in the postoperative room to avoid
the adverse hemodynamic consequences of hypoxia and
hypercarbia. There are no reasons to withhold adequate
treatment of pain with appropriate medication.
In general, drawing a single anesthetic management
protocol is an impossible task. Rather, the underlying
physiologic issues dictate the principles guiding the
perioperative anesthetic management of these children and this
needs emphasis. These children will present with a complex
cardiac physiology and in some cases, greater physiologic
complexity and less cardiovascular reserve to make them
pediatric age group. Cardiac anomalies vary from relatively

simple ASDs to complex congenital cardiac anomalies such
as hypoplastic left heart syndrome. Shunts may be present
at multiple levels and patients may be profoundly cyanotic.
Ventricular dysfunction may be severe with poor cardiac
reserve. Interventional catheterisation procedures can impose
acute pressure overload on the heart during balloon inflation.
Large catheters placed across mitral or tricuspid valves create
acute valvular regurgitation or in case of a small valve orifice,
transient valvular stenosis. When catheters are placed across
shunts, severe reduction in pulmonary blood flow and marked
hypoxemia may occur. These children may also have other
coexisting noncardiac congenital anomalies under the name
of several syndromes. In addition, these young patients may
be uncooperative and their parents may be severely stressed
and thus of limited assistance. Neonatal studies are frequently
performed on an emergency or time-bound basis, when these
patients are often deeply cyanotic and critically ill. Diagnosis
of the cardiac anomaly is usually made by echocardiography
before cardiac catheterisation, but determination of treatment
by catheter-based intervention is many times dependent on the
results of cardiac catheterisation.
Anesthetic techniques used in these cases range from
sedation and analgesia to complete anesthesia. Again, it
must be remembered that a steady state must be maintained
for diagnostic accuracy and during the delicate maneuvers
and placement of interventional devices. In general, older,
cooperative patients are readily managed with IV sedation and
analgesia. Even in cyanotic patients, supplemental oxygen is
not administered, unless oxygen saturation falls below baseline
levels. In general, care must be taken to maintain ventilation and
PaCO2 within normal physiologic limits to avoid alterations
in pulmonary vascular resistance. Medications administered
for sedation include fentanyl, midazolam, propofol, ketamine
and dexmedetomidine. Premedication with midazolam, 0.5
mg/kg orally, can be particularly helpful. Some evidence has
indicated that ketamine can increase oxygen consumption, so
care must be taken to ensure that it does not impair diagnostic
accuracy. Even small infants have been sedated in this manner
for these procedures.
It is said that infants and small children frequently
cannot tolerate the procedure under IV sedation alone and
are more readily managed with general anesthesia. As with
IV sedation for these procedures, premedication with oral
midazolam, 0.5 mg/kg, can be very helpful. If IV access is
not present, induction with inhaled nitrous oxide, oxygen and
a volatile anesthetic such as sevoflurane is performed. Potent
inhaled anesthetics are generally not used as the primary
anesthetic, because of their negative inotropic effects, they
are reserved for adjunctive anesthesia. In presence of an
IV access, induction and maintenance with thiopental,
ketamine, etomidate, propofol, dexmedetomidine, fentanyl,
alfentanil or remifentanil is used. Precise device placement
is also facilitated with muscle relaxants that eliminate patient
73
high operative risk subjects. Each child is unique and thus,

an anesthetic plan must be tailored to the specific needs of
that individual patient. The safe anesthetic management of
children with CHD during cardiac intervention requires not
only familiarity with the principles of pediatric anesthesia, but
a thorough understanding of the specific cardiac lesion and
residual problems that are likely to exist following any given
cardiac interventional procedure.
The anesthesiologist attending to these procedures must
understand the underlying pathphysiology, the purpose of the
study and the anesthesia-induced changes in the hemodynamic
parameters. The cardiovascular and respiratory side effects
of drugs, anesthetic techniques and the circuit chosen, must
be carefully considered to avoid distorting the hemodynamic
measurements. Room air ventilation may be required during
acquisition of hemodynamic and oxygen saturation data.
Drugs used for sedation and anesthesia should have minimal
cardiovascular side-effects and a normal acid-base balance
should be maintained, especially if shunt fraction are to be
calculated. Attention also to be given towards the blood loss
during repeated blood sampling and also the heparin level
before shifting the child out of the catheterisation laboratory.
The pediatric cardiac catheterisation laboratory provides
an opportunity to face the unique challenges for the
anesthesiologist, while anesthetizing the children with complex
cardiac physiology and in some cases, greater physiologic
complexity and less cardiovascular reserve, because of their
poorer operative risks. The anesthesiologists plan must
consider the specific cardiology objectives of the procedure
and the impact of anesthetic management in facilitating or
hindering the interventional procedure. Today, there is an
increasing demand to provide sedation or general anesthesia
for children undergoing diagnostic and therapeutic procedures
in the cardiac catheterisation laboratory. This demand is
driven by the pediatric cardiologists realization that general
anesthesia or sedation that provides analgesia, amnesia and
immobility by anesthesiologist is safe, reliable and efficient.
However, in clinical scenario it is not uncommon to encounter
a child who appears well sedated at the beginning of the case
only to start moving during vascular access and other critical
times. Additional doses of sedatives may then result unwanted
deeper sedation, resulting in loss of airway and desaturation.
The hues in these already blue baby can quickly change
to gray within seconds. The added complexity of the new
monitoring and rescue standards imposed by regulatory
agencies, such as the Joint Commission for Accreditation of
Healthcare Organization (JCAHO), the American Society
of Anesthesiologists (ASA) and the American Academy
of Pediatrics (AAP), have made it more attractive for the
pediatric specialists to delegate the responsibility for sedation
to properly trained and accredited cardiac anesthesiologists.
Anesthetic management for cardiac catheterisation in pediatric
patients can be uniquely challenging, since these patients
range in age from premature neonates to the upper limits of the
1015
General Issues
13
1016
movements and controlled ventilation, thereby reducing

the respiratory shifting of cardiac structures. Older patients
usually tolerate this procedure when local anesthetics are
infiltrated at the site of catheter entry. Intravenous sedation
with fentanyl, midazolam, and propofol attenuates discomfort
related to the environment and balloon inflation. When the
aortic valve is to be dilated, two IV catheters are inserted.
Valvuloplasty of other valves requires only a single IV
catheter. If the patient becomes hemodynamically unstable,
the balloon must be deflated immediately. Vagal stimulation
can occur with balloon inflation and may require treatment
with atropine. Should major complications ensue, prompt
surgical intervention may be necessary.
Nitrous oxide is also a direct myocardial depressant and its
effect seems to be more pronounced in children than adults.
Other effects of nitrous oxide include a more rapid uptake in
infants, an elevation in both systemic vascular resistance (SVR)
and pulmonary vascular resistance (PVR) and reductions in
HR and mean arterial pressure (MAP). The decision whether
to use nitrous oxide must be assessed in light of the individual
childs cardiovascular requirements. The augmentation of
PVR may be significant, especially in children with preexisting pulmonary hypertension. Isoflurane also produces a
dose-dependent depression of the myocardium, although to a
lesser extent than halothane. The primary reason isoflurane has
not replaced halothane as an inhalation induction agent is its
pungent odor, which results in a higher incidence of coughing
and laryngospasm. Sevoflurane produces less myocardial
depression than either halothane or isoflurane, which make it
a valuable induction agent for children with CHD.
An IV induction is a good alternative for children with
indwelling venous catheters, in children who prefer neither to
smell the gas nor to have a mask placed near their faces and
in patients with significant cardiovascular compromise who
might not tolerate the depressant effect of a potent inhaled
agent. Ketamines central sympathetic activation compensates
for its mild direct myocardial depressant effect, resulting in
hemodynamic stability in most patients. Other advantages
of ketamine include the ability to use a high FIO2, decreased
bronchial reactivity and some antiarrhythmogenic activity.
Intramuscular ketamine (2 to 10 mg/kg) can be particularly
helpful in the older extremely combative child.
Synthetic narcotics including fentanyl has theoretical
advantages in children with minimal cardiac reserve. Propofol
has been used as a safe induction agent in healthy children,
although significant fall in BP are frequently observed.
Intranasal midazolam, oral midazolam or intramuscular (IM)
midazolam; oral ketamine, rectal methohexital and transoral
mucosal fentanyl have also been tried. The art of anesthesia
requires not only the selection of the best possible anesthetic
combination to meet the patients hemodynamic requirements,
but also the appropriate clinical responses when undesired
effects materialize.
Regional anesthetic techniques serve as useful adjuvants
to general anesthesia in children with CHD, as in other
pediatric patients. With possible exception of the presence of

a coagulopathy, children with CHD should be considered for
regional anesthesia with the following caveats:
1. Because the lungs may absorb up to 80 percent if the local
anesthetic in the first passage, the risk of local anesthetic
toxicity is theoretically increased in children with right-toleft shunts.
2. Vasodilatation resulting from central axis blockade may be
hazardous in patients with significant aortic stenosis or other
left-sided obstructive lesions. It may cause an increased
right-to-left shunt in susceptible children. On the other hand,
peripheral vasodilatation in patients with polycythemia
may have benefit of improved microcirculatory flow and
decreased venous thrombosis. Children less than 6 years of
age will have little, if any, decrease in systolic BP as a result
of spinal anesthesia.
No agent exists that is always contraindicated in children
with CHD. All anesthetic agents, however, may cause
hemodynamic compromise when given to susceptible patients
in certain situations. Inhalational anesthetics are classic
examples. Because of their propensity to cause peripheral
vasodilatation, inhalational induction in children with rightto-left shunts may result in an increased shunt fraction and
cyanosis. Children with cyanotic CHD have less oxygenated
blood entering the systemic circuit. The brain is exposed to
a lower concentration of anesthestic gas, causing slowing of
anesthetic induction, This slowing is particularly pronounced
when the more soluble anesthetic agent is chosen. Theoretically,
IV induction agents like ketamine should have a more rapid
onset of action in patients with limited pulmonary blood flow,
since the agent would more rapidly reach the systemic circuit.
Congenital heart defects with left-to-right shunting of blood
have a relative over perfusion of the pulmonary circuit. The
blood from lungs, which already contains the inhalational
anesthetic agent, is recirculated through the pulmonary circuit,
thereby acquiring additional anesthetic. The result is a higher
peak anesthetic concentration in the blood that eventually
reaches the brain. The higher peak anesthetic concentration
would theoretically allow a more rapid inhalation anesthetic
induction. However, in clinical practice, the speed of induction
is insignificantly increased, unless there is a concurrent fall
in cardiac output. Intravenous anesthetic induction might
be expected to have a slower onset of action as a result of a
delay in reaching the brain during the period of recirculation
through the pulmonary circuit. However, in clinical practice,
this effect is of minimal importance. A comparison of onset
times for muscle relaxation in children with both cyanotic and
acyanotic CHD revealed no difference.
A non-depolarizing neuromuscular relaxant is administered
and endotracheal intubation is carried out when the patient is
fully relaxed. Correct endotracheal tube position is confirmed
by end-tidal CO2 measurement and position above the
carina is readily confirmed with fluoroscopy. Anesthesia is
maintained with volatile anesthetics and controlled ventilation
with room air, as long as oxygen saturation does not fall below
administered to balance the osmotic effects of contrast media,

which could result in hemoconcentration and microembolic
events.
Complications
There are numerous case reports describing pediatric sedation
complications during cardiac catheterisation and intervention,
but there are few hard data on the frequency of such incidents.
Thus it is difficult to assign a true incidence of risk to the
children with CHD undergoing elective cardiac intervention.
As in case of a child with CHD undergoing a noncardiac
surgery, many factors, such as the nature of the anomaly,
associated systemic disease, age of the child, level of sedation,
type of drugs used, monitors and most important, the training
and experience of the anesthesiologist, so forth will contribute
towards mortality if not morbidity. A retrospective chart
review by Hennein et al found that 14 children with simple
CHD died during or after 152 procedures (9%); 11 of these
children had a PDA. 14 children with complex CHD died
during or after 74 procedures (19%). Risk factors associated
with postoperative mortality include young age, low birth
weight, low Apgar score, presence of complex CHD, high
ASA score, emergency surgery, major surgery and duration
of preoperative hospitalization. Thus, when formulating an
anesthetic plan, incorporation of the specific hemodynamic
needs dictated by the cardiac lesion is best accomplished
through the development of a cardiac grid. The formation of
such a grid helps to sort out the often complex and contradictory
physiologic needs presented by the childs cardiac lesion, in
conjunction with the hemodynamic needs mandated by active
disease process for which surgery is being provided.
Complications are more common in infants younger than
6 months. During interventional catheterisation, arrhythmias,
especially heart block, bleeding at vascular access sites,
perforation of cardiac chambers or great vessels by catheters,
vascular dissection or hematoma, embolic phenomena and
arterial thrombosis, hemodynamic instability, embolization of
device or coils, perforation of major vessel or heart are the
most frequent complication. Supraventricular tachycardias
are the most common and are often related to catheter tip
placement, in which case the arrhythmias usually resolve on
withdrawal of the catheter. Occasionally, vagal maneuvers, IV
medication, or cardioversion may be necessary to terminate the
arrhythmia. Second- or third-degree heart block may also be
seen. Sinus bradycardia may require treatment with atropine.
Profound bradycardia may necessitate temporary ventricular
pacing, if hemodynamic instability results. Thus, constant
vigilance, correction of electrolyte imbalance, maintenance of
acid-base status and appropriate heparinization will mitigate
some of the morbidity. Appropriate and early transfusion with
deployment of rapid response ECMO or recently introduced
portable CPB machine in the resuscitation of an infant in
cardiac improves outcome. In a patient undergoing diagnostic
73
baseline levels. Controlled ventilation avoids the increase in

PaCO2 frequently seen with levels of IV sedation adequate
to allow performance of this invasive procedure in pediatric
patients. Controlled ventilation has not been found to affect
the diagnostic accuracy of cardiac catheterisation. Minute
ventilation and the respiratory rate are adjusted to maintain
normal PaCO2 based on analysis of arterial gases from blood
drawn by the cardiologist from the arterial catheter. The endtidal CO2 determination can be used to subsequently adjust
ventilation, but it must be remembered that physiologic
dead space is highly variable in these patients. Infiltration of
local anesthetic at vascular access sites limits postprocedure
discomfort. Small amounts of an opioid such as fentanyl (i.e.
1 to 2 g/kg IV) or midazolam may be administered to provide
postprocedure sedation, thus allowing the child to remain still
and avoid bleeding complications at the femoral vascular
access sites. As an alternative to a volatile anesthesia-based
technique, the patient can be managed with total IV anesthesia
using various combinations of opioids, benzodiazepines,
propofol and ketamine. Again, steady-state conditions are
essential and the anesthetic plan at any institution should be
consistent from patient to patient to provide reproducible
patient conditions for the interventional pediatric cardiologists
who must interpret the diagnostic data.
In the postprocedural period, the success and the
physiologic impact of the intervention are evaluated. Blood
pressure mixed venous oxygen saturation, ventricular enddiastolic pressure and cardiac output, when available, are used
to assess the impact of the intervention. During this period
close monitoring of these children is required. Especially in
neonates, deterioration can be rapid. These patients may be
very sensitive to anesthetics and hemodynamic instability
may ensue. Repeated blood gas analysis is necessary, because
metabolic acidosis may be the initial sign of a low cardiac
output state. Even mild degrees of metabolic acidosis should
be treated in critically ill patients and inotropic therapy may
be necessary. Hypocalcemia and hypoglycemia may develop
in neonates and require treatment. Hypothermia can be a
problem in young patients, especially those under general
anesthesia. The room may need to be warmed. In addition,
inspired gases may need to be warmed and humidified and
a warming blanket or forced-air warming system should be
available. Rectal temperature may need to be monitored in
small patients, because an esophageal or axillary probe may
intrude into the cardiologists imaging area. Substantial blood
loss and changes in ventricular function occur commonly
during intervention. This is less well tolerated than in
larger patients, because the loss may represent a significant
fraction of a smaller patients blood volume. Hematocrit
must be monitored carefully and anemia must be treated
appropriately. Blood volume replacement and inotropic
support may be necessary during or immediately after the
interventional procedure. Deeply cyanotic patients tend
towards polycythemia as they age and sufficient fluids must be
1017
General Issues
13
evaluation of pulmonary arterial hypertension, despite high

risk of the procedure in a child with suprasystemic right
ventricular pressure, they are best managed with general
anesthesia and controlled ventilation.
Pericardial tamponade can be detected by characteristic
hemodynamic alterations, as well as by a widened mediastinum
and reduced cardiac motion on fluoroscopy. A definitive
diagnosis of tamponade is best made by echocardiography,
which is readily available and can be used to guide emergency
pericardiocentesis. The pericardiocentesis catheter can cause
arrhythmias by mechanical irritation. These arrhythmias can
be supraventricular or ventricular and they may be poorly
tolerated in critically ill patients. As with coronary angiography,
emergency surgical procedures may be necessary and hospital
systems must allow rapid, safe transport of these patients to
the operating suite.
Special Considerations in Children Following

Interventional Procedures and the Associated
Anesthetic Implications
Pediatric Interventional Cardiology
1018
Pediatric interventional cardiology, a new and challenging

specialty was born in the year 1966, when William Rashkind
developed balloon septostomy in neonates for transposition
of the great arteries (TGA). The last two decades has seen an
exponential growth of this field.
During this period, improved versions of devices to close
septal defects and extracardiac shunts, as well as the techniques
to open up stenosed valves and vessels, has revolutionized the
therapy for CHD. This transcatheter approach has replaced the
cumbersome intracardiac surgical approach for simple intraand extracardiac lesions. Recent technological innovations
and miniaturization have greatly enhanced the possibility
of venturing into areas, where no one ventured before
under hybrid techniques and in utero interventions. Thus
interventional therapy has become an acceptable alternative
treatment for many congenital heart disease, including closure
of ASDs, muscular VSDs, PDA, dilatation of stenosed valves
(aortic and pulmonary) and dilatation of stenotic vessels
(branch pulmonary arteries, coarctation of aorta).
For a better understanding, the recent advances in pediatric
interventional cardiology one can broadly subdivide them
into:
Device closures for septal defects and other vascular
structures
Balloon dilatation of valves, vessels and stenting of
narrowed vessels, baffles and conduits
Percutaneous transcatheter valve implantation
Hybrid techniques involving transcatheter intervention as
well as surgical intervention
In utero interventions for aortic stenosis.
Procedures are performed using right and left heart study to
accurately diagnose and to get a proper anatomic perspective
of different congenital heart disease and the associated

altered cardiac anatomy. Commonly performed interventional
procedures are balloon atrial septostomy for TGA with intact
ventricular septum, embolization of major aortopulmonary
collateral arteries and PDA, closure of ASD as well as VSD,
using double-umbrella devices, balloon dilatation of stenosed
valves, coarctation of aorta and stenosed peripheral branches
of pulmonary arteries. Among these, the intense anesthetic
challenges during the balloon dilatation of congenital aortic
valve stenosis has drawn the attention of the anesthesiologists to
overcome the challenges towards improving the safety during
the critical phase of the procedure. Rarely the implantation of
a programmable pacemaker in a small childs abdominal wall
or changing the worn-out battery are carried out in the cath lab
under general anesthesia.
Practical Concepts Regarding the Interpretation of a

Catheterisation Report
Pressure Data
Atrial pressure tracings are characterized by several up waves
(a, c and v waves) and descents (x and y). The right atrial
pressures are normally less than 5 mm Hg. In the presence
of significant triscupid regurgitation (TR) or a junctional
rhythm, the v wave becomes the dominant wave. The left
atrial pressure (LAP) tracing in contrast to the right atrium,
displays v dominance, which is accentuated during mitral
regurgitation. The mean LAP rarely exceeds 8 mm Hg. The
reported values for atrial pressures correspond to the a and
v waves and the mean pressure. Ventricular pressures are
recorded and reported during systole, at end-systole and at
end-diastole. For the right ventricle, the systolic pressue is
normally in the 25 to 30 mm Hg range, with end-diastolic
pressure of 5 to 7 mm Hg. The systolic pressure in the left
ventricle normally increases with age and should equal the
systolic arterial pressure; the end-diastolic pressure is typically
less than 10 mm Hg. The pulmonary artery pressure (PAP) is
reported in terms of systolic, diastolic and mean pressures.
The systolic PAP in a normal child should be equal to the RV
systolic pressure and the mean PAP should not exceed 20 mm
Hg. The pulmonary artery wedge pressure (PAWP) is obtained
by advancing the catheter into a distal vessel until it is occluded
and it reflects the LAP. The aortic pressure and contour of the
tracing varies depending on the site of interrogation. Typically,
there is an increase in the systolic pressure as the catheter
navigates toward the peripheral circulation. This phenomenon
is known as pulse wave amplification.
Pressure gradient represent the differences between two
distinct sites and can be measured in a number of ways
(mean gradient and peak gradient). It is important to consier
that a number of factors may affect the determination of
pressure gradients. The flow across the lesion is significantly
influenced by the severity of the obstruction and the
ventricular function.
Shunt Calculations
Qp/Qs =
(SaO2 MvO2)
(PvO2 PaO2)
Where, SaO2 = systemic arterial saturation, MvO2 = mixed

venous O2 saturation, PvO2 = pulmonary venous O2 saturation
and PaO2 = pulmonary arterial O2 saturation. A Qp:Qs
ratio which exceeds 2:1 is considered a significant shunt,
although smaller ratios may be associated with significant
symptomatology.
Cardiac Output Determinations

The volume of blood ejected by the heart into the systemic
circulation, or cardiac output, can be derived in several ways.
Thermodilution measurements use saline as an indicator to
measure pulmonary blood flow. In the absence of intracardiac
shunts, this is equivalent to the systemic blood flow or cardiac
output and is expressed as liters per minute. In the Fick
method, oxygen is used as an indicator and cardiac output is
obtained by application of the following formula:
Qs(L/min) = Vo2 (L/min)/SaO2 content MvO2 content
Where Vo2 = oxygen consumption (assumed or measured),
SaO2 = systemic arterial O2 content, MvO2 = mixed venous
oxygen content. Oxygen content = oxygen saturation (1.36
10 hemoglobin concentration).
Vascular Resistance
Resistance represents the change in pressure in the systemic or
pulmonary circulation with respect to flow. This is expressed
as mm Hg/L/min (Wood units) and is usually normalized for
body surface area.
The systemic (SVR) and pulmonary vascular resistance
(PVR) are derived as follows:
SVR
=
(aortic mean pressureright atrial mean
pressure)/Qs.
PVR = (pulmonary artery mean pressurepulmonary
capillary wedge pressure or left atrial pressure)/
Qp.
Radiofrequency Ablation of
Accessory Pathways
Radiofrequency ablation is a nonsurgical approach designed to
eliminate atrial or ventricular reentrant tachyarrhythmias. The
technique requires pathway mapping and precision ablation
of the aberrant pathway using a radiofrequency ablation
catheter. During the ablation, unexpected patient movement
Electrophysiologic Studies and Catheter

Ablation of Abnormal Conduction Pathways
Electrophysiologic studies including cardiac event monitoring
and insertable cardiac recorders involve the placement of
special multipolar catheters within cardiac chambers to
define the mechanism, origin and pathways of arrhythmias
and to determine the best therapeutic options. Vascular
access is usually achieved through the femoral artery and
vein and frequently, additional catheters are placed through
the internal jugular vein, with obvious implications for
airway management. Programmed electrical stimulation
is performed at various locations with the use of standard
transvascular catheterisation techniques. By using specifically
timed electrical impulses, the arrhythmia is reproduced under
controlled conditions and monitored through the catheters
and the surface ECG leads. Electrical energy delivered
through appropriately positioned catheters can then be used
to ablate arrhythmogenic foci or accessory pathways. Another
intervention that may also be performed in the laboratory is to
place the electrodes precisely for subsequent connection to an
implantable defibrillator.
Antiarrhythmic drugs are stopped before these studies
and are avoided during the procedure, because they may
prevent detection of the accessory conducting pathways
and arrhythmogenic foci. Formerly, these procedures were
performed under sedation, because the lead technology
was exquisitely sensitive to subtle anesthetic drug effects
on the conduction pathways. However, improvement in the
technology has made this problem less of a concern and
we generally perform the more complex electrophysiology
procedures under general anesthesia, so as to avoid
unexpected movements during ablation, which in turn may
result in catheter displacement and damage normal conductive
tissue. Anesthetic agents and techniques should be chosen to
maintain circulating catecholamines and avoid suppression
of arrhythmias, for identification of aberrant pathways.
Continuous infusion of propofol and opioids or low-dose
volatile anesthetics are equally effective. Under certain
circumstances, inotropic support in the form of isoproterenol
infusion of rapid atrial pacing may be required, but this must
73
Shunts are characterized in terms of their direction, i.e. left

to right, right to left, bidirectional and the magnitude. Leftto-right shunts can be quantified based on the ratio of the
pulmonary (Qp) to systemic (Qs) blood flow ratio as follows.
may result in catheter dislodgment and damage to normal

conducting tissue, so general anesthesia is usually required
in younger children. Rapid atrial pacing and occasionally,
an isoproterenol infusion are required during the mapping
procedure. Severe postprocedural cardiomyopathy has been
described, but is very unusual. An underlying cardiomyopathy
from frequent episodes of supraventricular tachycardia and
myocardial oxygen imbalance caused by prolonged periods
of rapid atrial pacing and isoproterenol infusions are the
presumed causative factors. An arterial line is helpful during
these lengthy procedures for continuous monitoring of blood
pressure and blood gases.
1019
General Issues
13
1020
be discussed with the electrophysiologists and the procedure

may best be performed with temporary ventricular assist
device support, as discussed earlier.
Intraatrial tachycardia is associated with significant
morbidity and mortality for many children with repaired CHD,
particularly after extensive atrial surgery, such as Fontan
and atrial switch operations. Careful choice of anesthetic,
monitoring and early management of low cardiac output are
important.
Strict attention to arm support and padding of all pressure
points are essential. Tension on the brachial plexus must be
avoided, especially if arms are secured next to head at less
than 90 flexion/extension. In addition, pressure on the
radial nerve at the elbow can occur, especially for the longer
radiofrequency arrhythmia ablation procedures. A peripheral
arterial catheter is helpful during these lengthy procedures for
continuous monitoring of arterial blood pressure and blood
gases.
Automatic implantable cardioverter defibrillators (AICDs)

are placed for life-threatening ventricular arrhythmias, which
include long QT syndrome, hypertrophic cardiomyopathy,
and arrhythmogenic right ventricular dysplasia. These devices
are placed with the patient under general anesthesia with
endotracheal intubation and controlled ventilation. Invasive
pressure monitoring is typically used. Adequate analgesia can
be provided with local infiltration with local anesthetics and
short acting IV opioids.
Biventricular pacing is an attempt to resynchronize
ventricular function by pacing both ventricles, thereby
improving overall ventricular function. Multisite pacing has
been attempted in pediatric patients. Two atrial and three
ventricular epicardial leads are placed at the time of surgery,
with the ventricular leads placed as far from one another as
possible. Atrial synchronous ventricular pacing is established
postoperatively and the AV interval is adjusted to yield the
narrowest QRS complex, while simultaneously pacing two
ventricular sites.
Pacemaker and Cardioverter-Defibrillator

Implantation
Cardioversion
Permanent pacemaker and implantable cardioverterdefibrillator (ICD) are frequently implanted in the cardiac
catheterisation laboratory. Implantation of both devices
involves placement of transvenous leads into the cardiac
chambers (usually the right atrium or ventricle or both) with
tunneling of the leads to a subcutaneous pocket in which the
device is placed. Many of these procedures are performed
with sedation/analgesia. General anesthesia is necessary
during testing of the ICD. When the ICD is tested, ventricular
tachycardia or fibrillation is induced and the ability of the
device to sense the arrhythmia and deliver appropriate
cardioversion-defibrillation energy is confirmed. Many
patients undergoing ICD placement have poor ventricular
function. Return of hemodynamic variables to baseline after
cardioversion-defibrillation must be closely monitored. In
addition to placement of devices, obsolete, malfunctioning,
or infected pacemaker or ICD leads (or both) may need to
be removed. Pacemaker or ICD lead extraction is not to be
considered uncomplicated. Major complications are rare,
but complications such as rupture of the superior vena cava,
right atrium, or RV obviously require prompt intervention.
Additionally, severe tricuspid regurgitation may result from
removal of right ventricular leads adherent to the valvular
or subvalvular apparatus, but it generally requires less acute
intervention. Leads in place for longer than 1 year may
have extensive fibrosis, which may make removal difficult.
Placement of additional leads may result in additional fibrosis
and eventually lead to vascular occlusion. Therefore, lead
extraction before replacement may be beneficial. Clearly,
infected leads require extraction. Powered telescoping
sheaths, which detach the leads from fibrotic attachments
by means of lasers or mechanical means, have improved the
ability to remove adherent leads.
Cardioversion is used to convert supraventricular and

ventricular arrhythmias to sinus rhythm by delivery of
synchronized direct-current electric shock. Current evidence
indicates that biphasic shock delivery is superior to the damped
sinusoidal current formerly used. When these arrhythmias are
not causing hemodynamic instability or when the arrhythmia
is of long-standing duration and has not responded to drug
therapy, cardioversion can be performed on an elective and
possibly an outpatient basis. The patient's cardiovascular
status and medical therapy are optimized before elective
cardioversion. In contrast, emergency cardioversion is often
required when the arrhythmia causes hemodynamic instability
and the patient's condition may not allow full evaluation or
administration of anesthesia.
Elective cardioversion is uncomfortable and general
anesthesia is required. Many medications have been used,
including barbiturates, propofol, etomidate, opiates and
benzodiazepines. In the case of chronic atrial fibrillation,
echocardiography is performed before cardioversion to rule
out the presence of left atrial thrombi, which could cause
stroke. Standard monitoring is used and standards for the
availability of equipment must be observed. When all is in
readiness for cardioversion, the patient is preoxygenated and
then given small incremental doses of anesthetic, until the
eyelid reflex is abolished. Immediately before the counter
shock, the mask is removed and it is confirmed that no person
is touching the patient or cart. More than one shock may be
required to restore sinus rhythm and it is important to keep
the patient anesthetized, until the procedure is successful or
the attempt is terminated. After cardioversion, the patient
is ventilated with 100 percent oxygen, until consciousness
is regained and the patient is able to maintain the airway. It
should be noted that muscle relaxants are not typically needed
Typically, endomyocardial biopsies are performed both as
part of post-transplant surveillance catheterisation or to
confirm the diagnosis of myocarditis or cardiomyopathy. It
is done at regular intervals to ascertain absence of rejection
in patients after orthotopic heart transplantation. Right- sided
catheterisation is usually performed via access of the right
internal jugular vein, through which the long sheath and
biotome are introduced. Usually five to eight samples are
taken. Sedation or general anesthesia is required for smaller
children, although older children can undergo the procedure
with local anesthesia alone.
Cardiac catheterisation of patients supported by ECMO:
Indications include assessment of surgical repair, leftsided heart decompression, myocarditis/cardiomyopathy,
hemodynamic assessment, catheter interventions and ablation
of arrhythmias. The anesthesiologist coordinates safe
transport of the patient on mechanical support with perfusion
and nursing team. Anesthesia is provided using isoflurane or
sedatives on the ECMO circuit and paralysis must be achieved
before transport. Rest ventilation is continued.
CONCLUSION
Anesthesiologists caring for patients in the cardiac catheterisation laboratory must remain abreast of these developments
and understand the implications for intraoperative monitoring, such as invasive lines and TEE, as well as the anesthetic
implications of these developing procedures. Again, timely,
preprocedure communication with the cardiologists involved
is essential. Further, children with CHD undergoing interventional cardiac (surgical) procedures require that the anesthesiologist appreciate the cardiac physiology and formulate a plan
based on the principles dictated by that altered physiology.
Taking into confidence the child, caretakers and the primary
physician as partners and also strict adherence to the details

will enhance the possibility of a better outcome. However,
fully equipped catheterisation laboratory, surgical backup and
ECMO support capability should be available in any center
planning interventional cardiac catheterisation. These days,
the transcatheter interventional techniques have radically
altered the outlook for children with CHDs and close cooperation between the teams has gone a long way in developing techniques to improve the morbidity and mortality rates in
these young and often very sick patients.
Always laugh when you can, it is cheap medicine.
George Gordon Byron
Suggested reading
1. A practice of anesthesia in infants and children. Cote J, Lerman
J, Todres D (Eds), 4th edition: Saunders Elsevier; 2009. pp.
452-64.
2. Heart by Hurst. 12th edition, Fuster. O Rourke, Walsh. Poole
Wilson: King III Roberts Nash Prystowsky.
3. Hijazi ZM, Awad SM. Pediatric cardiac interventions. JACC
4. Jobeir A, Galal MO, Bulbul ZB, et al. Use of low dose ketamine
and/or midazolam for pediatric cardiac catheterisation. Pediatr
Cardiol. 2003;24:236-43.
5. Kumar RK, Srivastava S. Pediatric heart care in India. Heart.
2008;94:984-90.
6. Lucas VS. Pediatric cardiovascular interventions: the good, the
bad, and the ugly. Catheter Cardiovasc Interv; 2009;74:916.
7. Mehta R, Lee KJ, Chaturvedi R, Benson L. Complications of
pediatric cardiac catheterisation: a review in the current era.
8. Millers Anaesthesia: Anesthesia for Interventional or
Diagnostic Cardiac Procedures. Miller RD, Eriksson LI,
Fleisher LA, Wiener-Kronish JP, Young Wl (Eds). 7th edition:
Churchill Livingstone Elsevier. 2010. pp. 2638-42.
9. Nair SG. Pediatric Cardiac Program in India: Changing
Perspective. Ann Card Anaesth. 2011;14:79-81.
10. Saxena A. Congenital Heart Disease in India: A status report:
Ind J Pediatr. 2004;72:595-8.
11. Smiths Anesthesia for Infants and Children. Seventh edition.
Mosby Elsevier; 2006. pp. 635-8.
12. Verghese ST, Martin GR. Heavy sedation versus general anesthesia
for pediatric invasive cardiology: A grayer shade of blue versus a
pinker shade of pale? Pediatr Cardiol. 2003;24:193-4.
73
for this procedure. If cardioversion is required on an urgent

basis, it must be remembered that the patient may not have
been fasting before the procedure. To prevent aspiration during
anesthesia in this situation, it is appropriate to intubate the
trachea with a rapid-sequence induction technique involving
the use of cricoid pressure.
1021
C hapter
74
Anesthesia for Surgical Repair of

The process of intracardiac repair of congenital heart defect

pushes human physiology to its limits. No where else in
medicine are patients exposed to such biologic extremes as
during congenital heart surgery. Patients may be cooled to 15
to 18C, be acutely hemodiluted to upward of 50 percent of
their extracellular fluid volume, and undergo periods of total
circulatory arrest. Managing patients with abnormal blood
flow patterns exposed to these physiologic extremes is the
challenge facing the anesthesiologist. Knowledge generated
from operating rooms, intensive care units, catheterization
and echocardiography laboratories, and animal experiments
have been invaluable in improving care of these patients.
Clearly, the successful perioperative management of
these patients cannot occur without a skilled group of
multispecialty physicians, pediatric cardiologists, anesthe
siologists, perfusionists, nurses, and respiratory therapists
dedicated to the congenital cardiac patient. This team-oriented
approach has evolved from an idealized guidelines set forth
by the American Academy of Pediatrics (AAP) in 2002 to
establish pediatric cardiovascular centers. Paramount to the
AAP guidelines are dedicated facilities, personnel, and patient
volume. The basis for these guidelines is provided by studies
that have demonstrated a reduced mortality rate with increased
hospital and surgical volume. In fact studies have demonstrated
that regionalization reduces pediatric cardiac surgical deaths,
with evidence-based studies outlining the benefits of referral
to larger institutions and studies demonstrating a strong
relationship between operator volume and outcomes with
adult interventional catheterization procedures. In sixteen
New York hospitals evaluated who were performing fewer
than 100 congenital cardiac surgeries a year, the mortality
rate was 8.3 percent compared with a mortality rate of 6.0
percent for hospitals performing more than 100 cases per year.
Mortality also correlated with the individual surgeons annual
case volume. Surgeons performing 75 or fewer operations a
year had an in-hospital mortality rate of 8.8 percent versus
6.0 percent for surgeons with annual volumes of more than 75
operations per year.
Cardiac surgery is an established and effective treatment

for children with congenital heart defects. Early successes
in surgical treatment have led to a new therapeutic era in the
management of congenital heart disease (CHD) and have
fostered the development of the subspecialties, pediatric
cardiology and cardiac surgery and their collaboration.
Through this cooperative effort, tremendous progress in
medical diagnosis and surgical treatment has been achieved.
In turn, these accomplishments gave rise to the development of
pediatric cardiac anesthesiologists, individuals who understand
the pathophysiology of congenital heart malformations, the
diagnostic and surgical procedures used to treat heart disease,
and the principles of pediatric and cardiac anesthesia as well
as of intensive care medicine. Pediatric cardiac anesthesia
continues to evolve as an exciting and technically demanding
subspecialty in which anesthetic management is based on
physiologic principles.
The increased expectation for better outcomes has been a
driving force for the dedication of pediatric cardiac centers
and the increasing interest in pediatric cardiac anesthesia
support. This has had a dramatic impact on the volume
of cases undergoing anesthesia in the operating room,
catheterization laboratory, and echocardiography suite. It
has become imperative for the anesthesia team to understand
the principles underlying the management of patients with
CHD and to apply them to the field of clinical anesthesia.
This chapter provides an overview of some of the unique
features of the pediatric patient with CHD, and of the surgical
procedures; addresses perioperative anaesthetic management
for procedures requiring cardiopulmonary bypass (CPB).
Congenital cardiovascular surgery and anesthesia are often
performed under unusual physiologic conditions. Rarely
in clinical medicine patients are exposed to such biologic
extremes as during congenital heart surgery. Commonly,
patients are cooled to 18C, are acutely hemodiluted by
more than 50 percent of their extracellular fluid volume, and
undergo periods of total circulatory arrest lasting up to 1 hour.
Management of patients under these physiologic extremes is a
Pediatric Cardiac Surgery

Key Points
1. Organ system maturation occurs from birth: For example,
cardiovascular, central nervous system (CNS), pulmonary,
renal, hematology; affects physiologic function and there
fore anesthetic and surgical management and outcome.
2. Physiologic understanding of CHD and consequent
anesthetic management are based on the pathophysiologic
determinants of four categories of defects: shunts,
mixing lesions, stenotic lesions, and regurgitant lesions.
3. The chronic sequelae of CHDrepaired, palliated, or
unrepairedaffect anesthetic management: ventricular
failure, residual hemodynamic effects (e.g. valve
stenosis), arrhythmias, and pulmonary blood flow (PBF)
changes (e.g. pulmonary artery hypertension).
4. Preoperative assessment of cardiac status: For
example, review of history and physical examination,
echocardiography, and catheterization data and
consulting with the patient's cardiologist and planning
are the key factors to a successful anesthetic outcome.
5. Intraoperative transesophageal echocardiography (TEE)
and CNS monitoring (e.g. cerebral oxygen monitoring)
enhance surgical outcome and reduce morbidity.
6. Selecting an induction technique is dependent on the
degree of cardiac dysfunction, the cardiac defect, the
degree of sedation provided by the premedication,
and the presence or absence of an indwelling venous
catheter. The maintenance of anesthesia depends on
the age and condition of the patient, the nature of the
surgical procedure, the duration of CPB, and the need for
postoperative ventilation.
7. The physiologic effects of CPB on neonates, infants,
and children are significantly different from the effects
on adults. During CPB, pediatric patients are exposed

to biologic extremes not seen in adults, including deep
hypothermia (18C), hemodilution (threefold to fivefold
greater dilution of circulating blood volume), low
perfusion pressures (2030 mm Hg), and wide variation
in pump flow rates (ranging from 200 mL/kg/min to total
circulatory arrest).
8. After the repair of complex congenital heart defects,
the anaesthesiologist and surgeon may have difficulty
separating patients from CPB. Under these circumstances, the underlying cause must be determined, which
may be:

a. An inadequate surgical result with a residual defect
requiring repair.

b. Pulmonary artery hypertension or

c. Right or left ventricular dysfunction.
9. The use of modified ultrafiltration (MUF) reverses the
deleterious effects of hemodilution and the inflammatory
response associated with CPB in children. Perioperative
blood loss and blood usage are significantly reduced when
MUF is used. Modified ultrafiltration also improves left
ventricular function and systolic blood pressure and
increases oxygen delivery. Pulmonary compliance and
brain function after CPB are also improved.
10. Neonates, infants, and children undergoing cardiac
surgery with CPB have a higher rate of postoperative
bleeding than that seen in older patients. This is due to
several factors:
a. There is disproportionate exposure to the nonendothelialized extracorporeal circuit, which produces
an inflammatory-like response. This inflammatory
response to CPB is inversely related to patient age;
the younger the patient, the more pronounced the
response.

b. The type of surgery performed in neonates and infants
usually involves more extensive reconstruction and
suture lines, creating more opportunities for surgical
bleeding than in adult cardiac patients.

c. Operations are frequently performed using deep
hypothermia or circulatory arrest, which may further
impair hemostasis.

d. The immature coagulation system in neonates may
also contribute to impaired hemostasis.

e. Patients with cyanotic heart disease demonstrate an
increased bleeding tendency before and after CPB.
11. The guiding principle in the management of the
postoperative patient is an understanding of both normal
and abnormal convalescence after anesthesia and cardiac
surgery. The immediate postoperative period, even that of
normal convalescence, is one of continuous physiologic
change because of the pharmacologic effects of residual
anesthetic agents and the ongoing physiologic changes
secondary to abrupt alteration in hemodynamic loading
conditions, surgical trauma and extracorporeal circulation.
74
Anesthesia for Surgical Repair of Congenital Heart Diseases
vital function of the pediatric cardiovascular anesthesiologist.

As with other areas of medicine, the application and
management of technology preceded a comprehensive
understanding of its physiologic effects.
Clearly, the perioperative management of these complex
cases requires a group of physicians (surgeon, anesthesiologist,
cardiologist, critical care specialist), nurses, and perfusionists
to work as a team. This team orientation is essential to the
achievement of an optimal outcome. Although the quality of
the surgical repair, the effects of CPB, and postoperative care
are the major determinants of outcome, meticulous anesthetic
management is also imperative. Ideally, despite the complexity
of the cases and the marked physiologic changes attributed
to CPB and the surgical procedures, anesthetic care should
never contribute substantially to morbidity or mortality. The
challenge is to understand the principles underlying the
management of patients with CHD and to apply them to
clinical anesthesia.
1023
General Issues
13
Table 1
Unique characteristics of pediatric cardiac anesthesia

Child
Normal organ system development and maturational changes of infancy

Cardiovascular: Blood flow patterns of circulation at birth, myocardial compliance, systemic and pulmonary vasculature and
-adrenergic receptors
Pulmonary: Respiratory quotient, closing capacity, chest compliance
Central nervous system: Brain growth, cerebral blood flow, autonomic regulation
Renal: Glomerular filtration rate, creatinine clearance
Hepatic: Liver blood flow, microsomal enzyme activity
Disease/growth interrelationship
Effects of systemic disease alter somatic and organ growth
Compensatory ability of developing organs to recover from injury
Immunologic immaturity of the infant
Obligatory miniaturization (i.e. small patient size and body surface area)
Diverse anatomic defects and physiologic changes
Altered ventricular remodelling owing to myocardial hypertrophy and ischemia
Chronic sequelae of congenital cardiac disease
Surgical procedures
Diversity of operations
Frequent intracardiac and right ventricular procedures
Use of deep hypothermia and circulatory arrest during repair
Trend towards repair in early infancy
Evolution of surgical techniques to avoid residua and sequelae
Trend towards wider application of certain operations
Courtesy: Adapted from Miller et al.
Unique Features of Pediatric Cardiac Anesthesia

Pediatric cardiovascular management is unique. Important
differences from adult cardiac surgery do exist (Table 1). These
differences are attributable to normal organ system maturation
in the neonate and young infant, differing pathophysiologic
conditions in CHD, the diversity of surgical repairs, and the
use of specialized CPB techniques such as deep hypothermia
and total circulatory arrest.
Physiologic Consequences of Congenital Heart Disease
1024
It is obvious that the chronic effects of CHD are a consequence

of the imposed hemodynamic stress of the defect or the
residua and sequelae after cardiac repair or palliation. These
effects continue to alter normal growth and development of
the cardiovascular system as well as of other organ systems
throughout life. Decades ago, complete surgical cures were
rarely achieved and some repairs were used to be palliative
rather than corrective, abnormalities before and after repair
used to produce long-term effects that would affect the care
of patients with CHD. Fortunately with the advent of better

knowledge and facilities, now a days complete repair is aimed
at and achieved even in the newborn. The effects of altered
myocardial loading conditions after cardiac surgery early
in life, require close follow-up. For example, after cardiac
surgery for critical aortic stenosis (AS) in infancy, subsequent
operative or catheterization procedures often become
necessary due to the residual AS or insufficiency. Although
many of the abnormalities are trivial and have no major
impact, others affect major organ system processes such as
ventricular function, CNS growth, the conduction system of
the heart, and PBF. Under these circumstances, the long-term
quality of life is affected. While anesthetizing these patients
for their primary cardiac repair these chronic changes should
be ascertained and be reflected in the anesthetic protocol. In
this context, one should not forget the problem of managing
an increasing adult population who had intracardiac repair
done when they were young.
The myocardium is continually remodelled by specific
hemodynamic stresses throughout life. Right ventricular
growth and development are influenced by the low-resistance
high resting levels of circulating catecholamines, limited

recruitable stroke work, an immature calcium transport
system, and decreased ventricular compliance. This limits
contractile reserve and results in a LV with a high level of
resting tone. Although the resting performance of the neonatal
myocardium may be greater than in adults and older children,
there is a greater sensitivity to -blockade and only modest
increases in cardiac performance after administration of the
-agonist drugs dobutamine and isoproterenol.
On the ultrastructural level, a variety of cellular synthetic
functions are occurring in immature myofibrils that dominate
the newborn heart. Large nuclei, mitochondria, and surface
membranes predominate within the myofibrils. In neonates,
there is a 50 percent reduction in the number of myofibrils and
the myofibrils are arranged in a nonlinear, disordered array. As
a direct result, the contractile mass of the heart is effectively
reduced, resulting in a ventricle with low compliance. Preload
augmentation is effective at low filling pressures (17 mm
Hg). However, when left-sided filling pressures exceed 7 to
10 mm Hg and further increases in LV stroke volume are
minimal. As a consequence, neonates are more dependent on
heart rate and to a lesser extent on preload, to maintain cardiac
output at filling pressures of 7 to 10 mm Hg or greater.
In addition to a reduced contractile mass, the
calcium transport system in the neonatal myocardium is
underdeveloped. The transverse tubular system is absent, and
the sarcoplasmic reticulum, which has to store and release
calcium, is small and inefficient. The neonatal heart is therefore
more dependent on extracellular calcium levels than the adult
myocardium. Because intracellular calcium concentrations
play a central role in myocardial contractility, normal or even
elevated plasma levels of ionized calcium may be necessary
to augment or maintain an effective stroke volume. This is in
contrast to adult cardiac patients in whom calcium use during
cardiac surgery has fallen into some disfavor, owing to direct
concerns over myocardial ischemia and reperfusion injury
in children. Another unique feature relates to the pulmonary
circulation. The pulmonary circulation undergoes significant
changes during the first few months of life. These changes
are largely characterized by regression of the hypertrophied
medial smooth muscular layer in the pulmonary arteries that
exists in utero, resulting in a concomitant drop in pulmonary
vascular resistance (PVR). In the immediate newborn period,
the large decrease in PVR is due to lung expansion and the
vasodilatory effects of a higher PaO2 than existed in utero.
A corresponding decrease in pulmonary artery (PA) pressure
occurs as PVR declines. Acute physiologic stress in the
newborn period, such as hypoxemia or acidosis, can increase
PA pressure and thus PVR. If the resulting right ventricular
hypertension causes reduced right ventricular compliance,
right-to-left shunting can occur at the foramen ovale. Once
PVR exceeds systemic vascular resistance (SVR), right-to-left
shunting develops at the level of the patent ductus arteriosus
(PDA). Either phenomenon will worsen the hypoxemia and
74
afterload of the pulmonary circulation. The left ventricle

(LV) is coupled to the high-resistance systemic circulation,
which accelerates its rate of growth and development.
This situation gives rise to the adult heart where the LV
dominance of myocardial muscle mass occurs. Abnormalities
of ventricular performance at rest and with exercise can be
detected in patients with chronic hemodynamic overload and
complex cyanotic lesions. These abnormalities in ventricular
function are the consequences of chronic ventricular pressure
and/or volume overload, repeated episodes of myocardial
ischemia, and residua or sequelae of surgical treatment (e.g.
ventriculotomy, altered coronary artery supply, inadequate
myocardial protection). The modified Fontan procedure, for
example, has a 40 percent increase in hydraulic power cost to
move blood through the heart compared with the normal twoventricle circulation. Power is the rate at which work is done.
So although Fontan physiology is a significant improvement
over shunt physiology, it still requires a 40 percent increase
in myocardial work attributable to the lack of a pulmonary
ventricle. The physiologic adaptive responses to chronic
hypoxemia and ventricular pressure or volume overload
are the primary stimuli producing the long-term ventricular
dysfunction. For example, chronic volume overload of the
LV as seen with left-to-right shunts or a chronic pressureloaded LV due to left-sided obstructive lesions results in
congestive heart failure. Chronic right ventricular volume
overload as seen in pulmonic insufficiency after tetralogy of
Fallot repair or a pressure-loaded right ventricle (RV) such as
with residual pulmonary stenosis (PS) is also associated with
chronic ventricular dysfunction and failure. The mechanism
for the dysfunction and failure in pressure-loaded ventricles
is probably related to the development of myocardial
hypertrophy as an adaptive response to chronic hemodynamic
overload. The resultant myocardial hypertrophy outgrows
vascular supply and results in ischemia and fibroblast
proliferation. Permanent changes in myocardial structure
and function are the end result. In patients with volumeoverloaded ventricles, the heart contraction is inefficient due
to the extended sarcomere length and impaired actin-myosin
cross-bridging.
In patients with cyanotic conditions, the long-term
compensation for chronic cyanosis shows a major
redistribution of organ perfusion with selected blood flow
to the heart, brain, lung, and kidney and decreased flow to
the splanchnic circulation, skin, muscle, and bone. Chronic
cyanosis is associated with increased work of breathing in
an attempt to increase oxygen uptake and delivery. The most
dramatic complications are the decreased rate of somatic
growth, increased metabolic rate, and increased hemoglobin
concentration as seen in cyanotic children. Another unique
feature of the normal neonatal and infant cardiovascular
system is the reduced myocardial reserve compared with that
in the healthy adult. The newborn left ventricular function
is restricted by a reduced number of -adrenergic receptors,
1025
General Issues
13
1026
eventually limit tissue oxygen delivery to the point of lactic

acidosis. In contrast, left-to-right shunts, such as with a
ventricular septal defect (VSD), produce intimal changes in the
pulmonary vasculature and delay regression of medial muscle
hypertrophy. This results in persistent elevation of PVR.
Airway concerns are a major issue for children with
congenital heart lesions. Airway pathology related to heart
disorders fall into two broad categories:
1. Disorders related to anomalous relationships between
vascular structures and the tracheobronchial tree (e.g.
vascular rings), this is discussed further in Anesthesia for
Closed Heart Operations; and
2. Disorders related to enlarged cardiac structures (e.g.
dilated PAs, enlarged left atrium (LA), ventricular dilation,
and hypertrophy).
Enlarged cardiac structures can result from increased leftto-right shunting, LA enlargement, right and left ventricular
hypertrophy or dilation, and dilated PAs. Increases in left-toright shunting can dilate PAs and result in airway compression
at a number of sites:
a. Pulmonary artery enlargement can cause the aorta to
compress the left lateral trachea.
b. Pulmonary artery dilation can cause compression of the left
main bronchus at the origin of the upper lobe bronchus and
at the junction of the right intermediate and right middle
lobe bronchi.
c. Left atrial enlargement can affect the distal trachea and
main stem bronchus.
d. Ventriculomegaly can compress the left main bronchus.
These airway changes in the pediatric population may be
of importance at the time of passing the TEE probe.
Size differences between adult and pediatric cardiac
patients require different anesthetic techniques and
miniaturization. Anatomically, pediatric patients have small
upper and lower airways, small veins and arteries, and a
decreased body surface area, as compared with adult patients.
There are several anaesthetic implications related to patient
size. Some centers believe that the placement of arterial
catheters by cut-down in neonates and infants represents the
most expedient approach, particularly when optimal sites are
limited. Pulmonary artery catheters are used infrequently,
both because of the technical difficulties in positioning the tip
in the PA and because of the fundamental fact that pulmonary
flow bears no obligatory relationship to the systemic output
in children with either intra- or extracardiac communications.
Transthoracic catheters for pressure monitoring and delivery
of vasoactive substances are commonly placed from the
surgical field instead of percutaneous approach via the neck.
Adequacy of the repair and function can be assessed by TEE
with Doppler color flow imaging with miniaturized probes.
Cardiopulmonary bypass serves as another example of the
influence of patient size on management. The ratio of pump
priming volume to patient blood volume is considerably higher
in small children than in adults, resulting in a greater degree of
hemodilution. Several studies have demonstrated a heightened

inflammatory response to CPB in children compared with
adults. This effect is related to the disproportionate exposure to
the non-endothelialized surfaces of the pump circuit per body
surface area. Greater damage to the formed blood elements
and plasma proteins is incurred, resulting in activation of
mediators of inflammation.
PREOPERATIVE EVALUATION
The anesthesiologist who cares for children with CHD is
presented with a broad spectrum of anatomic and physiologic
abnormalities. Patients range from young, healthy,
asymptomatic children undergoing closure of a small atrial
septal defect (ASD) to the newborn infant with hypoplastic left
heart syndrome (HLHS) requiring aggressive perioperative
hemodynamic and ventilatory support. Intertwined with the
medical diversity of these patients are the psychological
issues of both the patient and the parents. Preparation of the
patient and the family is time consuming, but omitting or
compromising this aspect of patient care is a major deterrent to
a successful outcome and patient/parental satisfaction. Cardiac
surgeons, cardiologists, anesthesiologists, intensivists, and
nurses must work as a team in preparing the patient and the
family for surgery and postoperative recovery. This teamoriented approach also serves as a checkpoint to prevent
errors and omissions in preoperative, intraoperative, and
postoperative care necessitated by the complexity of cardiac
surgery for CHD. The preoperative visit offers the family the
opportunity to meet the surgeon and anesthesiologist and to
begin preparing the patient and family for surgery.
The preoperative evaluation should always start with a
careful history and physical examination. The history should
concentrate on the cardiopulmonary system. Parents should
be questioned about the general health and activity of their
child. Fundamentally, a child's general health and activity
reflect his or her cardiorespiratory reserve. Abnormalities
may point towards cardiovascular or other organ system
dysfunction that may pose anesthetic or surgical risk. Does
the child have normal or impaired exercise tolerance? Is he
or she gaining weight appropriately or exhibiting signs of
failure to thrive on the basis of cardiac cachexia? Does the
child exhibit signs of congestive heart failure (diaphoresis,
tachypnea, poor feeding, or recurrent respiratory infections)?
Is there progressive cyanosis or new onset of cyanotic spells?
Any inter-current illness such as a recent upper respiratory
infection (URI) or pneumonia must also be ascertained.
This may require delaying surgery, because of the negative
impact airway reactivity and elevation of PVR may have on
surgical outcome. It is becoming clear that a URI is not an
innocuous problem when elective cardiac surgery is planned.
A retrospective study of 713 children scheduled for elective
cardiac surgery found that 96 had symptoms of a URI
preoperatively. It was found that if symptomatic, they had a
reliable oral intake resumes; many clinicians avoid lactated

Ringers solution due to the lactate load. Aspiration risk (and
the presence of underlying lung disease and airway reactivity)
may be greater in some of these children, at least in part when
they develop muscle weakness that impairs swallowing and/
or coughing. In addition to standard non-invasive anesthetic
monitoring, one should have the ability to measure blood
glucose concentration frequently.
Laboratory evaluation should include hemoglobin,
hematocrit, and serum electrolyte measurements if the
patient is taking diuretics. An elevated hematocrit indicates
the chronicity of a relative hypoxemia. Levels above 60
percent may predispose to capillary sludging and secondary
end-organ damage, including stroke. Echocardiography with
Doppler color flow imaging (echo-Doppler) is invaluable,
providing a non-invasive means of assessing intracardiac
anatomy, blood flow patterns, and estimates of physiologic
status. For many cardiac defects, more invasive studies are
generally not required if a good echocardiographic assessment
is made. Echo-Doppler is especially helpful for defining
intracardiac abnormalities. Extracardiac abnormalities,
such as pulmonary artery or pulmonary vein stenosis, are
sometimes more difficult to definitively define by echoDoppler and may require cardiac catheterization or cardiac
computed tomography (CT) or magnetic resonance imaging
(MRI). As intraoperative TEE is becoming an increasingly
relied upon operative technique. The anesthesiologist must
understand the anatomy and views offered by TEE and assist
in the decisions based on the information available. Although
the complexity and variety of clinical defects are greater in
children, the anesthesiologist needs to be involved in the
interpretation, medical management, and additional operative
interventions based on intraoperative echocardiogram.
Cardiac catheterization remains the gold standard for
assessing anatomy and physiologic function in complex CHD.
A careful review of the cardiac catheterization data and an
understanding of how this information affects the operative
and anesthetic plans are essential. Not all of the medical
problems can be evaluated and corrected preoperatively;
the surgeon and anesthesiologist must discuss potential
management problems and any need for further evaluation
or intervention before operative intervention is considered.
Appropriate communication and co-operation between the
pediatric cardiologist and the surgeon maximize patient care
and facilitate perioperative clinical management. Typically,
most institutions have a regularly scheduled, combined
cardiology/cardiac surgery/anesthesiology/intensive care
unit (ICU) meeting to discuss candidates for surgery during
which all of the essential information regarding the previous
list is displayed and discussed. Such a meeting is invaluable
for learning about particular patients for surgery as well as
providing a continuing educational opportunity to understand
CHD and its medical, surgical, and interventional treatment
options.
74
higher incidence of respiratory and multiple postoperative

complications compared with children without a URI (29.2%
versus 17.3% and 25% versus 10.3%, respectively; P < .01)
and a higher incidence of postoperative bacterial infections
(5.2% versus 1.0%; P = 0.01). These children with a URI also
stay an average of 25 hours longer in the intensive care unit,
although total hospital stay may not be prolonged. Parental
confirmation of a URI is an important diagnostic indicator.
Recurrent pneumonia, as mentioned previously, is a
frequent finding in patients with congestive heart failure. In
particular, patients with shunt physiology or mixing lesions
with excessive PBF and altered lung compliance are at risk for
viral and bacterial lung infections. Respiratory syncytial virus
is a particularly common and poorly tolerated lung infection
in these patients.
A good history must delineate previous surgical interventions.
The presence of shunts, patches, and conduits has an impact on
the selected surgical and anesthetic approach. The presence
of a left Blalock-Taussig (BT) shunt , makes accessing a left
radial artery for invasive monitoring difficult and may not
provide accurate or useful information. Current medications,
previous anaesthetic problems, and family history of anesthetic
difficulties are equally important.
In the modern era of echocardiography and cardiac
catheterization, physical examination rarely contributes
additional information about the underlying cardiac lesion.
However, the absence of a previous shunt murmur or the
presence of a new murmur suggesting mitral regurgitation
could suggest partial occlusion of a shunt or endocarditis,
respectively.
It is extremely useful to assess the child's overall clinical
condition. For example, an ill-appearing, cachectic child in
respiratory distress has limited cardiorespiratory reserve, so
the use of excessive premedication or a prolonged inhalational
induction could result in significant hemodynamic
instability and even cardiac arrest. Events and outcomes in
the perioperative period include exacerbated myocardial
dysfunction, cardiac arrest, and severe neurologic and
metabolic decompensation. If anesthesia and surgery are to
be undertaken, it is imperative that one use the other members
of the consultant team to gain the best understanding possible
about the type and degree of the specific childs impairments.
Many of these children are maintained with one or more
nutritional supplements and other agents such as carnitine
analogues, other substrate precursors and cofactors (e.g.
nicotinamide, thiamine, succinate, creatine, folic acid), other
various vitamins and vitamin-antioxidants (e.g. C or E), coenzyme Q and so on. Few, if any (except perhaps for coenzyme
Q), have been shown to have meaningful benefit. Care must be
taken with NPO guidelines in these children (they and/or their
families are typically very reliable in terms of the permissible
duration and consequences of caloric deprivation). Prompt
institution of intravenous glucose-containing fluids is in order
as soon as NPO is initiated; these should be continued until
1027
General Issues
13
Anesthetic Challenges in Premature and

Ex-Premature Infants
Recent advances and knowledge in neonatal care in neonatal
intensive care have improved the survival of these infants
who have born early, mortality is still 42/1,000 live births
compared with 1.8/1,000 in term babies. The current interest
lies with the survivors who can have host of complications
related to the underdeveloped organ systems and may present
for a variety of surgical procedures.
Premature Surgical Baby

The term prematurity has conventionally been applied to
infants weighing less than 2,500 g at birth. Or a live infant
delivered before 37 weeks from the first day of last menstrual
period is defined as premature or preemies. Premature infants
are also classified aslow birth weight infants (3134 weeks,
11.5 kg), very low birth weight infants (2630 weeks, 600
g1 kg) and extremely low birth weight infants (< 26 weeks,
400600 g). However, the designation preterm infant is more
appropriate and is defined as one born before 37 completed
weeks of gestation. Generally, preterm babies are premature
and term babies are mature. Preterm birth (latin: partus
praetemp oraneus or pretus prematurus) refers to the birth of
baby before developing organs are mature enough to allow
normal postnatal survival. Thus, a premature is one that has
not yet reached the level of fetal development that generally
allows life outside the womb. Gestational age determines
the extent of physiological immaturity. In addition, infants
weighing less than 750 g are now being called micropremies;
there is very little published information regarding the
anesthetic management of this vulnerable subpopulation of
neonates.
Specific risks for preterm neonates: They usually show
physical signs of prematurity in reverse proportion to the
gestational age. As a result, they are at risk of numerous
problems affecting different organ systems. Thus, when they
need a variety of surgical procedures, they present enormous
challenges during anesthesia, surgery, and postoperative care.
Ex-premature: A large study on children born between 22 to 24
weeks who are currently at school age have shown moderate
to severe disabilities (46%) and cerebral palsy (12%).
Premedication
1028
The goal of premedication is to achieve adequate sedation

in a non-traumatic fashion and to maintain respiratory
and hemodynamic stability. In children with complex
CHD, premedication is advocated. This improves oxygen
saturation, diminishes myocardial oxygen consumption and
promotes a more satisfactory induction. Many premedication
combinations have been used, but reports of apnea,
bradycardia, and respiratory depression in 1 to 2 percent of
patients following premedication, mandate close observation

by skilled personnel. Bradycardia and apnea in particular
are poorly tolerated in the child with CHD and may result
in significant morbidity and mortality. Oral or intranasal
administration of premedication is effective and is the most
widely accepted premedication for children with heart disease.
In general, children younger than 6 months do not require a
premedication agent. In children between the age of 6 and 9
months, midazolam (0.30.7 mg/kg) may be administered
orally. In older children, 0.5 to 1.0 mg/kg (maximum dose,
20 mg) is effective. A calm, cooperative, sedated child is the
usual result.
Operating Room Preparation

Advanced, careful preparation of the operating room is
essential. The anesthesia machine must have the capacity to
provide air as well as oxygen and nitrous oxide to help balance
pulmonary and systemic blood flow. Intravenous tubing must
be free from air bubbles to prevent air embolism to the left
side of the circulation in patients with open communication,
such as an ASD. Resuscitative drugs, labelled and ready for
administration, should include injection calcium gluconate or
calcium chloride, sodium bicarbonate, atropine, phenylephrine,
lidocaine, and epinephrine. An inotropic infusion, usually
dopamine, should be premixed and ready for administration
for most cases, and additional infusions are made available
if there is a strong suspicion for their need (epinephrine
and milrinone). Injection atropine and succinylcholine are
usually loaded because of the potential for airway reactivity,
hypotension, and bradycardia during anesthetic induction. In
pediatric cardiac anesthesia, many of the patients have high
endogenous catecholamines as an adaptive response to their
underlying cardiac disease and have limited cardiovascular
reserve. Thus, resuscitative drugs should be drawn up prior to
anesthetic induction.
For congenital heart surgery, the ability to rapidly alter
body temperature for cooling and rewarming is essential.
During deep hypothermic CPB, patients are cooled to 15C to
18C. Surface cooling with a heating/cooling water mattress,
warm air convection device, and an efficient room cooling/
heating system are important in the operative management of
these patients. The use of ice packs to the head is generally
applied if circulatory arrest is part of the operative plan.
Physiologic Monitoring
The monitoring used for any particular patient should be
dependent on the condition of the patient and the type and
extent of the surgical procedure. Non-invasive monitoring
devices are placed before the induction of anesthesia. In
the crying pediatric patient, monitoring devices can be
applied immediately after the induction of anesthesia,
except for precordial stethoscope and pulse oximetry.
the superior vena cava (SVC) to the common atrium. Failure

to maintain this gradient results in no forward flow, low
cardiac output, and death. Monitoring of intracardiac common
atrial pressure is useful in the intraoperative and postoperative
management of these patients. In newborns, infants, and
young children, transvenous PA catheters are more difficult to
place. The use of intraoperative echo-Doppler has markedly
reduced the need for placement of indwelling intracardiac
catheters or transvenous PA catheters.
Echocardiography
Two-dimensional echocardiography combined with pulsedwave Doppler ultrasonography and color flow mapping
demonstrates detailed morphologic as well as physiologic
information in most cases. The availability of biplane and
omni plane TEE probes in smaller sizes has enabled
TEE to become the standard modality for intraoperative
echocardiography. The increased viewing angles available with
these multi plane imaging probes have significantly improved
the ability to evaluate the entire heart both before and after
the repair. In small neonates or when the surgeon attempts to
provide smaller, more cosmetically appealing incisions, the
exposed surface area of the heart is quite limited. Epicardial
imaging is generally reserved for neonates weighing 2 to 2.5
kg or less or for a child with esophageal anomalies (tracheaesophageal fistula repair). Although monoplane probes are
capable of being placed in infants weighing less than 2 kg,
the available views remain limited, particularly in the more
complex repairs performed in neonates. With the use of
TEE in the operating room, anatomic and physiologic data
can be obtained before CPB. Occasionally, the preoperative
evaluation may result in a revision of the initial diagnosis
or identify an additional defect not previously recognized.
In addition, TEE also helps to evaluate ventricular function,
intracardiac air, gradients across outflow tracts and may
help in the diagnosis of cardiac arrhythmias. It may help in
the evaluation of hemodynamic effects of sternal closure,
termination of ventricular assist devices or extracorporeal
membrane oxygenation. This evaluation may refine the
anesthetic and operative plans. Because of the unrestricted
TEE approaches in anesthetized patients, new anatomic
findings may be discovered and management plans changed
accordingly. It is generally recommended that for every child
who is to undergo an intraoperative TEE, a transthoracic
echocardiography (TTE) should be done and should be
reviewed by the echocardiographer before studying the TEE.
The intraoperative TEE should not be the sole diagnostic
study as there are inherent limitations with imaging certain
structures like the arch of aorta and left pulmonary artery.
Indications for performing intraoperative TEE is broadly
classified into 3 categories depending on surgical risk:
1. Low risk: ASD, VSD, valve replacements and extracardiac procedures.
74
Standard monitoring includes a precordial stethoscope

five-lead electrocardiographic system, pulse oximetry, an
appropriate-sized non-invasive blood pressure cuff, end-tidal
CO2 monitoring, and end-tidal gas monitoring. Additional
monitoring includes an indwelling arterial catheter, central
venous catheter, temperature probes and TEE. Foley catheters
are used in neonates and infants undergoing hypothermic
circulatory arrest or reoperations and may be electively
withheld in older children for less complex procedures
unless dictated by renal insufficiency, prolonged procedures,
significant fluid intake, or surgeon preference.
Continuous monitoring of arterial pressure is possible
only through the use of an indwelling intra-arterial catheter.
In young children, cannulation of the radial artery with
a 22-gauge catheter is preferred. In older children and
adolescents, a 20-gauge catheter may be substituted. Care
must be taken to ensure that previous or currently planned
operative procedures such as a radial artery cutdown,
subclavian flap for coarctation repair, or a classic BT shunt
do not interfere with the selected site of arterial pressure
monitoring. Other sites available for cannulation include the
ulnar, femoral, or axillary artery. Cannulation of the posterior
tibial or dorsalis pedis artery is not usually performed for
complex operative procedures. Peripheral arterial catheters
of the distal lower extremities function poorly after CPB and
do not reflect central aortic pressure when distal extremity
temperature remains low.
Myocardial and cerebral preservation is principally
maintained through hypothermia, so the accurate and
continuous monitoring of body temperature is crucial. Rectal
or urinary and nasopharyngeal temperatures are monitored
because they reflect core and brain temperatures respectively.
Monitoring of esophageal temperature is a good reflection of
cardiac and thoracic temperatures.
Pulse oximetry and capnography provide instantaneous
feedback concerning adequacy of ventilation and oxygenation.
They are useful in balancing shunt flow and providing data
about surgically created shunts and PA bands, especially
after the surgical procedure is completed. Peripheral
vasoconstriction in patients undergoing deep hypothermia
circulatory arrest (DHCA) sometimes renders digital oxygen
saturation probes less reliable. Alternative sites such as the
ear lobe or the tongue sensor have been used successfully in
the newborn to provide a more central measure of oxygen
saturation, with less temperature-related variability.
The use of transthoracic (right atrium [RA], LA or PA) or
transvenous PA catheters is determined on an individual basis
based on the disease process, surgical procedure, and needs of
postoperative monitoring. For example, in neonates with PA
hypertension or in children undergoing a Fontan procedure for
tricuspid atresia or univentricular heart, these measurements
can be especially useful. In the Fontan operation, no ventricle
pumps blood to the lungs; adequacy of flow through the
pulmonary bed is dependent on maintaining a gradient from
1029
General Issues
13
1030
2. Moderate risk: Atrioventricular (AV) canal defects, combined

ASD + VSD or combined VSD + PS, valve reconstruction
and subaortic stenosis;
3. High risk: Reoperation and neonatal surgery, Fontan
procedure, Fallots tetralogy, Ebstein anomaly.
Moreover, intraoperative TEE has limited potential for
Doppler alignment, constraints on time during the intraoperative
period and suboptimal ambient lighting. The preoperative
TEE confirms or refutes the TTE findings as well as provides
information on ventricular function before CPB. Preoperative
TEE also facilitates central line placements, drawing anesthesia
protocol and use of preoperative ionotropic supports.
Post-bypass echo-Doppler evaluation is able to immediately
assess the quality of the surgical repair and to assess cardiac
function by examining ventricular wall motion and systolic
thickening. This technique can show residual structural defects
after bypass, which can be immediately repaired in the same
operative setting and prevent the patient from leaving the
operating room with significant residual structural defects
that later require reoperation. The ability to identify patients
with new right and left ventricular contraction abnormalities
after bypass, as determined by a change in wall motion or
systolic thickening, allows for immediate and more thoughtful
pharmacologic interventions when guided by TEE evaluation.
Importantly, post-bypass ventricular dysfunction and residual
structural defects are identified by echo-Doppler assessment;
left uncorrected, these are associated with an increased
incidence of reoperation and greater morbidity and mortality.
This monitoring tool helps assess surgical outcome and
identify operative risk factors. Surgeons can demonstrate an
operative learning curve with a reduced incidence of residual
defects with experience. However, even when experienced
surgeons perform the procedures, the use of an intraoperative
echocardiogram can detect a 3 to 4 percent incidence of
clinically significant residual disease that requires further
surgical repair. Patients leaving the operating room with
residual disease have a considerable increase in hospital cost,
length of stay, and need for further operative or interventional
procedures. Cost and outcome benefits exist if residual
anatomic disease is minimized by ensuring the most complete
repair possible through the use of intraoperative TEE. Further,
the use of an intraoperative echocardiogram can detect a
3 to 4 percent incidence of clinically significant residual
disease that requires further surgical repair. The safety features
of TEE in children has been studied to find that TEE is a
relatively safe procedure in children. The complication rates
up to 3 percent has been reported. Damage to the oropharynx,
esophagus, brachial plexus, airway obstruction and various
degree of dislodgement of the endotracheal tube have been
reported. The probe related injuries include thermal injury,
mechanical problems resulting in lacerations or perforation of
the pharynx, hypopharynx, esophagus or stomach. Arrhythmias
and circulatory derangement can also occur. Children with
Down syndrome have intrinsic narrowing of the hypopharynx
in addition to having an increased incidence of cervical spine

narrowing that may result in difficult or failed probe placement.
Central Nervous System Monitoring

The goals of brain monitoring are three-fold. The first goal
is to improve understanding of the cerebral function and
dysfunction during cardiac surgery, so that effective brain
protection strategies can be developed. The second goal is to
provide online cerebral monitoring to elucidate correctable
cerebral perfusion abnormalities during CPB. Because many of
the determinants of normal brain perfusion become externally
controlled by the cardiac team during CPB (e.g. flow rate
(cardiac output), perfusion pressure, temperature, hematocrit,
arterial and venous cannula positions, and PaCO2), knowledge
of the effect of these factors on the brain in neonates, infants,
and children is essential. Furthermore, examination of the
brain under unusual biological circumstances, such as after
total circulatory arrest or during continuous-flow CPB at
deep hypothermia (1518C), permits a unique opportunity
to describe cerebrovascular physiology and pathophysiology.
Processed electroencephalography, trancranial Doppler (TCD),
cerebral blood flow (CBF), jugular venous oxygen saturation,
near infrared spectroscopy (NIRS) or cerebral oximetry and
cerebral metabolism measurements have provided important
information during pediatric cardiovascular surgery.
Electroencephalography
This is helpful in monitoring physiologic function of the
CNS during deep hypothermic bypass and total circulatory
arrest. For example, during deep hypothermia and before
total circulatory arrest, the electroencephalogram can identify
residual cerebral electrical activity. Isoelectric silence can
then be induced by further cooling. Because any residual
electrical activity during arrest is associated with cerebral
metabolism above basal activity, an isoelectric state may
minimize ischemic injury to the brain during circulatory arrest.
The use of drug-induced electrical silence does not have the
same protective effect as hypothermia and may contribute
to hemodynamic compromise in patients with postoperative
myocardial dysfunction. In addition, the absence of electrical
activity, particularly in newborns, does not necessarily
correlate with optimal brain cooling. And may not be as useful
in newborns as has been suggested in adults to ensure optimal
cerebral protection from hypothermia.
The electroencephalogram may also be useful in detecting
the depth of anesthesia. In particular, the bispectral index
(BIS), a processed electroencephalogram, has proved to be an
effective monitor in older children and adults. In newborns
and infants, its reliability has been questioned, as processed
electroencephalographic monitoring and its associated
numerical correlation with anesthesia depth are based on adult
electroencephalographic wave forms. Evidence from studies
Transcranial Doppler
Transcranial Doppler is one of a number of methods used to
monitor CBF during pediatric cardiac surgery. TCD technology
uses the Doppler principle to detect shifts in the frequency
of reflected signals from blood in the middle cerebral artery
to calculate blood flow velocity. Because the diameter of this
large cerebral artery is relatively constant, flow velocity should
approximate CBF. The principal advantages of TCD include
that it is non-invasive, it does not require radiation exposure,
and it is a continuous monitor. An additional advantage of this
technique is the capability of assessing rapid alterations in
blood flow velocity due to temperature or perfusion changes,
as commonly occur during cardiac surgery. The limitations
of TCD monitoring include reproducibility, especially at
low flows and the lack of validating studies of TCD during
hypothermic CPB, where temperature, reduced flow rates,
and the laminar flow characteristics of non-pulsatile perfusion
may limit the accuracy of CBF velocity measurements. TCD
has been used to investigate the effect of CPB and DHCA
on cerebral hemodynamics in children as well as to assess
the incidence of cerebral emboli and the presence of flow
reductions associated with cannula malplacement or perfusion
abnormalities during bypass. Studies using TCD have enabled
several investigative groups to provide important information
regarding questions of normal and abnormal brain perfusion
during cardiac surgery in children. Questions regarding
cerebral perfusion pressure, autoregulation, and effect of
PaCO2 and temperature have been addressed using TCD in
children. TCD has also provided qualitative and quantitative
information regarding the presence of gaseous emboli in the

middle cerebral artery during cardiac surgery. Quantification
of this important mechanism of cerebral injury during cardiac
surgery would be instructive, because it has been suggested
to be a contributor to neurologic injury. Effect of DHCA
on brain and the efficacy of brain cooling has been studied
by measuring TCD in children. TCD ultrasonography has
been used to determine the threshold of detectable cerebral
perfusion during low-flow CPB. TCD velocities reveal trends
or changes in cerebral blood flow and not absolute values.
Studies have shown that in neonates undergoing the arterial
switch operation using a-stat blood gas management; NIRS
and TCD may be useful to determine the minimum acceptable
bypass flow level for an individual neonate during low-flow
hypothermic bypass. Blood flow becomes insufficient at
bypass flow rates less than 30 mL/kg/min. Inadequate blood
flow to the brain during this technique could be undetected
without such monitoring, and low-flow bypass may confer no
advantage to the brain over DHCA in some patients.
Near Infrared Spectroscopy

Near infrared spectroscopy has the capability of measuring
regional brain tissue oxyhemoglobin and cytochrome aa3, the
terminal mitochondrial enzyme in the respiratory chain. With
the use of NIRS, intracellular brain tissue oxygen delivery and
utilization during CPB have been preliminarily observed. After
promising animal studies, the commercial devices measuring
oxyhemoglobin saturation were approved by the US. Food
and Drug Administration and are clinically available. This
device has two flexible pediatric disposable probes, which
are easily applied to a child's forehead. An oxyhemoglobin
saturation index is measured in both hemispheres of the brain.
Marked differences between perfusion to the right or the left
side have suggested problems with adequate surgical arterial
or venous cannulation placement. In addition, low cerebral
oxygen delivery can be inferred by reductions in the measured
oxyhemoglobin saturation index levels. Efforts to increase
cardiac output and oxygen-carrying capacity by raising the
hematocrit and lowering the SVR generally improve cerebral
oxygen saturation. In addition to operative monitoring, there
has been an increased interest in postoperative cerebral
monitoring that may help determine adequate cerebral
oxygenation trends. Clinically, NIRS may be used as an
adjunctive continuous monitor of cerebral oxygen delivery,
which at normothermia has a strong correlation with systemic
oxygen delivery as measured by mixed venous saturations.
Some congenital cardiac centers have begun to use a noninvasive cerebral oxygen saturation monitor as an adjunct for
trends in effective cardiac output and oxygen delivery. The
NIRS monitor is particularly useful in managing infants with
single-ventricle anatomy after the Norwood procedure with or
without the Sano modification in the ICU when optimization
of systemic cardiac output is required.
74
in newborns suggests a much poorer correlation with the BIS

number and the depth of anesthesia. In one observation, the
stimulus-induced elevations to the BIS occurred at much
lower BIS levels in infants than in children during emergence
from anesthesia. Similarly, children with cerebral palsy
and mental retardation demonstrate lower BIS values than
matched normal children when awake and at similar levels of
inhalational anesthetic.
After CPB, the presence of electroencephalogram-based
seizures has been an indicator of significant neurologic
injury. A strong correlation between post-CPB seizures and
measured reductions in intelligence quotient later in life
was demonstrated by the Boston Circulatory Arrest Study
Group. Possible seizure activity in the postoperative period
should be suspected when physiologic parameters such as
tachycardia or hypertension are seen. A low threshold for
electroencephalographic evaluation or the use of antiepileptic
agents as part of postoperative sedation (midazolam) should be
strongly considered in the neonatal population. The etiology
for post-CPB electroencephalographic seizures remains
unclear. However, there is an increased risk with the presence
of a VSD, suggesting that left-sided air and air embolism may
be factors.
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General Issues
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1032
Induction and Maintenance of Anesthesia

The principles of intraoperative management of cardiothoracic
surgical procedures are based on an understanding of the
pathophysiology of each disease process and a working
knowledge of the effects of the various anesthetic and other
pharmacologic interventions on the particular patients
condition. Selection of an induction technique is dependent
on the degree of cardiac dysfunction, the cardiac defect,
and the degree of sedation provided by the premedication.
Other anesthetic considerations include a potential en
hanced sensitivity to anesthetic drugs and correspondingly
diminished anesthetic requirements, cardiomyopathy,
cardiac conduction abnormalities and skeletal (specifically
bulbar, oropharyngeal, and respiratory) muscle weakness. In
addition to the increased sensitivity of the CNS to the effects
of anesthetics, narcotics, and sedatives, the possibility of
reduced organ-based clearance mechanisms (due to clinical
or subclinical liver or kidney damage, for example) should
be considered. Reducing the doses, delayed onset, and greater
time to recover from intravenous or inhaled agent, sedative,
narcotic, and/or muscle relaxant should be anticipated. It is
likely that many children will be more sensitive to and take
more time to recover after non-depolarizing muscle relaxants,
although here again, specific data are lacking. Few, if any, of
these children (except the minority who have demonstrable
multicore or minicore pathology) should be considered to
be susceptible to malignant hyperthermia. The molecular
pathophysiology of these disorders is quite different from that
believed to underlie susceptibility to malignant hyperthermia,
and there is little if any justification for avoiding known
triggering agents on that basis. What is less clear is whether
depolarizing muscle relaxants (and potentially inhaled agents
such as halothane) have the ability in some children to induce
sufficient and rapid skeletal muscle injury to provoke acute
rhabdomyolysis and severe hyperkalemia (resulting in cardiac
arrest, myoglobinuria, potential renal damage, etc.). Given
these considerations, controlled ventilation with endotracheal
intubation is probably prudent for most circumstances
given the potential for aspiration, airway obstruction, and
respiratory muscle weakness. Full return to baseline level of
consciousness, effort and strength are needed before extubation.
The potentially increased and additive or synergistic effects of
residual amounts of inhaled and intravenous agents must be
appreciated, as should the potential for very prolonged (and
seemingly idiosyncratic and/or related to the aforementioned
changes in pharmacodynamics and pharmacokinetics)
neuronal depression and delayed awakening. As with other
considerations, depending on the child and the procedure,
observation and monitoring in the ICU during the recovery
period (with or without delayed extubation to permit full
recovery of respiratory function) is advised.
In children with good cardiac reserve, induction techniques
can be quite varied as long as induction is careful and well
monitored. The execution of induction is more important than

the specific anesthetic technique in patients with reasonable
cardiac reserve. A wide spectrum of anesthetic induction
techniques with a variety of agents has been used safely and
successfully; such as sevoflurane, sevoflurane and nitrous
oxide, halothane, halothane and nitrous oxide, intravenous or
intramuscular ketamine, or intravenous fentanyl, midazolam,
propofol, dexmedetomidine or thiopental. In patients with
more limited cardiac reserve, the choice of induction agent
becomes more important. In a prospective double-blind
randomized study of inhalational agents in children undergoing
congenital heart surgery, the use of halothane was compared
with the use of sevoflurane for both induction and maintenance
of anesthesia. Sevoflurane demonstrated a significant
hemodynamic benefit compared with halothane. The most
widely practiced intravenous induction techniques today include
intravenous induction with a benzodiazepine such as midazolam
and an opioid such as fentanyl or sufentanil. Alternative
induction agents include etomidate, ketamine, dexmedetomidine
and propofol. Etomidate provides hemodynamic stability and
has been advocated for pediatric patients with limited cardiac
reserve. Ketamine is also an effective induction agent in children
and has been advocated for patients with tetralogy of Fallot and
other cyanotic lesions because it increases SVR, maintains
cardiac output, and promotes left-to-right shunting across a
VSD or extracardiac shunt. Ketamine can be administered
intravenously or intramuscularly. An intramuscular injection,
however, may result in pain, agitation, and subsequent arterial
desaturation.
Propofol is also an effective induction agent in congenital
cardiac patients. It does need to be titrated in patients with
limited cardiac reserve because it causes a decrease in
mean arterial pressure and SVR. In patients with singleventricle shunt-dependent physiology, propofol induction and
maintenance have been found to cause an increased right-toleft shunt with significantly decreased PBF. Another concern
with propofol has been the association with severe metabolic
acidosis after prolonged infusions described in children in the
ICU. This is rarely a problem if administered for less than 12
hours, but propofol kinetics are altered in infants recovering
from cardiac surgery. An increased volume of distribution and
reduced metabolic clearance after surgery cause prolonged
elimination.
Dexmedetomidine is a highly selective 2-adrenoceptor
agonist with sedative, anxiolytic and analgesic properties
and has minimal effects on respiratory drive. It is structurally
related to clonidine, but has a much greater affinity for 2adrenoceptor over 1-adrenoceptors with a ratio of 1,600:1.
Dexmedetomidine is initially administered as a bolus in the
doses of 0.5 to 1 g/kg over 10 min followed by its infusion at
the rate of 0.3 to 0.7 g/kg/h. However, because of the
possibility of bradycardia and hypotension, several authors,
particularly, in cardiac anesthesia practice avoid the loading
dose and administer it as a continuous infusion at the
protocol is essential. The maintenance of anesthesia in these

children depends on the age and condition of the patient, the
nature of the surgical procedure, the anticipated duration
of CPB, and the need for postoperative ventilatory support.
Choice of a particular anesthetic agent is less important
when the appropriate monitors are used and adherence to
the physiologic guidelines mentioned earlier are met. More
important than the specific anesthetic techniques and drugs
is the skilled execution of the anesthetic plan, taking into
account patient response to drugs, changes associated with
surgical manipulation, and early recognition of intraoperative
complications. In children with complex defects requiring
preoperative inotropic and ventilatory support, a carefully
controlled induction and maintenance anesthetic with a potent
opioid is usually chosen. In patients with a simple ASD or
small perimembranous VSD, a potent inhalation agent alone
or in combination with moderate opioid dosages is preferred
as the principal anesthetic agent. This allows for extubation in
the operating room or shortly after arrival in the ICU and a less
prolonged period of intensive care monitoring. The reported
changes in blood pressure and heart rate for the inhalation
agents in normal children are observed in pediatric cardiac
surgical patients as well.
Although sevoflurane, desflurane, halothane and isoflurane
decrease blood pressure in neonates, infants, and children,
the vasodilatory properties of isoflurane and sevoflurane
may improve overall cardiac output compared with those of
halothane. Despite improved cardiac reserve with isoflurane
and desflurane, the incidence of laryngospasm, coughing, and
desaturation during induction of anesthesia limits their use as
an induction agent in children with congenital heart defects.
Children with complex CHD and limited cardiac reserve
require an anesthetic technique that provides hemodynamic
stability. Inhalation agents are less well tolerated as a
primary anesthetic in patients who have limited cardiac
reserve, especially after CPB. Fentanyl and sufentanil are
excellent induction and maintenance anesthetics for this
group of patients. Low to moderate doses of these opioids
can be supplemented with incremental doses of inhalation
anesthetics. The advantage of adding low concentrations
of inhalation agents is a shortened period of postoperative
mechanical ventilation, while maintaining the advantage of
intraoperative hemodynamic stability. Clearly, postoperative
mechanical ventilation is required when a high-dose opioid
technique is used. The hemodynamic effect of fentanyl at a
dose of 25 mcg/kg with pancuronium given to infants in the
postoperative period after operative repair of a congenital
heart defect shows no change in LA pressure, PA pressure,
PVR, and cardiac index and a small decrease in SVR and
mean arterial pressure. Higher doses of fentanyl at 50 to 75
mcg/kg with pancuronium results in a slightly greater fall in
arterial pressure and heart rate in infants undergoing repair
for complex congenital heart defects. Fentanyl has also been
shown to block stimulus-induced pulmonary vasoconstriction
and contributes to the stability of the pulmonary circulation
74
rate of 0.3 to 0.7 g/kg/h. Several articles have described

successful management of arrhythmias by dexmedetomidine.
These reports clearly indicate that dexmedetomidine has
antiarrhythmic actions. The important cardiovascular effects
of dexmedetomidine are a decrease in heart rate, SVR and
antiarrhythmic effects. These pharmacologic actions of
dexmedetomidine are highly desirable in the post-bypass
period and intensive care management of pediatric cardiac
surgical patients. Finally, the well appreciated actions of
dexmedetomidine such as anesthetic and opioid sparing effect,
sedation and smooth emergence, and minimal interference
with respiratory system paves way for early weaning from
ventilatory support and extubation.
An inhalation induction with sevoflurane is generally well
tolerated and is the preferred approach in children without
intravenous access. Differential anesthetic uptake among
patients with cyanotic versus acyanotic defects is common.
Patients with reduced PBF have a delay in anesthetic uptake
and this is expected. In extreme cyanosis, sevoflurane, because
of its reduced solubility, may not achieve an adequate alveolar
concentration to fully induce anesthesia. Halothane, because
of its greater solubility, would be more efficacious in extreme
cyanosis. In more conventional congenital cardiac patients,
inhalation induction with halothane or sevoflurane can easily
and safely be performed and the effect of right-to-left shunting
on uptake and distribution is not clinically significant.
In patients who are at risk for right-to-left shunting and
systemic desaturation, oxygenation is well maintained
with a good airway and ventilation, even with halothaneinduced hypotension. Skilled airway management and
effective ventilation are essential and take precedent over
drug selection during anesthetic induction. It is essential to
understand the complexities of shunts and vascular resistance
changes, but airway, ventilation (CO2), and oxygen effects on
the cardiovascular system are of primary importance during
the induction of anesthesia.
After anesthetic induction, central venous access is
established or a larger, more appropriate-sized indwelling
intravenous catheter is placed. A non-depolarizing muscle
relaxant is usually administered, and an intravenous opioid
and/or inhalation agent is chosen for maintenance anesthesia.
The child is preoxygenated with 100 percent oxygen, and an
endotracheal tube is carefully positioned. Preoxygenation
is done even in the ductal-dependent patient with increased
PBF; this avoids desaturation during intubation. If the child
arrives in the operating room with an endotracheal tube in
place, replacement should be considered because inspissated
secretions in a tube with a small internal diameter can cause
significant obstruction to gas flow. During CPB, when
humidified ventilation is discontinued, airway secretions
increase and endotracheal tube obstruction can occur. This
effect can be minimized by starting with a new endotracheal
tube.
Due to the diverse array of congenital heart defects and
surgical procedures, an individualized anesthetic management
1033
General Issues
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1034
in neonates after congenital diaphragmatic hernia repair. The

use of fentanyl appears to stabilize the pulmonary vascular
responsiveness in newborns and young infants with reactive
pulmonary vascular beds and to be helpful in weaning from
CPB and stabilizing shunt flow.
Injections sufentanil and pancuronium provide the same
cardiovascular stability as fentanyl and pancuronium in
pediatric cardiovascular patients. Intubation and other stimuli
such as sternotomy do not produce clinically significant
alterations in hemodynamics, although changes are greater
than with equipotent doses of fentanyl. Injection sufentanil
as an infusion produces fewer alterations in heart rate and
blood pressure, which are particularly important in infants
where marked hemodynamic changes are poorly tolerated.
For neonates with critical CHD, a sufentanil anesthetic and
continued postoperative infusion have been shown to reduce
morbidity after cardiac surgery and to be superior to a halothane
anesthetic and routine morphine postoperatively. The blunting
of the stress response observed in this study was believed to
account for the differences in morbidity. Although high-dose
intraoperative opioids followed by postoperative infusion had
been the preferred approach in the 1980s and 1990s, evidence
suggests no real advantage to high-dose opioids in reducing
the stress response compared with moderate-dose opioids.
Lower doses facilitate early extubation and limit the need for
inotropes in the postoperative period. In general, the clinical
pharmacology of fentanyl and that of sufentanil share the
same age-related pharmacokinetic and pharmacodynamic
features. Furthermore, sequential sufentanil anesthetics in
neonates with CHD show marked increases in clearance and
elimination between the 1st week and the 3rd or 4th week of
life. The latter observation is most likely due to maturational
changes in hepatic microsomal activity and improved
hepatic blood flow from closure of the ductus venosus. The
variability in clearance and elimination, coupled with limited
cardiovascular reserve in the neonate during the 1st month of
life, makes opioid dosing difficult in this age group. Careful
titration of 5 to 10 mcg of fentanyl or 1 to 2 mcg of sufentanil
or a continuous infusion technique provides the most reliable
method of achieving hemodynamic stability and an accurate
dose-response.
Alfentanil and remifentanil are short-acting potent opioids
that have been used for cardiac surgery in children and show
some promise in pediatric anesthesia cases because of their
short elimination half-life and hemodynamic stability. A
significantly slower heart rate has been observed in children
anesthetized with remifentanil compared with fentanyl. As a
primary anesthetic in children undergoing CPB, remifentanil
and alfentanil must be administered via continuous
infusion due to their short half-lives. When the infusion
is discontinued, the patients plasma concentration falls
rapidly, particularly with remifentanil, and patients require
supplements of longer-acting opioids such as fentanyl or
morphine. The use of remifentanil and alfentanil is generally
limited to repairs where early extubation in the operating

room is planned. Remifentanil is an ultra-rapid-acting opioid.
Its unique metabolism by plasma and tissue esterases makes
it a more predictable drug. CPB can dramatically alter the
pharmacokinetic profile of a drug. It is known that in adults
the CPB prolonged the elimination half-life of alfentanil and
increased its central volume of distribution and volume of
distribution at steady state. Whereas, in children undergoing
CPB, the volume of distribution and elimination half-life of
remifentanyl is unaffected by CPB.
Transport and Handover to Pediatric Intensive Care Unit

Extreme vigilance is required during transfer of the child
from the cardiac operating room to the ICU. Monitoring of
the electrocardiography (ECG), arterial, venous and atrial
pressures, and end-tidal CO2 and pulse oximetry must be
maintained continuously; the battery charge of the monitor
and the infusion pumps should be checked before hand over
to prevent monitor failure and interruption of the infusions
of vasoactive medications. Resuscitation drugs, airway
equipment and blood products should accompany the child
to the ICU. Children who are transported with tracheal tubes
in situ are usually ventilated manually during transport via a
Jackson-Rees circuit, with either 100 percent oxygen or, for
those who require an FiO2 less than 1.0, an oxygen-air blender.
For children who require nitric oxide, a respiratory therapist
should assist with transport to ensure that no interruptions in
therapy occur and that a smooth transfer occurs in the ICU
as well. On arrival in the ICU, vital signs are confirmed, all
monitoring devices are transferred sequentially to the ICU
monitors and rechecked to ensure they are in working order.
POSTOPERATIVE CARE
Immediate postoperative care of the pediatric patient who has
undergone cardiothoracic surgery is an important period in
the overall sequence of anesthetic and surgical management.
Although the primary influence on outcome is determined by
the conduct of the operation, postoperative care is an important
factor. As a member of the operative team, it is necessary that
the anesthesiologist understand and become involved during
the immediate postoperative period. Detailed principles of
postoperative management of the pediatric cardiac surgical
patients are beyond the scope of this chapter. However, a
few general guiding principles and approaches are given to
provide fundamental knowledge for the anesthesiologist.
The postoperative period can be characterized by a series
of physiologic and pharmacologic changes as the body
convalesces from the abnormal biologic conditions of CPB
and cardiac surgery. During this period, the effects of the
cardiac operation, any underlying disorders, the effects of
hypothermic CPB and special techniques such as DHCA
may create special problems. In the immediate postoperative
gas (ABG) (including lactate levels) and serum electrolytes.

In children, the temperature monitoring is very important for
assessing the metabolism and the circulatory status. The probes
are placed in the rectum or near the esophagus to provide
adequate monitoring of the temperature. A nasopharyngeal
probe helps to assess the brain temperature. The recent
developments and recommendations that provide useful
physiologic information in this field include: transvenous
measurement of PA and LA pressures; echocardiographic and
on-line monitoring of arterial and mixed venous saturation.
Care should be initiated to stabilize the temperature, control of
bleeding, ventilation, and acid-base and electrolyte balance.
It is very important to stabilize the cardiac function
through maintaining an appropriate intravascular
volume, adequate heart rate and myocardial contractility.
Postoperative cardiovascular function can be periodically
reviewed by clinical examination, related tissue oxygen
indices, echocardiography and hemodynamic and/or
radioisotope evaluation. Important clinical signals for the
evaluation of cardiac output are perspiration, adequate level
of consciousness, color and temperature of the extremities,
thermal gradient between knees and feet, central and peripheral
thermal gradient, amplitude of the peripheral pulse, capillary
filling, arterial pressure and urinary output. Accordingly, the
cardiac output is considered adequate when there is no cold
perspiration or psychomotor agitation, extremities are warm
and colored, the feet are warmer than knees, the central to
peripheral thermal gradient is less than 4C, the peripheral
pulse is easily palpable, capillary filling is satisfactory, arterial
pressure is within the normal limits for the age group, and
the urinary output is greater than 1 mL/kg/h. It is important
to remember that adequate peripheral vasodilatation only
occurs after the fourth postoperative hour, with normal reestablishment of tissue perfusion around the sixth postoperative
hour. 2-D and Doppler echocardiography are valuable tools
for postoperative cardiac functional and structural evaluation.
These methods permit the analysis of cardiac chambers and
operative results, detection of residual defects, evaluation of
position and function of valvular prosthesis, segmental and
global myocardial analysis, calculation of shortening and the
ventricular ejection fraction and estimation of pressure inside
the cardiac chambers. Postoperative low cardiac output state
is commonly observed and is usually associated with left
anomalous coronary artery in the pulmonary trunk, HLHS,
transposition of the great arteries, severe tetralogy of Fallot,
and severe pulmonary hypertension. They are all associated
with significant risk of poor cardiac function after surgery.
Secondary hemodynamic instability is caused by inadequate
intravascular volume due to several factors including an
endothelial inflammatory process resulting from the CPB
procedure, which transfers fluids to the interstitial area during
the first 24 hours postoperatively. Control of intravascular
volume and indirectly of preload, should promote more
adequate systolic volume, according to the Frank-Starling law.
74
setting, abnormal convalescence and specialized problems

must be recognized and managed appropriately. Fortunately,
most patients are able to balance the cost imposed by the
physiologic trespass created by the surgical repair and the
effects of CPB against the benefit of reduced pathophysiologic
loading conditions, resulting in low morbidity and mortality.
Therefore, the guiding principle in the management of the
postoperative patient is an understanding of both normal and
abnormal convalescence after anesthesia and cardiac surgery
in children. The immediate postoperative period, even that
of normal convalescence, is one of continuous physiologic
change because of the pharmacologic effects of residual
anesthetic agents and the on-going physiologic changes
secondary to abrupt alteration in hemodynamic loading
conditions, surgical trauma and extracorporeal circulation.
Anesthesia and surgery affect not only the patient's conscious
state, but also cardiovascular, respiratory, renal, and hepatic
function; fluid and electrolyte balance; and immunologic
defence mechanisms. Despite all these changes, postoperative
care should be predictable and standardized for most patients
undergoing cardiac procedures.
In general, there are four temporal phases of postoperative
management in the pediatric cardiac patient:
1. Transport to the ICU,
2. Stabilization in the ICU,
3. Weaning from inotropic and ventilatory support, and
4. Mobilization of fluids.
Children proceed through these phases at variable rates based
on such factors as the underlying disease process, preoperative
medical condition, sequelae of the surgical procedure,
duration of CPB, and presence or absence of intraoperative
complications. One of the most important functions of
the ICU team is to identify postoperative complications
or adverse response or event in a child who convalesces
abnormally and to provide an aggressive interventional
therapy. Because physiologic change after cardiac surgery
is dramatic but self-limiting during normal convalescence,
recognition of abnormal processes can be difficult. Under such
circumstances a uniform, multidisciplinary approach with
experienced clinicians and nurses facilitates the identification
of any abnormalities in convalescence. These abnormalities,
often are indications for closer observation, more invasive
monitoring, pharmacologic intervention, and increased
cardiopulmonary technical support. Expected complications
include hypovolemia, residual structural heart defect, right and
left ventricular failure, hyperdynamic circulation, pulmonary
artery hypertension, cardiac tamponade, arrhythmias, cardiac
arrest, pulmonary insufficiency, oliguria, seizures and brain
dysfunction. It is critical to detect these departures from the
normal convalescent course and to treat them aggressively.
Standard monitoring at the pediatric postsurgical set-up
consists of ECG, SpO2, EtCO2, direct beat to beat arterial
pressure, temperature, central venous pressure, urine output,
ventilator parameters and laboratory values like arterial blood
1035
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13
During the postoperative period, the atrial pressure should

remain around 15 mm Hg, although it can reach 18 mm Hg in
the RA and 20 mm Hg in the LA when there is hypertrophy or
hypocontractility, partial obstruction in the ventricular outflow
or pulmonary artery hypertension. Afterload also influences
the cardiac output. It can be elevated by vasoconstriction
secondary to CPB, hypothermia, excessive endogenous
catecholamines or administration of vasoactive amines. Heart
rate is dependent on factors such as use of digitalis or beta
blocking agents in the preoperative period, type of surgery,
perioperative rhythm disturbances, volume, temperature,
pain, anxiety, anemia, metabolic disturbances and the use
of vasoactive agents with chronotropic action. In addition,
postoperatively myocardial edema could be responsible for
ventricular diastolic restriction. Recommended therapeutic
measures for the postoperative low cardiac output status
include three concomitant and related approaches: diagnosis,
reduction in metabolic demand and adequate tissue perfusion
and oxygen transport. Suspected cardiac dysfunction should
be promptly investigated for etiological diagnosis by clinical
or supplemental methods, so that specific and effective therapy
can be adopted. Reduction in metabolic demand requires the use
of measures that favor normalization of adequate temperature
and reduction in respiratory workload. Initial measures, even
during diagnostic investigation can be adopted to maintain
body temperature around 36.5C. Mechanical ventilation is
continued until the bleeding is controlled, hemodynamics are
stabilized, adequate body temperature is attained, metabolic
disturbances are corrected and acid-base balance is achieved.
Care of the right ventricle is equally important as that of left
ventricle.
Postoperative Pain Management
1036
One important area in which the anesthesiologist can aid

the recovery of the cardiac patient is pain control. Pain and
sedation are among the most common problems requiring
ICU intervention. Though these children demand elaborative
pain relief, it is vey much obligatory to keep them pain free in
presence of several tubes as well as the sternotomy incision.
Many factors influence the onset, incidence, and severity of
postoperative pain. The attenuation of the stress response
in the immediate postoperative period using infusions of
potent opioids in the critically ill infant reduces morbidity.
Attenuation of postoperative pain can be attempted with a
preoperative medication and an intraoperative anesthetic
management technique that includes the use of potent
opioids. Patients who receive no opioids preoperatively or
during the operative procedure will require analgesics in the
immediate postoperative period once the inhalation anesthetic
is eliminated. Most cases of postoperative pain can be
managed by the administration of small intravenous doses of
opioids, usually morphine. This is important in a patient being
weaned from the ventilator during the early postoperative
period. Patients who are intubated and ventilated overnight

should receive adequate sedation and pain control until
ventilatory weaning is begun. This is usually accomplished
by a continuous infusion of a benzodiazepine and an opioid.
Continuous infusion of sedatives and analgesics results in a
more consistent and reliable control of postoperative pain.
When separated from mechanical ventilation, the patient is
concurrently weaned from the sedatives and analgesics. Under
these circumstances, careful titration of opioids often results
in prompt pain relief. In patients with reactive pulmonary
artery hypertension, opioids have been shown to prevent
hypertensive crisis.
Regional Anesthesia
Good research into regional anesthesia and analgesia in
pediatric cardiac surgery is limited. The main concern is the
risk of bleeding and the potential for disastrous neurologic
complications. The risks may be greater in children than in
adults because of the presence of collateral vessels, increased
venous pressure, coagulopathy related to cyanosis, and the
use of aspirin. There remain many unanswered questions,
such as the true incidence of epidural hematoma in children,
the time delay required between placement of the epidural
catheter and full anticoagulation, and the correct management
if a bloody tap occurs. However, regional anesthesia may be
used for postoperative pain control in infants and children
after thoracotomy. Caudal morphine has been used to provide
postoperative analgesia. Caudal morphine can produce
good analgesia for about 6 hours and reduced the analgesic
requirement for up to 24 hours. This method avoids opioidinduced respiratory depression from intravenous doses of
these drugs. The administration of opioids in the epidural
space is a very effective approach to pain management. This
technique is used in children for postoperative pain control
when given in the epidural space via the caudal route as a
single shot or via a small caudal catheter. Morphine or
hydromorphone provides effective analgesia with a duration
of 6 to 12 hours, with no significant respiratory depression.
Caudal morphine diluted in 0.05 to 0.075 mg/kg delivered
in a total volume of 1.25 mL/kg of sterile saline has been
used with good success in our practice. The use of regional
anesthesia for postoperative pain appears to be best suited for
the child extubated in the early postoperative period. Relative
contraindications of this technique include hemodynamic
instability and patients with abnormal clotting profiles with
continued active bleeding. Using this regional technique,
better arterial oxygenation, a more rapid ventilator weaning,
and decreased postoperative respiratory complications may
be expected. However, urinary retention occurs frequently in
patients without a bladder catheter. Generally, no treatment is
required.
Children requiring large thoracotomies or a bilateral
thoraco-sternotomy (i.e. Clamshell) incision merit consider-
Summary of Surgical Management

The improvements in surgical technique, coupled with
advancements in anesthetic and technologic support, makes
repair in early infancy not only feasible, but in many cases
preferable. Currently, repair in infancy can be offered for a
number of congenital heart defects. The timing of surgical
intervention reflects medical necessity, physiologic and
technical feasibility, and optimal outcome. Cardiac defects that
require a PDA to sustain sufficient systemic blood flow or PBF
(e.g. pulmonary atresia, HLHS, interrupted aortic arch, critical
AS, and critical PS)) require an intervention in the neonatal
period. A variety of defects are optimally if not completely
repaired in early infancy. Lesions such as transposition of the
great arteries may exhibit better left ventricular function, if the
arterial switch operation is performed in the first few weeks of
life when the PVR has recently been high enough to increase
LV systolic pressure, whereas other repairs may manifest less
volatile postoperative physiology if deferred a few weeks or
months until PVR has consistently fallen (e.g. tetralogy of
Fallot, AV canal defect). Each defect may have mitigating
factors for which deferred definitive repair will enable optimal
surgical result (e.g. tetralogy of Fallot with aberrant coronary
branching pattern or multiple VSDs; transposition of the great
arteries with VSD and severe left ventricular outflow tract
obstruction).
Although some lesions merit repair whenever they are
diagnosed (e.g. total anomalous pulmonary venous return,
coarctation of the aorta), others exhibit such a wide spectrum
of physiologic disturbance that the timing of an intervention
must be made individually (e.g. VSD, AS, PS). A few cardiac
malformations produce pathophysiologic changes that are
sufficiently mild that repair is typically deferred to later
infancy or childhood (e.g. isolated ASD). Palliative surgery
is entertained when a physiologic derangement requires
intervention, but circumstances preclude definitive repair.
In general, the recent trend in pediatric cardiovascular

surgery has been to repair defects in infancy rather than
palliate. This trend reflects improved technical capabilities
coupled with a desire to limit the morbidity and mortality
associated with long-term medical management and the
sequelae of multiple palliative operations. Early corrective
surgery is expected to decrease the incidence of the chronic
complications of CHD, such as the problems associated
with ventricular overload, cyanosis, and pulmonary vascular
obstructive disease. Early infant repair may also have the
selective advantage of enhancing organ system protection
during repair because of poorly understood factors promoting
resistance to injury and enhanced recovery potential (i.e.,
enhanced plasticity). With the continued improvement in
surgical techniques and the early treatment of CHD, specific
organ systems such as the brain, heart, and lungs will be
spared the detrimental effects of chronic derangements of
hemodynamics and oxygen delivery.
Procedures for the treatment of CHD continue to evolve
to decrease long-term morbidity and enhance survival. For
example, the long-term problems with RV dysfunction and
failure associated with the Mustard procedure for repair of
transposition of the great arteries encouraged many surgical
groups to develop the neonatal arterial switch operation.
Early indications suggest that the latter procedure provides an
anatomic correction with better long-term results. A second
example of the continuing evolution of technique is surgery
for tetralogy of Fallot. Long-standing pulmonary insufficiency
after right ventricular outflow repair for tetralogy of Fallot
is associated with right ventricular dysfunction and failure.
Preservation of the pulmonary valve at initial repair using a
combined transatrial and transpulmonary approach during
correction and the early insertion of a pulmonary homograft
in the setting of pulmonary insufficiency are techniques being
used in an attempt to avoid the long-term problems of RV
dysfunction and failure.
Surgery for HLHS, once considered a fatal disease,
has achieved significant long-term survival in a growing
number of institutions after a series of staged reconstructive
procedures. The use of right ventricular to pulmonary artery
(RV-PA) conduits as an alternative to traditional systemic-topulmonary shunts has been shown to confer some advantage
in survival after stage 1 palliation owing to elimination
of diastolic runoff into the pulmonary circulation with
concurrent unloading of the systemic RV. There seems to be
an improvement in myocardial perfusion, with higher diastolic
pressures, lower aortic saturations, and decreased myocardial
work. The long-term impact of a right ventriculotomy in a
univentricular heart is unknown.The use of a low-resistance
strategy has been advocated for a stable postoperative course
with use of vasodilators such as phenoxybenzamine on CPB
and optimal reduction of PVR with inhaled nitric oxide and
100 percent oxygen after CPB.Several factors considered
to be associated with an increased risk for single ventricle
74
ation for thoracic epidural analgesia. This technique significantly

reduces the respiratory depression and pulmonary mechanics
abnormalities that accompany the quantity of systemic
opioids that would be necessary to provide adequate analgesia
for these excruciatingly painful incisions. If the procedure
requires systemic heparinization, one would typically defer
placement of these catheters until the heparin effect is
neutralized. For the patient undergoing coarctation repair via a
left thoracotomy, the caudal or epidural catheter is placed after
demonstration of motor function in the lower extremities. For
patients undergoing heart/lung transplantation, a thoracic
epidural catheter is placed at a time in the postoperative period
when the patient can be weaned from intravenous medications
that will adversely impact the patient's ability to breathe in
close proximity to the planned extubation. It is common for
these patients to need a functioning thoracic epidural catheter
for several days.
1037
General Issues
13
1038
palliation include anatomic variants such as aortic atresia,

mitral atresia, ascending aorta less than 2.0 to 2.5 mm,
restrictive atrial septum, obstructed pulmonary venous return,
the presence of other congenital anomalies, prematurity, birth
weight less than 2.5 kg, older age at time of surgery (> 14
days), surgical inexperience, and prolonged CPB and arrest
times. Perioperative factors can adversely affect outcome
and include preoperative metabolic acidosis, preoperative
inotrope support, morphologic RV in the systemic circuit,
RV dysfunction, presence of severe tricuspid regurgitation,
pulmonary valve regurgitation (beyond mild), and low ejection
fraction (< 30%) after a Norwood procedure. Neurologic
outcome after surgical repair is an ongoing concern.
Preoperative CBF was shown to be diminished in patients with
a variety of congenital heart defects, and low CBF values were
associated with periventricular leukomalacia. Some centers
routinely advocate regional low-flow cerebral perfusion and
measurement of regional cerebral oxygen saturation index
and CBF velocity using TCD during arch reconstruction in
this population. Reductions in the regional cerebral oxygen
saturation index or CBF greater than 20 percent of baseline
are treated aggressively in an attempt to increase cerebral
oxygen delivery by increasing the mean perfusion pressure,
red blood cell transfusion, and maintenance of high normal
levels of PaCO2 to achieve cerebral vasodilation.
Surgical management has evolved in a broader application
of certain surgical procedures initially designed for a specific
defect. For example, modifications of the Fontan operation,
which was originally devised for patients with tricuspid
atresia, are now being used to repair a variety of univentricular
hearts, including HLHS. Initially, the wider application
of the Fontan operation to include complex defects once
considered inoperable was associated with a rise in morbidity
and mortality. However, this trend has been reversed in
recent years by several groups who have demonstrated
improved outcome with the staging of the operation (superior
cavopulmonary anastomosis, subsequent completion of the
Fontan operation), the creation of a fenestration between the
right and left atrium at the time of the Fontan operation, and
the use of MUF (see later). The communication allows for
right-to-left shunting, thereby preserving cardiac output at
lower systemic venous pressure in the early postoperative
period. When necessary, once the patient has convalesced
from the acute postoperative changes, the fenestration can be
closed at the bedside with a snare placed at the time of the
operation or in the catheterization laboratory with a device.
In a substantial proportion of cases, these fenestrations close
spontaneously without further intervention.
Ingenuity and innovation such as demonstrated with
the difficult Fontan procedure have permitted continued
improvements in survival for all patients with congenital
heart disease. As incisions in the myocardium become smaller
and sutures more precisely placed, and as improvements in
surgical techniques continue to evolve, the complications of
ventricular dysfunction, arrhythmias, and residual obstruction

should decline, contributing to improved patient quality of
life.
One final difference unique to congenital heart surgery
that has a major impact on anesthetic management relates
to the type of cardiopulmonary support. Because of the
complexity of repair in small patients, surgery often requires
significant alterations in the bypass techniques, such as the
use of deep hypothermic CPB at temperatures of 18C and
total circulatory arrest. Many operations are undertaken in
this setting of extreme biologic conditions of temperature
and perfusion. Current methods of CPB management in
neonates, infants, and children involve extensive alterations in
temperature, hemodilution, systemic perfusion pressure, and
flow. Despite widespread use of these techniques during CPB,
their physiologic effects on major organ system function are
just beginning to be understood.
Cardiopulmonary Bypass
Prebypass Anesthetic Management: Anesthesia
on Cardiopulmonary Bypass and Changes in
Pharmacokinetics
The initiation of CPB introduces additional volume to the
intravascular space (hemodilution). This greatly affects
drug distribution, plasma concentrations and elimination.
The major factors responsible for this are hemodilution and
altered plasma protein binding, hypotension, hypothermia,
pulsatility, isolation of the lungs from the circulation, and
uptake of anesthetic drugs by the bypass circuit. Drugs
in the blood exist in the free (unbound and therefore the
active form) or plasma bound (inactive form bound to
protein, e.g. albumin) forms and therefore are subject to
marked changes with alterations in plasma protein levels.
CPB alters all these factors, which makes description of
pharmacokinetic parameters during CPB problematic. The
greatest changes occur within 5 minutes of initiation of CPB.
The addition of the prime volume immediately reduces the
protein concentration and the ratio of bound-to-free drug in
the circulation changes. A reduction in RBC concentration
occurs, and this reduces the free drug concentrations. This
will reduce the amount of drug available for interaction
with the receptors. Most studies show a reduction in total
drug concentration in plasma with little change in free drug
concentration over time, whereas on CPB there is transient
reduction at initiation of CPB. It would appear that the greatest
risk for unwanted lightening of anesthesia is within this time
frame and additional doses of fentanyl, muscle relaxant and
midazolam are generally administered just before or with the
onset of CPB. The explanation for why free drug levels are
sustained during CPB is that the volume of distribution (Vd)
for most anesthetic agents is large relative to the volume of
the CPB prime and serves as a huge reservoir for the drug
Changes in Pharmacodynamics
The pharmacodynamic effects of anesthetic agents are
affected primarily via the CNS, which undergoes major
changes during CPB. For example, hypothermia during
CPB reduces anesthetic requirements. Hypothermia
causes a host of other effects, including decreases in
receptor affinity (e.g. decreased opioid receptor affinity
and nicotinic acetylcholine receptor sensitivity), increases
in both the pharmacokinetic and pharmacodynamic
effects of neuromuscular receptor blocking agents, thus
enhancing their effects at the neuromuscular junction, and
alterations in tissue blood flow that may affect the response
to catecholamines. It also affects the degree of ionization
and protein binding (hence free drug levels) of weak
acids and bases as well as the electrolyte balance by the
blood gas management strategy used during CPB. Plasma
concentrations of calcium, magnesium, and potassium
decrease during CPB, and these changes may lead to
muscle weakness, dysrhythmias, and digitalis toxicity. The
number of receptors available for interaction with a ligand
will determine the subsequent magnitude of a drug effect.
A reduction in the number of cardiac receptors has been
observed in congestive heart failure, and defects in receptor
transduction and impairment of synthesis and reuptake
of norepinephrine occur. Changes in receptor density and
function may occur very quickly and have been observed
to occur during cardiac surgery. Many perfusionists, under
the direction of the anesthesiologist, can also administer

inhalation agents via a separate vaporizer mounted on
the bypass machine. Anesthetic requirements decrease
with systemic hypothermia, but as rewarming is initiated,
additional anesthetic drugs, including a benzodiazepine,
are added to the pump to ensure that anxiolysis/amnesia is
maintained.
Pre-Bypass Period
This phase begins with surgical incision and lasts through
initial dissection and preparation for cannulation. During
this period TEE is performed to confirm the diagnosis and
establish a basis for post-bypass comparison. The objectives of
the anesthetic management of children before bypass include
maintenance of normal sinus rhythm and ventricular function
and avoidance of extreme increases in heart rate, ventricular
contractility, and PVR. The duration of the pre-bypass period
varies greatly, particularly in children who have had previous
surgeries, and maintaining hemodynamic stability for pro
longed periods of time can often be challenging. Adequate
anesthetic depth should be ensured to avoid increases in
sympathetic stimulation and hypercyanotic spells, and
temperature homeostasis should be maintained to avoid
cardiac arrhythmias, especially when the duration of the preCPB surgical dissection is protracted. For children undergoing
repeat sternotomy, blood products with an appropriate-capacity
blood warmer should be readily available in case of emergent
need. Neonates and children who have been receiving total
parenteral nutrition preoperatively receive an infusion of 5 or
10 percent dextrose before CPB, with frequent monitoring of
glucose levels to avoid hypoglycemia or hyperglycemia. Older
children receive plasmalyte, a balanced electrolyte solution,
at a reduced maintenance rate, allowing the administration of
5 percent albumin, if necessary, for volume augmentation. The
placement of purse-string sutures before cannulation, as well as
the actual cannulation of the great vessels before CPB, can often
precipitate arrhythmias, hypotension, and arterial desaturation,
especially in small infants and children. It is not unusual for
volume replacement to be necessary during placement of the
cannula; and if the aortic cannula is already in place, it will be
easy to coordinate the administration of volume between the
anesthesiologist and perfusionist, while the surgeon completes
cannulation. Calcium chloride, 10 mg/kg, is also frequently
useful to support hemodynamics at this time.
74
after intravenous administration. A decrease in the plasma

concentrations of medications as a result of hemodilution,
shifts drugs down their concentration gradient from tissue to
plasma. Hypothermia contributes to the changes in plasma
concentrations primarily by depressing enzyme function and
slowing the metabolism of medications. Drug metabolism is
diminished during hypothermia; enzyme activity is halved
for every 10C reduction in temperature. This may increase
the free drug available for binding. When normothermia is
re-established, reperfusion of tissues might lead to washout
of drug sequestered during the hypothermic CPB period. This
may explain the secondary increases in plasma concentrations
of opioids reported during the rewarming phase. pH-stat
management also affects the degree of ionization and
protein binding of certain medications, leading to increased
free fractions (active) of these medications. During CPB,
the lungs are out of circuit and medications that are taken
up by the lungs (e.g. opioids) are sequestered during CPB.
These medications are released when systemic reperfusion is
established and concentrations are transiently increased. The
volume of distribution of many drugs is expanded due to the
priming volume of the bypass circuit, especially with neonates
and small infants, where the priming volume is often greater
than the childs blood volume. Finally, medications may be
taken up by various components of the CPB circuit itself.
Cannulation and Initiation of Bypass

After sternotomy and mediastinal dissection, the aorta
is cannulated, along with either the RA, if single venous
drainage is planned, or the superior and inferior venae cava
for bicaval venous drainage. Before initiation of CPB, the
surgeon will request that heparin is given. A large dose of
heparin (300400 units/kg) is administered intravenously,
1039
General Issues
13
1040
and the adequacy of anticoagulation is measured using the

activated clotting time (ACT) before initiating CPB. The
target ACT level is usually 480 seconds, but in the presence
of aprotinin, a target of 600 seconds is desirable because of
this agents effect on the test measurement. High levels of
ACT are maintained on CPB with the addition of heparin
to the prime and as needed because larger doses of heparin
lead to a reduced degree of consumptive coagulopathy, which
translates into reduced blood product therapy requirements.
Other methods of measuring anticoagulation include the
Hepcon system (a plasma heparin concentration assay),
which may allow for more accurate titration of heparin and
protamine dosages. The thromboelastogram may also be
utilized as a baseline measure of the coagulation system
and then may be repeated on bypass with heparinase added
to more objectively assess each childs anticipated need
for coagulation products. An improved preservation of
the hemostatic system with subsequent reduction of blood
loss and a reduction in transfusion requirements has been
demonstrated after maintenance of high heparin levels during
CPB. The additional maintenance of high antithrombin III
(ATIII) concentrations may further contribute to a reduction
of hemostatic activation.
In most centers, bicaval cannulation is used for all, but
the smallest children (< 2 kg) to prevent venous return from
interfering with the surgical field. A gradual transition to full
CPB is then performed to minimize myocardial stress, using a
prime that has essentially the same composition as the childs
blood with regard to temperature, pH, calcium, potassium,
and hematocrit. CPB flows of 150 mL/kg/min are used for
infants weighing less than 10 kg, and 2.4 L/min/m2 is used
for children weighing more than 10 kg. Flow rates may be
reduced during periods of hypothermia, although many centers
now prefer to maintain greater flows throughout the bypass
period. Misplaced cannulas can lead to significant morbidity.
Obstruction of the inferior vena cava (IVC) by a misplaced
IVC cannula can lead to increased venous pressure, which
causes ascites and decreased perfusion pressure in mesenteric,
hepatic, and renal vascular beds. Misplacement of the cannula
in the SVC can result in increased venous pressure in the
cerebral venous system. Subsequent cerebral edema results
from inadequate venous drainage and a consequent reduction
in CBF, potentially resulting in ischemia. Arterial cannula
misplacement can also occur. If the cannula inadvertently slips
beyond the takeoff of the right innominate artery, preferential
perfusion to the left side of the brain can be observed. This can
be detected on the NIRS monitor, which may be an important
monitor, particularly in pediatric-cardiac surgery. The
presence of any anomalous systemic-to-pulmonary shunts can
lead to shunting of blood away from the systemic circulation,
through the pulmonary circuit, and then through the venous
cannula to the CPB machine. Thus, the systemic perfusion is
shunted away from the body in a futile circuit back to the CPB
machine. Anatomic lesions where such shunting can occur
include an unrecognized PDA and large aortopulmonary

collaterals as found in pulmonary atresia. Bypass flow needs
to be adjusted to compensate for these shunts.
Cooling Phase
Systemic cooling is utilized for nearly every case. Hypothermia
is classified as mild (30C36C), moderate (22C30C), or
deep (17C22C). In general, lower temperatures are used
for more complex operations that carry a greater potential for
requiring periods of low-flow bypass or circulatory arrest.
Cooling is primarily achieved extracorporeally through the
heat exchanger in the bypass circuit, although some surgeons
also request that ice be applied to the head.
Aortic Cross-clamping and Intracardiac Repair Phase

The aorta is cross-clamped, with the heart then rendered
asystolic after infusion of a high-potassium cardioplegia
solution into the aortic root. Both hypertension and
hypotension may complicate bypass. Blood pressure may
be controlled within the normal range using -adrenergic
blockers or agonists. Phenylephrine is commonly used to
increase blood pressure, and phentolamine is often used to
lower blood pressure. The child is usually cooled at this stage,
using the nasopharyngeal temperature as a guide. Cardioplegia
is given by the perfusionist after cross-clamping the aorta to
stop the heart and provide cardioprotection during the period
of ischemia. This is usually repeated every 20 to 30 minutes.
Young children are more susceptible to the adverse effects
of CPB than adults, and the inflammatory response to CPB
may have serious consequences for neonatal and pediatric
patients. This is in part related to the surface area of the CPB
circuit, which is large relative to the childs blood volume when
compared with an adults blood volume. For example, a 3 kg
neonate with a blood volume of 90 mL/kg has a total blood
volume of 270 mL, and with an average priming volume in
many centers of 350 mL, the CPB circuit volume thus causes
greater than 100 percent dilution (adults 35% dilution). Recent
technical advances in the field of oxygenator construction and
size and reduction of priming volumes to as low as 45 mL
for neonatal oxygenators have allowed significant reductions
of circuit volumes over the past decade. As the circuit prime
volume is reduced, the dilutional effects of bypass become
less dramatic, and plasma concentrations of anesthetic drugs
should be maintained at a higher level compared with earlier
reports. Also, tubing sizes can be reduced to 3/16-inch
diameters, which, in combination with shorter length tubing,
allow reduction of priming volumes to the range of 100 to 150
mL for neonates. An additional consideration is the success
with circuit miniaturization and heparin-coated oxygenators
and circuits. Heparin and biological coatings designed to
minimize activation of proinflammatory mediators and
endothelial cell damage are applied to oxygenators and tubing.
an average decrease in plasma concentrations of hemostatic

proteins by 56 percent immediately on initiation of bypass
can be observed. Overall, younger age represents the single
most important risk factor for coagulopathy and bleeding
complications.
Infusion of fresh frozen plasma (FFP) may be safely
substituted by albumin 5 percent in the prime in children
with less-complex repairs and acyanotic lesions. Whenever
possible, fresh blood less than 5 days old is preferred. Fresh
packed red blood cells (PRBCs) are presumably more balanced
metabolically than stored PRBCs; the former contain less
potassium and they have greater concentrations of glucose,
reduced concentrations of lactate and a greater pH. As far
as potassium levels and acid-base balance are concerned,
PRBC priming can be safely performed with stored PRBCs,
if the priming solution is circulated for 20 minutes before the
initiation of CPB. Depending on the size, age and complexity
of the repair, a target hematocrit is chosen. Based on the childs
blood volume and the prime, homologous blood is added. The
required amount to be add is calculated as:
Target haemocrit =

Patients blood volume Patients haemocrit

Total circulating volume
(Priming volume + Patients blood volume)
The prime blood gas and electrolytes should mimic

physiologically to the childs ABG as closely as possible. If
whole blood or packed cells are added to the prime, the target
hemodilution range should be 28 to 30 percent; the prime
should be recirculated continuously and warmed between
35.0C and 36.5C before initiation of bypass. Other prime
additives are heparin, antifibrinolytics, anti-inflammatory
agents (aprotinin, corticosteroids), antibiotics, vasodilators,
and sometimes, diuretics (mannitol, furosemide). At the end
of the case and before separation from bypass, blood gas
analysis is repeated to ensure that the electrolytes, glucose,
and hematocrit are within a desired range. Acid-base
changes and sodium concentration are corrected with sodium
bicarbonate, and residual lactate is washed out with the help
of the hemofiltration.
Myocardial damage is related to both the duration of the
aortic cross clamping and the effectiveness of the myocardial
protection. Myocardial protection by using potassium containing
cardioplegia is used routinely. Potassium concentrations
in cardioplegic solutions ranging from 12 to 30 mEq/L are
typically used to achieve cardiac standstill within 1 to 2 minutes
under hypothermic conditions, with higher concentrations (or
longer induction times) required for normothermic conditions.
Myocardial edema after bypass and global ischemia can
be reduced by a number of strategies that involve modifying
the conditions of delivery and composition of cardioplegia
solutions as they affect the movement of intracellular and
interstitial fluid. In contrast to studies in adults, most studies
conducted in newborns have shown little difference between
74
Reducing endothelial cell leakage should stabilize the patient's

plasma volume and, by reducing renal and hepatic injury,
improve drug clearance. They also have been shown to reduce
the activation of factor XII and the complement system. This
results in less production of kallikrein and bradykinin, which
in turn reduces the secretion of tissue plasminogen activator
from endothelial cells. Studies have evidenced that the
children operated on with heparin-coated circuits will have
a significant reduction in inflammatory mediator release and
fewer consequences thereof, such as prolonged postoperative
ventilation and stay in the ICU. The two types of pumps that
are most commonly used for CPB are:
1. Roller pumps and
2. Centrifugal pumps.
In the setting of short-term CPB for cardiac surgery, it
remains uncertain whether the selection of a roller pump
over a centrifugal pump or of any specific centrifugal pump
over another has clinical importance. Likewise, the optimal
priming fluid in cardiac surgery is a topic of enduring debate.
Crystalloid solutions, colloids, and mixtures of both are used.
Children appear to benefit from a colloid prime. If crystalloid
is used for priming, it should not contain lactate or dextrose
because CPB induces a metabolic acidosis that has been
shown to be iatrogenic and not splanchnic in origin. The
addition of lactate to the prime increases postoperative serumlactate concentrations and should be avoided. Hyperchloremic
metabolic acidosis is the second contributing component of a
metabolic acidosis on CPB.
This is often only detected by measuring the strong
ion difference via the Stewart approach to the acid-base
homeostasis. Both acidifying events are attenuated by the
dilutional hypoalbuminemia induced by the administration of
the pump prime. Because a hyperchloremic acidosis of a mild
degree seems to be well tolerated and not associated with a poor
outcome, no intervention seems necessary. Understanding
the nature of CPB associated acidosis, however, is likely to
prevent unnecessary investigations or interventions. The
avoidance of dextrose is especially important during complex
repairs using deep hypothermic cardiac arrest in which the risk
of neurologic injury is substantive. The additives in banked
blood, namely glucose in citrate-phosphate-dextrose (CPD)
storage solutions, also need to be considered as a source of
glucose (together with the increased plasma concentrations of
potassium in stored blood). Now a days a balanced electrolyte
solution such as Plasmalyte is used for the crystalloid
component of the prime. The proportionally large volume of
the bypass circuit compared with the childs blood volume has
a significant impact on the coagulation factors and cellular
components. Platelet count decreases and coagulation factors,
including fibrinogen, are diluted after bypass and these may
contribute to a coagulopathy. The fibrinogen concentration
at the end of bypass has been shown to correlate with the
24-hour chest drainage in children weighing less than 8 kg.
This is seen more frequently in infants and neonates in whom
1041
General Issues
13
blood and crystalloid cardioplegia. Hypothermia also

decreases myocardial oxygen consumption. The benefits
of this approach appear to be optimal at myocardial
temperatures between 24C and 28C. Avoidance or reduction
of myocardial edema occurs by limiting the pressure
of cardioplegia infusions and by providing moderately
hyperosmolar cardioplegia solutions that contain blood.
Buffering the acidosis that results from ischemia is achieved
by including tromethamine (THAM), histidine-imidazole,
or both in the cardioplegia solution. Close management
of myocardial calcium balance to avoid extremes of intra
cellular hypercalcemia or hypocalcemia, especially during
reperfusion, is very important. The addition of magnesium
may solve this dilemma by preventing damage from higher
cardioplegic calcium concentrations by its action as a calcium
antagonist. This prevents mitochondrial calcium overload as a
consequence of reperfusion injury. Magnesium also prevents
the influx of sodium into the postischemic myocardium, which
is exchanged for calcium during reperfusion. Every cardiac
program has their own philosophy regarding cardioplegia
and myocardial protection. Some use plain crystalloid
cardioplegia. In neonates and infants, albumin is added to
the cardioplegic solution to maintain an appropriate colloid
osmotic pressure. This may decrease edema formation of the
arrested heart. In children undergoing circulatory arrest, long
cross-clamp times, and large pump suction return cases, 20
mg/kg methylprednisolone is used up to a maximum of 500
mg, to reduce the production of inflammatory mediators that
result in myocardial dysfunction.
Rewarming
1042
Rewarming may have begun before release of the crossclamp, but more usually the child is rewarmed only after
release of the clamp. After completion of the intracardiac
repair and deairing of the heart, the aortic cross-clamp is
removed, allowing reperfusion of the myocardium. Optimally,
normal sinus rhythm and myocardial contractility are restored
during this time, while the child is slowly rewarmed. During
rewarming, surgery is completed, inotropic and vasoactive
agents are started, and ventilation resumes. Hemofiltration
and blood transfusion are used to achieve the desired
hematocrit. Left atrial and/or pulmonary artery monitoring
lines, if indicated, are placed at this time. Various degrees
of heart block are common after heart surgery and it is most
frequently associated with the administration of cardioplegia.
As the heart is reperfused for a longer time, and the effects
of cardioplegia are reduced, normal sinus rhythm is usually
restored. However, heart block may result from damage to the
conducting system during surgery and may require temporary
atrial and ventricular pacing. If the child is incompletely
rewarmed before separation from CPB, a significant after
drop with precipitous post-bypass reduction in core body
temperature can occur. This would lead to vasoconstriction,
shivering, increased oxygen consumption, and acidosis.

However, postischemic hyperthermia can lead to delayed
neuronal cell death. Mild degrees of hypothermia and
certainly the avoidance of hyperthermia are essential in the
perioperative period. In children, rectal temperature mostly
reflects peripheral temperature. Studies have shown that the
temperature of the foot is more sensitive than the temperature
of the hand and for anatomic or physiologic reasons,
temperature gradients in the toes develop more readily than
those in the fingers. Several end points have been proposed,
such as nasopharyngeal temperatures greater than 35.0C,
bladder temperature greater than 36.2C, or skin temperatures
greater than 30C, or 35.5C rectal temperature. When the
child has adequately rewarmed, as reflected by a normal core
and minimal core-peripheral temperature difference, a warm
liver, good heart function has returned, the childs lungs are
adequately ventilated, and any inotropes required have been
started, the child is ready to be separated from bypass. If a
TEE probe is in place, the heart should be scanned for the
presence of any air. If air is present, further deairing should
occur before attempting to come off bypass.
Separation from Bypass

The childs core body temperature, hematocrit, and
metabolic parameters should be optimized before attempting
separation from CPB. Careful observation for left-sided air,
confirmation with the TEE, and concurrent ECG changes
continue throughout the weaning process, with the child in
Trendelenburg position and the aortic root vented. CPB flow
is then gradually reduced to zero, while volume is added to
the child from the reservoir until optimal filling pressures are
achieved.
In the initial stages, after separating from bypass,
additional volume can be administered by the perfusionist
via the aortic cannula, usually under the direction of the
surgeon or anesthesiologist. Many centers at this point would
institute MUF. This involves taking arterial blood from the
aortic cannula and passing this blood through the ultrafilter.
This blood, which is oxygenated and warm is then reinfused
into the RA. When this process is complete, a thorough TEE
examination can be undertaken. When the team is satisfied
with the TEE result, the surgeon will ask for protamine to be
administered. Before this is done, both the perfusionist and
the surgical team should be informed that protamine is about
to be administered. The surgeons should remove any pump
suckers from the field and the perfusionist should stop all
pump suction. This is to ensure that no protamine enters the
bypass circuit in case it is necessary to go back on bypass
for any reason. The ACT can now be checked along with
blood gas analysis. The ACT should return to pre-bypass
levels. Any blood products required are usually given after
the administration of protamine, and these are usually given,
while the surgeons are achieving hemostasis. As soon as the
chest is closed the child can then be transferred to the cardiac

ICU.
This phase lasts until chest closure and transfer to the ICU
have been accomplished. During this time, MUF may be
performed for 10 to 15 minutes after cessation of CPB.
Cardiac function and the quality of the surgical repair are
assessed via TEE, and, if found to be satisfactory, protamine
is then administered to neutralize residual heparin. The usual
dose of protamine is 1.0 to 1.3 mg/100 units of heparin
given at the onset of bypass. Limiting protamine to this
dose prevents overdosing of protamine with its associated
effects on platelet function (reduction of the interaction of
glycoprotein Ib receptor interaction with von Willebrand
factor). If the ACT is still elevated or prime blood is given
back to the child, an additional 25 percent of the initial dose
of protamine is added and the ACT is rechecked. However,
particularly in infants, the administration of protamine and
the persistent treatment of a suspected incomplete heparin
reversal should not distract and delay the treatment of
other commonly associated post-bypass coagulopathies
such as thrombocytopenia, platelet dysfunction, and other
coagulation factor deficiencies. Protamine reactions are much
less frequent in children younger than 16 years of age and are
reported as 1.76 to 2.88 percent. Independent risk factors are
a female gender, a larger protamine dose, and smaller heparin
doses. Type I reactions or effects during administration are
rare and adding calcium does not change the hemodynamic
consequences of injection. Fortunately, severe anaphylactic
reactions (type II) or catastrophic pulmonary vasoconstriction
(type III) are rare, but have been observed by us and others.
Administering the protamine over no less than 5 minutes
reduces the severity and precipitous nature of any protamine
reaction. Unstable neonates and small infants may have their
sternums temporarily left open, with surgical closure planned
24 to 72 hours later when cardiac function has improved
and myocardial edema diminished. Because CPB can have a
multitude of adverse physiologic effects, attempts are made
to minimize both the duration of CPB and ischemic (aortic
cross-clamp) time; thus as much of the surgery as possible
is performed outside of these phases. In general, physiologic
responses to bypass are more extreme with decreasing age and
size of the child. The neonate experiences a greater degree of
hemodilution on bypass and colder temperatures on bypass
and frequently requires longer aortic cross-clamp times, all of
which can result in a greater inflammatory response.
Conventional Ultrafiltration vs Modified Ultrafiltration

Ultrafiltration involves placing a hemofilter (similar to
those used for continuous arteriovenous or venovenous
hemofiltration in the ICU) in the CPB circuit and has become
74
Post-Bypass Period
the standard of care for nearly all congenital heart surgery

programs. Conventional ultrafiltration (CUF) is performed
during CPB, with the filter placed between the arterial and
venous sides of the CPB circuit. The hemofilter has thousands
of fibers with pores, which allow water, electrolytes and small
molecules to be filtered out of the blood. Suction is applied
to the hemofilter on CPB, and an ultrafiltrate of plasma is
produced. Advantages of ultrafiltration include the ability
to increase the hematocrit, fibrinogen, plasma proteins and
platelet count, without necessitating further blood transfusion,
the ability to remove excess free water and sodium (which
contribute to excess intravascular volume, tissue edema,
pulmonary and myocardial edema), as well as the ability to
correct acid-base and electrolyte imbalances and to remove
small molecules, such as interleukins (IL) and tumor necrosis
factor-a (TNF-a) in particular, which are involved in the
post-bypass inflammatory process. This improves systolic and
diastolic function of the myocardium and reduces endothelial
dysfunction in the systemic and pulmonary vasculature.
Pulmonary function is better preserved, probably owing to a
slight reduction in interleukin-6 (IL-6) and thromboxane-B2
(TXB2), even though this is not a consistent finding in
the literature. Endothelin-1 (ET-1), another mediator of
pulmonary damage and hypertension, was not reduced by
any filtration method. Clinically, however, any ultrafiltration
method seems to benefit children, especially those undergoing
complex repairs, neonates, and children with pre-existing
pulmonary hypertension. The MUF is performed for 10 to
15 minutes immediately after the conclusion of CPB. It can
be performed in an arteriovenous manner with a hemofilter
placed between the aortic cannula and the IVC cannula or in
a venovenous fashion using bicaval cannulation or an internal
jugular venous catheter. It was developed as an alternative
method to reduce the side effects of CPB. CUF during bypass
is often limited by the minimal venous reservoir levels and
requires the addition of crystalloid or colloid to be able to
continuously remove cytokines during ultrafiltration. During
MUF, blood passes out of the aorta, through the hemofilter,
and is returned through the IVC cannula. The theoretical
advantage of MUF over conventional ultrafiltration is that
only the childs blood volume is filtered, yielding a more
efficient system for achieving the goals. The disadvantages
are that the child remains heparinized, body temperature may
decrease during the process (unless the circuit is modified to
include the heat exchanger). It requires extra time, an aortic
cannula is needed that can obstruct the aorta in small infants,
and acute intravascular volume shifts may occur at a time
when the child is prone to hemodynamic instability. Opposite
to the expected effects of fluid removal, MUF actually
increases arterial pressures despite decreasing filling pressures
and improving myocardial performance. There is increasing
evidence that the use of ultrafiltration reduces bypass-related
postoperative morbidity. Outcome studies have demonstrated
that ultrafiltration improves myocardial and pulmonary
1043
General Issues
13
function, lessens tissue edema, allows faster weaning from

mechanical ventilation, and decreases the need for inotropic
support. The reduction of inflammatory transmitters is only
temporary because the levels of cytokines will be similar
after 24 hours. Although each method has its proponents, and
some centers perform both techniques in the same children,
controlled comparative studies revealed no difference in
outcome between MUF and CUF. The balanced ultrafiltration
technique will remove fluids and cytokines, as well as reduces
lactate, which in turn prevents reperfusion injury.
Deep Hypothermic Circulatory Arrest or

Selective Cerebral Perfusion
1044
If circulatory arrest is to be used, it is initiated after a cooling

period of at least 20 minutes, and an attempt is made to limit
the total duration of DHCA to less than 40 minutes. Special
bypass techniques have been developed to avoid the necessity
of using DHCA and may also be performed during this time.
To avoid the use of DHCA, several novel CPB techniques
have been developed. The purpose of these techniques is to
allow perfusion of the brain during critical periods of surgery,
such as aortic reconstruction during the Norwood operation.
These techniques are collectively referred to as selective
cerebral perfusion. Regional low-flow cerebral perfusion
(RLFP) is one variation in which a small Gore-Tex graft of 3
to 4 mm is sewn onto the innominate artery before initiation
of CPB and is then used as the aortic cannula during CPB.
During aortic reconstruction, snares are placed around the
brachiocephalic vessels and CPB flow is decreased, with
only the brain receiving perfusion via the right carotid artery
during this period. In this way, a bloodless operative field
is achieved, just as if DHCA was being performed, yet the
brain is still receiving blood flow and oxygen, theoretically
increasing protection from hypoxic ischemic brain injury.
Another potential advantage of this technique occurs in
neonates, who frequently have extensive arterial collaterals
between the proximal branches of the aorta and the lower
body via the internal mammary and long thoracic arteries.
In this instance, the use of selective cerebral perfusion also
provides some blood flow to the lower body, protecting renal,
hepatic, and gastrointestinal systems from hypoxic damage
as well. The protection is, however, incomplete; and RLFP
at 25C is no more protective than DHCA. Also, the ongoing
perfusion prolongs the effective bypass time, leading to more
cytokine release and capillary leakage with worse pulmonary
function, more weight gain, and decreased right ventricular
function. Despite the theoretical advantages of selective
cerebral perfusion and having demonstrated that selective
cerebral perfusion does provide oxygenated blood flow to
both cerebral hemispheres, no long-term outcome studies
have been performed that prove it is superior to standard
techniques. This may in part be related to the novelty of this
procedure. Neurologic monitoring has been used to determine
the flow rate that is necessary during RLFP. Usually, one

would use 40 to 50 percent of full flow and adjust it according
to brain saturation or Doppler measurements, maintaining
baseline saturation before the onset of RLFP. If a left radial
arterial line or a femoral arterial line/umbilical artery line
(UAC) is in place, an abdominal perfusion pressure of about
12 mm Hg, which correlates with radial artery pressures of 25
to 30 mmHg, is the goal.
Neurologic Monitoring and Effects of

Cardiopulmonary Bypass on the Brain
Cerebral monitoring can help to detect those children who
are at risk for neurologic sequelae after bypass, promptly
recognize and treat changes in CBF/oxygenation, evaluate
the effect of therapeutic interventions on cerebral physiology,
optimize brain protection during the vulnerable periods
of CPB, and potentially improve short- and long-term
neurologic outcomes. NIRS is a monitor that measures brain
tissue oxygenation. This device non-invasively measures the
concentration of oxyhemoglobin and deoxyhemoglobin and
determines the cerebral tissue oxygen saturation. The cerebral
oximeter probe, a light-emitting diode, is placed on the skin
of the forehead and uses near-infrared light similar to a pulse
oximeter that measures the hemoglobin oxygen saturation.
Commercially available devices use two different
wavelengths, i.e. 730 and 810 nm, that pass through brain
tissue 2 to 5 cm beneath the probe in the frontal cortex. The
light absorbed by extracranial tissues is subtracted from the
total signal (detected by the distal electrode), leaving only the
intracranial contribution.The monitor displays a numerical
value for the regional cerebral oxygen saturation = rSO2,
the ratio of oxyhemoglobin to total hemoglobin in the light
path. rSO2 is a measure of local microcirculatory oxygen
supply-demand balance and is reported on a scale from
15 to 95 percent. It has been assumed from anatomic models
that 75 percent of the cerebral blood volume in the light path
is venous and 25 percent is arterial. The study that verified this
in children with CHD by directly measuring the jugular venous
bulb and arterial oxygen saturations and compared these with
the cerebral oxygen saturation measured with NIRS.The actual
ratio in children varied widely, but on average the venous to
arterial ratio was 85 : 15. All devices measure both the arterial
and venous blood oxygen saturations. Accordingly, this device
does not provide a measure of the jugular venous bulb oxygen
saturation (SjvO2). A corollary of this is that maneuvers that
increase arterial oxygen saturation (e.g. increasing FiO2) increase
cerebral oxygenation as measured by these devices, although the
SjvO2 may remain unchanged.
pH-Stat vs Alpha-Stat Management

Some degree of hypothermia is utilized for nearly every cardiac
operation to slow the metabolism and oxygen consumption of
Hematocrit on Bypass
The relatively small total blood volume in children, along
with the volume required to prime the CPB circuit, means that
adding blood to the CPB prime is mandatory for small infants.
Practice is institution specific; but in many centers adding
either whole blood, PRBCs with FFP (for children below
8 kg), or PRBCs alone (for children between 12 and 15 kg) is
necessary to ensure that the hematocrit on bypass is not less
than 20 percent. Due to increased transfusion-related concerns
and given that a low hematocrit is thought to be necessary
to ensure adequate blood flow through capillary beds due to
increased blood viscosity at low temperatures, hematocrits
of 20 percent or lower on CPB with deep hypothermia were
frequently tolerated.There is increasing evidence that the
practice of extreme hemodilution is detrimental to neurologic
outcome in children. The hypoxic-ischemic damage most
likely occurs during the cooling and rewarming phases of
bypass, when cerebral oxygen metabolism is not suppressed,
yet hematocrit and, thus, oxygen delivery, is low. Many
centers are therefore now maintaining higher hematocrits on
CPB, which either means using more donor blood products
or utilizing hemofiltration to raise the hematocrit, while on
bypass. The current estimate by the risk-benefit ratio of greater
hematocrit therefore favors this approach and it is a definitive
change from previous practice patterns.
Flow Rates on Bypass

The traditional practice in many institutions has been to
decrease CPB flows, particularly during hypothermia, to
reduce the blood returning to the surgical field and allow
more efficient completion of the surgery, particularly in
small infants. This concept has been questioned in recent
years owing to the inability to determine in the individual
child the safe level of low flow bypass. Under one report,
28 neonates who underwent arterial switch operation with
-stat blood gas management during CPB.136 at 14C
to 15C, bypass flow was sequentially reduced from 150
mL/kg/min to 50 mL/kg/min, and then further decreased
in increments of 10 mL/kg/min until circulatory arrest
was begun (to 0 mL/kg/min). All neonates had detectable
cerebral blood flow by transcranial Doppler at CPB flows
above 20 mL/kg/min, but one had no detectable perfusion
at 20 mL/kg/min, and eight had none at 10 mL/kg/min,
leading to conclude that 30 mL/kg/min was the minimum
acceptable flow in this population. Clinical studies of a
high-flow bypass strategy, which included flows of 150
mL/kg/min at all phases of bypass except during DHCA,
minimal use of DHCA, and -receptor blockade with
phenoxybenzamine to produce long-duration systemic
vasodilation, demonstrated excellent short- and long-term
clinical and neurodevelopmental outcomes.
74
all organs, particularly the brain and heart. During cooling, the
carbon dioxide contained in blood becomes more soluble and
its partial pressure decreases. The PaCO2 sensed by the body
decreases as body temperature decreases, with the result that
at a core temperature of 17C to 18C, if pH and PaCO2 have
not been corrected for temperature, the body is experiencing
a pH of about 7.6 and PaCO2 of 15 to 18 mm Hg. This very
low PaCO2 causes cerebral vasoconstriction, particularly
during the cooling phase of bypass, which in turn leads to less
CBF, less efficient brain cooling, and less cerebral protection
at a given temperature. Because blood samples are normally
heated to 37C before measurement of pH, PaCO2, and PaO2,
the use of pH-stat management indicates that blood gases are
being corrected for the childs actual body temperature by
increasing the PaCO2 on bypass as it is measured at 37C,
so that the body experiences a PaCO2 of approximately
40 and a pH of 7.4 at all temperatures. Conversely, pHstat management means not correcting the blood gases for
temperature, as if the patients blood was always at 37C,
with the goal of pH 7.4 and PaCO2 = 40. In the early days of
CPB, pH-stat was utilized to preserve CBF. Subsequently, in
the 1970s and 1980s, randomized controlled studies in adults
undergoing CPB confirmed that acute, post-CPB neurologic
problems were worsened with the use of pH-stat management.
-stat management was therefore adopted for both adult and
pediatric CPB. However, recent animal studies in a neonatal
piglet model have challenged this conclusion, proving that
neurologic outcome, both behavioral and neuropathologic,
is significantly worse when -stat management is used in
infants.
Advantages of pH-stat CPB have been shown to include:
A decreased brain metabolic rate; An increased rate of brain
cooling and reperfusion, thereby providing better protection
through more even and faster cooling and rewarming
secondary to increased CBF; Molecular effects of altered
PaO2 and pH including changes in cerebral oxygenation and
brain enzyme activity as well as decreased brain electrical
activity; Decreased oxyhemoglobin affinity; Increased
cortical oxygenation before arrest (through hypercapnic
capillary vasodilation) and decreased oxygen metabolic
rate, providing slower deoxygenation compared with -stat
management (~10 vs ~7 minutes). Cortical anoxia occurs
at 36 minutes versus 24 minutes for -stat management.
In cyanotic infants with aortopulmonary collaterals, pHstat management results in significantly improved brain
oxygenation as measured by near-infrared cerebral oximetry.
Most congenital heart surgery programs have reverted to pHstat management in the past 5 years. This necessitates careful
attention to PaCO2 during all phases of bypass, potentially
reducing the sweep gas flow into the CPB oxygenator
flow to decrease the efficiency of CO2 removal and often
adding inspired CO2 to the sweep gas of the bypass circuit,
particularly in small infants.
1045
General Issues
13
Vasoconstriction and increased vascular resistance, resulting

in uneven regional organ perfusion, are among the undesired
side effects of CPB. Endogenous catecholamine production
and the alkaline -stat CPB technique, if used, are responsible
for these effects. To be able to run full flow during hypothermic
CPB without significant hypertension, vasodilators are often
used. Agents used are phenoxybenzamine, phentolamine,
nitroprusside, or nitroglycerin to provide systemic vasodilation
and more even cooling and rewarming. Phenoxybenzamine is a
haloalkylamine closely related to nitrogen mustard that blocks
1 and 2 receptors non-competitively, with higher affinity for
the 1 receptor. Phenoxybenzamine improves the CPB flows and
decreased metabolic acidosis as well as the cellular response to
stress after CPB. Phenoxybenzamine, used as part of a treatment
strategy after stage 1 palliation for HLHS, has been associated
with improved outcome. Phenoxybenzamine is more effective
than sodium nitroprusside in improving peripheral circulation,
as shown by temperature gradients intraoperatively. In addition,
phenoxybenzamine improved tissue perfusion and increased
CPB flow, as evident by a decreased base deficit in comparison
with sodium nitroprusside. Phenoxybenzamine increases the
flow on CPB to achieve the same mean arterial pressure. Greater
CPB flows are associated with an improved oxygen delivery,
which can improve patient outcome. Excessive blockade
can be antagonized by vasopressin. Phentolamine is a nonselective competitive 1 and 2 catecholamine receptor blocker.
It has a vasodilating and hypotensive effect that can improve
cardiovascular parameters and metabolic acidosis during CPB
management. In children receiving phentolamine, increasing
lactate levels at the end of the CPB period show a steady state
toward the end of the surgery, whereas it continues to rise in
patients who did not receive phentolamine. These findings
suggest that the use of phentolamine limits lactic acid production
during the hypothermic period and aids the disposal of lactic
acid from tissues. The physiologic state after hypothermia
is ofen called oxygen debt repayment period in infants.
Nitroprusside has been used as an easily titratable agent with
-blocking capacity. Nitroglycerin has been used with the same
success. The only proven benefit over other agents is its nitric
oxide donation capacity. In Japan, high-dose chlorpromazine
has been used as part of a low-resistance strategy during CPB
for the Norwood procedure. Hypotension : often, severe
hemodilution with oxygen debt is the cause and should be treated
as such. After exclusion, the hypotension is carefully treated with
vasoconstrictors, knowing that normal systemic pressures will
not restore splanchnic hypoperfusion and that vasoconstrictors
will often lead to a greater acidosis. It has been demonstrated
that vasoconstrictor treatment results in more sodium bicarbonate
administration to treat the acidosis and is associated with a later
time to extubation and return of bowel function.
Protamine Reactions
1046
Incidence of protamine reactions in children following cardiac

surgery is believed to be substantially lower than in adults.
The risk factors for protamine reactions are few and may
differ in children. This may be due to the fact that in children
duration of exposure and frequency to cross reacting antigens
is less and a lesser sensitivity of their pulmonary intravascular
macrophages to heparin-protamine complexes. A retrospective
analysis of 1249 children revealed the incidence of hypotension
(at least 25% decrease in mean arterial pressure) following
protamine administration was 1.76 to 2.88 percent. No
episodes of pulmonary hypertension or RV dysfunction were
noted. However, pulmonary hypertension and cardiovascular
collapse following protamine administration in a 6 weekold infant have been reported. Clinical experience indicates
that pulmonary hypertensive episodes following protamine
administration in children are very rare and does not warrant
the routine administration of calcium in conjunction with
protamine.
Cardiac Effects of Cardiopulmonary Bypass

In addition to myocardial ischemic injury secondary to
aortic cross-clamping, several other factors can contribute to
perioperative myocardial dysfunction. The first is entrainment
of air into the coronary arteries, which frequently occurs
during weaning from bypass. Despite meticulous de-airing of
the heart, air may enter the right coronary artery, producing
ischemia that is heralded by a pale myocardium, poor
contractility and ST-segment elevation of the ECG. Should this
occur, appropriate management involves remaining on CPB,
increasing perfusion pressure, and milking the air through the
coronary arteries, allowing time for recovery of the ECG and
ventricular function before attempting to wean from bypass.
Surgical factors, such as reimplantation of coronary arteries
with possible resultant ischemia or residual surgical defects,
can also occasionally contribute to myocardial dysfunction.
The inflammatory response to CPB has important
implications for cardiac function. This systemic response
results in a capillary leak syndrome, which in turn leads to
accumulation of edema fluid in interstitial and extravascular
spaces, including the myocardium. Myocardial edema can
contribute to post-CPB myocardial dysfunction by impairing
diastolic function and causing mechanical limitation of cardiac
filling and outflow in small infants whose sternums have been
closed. Additionally, myocardial edema has been implicated
as a causative factor in the frequent decline in myocardial
function that occurs 6 to 12 hours after conclusion of CPB.
Inflammatory mediators also affect the responsiveness of
the myocardium to catecholamines by interfering with their
binding to the cell surface receptors, rendering exogenously
administered drugs such as dopamine and epinephrine, as
well as the childs endogenous catecholamines, less effective
at increasing cardiac output in the perioperative period.
Mechanisms for prevention and treatment of myocardial
dysfunction include the use of ultrafiltration and antiinflamatory drugs such as corticosteroids and aprotinin. The
prophylactic use of non-catecholamine inotropic agents such
Indeed, when pulmonary artery pressure is measured directly,

it is often significantly increased immediately after bypass,
even if surgical results are optimal. This increase can be
extremely detrimental in children with large left-to-right
shunts, those undergoing cardiac transplantation secondary to
dilated cardiomyopathy, and those undergoing bidirectional
cavopulmonary anastomosis, where right ventricular output
depends on maintaining low PVR. Prevention and treatment
of increases in PVR include maintaining an adequate depth
of anesthesia, ventilating with 100 percent oxygen, and
judicious use of hyperventilation. Milrinone will increase
right-sided heart output via its actions as both an inotropic
agent and a pulmonary vasodilator. When PVR is significantly
elevated, inhaled nitric oxide is often used to assist in the
early postoperative period. Although effective, its cost
is not inconsequential, and because PVR almost always
decreases with time, nitric oxide is generally reserved for
selected cases of pulmonary hypertension. Other simpler,
less expensive treatments are being investigated for the
treatment of significant pulmonary hypertension after bypass,
including oral or intravenous sildenafil and inhaled nebulized
prostacyclin.
Pulmonary effects: The lungs are not ventilated during
CPB and are usually totally collapsed by intention, with the
ventilator circuit disconnected, especially in small infants.
This leads to significant atelectasis. The lungs are also at
least partially ischemic during the bypass period, resulting in
decreased production and alveolar levels of surfactant after
CPB. In addition, reperfusion injury (pulmonary edema or
hemorrhage after a sudden increase in pulmonary flow) can
also occur after creation of a systemic-to pulmonary artery
shunt or pulmonary artery unifocalization. Inflammatory
mediators liberated by the bypass run also predispose to
increases in smooth muscle tone and resistance and can result
in bronchospasm. In addition to complement, endotoxins and
certain cytokines can also activate neutrophils and attract
them toward sites of inflammation. Endotoxin-induced lung
injury can lead to rapid (within 45 minutes) accumulation of
neutrophils within lung capillaries. Activation of neutrophils,
with upregulation of adhesion molecules, neutrophil adhesion
to the endothelium of lung vessels, and endothelial damage
through proteases, appears to be the main step of the underlying
pathophysiologic mechanism. Macrophages play an important
role in the evolution of the inflammatory acute lung injury
through the secretion of cytokines, cytotoxic metabolites, and
chemoattractants for leukocytes. At the clinical level, acute
respiratory distress syndrome (ARDS) is often only one part
of multiorgan failure and lung injury should be seen as part of
a more general state of systemic inflammation. The reported
prevalence of ARDS after CPB in adults is 0.5 to 1.7 percent;
the incidence in children is unknown. Interesting enough was
the failure of general hypothermia at 28C to prevent the loss of
ATP and the accumulation of lactate in lungs. Different methods
that aim to protect the lungs during CPB, such as continuous
74
as milrinone has also been shown to prevent low cardiac output

syndrome in infants, even if cardiac function is adequate in
the immediate postoperative period.
In cardiac surgery, systemic inflammatory response syndrome
(SIRS) is thought to result from four main sources of injury:
1. Contact of the blood components with the artificial surface
of the bypass circuit.
2. Ischemia-reperfusion injury.
3. Endotoxemia.
4. Operative trauma.
Inflammatory cytokines, together with endothelial
activation and endothelial leukocyte interactions, appear
to play an important role in the induction of this systemic
inflammatory response. Exposure of blood to the artificial
materials in the bypass circuitplastics, polypropylene
oxygenator fibers, and metal suction devicesinitiates a
cascade of inflammatory responses, including activation of the
complement system, the kallikrein system, and the coagulation
system. As a result, IL, TNF, endotoxin, heat shock protein,
and many other inflammatory mediators are released into the
circulation. Leukocyte activation also results in secretion of
inflammatory mediators, such as proteases and cytokines such
as TNF and IL-1, which are secreted early in the evolution
of the inflammatory process. This chemokine-mediated
increased leukocyte activation constitutes an important link
in the chain of the propagation of the inflammatory response.
This inflammatory response is counter balanced by a complex
system of inhibitors such as IL-10 and soluble cytokine
receptors. Also, the inflammatory response of the neonate
may be more exaggerated than that of the infant or older
child, justifying a more aggressive approach to its modulation
in the neonate. A number of novel treatments have been
studied, including monoclonal antibodies for inflammatory
products such as complement, endotoxin and TNF. Although
theoretically attractive, no clinical difference has been noted
with any of these treatments.
Effective treatments used every day in the operating
room. Corticosteroids interrupt the inflammatory response at
several levels by entering cell nuclei and changing the rate of
transcription of inflammatory molecules. Increasing evidence
suggests that glucocorticoids act by regulating transcription
or translation of anti-inflammatory cytokines, such as IL-10,
and altering expression of other proteins, such as endothelin-1
and inhibitor B. Because these processes take time to develop,
the effects of corticosteroids are not immediate, taking
up to several hours. Thus, the common practice of adding
corticosteroids to the CPB prime will not fully prevent the
inflammatory response; to be effective, corticosteroids may
need to be administered 4 or more hours before the onset of
CPB.
Systemic and pulmonary vasculature effects: The
inflammatory response to CPB often produces mediators that
directly increase pulmonary and systemic vascular resistance.
These include interleukins, leukotrienes, and endothelin.
1047
General Issues
13
lung perfusion, pneumoplegia, and nitric oxide ventilation

at lung reperfusion prevent more severe hemodynamic
deterioration and preserve reactivity of the pulmonary
vasculature but fail to prevent pulmonary dysfunction. The
severity of pulmonary dysfunction after CPB can be measured
via changes in the alveolar-arterial oxygenation gradient,
intrapulmonary shunt, degree of pulmonary edema, pulmonary
compliance, and PVR. Treatment of pulmonary atelectasis
includes measures that decrease inflammatory mediators,
careful reinflation of the lungs when weaning from bypass
(by administering several vital capacity breaths), gentle, but
thorough suctioning of the endotracheal tube, and prophylactic
use of inhaled bronchodilators before separation from CPB.
Using these measures, pulmonary function has been shown
to improve immediately in most children with large left-toright shunts, with the duration of CPB seemingly having little
effect on pulmonary outcomes. Thus, CPB itself has little
effect on pulmonary function in most children. There is still
an occasional child, however, who experiences classic pump
lung ARDS, caused by the factors noted earlier. Treatment is
supportive as for anyone with ARDS.
Impaired Hemostasis: Coagulation Effects
1048
Blood coagulation is frequently abnormal after CPB for several

reasons. The inflammatory cascade activates the coagulation
system, resulting in factor consumption and fibrinolysis, which
in turn, breaks down existing blood clots, leading to increased
bleeding. Treatment is adequate heparinization, reversal with
protamine, and the use of aprotinin to inhibit fibrinolysis and
improve platelet function. In addition, the smaller the child, the
greater the dilution of clotting factors by the bypass prime, and
the greater the risk for low concentrations of clotting proteins
and fibrinogen postoperatively. Platelets are also degranulated
and consumed by the CPB circuit, leading both to low platelet
counts and non-functioning platelets. The smaller the infant,
the greater the duration of bypass, and the more complicated
the surgery, the greater the incidence of coagulopathy after
bypass. Efforts to minimize the post-bypass coagulopathy
in infants includes priming the CPB circuit with fresh whole
blood for small infants if available or packed cells plus FFP if
fresh whole blood cannot be obtained.
Treatment involves administration of platelets to small
infants as the first line of therapy, followed by cryoprecipitate
to replace fibrinogen and FFP to replace clotting factors. If
these factors are not effective after correcting coagulation
parameters such as platelet count, prothrombin/PTT, fibrinogen
and thromboelastogram (TEG), then surgical bleeding may be
the cause and surgical re-exploration may be warranted. Factor
VIIa has also been used as a last resort in children who have
significant post-bypass bleeding.
Hemostasis is impaired after bypass in infants and
children. This results from a combination of immature
coagulation factor synthesis, hemodilution after bypass, and a
complex interaction involving consumption of clotting factors

and platelets. At birth, the levels of vitamin K-dependent
coagulation factors in healthy full-term neonates are only 40 to
66 percent of adult values. During the first month of life, these
levels increase to 53 to 90 percent of adult values. However,
in children with CHD, especially those with cyanosis or
systemic hypoperfusion, coagulation factors often continue to
be depressed secondary to impaired hepatic protein synthesis.
Although AT-III levels are also low, true heparin resistance is
rare in infants because of the equal decrease in coagulation
factors. At the onset of CPB, the introduction of the prime
volume, which is 2 to 3 times greater than the childs blood
volume, dilutes the factor levels, in particular fibrinogen to
50 percent and the platelet count to 30 percent, of pre-bypass
levels. This degree of dilution occurs even when the pump
circuit is primed with whole blood. Greater dilution may
occur when packed red cells are used in the priming volume.
Thus, at the conclusion of neonatal bypass, the activity of
clotting factors is often extremely low, the fibrinogen level is
frequently below 100 mg/dL, and the platelet count may be as
low as 50,000 to 80,000/mm. In addition to these quantitative
changes, platelets undergo functional changes during bypass.
Extracorporeal circulation causes a loss of platelet adhesion
receptors, activation of platelets, and formation of leukocyte
platelet conjugates. Platelet adhesion receptors are more
depressed in children with cyanotic compared with acyanotic
cardiac defects. Heparin also impairs platelet function
independent of CPB. Cardiac surgery is also associated with
significant activation of the fibrinolytic system. Inadequate
heparin levels during CPB in children may also contribute to
postoperative bleeding because inadequate anticoagulation
may allow activation of the hemostatic pathways. This
activation causes the consumption of platelets and clotting
factors. It has been shown that the standard measurement
of anticoagulation, the ACT, shows a poor correlation
with heparin levels in children undergoing CPB. It has
been demonstrated that the use of heparin monitoring and
heparin titration was associated with the use of larger doses
of heparin, but smaller doses of protamine for antagonism.
Activation of clotting cascades is also reduced, thus resulting
in less bleeding in the postoperative period. As a result of this
multifactorial coagulopathy, blood loss is a greater problem in
children than in adults and is a particular problem in neonates
and small infants.
Strategies to Reduce Bleeding after Bypass

In an effort to normalize factors and platelets to effective
levels, some centers utilize fresh whole blood in the cardio
pulmonary circuit prime. In children, transfusion of fresh
whole blood less than 48 hours from harvest is associated with
less blood loss compared with transfusion of reconstituted
whole blood (packed erythrocytes, fresh frozen plasma, and
platelets). However, fresh whole blood is often difficult to
Antifibrinolytics
The antifibrinolytics used in pediatric cardiac surgery
include epsilon, aminocaproic acid (EACA), tranexamic
acid (TA), and aprotinin. EACA and TA are both lysine
analogues that have been shown to reduce bleeding after
cardiac surgery in adults and children. They do not appear
to have any anti-inflammatory activity, and the doses for
use in pediatric cardiac surgery have not been clearly
established. Aprotinin is a serine protease inhibitor that
is well studied in adults. Many studies had shown it to
significantly reduce bleeding, reduce the time taken to
extubation, shorten ICU stay and reduce overall mortality.
However, subsequent studies have contradicted these
earlier findings. It may be that the doses used in pediatric
studies do not take into account the large pump prime to
blood volume difference that occurs when children are
placed on the bypass circuit. There is also a concern that it
may be associated with thrombosis.
Topical Agents
The use of topical agents to promote clot formation
and reduce bleeding in children after cardiac surgery is
becoming increasingly widespread. They have been shown to
significantly reduce bleeding in children.
Ultrafiltration
Ultrafiltration is a process that removes ultrafiltrate from a child
during and after CPB. It provides many benefits, including
increasing the hematocrit, concentrating the clotting factors
and platelets, increasing blood pressure and reducing PVR,
and removing inflammatory mediators in the ultrafiltrate. It
has been shown to significantly reduce bleeding after cardiac
surgery in children.
Desmopressin
Desmopressin acts by increasing plasma levels of factor VIII
and von Willebrand factor. It has been shown to be effective
in reducing bleeding after CPB in adult cardiac surgery.
Unfortunately, similar studies in children failed to demonstrate
that desmopressin is as effective in reducing either bleeding or
transfusion requirements.
Bleeding in Cyanotic Children

Inherently, children with congenital cyanotic heart disease have
predisposition to coagulopathy because of several inherent
coagulation defects. The list includes: thrombocytopenia,
factor deficiencies, fibrinolysis and dissemiated intravascular
coagulation (DIC). Surgical correction of the complex
mandates prolonged cardiopulmonary bypass and aortic crossclamp under deep hypothermia. The required intracardiac
repair will be associated with several extracardiac suture lines
with the resultant risk of excessive perioperative hemorrhage
and transfusions, which compounds the coagulation defect
and affects surgical outcome. Apart from decreased levels of
coagulation factors due to hemodilution from high priming
volume relative to small blood volume, the delayed hepatic
maturation secondary to poor organ perfusion also contributes
to an excessive perioperative bleeding. Thus, a child with
cyanotic heart disease undergoing intracardiac repair should
be considered under a different entity and evolve therapeutic
strategies to prevent and manage excessive perioperative
hemorrhage.
Pathological outlook of factors that would contribute
include hyperviscosity due to polycythemia (erythrocytosis),
thrombocytopenia, platelet function abnormalities, DIC,
decreased production of coagulation factors (corrected by
parentral administration of vitamin K), impaired liver function;
vitamin K deficiency and primary fibrinolysis. These defects
may have multifactorial in origin. For example, erythrocytosis
is an adaptive response intended to compensate for inadequate
tissue oxygenation. Paradoxically, as the child ages, blood
viscosity increases and contributes to a decrease in systemic
oxygen transport. Likewise the type and magnitude of these
abnormalities are proportional to the degree of erythrocytosis
and inversely proportional to platlet count, and hematocrit
values. Platelet dysfunction and lowered prothrombin levels
74
obtain. Furthermore, the units must be refrigerated for 24 to

48 hours, while donor screening is performed and this storage
causes significant platelet injury. Alternatively, individual
component therapy may be utilized. Platelets should be used
first in treating coagulopathy after bypass in children and
when given in a dose of 10 mL/kg will usually correct the
clotting defect. Furthermore, platelets may be administered if
bleeding persists and the platelet count is less than 100,000/
mm3. If platelets are required, one might also anticipate that
cryoprecipitate will also be required. This follows because if
platelets are substantially reduced, the other important factors
such as fibrinogen (II) and factor VIII will also be reduced.
In addition to high levels of fibrinogen, cryoprecipitate
contains high levels of factor VIII and von Willebrand factor
as well as factor XIII. Fibrinogen and von Willebrand factor
are required for platelet adhesion and aggregation to occur.
Platelet adhesion and aggregation are the fundamental first
steps in primary hemostasis. The subsequent step of platelet
degranulation switches on the entire coagulation cascade
and cannot take place without adhesion and aggregation. Use
of fresh frozen plasma in the infant may result in excessive
dilution of red cell mass and platelets, and there is no evidence
that it is effective in treating this type of coagulopathy.
Transfusion guidelines have not been forthcoming in children
and practice appears to be more empirical. The TEG and the
platelet count may be used to identify, which children are
likely to bleed after cardiac surgery.
1049
General Issues
13
1050
are the principal hemostatic defects and are related to the

severity of polycythemia. Besides the risk of excessive
bleeding, there is concern regarding the large number of
blood donors to whom a child is exposed during the surgery.
Several pharmacological agents including aprotinin, EACA,
TA, and desmopressin and rVIIa have been used with variable
success. Techniques like ultrafiltration, maintaining optimal
hematocrit, and autologous blood transfusion also have been
shown to improve the situation.
Hepatic, Renal, and Gastrointestinal Effects: The liver,
kidneys, and gastrointestinal tract, like the brain and heart,
may be rendered ischemic by prolonged CPB, DHCA, or low
cardiac output syndrome. Renal function is compromised
on CPB. This is manifested by the appearance of proteinuria
and impaired tubular cellular function immediately after
CPB. Renal dysfunction from ischemia is also common. Low
urine output may occur secondary to secretion of antidiuretic
hormone, a response to surgical stress. However, the latter
appears to be transitory and usually resolves spontaneously.
The incidence of acute renal dysfunction after congenital
heart surgery with bypass is 17 percent, ranging from 0.7
percent for ASD closure to 59 percent for arterial switch
operations. Deep hypothermic cardiac arrest subjects the
kidney to additional ischemia reperfusion injury. Acute
renal failure after CPB is uncommon in children, with fewer
than 3 percent requiring dialysis perioperatively. Infants
who undergo cardiac surgery routinely receive diuretics
or a peritoneal dialysis catheter, the latter prophylactically
in some instances. Although some have attributed the
improved survival with early peritoneal dialysis to the
prevention of fluid overload, others have attributed it to
a more rapid clearance of CPB-induced proinflammatory
cytokines. Recovery of hepatic and gastrointestinal function
follows hemodynamic recovery, but may require several
days. Therapy is mainly supportive with increasing oxygen
delivery, initiating parenteral nutrition, and awaiting return
of function before restarting enteral feedings. Splanchnic
and renal perfusion can be monitored non-invasively using
somatic oximetry. Somatic oxygenation may predict renal
dysfunction and predict organ failure. Interventions based
on the somatic NIRS may improve outcome.
Immune System Effects: Leukocytes are activated by the
CPB circuit, although their numbers may be depleted by
leukocyte filters, which are sometimes used to attenuate the
inflammatory response. Despite the theoretical potential that
this may increase the risk of infection or neutrophil function,
this has not been observed in published studies or clinical
practice.
Endocrine System Effects: The magnitude of the inflam
matory and endocrine responses after cardiac surgery depends
in part on the duration of the surgical procedure and CPB. In
children undergoing brief operating times, postoperative blood
concentrations of cortisol, adrenocorticotropic hormone, and
endorphins are significantly greater than those in children
undergoing prolonged operation times. In contrast, the serum

concentrations of the pro-inflammatory cytokines IL-6, IL-1,
and TNF-a are similar in the two groups. Adrenocorticotropic
hormone and cortisol concentrations correlated positively
with the blood concentrations of IL-1, IL-6, and TNF-a in
the group of children with prolonged operation times. The
plasma concentrations of both epinephrine and cortisol
increase after cardiac surgery. In children, pre- and postbypass cortisol and norepinephrine increase significantly
during isoflurane anesthesia when 2 g/kg of fentanyl is used
rather than 25, 50, 100, or 150 g/kg. No significant increase
in the blood concentrations of these hormones occurred with
any of the fentanyl doses of 25 g/kg or greater. In addition
to cardiovascular stability, continued use of high doses of
opiates during bypass minimizes the stress responses and
stabilizes hemodynamics during and after bypass. Also,
growth hormone, glucose and insulin, lactate, glutamate,
aspartate, and free fatty acid concentrations increase after
cardiac surgery, whereas total tri-iodothyronine concentrations
decrease.
Stress Response to Cardiac Surgery: Cardiac surgery
and CPB are altered physiologic conditions associated with
exaggerated stress responses characterized by the release
of numerous metabolic and hormonal substances, including
catecholamines, cortisol, growth hormone, prostaglandins,
complement, glucose, insulin, and -endorphins. The cause
of the elaboration of these substances is multifactorial:
contact of blood with foreign surfaces, low perfusion
pressure, anemia, hypothermia, myocardial ischemia, low
levels of anesthesia, and non-pulsatile flow. Other factors
that contribute to the increase in stress hormones are
delayed renal and hepatic clearance and exclusion of the
pulmonary circulation during extracorporeal circulation.
Neonates of all viable gestational ages, as well as older
infants and children, have nociceptive systems that are
sufficiently developed and integrated with brainstem
cardiovascular control centers to trigger both humoral
and circulatory responses to pain and stress. Substantial
humoral, metabolic, and cardiovascular responses to
painful and stressful stimulation during surgery have been
documented in neonates of all gestational ages and older
infants. Hormonal stress responses in neonates subjected to
cardiac and non-cardiac operations are three-fold to fivefold greater than those in adults after similar surgeries.
Circulatory responses to stressful stimuli in children
include systemic and pulmonary hypertension. Humoral
stress responses are particularly extreme during and after
cardiac surgery. These responses are characterized by
increase in circulating catecholamines, glucagon, cortisol,
endorphins, growth hormone and insulin. In these studies,
circulating concentrations of catecholamines increased
by as much as 400 percent over baseline preoperative
concentrations. This is evidence of a massive activation
of sympathetic outflow in response to surgical stimulation.
may lessen the risk of neurologic injury. In sufficient doses,

opioids can blunt the stress responses in neonates, infants, and
adults.This blunting results in a more normal, homeostatic
humoral and metabolic milieu in the circulation by reducing
neuroendocrine activation and levels of regulating hormones.
In infants, the use of high-dose opioids for major surgical
procedures and postoperative sedation substantially attenuates
the neuroendocrine response to surgically induced pain and
stress. Catecholamine release that results from intraoperative
stress responses may predispose the vulnerable myocardium
to dysrhythmias. In neonates with HLHS, sudden ventricular
fibrillation occurred in 50 percent of neonates during surgical
manipulation until high doses of fentanyl were introduced as
the primary anesthetic agent. With the use of high-dose opioids,
intraoperative ventricular fibrillation has virtually disappeared
as a problem in this group of neonates. In several studies,
opioids have been shown to increase the ventricular fibrillation
threshold in isolated cardiac Purkinje fibers and to alter action
potential duration similar to that with class III antiarrhythmic
agents. Thus, even electrophysiologic events in the neonatal
heart, in addition to humoral and hemodynamic responses, may
be altered by using high-dose fentanyl anesthesia to attenuate
the effects of pain and stress in neonates.
Reducing the Stress Response to Surgery and Bypass

Corticosteroids
Corticosteroids are used in many centers in an attempt to
reduce the inflammatory response to surgery and bypass.
However, there is a huge variability in the formulation of the
corticosteroids used, the doses, the timing of administration,
and the indications for their use. The literature lacks adequate
evidence for the use of corticosteroids, although there are a
number of small studies in humans and animals that suggest
they confer a benefit.
74
Some of these responses may continue for several days

postoperatively. It has been suggested that such extreme
stress responses and neuroendocrine activation may be
associated with greater mortality and morbidity during the
postoperative period. In adults, intraoperative adrenergic
activation of 50 percent above baseline is associated with
significant postoperative alterations in adrenergic receptor
function, including increased -receptor density and
decreased receptor affinity. Mortality among adults with
severe congestive failure is associated with increased levels
of hormones regulating cardiovascular function, including
aldosterone, epinephrine, and norepinephrine. In neonates
undergoing cardiac surgery, increased concentrations of
stress hormones are associated with increased hospital
mortality.
The metabolic response to stress in children includes
increased oxygen consumption, glycogenolysis, gluconeogenesis, and lipolysis. These metabolic responses cause
substantial intraoperative and postoperative catabolism.
The metabolic stress responses after comparable operative
stresses in neonates exceed those in adult patients and result
in substantial alterations in metabolic balance and levels of
various metabolic substrates. These metabolic responses are
usually related to changes in plasma cortisol, catecholamines,
and other counter regulatory hormones such as glucagon and
growth hormone. The most prominent clinical effects that
result from activation of these processes are perioperative
hypoglycemia and hyperglycemia, lactic acidemia, and
negative nitrogen balance extending well into the postoperative
period. Neonates and infants tolerate such metabolic
derangements poorly. Their impaired tolerance is the result
of a relative lack of endogenous reserves of carbohydrates,
proteins, and fats, the large metabolic cost of rapid growth,
a high obligate requirement for glucose by the relatively
large brain, the immature hormonal control of intermediary
metabolism, and the limited functional capabilities of
immature enzyme systems in the metabolic organs. Thus,
severe stress responses superimposed on the normal neonatal
and infant physiology may be poorly tolerated. However, it
remains unclear whether these metabolic alterations might
provide some beneficial effects toward mobilizing the bodily
resources to provide a metabolic milieu for healing tissues or
whether they are purely maladaptive, resulting in detrimental
effects on postoperative outcome.
Another factor is the potential effect of stress-induced
hyperglycemia on the neurologic outcome. Neonates and
young infants are capable of substantial rates of glucose
production, mainly from glycogenolysis and gluconeogenesis
during stress. This can result in substantial hyperglycemia
during major surgery in neonates. Such hyperglycemic
responses may be associated with poorer neurologic outcome,
particularly after a period of cerebral ischemia. The use of
high doses of fentanyl (50 g/kg) has been shown to reduce
the hormonal stress response and resultant hyperglycemia and
Aprotinin
Aprotinin, which was originally used to reduce bleeding
after CPB, is now also appreciated to confer significant antiinflammatory effect. In adults, it was shown to reduce mortality
and length of ICU stay. In children, it improves pulmonary
function in the postoperative period and also reduces the time
to extubation and ICU stay.
Allopurinol
Allopurinol is thought to provide protection against oxygen
free radicals during reperfusion by inhibiting xanthine
oxidase. It reduces oxygen free radical production and may
reduce neurologic and cardiac damage after deep hypothermic
cardiac arrest. This strategy does not appear to have developed
widespread use.
1051
General Issues
13
1052
Fast Tracking: The desire to reduce hospital cost and

iatrogenic complications due to traditional cardiac surgical
care have triggered research and interest in the innovations
towards fast racking. Under this regimen and the new
guidelines admission to the hospital on the day of surgery,
use of short acting anesthetic drugs, early extubation, and
reduced ICU stay for pediatric cardiac surgical paients. The
ensuing fast tracking refers to abbreviating the perioperative
period of children undergoing cardiac surgery. Fast track is a
care plan in which cardiac surgical patients progress quickly
through the perioperative course to hospital discharge. It is
a multidisciplinary approach that include every phase of the
childs journey from referral and preoperative evaluation
to less invasive surgery, early weaning from respiratory
support and extubation, and early discharge from the ICU and
hospital. Early extubation of pediatric patients within 1 to 6
hours (or 810 hours) after cardiac surgery has been shown to
offer advantages in terms of cost as well as reduced morbidity
associated with longer ICU stays. The success of this approach
depends on the close teamwork of a multidisciplinary team,
with every member of the team working toward the same
goal to improve efficiency of care of cardiac surgical patients.
Successful fast tracking usually requires the development of
care pathways to ensure that the quality of patient care is not
compromised. Early extubation anesthesia is a major key to
the success of fast track pediatric cardiac sugery pathways.
Fast racking requires preplanning and the adoption of a
technique that facilitates this goal. To achieve this goal, various
alternative techniques have been used, including smaller doses
of fentanyl in combination with inhalational agents or the use
of remifentanil either in combination with inhalational agents
or with Propofol/Dexmedetomidine. Others have advocated
regional anesthesia as a means of speeding extubation, but this
remains controversial. It is also important to choose a muscle
relaxant with a shorter duration of action than pancuronium to
ensure that it is easy to reverse the neuromuscular block at the
end of surgery. Other important considerations to ensure that
early extubation is a success include adequate pain relief in the
form of intravenous paracetamol (where available), patientcontrolled or nurse-controlled analgesia, and antiemetics
because nausea appears to be more of a problem in children
who are extubated early. Some clinicians advocate extubating
the trachea in the operating room, whereas others advocate
waiting until the child is in the ICU. Delaying extubation
until the child is in the ICU may save time in the operating
room and may reduce the risks of cardiovascular instability,
bleeding, and hypothermia. Despite these concerns, many units
frequently extubate children in the operating room after cardiac
surgery with good results. There is an increasing evidence
of safety concens under fast track approach in children with
congenital heart diseases. Various studies indicate that the
rate of reintubation, need for re-exploration and perioperative
mortality is low and comparable in children of older age
group and those who have undergone comparatively routine

intracardiac repairs. Thus, the fast track approach in pediatric
age group should be reserved for a selective group of childen
without compromising the safety. This approach calls for a
streamlined, organized protocol, which has a scope for a
continuous assessment of childs recovery.
Neurological Injury
Postoperative Neuropsychologic Morbidity
Neurologic morbidity has been identified to be increasingly
problematic in neonates and infants with CHD as surgical
mortality rates have improved. Although early postoperative
CNS sequelae such as stroke and seizures occur in a small
percentage of neonates with CHD, the importance of more
subtle neurologic abnormalities at long-term follow-up is
being increasingly recognized. These findings may include
fine and gross motor impairments, speech and language delays,
disturbances in visual-motor and visual spatial abilities,
attention-deficit disorders, learning disorders, and impaired
executive functioning. The presence of congenital brain
disease in patients with congenital heart disease represents
a challenge in improving long-term neurologic outcomes.
Many neonates with CHD have congenital structural brain
abnormalities or chromosomal abnormalities or both, as
well as physiologic abnormalities that may impair brain
development. Brain abnormalities on head ultrasonography
have been noted in one-fifth of full-term infants undergoing
heart surgery.
Postoperatively, secondary neurologic injury may be
related to post-CPB alterations in cerebral autoregulation and
additional hypoxic-ischemic insult, seizures, or other issues
associated with prolonged ICU stay. In addition to prenatal and
modifiable perioperative factors, genetic and environmental
factors are known to be important. Unfortunately, modifiable
perioperative factors may explain less of the variability in
long-term outcomes than do patient-specific factors. New,
postoperative neurologic injury may be detected clinically
in over 10 percent of infants, and in over 50 percent using
more sensitive brain imaging techniques such as MRI. Given
that new neurologic injury can occur at various time points
during the neonate's hospitalization, perioperative attention to
reducing known risk factors is critical. Mechanisms of CNS
injury in infants undergoing cardiac surgery include hypoxiaischemia, emboli, reactive oxygen species, and inflammatory
microvasculopathy. Preoperatively, the primary focus is on
preventing hypoxic-ischemic injury and thromboembolic
insults. Modifiable intraoperative factors associated with
CNS injury include, but are not limited to, pH management,
hematocrit during CPB, regional cerebral perfusion, and the
use of DHCA. The adverse effects of CPB may be greater
in infants compared with larger children or adults given
Mechanical Assist Devices

Survival in children with congenital cardiac as well as
pulmonary defects has improved over recent decades due
to improved preoperative management, surgical techniques,
anesthesia management, drug therapies, and postoperative
management. Despite these advances patients may still
require therapies for both acute and chronic heart failure
that are refractory to medical therapy. Mechanical support in
the form of extracorporeal membrane oxygenation (ECMO)
or ventricular assist devices (VADs) may then need to be
instituted. Examples of conditions that may require support
include failure to wean from CPB, acute cardiac arrest,
malignant arrhythmia, and worsening myocardial function
secondary to the underlying congenital defect or related
to acquired cardiomyopathy. Fortunately, however, the
numbers are small, with less than 2 percent of post-CPB
patients requiring this intervention. Mechanical support can

thus be used as a treatment option to allow for recovery of
ventricular function, as a bridge to transplant, or to support
the heart in those with marginal functional reserve requiring
invasive diagnostics or treatments (e.g. Williams syndrome
with severe supravalvar pulmonary or aortic stenosis). As
with any therapy, contraindications must be excluded before
embarking on the use of a mechanical assist device. These
contraindications may include extreme prematurity, severe
and irreversible multiorgan failure, incurable malignancy, and
preexisting neurologic devastation. Anesthetic management
in the use of ECMO is supportive with management limited
to assistance in the resuscitative efforts and hemorrhage
associated with the cardiac surgery that was ongoing at the
time of conversion to ECMO. Once the patient is on full
ECMO support, ventilation is continued, but at a slower rate
of ventilation in the order of 10 breaths/min with peak pressure
of 20 cm H2O with PEEP set at 5 to 10 cm H2O and FiO2
also decreased to about 40 percent. These settings will aid in
the prevention of atelectasis with management of CO2 and
O2 related to flow across the circuit membrane. This is very
different from the patient into whom a VAD is placed. Here the
anesthesiologist continues to manage the patient as for routine
CPB weaning. Obviously differences exist in this scenario. If
a systemic VAD is placed, careful attention must be given to
the ventricle pumping blood into the pulmonary bed, because
failure of this ventricle will have disastrous consequences.
Thus, management tailored to unload this pulmonary
ventricle is vitally important and will include inodilators in
the form of phosphodiesterase inhibitors, inotropic support,
and possibly even inhaled nitric oxide to decrease PVR and
promote forward flow. In association with the perfusionist,
intravascular volume loading is assessed and maintained for
effective functioning of the VAD and thus adequate offloading
of the assisted ventricle. Careful attention to pulmonary
function is also vital. Adequate pulmonary toilet, recruitment
maneuvers, and appropriate ventilatory parameters must be
utilized. As will be alluded to later, bleeding is a potential in
the implantation of the VAD and thus a clear strategy must
be planned for in the form of antifibrinolytics, adequate
volumes of blood and blood products, and even possibly the
use of activated clotting factors (e.g. factor VII). The potential
for bleeding exists at the time of insertion of both of these
modalities; however, it would seem from clinical experience
that due to the extensive dissection and need for sizeable
ventriculotomy that implantation of a VAD (and especially
Bi-VAD) is more problematic. That being said, however, the
requirements of anticoagulation to keep the activated clotting
time in the range of 180 to 200 for ECMO may also lead to
ongoing and significant bleeding, especially if placed into a
patient who requires support in the immediate perioperative
phase. The use of an ECMO circuit with a membrane
oxygenator requires ongoing intravenous anticoagulation
with maintenance of the ACT in the aforementioned range.
74
their immaturity in organ function and tissues as well as the

size of the CPB circuit relative to their body size. However,
a significant amount of research has been conducted in the
area of intraoperative prevention of neurologic injury. With
ongoing changes in technology and new therapies, the conduct
of CPB and other support techniques have been actively under
investigation. Neurological injury is a major cause of morbidity
in pediatric cardiac surgical patients undergoing correction of
congenital cardiac defects. MRI identified abnormalities are
present preoperatively in 33 percent of cardiac neonates, and
in as many as 93 percent postoperatively. Early in life, the
brain undergoes an intensive period of neuronal development
and axonal growth. The immature brain's fragile vasculature,
high metabolic activity, and immature cerebral autoregulation,
make it particularly susceptible during CPB to hypoperfusion
as well as hyperperfusion, increased permeability, edema
formation and ischemia-reperfusion injury. Presently, in
neonates, the post-CPB neurologic injury is estimated to
range from 2 to 30 percent. The evidences strongly indicate
necessity to provide neuroprotection to pediatric patients
undergoing cardiac surgery with CPB. There is an increasing
body of both in vitro and in vivo evidences, which indicates
that dexmedetomidine exerts a cell-protective effect on
nervous tissue under ischemic conditions. Recent evidence
suggest that this effect is mediated by dexmedetomidines
2-agonistic properties and also by imidazoline type
1-recepors. Experimental studies have compared the
combination of dexmedetomidine and hypothermia with
the controls and found improved short-term neurologic
outcome with combination therapy. Dexmedetomidine seems
to have promising future applications in neuroprotection,
cardioprotection and renoprotection. It is apparent that
dexmedetomidine have several beneficial cardiovascular and
neuroprotective properties; therefore, there is an urgent need
to confirm these beneficial effects in well-designed studies to
establish its place in pediatric cardiac anesthesia.
1053
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1054
Apart from the immediate postoperative phase, patients with

VAD systems can be transitioned to oral agents. A two-part
therapy is recommended. Antiplatelet therapy includes aspirin
or clopidogrel. The second part of the therapy will entail the
use of anticoagulation with either warfarin (Coumadin) or
subcutaneous low-molecular-weight heparin.Three potential
disadvantages exist in the use of the VAD system. There is
no pulmonary support when using the VAD, and this limits
its use to patients whose lung function is adequate. When
biventricular support is needed the patient will require two
separate VAD devices necessitating the placement of four
cannulae that may be technically difficult in a very young
child. The third disadvantage is that VAD placement cannot be
performed in a code situation or at the bedside as with ECMO.
Important advantages of the VAD system are the ability of
patients to ambulate, while on support and that VAD support
can be maintained for months in comparison to the weeks only
of ECMO support. Another important advantage over ECMO
is that these patients will not require further venting of the left
atrium. In ECMO patients this is achieved by the placement
of a left atrial vent at the time of sternotomy or a balloon atrial
septectomy, which may require transfer to the catheterization
laboratory with the possible complications associated with
transport of a patient on an ECMO circuit. Despite successful
resuscitation and placement onto mechanical assist devices,
morbidity and mortality remain high, with ECMO appearing
to have worse outcomes. The mortality rate for ECMO in the
1990s was on the order of 47 percent, with survival in series
published in the early 2000s not showing much improvement.
In contrast, the survival in those into whom a VAD is
placed appears to be superior within the quoted series up to
80 percent of patients surviving to transplantation or being
successfully weaned from support. In the study by Blume and
coworkers, it was, however, noted that associated congenital
heart disease, and patients who are younger and smaller, have
a higher mortality when compared with those with fulminant
myocarditis and cardiomyopathy. Alongside survival data,
the next most important marker is neurologic outcome and
it appears that this is better in the VAD group. Risk factors
for poor neurologic outcome were once again low weight
and duration of DHCA, both of which place ECMO patients
at a survival disadvantage, because ECMO patients will be
smaller and a number of those who undergo DHCA for repair
of congenital anomalies will require emergent ECMO support
to wean from CPB or in the immediate postoperative phase.
Although these modalities are often compared alongside each
other, they both have unique places in the care of children
with cardiac disability. ECMO has a great advantage in that
it can be employed rapidly in a code situation for a patient of
any age or size. In the past, size has been the limiting factor
for implantation of VAD systems into pediatric patients.
The Berlin Heart VAD (Berlin Heart AG, Berlin, Germany)
is available for use even in neonates. From this, however, it
can be appreciated that these two modalities can certainly
complement each other, with ECMO being used acutely; once

the patient is physiologically stable, but still requiring support,
a VAD can be used should long-term support be warranted.
Anesthesia for Heart and Lung

Transplantation
Although perioperative management for thoracic organ
transplantation is considered elsewhere in this text, the
application of these procedures to children requires some
specific modification. Differences include the characteristics
of the candidates, preparation of these children, anesthetic
management, surgical considerations, post-CPB management,
and outcome. Even though some of the earliest heart
transplant procedures were performed for congenital heart
malformations, this indication became rare by the early
1980s. In 1984, over 60 percent of the few pediatric heart
transplant procedures were performed in patients with
cardiomyopathy, usually adolescents. In the next decade, a
dramatic rise in the number of infants and young children
with congenital heart malformations treated with heart
transplantation resulted in a marked shift in the demographics
By 1995, over 70 percent of the children receiving heart
transplants were younger than 5 years of age, with half of
those younger than age 1 year. The overwhelming majority
of these infants received transplants for congenital heart
malformations for which reconstructive options either had
failed or were not believed to exist. The implications of this
shift reach into every element of perioperative management.
Children considered for heart transplantation are more likely
to have pulmonary hypertension than adults. Most adult
transplant programs will not offer heart transplant therapy
to patients with PVR over 6 Wood units/m2. The exclusion
threshold in infants and children remains controversial. Some
programs accept patients with PVR as high as 12 Wood
units/m2, particularly if the pulmonary vasculature responds
to vasodilators such as oxygen, nitric oxide, calcium channel
blockers, or prostacyclin. Neonates are generally assumed to
have elevated PVR, but outcome data from some programs
suggest that the importance of this factor for postoperative
outcome is substantially less in the 5 year of life, perhaps
because the infant donor hearts having recently undergone
transitional circulation, are better prepared to cope with the
right ventricular pressure load that elevated PVR imposes.
The anesthetic plan for pediatric heart transplantation must
accommodate a wide spectrum of pathophysiology. Recipients
with congenital heart malformations benefit from the analysis
of loading conditions and optimizing hemodynamics discussed
previously. Although a few of these patients undergo heart
transplantation, because the natural history of reconstructive
heart surgery poses greater risk despite reasonable ventricular
function, most candidates exhibit some manifestations of
impaired ventricular performance. Accordingly, they require
careful titration of anesthetic agents with minimal myocardial
lower PVR. In the event that these do not provide sufficient

inotropy in the presence of more significant postischemic
dysfunction, additional agents are added (e.g. milrinone,
epinephrine). Most transplant centers have a specific regimen
for immunosuppression to be initiated in the perioperative
period. As with adults, pediatric transplant programs typically
employ triple-drug immunosuppression with a calcineurin
inhibitor (e.g. cyclosporine, tacrolimus), antimetabolite (e.g.
azathioprine), and steroid. After an interval without rejection,
some pediatric programs will taper and discontinue one or even
two of these agents, particularly in neonates, in whom some
element of tolerance is thought to develop. National statistics
indicate that the outcome from pediatric heart transplantation
is slightly less favorable than comparable adult results. The
principal risk factors are age younger than 1 year and congenital
heart defects. Because these factors are closely related (i.e.
the vast majority of infants younger than age 1 year undergo
transplantation for a congenital heart defect), it is difficult to
determine the independent effect of age. Concurrent repair
of structural cardiovascular anomalies substantially increases
perioperative risk of hemorrhage, residual hemodynamic
loading conditions, and right-sided heart failure from elevated
PVR. When these two factors are taken together, infants
younger than 1 year of age have an operative mortality rate of
24 percent, more than twice that of older children. Beyond the
early postoperative period, mortality rates are quite comparable
for all age groups. Nevertheless, the sequelae of rejection and
the consequences of the requisite immunosuppression result
in significant ongoing morbidity and mortality. Because even
the best transplant recipients have achieved only a 28 percent
14-year survival rate, these procedures must be considered
palliative for children.
Lung and heart-lung transplantation have achieved
respectable operative survival rates in children. They remain
the only viable surgical therapy for infants and children with
severe pulmonary vascular disease and selected progressive
pulmonary diseases. These remain uncommon procedures
in pediatrics. Lung transplantation carries the additional
morbidity of obliterative bronchiolitis, a debilitating small
airway disease that results in gradual deterioration in flowrelated pulmonary functions over time. Despite an operative
mortality rate that is currently less than 20 percent, the 3-year
survival rate is only 50 to 60 percent.
Patients with transplanted hearts also present for
surveillance cardiac catheterizations, biopsies, and other
procedures. The anesthesia plan in these patients should take
into effect the physiologic and pharmacologic problems of
allograft denervation, the side effects of immunosuppression,
the risk of infection, and the potential for rejection. Cardiac
allograft vasculopathy is the leading cause of morbidity
and mortality after transplantation, leading to progressive
graft dysfunction with heart failure, an increased risk
of dysrhythmia, and the possibility of arrhythmogenic
74
depressant characteristics to avoid cardiovascular collapse.

In this fragile population, even modest doses of opioids
can be associated with marked deterioration in systemic
hemodynamics, presumably by reducing endogenous
catecholamine release. As with most congenital heart patients,
skilled management of the airway and ventilation represents
crucial elements in a satisfactory induction, particularly in
the presence of elevated PVR. No matter how elegant the
anesthetic plan in conception and implementation, a certain
proportion of these children will decompensate on induction,
necessitating resuscitative therapy.
Although orthotopic heart transplantation poses some
technical challenges in neonates and young infants, the
replacement of an anatomically normal heart is less complex
than several reconstructive heart procedures commonly
performed in patients at this age. However, the need to adapt
this procedure to incorporate repair of major concurrent
cardiovascular malformations requires the consummate skill
and creativity that remain the province of a few exemplary
congenital heart surgeons. Having withstood extended
ischemic periods, heart grafts are extraordinarily intolerant
of superimposed residual hemodynamic loads that may
accompany imperfect vascular reconstruction. The extensive
vascular repair and, particularly in older children with
longstanding hypoxemia, the propensity to coagulopathy
together elevate hemorrhage to a major cause of morbidity and
even mortality in pediatric heart transplantation. Nevertheless,
once successfully implanted, these grafts will respond to
physiologic factors that stimulate growth and adaptation in
the developing infant and child. Management considerations
during separation from CPB and the early postoperative period
are primarily focused on three pathophysiologic conditions:
myocardial preservation, denervation, and PVR. Even
expeditious transplant procedures usually force the heart to
endure ischemic periods that exceed those encountered during
reconstructive surgery. Although some researchers believe the
infant heart is more tolerant of extended ischemia, these hearts
will demonstrate a period of reperfusion injury, and virtually
all require pharmacologic and, in some cases, mechanical
support. In addition, endogenous adaptive responses and
exogenous pharmacologic agents that act via myocardial
sympathetic activation are ineffective in the denervated
graft. Because the majority of children presenting for heart
transplantation exhibit some element of elevated PVR, even
with isolated end-stage cardiomyopathy, the RV of a newly
implanted heart is particularly vulnerable to failure.
As such, ventilatory and pharmacologic interventions are
usually configured to exert a favorable impact on PVR and
provide inotropic and chronotropic support. Once the lungs
are fully expandedthey are ventilated to PaCO2 values in the
low 30s using an FiO2 of 1. Virtually all recipients receive
low-dose dopamine (35 g/kg/min) and isoproterenol
(0.020.05 g/kg/min) to promote inotropy, chronotropy, and
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1056
sudden death. Conventional revascularization procedures

are ineffective because cardiac allograft vasculopathy is
caused by intimal proliferation; thus, retransplantation is
the only therapeutic option. Hyperlipidemia after heart
transplantation is a common occurrence in both adults and
children and is aggravated by chronic steroid therapy and
other immunosuppressive agents. Statins are used with good
results in controlling hyperlipidemia after transplantation
and are likely to manifest inherent immunosuppressive
effects. Risk factors for post-transplant renal dysfunction
are the use of calcineurin inhibitors, mechanical circulatory
support, prolonged inotropic support, and preexisting renal
dysfunction. Newer, more potent immunosuppressive agents
(e.g. tacrolimus) have led to steroid-sparing regimens late after
transplantation, eliminating the detrimental effects of longterm steroid administration. Agents such as sirolimus may
now be used in combination with lower levels of calcineurin
inhibitors, thus minimizing long-term nephrotoxicity.
Post-transplant lymphoproliferative disorders represent a
pathologic spectrum of abnormal lymphoid proliferation
ranging from localized early lesions to polymorphic disease
or, in some cases, monomorphic lymphomatous disease. From
a clinical perspective, the most common sites of disease and
presenting symptoms included the gastrointestinal tract and
pulmonary systems. Patients with polymorphic disease are
treated primarily by a reduction or temporary cessation of
immunosuppression along with adjunctive surgical therapy for
tissue diagnosis or obstructive lesions. Most centers reserve
traditional chemotherapeutic regimens for patients with nonresponsive polymorphic disease and monomorphic disease.
As a result of cardiac denervation, autonomic regulatory
mechanisms are not available to prevent the wide swings in a
patient's hemodynamic state, and the stress response is slower
than usual. Cardiac parameters are significantly altered, and
patients may experience a decrease in systemic blood pressure
and cardiac filling pressures. Compensatory mechanisms are
delayed, and reductions in cardiac output lead to decreased
coronary and cerebral perfusion, especially on the background
of hypertension. Drugs with direct myocardial and vascular
effects are the mainstay of therapy. Most immunosuppressive
agents affect hepatic and renal functions and interact with
anesthetic drugs.
In summary, there are unique features that need to be
considered in caring for children with congenital heart disease
who are undergoing pediatric cardiac surgery. These features
include the patient's growth and development, the developing
cardiovascular system of the young, the pathophysiology
of congenital heart disease, the surgical procedures, and the
CPB techniques. A basic understanding of these differences
coupled with the fundamental knowledge of adult and
pediatric cardiac anesthesia principles underlies the approach
to the perioperative management of these patients. CPB is a
necessary technique for intracardiac and major extracardiac
surgery on the great vessels. CPB induces a multitude of
physiologic and inflammatory derangements, but, through
extensive experience and research, these ill effects can be

largely mitigated by a number of evidence-based strategies.
Therefore, outcomes after CPB have improved dramatically,
and CPB is no longer a barrier to accomplishing complex
congenital heart surgery, even in neonates.
Fetal cardiac surgery:

a Big challenge of the Century
Introduction
Tremendous progress has been made in the diagnosis and
surgical therapy of children born with complex CHD. It is
for sure that early intervention is desirable to allow optimal
postnatal cardiac development and to avoid sequelae of
chronic cyanosis or pulmonary over-circulation be returning
the infant to normal CVS physiology and anatomy as soon as
possible after birth. Prenatal echocardiography now has the
ability to recognize, document and postulate pathophysiologic
mechanisms due to the structural congenital defects as
early as 16 weeks after fertilization. This information allow
interventionalists the hope of altering the in utero natural
history and possibly the postnatal course of lesions with poorer
long-term prognosis. Examples of lesions with poor in utero
natural histories include congenital heart block, some asplenic
syndromes, some forms of interrupted aortic arch, hypoplastic
heart syndrome. Examples of lesions requiring early postnatal
intervention are transposition of the great arteries and
tetrology of Fallot, both of which require pharmacological
palliation at birth to maintain pulmonary blood flow. Most of
these children survive intrauterine life as a consequence of
parallel circulations connected by the patent foramen ovale
or ductus arteriosus, but die postnatally when that structure
closes. Other lesions, despite careful postnatal management in
a single ventricle physiology, the therapeutic options available
are either orthoterminal correction Fontan-Kreutzer or cardiac
transplantation.
In utero Intervention
The fetal circulation that lend support to in utero intervention
are:
1. The contractile elements of the fetal myocardium differ
from those of the adult myocardium. In general there are
fewer sarcomeres per unit mass of myocardium in the fetal
heart, i.e. Fetal myocardium is less compliant and develops
greater tension when stretched during diastole. This reduced
compliance may contribute to ventricular underdevelopment
when intracavity blood volume is reduced.
2. Studies on cellular proliferation during various stages of
cardiac growth have shown that cardiac ventricle muscle is
derived from a discrete population of myogenic precursor
cells. These cells have the ability to acquire contractile
myofibrils during early embryonic life, when cell division
is high. Not only does the rate of cell division decline
Fetal Echocardiography
A 2D, real-time, Doppler echocardiography are excellent to
detect the flow disturbances as early as 16 weeks of gestation.
This has helped to establish:
1. Cardiac anatomy and function at various stages of gestation;
2. Simple and Complex congenital anomalies have been
distinguished;
3. Risk factors for chd have been identified; and
4. The intrauterine natural history of many lesions is
emerging.
Fetal Cardiac Surgery

The theoretical insight gained from cardiac embryologic and
physiologic studies indicate that a significant benefit may
be obtained by intrauterine correction of certain CHD. Fetal
ECG has defined the natural history of congenital cardiac
defects in utero and recognizes the specific defects that
lead to intrauterine death or to a poor postnatal prognosis,
interventions will be considered. To date, surgical interventions
have successfully treated, in utero, human hydronephrosis,
diaphragmatic hernia, cystic adenoid formation of the lung,
and sacrococcygeal tumors. Invasive procedures in utero have
also been successful in draining congenital hydrothorax and
chylothorax.
Recent Findings: Practical

problems and solutions
Fetal Cardiopulmonary Bypass
Congenital heart defects, which present at birth as complex
morphology, are actually the result of a relatively simple
primary lesion and the subsequent development of a complex
secondary lesion during gestation. Fetal cardiac intervention
can prevent simple cardiac lesions from such development.

Congenital heart defects can be detected as early as 12 weeks
gestation by transvaginal fetal echocardiography. The success
of non-cardiac fetal surgery has inspired the innovation of
fetal cardiac surgery. A number of animal experiments have
shown that direct or indirect fetal cardiac approach and fetal
cardiac bypass have their own feasibility, reasonability and
effectiveness. Effective cardiopulmonary bypass supports
the implementation of fetal cardiac surgery. However,
the fetal cardiac surgery is a more complex challenge than
adult or pediatric open heart surgery. To overcome surgical
stress on the fetus and placental dysfunction after bypass is
of paramount importance. Elucidation of the mechanisms of
placental dysfunction after bypass and the negative effects of
fetal stress has allowed these issues to be addressed effectively
using indomethacin and appropriate fetal anesthesia. The
effective management of these two major problems has
made a dramatic difference in the ability of fetal animals to
survive surgical intervention and extracorporeal circulation.
Characterization of various aspects of placental vascular
hemodynamics using the isolated placental preparation also
has added new insights into the behavior of the placental
vasculature during extracorporeal circulation. These insights
have been and will continue to be extremely useful in
designing the ideal method of fetal extracorporeal circulatory
support. Many researchers have shown that non-physiologic
perfusion resulted in endothelial damage to the producing
a series of secondary changes. Therefore, research into the
mechanism of endothelial damage and its alleviation must be
carried out to protect placental function. The use of normal
temperature and moderate pulsatile perfusion according to
fetal circulatory physiology might mitigate the release of
inflammatory intermediators, thus decreasing the endothelial
damage. However, its clinical practice has a long way to go.
Minimally invasive fetal cardiac approach can minimize
maternal and fetal damage, so fetoscopic cardiac intervention
is another valuable choice. Minityping and no-prime/ultra-low
prime are the basic characteristics of a fetal cardiac bypass
circuit. It has been found that pulsatile flow was conducive to
the release of endothelium-dependent vasodilator, mitigating
the contraction of placental vasculature. They do not tolerate
cardiopulmonary bypass for more than an hour. The in utero
correction of congenital cardiac malformations requires the
availability of fetal cardiac bypass. One difficulty with fetal
cardiac bypass is that very high flow rates are necessary when
the placenta is left in the bypass circuit; the placenta requires
about 40 percent of fetal cardiac output, which results in a
normal cardiac output of 400 mL/kg per minute. Pulsatile
perfusion with high blood flow is beneficial to preservation
of the placental function and improves microcirculation.
Moderate high flow perfusion mimics the physiology of
placental circulation and lowers resistance. They both
improve endothelial function. During fetal pulsatile-flow
bypass, improved placental and peripheral perfusion may be
mediated by preservation of fetal/maternal endothelial nitric
74
during later embryonic life, but ventricular growth after

birth occurs by cell enlargement (hypertrophy) alone.
These findings suggest that: if an intervention is to
result in enlargement of cardiac structure (ventricular
muscle) through the addition of contractile myofibrils,
the intervention should occur early, before birth. On the
other hand, early stimulation of the ventricle muscle in
utero may result in irreversible muscle hyperplasia rather
than hypertrophy, as in some variants of pulmonary valve
atresia, wherein the ventricle chamber is almost obliterated
by birth. In addition the altered hemodynamics may also
affect the development of the coronary circulation in
response to pressure loading. Finally, the sympathetic
nervous system does not fully develop until late in
gestation. This impairs the fetal hearts ability to respond
to endogenous catecholamines by altering its contractility
or its Frank-Starling mechanisms. Thus the fetal hearts
adaptive abilities are limited.
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General Issues
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1058
oxide biosynthesis and/or decreased activation of the fetal

rennin-angiotensin pathway. The experimental results have
shown better aortic and umbilical flow and lower placental
umbilical vascular resistance in pulsatile-flow compared with
steady-flow.
In a study, the researcher established RA-PA bypass in lamb
fetuses by axial flow pump driving. At normal temperature
and without prime after 30 minutes of bypass, fetuses were
returned to the womb and 89 percent of the fetal lambs reached
full term. There are two types of circuit, one of which includes
the placenta, and the other excludes placental circulation by
replacement with an oxygenator (artificial placenta). Using
autoplacenta may simplify the circuit. However, the studies
have shown that the autoplacenta cannot bear the prolonged
bypass, for its oxygenation capacity might decrease when
bypass time is prolonged. This is the weakness of autoplacenta
owing to the placental dysfunction. Therefore, maintaining
and restoring placental function after fetal cardiac bypass is a
big challenge. A large amount of primed maternal blood may
dilute the hemoglobin of the fetus, decrease its capability of
binding oxygen so as to disturb the fetus homeostasis. A large
amount of priming fluid in contact with a non-physiologic
surface might further activate cytokines, eventually leading
to placental dysfunction. A mini-typing circuit and axial
flow mini-pump can decrease the primed volume effectively.
After exposing fetal lamb to non-physiological CPB, multiple
cytokines are activated and inflammatory reaction is induced,
which will increase placental vascular resistance, lower gas
exchange and lead to refractory hypoxemia, hypercapnia
and acidosis. Placental dysfunction may be the most severe
obstacle to fetal cardiac bypass. Fetal cardiac bypass damages
endothelium dependent relaxation function selectively,
so protection of the endothelium and avoidance of the
inflammatory response during fetal cardiac bypass would be
a key to preserving placental function. It is suggested that the
use of continuous hemodiafiltration combined with steroid
administration to suppress the inflammatory response, which
causes post-bypass placental dysfunction. Xiao Bing Liu group
from China have come out with a miniature version of fetal
CPB circuit with cardioplegic arrest. They could successfully
wean off from CPB following intracardiac review in a fetal
goat model. The study included surgery on 14 pregnant
goats. The extracorporeal circulation circuit consisted of a
centrifugal pump, silicone tubings with an inner diameter of 6
mm, a roller pump, and a reservoir. The placenta was the sole
oxygenator. CPB was maintained at a mean flow rate of 344
68 mL/kg/min, including 30 minutes of cardiac arrest and 15
minutes of reperfusion. Mean APB and hr were monitored.
Results: Experiments were completed in 11 cases (79%),
with the fetuses weighing 0.65 to 1.8 kg. Fetal mean arterial
blood pressure and heart rate remained stable throughout the
experiments. A large amount of primed maternal blood may
dilute the hemoglobin of the fetus, decrease its capability
of binding oxygen so as to disturb the fetus homeostasis.
Hypothermia induces the activation of the sympathetic

nervous system, increases blood viscosity, which lowers
placental perfusion and decreases oxygen. Hypothermia also
induces uterine contraction, especially during the rewarming
stage, which further damages placental function, resulting
in fetal asphyxia and spontaneous abortion. Hypothermia is
therefore not a protective factor in fetal cardiac bypass.
Since the fetus is a very vulnerable organism, any
disturbance of the external or internal environment toward
the end of gestation may cause fetal stress and abortion. The
adrenal gland plays a major role in response to the outside
stimulus. The endothelium is not only the interface between
blood and vessel tissue, but also the sensor receiving signals,
which regulate dilation of constricted vessels. They release
NO to regulate the tension of umbilical vessels, and mitigate
the constrictive effect of embroxane and endothelin. It is
observed that increased umbilical artery resistance is due to
deterioration of the endothelium dependent vasodilator effect.
The endothelium independent vasodilator (nitroprusside)
function is not altered by indomethacin, halogen inhalant,
combined with magnesium sulphate and -sympathomimetic
agents, which may be effective in monkeys. Inhalation of
halogenoid during the course of procedure can relax the
uterus but suppress the myocardium of the fetus and mother.
Also, although the fetal stress response can be blocked
adequately using fetal total spinal anesthesia, with a dramatic
improvement in cardiovascular stability, this technique of
anesthesia not only would be cumbersome, but also would be
potentially dangerous in the human fetus. High-dose narcotic
anesthesia has been shown to be very effective in neonates and
infants undergoing cardiac procedures, with respect to both
blockage of the stress response and maintenance of cardiac
function. This technique also may be applicable in the human
fetus as an effective method of blocking the stress response
without causing myocardial depression or affecting peripheral
vascular resistances. Unfortunately, sheep do not possess
opiate receptors and, therefore, are not an appropriate model
for testing narcotic anesthesia in the fetus. Future studies
in the primate model using high-dose narcotic anesthesia
could provide important information regarding this problem.
Indomethacin may result in closing of the ductus arteriosus.
Magnesium sulphate combined with -sympathomimetic
agent may induce pulmonary edema in the mother. Because
NO showed outstanding tocolysis in rhesus experiments,
further case control studies are desirable. Spontaneous
abortion may occur after the womb is incised in most pregnant
animals, and there is no exception in humans. Therefore, to
find tocolytic agents is of extreme importance in the field
of fetal cardiac surgery. For achieving tocolysis in baboons,
Fenton and his colleagues used spinal anesthesia, and Ikai
et al used isoflurane inhalation, and the fetuses were still alive
after cpb. Using microinvasive fetal cardiac intervention to
decrease the damage to fetus/mother is a new approach to
correcting congenital cardiac disease before birth. Through
subendocardial region. Although a single dose of crystalloid

cardioplegic solution and ventricular fibrillation might
simplify fetal cardiac surgery, the ultimate goal of myocardial
protection is not simplicity. As with the technical aspects
of the repair, the primary objective is use of the optimal
strategy. Integration of surgical techniques is usually required
to perform the best possible operation. Optimal myocardial
protection also requires integration of various techniques
and strategies. Most surgeons would not abandon a complex
surgical procedure that was proved superior solely because
of its lack of simplicity. Likewise, we should not choose a
protection strategy for its simplicity unless it provides optimal
and complete myocardial protection. Optimal myocardial
protection is as important as an excellent technical repair to
achieve a good long-term outcome with surgical correction.
Although the surgeon might desire simplicity, the patient is
only concerned with success.
Conclusion
Since 1977, many have demonstrated the feasibility of this
innovation in fetal lamb experiments, they analyzed the
results of dilation for fetal aortic stenosis in humans. Though
the results are not satisfactory at present, there is a hope
that further researches might improve the condition. Fetal
cardiac surgery aims to deal with serious heart lesions in the
womb, which have poor prognosis post partum, reduce the
high incidence of critical congenital heart diseases, and lower
operative mortality and morbidity in cardiac surgery after
birth. The prerequisite is the optimal placental preservation
technique during fetal cardiac surgery. The management of
negative effects on the mother/fetus from a cardiac procedure
is another major concern before it becomes a clinical practice.
By fetoscopy technique, fetal cardiac lesions may be corrected
without complex CPB. Not only can it correct fetal cardiac
defect, but may also lessen the harmful effects to the mother
and fetus. Further, it would be a promising and potential therapy
for fetal cardiac defects. All forms of fetal intervention for
cardiovascular disease require an extensive understanding of
the fetal pathophysiologic responses to intervention, whether
the intervention involves open techniques that necessitate
extracorporeal circulatory support or closed interventional
techniques.
Future of fetal cardiac surgery: During the last
two decades, the trend has clearly been toward earlier
correction, to avoid long-term sequelae of chronic cyanosis
or pulmonary over circulation. Refinements in CPB,
myocardial protection, intensive care management, and
surgical techniques have made these advances possible.
Most recently, addition of orthoterminal correction and
cardiac transplantation have added new therapeutic options.
What is the future? Possibly we will someday understand
the molecular biology of congenital heart disease, which
74
abdominal wall puncture and insertion of a cannula into the

uterine cavity by fluoroscopy, a balloon catheter or pacemaker
wire can be inserted into the umbilical artery to alleviate fetal
cardiovascular lesions.
Myocardial Protection: Methods of myocardial protection
must be evaluated in the fetal heart and not simply
extrapolated from adult and infant studies because the
immature fetal myocardium might react quite differently
to various interventions. However, the myocardium must
be optimally and fully preserved for fetal surgery to be
successful. Myocardial dysfunction likely dooms the fetus
to death before delivery because the stress of CPB alone
(without myocardial ischemia) uniformly leads to fetal death
from progressive metabolic acidosis caused by low cardiac
output. An injured heart will only exacerbate this post-CPB
stress. Furthermore, even if the fetus survives, when born,
it will be left with a heart that is destined to fail despite
its structural normality. It makes no sense to perform an
intervention to alter the flow dynamics of the myocardium
only to end up with heart muscle that is severely damaged
and unable to support the circulation. Protection of the fetal
heart is complicated by immature calcium regulation and
energy use, decreased tolerance to ischemia, limited coronary
vascular response, an impaired length-tension relationship,
and a reduced cardiac and inotropic reserve compared with
that of the mature infant. Moreover, the clinical fetal heart
is likely to be further stressed by the structural abnormality
that requires intervention, thus making it evenless tolerant
to ischemia than the unperturbed (morphologically normal)
fetal heart used in experimental studies. This makes complete
recovery of myocardial function in the experimental setting
absolutely critical before fetal intervention is undertaken
clinically. Several cardioplegic constituents (i.e. calcium and
glucose) that have been found to be protective or deleterious in
the isolated heart have been found to have the opposite effect
in the intact (in vivo) heart as a result of cardioplegic washout.
One might also question whether the fetal heart is damaged
by excision alone because baseline measurements were not
taken until the heart was placed in an isolated preparation.
Moreover, the authors used a crystalloid (Krebs-Henseleit)
solution containing high calcium, the harbinger to damage,
to perfuse their isolated heart preparation. A blood perfused
model would have been more physiologic and alleviated some
of these concerns. Nevertheless, the intact (in vivo) animal is
still preferable because differences will always remain, and
no interventions should be applied clinically until proved
successful in the intact animal.
Many surgeons previously used the technique of
ventricular fibrillation with continuous perfusion because it
was simple. However, they found, to their dismay, that hearts
(especially those with hypertrophy) that were fibrillated
during extracorporeal circulation frequently sustained some
degree of ischemic damage, especially to the vulnerable
1059
General Issues
13
could lead to detection, prevention, or genetic manipulation.

Nevertheless, the most exciting frontier to-day is in the
diagnosis and treatment of congenital heart diseases.
Success must be achieved in an appropriate clinical
(in vivo) model before clinical application. Moreover,
no matter what the risk of subsequent repair, unless fetal
surgery can be done safely with minimal myocardial injury
and complete preservation of cardiac function, we have
simply traded one problem for another (i.e. a heart with
normal structure for one with myocardial dysfunction).
Hopefully, this important initial study will spur others to
continue investigations in this field, so that fetal cardiac
surgery can become a reality in the future. Although the
task seems daunting, it is probably no more daunting than
infant surgery appeared to those surgeons 50 years ago.
If we show the same perseverance and dedication as our
predecessors, there is no reason this new frontier cannot be
tamed in the same way heart disease lies in utero.
The patient who has been fed, does not faint, and he who is
rendered intoxicated, does not feel the pain of the operation.
Sushruta (400 BC)
1060
Suggested Readings
1. A Practice of Anesthesia in infants and children: Cote J,
Lerman J, Todres D (Eds), 4th edition: Saunders Elsevier 2009.
2. Edward D Verrier, Gus J Vlahakes. The foundation of Fetal
Cardiac Surgery. Tex Heart Inst J. 1992;3(9):210-6.
3. Fenton KN, Heinemann MK, Hanley FL. Exclusion of the
placenta during fetal cardiac bypass augments systemic flow
and provides important information about the mechanism of
placental injury. J Thorac Cardiovasc Surg. 1993;105(3):502-10.
4. Harrison MR, Jester JA, Ross NA. Correction of congenital
diaphragmatic hernia in utero: Surgery. 1980. pp. 174-82.
5. Millers Anesthesia, Ronald D Miller. Churchill Livingstone
Elsevier, 7th edition.
6. R Scot Bakers. Cardiopulmonary support: Dynamic fluid
shifts induced by fetal bypass: Advances in Cardiac Surgery:
1994;5:47-74.
7. Smiths Anesthesia for Infants and Children. Mosby Elsevier,
7th edition.
8. Su ZK, Chen E. Fetal cardiac surgerya big challenge in the
21st century. World J Pediatr. 2008;4(1):5-7.
9. Xiao Bing Liu et al. A fetal goat model of cardiopulmonary
bypass with cardioplegic arrest and hemodynamic assessment:
JTCVS: 2011;142:5.
C hapter
75
Postoperative Issues in
Shilpa Suresh Mavanoor, Prasanna Simha Mohan Rao
Introduction
Postoperative care of an infant or child after cardiac
surgery differs considerably from that of adults. Specific
techniques used to accomplish a smooth postoperative
course are determined by the patients age, nature of cardiac
defect, clinical condition and the type of repair performed.
A thorough understanding of the preoperative and postoperative pathophysiology associated with each cardiac lesion
is necessary for delivery of optimal care to these patients.
Improved results after surgical management of congenital
heart defects can be attributed in part to the attention now
focussed on postoperative care in congenital cardiac surgery.
This chapter discusses complications that are encountered in
congenital cardiac surgery.
Neonatal heart
The neonatal heart presents physiological characteristics
that differ significantly from children of other ages or from
adults and these should be considered in the perioperative
approach.1
First, the contractile force of the neonatal heart is less
than that of the adult heart because of a series of structural
alterations. The neonatal heart has 50 percent fewer
myofibers and a greater quantity of nonconnective tissue,
which limits the systolic capacity, as in the case of obstructive
cardiopathies. The myofibers are arranged in a chaotic or
nonlinear pattern. Additionally, the neonatal myocardium
has a smaller number of sarcomeres and mitochondria
and the calcium storage capacity of the sarcoplasmatic
reticulum is immature. The immature sympathetic nervous
system reduces the myocardial storage of catecholamines.
Moreover, myocardial contractility during the 1st week of
life occurs because of circulating catecholamines, especially
epinephrine; adequate cardiac output is maintained primarily
by an elevated heart rate.
Second, the myocardial fibers have greater length at baseline

conditions, resulting in less diastolic reserve for volume
overload. Therefore, contractility and ventricular compliance
are effectively reduced, and the neonatal myocardium is near
its functional limit at baseline conditions.
Third, the neonatal and fetal myocardial function is
characterized by ventricular interdependency.2 An overload
in volume or pressure imposed on one of the ventricles
influences filling characteristics of the other ventricle. In this
way, the dilated right ventricle increases the filling pressure of
the left one and this increased pressure then generates elevated
pressure on the right side in order to maintain transatrial flow.
Fourth, immature fetal and neonatal myocardium uses
the metabolites of carbohydrates and amino acids (glycogen,
glutamate, pyruvate and lactate) for contraction. Elevated
stores of glycogen and reduced numbers of mitochondria
reflect adaptation to anaerobic conditions, with greater
recovery capacity and tolerance for hypoxic and ischemic
insults. Therefore, the neonate is more vulnerable to
hypoglycemia and reacts to stress situations with rapid
alterations in pH, lactic acid, glycemia and temperature. These
characteristics are perpetuated beyond the neonatal period.
Gradual transformations occur during all the first year of life
and complete maturity of the myocardium occurs only after 2
years of age.1,2
Postoperative care
The transportation of the child from the theatre to the
intensive care unit requires special care. It is one of the most
dangerous periods in the perioperative period. A member of
both the surgical and anesthetic teams should accompany the
child and heart beat and arterial pressure are to be monitored
(Table 1).3
Adequate monitoring in the postoperative period involves a
combination of clinical or auxiliary methods for evaluating the
surgical correction, myocardial function and the relationship
General Issues
13
Table 1
Post-Operative Assessment3
I. Lesion
Pre-/post-operative anatomy
Procedure
Anesthetic agents used
Pressure measurements in OR
Complications
Central lines
II. Vital signs
Blood pressures
(aortic, central venous or right atrial, left
atrial, pulmonary arterial)
Heart rate
Temp core
Respiratory rate
III. Central Nervous System
Level of consciousness
Pupils
Motor movement
IV. Respiratory System
Breath sounds
Ventilation
Spontaneous-describe pattern
Controlled
Chest movement
Rate
FiO2
TV
PIP
PEEP
CXR-Lung fields
Mediastinal width
Heart size
ET tube position
Central lines
NG tube
Foreign bodies
Arterial blood gases
V. Cardiovascular System
Heart sounds
Murmurs
Pulses- femoral
radial
dorsalis pedis
posterior tibial
Perfusion- capillary filling
temp feet
temp knees
Estimation of cardiac output (include
pressure of mixed venous O2)
EKG
Rate
Rhythm
Conduction
Vascular pressures
Pacemaker settings
Liver size
VI. Fluids-patients weight
Intake-type, volume
Assessment of vascular volume
Electrolytes
Dextrostix
VII. Hematologic System
Clotting status
Hematocrit
VIII. Medications
Vasoactive drugs (quantity/weight/time)
PRN drugs
IX. Plans
EKG = Electrocardiogram; ET = Endotracheal tube; FiO2 = Fraction of inspired oxygen; NG = Nasogastric; O2 = Oxygen; OR = Operation
room; PEEP = Positive end-expiratory pressure; PIP = Peak inspiratory pressure; PRN = Pro re nata (as the circumstances); TV =
Tidal volume
1062
between systemic and pulmonary blood flow. Standard

monitoring in the postoperative period is similar to that
during anesthesia and surgery. Standard monitoring consists
of electrocardiogram, direct arterial pressure, temperature
probe and central venous pressure. Pulse oximeters and
capnography are useful for accompanying mechanical
ventilation and can provide information also on adequacy of
perfusion. To obtain direct arterial pressure, radial or femoral
arterial catheters are placed. Temperature monitoring is
very important for assessing the metabolism. Probes can be
placed in the rectum or nasopharynx or esophagus to provide
adequate assessment of body and core temperature. The
central venous line is generally established by insertion of
a catheter utilizing the Seldinger technique into the internal
jugular vein of choice. Depending on the degree of severity

and type of cardiac disease, transthoracic or transvenous
measurement of pulmonary and left atrial pressures may
give useful physiologic information. Cardiac output can be
also be determined by thermodilution. In small children, the
traditional Swan-Ganz 7 or 5F catheter cannot be used, but
cardiac output can be measured by means of a thermodilution
2F probe inserted by the surgeon into the pulmonary artery.
Newer techniques including echocardiography and on-line
monitoring of arterial and mixed venous saturation obtained
by fiberoptic catheters are increasingly used in postoperative
care.4
Mixed venous oximetry may be done intermittently or
continuously using an oximetry catheter. Pulse oximetry
Fluid and electrolyte replacement

Standard maintenance fluid therapy (Table 2) is administered
to prevent hypovolemia.5 Extra intravascular fluid is then
relatively easily removed with small doses of diuretics

(furosemide, 1 mL/kg intravenously every 8 hours).
The amount and composition of intravenous fluids may
vary depending on the clinical situation and serum electrolyte
levels. It is very difficult to calculate precise fluid needs
for children who have been on cardiopulmonary bypass
(CPB) since there may be a considerable amount of fluid
accumulated in extravascular spaces, and with hypothermia
there may be considerable peripheral vasoconstriction.
Initially, it is simplest to provide approximately one half
the usual maintenance fluid requirements. This will provide
enough fluid for insensible water losses and can be given as
dextrose in water. In the child who has not been on CPB, usual
maintenance fluids are appropriate.6
Sufficient electrolytes are usually provided from the
blood transfusions and saline in various monitoring lines. If
potassium needs replacing approximately 0.2 meq/kg/hour
can be given intravenously and repeated one or two times.
Respiratory Care
Respiratory management very much needs to be tailored to the
particular patient and no simple algorithm can be applied to
all children. Some patients may be extubated in the operating
room or very shortly thereafter. These are usually children
who have the more simple surgical repairs, who have not been
on CPB, and who are very stable hemodynamically. Others,
such as those with preoperative pulmonary edema, major
intraoperative complications, or prolonged CPB, may need
mechanical ventilation for a variable period of time.7 Most
centers are now successfully using protocols that lead to early
extubation.8
75
Postoperative Issues in Congenital Heart Diseases
has evolved to become a standard bedside monitoring

technique. In the intensive care unit (ICU) environment,
it is invaluable in allowing continuous monitoring of
the patients oxygen saturation (SpO2) and pulse rate. It
is particularly useful for the rapid detection of falls in
saturation (e.g. ventilation problems) or undesirably rapid
rises in saturation in univentricular circulations. The
calculation of the oxygen excess factor (OEF, ) which
represents the ratio of the systemic oxygen delivery to
systemic oxygen consumption (SaO2/SaO2-SvO2) is a
useful monitor of the patients adequacy of cardiac output
and ability to extract oxygen and correlates well with
the variations in the systemic vascular resistance and is
particularly useful in patients with balanced circulations
and univentricular hearts postoperatively.
End-tidal expired carbon dioxide (CO2) tensions closely
approximate actual arterial CO2 tensions. The technique
of measuring end-tidal CO2 (ETCO2) permits reasonable
estimations of arterial CO2 levels. ETCO2 monitoring is
standard practice in anesthesia and in the ICU. It is used
to confirm correct endotracheal tube placement, monitor
adequacy of ventilation and identify ventilatory problems
early. The usual technique uses infrared light absorption to
detect CO2.
Serial serum lactate levels can readily identify early low
ouput and can help in rectifying the same.
Early Postoperative Complications
Table 2
Intravenous fluid requirements in the post-operative period5

Patient size
mL/kg/hr
Low Cardiac Output
mL/kg/day
Infant/child
D5.2NS with
20 meq KCl/L
010 kg
100
1020 kg
50 (plus 1,000 mL/

day for first 10 kg)
>20 kg
20 (plus 1,500 mL/

day for first 20 kg)
Day 1
5075 D10W.
No electrolytes
Day 2 and 3
80100 D10W.2NS
with 20 meq Kcl
Day 47
100 D10W.2NS
with 20 meq KCl
Newborn
D5.2NS with 20 meq KCl/L = Dextrose 5% in normal saline solution 0.2%

with potassium chloride 20 meq; D10W = dextrose 10% in water.
Fluctuations in cardiac output can occur rapidly in the post

operative period, making frequent assessments imperative.
Assessment of cardiac output includes evaluation of capillary
refill, peripheral pulses, urine output, arterial blood pressure
(BP), atrial filling pressures, acid base status and peripheral
and core temperatures. Causes of low cardiac output may
include one or more of the following:
1. Alteration in heart rate or rhythm.
2. Decreased preload from hemorrhage, excessive diuresis,
insufficient fluid replacement or cardiac tamponade.
3. Increased afterload from pulmonary hypertension or
peripheral vasoconstriction.
4. Decreased contractility from acidosis, electrolyte imbalance
or myocardial injury secondary to hypoxia and ischemia,
ventriculotomy or inadequate myocardial protection.
5. Suboptimal intracardiac repair with residual intracardiac
shunt or valvar lesion.5
1063
General Issues
13
In neonates ventricular diastolic compliance is diminished,

and newborn infants have a limited ability to increase their
stroke volume.9,10
Echocardiography or cardiac catheterization may be
warranted for further exploration of potential causes of low
cardiac output. Measures to assess and treat low cardiac
output are necessary to reduce time on mechanical ventilation,
hospital length of stay and overall mortality and morbidity.8
Cardiac index may progressively decrease in the perioperative
phase and is lowest at approximately 9 to 12 hours following
CPB.11 This progressive decline in cardiac index is usually
associated with elevations in systemic vascular resistance
(SVR) and pulmonary vascular resistance (PVR). Maintaining
adequate preload, administering vasoactive infusions to
improve cardiac contractility, and taking measures to reduce
SVR and PVR are essential in managing low cardiac output.
Inotropic support with a dopamine infusion of 5 to 15 mcg/
kg/min may assist with cardiac contractility and treating
hypotension associated with low cardiac putput. After
dopamine is titrated beyond 10 to 15 mcg/kg/min, epinephrine
may be considered as an additional therapy. The potent 1 and
1 effects of epinephrine initiated at 0.01 to 0.1 mcg/kg/min
are indicated in treating severe hypotension.12
Milrinone,
a noncatecholamine phosphodiesteraseinhibiting medication, has combined effects of inotropy and
afterload reduction and may be used in combination with
other vasoactive therapies in preventing or managing low
cardiac ouput. A loading dose of 50 mcg/kg/min followed
by a continuous infusion was found to increase cardiac index
in pediatric patients following CPB.13,14 For persistent low
cardiac output, afterload-reducing agents such as nitroprusside
may be considered after BP has stabilized.15 Factors that
contribute to increased SVR and PVR, such as pain, hypoxia
and acidosis, are avoided. Adjunct therapies may include
mechanical ventilation strategies, adequate patient sedation
and analgesia, pharmacologic paralysis and arrhythmia
management.
Atrioventricular (AV) synchrony may provide a critical
advantage in the postoperative patient who has low cardiac
output. Cardiac pacing or antiarrhythmic medications may be
indicated.16
Extracorporeal membrane oxygenation (ECMO) may
be a consideration for progressive myocardial dysfunction
refractory to conventional therapies. This form of mechanical
circulatory support is also indicated for failure to wean from
CPB and for cardiopulmonary failure causing profound low
cardiac output, hypoxemia and cardiac arrest.17,18
Arrhythmias
1064
Disturbances of heart rhythm and rate are important causes

of low cardiac output. Accurate diagnosis and immediate
intervention are essential to the successful management of
arrhythmias. Supraventricular tachycardia includes sinus

tachycardia, atrial fibrillation, atrial flutter, automatic atrial
tachycardia, orthodromic reciprocating tachycardia (ORT),
antidromic reciprocating tachycardia (ART), junctional ectopic tachycardia (JET) and atrioventricular node re-entry
tachycardia (AVNRT). Sinus tachycardia may be secondary
to hypovolemia, pain, anemia or administration of inotropic
drugs. Supraventricular tachycardia also can result from low
cardiac output due to impaired myocardial contractility or cardiac tamponade.5
Supraventricular tachycardia is a re-entry tachycardia
that has an abrupt onset with a regular rate. It is often poorly
tolerated in infants, although it usually responds to vagal
stimulation, cardioversion, or overdrive burst pacing. In
stable patients, adenosine is the first-line drug used to block
the AV node and break the re-entry circuit.19 A patient who has
unstable hemodynamics should be treated with synchronized
cardioversion. Ventricular arrhythmias are uncommon in
infants and children but occur with increased frequency in
adolescents and adults. Conditions that predispose patients to
ventricular arrhythmias include acidosis, low cardiac output,
electrolyte imbalance and myocardial ischemia.20
Junctional ectopic tachycardia is the most common
postoperative arrhythmia in infants and children less than
2-year-old.19 Findings include a rapid ventricular rate with
normal QRS morphology. The atrial rate is typically slower
than the ventricular rate and the P wave is usually inverted
and may occur before, during, or after the QRS complex.
The rapid ventricular rate and dissociated atrial contraction
produce a reduction in BP and a rise in atrial pressures.
Treatment includes mild hypothermia, a reduction in
exogenous catecholamines, pacing to restore AV synchrony
and the use of procainamide or amiodarone.21 Third-degree
heart block involves the complete dissociation of the atria
and the ventricles. The atria and ventricles depolarize
independently of each other, with the atrial rate being faster
than the ventricular rate. Treatment for complete heart block
is temporary external AV sequential pacing. Postoperative AV
block is usually transient and often resolves within 10 days.19
A permanent pacemaker is implanted in patients who have
complete heart block that persists beyond 10 to 14 days after
cardiac surgery.22
Bleeding
Altered hemostasis in the postoperative period results from
surgical trauma, dilution of clotting factors, inadequate
heparin reversal or destruction of platelets and blood
products post CPB. Management involves replacement of
blood products, avoiding hypertension and correcting the
underlying cause of bleeding. Assuring patency of chest tube
drains facilitates evacuation of blood and chest cavity fluids.
Significant blood loss may necessitate surgical intervention.
Cardiac Tamponade
Cardiac tamponade can complicate any cardiac operation
and should always be excluded in the setting of sustained
hypotension or low cardiac output. Classic signs include
systemic hypotension, low pulse pressure, thready pulse, high
atrial pressures and decreased urine output. The diagnosis
may be conrmed by echocardiography. Treatment generally
requires reopening of the chest and relieving the tamponade
to restore hemodynamic stability. If the patient is in a severe
state of low cardiac output, there should be no delay in chest
reopening. One should be cautious when chest drainage
suddenly ceases, as this may reect chest tube occlusion with
ongoing bleeding into the pleural spaces. If clinical suspicion is
high, chest reopening should occur without delay, even before
a conrmatory diagnostic echocardiogram is performed.
While preparing to reexplore the chest, resuscitation includes
uid boluses, increasing or starting inotropes and stopping
vasodilators and diuretics.23
Any abrupt cessation of chest tube output accompanied by
tachycardia and increased filling pressures may be indicative
of cardiac tamponade. Tamponade produces compression
of the cardiac chambers, restricting venous return to the
heart and limiting contractility. Narrowed pulse pressure

and hypotension unresponsive to volume administration
may occur.16 Cardiac tamponade demands prompt surgical
reexploration for evacuation of the pericardial hematoma
and control of bleeding. Some patients may have myocardial
swelling and chamber dilatation that prevent closure of
the chest because of hemodynamic instability. In these
circumstances, it may be advantageous to leave the sternum
open and cover the mediastinum with an impermeable sheet
of silastic sutured to the skin edges.27 Once myocardial
swelling has resolved and cardiac and pulmonary function has
stabilized, the sternum may be electively closed in the ICU
within 48 to 72 hours.
Cardiac Arrest
Cardiac arrest is an unusual occurrence after most pediatric
surgical repairs. Hypoxia, acidosis, drug toxicity, electrolyte
imbalance, arrhythmia, and cardiac tamponade are the most
common causes of cardiac arrest. Diagnosis is usually prompt
in the monitored environment of the ICU. However, delays can
occur in patients undergoing temporary pacing. Management
of cardiac arrest after cardiac surgery follows the (ABCs)
airway, breathing, circulation. A patent airway and adequate
ventilation are the first priority. In nonintubated patients, an
oral airway is inserted and ventilation is started with a face
mask and Ambu bag (100% O2). Endotracheal intubation
follows. Simultaneous attempts should be directed at restoring
effective circulation. The first step is external cardiac massage.
For infants massage is best done by placing both thumbs in
front of the sternum and all other fingers on patients back.
The precordium should be compressed 60 to 120 times per
minute, depending on the size of the child. If adequate cardiac
output cannot be obtained with external cardiac compressions,
or if tamponade is suspected, the chest should be immediately
opened and manual internal cardiac massage instituted.5
Rapid restitution of CPB or ECMO can help resuscitate
children who have arrested in the postoperative period.
75
It is necessary to exclude or treat coagulation defects or

residual anticoagulant effects before embarking on surgical
exploration.23 It is somewhat more frequent in severely
cyanotic patients, polycythemic patients and patients who
are undergoing a reoperation.24 Alterations in the normal
hemostatic mechanisms occur during CPB. These changes
may be attributed to oxygenator platelet adherence and
mechanical trauma to the platelets and blood components by
cardiotomy suction. Postoperative bleeding can result from
inadequate heparin neutralization, thrombocytopenia or
perfusion related dilution of clotting factors. Management
of the bleeding requires correction of the underlying cause,
management of systemic hypertension, and simultaneous
replacement of platelets and other deficient clotting factors.
Thrombocytopenia (< 50,000 platelets/mm2) necessitates
transfusion of platelets. Surgical reexploration is indicated
whenever the hourly chest drainage, in the absence of
clotting abnormalities, exceeds 3 mL/kg/hour for three
consecutive hours after surgery or if there is a sudden,
marked increase in chest tube drainage of 5 mL/kg/hour in
any 1 hour.3
Aprotinin is a protease inhibitor extracted from
bovine lung that modulates the bypass induced systemic
inflammatory response syndrome by inhibiting kallikrien.25
In a specific group of children, namely those undergoing
open heart reoperations, aprotinin can provide acost-effective
means of limiting blood loss and thereby decreasethe risks
that accompany exposure to multiple blood component.26
Tranexamic acid has now superceded Aprotinin due to its
nonavailability.
Pulmonary hypertensive crisis

Pulmonary hypertension is a feared complication following
surgery for certain forms of congenital heart diseases. In the
early postoperative period this may become sufficiently severe
to be labelled as a crisis that often assumes life threatening
proportions.28 Pulmonary hypertensive crisis describes a
serious syndrome characterized by an acute increase in
pulmonary arterial pressure followed by a reduction in cardiac
output and a decrease in oxygen saturation. The definition of
pulmonary hypertensive crisis has been somewhat arbitrary.
In a recent clinical trial all episodes in which the pulmonary/
systemic artery pressure ratio rose to more than 0.75 were
labelled as pulmonary hypertensive crisis.29 Episodes were
classified as major pulmonary hypertensive crisis if there was
1065
General Issues
13
an associated fall in the systemic artery pressure of atleast

20 percent or a fall in transcutaneous oxygen saturation to
< 90 percent or both. Episodes were labelled as minor
if the systemic artery pressure and oxygen saturation
remained stable.30 This syndrome occurs most commonly
among neonates and infants who have undergone repair of
a congenital cardiac defect associated with a large left to
right shunt and pulmonary arterial hypertension. Classic
examples are truncus arteriosus and complete AV canal. Often
the episodes occur after suctioning the endotracheal tube.
Pulmonary hypertensive crisis appears to occur as a result
of hypoxemia, hypothermia, hypercarbia, acidosis, or use of
alphaadrenergic inotropic agents.5
Most modern centres place pulmonary arterial lines
whenever there is a possibility of pulmonary hypertensive
crisis developing in the postoperative period. Apart from
monitoring the pulmonary artery pressures the pulmonary
artery line can be used for vasodilator infusion. Once the
pulmonary hypertensive crisis begins, it can be difficult to
break the vicious circle of right ventricular dysfunction and
low cardiac output. Treatment includes hyperventilation
with 100 percent oxygen to induce mild respiratory alkalosis
(pCO2 < 35, pH 7.4-7.5); use of deep sedation, analgesia
and muscle relaxation; cautious tracheal suctioning after
preoxygenation; routine use of pulmonary vasodilators:
phenoxybenzamine (infusion of 1 mg/kg IV over 1-4 hours
as a bolus followed by infusion of 1-4 mg/kg/day, often
administered via the pulmonary artery line), inhaled nitric
oxide (10-40 parts per million) and sildenafil (0.3-0.5 mg/kg/
dose Q 6-8 hourly). Delayed sternal closure in selected cases
such as newborn with obstructed total anomalous pulmonary
venous connection and avoiding extubation for atleast 6-12
hours after the last crisis.30
Severe postoperative pulmonary hypertension occurred
after 2 percent of the cardiac procedures and in most cases
was managed successfully with conventional treatment and
had a favourable postoperative outcome. The low incidence
relative to previous reports may reflect the benefits of early
correction and improved intraoperative and postoperative
care.31
Renal Failure
1066
Urine output is monitored as a gauge of renal perfusion and

cardiac output. Minimal urine output is 0.5 to 1.0 mL/kg/h in
pediatrics and 30 mL/h in adults. In the perioperative phase
following CPB, urine output may be sufficient due to the
stress response of surgery, intraoperative fluid administration,
and osmotic diuresis from elevated glucose levels in the
CPB priming solution. Within several hours postoperatively,
urine output usually diminishes in response to the effects of
CPB and decreased perfusion. The use of hypothermia may
further decrease renal perfusion. Inadequate intravascular
volume stimulates the reticular activating system, increasing
vasopressin production and the syndrome of inappropriate

antidiuretic hormone secretion.32,33
Diuretic therapy is usually initiated on the first postoperative
day after the initial adverse effects of CPB diminish. Neonates
require more time to diurese due to immature renal systems
that have decreased glomerular filtration rates. Throughout
the postoperative period, any decrease in cardiac output
and tissue perfusion may impact renal function, resulting
in decreased urine output. Excessive use of diuretics in an
attempt to increase urine output and decrease edema may cause
hyponatremia, hypokalemia, hypochloremia, and metabolic
alkalosis.32 Renal failure should be suspected when oliguria
persists despite high doses of furosemide (upto 5 mg/kg) in
the absence of hypovolemia. Renal failure is often caused by
a combination of factors, including marginal cardiac output,
nephrotoxic drugs and prolonged CPB. Once renal failure has
been diagnosed, care must be taken to avoid fluid overload
and hyperkalemia.5
Infection
Prophylactic antibiotics are used to reduce the risk of
pneumonia and blood stream, urinary tract, and surgical site
infections. A broad-spectrum antibiotic should be given before
surgical incision and continued in the immediate postoperative
period following cardiac surgery.34 Data suggest that patients
may benefit from antimicrobial therapy until all chest tubes
have been removed.35 Preventive strategies for the reduction
of postoperative infections include strict adherence to sterile
technique and prompt removal of invasive lines, catheters, and
tubes. Fever in the immediate postoperative period is treated
aggressively with antipyretic agents and cooling devices to
reduce oxygen consumption. If fever persists, blood cultures
are obtained to identify a specific organism.
Neurological Dysfunction
Both acute and chronic neurological morbidity are significant
concerns for children with congenital heart disease. It may
result from an acute perioperative insult. Neurological injury
may be caused by reduced cerebral perfusion during periods of
low cardiac output, chronic hypoxia or thromboembolism.36
Common acute manifestations of neurological damage
associated with cardiac surgery and intensive care include
alterations of consciousness, seizures, hemiparesis, choreoathetoid movements, neuro-ophthalmic deficits, global
hypoxicischemic encephalopathy and intracranial bleeds.
Although the incidence of acute neurological complications is
low,37 their impact on both the child and family is substantial.38
Maintenance of adequate cerebral blood flow throughout the
perioperative period, especially by optimizing cardiac output,
is a key factor in the prevention of neurological morbidity.
Modified ultrafiltration may improve cerebral recovery.39
End of Life Issues

Dealing with a dying child can be an extremely stressful
situation for both the parents and the care giver. Care of
such children and family requires extensive management of
clinical, social and spiritual issues. Terminal care with focus
on quality of life should also be emphasized.
Death of a child is viewed as an anomaly as children
represent growth, hope and energy and longevity and species
preservation.
Cognitive development has a bearing of the childs
perception of death and dying. An infant and a toddler up to 2
years have no concept of death and reactions are more related
to separation from parents and at this stage minimization
of separation from parents, establishment of routines and
provision of maximal physical relief and comfort is required.
Between the age of three to five years children have a
dichotomous thinking of good and bad, magical ideation is in
place and these have a bearing in relation to their responses and
reaction to parenteral and caregiver emotions and behavior.
Death is often considered a temporary reversible thing like
sleep. Illness and separation may be viewed as punishment
for bad actions and children may regress behaviourly in an
attempt to feel secure. These require simple explanations,
minimization of separation from parents and allowing the
child to express itself and provision of adequate pain and
physical relief and comfort measures. Older children between
six and nine years may perceive that they may be punished for
wrong doing and parents may be held responsible for illnesses.
Children do not develop a realistic view of death till they
reach ten to twelve year-of-age and may exhibit regression in
response to physical discomfort and separation from parents.
Teenagers have developed a sense of identity and body image
and sexual identity. An adult belief of death is developed, but
they may still feel immortal. They may be able to appreciate
the irreversibility of death and have a sense of loss of control
and require reassurance, maximal physical relief and comfort.
Family members often have a feeling of guilt and display
grieving with anger, grief and helplessness, which can be
projected on the other family members and caregivers and

rarely on the patient. Financial burden may cause additional
strain and may need addressal by social workers. Involvement
of religious heads and psychologists may play a role in
management of their emotional needs.
Parental presence helps manage separation anxiety and
simple explanations may alleviate fears.
Different cultural values may be present and those may
alter the management of presence of parent at the time of
death and the management of both patients and the parents
at that time. Cultural sensitivity needs to be in place and a
place and time for grieving is needed. Explaining to siblings
may need to be done taking appropriate measures based on the
childs comprehension of death and dying.
Grieving after death is usually usually associated with an
initial period of shock and disbelief and denial. This denial
phase allows an unconscious way of preventing an emotional
overload. This will be followed by classical stages of grieving
including anger, possible hostile reactions, followed by
bargaining, depression and final acceptance and all these
stages need to be recognized as normal and parents need to be
guided through them to allow normal grieving process.
Health professionals will also experience significant
emotions and reactions to death of a child. Expectations
and the nature of relation with the child will have bearing
on the reaction and there may be a measure of difficulty in
letting go and altering care to comfort measures when the
child is dying. The professional caregivers value systems
and beliefs may modify the response and management in
relation to a dying child and needs to be recognized with the
understanding that dying is a normal process in the life cycle
and the care givers role is also to assist and guide through
this difficult stage and coordinate with parents regarding the
dying process and the management of the parents after the
event.42-44
75
A structured approach must be adopted to the management

and investigation of acute postoperative central neurological
dysfunction.40 Therapy is mainly supportive, with an
emphasis on the maintenance of adequate cardiac output,
cerebral perfusion and oxygen delivery. Seizures should
be suppressed with anticonvulsants and measures taken to
prevent aggravation of cerebral edema through appropriate
use of positioning, ventilation strategies to lower PaCO2 and
the administration of analgesia.
Spinal cord injury may occur during cardiac surgery and
anesthesia, especially in children undergoing repair of aortic
coarctation, where spinal cord ischemia and permanent
damage may occur, especially if the cross clamp time exceeds
30 minutes.41
Conclusion
Pediatric patients are not small adult patients undergoing
cardiac surgery but have unique problems that need to
be attended to. Extreme vigilance with anticipation and
pre-emption of low cardiac output is the corner stone of
postoperative management of the cardiac surgical patient.
Early identification of inadequate correction (mechanical
issues) or tamponade, skilled management of balanced
circulations and rapid response to metabolic issues are
important in the postoperative period to ensure good outcome.
Adequate communication between the operative team and the
ICU team are very essential to ensure a successful outcome.
Surgery is the first and the highest division of the healing art,
pure in itself, perpetual in its applicability, a working product
of heaven and sure of fame on earth.
Sushruta (400 BC)
1067
General Issues
13
1068
References
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and carbohydrate consumption in fetal lambs in adult sheep.
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2. Fisher DJ, Heyman MA, Rudolph AM. Myocardial
consumption of oxygen and carbohydrates in newborn sheep.
Pediatr Res. 1981;15:843-6.
3. Lister G. Management of the pediatric patient after cardiac
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4. Auler JO Jr, Barreto AC, Gimenez SC, et al. Pediatric cardiac
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5. Backer CL, Baden HP, Costello JM, Mavroudis C. Perioperative
care. In Pediatric Cardiac Surgery. 3rd edition. Mavroudis C,
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7. Downes JJ, Nicodemus HF, Pierce WS, et al. Acute respiratory
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8. Odegard KC, Laussen PC. Pediatric anesthesia and critical
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PJ, Swanson SJ, (Eds). 7th edition. Sabiston and Spencer:
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Physiol. 1972;222:1285-90.
10. Bryant RM, Shirley RL, Ott DA, et al. Left ventricular
performance following the arterial switch operation: use of
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11. Wernovsky G, Wypij D, Jonas RA, et al. Postoperative
course and hemodynamic profile after the arterial switch
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1995;92:2226-35.
12. Roth SJ. Postoperative care. In: Chang AC, Hanley FL,
Wernovsky G (Eds). Pediatric cardiac intensive care.
Philadelphia Philadelphia. Lippincott Williams and Wilkins;
1998. pp. 163-87.
13. Bailey JM, Miller BE, Lu W, et al. The pharmacokinetics
of milrinone in pediatric patients after cardiac surgery.
Anesthesiology. 1999;90:1012-8.
14. Chang AC, Atz AM, Wernovsky G, et al. Milrinone: systemic
and pulmonary hemodynamic effects in neonates after cardiac
surgery. Crit Care Med. 1995;23:1907-14.
15. Wessel DL. Managing low cardiac output syndrome after
congenital heart surgery. Crit Care Med. 2001;29:S220-30.
16. Dorothy M Beke, RN, MS, CPNPT, Nancy J Braudis, et al.
Management of the pediatric postoperative cardiac surgery
Patient Crit Care Nurs Clin N Am. 2005;17:405-16.
17. Laussen PC, Roth SJ. Mechanical circulatory support. In: Sellke
FW, delNido PJ, Swanson SJ, (Eds). 7th edition. Sabiston and
Spencer: Surgery of the Chest, vol. 2. Philadelphia, Elsevier;
2005. pp. 185-62.
18. Wessel DL, Almodovar MC, Laussen PC. Intensive care

management of cardiac patients on extracorporeal membrane
oxygenation. In: Duncan B, (Ed). Mechanical circulatory
support for cardiac and respiratory failure in pediatric patients.
New York. Marcel Dekker; 2001. pp. 75-111.
19. Perry JC, Walsh EP. Diagnosis and management of cardiac
arrhythmias. In: Chang AC, Hanley FL, Wernovsky G, et al
(Eds). Pediatric cardiac intensive care. Philadelphia. Lippincott
Williams, and Wilkins; 1998. pp. 461-80.
20. Craig J, Fineman LD, Moynihan P, et al. Cardiovascular
critical care problems. In: Curley MAQ, Moloney-Harmon P,
(Eds). Critical care nursing of infants and children. 2nd edition.
Philadelphia. WB Saunders; 2001. pp. 579-654.
21. Walsh EP, Saul P, Sholler GF, et al. Evaluation of a staged
treatment protocol for rapid automatic junctional tachycardia
after operation for congenital heart disease. J Am Coll Cardiol.
1997;29:1046-53.
22. Drifus LS, Fisch C, Griffin JC, et al. Guidelines for implantation
of cardiac pacemakers and antiarrhythmia devices ACC/AHA
task force report. J Am Coll Cardiol. 1991;18:1.
23. Cho Ng, Goldman A. Management of the pediatric cardiac
surgical patient. In Johns Hopkins Manual of Cardiothoracic
Surgery. Yuh DD, Vricella LA, Baumgartner W. The McGraw
Hill Companies Inc. USA. 2007. pp1019-39.
24. Gomes MM, McGoon DC. Bleeding patterns after open heart
surgery. J Thorac Cardiovasc Surg. 1970;60:87-97.
25. Murkin JM. Cardiopulmonary bypass and the inflammatory
response: a role for serine protease inhibitors? J Cardiothorac
Vasc Anesth. 1997;11(2 suppl 1)19-23.
26. DErrico C, Shayevitz J, Martindale S, et al. The efficacy and
cost of aprotinin in children undergoing repeat open heart
surgery. Anesth Analg. 1996;83:6:1193-9.
27. Odim JN, Tchervenkov CI, Dobell AR. Delayed sternal closure:
a lifesaving maneuver after early operation for complex
congenital heart disease in the neonate, J Thorac Cardiovasc
Surg. 1989;98:413-6.
28. Lindberg L, Olsson AK, Jogi P, et al. How common is severe
pulmonary hypertension after pediatric cardiac surgery? J
Thorac Cardiovasc Surg. 2002; 123(6):1155-63.
29. Miller OI, Tang SF, Keech A, et al. Inhaled nitric oxide and
prevention of pulmonary hypertension after congenital
heart surgery: a randomised doubleblind study. Lancet.
2000;356:1464-9.

30. Kumar RK. Pulmonary hypertension and pulmonary
hypertensive crisis after surgery for congenital heart disease:
Pathophysiology and diagnosis. Pediatric Cardiac society of
India. 2003;2:1-4.
31. Lindberg L,Olsson AK,Jgi P,Jonmarker C. How common is
severe pulmonary hypertension after pediatric cardiac surgery?
J Thorac Cardiovasc Surg.2002;123:1155-63.
32. Roth SJ. Postoperative care. In: Chang AC, Hanley FL,
Wernovsky G, et al, editors. Pediatric cardiac intensive care.
Philadelphia, Lippincott, Williams, and Wilkins; 1998. pp.
163-87.
33. Craig J, Fineman LD, Moynihan P, et al. Cardiovascular
critical care problems. In: Curley MAQ, Moloney-Harmon P,
(Eds). Critical care nursing of infants and children. 2nd edition.
Philadelphia7 WB Saunders; 2001. p. 579-654.
39. Skaryak LA, Kirshbom PM, DiBernardo LR, et al. Modified

ultrafiltration improves cerebral metabolic recovery after
circulatory arrest. J Thorac Cardiovasc Surg. 1995;109:744-51;
discussion 751-52.
40. Tasker RC. Neurological critical care. Curr Opin Pediatr.
2000;12:222-6.
41. Macrae D, Larovere J. Intensive care management of the
postoperative patient. In Surgery for Congenital Heart defects.
3rd edition. Stark JF, de Leval MR, Tsang VT, Courtney M (eds).
John Wiley & Sons: West Sussex, England. 2006. pp 203-28.
42. Smith SC. The Forgotten Mourners: Guidelines for Working
with Bereaved Children. London; Philadelphia, pa: Jessica
Ringsley Publications; 1999.
43. McQuillan R, Finlay I. Facilitating the care of terminally ill
children. Journal of Pain and Symptom Management. 1996;
12:320-4.
44. Worden JW. Bereavement. Seminars in Oncology. 1985;12:
472-75.
75
34. Mangram A, Horan T, Pearson M, et al. Guideline for

prevention of surgical site infection, 1999. Centers for
Disease Control and Prevention (CDC) Hospital Infection
Control Practices Advisory Committee. Am J Infect Control.
1999;27:97-134.
35. Maher KO, VanDerElzen K, Bove DL, et al. A retrospective
review of three antibiotic prophylaxis regimens for pediatric
cardiac surgical patients. Ann Thorac Surg. 2002;74:1195-200.
36. Fallon P, Aparicio JM, Elliott MJ, et al. Incidence of
neurological complications of surgery for congenital heart
disease. Arch Dis Child. 1995;72:418-22.
37. Menache CC, du Plessis AJ, Wessel DL, et al. Current incidence
of acute neurologic complications after open heart operations
in children. Ann Thorac Surg. 2002;73:1752-8.
38. Mahle WT, Clancy RR, Moss EM, et al. Neurodevelopmental
outcome and lifestyle assessment in school aged and adolescent
children with hypoplastic left heart syndrome. Pediatrics.
2000;105:1082-9.
1069
C hapter
Pediatric Heart and

Lung Transplantation
76
Brannon Hyde, Deborah J Kozik, Charles W Hoopes, Mark D Plunkett
Pediatric Heart Transplantation

The history of clinical cardiac transplantation begins with
the first successful human heart transplant performed by
Christian Bernard in a 54-year-old man on December 3, 1967
at Groote Schuur Hospital in Capetown, South Africa. This
clinical breakthrough was based on extensive animal research
by Drs Richard Lower and Norman Shumway at Stanford
University.1 During the following year, over 100 heart
transplants were performed throughout the world. Most of
these patients succumbed to acute rejection or severe infection
early postoperatively. Many centers abandoned the procedure
due to these early poor results. Stanford University remained
as an exception and continued with basic science research and
clinical advancements in heart transplantation over the next
decade. The introduction of cyclosporine A in the early 1980s
ushered in a new era for heart transplantation by giving heart
transplant centers an immunosuppressant drug that allowed
longer term survival with fewer postoperative complications.
There was an immediate resurgence of interest around the
world and numerous medical centers reopened their heart
transplant programs.
The first neonatal heart transplants were performed in
1984 both in London and Loma Linda, California, 16 years
after Bernards first adult heart transplant in South Africa.
The transplanted infant in California, 'Baby Fae,' received
a baboon heart and lived only 21 days, but provided the
much needed exposure of infant heart transplant to the
public consciousness. The first successful infant cardiac
transplantation was performed one year later, for hypoplastic
left heart syndrome (HLHS), by Dr Leonard Bailey at Loma
Linda University on November 20, 1985.2 Remarkably, that
initial patient, 'Baby Moses', is still alive at the time of this
writing.2 This pioneering effort was the result of extensive
research and investigation into clinical transplantation and
xenotransplantation.3,4
From 1982 until 2009, 9,566 heart transplants in pediatric

recipients (under 18 years of age) had been reported to the
International Society for Heart and Lung Transplantation
(ISHLT) Registry.5 In the current era, approximately 350 to
450 pediatric and neonatal heart transplant procedures are
reported annually to this registry.2,6 Ninety-six pediatric
heart centers reported transplants in 2009, with 56 percent
from North America and 41 percent from Europe. Congenital
heart disease (CHD) and cardiomyopathy (CM) remain
the primary indications for heart transplant (infants, 58
percent CHD vs 39 percent CM; 1 to 10 years, 54 percent
CM vs 39 percent CHD; age > 11 years, 62 percent CM)
(Figure 1).7 Retransplants comprise only 6 percent of all
pediatric heart transplants, 50 percent of which occur more
than 5 years after the first graft implant. Over the last decade
in the North America, slightly less than one-third of pediatric
heart transplants were performed in infants, one-third in 1
to 10year-old and slightly more than one-third in 11 to 18
year-olds. Most programs now report a greater than 70 percent
5-year survival of pediatric heart transplant recipients.8
Despite this clinical progress, pediatric and neonatal heart
transplants still account for only 10 percent of the overall
heart transplants performed in the US and worldwide.8
Indications for Pediatric Heart

Transplantation
The primary indications for orthotopic heart transplantation
(OHT) in children are CHD, either primary or after semicorrective operative intervention and CM from metabolic or
traumatic/toxic causes (Table 1).9
Dilated cardiomyopathy (DCM) accounts for over half
of all heart failure in children. Five-year survivals are
reported anywhere from 40 to 83 percent.9-12 Acute fulminant
myocarditis requiring mechanical support may be a good
prognostic indicator as up to 50 to 80 percent of children will
have complete resolution of their dilated CM within 2 years
and avoid transplantation.9 Hypertrophic cardiomyopathy
76
Table 1
Anatomic diagnoses in heart transplant recipients < 6 months

of age within the PHTSG and CTRD databases with previously
repaired or palliated congenital heart disease
Diagnosis
n (N = 488)
Single ventricle
176
36
D-transposition of the great arteries
58
12
Right ventricular outflow tract lesions
49
10
Ventricular/atrial septal defect
38
Left ventricular outflow tract lesions
38
L-transposition of the great arteries
39
Complete AV canal
37
Other
53
11
AV = Atrioventricular; CTRD = Cardiac Transplant Research Database;

PHTSG = Pediatric Heart Transplant Study Group.
Courtesy: With permission from Canter, et al. Circulation. 2007;115:658-76,
Box 2.
(HCM) is the second most common CM (2542%), but

accounts for only 5 percent of pediatric heart transplants.
Malformation syndromes such as Noonans syndrome and
Beckwith-Wiedemann syndrome comprise approximately
25 percent of HCM cases in the American and Australian
registries. Risk factors for death or transplantation in HCM
include presentation under 1 year of age and echocardiography
findings of lower initial shortening fraction and higher
initial left ventricle (LV) posterior wall thickness. Duchenne
muscular dystrophy and other muscular dystrophies also
contribute to the development of CM and heart failure in
children. Those with severe cardiac failure who are otherwise
functional and physically active may also be considered for

heart transplantation.
Restrictive CM (RCM) is characterized by an LV with
normal size and wall thickness, but with poor compliance and
restrictive filling (diastolic dysfunction). RCM accounts for
only 2.5 to 3 percent of CMs in children, but comprises 12
percent of heart transplants performed among CM patients.9
Long-term survival is reduced in patients with RCM (less than
50 percent at two years)13 and the incidence of progressive
pulmonary hypertension is high, often precluding heart
transplant. Consequently, listing for heart transplant at the
time of diagnosis of RCM is a common practice.9,13
Heart transplantation for CHD falls under two broad
categoriesprimary therapy and therapy in previously
palliated or repaired defects. Primary therapy has been used
in HLHS, pulmonary atresia with intact ventricular septum
(PAIVS) and right ventricle-dependent coronary circulation
(RVDCC) and single ventricle lesions with anomalous
pulmonary venous return and severe valvular disease. The
recent increased percentage of infant heart transplants
performed for CM is primarily due to the recent increased
success of surgical palliation for HLHS.9 As a consequence
of successful palliative procedures, many patients survive
into early childhood, adolescence and adulthood. These
patients often have significant morbidity including congestive
heart failure, valvular disease, pulmonary hypertension and
arrhythmias that may ultimately result in the need for heart
transplantation.14 Patients who have previously undergone
palliative operations and later receive OHT account for
approximately 40 percent of all pediatric heart recipients.9
Pediatric heart transplant recipients have a 2 to 3 percent
annual risk of death or graft failure with most events occurring
Pediatric Heart and Lung Transplantation
Figure 1: Diagnosis in pediatric heart transplant recipients aged 1 to 10 years.

Courtesy: From Kirk, et al. J Heart Lung Transplant. 2011;30:1095-1103; Figure 6
1071
General Issues
13
due to graft coronary vasculopathy, acute or chronic rejection,

or both.9 Indications for retransplantation in pediatric heart
transplant recipients include graft coronary vasculopathy
(51%), nonspecific graft failure (16%), acute rejection (9%),
chronic rejection (7%), primary failure (5%), hyperacute
rejection (3%) and others (10%).6 Retransplant accounts
for only 6 percent of heart transplants in the pediatric
population. Survival after early (< 5 years) retransplantation
is significantly lower than after primary transplantation. If,
however, the intertransplant interval is greater than 5 years,
then survival following retransplantation is comparable to
primary transplant.7
Heart failure staging systems vary widely, but current
guidelines are based on the ISHLT classifications outlined
in Box 2.15 Recommended clinical guidelines for heart
transplantation are summarized in Box 3.9
Fetal Listing
The criteria for initiating a cardiac transplant evaluation
in utero with fetal listing include:
Box 1: Proposed heart failure staging for infants

and children
Stage Interpretation
A
Pretransplant Evaluation
Pediatric patients with heart disease undergo extensive
evaluations before being considered as heart transplant
candidates. Evaluation includes assessment of:
1. The cardiovascular anatomy and hemodynamics.
2. Presence of chronic noncardiac disease and magnitude of
dysfunction in other organ systems.
3. Magnitude of sensitization to human leukocyte antigens
(HLA) and HLA-specific antibodies.
4. Psychosocial evaluation of the patient and the patients
family to screen for the presence of psychological,
cognitive, behavioral and adjustment disorders.
C
D
Patients with increased risk of developing HF, but

who have normal cardiac function and no evidence
of cardiac chamber volume overload. Examples:
previous exposure to cardiotoxic agents, family
history of heritable cardiomyopathy, univentricular
heart, congenitally corrected transposition of the
great arteries.
Patients with abnormal cardiac morphology or
cardiac function, with no symptoms of HF, past
or present. Examples: aortic insufficiency with
LV enlargement, history of anthracycline with
decreased LV systolic function.
Patients with underlying structural or functional
heart disease and past or current symptoms of HF.
Patients with end-stage HF requiring continous
infusion of intropic agents, mechanical circulatory
support, cardiac transplantation or hospice care.
HF = Heart failure; LV = Left ventricular.

Courtesy: From Rosenthal, et al. J Heart Lung Transplant. 2004;
23:1313-33, Box 1.
Box 2: Clinical guidelines for heart transplantation

Cardiomyopathies and congenital heart disease in pediatric patients
Class I
Heart transplantation is indicated as therapy for stage D heart failure associated with systemic ventricular dysfunction in
pediatric patients with cardiomyopathies or previous repaired or palliated congenital heart disease (Level of Evidence B).
Heart transplantation is indicated as therapy for stage C heart failure in pediatric heart disease associated with severe
limitation of exercise and activity. If measurable, such patients would have a peak maximum oxygen consumption < 50
percent predicted for age and sex (Level of Evidence C).
Heart transplantation is indicated as therapy for stage C heart failure associated with systemic ventricular dysfunction in
pediatric patients with cardiomyopathies or previously repaired or palliated congenital heart disease when heart failure is
associated with significant growth failure attributable to the heart disease (Level of Evidence B).
Heart transplantation is indicated as therapy for stage C heart failure in pediatric heart disease with associated near sudden
death and/or life-threatening arrhythmias untreatable with medications or an implantable defibrillator (Level of Evidence C).
Heart transplantation is indicated as therapy for stage C heart failure in pediatric restrictive cardiomyopathy disease
associated with reactive pulmonary hypertension (Level of Evidence C).
In the presence of other indications for heart transplantation, heart transplantation is feasible in patients with pediatric
heart disease and an elevated pulmonary vascular resistance index > 6 Woods units/m2 and/or a transpulmonary pressure
gradient >15 mm Hg if administration of inotropic support or pulmonary vasodilators can decrease pulmonary vascular
resistance to < 6 Woods units/m2 or the transpulmonary gradient to < 15 mm Hg (Level of Evidence B).
1072
Contd...
76
Contd...
Heart transplantation is indicated as therapy for stage C heart failure in pediatric heart disease associated with reactive
pulmonary hypertension and a potential risk of developing fixed, irreversible elevation of pulmonary vascular resistance
that could preclude orthotopic heart transplantation in the future (Level of Evidence C).
Certain anatomic and physiological conditions likely to worsen the natural history of congenital heart disease in infant
patients with a functional single ventricle, which can lead to use of heart transplantation as primary therapy. These
conditions include:
1. Severe stenosis (stenoses) or atresia in proximal coronary arteries.
2. Moderate to severe stenosis and/or insufficiency of the atrioventricular and/or systemic semilunar valve(s).
3. Severe ventricular dysfunction (Level of Evidence C).
Several anatomic and physiological conditions likely to worsen the natural history of previously repaired or palliated
congenital heart disease in pediatric patients with stage C heart failure that may lead to consideration for heart
transplantation without severe systemic ventricular dysfunction, including:
1. Pulmonary hypertension and a potential risk of developing fixed, irreversible elevation of pulmonary vascular resistance
that could preclude orthotopic heart transplantation in the future.
2. Severe aortic or systemic A-V valve insufficiency that is not considered amenable to surgical correction.
3. Severe arterial oxygen desaturation (cyanosis) that is not considered amenable to surgical correction.
4. Persistent protein-losing enteropathy despite optimal medical-surgical therapy (Level of Evidence C).
Class IIB
Class IIA
The efficacy of heart transplantation as therapy for pediatric heart disease is not established for patients with previous
infection with hepatitis B or hepatitis C or with human immunodeficiency virus (HIV) infection (Level of Evidence B).
The efficacy of heart transplantation for pediatric heart disease is not established for patients with a history of recent use
of illicit drugs or tobacco or a recent history of alcohol abuse (Level of Evidence B).
The efficacy of heart transplantation for pediatric heart disease is not established for patients with a history of psychological,
behavioral, or cognitive disorders; poor family support structures; or documented noncompliance with previous therapies
that could interfere with successful performance of care regimens after transplantation (Level of Evidence B).
Class III
Heart transplantation for pediatric heart disease is not efficacious when heart disease is associated with severe, irreversible
disease in other organ systems or when it is part of a severe, irreversible, multisystemic disease process. Multiorgan
transplantation may be considered (Level of Evidence C).
Orthotopic heart transplantation for pediatric heart disease is not efficacious when heart disease is associated with severe,
irreversible, fixed elevation of pulmonary vascular resistance (Level of Evidence C).
Heart transplantation is not feasible in the presence of severe hypoplasia of the central branch pulmonary arteries or
pulmonary veins (Level of Evidence C).
The limited supply of pediatric donors, especially infant donors, makes heart transplantation not a feasible standard
therapy for any specific congenital heart lesion (Level of Evidence B).
Cardiac retransplantation in pediatric patients
Class I
Retransplantation is indicated in children with abnormal ventricular function and at least moderate graft vasculopathy
(Level of Evidence B).
Class IIA
Retransplantation is indicated in children with normal ventricular function and at least moderate graft vasculopathy (Level
of Evidence B).
Class III
Retransplantation should not be performed during an episode of ongoing acute allograft rejection, even in the presence of
graft vasculopathy (Level of Evidence B).
Retransplantation is not efficacious when performed during the first 6 month after primary transplantation (Level of
Evidence B).
Courtesy: Adapted from Canter, et al. Circulation. 2007;115:658-676.
1073
General Issues
13
1. A congenital heart defect not considered correctable by

postnatal surgical repair.
2. Normal pulmonary artery anatomy.
3. Estimated fetal weight greater than 2.0 kg.
4. Greater than 35 weeks gestation.
5. Normal chromosomes.
6. No significant extracardiac defects identified by prenatal
level three ultrasound.16,17
After cord blood sampling and typing, the fetal candidate
is listed in the US under a special status code on the United
Network of Organ Sharing (UNOS) waiting list. If the
candidate does not undergo transplantation immediately after
delivery, then the waiting time restarts from the time of birth
with listing under the regular UNOS status codes.
Contraindications
Contraindications to heart transplant include irreversible
pulmonary hypertension (pulmonary vascular resistance index
[PVRI] > 6 Woods units/m2), active infection, malignancy,
other end-organ failure and major central nervous system
defects (Box 3).18 In a report from Chiu et al,19 158 CM
patients were reviewed who underwent OHT between June
1984 and November 1010. Four of 19 patients (21.1%) with a
PVRI > 9 had early mortality (death < 30 days) versus 1 of 139
patients (0.7%) with PVRI < 9. The authors concluded that a
PVRI < 6 cutoff was too restrictive as a contraindication to
OHT.19 Although not widely accepted, the improved medical
management of perioperative pulmonary hypertension
has made high risk OHT (PVRI > 6) more acceptable. The
availability and use of pulmonary vasodilators (e.g. nitric
oxide, sildenafil, etc.) has improved heart transplant outcomes
in pediatric patients with elevated PVRI.
Box 3: Contraindications for pediatric heart

transplantation
Absolute
Irreversible pulmonary artery hypertension (45 Woods/
m2 )
Inactive systemic infection
Uncontrolled malignancy
Severe primary renal or hepatic failure
Major abnormalities of the central nervous system
Severe dysmorphism
Relative

1074
Marked prematurity (36 weeks)

Low birth weight (< 2 kg)
Positive drug screen
Lack of family support
Courtesy: With permission from Tjang, et al. J Card Surg. 2008;23:

87-91; Box 1.
Donor Hearts Selection

Donors must meet requirements for brain death as outlined in
recent guidelines both in adults and children.20,21 Consent must
be obtained from nearest relatives for organ procurement. ABO
compatibility is favored for acceptable long-term outcome
and to avoid hyperacute rejection.22 An exception to this is
ABO incompatible heart transplants in infants less than 6
months of age that is currently being studied at several centers.
In general, donors should be one to three times the recipient
weight for an acceptable size match. Echocardiography
should demonstrate normal cardiac anatomy and function
after resuscitation. Mechanism of death should be considered
with regards to possible myocardial damage or contusion. If
the donor suffered cardiac arrest and was resuscitated with
cardio pulmonary resuscitation (CPR), then the duration
of arrest is of importance and must be determined. Donors
should have no active infection (including HIV or hepatitis
B) or malignancy. Hepatitis C (HCV) positive donors may be
acceptable for HCV positive recipients, but this is controversial
and currently avoided at most centers. Evaluation of the donor
should include physical exam, assessment of hemodynamics
and any inotropic medications used during resuscitation, renal
function, chest X-ray and electrocardiogram (ECG). The
anticipated length of ischemic time and the travel distance to
the donor facility must be determined. Visual inspection by
the procurement team is necessary, before final acceptance of
the heart for transplantation; (Figure 2).
Surgical Management
General Considerations
Pediatric patients receiving a heart transplant for CHD
have often undergone one or more median sternotomies or
thoracotomies for palliative operations. Unlike adults, who
often receive transplantation due to DCM or ischemic DCM
disease, children with CHD often have complex anatomy
requiring tailoring of the implantation techniques. These
patients also tend to be highly sensitized from previous blood
transfusions and use of homograft material for repairs. They
often have elevated panel reactive antibodies (PRAs) making
them at higher risk for rejection complications. Pulmonary
vascular resistance is often higher in children, making
postoperative management more difficult. Donor organs
from children are more resistant to prolonged ischemic times;
however, time to graft failure is still essentially the same as
donor hearts in adults.23
Heart Procurement Techniques

A coordinated effort is essential in multiorgan procurements.
Donor heart procurement is performed through a median
sternotomy, usually in conjunction with a lung and/or
Figure 2: A donor heart removed at the time of procurement with

additional great veins, pulmonary artery and aortic arch. The removal
of additional donor tissue at the time of organ removal is important
for patients with congenital heart disease who have had previous
operations. Courtesy: Reproduced with permission from Kapour AS,
Laks H. Atlas of Heart-Lung Transplantation. New York: McGraw Hill,
Inc; 1984
abdominal transplant procurement team. If the lungs are being

procured, both heart and lung teams should agree on the lines
of division in the left atrium (LA) and pulmonary artery (PA).
The line of division in the inferior vena cava (IVC) should
be done in conjunction with the liver procurement team.
Dissection begins by separating the main pulmonary artery
and aorta to allow easy placement of a cross clamp. The
superior vena cava (SVC) and innominate veins are dissected
free. If the recipient has a left SVC, the donor innominate
vein will be needed for heart implantation. The azygos vein
is ligated and divided. The attachments surrounding the SVC
and IVC are freed, sharply. Full systemic heparinization dose
is administered (300 units/kg). The aorta is cross-clamped and
the cardioplegia solution is administered (approximately 30
mL/kg). Pressure monitoring of the aortic root is preferable
to avoid high perfusion pressure in pediatric patients and
injury to the coronary microvasculature. The right superior
pulmonary vein (or the left atrial appendage if the lungs are
being procured) is incised to decompress the left heart. The
IVC is incised to decompress the right heart. We place a right
angle clamp on the left atrial appendage and amputate the
tip, before cross-clamping. Removing the LA clamp allows
decompression of the left heart, during harvest. Ice saline
slush is poured on the heart while suctioning warm blood
from the pericardial well at the vent sites.
Heart Transplantation Techniques

Once on bicaval cardiopulmonary bypass (CPB), the recipient
cardiectomy is started by vertically incising the right atrium
(RA). Both venae cavae are snared and blood is returned to
the CPB circuit. The fossa ovalis is incised and an incision is
continued vertically onto the dome of the LA. The RA incision
is continued inferiorly leaving a small cuff of atrium on the
medial border of the IVC. A circumferential incision is then
completed around the LA, leaving a sewing cuff well away
from the pulmonary veins (PV). The pulmonary artery and the
aorta are usually divided just above their respective valves.
Suture lines are performed with continuous polypropylene
sutures. Some use polydioxane for neonates to small children
for the theoretical growth advantages.23 Three basic techniques
for implantation have been described23,24biatrial,25 bicaval26
and bicaval and bipulmonary vein;27 (Figures 3A to C). In any
technique, the LA suture line is performed first. We place a
left ventricular (LV) vent through the right superior PV after
completion of the LA suture line. The aorta on recipient and
donor are trimmed and the aortic end-to-end anastomosis is
completed. The patient is placed into a head down position
with the LV vent on, and the aortic cross clamp can then be
removed. The PA end-to-end anastomosis is performed after
appropriate trimming of both ends. Leaving redundant main
PA length can lead to kinking and a pressure gradient from
the RV to branch PAs. Finally, whether biatrial or bicaval
anastomoses are performed, the RA is sewn to the venae
cavae.
The biatrial technique is considered to be less anatomic
resulting in distortion of the tricuspid valve (TV) annulus
and a predisposition to TV or sinus node dysfunction. Mitral
insufficiency and atrial arrhythmias have also occurred, but
are rarely clinically significant.23 The bicaval technique may
76
Cardiectomy begins by dividing the IVC. Once divided,

the LA is incised circumferentially to preserve a left atrial cuff
for the lungs. If the lungs are not being procured, the veins can
be divided at the pericardial reflection. The main PA is divided
at the bifurcation if the lungs are being procured; if not, the
branch PAs can be divided at the pericardial reflection. The
posterior pericardial attachments of the oblique and transverse
sinuses are divided followed by the SVC or innominate,
depending on how much vein is needed for implantation.
The ascending aorta is usually divided at the level of the
innominate artery. If the recipient has HLHS or a hypoplastic
arch, then the aorta is harvested to the level of the proximal
descending segment. The heart should then be placed in cold
saline (4C) in a handheld cooler for transport to the recipient
operating room, even if the procurement is performed in the
OR at the same facility. Consideration of recipient anatomy
is essential in those patients with CHD and may alter the
harvest technique to allow additional tissue for anatomic
reconstruction at the time of implantation.
1075
General Issues
13
Figures 3A to C: Standard surgical heart transplantation techniques: A. Biatrial (left); B. Bicaval (middle); C. Bicaval and bipulmonary vein
(right) technique. Courtesy: From Schmid, et al. Thorac Cardiovasc Surg. 2005;53 Suppl 2:S141-5. Figure 1
1076
cause less tricuspid annular distortion since the atrioventricular

groove sits in a 'normal' plane. Furthermore, preservation of
the donor SVC decreases the risk of sinoatrial nodal injury.
The bicaval technique, however, is prone to purse-stringing
at the SVC anastomosis and subsequent stenosis. The
bipulmonary vein technique is primarily used for larger donor
organs, where size mismatch is a concern. Resecting the LA
posterior wall allows a larger organ to be placed between the
PV cuffs. Care must be taken to avoid PV stenosis with the
latter technique.23,28
Implantation techniques may require modification for
children with CHD, some of whom may have undergone
multiple sternotomies and palliative procedures. In HLHS
babies who have not undergone palliation, the entire aortic
arch and several centimeters of descending aorta should be
procured to use in reconstruction of the hypoplastic arch and
coarctation in the recipient; (Figures 4A to D). In patients that
have undergone a Glenn or Fontan procedure, the absence of a
main PA requires that the donor cardiectomy include the branch
PAs. In Fontan patients, if an atriopulmonary connection was
used, atrial anatomy is distorted; moreover, in patients who
have an extracardiac or lateral tunnel the RA is essentially
absent. In both of these cases, bicaval anastomoses greatly
facilitate implantation. The bicaval technique also is helpful
in patients who have undergone an atrial switch (Mustard
or Senning procedure) for transposition of the great arteries
(TGA). Essentially, all atrial tissue and baffles are resected
during cardiectomy and the donor heart is sewn directly to
the venae cavae. Care should be taken in procurement of a
heart for a TGA patient to obtain as much length as possible of
the aorta and pulmonary artery. Extra arterial length facilitates
the anastomoses to the unusual anatomy of the great vessels.
Reversal of the LeCompte maneuver and repositioning
of the branch pulmonary arteries behind the aorta may be
necessary in these patients to achieve alignment of the great

vessels for anastomosis. The venous connections in TGA
have normal anatomy. In situs inversus, pericardial baffles
and venous relocations have been used to bring blood from a
left-sided SVC and IVC to the right side for connection to an
anatomically normal heart. In many patients, the left pleural
space must be widely opened to accommodate the apex of the
transplanted heart.23,24,29
Before coming off CPB, infusions are initiated with a
combination of dobutamine (and/or dopamine) and milrinone
in younger children or epinephrine, norepinephrine and
milrinone in adolescents and young adults. Milrinone
is continued several days postoperatively as changes in
pulmonary vascular resistance can be unpredictable and
sudden. For patients who have known elevated right-sided
pressures (mean PA pressure greater than 25 mm Hg or PA
systolic roughly greater than one-third of systemic) preoperatively, nitric oxide will be administered upon initiation
of ventilation, while still on cardiopulmonary bypass and
continued several days in the intensive care unit (ICU). Pacing
may be necessary to increase heart rate and reduce diastolic
filling time in the early postoperative period. After chronotropic
and inotropic infusions are weaned, most patients require
afterload reduction in the form of an angiotensin converting
enzyme (ACE) inhibitor or calcium channel blocker that will
be continued after discharge.
Immunosuppression
Effective immunosuppression is paramount to successful
pediatric heart transplantation. Transplant registries have
76
Figures 4A to D: Transplantation for hypoplastic left heart syndrome (HLHS): A. Under profound cooling and circulatory arrest, the ascending
aorta and the proximal ductus arteriosus are tied; B. The heart is excised, leaving as much atrial tissue as possible and the inner curvature of the
recipient aorta is opened with an incision extending from the proximal transverse arch to the descending thoracic aorta, just beyond the junction
of the ductus arteriosus; C. The donor heart is implanted starting with the atrial anastomoses; D. After the aortic anastomosis is completed,
the arterial perfusion cannula is placed in the donor innominate artery and the patient is rewarmed as the pulmonary artery anastomosis is
completed. Courtesy: Reproduced with permission from Baue AE, Geha AS, Hammond GL, Laks H, Naunheim KS. Glenns Thoracic and
Cardiovascular Surgery. Norwalk, CT: Appleton and Lange; 1991
shown an increasing use of induction therapy during the

perioperative period over the last 5 to 10 years.5,30,31 However,
there is a lack of consistency with the frequency of induction
treatment and the specific agents used. Most centers use a
combination of a calcineurin inhibitor, cell-cycle inhibitor,
and corticosteroid according to a 2011 ISHLT report.7 After
one year of immunosuppression, tacrolimus is used in 66
percent of patients, mycophenolate mofetil in 69 percent and
prednisone in 66 percent. Use of cyclosporine, azathioprine,
and a mammalian target of rapamycin (mTOR) inhibitor is
variable. The ISHLT report also shows over a four-year period
in a cohort of 984 patients, cyclosporine use decreased from
40 to 26 percent and tacrolimus use increased from 47 to 54
percent.
Rejection Surveillance
A key issue in pediatric heart transplantation, as with any
solid organ transplant, is the prevention of antibody-mediated
rejection (AMR). There have been numerous reports of AMR
in the adult heart transplantation population, but surveillance
in pediatric patients has been limited and much less routine.
Adult studies have shown a higher incidence of hemodynamic
compromise at the time of AMR32-34 and a significantly higher
incidence of cardiac allograft vasculopathy (CAV).33 A recent
report by Everitt et al. compared outcomes of pediatric OHT
recipients with and without AMR.35 In 1,406 patients with at
least one endomyocardial biopsy, AMR severity was assigned
retrospectively using the proposed 2011 ISHLT grading system
for pathologic AMR (pAMR). Outcome comparisons were
made between patients with histologic and immunopathologic
evidence for AMR (pAMR 2), those with severe AMR (pAMR
3) and those without evidence of AMR (pAMR 0) or without
both histologic and immunopathologic findings (pAMR 1).
Biopsy findings of AMR (pAMR 2 or higher) are common after
pediatric OHT. The results reported by Everitt et al suggest that
pAMR 3 is associated with worse outcomes.35 Biopsy grading
of AMR seems important to delineate those at risk of adverse
events. Surveillance for pAMR using a uniform grading system
as proposed by the ISHLT is an important next step to further
validate these findings in the pediatric OHT population.
Cardiac Allograft Vasculopathy

Cardiac allograft vasculopathy is one of the primary causes
of graft failure in pediatric OHT recipients. Risk factors for
development of CAV in adult OHT recipients include older
donor age, male sex and hypertension, but there is limited
data regarding CAV in pediatric OHT recipients. According
to ISHLT registry data, 60 percent of pediatric patients are
free of CAV at 11 years post-OHT, but graft survival is 48
percent five years after diagnosis of CAV.7 Detection of CAV
can be difficult in pediatric patients, due in part to its variety
of presentations. Coronary angiography is the current gold
standard for detecting CAV, but can be technically challenging
in children less than 10 kg. The Stanford classification used in
CAV describe vessel lesions in terms of appearance astype
A, discrete or with focal stenosis; type B, lesions with abrupt
changes in vessel caliber; and type C, lesions with diffuse
irregular changes and loss of smaller vessels. The ISHLT
has suggested instead a grading system that emphasizes the
percentage of stenosis seen in the left main coronary artery,
1077
General Issues
13
two or more primary vessels, or branch stenosis.36 How well

this grading system will apply to the pediatric population is
yet to be determined. Some recent studies by Brouard et al
have shown promise using gene expression in the search for a
biomarker for early detection of CAV and rejection.37-39
Morbidity and Complications

Cardiac allograft vasculopathy is of uncertain etiology, but
results in decreased graft survival times. The most likely
etiology is immunologic damage with resulting infiltration of
the coronary endothelium and concentric intimal proliferation
of smooth muscle cells and consequent luminal narrowing.40
Diagnosis may be confirmed by intravascular ultrasound.
Treatment consists of immunosuppression, ACEI, and 3hydroxy-3-methylglutaryl (HMG) coreductase inhibitors.
Percutaneous coronary intervention (PCI) with dobutamine
stress echocardiography (DSE) has a limited role. The only
definitive treatment is retransplantation. Fortunately, longer
graft survival times have a linear decrease in freedom from
CAV. At 8 years after transplant, 78 percent of infants and 75
percent of 1 to 10-year-old at the time of transplant were free
of CAV compared with only 55 percent of patients if over 11
years old at the time of transplant. At 11 years after transplant,
60 percent of pediatric patients are free of CAV.7
Rejection during the first year after transplant is associated
with a 6 percent decreased survival at 5 years. Patients taking
tacrolimus rather than cyclosporine had fewer rejection episodes
in the first year after transplant (27% versus 42%) according to
the ISHLT registry.7 Surveillance for rejection varies, but in
general, an endomyocardial biopsy is recommended for 6 to
12 months after transplant in adolescents. In younger children,
echocardiography is more often used as a screening tool to reduce
the frequency of endomyocardial biopsy (EMB).41 If clinical
assessment or echocardiography warrants, additional biopsies
may be performed and acute rejection treated. Treatment
regimens may include methylprednisolone, plasmapheresis
and lymphocytic agents as well as supportive care including
continuous venovenous hemodialysis (CVVHD), mechanical
cardiac support, or mechanical ventilation.24
Morbidity after OHT also includes renal failure (10%
at 11 years) and malignancy (almost all lymphoma, 15%
at 13 years).7 Half of patients with renal dysfunction may
require dialysis. Standard treatment for post transplant
lymphoproliferative disease, usually caused by Epstein-Barr
virus (EBV), is to reduce immunosuppressive regimens and
aggressively treat EBV.
Neurodevelopmental
1078
In OHT for under 6-year-old in one series, survivors at 19

months follow-up had frequent low weight (28%), height
(31%) and delay in language (41%) and motor (52%) skills. A
diagnosis of CHD was associated with death-disability-mental

delay on multiple regression analysis (or 7.94, P < 0.05 for CI
1.6 to 39.4).42 In the ISHLT registry, approximately 3 to 4
percent of infants and children ages 0 to 10-year-old required
total assistance 1 year after transplant. Only 0.4 percent in
the 11 to 17-year-old group required total assistance at 1-year
follow-up.7
Results and Outcomes

Survival for pediatric heart transplant recipients has increased
in each decade since 1982. Younger patients receiving OHT
have longer median survival18.4 years for infants, 16.4
years for 1 to 10-year-old and 12.0 years for adolescents.
If, however, the patient was alive at 1-year post-transplant,
median survival was < 20 years for infants, 19.3 years for 1
to 10-year-old and 16.0 years for adolescents. The survival
differences over time are statistically different in comparing
2005-June of 2009 versus 19951999, but not compared with
2000 to 2004. In general, CM patients have better outcomes
compared with patients with CHD or patients who undergo
retransplant. The difference between CM and CHD recipients
age 1 to 17-year-old, however, between 1996 and 2009 in the
ISHLT registry, was due to a higher early mortality (< 1 year)
among CHD patients. The survival curves of CM patients
versus retransplant patients (p < 0.0001) and CHD patients
versus retransplant patients (p = 0.017) diverges on long-term
follow-up among children 1 to 10 years old. In adolescents
who survive the first year after retransplant, their survival
curve parallels CHD and CM primary transplants; (Figures
5 and 6). In the first 30 days after transplant, primary failure,
graft failure, multiple system organ failure (MSOF), nonCMV infection, stroke and acute rejection accounted for < 80
percent of all-cause mortality. After one year, cardiac allograft
vaculopathy and secondary graft failure make the most
significant contributions to mortality.7 Recent data would
suggest that for centers that perform less than 10 transplants
per year, recipients are at increased risk of 1-year and 15-year
mortality.7
Since the initial success in 1985, there have been
continuous advances and improvements in the field of
pediatric heart transplantation. Current 5 year and 10 year
survival for pediatric heart recipients rival those of adult heart
transplantation. Retransplantation continues to have reduced
survival outcomes, but results have steadily improved.
Creative reconstructive techniques have allowed successful
heart tranplants in even the most complex congenital heart
disease patients. Donor shortage has prompted investigation
into ABO incompatible transplants in neonates with promising
short-term results. Future advances in immunosuppressive
therapy will be needed to allow even longer graft survival
free of transplant coronary vasculopathy in these younger
patients.
76
Figure 5: Kaplan-Meier survival by diagnosis for patients aged 1 to 10 years for transplants from January 1996 through June 2009.
Courtesy: From Kirk, et al. J Heart Lung Transplant. 2011;30:1095-1103
Figure 6: Kaplan-Meier survival by diagnosis for patients aged 11 to 17 years for transplants from January 1996 through June 2009.
Courtesy: From Kirk, et al. J Heart Lung Transplant, 2011;30:1095-1103
Pediatric Lung Transplantation

James Hardy performed the first human lung transplant at the
University of Mississippi in 1963 for an isolated lung cancer
in a patient with chronic anemia, mild renal dysfunction and
diminished functional status. Using azathioprine, prednisone,
and cobalt irradiation as immunosuppression, the patient lived
for 18 days with adequate lung function (oxygen saturation
of 98%), but succumbed to renal failure and pneumonia. No
allograft rejection was seen on the pathology exam. Over
the next 20 years, more than 40 attempts were made at lung
transplantation with dismal outcomes (most died within
2 weeks). Many died of airway problems due to inhibition
of healing from excessively high steroid doses. With the
availability of cyclosporine A in 1983, Joel Cooper performed

the first long-term successful lung transplant (8-year
survival in a 58-year-old hardware executive with idiopathic
pulmonary fibrosis [IPF]) on an immunosuppressive regimen
consisting of azathioprine, cyclosporine and reduced levels
of prednisone.43 In 1987, the first reported pediatric lung
transplant occurred in Toronto in a 16-year-old male with
pulmonary fibrosis.44 Since that time, 1,664 pediatric lung
transplant procedures have been reported between 1986 and
June of 2010. In 2009, 49 centers reported pediatric lung
transplant procedures, from approximately 30 centers between
1998 and 2003. Of the 49 reporting centers, 84 percent did
less than five procedures annually, but this accounted for
50 percent of lung transplants. The three highest-volume
centers reported 10 to 19 procedures annually, accounting
1079
General Issues
13
for 28 percent of pediatric lung transplants. Pediatric lung

transplants performed annually has increased steadily from
72 transplants in 2001 to 127 in 2009. Most recipients (70%
in the 1996 to 2010 era) were 12 to 17 years old. Of note, only
three lung transplants were reported in infants (< 1 year) in
each of 2008 and 2009.45
Indications for Lung Transplantation

Irreversible pulmonary vascular conditions or end-stage
lung disease, for which optimal medical treatment has
failed, comprise the primary indications for lung transplant
in children. In the pediatric population, the most common
indication for lung transplantation is cystic fibrosis (CF). In
children 5 years and younger, the most common diagnosis in
the ISHLT database from 1990 to June 2010 were idiopathic
pulmonary hypertension, IPF, CHD and surfactant protein B
deficiency. Other indications reported for lung transplant in
children (Table 2) include retransplant (for both obliterative
bronchiolitis and nonobliterative bronchiolitis), interstitial
pneumonitis, Eisenmenger syndrome, chronic obstructive
pulmonary disease (COPD)/emphysema, bronchopulmonary
dysplasia and bronchiectasis.45
Lung transplant candidates should have a clear diagnosis
with a predicted natural history of death without transplant,
adequate family support, access to a transplant facility, access
to medications, and a willingness to comply with a lifetime of

follow-up.46,47 Referral to a pediatric transplant center should
occur as early as possible to allow the child and family to
develop a working relationship that will last for several years.
Obviously, listing for transplant should take place when life
expectancy without transplant is longer than the expected time
on the waiting list.47 For children 12 years and over, a UNOS
allocation score is calculated once the child is listed. For
children < 12 years-old, donor lungs are allocated based on time
accrued on the waiting list.46 Transplantation should occur once
life expectancy without transplant is predictably less than with
transplant. Ultimately, the decision for listing rests with local
expertise at transplant centers. Inevitably, variability in practice
is common. Most importantly, the goal of lung transplant is to
increase survival. Clearly, patients with CF, IPF, and primary
pulmonary hypertension have increased survival. Conversely,
no significant survival advantage has been found in patients
undergoing lung transplantation for emphysema.47
Indications for Pediatric Lung Transplantation

Patients with suspected surfactant protein B deficiency
should be referred for lung transplantation immediately.
Genetic analysis, bronchial washings, or lung biopsy confirms
the diagnosis. Extracorporeal membrane oxygenation
(ECMO), cerebral hemorrhage, or a second organ failure
Table 2
Indications for pediatric lung transplantations occurring from January 1990 through June 2010
Age
1080
Diagnosis
< 1 year
No. (%)
15 years
No. (%)
611 years
No. (%)
1217 years
No. (%)
Cystic fibrosis
1(1.2)
5(4.5)
167(56.0)
775(71.7)
Idiopathic pulmonary arterial hypertension
12(14.0)
25(22.5)
30(10.1)
75(6.9)
Retransplant: obliterative bronchiolitis
7(6.3)
9(3.0)
34(3.1)
13(15.1)
8(7.2)
4(1.3)
9(0.8)
Idiopathic pulmonary fibrosis
9(10.5)
20(18.0)
13(4.4)
38(3.5)
Obliterative bronchiolitis (not retransplant)
10(9.0)
19(6.4)
45(4.2)
Retransplant (not obliterative bronchiolitis)
3(3.5)
4(3.6)
8(2.7)
27(2.5)
Interstitial pneumonitis
1(1.2)
2(1.8)
2(0.7)
Pulmonary vascular disease
8(9.3)
7(6.3)
3(1.0)
1(1.2)
5(4.5)
5(1.7)
7(0.6)
Pulmonary fibrosis, other
5(5.8)
5(4.5)
12(4.0)
22(2.0)
Surfactant protein B deficiency
15(17.4)
3(2.7)
1(0.4)
1(0.1)
COPD/emphysema
4(4.7)
2(1.8)
3(1.0)
9(0.8)
Bronchopulmonary dysplasia
2(2.3)
2(1.8)
6(2.0)
1(0.1)
Bronchiectasis
1(1.2)
0(0)
5(1.7)
13(1.2)
Other
11(12.8)
6(5.4)
12(4.0)
26(2.4)
Courtesy: With permission from Benden, et al. J Heart Lung Transp. 2011;30:1123-1132; Table 1
COPD = Chronic obstructive pulmonary disease
Contraindications
Contraindications to lung transplant include active malignancy
(with the exception of squamous and basal cell skin cancer),
other end-organ failure (unless liver, kidney, or a heart-lung
block transplant is also being considered), untreated or noncurable chronic infection (including HCV with histologic liver
disease and HIV), untreated sepsis, noncompliance (whether
willingly or because of untreatable psychiatric conditions),
absence of reliable social support, active substance addiction,
and advanced or severe neuromuscular disease.46,47 Cerebral
hemorrhage with severe developmental delay or other
untreatable, irreversible brain or other organ dysfunction also
precludes lung transplant.46
Relative contraindications include history of pleurodesis,
chronic kidney disease, markedly abnormal body mass
index (BMI), mechanical ventilation, scoliosis or spinal

deformity, poorly controlled diabetes, osteoporosis, chronic
airway infection with multiple drug resistant organisms,
fungal infection and HBV positivity.46 Burkholderia cepacia
airway colonization in CF patients has been associated with
significantly reduced outcomes (3040% increase in 1-, 3and 5-year mortality47); consequently, many centers consider
colonization with this species an absolute contraindication to
lung transplantation. However, with sensitivity testing, directed
antibiotic therapy, and reduced levels of immunosuppression,
successful transplantation with acceptable outcomes has
been attained.44 The decision of whether to proceed with
transplantation in CF patients with B. Capacia colonization is
center-specific.
Donor Selection
The ISHLT criteria for ideal lung transplantation donors
include age less than 55 years, smoking history of less than 20
pack-years, absence of chest trauma, duration of mechanical
ventilation less than 48 hours, no history of asthma or cancer,
negative Gram stain on bronchoalveolar lavage (BAL),
arterial partial pressure of oxygen greater than 300 mm Hg
on positive end-expiratory pressure (PEEP) of 5 cm H2O and
inspired oxygen 100 percent, no infiltrates on current chest
radiograph and clear bronchoscopy. Of course, very few
donors will meet all these criteria and be classified as ideal;
donors who meet most, but not all criteria are classified as
extended donors.44,48,49 Extended criteria have included age
greater than 55 years; compatible, but not identical blood
grouping; chest X-ray with a focal abnormality; PaO2 less than
300 mm Hg, smoking greater than 20 pack-years; some, but
not extensive chest trauma; prior cardiopulmonary surgery;
and some secretions in the upper airways.50,51 In most series,
results are equivocal when comparing ideal donor criteria to
extended criteria.51 When selecting a donor for a particular
recipient, lung transplant surgeons may use marginal donors
for relatively well recipients, while using ideal donor lungs
on recipients with marginal multisystem organ dysfunction.
Either extreme causes mixed outcomes. Ideally, the best lungs
in the healthiest recipients provide the best possible long-term
outcomes.
Pediatric donor organs were used in 64 percent of pediatric
lung transplant recipients from January 1986 to June 2010,
according to the ISHLT database. Only 6 percent of recipients
had lungs from donors over 50 years.45 Although living-donor
lobar transplantation enjoyed success in 39 pediatric patients
over a 10-year experience with a 45 percent 5-year survival,52
only one pediatric lung transplant from a living donor was
reported to the ISHLT registry over the last 5 years.45 In one
series, donor lobectomy had a 20 percent complication rate,
3.2 percent reoperation rate and no mortality. Complications
included pulmonary artery thrombosis and prolonged airleak
(>14 days).53 Initially, living donor lobes were given to
76
is a contraindication to transplant. Idiopathic pulmonary

hypertension patients with New York Heart Association
(NYHA) or World Health Organization (WHO) functional
class III or IV symptoms unresponsive to vasodilator therapy
should be referred for transplant. A six-minute walk test of <
350 meters, uncontrolled syncope, hemoptysis and right heart
failure are all indications to consider listing for transplant.
Treatable diagnosis that should be ruled out before transplant
include collagen vascular disease, primary lung pathology,
chronic thromboembolism and pulmonary vein obstruction
that may be surgically corrected. Lung transplantation is
indicated in Eisenmenger syndrome, when progressive
pulmonary hypertension has significantly impaired a patients
quality of life in the absence of LV failure or irreparable
congenital heart defect. If these cardiac conditions exist
concurrently, then consideration may be given to a heartlung transplant. A cardiac catheterization is necessary for
diagnostic confirmation and assessment of oxygen and
vasodilator response. Primary pulmonary vascular disorders
do not respond to medical management and referral to a
transplant center should be expedited. Cardiac catheterization
and computed tomography (CT) angiography are necessary
to evaluate PV stenosis and pulmonary veno-occlusive
disease. If alveolar capillary dysplasia is suspected, open lung
biopsy may be needed.46
Lung transplantation is indicated in CF patients, when lung
disease is progressing despite optimal medical management
and forced expiratory volume in 1 second (FEV1) has
dropped below 30 percent predicted. Referral should occur
when patients begin having frequent hospitalizations due
to hypoxemia and/or hypercapnia. Management should
include gastrointestinal and nutritional evaluation, a bone
density scan and treatment of sinus disease. In children
with bronchopulmonary dysplasia (BPD), transplant may be
necessary in those requiring extended ventilator support or
those with pulmonary hypertension unresponsive to oxygen
challenge.
1081
General Issues
13
the sickest children on the transplant wait list. With the

lung allocation scoring system (LAS), however, the sickest
patients now have the shortest wait times. A relatively high
complication rate for donor lobectomies, as well as the advent
of the LAS, have both likely contributed to the decline in
enthusiasm (and almost a disappearance within the ISHLT
database) of living lobar donors for pediatric lung transplant.
Recipient Evaluation
All recipients undergo evaluation that includes ABO group,
viral serology (HIV, HBV, HCV, cytomegalovirus {CMV},
EBV, varicella, and toxoplasma), urine and sputum cultures,
tuberculin skin testing, bone density scan, chest radiograph,
CT scan of chest, complete pulmonary function tests, 6-minute
walk test, ECG and cardiac echocardiography. Evaluation for
transplant is a coordinated effort among a multidisciplinary
group of specialized pediatric clinicians, transplant surgeons,
pulmonologists, nurse transplant coordinators, dieticians and
social workers. In addition, disease specific considerations
may involve a psychiatrist, infectious disease specialist, or
pediatric cardiologist.44
Surgical Management
General Considerations
The technical aspects of implantation do not differ significantly
whether in adults or children. At our institution, soft tissue
flaps are created under each breast, before performing a
traditional bilateral thoracotomy with sternal division at least
one-third of the sternal distance away from the inferior aspect
of the sternum. A lower division of the sternum results in
instability, patient discomfort and possibly the need for plate
reconstruction.
Lung Procurement Techniques
1082
During procurement, if the heart is being harvested for

another institution, the division of the atrial cuff should be
performed in conjunction with the heart procurement team.
Different methods of procurement have been performeden
bloc with the trachea or each lung in sequence. In either case,
care must be taken to avoid procuring too little pulmonary
vein or denuding the bronchus. An optimal technique for
lung preservation has not been clearly defined; in one model,
hyperinflation to 30 cm H2O with low oxygen concentration
(30%) had a protective role in ischemia reperfusion injury.54
In another model, hyperinflation to 20 mm Hg resulted
in acute pulmonary dysfunction.55 Many agree that some
hyperinflation, to stimulate surfactant release, coupled with
low oxygen concentration, to minimize reactive oxygen
species, provides the best prophylaxis for preventing primary
graft dysfunction (PGD).54
Living Donor Lobar Lung Transplantation

Living donor lobar lung transplantation was first performed
in 1993 at the University of Southern California and was the
result of a lack of deceased donor organs.52 A living donor
lobar lung transplant (LDLLT) requires two living donors,
each undergoing one lower lobectomy; the left lobe is
removed from one donor and the right lobe from the other.
These lobes are then implanted into the recipient in lieu of the
whole left and right lung. LDLLT is particularly well suited
for pediatric recipients for whom adults serve as donors. A
retrospective review of a prospectively collected database
reported in 2006 by Kozower et al identified 39 children
who underwent lung retransplantation from 1991 to 2001.56
Their findings showed improved 5-year survival for LDLLT
as compared to deceased donor lung transplantation. Similar
findings were reported by Sweet in a cohort of 38 pediatric
LDLLT recipients.57 Deceased donor lung transplantation
is still preferred in order to avoid the risk to two healthy
donors; however, LDLLT is still an acceptable alternative
when the recipient is not likely to survive to deceased organ
transplantation. The use of LDLLT has decreased in the US
due to changes by the Organ Procurement and Transplantation
Network (OPTN) to an urgency/benefit allocation system for
deceased donor lungs in recipients 12 years and older.58 It is
almost certain that LDLLT will continue to be used, especially
in children under 12 who do not benefit from the recent OPTN
allocation system changes.
Lung Transplantation Techniques

For bilateral lung transplantation, exposure is obtained through
a transverse thoracic sternotomy incision allowing exposure to
the heart and both hila; (Figures 7A and B). Before initiating
CPB, hilar dissection is performed, preparing the PV cuff, PA
and bronchus for division. Often, initiation of CPB is needed,
before completion of dissection (especially on the left side)
due to hemodynamic instability, while lifting the heart. Once
on bypass and meticulous hemostasis behind each hilum is
achieved, sequential implantation is performed. The bronchus
is sewn end-to-end without telescoping using a running 4-0
polydioxaone (PDS) suture. The PV and PA anastomoses are
sewn with 4-0 and 6-0 polypropylene suture, respectively. The
left atrial clamp is removed first to allow retrograde filling of
the PA, before removing the PA clamp. The implanted lung
is gently inflated and ventilated with enough tidal volume to
prevent atelectasis. If the lungs are oversized for the pediatric
recipient, lobar implantation or wedge resection may be
necessary to achieve an appropriate size match. Single lung
transplantation is rarely performed in children. One indication
may be when a child has had a previous pneumonectomy and
has significant volume loss into one side of the chest.
As mentioned above, living donor lobar transplantation
is rarely performed. When necessary, the primary technical
B
Figures 7A and B: A. Chest incision utilized for lung transplantation in
children; B. Exposure through the bilateral thoracosternotomy incision with
cannulation for bypass, aortic cross-clamping if necessary and excision of
both recipient lungs prior to implantation of each donor lung sequentially.
Courtesy: Reproduced with permission from Spray TL, Heart-lung and
lung transplantation in children. In: Glenns Thoracic and Cardiovascular
Surgery. Norwalk, CT: Appleton and Lange; 1991
difference in operative conduct is the vein anastomosis. Since

only PV (and not atrial cuff) is procured from the donor, the
implant is a vein-to-vein anastomosis rather than a large left
atrial-to-left atrial anastomosis.44
Heart-Lung Transplantation
Pediatric heart-lung transplantation is an uncommon
procedure. Only 17 procedures were performed in 2008
76
200945 with only four transplant centers reporting in 2008.

Since a peak of 46 heart-lung transplants in 1989 and 40 in
1994, the number of procedures has steadily declined. Graft
half-life has increased in each era since the first heart-lung
transplant in 1984. The half-life was 19 years from 1982 to
1988 compared with 4.7 years in the 1999 to 2008 era. The
5-year survival in the latest era (19992008) was 49 percent,
comparable with the 5-year survival after lung transplant in
children.59
The primary indications for heart-lung transplants in
children are idiopathic pulmonary arterial hypertension
(IPAH), CF and CHD.60 In North America, heart-lung
transplant is usually performed in children with uncorrectable
congenital heart defects (systemic ventricular failure) coupled
with pulmonary vascular disease.
The surgical technique requires procurement of a heartlung block, dividing high on the ascending aorta and the
trachea well above the carina. Cardioplegia and pulmoplegia
are administered as they would be for a single organ
transplant. In the recipient, a pericardiectomy is performed
from phrenic nerve to phrenic nerve. Bicaval venous drainage
cardiopulmonary bypass is initiated with an arterial cannula
high on the ascending aorta. The heart is explanted, dividing
the aorta and PA just above the valves and the atria at the
atrioventricular groove. Care should be taken throughout
the dissection to protect the phrenic and vagus nerves on
each side as well as the recurrent laryngeal nerve around the
ligamentum. The bronchi and right and left PAs are divided
at the hilum. The PVs are separated from the inside of the
open LA, divided, and the lungs are then separately explanted.
The trachea is transected just above the carina and the PAs
and bronchial remnants now in discontinuity are removed.
The heart-lung block is then placed in the recipient chest,
placing both hila beneath the phrenic nerves; (Figures 8A
and B). The tracheal anastomosis is performed first, end-toend with two running 4-0 PDS sutures, one membranous and
one cartilaginous. The RA is then opened on the graft and
anastomosed to the recipient right atrial cuff. Finally, the aortic
anastomosis is performed and the cross-clamp is removed.24
Intense perioperative critical care is essential for optimal
outcomes in lung transplantation. At our institution, epidurals
are usually placed within four hours of admission to the
ICU. In the absence of PGD, patients are extubated within
12 hours. We attempt to have all patients ambulating on the
first post operative day. Daily bronchoscopies are performed
when needed for copious pulmonary secretions or infiltrates
on chest roentography. Diligent care must be taken to identify
early signs of graft dysfunction. Ischemia reperfusion injury
to alveoli results in lung edema and hypoxemia in the first
72 hours post-transplant and may or may not progress to
PGD.61 Alveoli damage occurs as a result of hypoxemia,
1083
General Issues
13
Figures 8A and B: Heart-lung transplantation: A. The recipient cardiectomy and bilateral pneumonectomies have been performed with the patient
on cardiopulmonary bypass. Phrenic nerve pedicles are fashioned and present in each pleural cavity. Dissection around the trachea is limited;
B. The completed procedure shows anastomoses of the trachea, right atrium and aorta. Coutesy: Reproduced with permission from Franco KL, Lung
transplantation for pulmonary hypertension. In: Franco KL, (Ed). Pediatric Cardiopulmonary Transplantation. Armonk, NY: Futura Publishing Company,
Inc; 1997
surfactant inactivation (decreased compliance), and capillary

permeability.54,61 Lung ischemia reperfusion injury risk is
decreased by careful preservation during procurement, as
discussed above. Clinically, PGD in a freshly transplanted
lung is graded on a scale of 0-3. Dysfunction with a PaO2 to
FIO2 ratio < 300 mm Hg and no infiltrate on chest radiograph
is defined as grade 0. Characteristics of worsening dysfunction
include radiographic infiltrates consistent with pulmonary
edema, PaO2 to FiO2 ratio of < 300 (grade 1), 200 to 300
(grade 2) and < 200 (grade 3).62 PGD is a risk factor for later
development of bronchiolitis obliterans syndrome (BOS) and
decreased survival for patients who survive to 1 year. Early
ECMO may be life-saving; in any case, treatment (mechanical
ventilation, prostaglandin E1, nitric oxide, or pharmacologic
intervention) is entirely supportive.44
Morbidity and Complications
1084
Complications in lung transplant recipients can be devastating.

Diligent postoperative care is imperative for a successful
outcome and achieving years of optimal graft function. The
most devastating surgical complication is an airway dehiscence

or stenosis. Bronchial stenosis presents with wheezing or an
obstructive pattern on a flow-volume loop.46 At our institution,
stenoses are treated with balloon dilation and, occasionally, laser
ablation of fibrous tissue at the anastomotic site. Dehiscence
may require lobectomy or pneumonectomy, but stents should
be avoided due to excessive ingrowth of granulation tissue.
Other surgical complications may include phrenic or vagal
nerve injury, chylothorax, or wound infection.44
Immediate, non-technical, perioperative complications
include hyperacute rejection and ischemia reperfusion
injury (which may be mild or lead to any degree of PGD).
Hyperacute rejection occurs from complement-mediated graft
injury secondary to preformed recipient antibodies. Elevated
PRA indicate an elevated risk for hyperacute rejection and
may influence the decision to transplant. For patients with
elevated PRA, a virtual crossmatch should be done, before
transplant followed by an actual crossmatch at the time of
surgery using donor leukocytes. Treatment for a positive
crossmatch includes early plasmapheresis, thymoglobulin and
intravenous immunoglobulins.44,63
Immunosuppression
At most lung transplant centers, the most common immunosuppressive regimen consists of tacrolimus, mycophenolate
mofetil (MMF) and prednisone. Even at 5-year follow-up, 100
percent of patients remain on prednisone therapy. Although no
significant difference exists between recipients who do and do
not receive induction therapy, 60 percent of recipients between
January 2001 and June 2010 received one of anti-lymphocyte
globulin, anti-thymocyte globulin, or interleukin-2 receptor
antagonist therapy. In the previous decade, less than 50
percent of recipients had received induction therapy.45
Since larger doses of steroids and higher levels of tacrolimus
are usually needed for lung grafts compared with heart grafts,
postoperative immunosuppression regimens for heart-lung
patients generally follow the institutional preferences for
management of lung transplant patients.
Results and Outcomes

The survival rate following lung transplantation in children
is similar to that of adult recipients. The ISHLT database
reported 1-year survival of 83 percent and 4-year survival of
50 percent in children transplanted between 2002 and 2007.60
From January 1990 to June 2009, the half-life of transplanted
lungs was 5.5 years (51% 5-year survival). In the most recent
era (2002 to June 2009), 5-year survival was 53 percent.
Among the different age groups, the half-life of graft survival
was 6.4 years for infants (< 1 year), 7.3 years for 1 to 11-yearold, and 4.6 years for 12 to 17-year-old. Infection (non-CMV)
and graft failure are the two primary causes of death in the first
year after transplant. After the first year post-transplantation,
BOS (< 40% of causes of death 1-3 years, 3-5 years, and <
5 years after transplant), graft failure (1325%), and non-
CMV infection (1320%) were the leading causes of death.45

According to an ISHLT database report, hypertension (68%
at 5 years), kidney injury (20%), diabetes mellitus (34%) and
BOS (36%) are the most common comorbidities following
lung transplantation in children. For children who survive to 5
years, 86 percent report no limitation in activities.
Since the initial case in 1987, the field of pediatric lung
transplantation has continued to evolve with significant progress
and advancements. Long-term success will be achieved as
laboratory research elucidates how to prevent acute rejection
and BOS. Perhaps the most exciting future developments will
revolve around exvivo lung perfusion. Exvivo lung perfusion
promises to provide patients, families, and surgeons the
opportunity to have elective, scheduled transplantation with
optimally matched lungs. Until widely available, however,
most pediatric lung transplant centers will continue to strive
for increased long-term survival and decreased morbidity with
diligent patient selection and perioperative care.
There are few people who have not benefited in some way,
either directly or indirectly, from advances made in surgical
research.
Peter Bell, 1938
76
Complications occurring after the first 72 hours posttransplant are broadly categorized as early (< 90 days) or late (>
90 days). Acute rejection (cellular, T-cell mediated) is not timelimited, but occurs more commonly in the first three months
after transplant. Patients may present with chills, malaise,
chest tightness, cough, or dyspnea. If daily home spirometry
is used, a 10 percent drop in FEV1 may indicate a rejection
episode. However, diagnosis is only made by the presence
of perivascular and interstitial mononuclear cell infiltrates.64
Treatment usually only requires methylprednisolone for
three days followed by an oral prednisone taper; however,
adjuvant treatment with immunoglobulin or plasmapheresis
may be necessary. Infectious complications due to
immunosuppression are also a common cause of morbidity.
Common infectious organisms in lung transplant patients
include Pseudomonas species, adenovirus, rhinovirus,
respiratory syncytial virus, parainfluenza virus, CMV (treated
prophylactically in many centers) and fungal organisms (also
often treated prophylactically).44
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International Society for Heart Transplantation. [Comparative
Study]. 2000;19:1199-204.
50. Pego-Fernandes PM, Samano MN, Fiorelli AI, et al.
Recommendations for the use of extended criteria donors in
lung transplantation. Transplant Proc. 2011;43:216-9.
51. Schiavon M, Falcoz PE, Santelmo N, et al. Does the use of
extended criteria donors influence early and long-term results
of lung transplantation? Interact Cardiovasc Thorac Surg.
2012;14:183-7.
52. Starnes VA, Bowdish ME, Woo MS, et al. A decade of living
lobar lung transplantation: recipient outcomes. J Thorac
Cardiovasc Surg. [Comparative Study Research Support, NonU.S. Govt]. 2004;127:114-22.
53. Bowdish ME, Barr ML, Schenkel FA, et al. A decade of living
lobar lung transplantation: perioperative complications after
1087
Epilogue
We can say with some assurance that although children may be victims of fate, they will not be the victims of our neglect.
John F Kennedy
Circa 1963
According to the Oxford English Dictionary, the meaning of Epilogue is the concluding part of a literary work, or a speech
or short poem addressed to the spectators by one of the actors after the play is over. As the Editor-in-chief of this book
entitled, A Comprehensive Approach to Congenital Heart Diseases, it is my honorable privilege to write the conclusion
for this mammoth effort by all our esteemed authors, with their globally-enriched experiences, and especially from my
co-editors, Dr P Syamasundar Rao and Dr Reema Chugh.
In his foreword, Dr Joseph K Perloff eloquently wrote that, An attractive feature of this book is the seamless continuity
from embryo, to neonate, child, adolescent, and adult. This is true indeed! This book has the whole gamut of congenital
heart diseases described from womb to tomb as a lifelong journey. However, our legendary Dr Padmavati who kindly
wrote the prologue felt quite strongly that it was inappropriate to use the word Tomb. We therefore christened this book
and called it, A Lifelong Journey, as rightly suggested by my good friend Dr Reema Chugh.
I was practicing cardiology only in adults until my late 40s. It then dawned on me that serving to save a child from the
jaws of death can be both satisfying and gratifying. Children are unique and special creations of God, worth far more than
any earthly treasure! They need specialized care when they are born with disabling heart diseases. Heart care in children
requires a highly skilled team of care providers including dedicated pediatric cardiologists and cardiac surgeons, with
appropriate equipment and technology to improve their precious lives. The smile on the face of a sick child is worth far
more than millions!
I have since then worked with the zeal of a missionary to help thousands of poor children with congenital heart disease
(CHD) in India. The technique of trans-catheter device closures has come as a boon to the children with holes in their hearts.
One of my earlier patients, among those undergoing device closures for an atrial septal defect, wrote to me before joining
the medical school, God has devotees, but great people have followers and I am following you! We cannot be Gods, but
surely we can give better quality of life to these special children if we learn the right methods of diagnosis and management.
Nothing in the world can be more satisfying than giving the best possible life to a child. This book not only emphasizes on
accurate clinical diagnosis but also on appropriate medical, surgical and supportive management for each condition.
Interventions like aortic balloon valvuloplasty performed in neonates with hydrops fetalis can be like a miraculous
escape from death. Though innovations in technology that allow excellence in medical diagnosis/management, as well
as heroic measures such as interventional/surgical corrections for complex congenital CHD are fascinating, at times care
providers feel helpless because of their limitations in certain cases. Dealing with a dying child or an adult who is in a
critical condition due to CHD can be an extremely heart-breaking and stressful situation for the family and health care
providers. Complete care of these patients and their families requires extensive management of clinical, social, financial
and philosophical issues. Therefore, focus on treatment preferences, palliative care, and end-of-life issues are also crucial.
Each medical facility should have a dedicated clinical social worker and palliative care team to help patients and their
families through this painful journey.
Sometimes we are humbled by severe life-threatening complications such as bacterial endocarditis that can cause high
morbidity and mortality in those born with simple lesions such as a ventricular septal defect or a bicuspid aortic valve or mitral
valve prolapse. In the last but not the least important Section 13, entitled General Issues, there are chapters on the importance
of oral hygiene, bacterial endocarditis, anesthesia, postoperative care, and the possibilities of heart and lung transplantation
to address some of these issues.
Congenital cardiac malformations have a global prevalence. As mentioned previously in this book, the last seventy
years have witnessed spectacular advances in the treatment of CHDs with palliation as well as amazing repairs of a number
of malformations, from simple to complex CHD. All those who are born with CHD need long-term follow-up and care
through all the stages of life, with attention to specific issues and the complexities arising from the impact of pregnancy
and acquired diseases, thus making care of CHD a lifelong journey.
We truly hope that this book will give a comprehensive insight into CHD to all our readers and go a long way in improving
the lives of children and adults with CHD.
IB Vijayalakshmi
Index
Page numbers followed by f refer to figure and t refer to table, respectively.
A
Abdominal
aorta149f
jugular reflux 784
situs 46, 53
wall defects 44
Aberrant
left subclavian artery 528, 530f
right subclavian artery 507, 530
subclavian artery 519
Ablation of arrhythmias in children 871
Abnormal
cardiac screen 44
cellular death 25
flow during bilocular stage of heart
tube604
intracardiac blood flow 25
migration of
cardiac neural crest cells 604
ectomesenchymal tissue25
mitral arcade 445
numbers of pulmonary veins 224
origin of right subclavian artery 13f
renal clearance of urate 776
sinus node function 839
targeted growth 25
Abnormalities of cardiac looping 4
Abortion 801, 803
Absence of
atrioventricular connection 649
ductus venosus 44, 221
Absent pulmonary valve
syndrome 65, 441, 541
with ventricular septal defect 442
without ventricular septal defect 442
Abstein anomaly 426
Abstinence 801, 803
Accessory mitral
orifice449
valve tissue/orifice 380, 445
Acquired immunodeficiency syndrome 901
Actinobacillus actinomycetemcomitans 980,
996
Activated partial thromboplastin level 796
Acute
alcoholic hepatitis 181
myocardial infarction 865
pericarditis/myocarditis865
Acyanotic congenital heart disease 166, 167t,
937
classification of 167t
Adenosine797
Adult
Congenital Heart
Association748, 752
disease 751, 752, 787, 830
TOF550
Advanced cardiac life support 798
Advantages of
ductal stenting 93
pulmonary balloon valvuloplasty 555
AGA medical corporation 262f
Agenesis of ductus venosus 65
Aggregatibacter actinomycetemcomitans 980
Airway pressure 934f
Alagille syndrome 103, 184, 362, 435
Aldosterone antagonists 691
Allocation scoring system 1082
Allopurinol1051
Alveolar hypoventilation 918f
disorders934
Alzheimer disease 963
Ambulatory Holter and event recording 814
American Academy of Pediatrics 1022
American College of Cardiology 748, 793
American Heart Association 685, 748, 981,
983t, 1005
Amniocentesis111
Amplatzer
devices 319, 678f
duct occluder 319, 320, 325, 342
device into aorta 323f
in place914f
muscular ventricular septal defect
occluder890f
plug device 320
septal occluder device 262f
Anatomic
classification of cor triatriatum 381
pathways for CCTGA with associated
defects633t
Anatomical configuration of cardiovascular
system148
Anatomy of
fetal circulation 17
pulmonary circulation 568
Ancillary tests 1005
Andersons system 645
Anesthesia
on cardiopulmonary bypass and changes in
pharmacokinetics1038
induction and maintenance of 1032
Aneurysm of sinus of Valsalva 338, 347, 348,
348f, 350f, 351f, 352
Aneurysmal dilatation and vessel wall

edema92
Angiogram
in LPA in levophase left pulmonary
veins236f
of left subclavian artery 556f
Angiosarcoma896
Angiotensin
converting enzyme 278, 452, 480, 631, 690,
777, 794, 795, 953
receptor blockers 691
Angled Amplatzer duct occluder 320
Annular Doppler tissue velocity 688
Anomalies of
ductus venosus 213, 221
inferior vena cava 213, 218
leaflets385
papillary muscles 387
pulmonary veins 224
superior vena cava 213
systemic veins 213
tension apparatus 387
vena cavae 15
Anomalous
connection of
left pulmonary veins 226f
right pulmonary veins 226f
left coronary artery from pulmonary
artery 739, 881
left main coronary artery 816
mitral arcade 380
origin of left coronary artery from pulmonary
artery445
pulmonary venous connection 235f
to venous atrium, partial 146
to venous atrium, total 146
pulmonary venous return 57f
right coronary artery from pulmonary
artery886
Anomalously draining scimitar vein 227f
Anterior
cardinal vein 7f
mitral leaflet 368f, 384f
papillary muscle 127, 698f
Antibiotic prophylaxis 162
for prevention of infective endocarditis in
CHD, recommendations for 1001t
Antidromic
atrioventricular reentry tachycardia 848
reciprocating tachycardia 1064
Antiepileptic drugs 26
Anti-fibrinolytic tranexamic acid 805
1092
Antimicrobial therapy 1000

Anuria92
Aorta228f, 234f, 536f, 566, 573f, 595f, 596f,
686f
abdominal149f
right atrial tunnel 342
Aortic
angio in left lateral 322f
annulus469
arch 11, 52f, 62, 606
anomalies11, 208
coronary sinus235f
derivatives10
balloon valvuloplasty 999f
component of second heart sound 180f
dissection in marfan syndrome, risk factors
for954t
dissections947
hypoplasia366
regurgitation 172, 272, 348f, 482f, 488-490,
489t, 1008
root 469, 469f
and aortic valve aredirectly manipulated
475
and conduction system 474
and left ventricular outflow tract 472
and membranous septum 472
angio in left anterior oblique 342, 377f,
574f
angiogram in left lateral 282f
dilatation489
in Marfan syndrome, assessment of 951f
relationship of472
stenosis 45, 101, 170, 172, 180f, 179, 474t,
482f, 488, 494, 499, 1008
valve373f, 468-470, 484-486, 686f, 932f
diseases468
disorders60
histological aspect of 471
prolapse in ventricular septal defect 489
regurgitation820
repair in aortic valve prolapse 494
repair techniques496f
replacement496
structure of470
Aorticocameral tunnels 337
Aortoatrial tunnels 342
Aorto-left ventricular tunnel 337
Aortopulmonary
collateral362
arteries565
window 204, 315, 332, 334f , 335f
Aorto-right
atrial tunnel 343f
ventricular tunnel 337
Aortoventricular tunnel 337
Apical
four-chamber585f
view234f
trabecular component 282f
Apnea92
Apoptosis25
Appearance of anterior leaflet of mitral
valve698f
Applying hyperoxia test 90
Arginine vasopressin 20
Array comparative genomic hybridization 107
Arrhythmia 63, 92, 416, 426, 616, 658, 764, 767,
794, 819, 820, 823, 1064
Arrhythmogenic right ventricular
cardiomyopathy 817, 865
dysplasia856
Arterial
blood gas 90, 246, 926
desaturation400
Doppler 66, 68
partial pressure of
carbondioxide90
oxygen90
pulse 173, 271, 312, 910
switch
operation 621, 622, 765
repair790
system defects 12
valves128
Arteriosus with severe pulmonary hypertension
200f
Arteriovenous malformation 44, 65
Ascending
aorta51f, 204f, 519, 520f, 527f,
532f, 536f
bifurcating into right aortic arch 536f
aortic systolic pressure 729f
azygos vein beside descending aorta 151f
thoracic aorta 229f
Asplenia syndrome 145
Assisted reproductive technology 34
Asymmetric septal hypertrophy 726
Asymptomatic aortic stenosis 488t
Atresia21
of common pulmonary vein 240
Atretic
mitral valve 463f
tricuspid valve 650f
Atria 130, 152t, 458
Atrial
arrhythmias 255, 754, 762, 820, 851, 866, 911
ectopic tachycardia 74f
fibrillation 820, 873
flutter 72, 873
premature contraction 854f
re-entrant tachycardias 873
rhythm72f
septal
aneurysm752
defect 57, 100, 150, 170172, 180f, 206f,
226, 244, 253, 266, 267, 398f, 415, 461f,
475, 520, 548, 562, 640, 753, 787, 819,
848, 908, 909, 911, 913f, 965, 973, 1005,
1008, 1009
defect with pulmonary arterial
hypertension195f
septation98f
septostomy941
septum 152, 459
situs 137, 147
switch
operation622
repair 763, 790, 822
tachycardia873
Atriopulmonary connection 792

Atrioventricular76f
block841
canal defect 151, 184, 267
connection 150, 649
discordance822
junction 131, 645f
nodal
reciprocating tachycardia849f
re-entry tachycardia74f, 1064
node125
reciprocating tachycardia 849f
re-entry tachycardia 427
relationship74f
septal defect 45, 99, 151, 214, 292, 633, 788
valve 126, 131, 150, 458, 641f
regurgitation, mechanism of 303
Attention deficit hyperactivity disorder 103,
833
Atypical atrial flutter 764, 768
Augmented vector foot 256f
Auscultation 176, 185, 271, 312, 436, 440, 455,
910, 965
Automatic implantable cardiac
defibrillator 799, 818
Autonomic dysfunction 724
Autopsy specimen of coarctation of aorta 520f
AV discordance 872
Axial skeleton 155
B
Bacterial endocarditis 488, 493
Balloon
angioplasty 363, 512
treatment of neonatal coarctation of
aorta and childhood recoarctation of
aorta513f
aortic valvuloplasty 487f, 679
atrial septostomy 407
dilatation494
of aortic valve 494
mitral-valvotomy with inoue-balloon 914f
occlusion to facilitate delineation of coronary
to pulmonary artery supply 574f
pulmonary valvuloplasty 358
valvuloplasty 438, 440
of aortic valve 64
Barium
esophagogram 533, 538
meal156f
Barrier
contraceptives802
methods801
Baseline electrocardiogram 358
Bat-wing appearance 194, 196f
Becker sign 490t
Beginning of ventricular ejection 70f
Benefits of exercise 812
Benign
cardiac tumors 896
tumor901
Bernoulli equation, modified 403
Biatrial enlargement 714f
Bicaval cardiopulmonary bypass 1075
Brugada syndrome 818f, 863, 864t, 865

BT shunt, modified 558
Bulboventricular foramen 650
Bundle of Kent 848
Burkholderia cepacia 1081
Bypass tube 509
C
Calcium channel blockers 730, 798, 939
Calculation of
isovolumic relaxation time 715f
pressure gradient 484
Caliber of central pulmonary artery 566
Cardiac
allograft vasculopathy 1077
amyloidosis718
arrest1065
catheterization 230, 230f, 235, 238, 240,
258, 334, 361, 369, 392, 404, 421, 430, 437,
551, 529, 716, 818, 884, 926, 953
and angiography 302, 535, 538, 563,
585, 586, 6642, 671
and cineangiography277
for pre-Fontan evaluation 655
mandatory before fontan 656
computed tomography 642
cushions98f
disease90
diverticulum63
function 66, 69
grid for common congenital heart
diseases1008t
magnetic resonance imaging 572, 629, 688,
728, 903, 1009
malposition 136, 146
myxomas896
position and axis, variations in 50t
resynchronization therapy 875, 1013
resynchronization therapy, indications
for692t
silhouette 190, 196
tamponade1065
transplantation677
troponin mutations 722
valves causing valvular regurgitation 718
Cardiectomy and bilateral
pneumonectomies1084f
Cardinal veins 213f
Cardiobacterium hominis 980, 996, 998
Cardiophrenic angles 201
Cardiopulmonary
bypass 1009, 1022, 1038, 1046
on brain, effects of 1044
exercise testing 815
manifestations in heterotaxy syndrome 153
Cardiothoracic ratio 190, 193, 422
Cardiovascular
assessment in Marfan syndrome 949, 950t
magnetic resonance imaging 228
manifestations of Marfan syndrome 951t
profile score 69t
system 148, 1010
Care in people with congenital heart disease,
recommendations for 835
Carotid stenosis 181
Carpenters syndrome 172

Carvallos sign 910
Cat eye syndrome 101
Catecholamine-induced ventricular
tachycardia861
Catheter
directed cardiac angiography 203
intervention 159, 317, 359, 661, 671
occlusion of coronary artery fistula 890f
Cause valvular dysfunction 65
Causes of
Aortic
regurgitation488t
stenosis476t
congestive heart failure 167t
dilated cardiomyopathy 686
fetal congestive heart failure 65
left ventricular outflow tract obstruction in
AVSD301
right ventricular failure in tetralogy of
Fallot550
vascular compression of airways 540
Cavopulmonary connection 159
Celermajer index 420f, 422
Celiac mesenteric stenosis 181
Central
cyanosis554
interposition tube graft 557
nervous system 155, 173, 243, 772, 1023
monitoring1030
position of aortic root 475
pulmonary arteries 188f
venous pressure 586, 1012
Cephalocaudal section of embryo 3f
Cerebral arterial thrombosis 772
Cerebrovascular disease 801
Cervical arch 531
Cesarean delivery 799
Chagas disease 686
Chaotic atrial tachycardia 74f
Charge syndrome 184, 1005
CHDs with duct dependent circulation,
classification of 87t
Chemotherapy27
Chest
pain168
retractions169
roentgenogram 137, 401
Child with
Ellis-Van creveld syndrome 105f
Holt-Oram syndrome 105f
Marfan syndrome 551f
partial atrioventricular septal defect trileaflet
left atrioventricular valve 300f
Children with williams syndrome 103f
Chlorhexidine mouthwash 989, 989f
Chordae tendinae 9f, 389
abnormalities of 448
Chorionic villi sampling 111
Chromosomal
aberration99
anomaly44
Chromosome deletion syndrome 101
Chronic
constrictive pericarditis 722
hypoxia934f
index
Bicuspid aortic valve 150, 366, 468, 477t, 478f,

483f, 488, 510f, 755t, 759, 788, 947
classification of 478f
Bidirectional
Glenn procedure 676
shunt771
Bifurcation stenosis 362
Bigger right aortic arch 536f
Bilateral
absent eyelids 972f
branch pulmonary arteries stenosis 614f
congenital cataract with
microphthalmia972f
Harrison sulcus 312
inferior vena cava 220
superior vena cava 146, 148, 216
Bioengineering in duct patency 94
Bipartite RV 582
Bisferiens pulse 490t
Bispectral index 1030
Biventricular
hypertrophy713f
repair in heterotaxy syndrome 160
Blalock-Taussig shunt 192, 362, 557, 654f
opacifying confluent pulmonary
arteries573f
Blalock-Thomas-Taussig shunt 761
Bland-White-Garland syndrome 207f, 881
Bleeding92
in cyanotic children 1049
Blocked atrial bigeminy 74, 75
Blood
flow analysis 206
pressure 173, 174, 184, 730
test713
Blunt right ventricular outflow tract 571
Bone morphogenetic protein 923f
Boot-shaped heart 195f
with empty pulmonary 198f
Bosentan940
Brachiocephalic
artery536f
compression of airways 540
vein215f, 240
Bradyarrhythmia-induced torsades 843f
Bradyarrhythmias 794, 842
Bradycardia suggestive of complete heart
block184
Brain
abscess772
natriuretic peptide 713
Branch pulmonary artery 51f, 153, 181
stenosis589f
Branches of dorsal aorta 11
British Society of Antimicrobial
Chemotherapy981
Brockenbrough sign 729f
Brockenbrough-Braunwald-Morrow sign 728
Bronchial artery 934f
Bronchiectasis1080
Bronchiolitis obliterans syndrome 1084
Bronchopulmonary
arterial into systemic circuit 240
dysplasia 1080, 1081
venous anastomoses 240
Bronchoscopy 535, 539
1093
1094
metrorrhagia and menorrhagia 805

obstructive pulmonary disease 918f, 923,
1080
Churg-Strauss syndrome 713, 718
Cineangiography405
Circumflex aortic arch 530, 532f
Citrate-phosphate-dextrose1041
Classic
Blalock-Taussig shunt 558
fontan654f
repair804
Classical
appearance of myxoma 897f
figure-of-8 appearance of total anomalous
pulmonary venous connection 187f
Cleft
anterior mitral leaflet 293
mitral
leaflet445
valve448, 760
Clomiphene27
Closure of
patent ductus arteriosus 316
septal defect 303
Clubbed hand 105f
Coarctation of aorta 13f, 89, 100, 170, 173, 181,
192, 204, 204f, 266, 323, 366, 415, 505, 512f,
519, 757t, 760, 789, 814, 821
interruption of aortic arch hypoplastic left
heart syndrome 87
Cocaine intoxication 865
Cognitive
disorders657
impairment963
Collagen vascular disease 686, 918f
Collateral
pulmonary artery anastomosis 567
vessel and sternal wires 678f
Combination of
hydralazine and nitrates 691
multiple levels of stenosis 362
Combined hormonal contraceptive 801
Common
arterial trunk 131, 605, 610f
atrioventricular
junction301f
valve57, 650f
atrium 297, 639, 650f
cardinal vein 7f
carotid artery 506f
pulmonary vein 224f, 231f, 235f
confluence235f
symptoms, pathophysiology of 169t
Comparison of ductus and systemic collateral
arteries sources of pulmonary blood flow in
PA-VSD567t
Compensated erythrocyosis 773
Complete
abdominal heterotaxy 146
absence of interatrial septum 641f
atrioventricular valve septal defect 303
blood count 671, 1005
heart block 74, 732, 842f
transposition of great vessels 168
vascular ring 526
Complex
atrioventricular septal defect 301
congenital heart defects 757t
Compliant small vessels 932f
Complicated valvular disease 801
Complication of congenital heart disease 995,
998
Components of aortic root 469
Computed tomography angiography 147f
Computerized tomography 571
Conclusion of balloon dilatation 464f
Conduction system 151, 152t, 415, 596, 606,
626
Confluent pulmonary arteries 571f
Congenital
absence of pericardium 944
aortic valve defects 759
atrioventricular block 844
bicuspid aortic valve 477
cardiovascular malformation 267
contractural arachnodactyly 947
coronary artery anomalies 816, 879
corrected transposition of great
arteries199
cystic adenomatoid malformation 44, 50,
65
extrahepatic portosystemic shunt 158
heart
blocks and bradyarrhythmias 839
disease 16, 25, 43, 44, 45t, 65, 76f, 84,

88, 89t, 97, 145, 166, 183, 190, 203,
244, 266, 292, 307, 380, 434, 445, 470,
518, 547, 618, 625, 639, 745, 751,
771, 783, 784, 787, 812, 824t, 827,
835, 871, 879, 967, 971, 979, 980,
996, 996f, 997, 999, 1006, 1022, 1070,
1071t, 1080
disease in offspring, screening for 786
disease, physiologic consequences of
1024
Surgeons Society581
surgery and database project 568
high airway obstruction 50
mitral
regurgitation447, 739
stenosis380, 385f, 760
valve defects759
valve diseases445
ostial stenosis of left main coronary
artery888
pericardial
defects141
diseases944
pulmonary
arteriovenous fistula243
valve disorders434
valve lesions754
rubella syndrome 362, 972
systemic-to-pulmonary shunts 918f
tricuspid valve defects 756
Congenitally
corrected transposition of great
arteries 625, 633t, 766, 791, 822
hypoplastic coronary arteries 816
stenotic tricuspid aortic valve 479
Congestive
cardiac failure 936
heart failure 92, 167, 182, 270, 311, 375,
426, 626, 627f, 647, 652f, 737, 936
Connective tissue disorders 445, 937f
Conotruncal
anomaly face syndrome 101
development, abnormalities of 10
Consanguinity35
Conscious
competence182
incompetence182
Constrictive pericarditis 721
Continuous
murmurs181
classification of181
positive airway pressure 537, 693
venovenous hemodialysis 1078
Contraceptive748
counseling804
options for women with congenital heart
diseases 800, 810
Contrast
echocardiography 246, 258
enchanced computer tomography 897f
enhanced MR angiography 206
Control of fetal circulation 20
Convex left ventricular contour 483f
Cor triatriatum 932f
Cordocentesis111
Coronary
anomalies from angelini, classification of 882
artery
and cardiac veins 626
anomalies596, 815
disease730, 801
dissection951
fistulae888
in heterotaxy152
computed angiography 816
cusp273f
ostial anomalies 605
sinus216f, 231f, 254f, 463f
obstruction383
stenosis181
termination, abnormalities of 888
Corrective surgery for tricuspid atresia, historical
aspects of 408
Corrigan sign 490t
Corticosteroids 27, 1051
Cranial directed head and neck vessels 52f
Critical
aortic stenosis 87, 89
pulmonary stenosis 87
Cross-section
in middle of heart 52f
of main pulmonary artery 51f
Cross-sectional echocardiography 391
Cusps of aortic valve 446f
Cutaneous vasodilation 92
Cutis laxa 362
Cyanotic
congenital heart disease 183, 184, 780t,
789, 804
clinical approach to 188
D
Danon disease 726
Decompensated erythrocytosis 773
Deep
hypothermic circulatory arrest 1044
venous thrombosis 776, 778, 793
Definition of aortic root 469
Degree of inspiration 190, 194
De-Musset sign 490t
Dental
caries984
of maxillary and mandibular arches 984f
disease in children and adolescents 984
floss987
procedures requiring antibiotic
coverage982
Deoxyribonucleic acid 30
Depomedroxyprogesterone acetate 748
Descending
aorta 204, 532f, 536f
angiogram573f
common pulmonary vein 235f
thoracic aorta 519, 519f, 520f, 522f
Description of
cardiac and non-cardiac thoracoabdominal
structures148
double aortic arches 527f
Development in respiratory disorders 934f
Development of
atrioventricular valves 8
cardiovascular system 3
central pulmonary artery 568, 568f
conotruncal ridges 11f
heart3
pulmonary
arterial hypertension921f
hypertension, mechanism of 919
veins224f
superior vena cava 213
Device
closure of muscular VSDS, recommendations
for281
therapy in heart failure 692
Dextrocardia 136, 190
Dextroversion dextrocardia 136
Diabetes mellitus 28, 170
Diagnosis of aortic interruption 612
Diameter of aortic annulus 601f
Diaphragmatic hernia 44, 50, 65
Diarrhea92
Diastolic
blood pressure 785
dysfunction 724, 951
murmur 167, 180, 368
velocity68
Differences between
fetal/neonatal and adult myocardial
physiology19t
tetralogy and trilogy of Fallot 561t
Digeorge syndrome 102f, 109, 112, 146, 172,
184, 267, 790
Digital subtraction angiography 247
Digoxin 691, 797, 938
Dilated
cardiomyopathy 196, 445, 685
inferior vena cava 715f
right
atrium188f
pulmonary artery and left pulmonary
artery with peripheral pruning 200f
Dilation of coronary sinus 215f
Dilemma of managing patent ductus arteriosus
in sick newborn units 85
Diltiazem940
Dimensions of aortic root 476
Diminished right ventricular forces 186f
Discrete
membranous stenosis 366
subaortic membrane 367, 301
Diseases of
aortic valve 475
heart and circulation 751
tricuspid valve 414
Distal pulmonary arteries 362, 918f
Distinctive webbed neck 171f
Disuse hypofunction 657
Diverticulum of kommerell 529f, 534f
Donor
hearts selection 1074
selection1081
Doppler
aortic valve 485f
cursor abdominal aorta in chronic aortic
regurgitation492f
tissue imaging 716
Dorsal view of stages of development of sinus
venosus7f
Double
aortic arch 14f, 526
with PDA forming vascular ring 536f
barreled aorta 542
chambered right ventricle 357, 360
inlet
connections649
left ventricle 645, 646f
right ventricle 645, 646f
orifice mitral valve 380, 445, 449
outlet right ventricle 45, 62, 147, 266, 267,
297, 415, 594, 645, 760
subaortic VSD with pulmonary
stenosis601
subaortic VSD without pulmonary
stenosis601
with doubly committed VSD 602
with severe pulmonary stenosis 60f
with subpulmonic VSD602
Down syndrome 99, 112, 171, 172, 184, 267,
299, 305, 548, 760, 960, 963, 967
Drains into right superior vena cava 151f
D-transposition of great arteries 618, 763,

790, 822
Dual
chamber pacing 732
orifices of mitral valve 386
Duchenne muscular dystrophy 865
Duct dependent
congenital heart diseases, classification
of85
pulmonary circulation 85
systemic circulation 85
Ductal
arch52f
closure, mechanism of 310
constriction362
ligation675
stenting, recommendation for 93t
Ductus567
arteriosus 18, 84
arteriosus, morphology and physiology
of84
venosus 68, 69
Duke criteria for diagnosis of infective
endocarditis998
Duodenal atresia 44
Duodenojejunal junction 154
Durozeiz murmur 490t
Dysfunctional uterine bleeding 805
Dysphagia lusoria 532, 533f
Dysplasia of mitral valve 445
Dysplastic
common atrioventricular valve 65
mitral valve 385f
pulmonary valve 359
tricuspid valve 582
truncal valve 65
Dyspnea169
index
heart diseases 183

spells, mechanism of 549
Cystic
adenomatoid malformation 44
fibrosis 933, 1080
hygroma44
E
Early fetal heart block 161
Ebsteins anomaly 45, 184, 185, 186f, 187, 187f,
360, 415, 417, 424, 427, 582, 589, 590, 755t,
756, 791, 821
Ebsteins
anomaly of
mitral valve 445, 449
tricuspid valve 87, 183
malformation 65, 414
of mitral valve 386
of tricuspid valve 59, 414
Ebsteinoid malformation of left AV valve 427
Eccentric
hypertrophy651
thrombus in left pulmonary artery 927f
Echocardiogram
in apical four-chamber view with color
doppler340f
of univentricular heart 652f
Echocardiographic evaluation of diastolic
function of left ventricle 486
Echogenic foci 63
Ectopia cordis 97f, 142
Ectopic atrial tachycardia 871
1095
1096
Edwards syndrome 100, 112, 267

Effect of prostaglandins 92
Ehlers-Danlos syndrome 362, 488, 489, 947
Eikenella corrodens 980, 996, 998
Eisenmenger
patent ductus arteriosus 184
syndrome 183, 185, 255, 270, 271, 792, 803,
804, 823, 935, 935t, 1080, 1081
Ejection systolic murmur 89, 562
Ellis-Van Crevald
syndrome 104, 172
and polydactyly of hands 105f
syndrome640f
Elongated aortic arch 541
Emergency contraception 801, 802
End diastolic volume 479
Endocardial
cushion defect 57, 172
fibroelastosis 736, 738f
Endocarditis762
in prosthetic aortic valve 498
prophylaxis 768, 793, 955, 980
Endocardium of dilated right ventricle 686f
Endocrine disorders 967
Endomyocardial
biopsy 688, 717, 1021, 1078
fibrosis712
Endothelin receptor
antagonists941
blockers940
Endotoxemia1047
Environmental hazards 33
Epilepsy29
Epinephrine challenge test 859
Epoprostenol940
Epstein-Barr virus 1078
Erythrocytosis771
Eustachian valve 125, 261
Evaluation of
fetal cardiac function and changes in fetal
heart failure 66
interventricular communication 650
tricuspid valve 418
Examination of heart 119
Excessive
mitral valvular 388
pulmonary blood flow 269
Exercise in patients with congenital heart
defects, guidelines for 818
Extended cardiac screening views 46
Extent of aortic root 469
External jugular veins 1013
Extra-anatomic bypass grafts 509
Extracardiac
anomalies 44, 459
Fontan 653, 654f
Extracellular matrix 919f
abnormalities of 25
Extracorporeal membrane oxygenation 148,
153, 279, 1009, 1064, 1080
Extraskeletal osteosarcoma 896
Extrinsic cardiac compression 65
F
Fabry crisis 721
Fabrys disease 476t, 713, 720, 726
Familial
pulmonary arterial hypertension 918f, 929
syndromes44
thoracic aortic aneurysms 947
Fanconi syndrome 172
Fatigue773
Features of pulmonary capillary
hemangiomatosis932t
Female hormones 27
Femoral stenosis 181
Fenestrated Fontan 677
Fetal
alcohol syndrome 172
anemia65
aortic
balloon valvuloplasty499
valvotomy499
arrhythmia 44, 65, 69
blood volume 18
bradycardia72f, 74
cardiac
function18
function and myocardial performance,
assessment of66
function, functional assessment of 65
interventions64
surgery1056, 1057
cardiology43
cardiomyopathy 65, 694
cardiopulmonary bypass 1057
circulation 15, 16
in congenital heart diseases 21
ductus arteriosus 23
echocardiogram45
echocardiography 598, 1057
electrocardiogram71
heart failure, functional assessment of 65
left49f
myocarditis65
pulmonary vascular resistance 20
rhythm, assessment of 69
right49f
tachycardia72
Fibrinoid necrosis 921f
Fibromas905
Fibromuscular
ridge367
subaortic ridge 367
Fibrosarcoma 896, 900
Fibrosing mediastinitis 362
Figure-of-eight sign 197
Figureunequal distance between medial end of
clavicle and central line 193
Financial costs of health care and
insurability746
First heart
field98f
sound180f
First-degree AV block 840
Fixed infundibular and supravalvar stenosis with
pulmonary valvar stenosis 359
Fixed pulmonary hypertension 255
Fixed splitting 176
Flecainide798
Fleischner lines 200
Flow rates on bypass 1045
Fluconazole26
Fluid
and electrolyte replacement 1063
management1013
Fluorescent in situ hybridization 106
Fluoride
delivery methods 988f
toothpaste987
Flutter isthmus 125
Foam cleaning sponges 987
Folic acid 31
Fones technique 990f
Fontan
circuit651
circulation 208, 651
operation425
ideal patient for 654
procedure 677, 822
surgery, variations of 654f
Fontan-Kreutzer operation 408410
Foramen
flap49f
ovale53f, 65
Formation of
Atrioventricular
canal8f
valves9
cardiac loop 4, 5
interventricular septal development 11f
left
atrium7
brachiocephalic vein214f
right aortic arch 530f
superior vena cava 214f
Four chamber view 47
Fourth intercostal space 175
Fraction of inspired oxygen 90
Friedreichs ataxia 726, 865
Fulminating type 736
Functional
pulmonary atresia 357
single ventricle 577
status and exercise tolerance 657
status of spleen in heterotaxy
syndrome161
Functioning of aortic valve 471
Funnel-shaped valve 386
Fusion of endocardial cushions 8f
Fusobacterium nucleatum 980
Future directions 76, 286
G
Gallbladder and biliary atresia 155
Gastric
outlet obstruction 92
regurgitation92
Gastrointestinal tract congenital defects 967
Gaucher disease 720, 918f
General manifestations of cardiac tumors 894t
Genes
associated with CHD 106
causing different types of CHDs with
chromosomal region in humans 106t
Genetic
and differential diagnosis of Marfan
syndrome946
H
Haemophilus
aphrophilus 980, 996
influenzae161
parainfluenzae 980, 996
paraphrophilus996
species996
Hammock valve 387
Hand injection of contrast RPV draining into
azygos vein 236f
Hangout interval 176
HD-flow demonstrates flow in pulmonary
veins49f
Health passport 748
Heart
and estrogen/progestin replacement
study806
and lung transplantation, international
society for 1070
defects8
development640f
disease evaluation 209
failure 65, 768, 794
by ross, modified classification of 170t
muscle disease 685
procurement techniques 1074
rate1008
and respiratory173
at different age 173t
sounds176
transplantation1072
techniques1075
Heart-lung
and lung transplantation 941
transplantation 1083, 1084
Hearts with one big and rudimentary
ventricle646
Heavy exercise and athletics, restriction
for823
Helex septal occluder device 263f
Hemangiomas 181, 896, 899
Hematocrit on bypass 1045
Hematological
and hemodynamic changes in
pregnancy784
issues, leukemia 967
Hematuria92
Hemiazygos vein into left superior vena cava
into coronary sinus 220f
Hemochromatosis719
Hemodynamic
and clinical expression of ASD and MS 909t
assessment of atrioventricular septal
defect302
changes259
consequences, assessment of 66
evaluation611
and ventriculography727
of single ventricle and fontan circuit 651
Hemoglobin1011
Heparin-induced thrombocytopenia 796
Hepatic
sinusoids231f
vein235f, 655f
Hepatitis B virus 967
Hepatoma181
Herbicides, pesticides and rodenticides 32
Hereditary hemorrhagic telangiectasia 243,
918f
Heterotaxy 145, 872
in adulthood 161
syndrome145
Heterotopia899
Hetrotaxy syndromes 297
Hidden flutter waves 765f
High
dynamic range 108
output states 65
oxygen saturation 676

pulmonary vascular resistance 926f
Hills sign 490t
His-purkinje system 870
Holmes heart 649
Holter monitoring 482
Holt-Oram syndrome 104, 172, 784
Homocystinuria947
Horizontal position of atrioventricular
valves964f
Hormone replacement therapy 806
Horner syndrome 558
Host factors for infective endocarditis 997
How deal with stigma? 832
Human
immunodeficiency virus 937f, 971, 973
infection686, 918f, 973
leukocyte antigens 1072
Hybrid
approach279
to hypoplastic left heart syndrome 678
surgery285
Hydralazine797
Hydration773
Hydrops fetalis 44
Hypercalcemia865
Hypercapnic acidosis 91
Hyperemia of neoplasm 181
Hypereosinophilic syndromes 717
Hyperkalemia 92, 865
Hyperostosis92
Hypertelorism104f, 171f
Hypertension801
and idiopathic pulmonary arterial
hypertension933t
Hyperthermia92
Hyperthyroidism181
Hypertrophic
cardiomyopathy 168, 445, 723, 814, 815,
816f, 824t, 862
obstructive cardiomyopathy 366, 723, 725
osteoarthropathy772
Hypertrophy of left ventricle 9
Hyperviscosity syndrome 773
Hypnotics27
Hypoglycemia92
Hypokalemia 92, 796
Hypoplasia of
Mitral
apparatus445t
valve385
leaflets386
ventricles622
Hypoplastic
coronaries824t
left heart 45
syndrome87f, 88, 89, 91, 170, 196, 645,
665, 679, 1070, 1077f
mitral valve 380
pulmonary veins 380
right ventricle 650f
Hyposplenia161
Hypothermia 865, 1010
Hypoxic hypometabolism 88
76
index
and familial inheritance 468

associations605
cardiomyopathies in children 719
diseases with left ventricular
hypertrophy726
in congenital heart diseases 97
mutations in HCM 723
Gerbode defect 268, 273
Gerhardt sign 490t
Giant cell arteries 686
Gianturco-Grifka vascular occlusion device 317
Gingival
and periodontal diseases in children and
adolescents986
inflammation985f
Glenn
procedure407
shunt159
surgery408
Glutathione S-transferase 30
Glycogen storage diseases 720, 918f
Goals of management 90
Goldenhar syndrome 172
Good right ventricular size and
morphology587
Gooseneck deformity 293f
Grading of murmurs 178
Graham steell murmur 271, 390
Great
arteries131
with left superior axis 186f
artery relationship 596
vessels459
Ground
glass appearance 194, 233f
water contamination 32
Group for pediatric and congenital heart
disease146
Growing up with congenital heart disease 827
Grown up congenital heart diseases 190
Growth
impairment in infant 167
retardation or failure to thrive 168
Guanosine triphosphatase activating
protein920f
Guntheroths theory 549
Gynecological issues in women with congential
heart diseases 804, 810
1097
1098
Iatrogenic lutembacher syndrome 908

Ibuprofen316
Identifying fetus risk for congenital heart
disease43
Idiopathic
hypereosinophilic syndrome 718
hypertrophic
obstructive cardiomyopathy366
subaortic stenosis 723, 1008
pulmonary
arterial hypertension918f, 932f, 937f,
1080
fibrosis1080
hypertension929
Iloprost940
Immune-mediated therapy 692
Immunoglobulin treatment 692
Immunological disorders 967
Immunosuppression 1076, 1085
Impaired hemostasis 1048
Imperforate
pulmonary valve 566f
valve385
Implantable
cardiac defibrillator in hypertrophic
cardiomyopathy, indications for 733t
cardioverter-defibrillator 693, 860, 875, 1020
complications860
loop recorder 814
Implications of differential pre- and postductal
saturation90
In utero
constriction of ductus arteriosus 65
course and implications for delivery
planning63
In utero intervention 1056
In vitro fertilization 44
Inadequate repair of common atrioventricular
valve304
Incidence of different types of vascular
rings532
Incomplete vascular ring or vascular sling 526
Increased nuchal translucency 44
Increased pulmonary blood flow 401, 406,
407
evidence of 609
with interatrial obstruction 464
with or without heart failure 464
Indices for prediction of success of intracardiac
repair553
Indirect evidence 31
Individual anomalies 526
Indomethacin316
Infant with
central cyanosis 554
dextrocardia and cctga628f
Infantile
aortic stenosis 486
hypotonia962t
Infants with heart failure 609
Infarction865
Infections 25, 1066
and fever 26
Infectious cardiomyopathy 686

Infective endocarditis 273, 325, 456, 490, 979,
995, 996
in congenital heart diseases 995, 999
with congenital heart disease 996t
risk factors for 997
Infective endocarditis without congenital heart
disease996t
Inferior vena
cava 17, 68, 149f, 190, 218, 220, 226, 231f,
253, 254f, 257f, 259f, 382f, 626f, 656f,
1075
caval drainage to left atrium 219
Infiltrating and storage disease 739
Inflammatory and postinfective subtype
685
Influence of associated lesions 510
Infracardiac TAPVC 233
Infundibular septum 595f, 596f
Infundibular stenosis 357
Infusion of prostaglandin 85
Inheritance267
Inoue-balloon catheter 914
Insertion of ductus arteriosus 520f
Intact
interatrial septum 301f
ventricular septum 89
Intensive care unit 1076
Interaction of
genetic factors 35
non-genetic factors 35
Interatrial
defects253
obstruction 407, 463
septal aneurysm 951
septum124
Interleaflet fibrous triangles 469, 470
Intermediate AVSD 293
right ventricular 588
Internal
anatomy124
jugular veins 1013
International Society
and Federation of Cardiology 685
of Congenital Heart Defects 748
Interplay of pressure dynamics between LV and
aorta471
Interposition grafts 509
Interpretation of hyperoxia test 90t
Interrupted
aortic arch 103, 109, 204, 269, 366
Interruption of
aortic arch 518, 522f
inferior vena cava with azygos
continuation146
Intersegmental arteries 12
Interstitial
fibrosis934f
lung disease 918f
pneumonitis1080
Intervention in
aortic stenosis 494
duct dependent congenital heart
diseases93
heterotaxy159
Intervention, indications for 363

Interventional treatments 512
Interventions in blalock-taussig shunt 555
Interventricular
communication566
obstruction407
septum 132, 150, 273, 560, 562, 570f, 619,
714, 727
Intimal
hyperplasia919f
tears within pulmonary arteries 92
Intracardiac
anomalies203
echocardiography258
lateral tunnel fontan 654f
masses63
obstruction 406, 407
repair762
TAPVC233
tumors65
Intracavitary tumors 894
Intramural tumors 896
Intraoperative assessment 304
Intrauterine
devices 800802, 804
growth restriction 109, 785
Intravenous
fluid requirements in post-operative
period1063t
immunoglobulin76f
Intraventricular septum 348f
Intrinsic coronary arterial anatomy,
Invasive
blood pressure 721, 1012
electrophysiology
in children870
testing and devices in children 870
Involvement of papillary muscles 448
Ionic tooth brushes 987
Ionizing radiation 32
Ipsilateral common carotid and subclavian
arteries527f
Iron
deficient rigid microspherocytes 772
replacement therapy 773
Irregular rhythms 71
Ischemia-reperfusion injury 1047
Ischemic cardiomyopathy, must be
excluded686
Isolated
circumflex886
infundibular stenosis 360, 360f
levocardia141
origin of left subclavian artery from left
pulmonary artery 542
subclavian artery arises from ductus
arteriosus519
Isomerism of
left atrial appendage 145, 147f, 148, 149f
right atrial appendage 145, 148, 149f
right bronchus 154f
Isometric exercise 812
Isotonic exercise 812
Isotretinoin26
Ivemark syndrome 145
K
Kabuki syndrome 105
Kartagener syndrome 141, 172
Kawasaki disease 686
Kawashima operation 653
Kawashimas modification in patients of
univentricular heart with interrupted inferior
vena cava 655f
Kingella kingae 980
Kirklins classification 269
Kissing atrioventricular valves 649
Klinefelter syndrome 112
Knuckle sign 200
Koch triangle 415
Konno-Rastan procedure 370
Kotharis theory 549
Kussmauls sign 720t
Kyphoscoliosis823
L
Lactic acidemia 88
Lamin a/c mutation 694
Laminar flow within stent 466f
Landmark of triangle of koch 125
Laplaces law 368
Large
aneurysm of right ventricular outflow
tract208f
fresh mural thrombus 686f
main pulmonary artery 669
midmuscular ventricular septal
defect 286f
or nonrestrictive 270
right atrial myxoma obstructing tricuspid
valve897f
subaortic ventricular septal defect 367f
ventricular septal defect 195f, 646
Late gadolinium enhancement 729
Lateral tunnel 657f
procedure with fenestration 657f
technique652
Laterality of arch in posterioanterior view 533
Laurence-Moon-Biedl syndrome 172, 184
Leaflets of mitral valve 447f
sinus of valsalva 338

sternal border 271
subclavian artery 310, 519f, 520f, 522f, 525f,
526f529f, 531f533f, 536f
superior
pulmonary vein229f
vena cava 56, 148, 215f217f, 548
upper pulmonary vein 228f
ventricle98f, 141, 228f, 234f, 382f, 552,
932f
dominant185
in aortic stenosis 479
oxygen saturation552
ventricular angiogram in frontal view 536f
ventricular angiogram in left anterior
oblique278f, 283f, 286f
view282f
view typical gooseneck deformity 302f
ventricular angiogram in right anterior
oblique699f
view non-compaction of left ventricle 287f
ventricular
assist device693
dilatation688
dysfunction 448, 494, 761
ejection fraction 688, 801
end diastolic pressure 170, 737, 933
enlargement with T wave changes 186f
failure934f
function476
hypertrophy 89, 367, 368f, 480, 480f,
726, 784
hypertrophy by echocardiography,
assessment of 727t
inflow obstructions380
internal dimension688
internal dimension in diastole 729
non-compaction694, 697
outflow abnormality leading to aortic
regurgitation488
outflow obstruction 619, 727
outflow obstruction, classification of 366
outflow tract47f, 48, 151, 292, 347, 366,
468, 480f, 952
outflow tract obstruction 168, 300, 304,
366, 518, 619, 724
tumors896
volume overloading400
vertebral artery 532f, 543f
vs right-sided lesions 35
Left-sided atria 151f
Leftward-positioned ascending aorta 628f
Leimyosarcomas900
Lethargy773
Levels of intensity and duration of exercise 813
Levoatriocardinal vein 382f
Lifestyle
changes938
management693
Lifetech duct occluder 321
Lighthouse sign 490t
Limitations of fetal echocardiograms 63
Lipomas 896, 898
Lithium975
Living donor lobar lung transplant 1082
L-loop transposition of great vessels 61
index
Jitteriness92
Joins portal vein 235f
Joint
Commission for Accreditation of Healthcare
Organization1015
pains and swelling 773
Joseph mitral balloon valvuloplasty 914
Jug-handle appearance 200, 200f
Jugular venous 435
pressure 174, 357, 440, 712, 725
pulse175f, 184, 271, 435, 562, 910
Junctional
ectopic tachycardia 847, 855, 871, 1064
reciprocating tachycardia 72, 872
Juxtaposition of
IVC and descending aorta 161
right atrial appendage 214
Lecompte maneuver of pulmonary

arteries633
Left
anterior descending 548
artery471f
artery from pulmonary artery 886
aortic arch 525f, 526f, 527f, 529f, 530f, 536f
with aberrant right subclavian artery with
persistent left ductus 530
atria98f
atrial
and left ventricular trace 279f
appendage151f, 497f
enlargement911
morphology122
myoxoma932f
myoxoma obstructing mitral valve 897f
or biatrial drainage of right superior
vena cava214
pressure932f
tumors894
atrioventricular valve
regurgitation304
repair of304
stenosis304
atrium 125, 141, 228f, 552
brachiocephalic
artery528f
vein229f
bundle branch block 358, 688, 865
carotid artery 528f
circumflex548
common
cardinal vein224f
carotid519f
carotid artery506f, 510f, 519f, 520f, 525,

525f, 526f, 527f, 528f, 529f, 530f, 531f,
532f, 533f, 536f
coronary artery 699, 879, 882
from right aortic sinus 886
coronary
ostium469f
sinus471f, 816
descending coronary artery 882
heart934f
hepatic vein 231f
inferior
pulmonary vein235f
truncus swelling9
innominate artery 528f
internal mammary artery 528f, 672f
isomerism639
lower pulmonary vein 228f
main coronary artery 574f
atresia887
or right coronary artery from non-coronary
sinus887
portal vein 231f
pulmonary artery 84, 204f, 235f, 236f, 309f,
443f, 519f, 522f, 525f, 526f, 527, 528f, 529f,
530f, 531f, 537, 538f, 571f, 630f, 657f
to descending aorta 538f
pulmonary
veins236, 236f
venous channel235f
sided inferior vena cava 220
1099
Localizing confluence of pulmonary veins 233

Location of infective endocarditis in congenital
heart disease 997
Locomotor brachii 490t
Loeys-Dietz syndrome 946, 947
Long
bones pain 773
QT syndrome 73, 74f, 76f, 857
segment stenosis 539
Long-term
follow-up556
issues postcorrection 623
issues with atrial switch repair 764
management of asplenia/hyposplenia 162
pharmacologic therapy 852
sequelae after surgical repair 615
surgical outcome 614
Low
cardiac output 1063
hairline in child with noonan
syndrome104f
set ear 171f
Low-molecular weight heparin 795
Lung
and bronchial anatomy 153
and with non-confluent pulmonary
arteries573f
biopsy928
fields200
procurement techniques 1082
scintigraphy926
transplantation
techniques1082
indications for1080
Lutembacher syndrome 174, 908911, 911f,
913915
Lyme disease 686
Lymphatic dysfunction 660
Lysosomal storage disease 720
Lysosome-associated membrane proteins-2
cardiomyopathy726
1100
Magnetic resonance imaging sequences and

techniques205
Main intraembryonic and extraembryonic
vessels14f
Main pulmonary artery 84, 188f, 229f, 276,
309f, 313, 318f, 335f, 360f, 421f, 425f, 428f,
443f, 472, 521f, 522f, 543f, 562f, 574f, 583,
612f, 626f
dilated with plethora 195f
left pulmonary artery 194
sinuses587f
stenosis362
Major aortopulmonary collateral 528f
arteries552
Major role of endothelial injury in pulmonary
arterial hypertension 918f
Malaligned atrial septum or double-outlet right
atrium297
Malformation syndromes 720
Malignant
cardiac tumors 899
lymphoma896
tumor901
Malocclusion of teeth 171f
and wide-spaced nipples in noonan
patient171f
Malrotation of gut 148, 154, 156f
Mammary souffl 181
Management issues in adults with congenital
heart diseases 751
Management of
aortic valve disease 493
atrial fibrillation 732
autoimmune heart block 75
AVSD303
children growing up with
chronicdisabilities 832
depression and anxiety disorders 832
pulmonary
arterial sling539
veno-oclusive disease931t
transposition of great arteries 621
Management time of initial presentation 463
Manual tooth brushes 987
Marfan
population954
syndrome 172, 172f, 324, 468, 488, 489,
784, 803, 804, 824t, 946, 947t, 948, 948f,
949, 949t, 951-957
and type B aortic dissection 955t
Marfanoid body habitus 948
Marijuana ingestion 975
Maternal
alcohol ingestion 975
CHD44
cocaine975
diabetes mellitus 971
drug exposure 26
infection44
parvovirus infection 65
phenylketonuria 971, 973
psychology and stress 33
rubella25
tobacco consumption 976
Matrix metalloproteinase inhibitors 953
Maximal wall thickness 727
Maximum intensity projection 204f
Mcgoon ratio 553
Mean
corpuscular volume 774
velocity68
Measurement of right ventricular cardiac
output68f
Mechanical
assist devices 1053
valve496
Mechanism of
action of dysfunctional endothelial cell 919f
cyanotic spells 549
pulmonary smooth muscle cell
proliferation920f
Medial hypertrophy 931f
Mediastinal tumor 362
Medical
Management
and timing of intervention 393
palliative surgery408
time of initial presentation 406
termination of pregnancy 805
therapies 850, 938
Medications in pregnancy, classification
of795t
Medroxyprogesterone acetate 806
Melting ice cube sign 201
Membranous atresia 581, 582, 589f
with moderate right ventricle hypoplasia
(intermediate)282f
Menarche805
Menopause806
Menorrhagia773
Menstrual disorders 772
Menstruation805
Mental retardation 962
Mercedes-benz sign 476f, 759
Mesocardia141
Mesothelioma 896, 900
of atrioventricular node 896
Metabolic
cardiomyopathies720
diseases476t
disorder105
Methemoglobinemia90
Metronidazole26
Mid diastolic murmur 911
Middle cerebral artery 68
Mid-muscular ventricular septal
defect641f, 701
opacifying right ventricle 707f
occlude280f
Midsystolic
click or non-ejection clicks 178
murmur left upper sternal border 368
Mild
RV hypoplasia 581
to moderate mitral valve regurgitation 820
tricuspid regurgitation 582f
Miscellaneous heart defects 63
Mitral
annulus, abnormalities of 448
arcade449
atresia 214, 458
or left atrioventricular valve atresia 458
regurgitation180f, 456, 820, 1008
to other congenital causes 445
stenosis180f, 820, 909, 911, 1008
valvar dysplasia 385
valve932f, 737f
abnormalities59
atresia385
calcification912
dysplasia45, 65
orifice912
prolapse 172, 387, 445, 447, 453, 457,
755t, 759, 820, 984
repair393, 453
replacement453
Mixed venous oxygen saturation 552
M-mode echocardiography 391
Mode of delivery 799
Moderate
or moderately restrictive defects 270
N
NADAS criteria for diagnosis of congenital heart
diseases167t
Nakata index 553
Narcotics27
National Institute of Health and Clincal
Excellence981
National Marfan Foundation 955
Native pulmonary arteries 566, 568f
Natural history of
aortic valve lesions 491
ductus arteriosus 84
Near infrared spectroscopy 1031
Necrotizing enterocolitis 92
Neisseria meningitides161
Neoaortic regurgitation 624
Neonatal
aortic stenosis 487f
coarctation511f
heart1061
intensive care unit 972
Neonates and infants 416
Nephritic syndrome presented with subaute
pulmonary thromboembolism 927f
Neural crest cells 10
Neurologic
disease90
monitoring1044
Neurological
dysfunction1066
injury1052
New York Heart Association 783, 917, 1081
Newborn with severe ebstein anomaly of
tricuspid valve 92
Nifedipine940
Nitrates797
Nitric oxide synthase 30
Nodule of arantius 470f
Nomenclature 565, 697
and segmental analysis in
heterotaxy147t
Non-accessory mitral valve tissue 622
Noncardiac surgery in congenital heart
diseases1004
Non-compaction of
apex703f, 704f
ventricles697
Non-coronary cusp 469f
Non-Hodgkin lymphoma 900
Noninvasive
blood pressure 1012
evaluation 401, 609
Nonischemic dilated cardiomyopathy 693
Non-steroidal anti-inflammatory drugs 27, 44,
85, 86, 774, 775, 805, 975
Non-sustained ventricular tachycardia 732
Non-therapeutic drug exposure 28
Non-thrombotic pulmonary embolism 918f
Nonvisualization of aortic arch 522f
Noonans syndrome 104, 171, 172, 358, 362,
505, 726, 784
Norethindrone acetate 806
Normal
coronary arteries 879
fetal echocardiogram 46
four chamber view of heart 49f
heart sounds 482f
human fetuses during second half of
pregnancy20t
left
pulmonary artery539f
ventricular function494
major hemodynamic and hematological

changes in pregnancy 785t
pulmonary
artery anatomy1074
capillary wedge pressure 195
range of blood pressure values 174t
sagittal
short-axis image of heart 53f
views of fetal arches 52f
size of aorta above aneurysm 350
subclavian artery 519
tracheal bifurcation 191f
Normally related great arteries 596
Norwood procedure 671, 675
Nuchal translucency 110
index
or severe ventricular dysfunction 823

RV hypoplasia 582
Modes of prevention 971
Modification of
Barrett-boyes classification 225
Kirklin classification 225
Modified bass technique 990f
Modified Blalock-Taussig shunt 558
Monochorionic twinning 44
Morbidity and mortality
during pregnancy in women with Marfan
syndrome, risk factors for 956t
in Down syndrome, risk-factors for 967
Morgans theory 549
Morphogenesis of right aortic arch with
aberrant origin of left subclavian artery and
left-sided arterial ductus 529f
Morphological features in heterotaxy 152t
Mller sign 490t
Multi-detector computerized tomography 571
Multiorgan manifestations of cyanotic
congenital heart disease 772t
Multiple
aortopulmonary collateral arteries 573f
lentigenes172
pale brown thrombi 686f
system organ failure 1078
Multistage surgery 675
Multisystem disorder 771
Mural tumors 899
Murdoch-Walker wrist sign 172f
Murmurs178
Muscle pains and weakness 773
Muscular
atresia566f, 581
with generally hypoplastic right
ventricle582f
subaortic stenosis 723
tissue931f
ventricular septal defect 281
Mustard
operation765f
procedure790
Myeloproliferative disorders 918f
Myocardial
bridging888
dysfunction616
infarction 349, 767f
ischemia and viability 207
performance index 67f
Myocarditis and dilated cardiomyopathy 739
Myxoma896
O
Obesity 29, 971, 973
Oblique coronal maximum intensity
projection204f
Obliterative bronchiolitis
not retransplant 1080
retransplant1080
Obsessive compulsive disorder 833
Obstructed pulmonary venous return 65
Obstruction
above mitral valve 380
level of mitral valve 380
mitral valve 384
Obstructive
hypertrophic cardiomyopathy 448
outflow tract defects 788
Occurrence of bacteremias with various dental
procedures and oral activities 981t
Older infant and children with continuous
murmur609
Oligemia194
Omphalocele44
One and half ventricle repair 425
Open mitral valvotomy 911
Operating room preparation 1028
Operative trauma 1047
Oral
health care in children and adolescents with
congenital heart diseases 979
hygiene aids 986
Oram syndrome familial ASD 105f
Organic solvents 32
Origin of
both great vessels from right ventricle 60f
coronary arteries, concept of facing
sinuses471
Origin of right and left pulmonary arteries from
posterior aspect of TA 612f
Original criteria proposed for fontan completion,
ten commandments 654
Orthodromic atrioventricular reentry
tachycardia849
Orthodromic AVRT 852
reciprocating tachycardia 1064
Orthotopic heart transplantation 1070
Ostium of right and left coronary artery 469
1101
1102
Outflow
in heterotaxy 151
tract98f
view48
Overestimation of gradient across AV 484
Overriding of valvar leaflets 386
Oximetry run in tetralogy of Fallot 552
Oxygen saturations 20, 174, 322f,
404
P
Pacemaker
and cardioverter-defibrillator
implantation1020
in children 873
Pagets disease 181
Palliative
procedures 761, 763
augmenting pulmonary blood
flow557
surgery623
treatment of specific physiologic
palpation175
Pallister-Killian syndrome 101
Pancreas in heterotaxy 155
Pansystolic murmur 89
Papillary
fibroelastoma 896, 898
muscles53f
Parachute mitral valve 380, 387, 445
Paradox of fontan circulation 654
Paradoxical
embolism and stroke 754
splitting177
Paragangliomas 896, 901
Parallel great artery relationships 596
Parasternal
long axis view 141
short axis view 141
Parental
alcohol intake 30
medical conditions 28
smoking29
Paroxysmal
nocturnal dyspnea 933
reciprocating tachycardia 74f
Partial
abdominal heterotaxy 146
anomalous pulmonary venous 148
connections 176, 225, 226
atrioventricular septal defect 293, 303
thrombo plastin time 1005
Partitioning of primordial
atrium5
heart5
ventricle7
Patau syndrome 100, 112
Patch aortoplasty 510
Patency of oval foramen 9
Patent ductus arteriosus 93, 100, 170173,
180f, 190, 192f, 204, 266, 307, 309f, 314f, 316,
318f, 326f, 415, 483, 483f, 518, 522f, 537, 550,
552, 568f, 571f, 575f, 581f, 583, 618, 753, 754,
787, 788, 820, 972, 1008, 1009
dependent congenital heart diseases 85

murmur349
stenting575
Patent foramen ovale 84, 150, 253, 560, 674,
737f, 752, 911, 1009
in right-hand panel 670f
Patients with IRAA 151
Patterns of
coronary artery anomalies in tetralogy of
Fallot548
right ventricular outflow tract obstruction in
tetralogy of Fallot 548
Patulous lips 171f
PDA closure, indications for 316
Pectus
carinatum175f
excavatum175f
Pediatric
cardiac surgery 1023
heart and lung transplantation 1070
Heart Transplant Study Group 1071
heart transplantation 1070, 1074
indications for1070
interventional cardiology 1018
lung transplantation 1079
indications for 1080, 1080t
tumors905
Peg teeth and malocclusion 640f
Pentacuspid aortic valve 477t, 479
Percutaneous
aortic valve implantation 498
transluminal
coronary angioplasty balloon 439f
septal myocardial ablation 730, 731
trans-septal mitral commissurotomy 911,
913
transcatheter treatment 913
Pericardial
cysts 899, 945, 1010
tumors 896, 899
Pericardium producing constriction 718
Perimembranous defects 268
Periodontal disease 985
Perioperative pain management 1008
Peripartum cardiomyopathy 694
Peripheral
airway inflammation 934f
edema169
pulmonary artery stenosis 357
classification of362f
signs of aortic regurgitation 490t
Peritonitis92
Persistent
ductus venosus 221
eustachian valve 220f
interatrial shunt 761
junctional reciprocating tachycardia 854
left ductus 530
pulmonary hypertension of newborn 930
Phenothiazine27
Phenotypic features of Down syndrome 962t
Phenylketonuria 29, 44, 170
Pheochromocytoma896
Phlebotomy774
Phonocardiogram482f
Phosphodiesterase type 5 inhibitors 941

Physiologic monitoring 1028
Physiology of fetal circulation 18
Pigeon chest 312
Pigtail catheter
and sternal wires 428f
in descending aorta 678f
Pit and fissure sealants 988, 989f
Pitfalls and limitations in interpretation of
pulmonary wedge angiogram 928
Placental chorioangioma 65
Plasma volume 785
Plasminogen activator inhibitor 920f
Plastic bronchitis 657, 661
Platelet-derived growth factor 920f
Plethora194
Pleurohilar bronchial veins 240
Pocket-like attachment of leaflets 469
Polycythemia771
rubra vera 774
Polyhydramnios44
Polymerase chain reaction 108, 692
Polymouth262f
Polysaccharide vaccine 161
Polysplenia syndrome 145
Polyvalvular heart diseases 489
Pompe disease 105, 720, 726
Portal hypertension 918f
Position of
aorta406f
heart tube 3
Positive
blood cultures 981t
end-expiratory pressure 1081
Positron emission tomography scan 904
Post procedure angiogram 318f
Post-aortic valvuloplasty aortic
regurgitation490
Postaxial hexadactyly of hands with hypoplastic
nails640f
Post-bypass period 1043
Posterior
aorta474
cardinal vein 7f
descending branch 882
mitral leaflet 446f
papillary muscle 698f
Posteriorly displaced ascending aorta 541
Post-extracardiac fontan
stenosis363f
surgery159f
Postfontan
IRAA supraventricular tachycardia 157f
LPA stenosis-stent positioning 363f
Postnatal circulation 399, 666
Postoperative
care 1008, 1034, 1061
coarctation with controlled blood
pressure804
course540
issues in congenital heart diseases 1061
neuropsychologic morbidity 1052
pain management 1036
period1008
Presence of fetal hydrops 65

Pressure data 1018
Preterm infants 316
Pretransplant evaluation 1072
Prevalence of
CHD25
primary cardiac tumors 896t
pulmonary valve lesion 548
Prevention by fetal intervention 678
Prevention of
sudden cardiac death 732
Primary
cardiac lymphoma 900
ciliary dyskinesia 145
endocardial fibroelastosis 736
graft dysfunction 1082
myocardial dysfunction 65
pulmonary hypertension 911
Primordial heart 3
Primum atrial septal defect 45
Prinzmetals angina 865
Production of pulmonary arterial
hypertension919f
Profiling superior vena cava 53f
Progestin-only contraceptives 801, 802
Progression of
gradient across aortic valve 491
lesions63
pulmonary
arterial hypertension920f
vascular disease761
Progressive
liver failure 657
pulmonary vascular disease 616
systolic dysfunction 723
ventricular dysfunction 657
Prominent
anterolateral muscle bundle 301
aortic knuckle and bulging 483f
main pulmonary artery 912f
pulmonary artery 927f
Proposed heart failure staging for infants and
children1072
Propranolol 796, 797
Prostacyclins939
Prostaglandin93
doses, preparation, monitoring 91t
infusion91
Prosthetic valve 393
endocarditis498
Protamine reactions 1046
Protein-losing enteropathy 657, 768
Proteinuria776
Prothrombin time 1005
Proximal
ascending aorta 951f
main pulmonary artery stenosis 362
pulmonary arteries 918f
PS with atrial septal defect 183
Psychiatric issues 827, 830
Psychosocial challenges 827
Pulmonary
and systemic vessels 533f
angiography928
annular stenosis 622
arterial
disease569
endothelial cell923f
arterial hypertension 196, 334f, 737, 918f,
919, 920f, 921, 935, 935t
related to anorexigens 930
to HIV937f
with congenital heart disease 929
with connective tissue diseases 929
with disorders of respiratory system 933
with human immunodeficiency virus
infection930
with portal hypertension 930
arterial
pressure931f, 932f
sling537, 538f
thrombosis934f
arteries 240, 583, 605
with dual supply to left lung 573f
with ostial stenosis of left pulmonary
artery573f
arterioplasty362
arteriovenous
fistula 183, 243, 246f, 247f, 761
malformations243, 659f
artery 87f, 98f, 204f, 254f, 273f, 292f, 309f,
336f, 406f, 422f, 471f, 497f, 552f, 536f, 548,
552, 566, 570f, 572f, 595f-598f, 601f, 612f,
614f, 620f, 630f, 672f, 881, 884f, 923f, 932f,
934f, 1075f
anastomosis406
band362, 633
branches154f
diastolic pressure924
endothelial cell919f
hypertension 196, 322, 936, 937
junction672f
originating from coronary artery 574f
pressure917
rehabilitation575
sinuses583f
sling204
stenosis362
stenosis in alagille syndrome 104f
stenting363
wedge pressure1018
atresia51f, 84, 87f, 89, 415, 611f
intact ventricular septum 89
ventricular septal defect 566f
atresia with intact
interventricular septum183
ventricular septum 580, 590, 1071
ventricular septum586
ventricular system185
atresia
with ventricular septal defect 87, 203, 565
without ventricular septal defect 87
balloon valvuloplasty 438, 439f, 553, 555
blood
flow 90, 168, 170, 183, 400, 401, 406,
648, 464, 619, 931f, 932f, 934f, 991f
supply568f
capillaries240
capillary
hemangiomatosis918f, 930
wedge pressure933
index
right ventricular systolic pressure 576

shunt repairs in absence of pulmonary
hypertension804
tachycardia865
valve repair 804
Postpartum care 800
Postsurgical
atrioventricular block 843
follow up 558
sinus node dysfunction with or without atrial
tachyarrhythmias843
Post-tetralogy of Fallot 208f
repair208f
Post-traumatic stress disorder 831, 833
Potential use of cryoablation 873
Potts shunt 557
Powered tooth brushes 987, 987f
Practical concepts regarding interpretation of
catheterisation report 1018
Prader-Willi syndrome 112
Preanesthetic medication 1012
Prebypass
anesthetic management 1038
period1039
Preconception clinical assessment in women
with congenital heart diseases 784
Precordium185
Predicting pregnancy-related complications, risk
score for 787
Predictors of asplenia syndrome 156
Pre-excitation syndromes 872
Pregestational diabetes 44
Pregnancy 635, 733
contraception and gynecological issues in
women with congenital heart disease 783
in women with
CHD783, 807
Marfan syndrome956
issues938
risk assessment in women with congenital
heart diseases, preconception assessment
for783
Pregnancy-associated plasma protein 786
Preimplantation genetic diagnosis 113
Premature
Alzheimer disease 967
atrial contractions 71
infants316
pulmonic valve opening 442f
surgical baby 1028
tricuspid valve closure 442f
ventricular
complexes763
contractions71
Premedication1028
Prenatal
circulation 399, 666
diagnosis 574, 627
restriction of foramen ovale 57
screening961
Preoperative
evaluation 1010, 1026
fasting recommendations 1011
medical care 674
preparation1005
1103
1104
circulation184
complications533
component of second heart sound 180f
congestion in case of restrictive ASD 911
disease90
edema 194, 196
function tests 925
hemorrhage772
hypertension 180f, 275f, 276f, 688, 754, 801,
803, 804, 819, 917, 931f, 934
hypertension caused by
chronic thrombotic or embolic
obstruction of pulmonary
arteries934
disorders directly affecting pulmonary
vasculature935
hypertension
classification of 917, 918f
related to sickle cell disease 930
hypertensive crisis 1065
lobulation, abnormalities of 146
oligemia187f
of left lower lobe 927f
regurgitation 440, 557, 755t, 756, 820
resistance vessels 934f
segment artery ratio 576
stenosis 89, 170, 172, 180f, 183, 185, 266,
303, 415, 434, 560, 596, 629f, 754, 755, 755t,
788, 820, 1008
with interatrial communication 560
trunk 519f, 520f, 526f, 528f, 529f, 530f, 531f,
532f, 538f, 539f, 686f
valve 9, 147, 473f, 583, 630f, 633
abnormalities59
anatomy434
atresia59
configuration in patients with tetralogy
of Fallot548
diseases434
replacement762, 790
stenosis59, 357
valvuloplasty64
vascular
bed931f
disease 266, 764, 1080
markings275
obstructive disease 270, 273, 619
resistance 88, 177, 261, 269, 416, 785,
881, 917, 921f, 932f, 935, 1016, 1064
vascularity 190, 194
vasodilators and dosage 940t
vein 49f, 152t, 231f, 552, 655f, 932f, 934f, 964f
bed congestion657
confluence57f
stenosis380, 384
veins, assessment of 651
venoatrial connections 148
venolobar syndrome 226
veno-occlusive disease 918f, 930, 934f
venous
anomalies57
confluence235f
drainage932f
hypertension195, 197f, 487f, 737, 930,
932f
plexus224f
pressure932f
wedge angiography575f
wedge angiogram 928
Pulmonic stenosis 45
Pulsatility index 68
for veins 68
Pulse 173, 184
oximetry 90, 245
Pulsed Doppler echocardiography 238
Pulsus
paradoxus720t
parvus et tardus 173
Purkinje tumors/hamartomas 905
PVC and left innominate vein 382f
PVC decompresses via vertical vein to portal
vein382f
Q
Quadricuspid
aortic valve 477t, 479, 479f, 488
valves499
Quality of life 828
Quantified in congenital heart defects 920
Quincke sign 490t
R
Radiofrequency ablation 758, 764
of accessory pathways 1019
Radionuclide
angiography451
ventriculography925
Radio-opaque ring of St. Jude valve 428f
Raghib syndrome 258f
Rastelli
classification296
repair764
Ratio of
minute volume to functional residual
capacity1010
pulmonary vascular resistance to systemic
vascular resistance 754
Raynaud syndrome 929
RCA from left aortic sinus 887
Recipient in twin-to-twin transfusion
syndrome65
Recurrences of CHD in families 34
Recurrent respiratory infections 167, 169
Red blood cell mass 771
Reduced
absent pulmonary valve flow 422
life expectancy 255
pulmonary functional capacity to thoracic
abnormalities823
systemic cardiac output 269
Reducing stress response to surgery and
bypass1051
Regional anesthesia 1036
Regulators of ductal patency 86t
Regurgitation and branch PA stenosis 615
Reimplantation of pulmonary artery 362
Re-intervention in tetralogy of Fallot 558
Rejection surveillance 1077
Relieve left pulmonary artery stenosis and
coil678f
Remote VSD type 597

Renal
cell carcinoma 181
failure1066
stenosis181
Rendu-Osler-Weber syndrome 243
Renin-angiotensin system 20
Repeated lower respiratory infections
168
Reproductive history 33
Residual
atrial septal defects 304
left-to-right shunt 659
shunts325
Resistive index 68
Respiration173
Respiratory
care1063
depression92
distress168
syndrome232
rate at different age 173t
system examination 181
tract infections 967
Response to pulmonary vasodilator
therapy926
Restrictions for moderate exercise 823
Restrictive
cardiomyopathy712
cardiomyopathy in children 719
Retinoic acid 971, 974
Retinopathy of prematurity 1012
Retroaortic innominate vein 214, 218
Retroesophageal circumflex arch 532f
Retrograde
ductus arteriosus flow 422
filling of aortic arch 54f
Rhabdomyomas 896, 905
Rhabdomyosarcomas 896, 906
Rheumatic
fever 475, 488
heart disease 488
Rhythm
disturbances1010
method 801, 803
Rib notching 199
Right
aberrant subclavian artery 533f
and left
heart49f
pulmonary veins235f
ventricular outflow tracts to aortic root,
relationship of472
anterior oblique 278, 360
aortic arch 415, 525f, 526f, 527, 527f, 528f,
529f, 531f, 534f, 536f
with aberrant left subclavian artery with
left-sided ductus528
with aberrant left subclavian artery with
persistent right ductus
528
with aberrant origin of left
brachiocephalic artery 530
with mirror image branching 527
aortic sinus 886f
atria98f
obstruction615
ventriclular
angiogram in neonate 699f
angiogram in posteroanterior view 421f
cineangiogram428f
decompression577
diastolic pressure442f
dilatation and dysfunction 688
end diastolic pressure 716, 1009
hypertrophy 180, 313, 334f, 362, 482,
560, 784
ouflow tract 151, 320, 347, 357, 472, 580,
761
outflow obstruction272
outflow tract47f, 208f, 348f, 443f, 557,
865
outflow tract obstructions 66f, 301, 357,
360, 549
systolic pressure 784, 819
tumors895
vertebral artery 532f, 543f
Right-sided
morphologic left ventricular
angiogram428f
stomach156f
Role of
3D echocardiography: 642
cardiac CT in congenital heart disease 203
endovascular stents in Marfan
syndrome955
exercise testing in diagnosis of aortic
stenosis488
guardians990
mental health services 832
newer cardiac imaging in congenital heart
diseases203
parents990
pediatricians and pedodontists 991
prostaglandins in patency of ductus 85
provider caring for patients with congenital
heart disease 828
radiography in congenital heart
diseases190
Root
canal therapy 981
of aneurysm above aortic annulus 350
Rosenbach sign 490t
Rubella971
syndrome 172, 972f
Rubinstein-Taybi syndrome 172
Rudimentary
left ventricle 386f
pulmonary valve 443f
Rudolphs hypothesis 507
Rupture of sinus of valsalva 349
surgical management of 352
RV index of myocardial performance 924
RV-dependent coronary circulation 583
S
Saccular-shaped aneurysm 350
Sacrococcygeal teratomas 65
Safety
of radiofrequency 873
vs efficacy of radiofrequency ablation 873
Sagittal planes 51
Sakakibara and Konnos classification of
ASV348
Sarcoidosis719
Sarcomas900
Schistosomiasis935
Schwartz/moss score for long QT syndrome
diagnostic criteria 858t
Scimitar
sign197
syndrome 138, 139, 226, 226f, 227
Scleroderma686
Scoliosis192f
SD ratio 68
Second
digeorge syndrome locus 108
heart field 97, 98f
Secondary
endocardial fibroelastosis 736
erythrocytosis772
polycythemia934f
pulmonary
arterial hypertension929
hypertension911
tumors901
Second-degree AV block 840
Secundum atrial septal defect 753
Segmental analysis of cardiac anatomy 47f
Seizure disorders and seizure medications 971
Seldinger technique 404
Selective
pulmonary angiograms 612
serotonin reuptake inhibitors 806, 833
Semilunar valves 10
Senning procedure 790
Separation
from bypass 1042
of tric 601f
Sepsis92
Septal reduction therapy 731
Septomarginal trabeculation 595f, 596f
Septum
formation in truncus arteriosus and conus
cordis9
formation in ventricles 10
Sequelae of fontan operation 656
Sequential segmental analysis 129
Serotonin
and norepinephrine reuptake inhibitor 833
reuptake inhibitors 834t
Seven key elements of effective transfer
program from childhood to adulthood 745
Severe
aortic stenosis 168
brain edema 776
cardiac diseases 155
coarctation of aorta 760
Ebsteins malformation of tricuspid
valve584f
hypertrophic cardiomyopathy 815f
hypoxemia, post fontan 658
infundibular stenosis 552f
left ventricular hypertrophy 369f
pulmonary
arterial hypertension333
hypertension168
index
atrial appendage 398f, 471f, 520f, 686f

left-sided151f
atrial
distension657
enlargement89, 911
morphology121
tumors895
atrioventricular valve stenosis or
regurgitation304
atrium 124, 141, 195f, 228f, 234, 415, 548,
552, 582, 738f
brachiocephalic
artery519f, 520f, 526f
vein229f
bronchus191
bundle branch block 358, 417, 762f, 865
carotid artery 528f
common
cardinal vein224f
carotid artery 525, 525-533f, 536f
coronary artery 471f, 547, 548, 557, 584f,
699f, 880, 882
from pulmonary artery 886
coronary
ostium469f
sinus471f
sinus of valsalva 338
heart catheter 422f, 599f
azygos system into right pulmonary
vein236f
heart failure 754
hepatic vein 231f
inferior pulmonary vein 235f
innominate artery 519f
isomerism639
lower pulmonary veins 228f
mediastinum628f
middle pulmonary vein 228f
portal vein 231f
pulmonary artery 53f, 188f, 195, 204f, 443f,
522f, 525f, 228f, 235f, 526f, 528-531f, 538f,
539f, 571f, 574f, 571f, 525f, 536f, 630f, 655f,
657f, 678f
posterior to ascending aorta 52f
pulmonary
vein228f, 236f
venous channel235f
sided aortic arch 195
sided heart failure 911
subclavian artery 518, 527f, 528f, 529f, 530,
532f, 536f
superior
pulmonary235f
truncus swelling9
superior vena cava 217f, 225, 548
draining into left atrium 218
upper
pulmonary vein254f, 257f, 257f, 259f
sternal border368
ventricle 17, 49f, 53f, 98f, 141, 195f, 235f,
382f, 415, 552, 557, 582, 580, 738
dependent coronary circulation 1071
dominant185
ejection function557
end diastolic pressure 557
pulmonary artery conduit
1105
1106
regurgitation442f
stenosis65, 437f, 438f
right ventricular
hypoplasia with muscular atresia 587
outflow obstruction22
RV hypoplasia, unipartite 581
sepsis155
subaortic
or subpulmonic obstruction 822
stenosis369f
tricuspid
regurgitation585f, 589
valve stenosis or atresia 59
uteroplacental insufficiency 65
valvar pulmonic stenosis 437f
Severely decreased systemic RV function 822
Severity of
Aortic
regurgitation on angiogram 493t
stenosis485t
regurgitation491
valvar obstruction 476
valve stenosis 820
Sexuality and reproductive issues 746
Sheath and catheter placement 870
Shones
anomaly 374, 377
complex bicuspid aortic valve 376f
syndrome cardiomegaly with left
ventricular197f
Short
neck with low set ears with abnormal auricle
and low hairline 171f
segment tracheal stenosis 539
upper lip bound by frenula to alveolar
ridge105f
Short-axis images 51
Shortness of breath 169
Short-webbed neck 104f
Shprintzen-Goldberg syndrome 948
Shunt
arterial level 936
atrial level 936
calculations1019
defects787
lesions 752, 753t, 819
ventricular level 936
Sick
sinus syndrome 840
ventilated small infants 324
Side effects of prostaglandins 92t
Sideris buttoned device 317
Signs of congestive heart failure 66
Sildenafil940
Silent patent ductus arteriosus 316
Silver syndrome 362
Simple closure of ASD 424
Simultaneous opacification of aorta 552f
Single
coronary artery 887
gene
defects44
disorder104
outlet54
umbilical artery 44
ventricle644
physiology766, 822
Sinoatrial portion of heart 224f
Sinotubular junction 469, 470f
outlet of aortic root 470
Sinus
arrhythmia839
bradycardia 74, 839
of valsalva 489, 816
aneurysm341
structure and function 470
pause840
tachycardia72
venosus213f, 214f
atrial septum53f
defect254f
venous98f
Sinuses of valsalva 469, 951
in Marfan syndrome 952f
Situs 129, 190
ambiguous 130, 145
and looping, abnormalities of 25
inversus 44, 53, 130, 141, 145
solitus 130, 145, 191f
Size of
interatrial communication 400
left atrium 820
shunt936
Sleep disorders 693
Sleep-disordered breathing 918f, 934
Slings anomalies 525
Small
chin171f
inlet ventricular septal defect with
left-to-right shunt 301f
or restrictive defects 270
pulmonary artery 60f
right ventricle 403f
Smaller genitalia 962
Smith-Lemli-Opitz syndrome 106
Smooth muscle cell 919f, 920f
Snowman
appearance187
in snow storm 197
Sociodemographic factors 33
Solitary arterial trunk 131
Solitus53
Somerville classification 568
Sonic and ultrasonic tooth brushes 987
Spatiotemporal image correlation
technology46
Special
challenges of preoperative management 91
forms of AVSD 297
postoperative care 537
Specific cardiomyopathies 694, 717
Spectrum of congenital anomalies of mitral
valve445t
Spherical remodeling with reorientation of wall
fibers651
Spine53f
Spiritos score 727
Spirito-Maron index 727

Splanchnic venous plexus 224f
Spleen154
in ILAA, morphology of 154
Splenic
morphology148
vein231f
Spontaneous
closure of VSD 271
echo contrast 688
Square-root sign 716f
Stable heart failure 796
Staphylococcus aureus161
Starlings concept of transvascular fluid
exchange389
Starnes procedure 425
Steady state free precession sequence 704
Steinberg thumb sign 948f
Stem cell therapy 693
Stenosis or atresia of individual pulmonary
veins237
Stenotic
aortic valve, morphology of 476
connections224
valve, morphology of 476
Stent placement 513
Sterilization 801, 803
Stickler syndrome 947
Stigma831
Stokes-Adams syncope 896
Storage disease 720
infiltration445
Strategies to reduce bleeding after
bypass1048
Streptococcus
pneumoniae161
sanguis980
viridans 776, 787
Stress
echocardiography815
response to cardiac surgery 1050
Stress-induced cardiomyopathy 686
Structural heart disease, namely CAVSD
161
Studies on risk factors for CHD 36
Subacute bacterial endocarditis 913, 1004
prophylaxis American Heart Association,
guidelines for 1006t
Subaortic
membrane369f
stenosis 273, 366, 371, 377f, 596
ventricular septal defect 595f
Subcategory of SVC anomalies 214
Subclavian
flap repair 509
steal syndrome 558
Subcostal recession 167
Subpulmonary ventricular septal defect 598f
Subpulmonic ventricular septal defect 208,
595f
Subtotal cor triatriatum 382f
of right pulmonary veins 382f
Subvalvar lvoto622
Subvalvular fibromuscular collar or tunnel 367
pulmonary shunts 575

vascular resistance 269, 549, 785, 1025,
1064
veins152
assessment of651
venoatrial connections 148
venous
abnormalities56
anomalies, classification of 213
hypertension657
ventricular dysfunction and heart
failure764
Systolic
anterior motion 729
of MV480f
blood pressure 785
closure of aortic valve 369f
diastolic ratio 68
ejection
clicks178
period67f
murmurs179
pulmonary artery pressure 924
velocity68
T
Tachyarrhythmias 794, 847
Tachycardia92
mechanism of 847, 852
Tachycardiomyopathy686
Tachypnea 167, 169
Tadalafil940
Takayasus arteritis. 362
Teratogen exposure 44
Terminologies related to aortic valve 474t
Tetralogy of Fallot 22, 28, 61, 93, 99, 139, 142,
172, 187f, 194, 203, 204f, 214, 227, 267, 297,
360, 390, 415, 434, 435, 527, 547, 548, 551f,
552, 556f, 558, 560, 565, 594, 761, 762f, 789,
821, 865, 921, 972
post repair 757t
pulmonary atresia 565
severe form 87
with absent pulmonary valve 204
with dilated pulmonary artery 198f
with severe
oligemia195f
PS89
Thalidomide 26, 975
and sulfa drugs 971
Therapeutic drug exposure 26
Thermal stabilization 1013
Thickened interventricular septum 726
Thinned and dilated right ventricular 582, 589
Third and fourth heart sound 177
Third-degree AV block 841
Thoracic
aneurysms and chronic dissections 955
aortic aneurysms and aortic
dissections946
aortogram612
Thoracoabdominal organs in heterotaxy
syndrome, abnormalities of 148
Three fetuses with irregular rhythm 72f
Three-dimensional echocardiography 421

Thrombocytopenia 92, 172
hemorrhage796
Thromboembolic
episodes657
obstruction918f
Thymic shadow 190, 193
Thyroid disorders 918f, 963
Tissue
Doppler imaging 953
in aortic stenosis 486
or bioprosthetic valve 497
plasminogen activator 920f
valved pulmonary artery conduits 804
valves496
Tooth
brushes986
brushing techniques 989
Topical agents 1049
Tortuous extracardiac portion of tunnel 343f
Total anomalous
coronary circulation from pulmonary
artery886
pulmonary venous connection 92, 196,
198f, 204, 230, 921
cardiac231
mixed231
supracardiac231
pulmonary venous
drainage183
return609
systemic venous
connection213
drainage220
drainage into left atrium 220
Total cardiopulmonary
bypass323
connection 653, 767, 792, 801
Total neopulmonary artery index 576
Toxic epidermal necrolysis syndrome 777
Trabecular septomarginalis 127, 132
Trachea and esophagus to reach descending
aorta532f
Tracheal bifurcation 191
Tracheoesophageal fistula 44
Transabdominal chorionic vill sampling 111f
Transcatheter
closure of atrial septal defects 262
intervention363
PDA occlusion, recommendations for 317
procedures in pulmonary atresia with
pulmonary valve replacement 441
techniques279
Transcranial Doppler 1031
Transcutaneous aortic valve implantation 498f
Transesophageal
2D echocardiography 258
and 3D echocardiography 277
echocardiography 227, 277, 368, 421, 597,
629, 897, 953, 1023
midesophageal short-axis497f
Transforming growth factor 244, 952
Transient ischemic attacks 245, 426
Transition from childhood to adulthood 966
index
Sudden cardiac death 456, 693, 723, 730, 765,

814, 849, 886, 894
in athletes 814
in hypertrophic cardiomyopathy, risk factors
for730t
Sudden death 863
Superior
mesenteric
artery155
vein231f
vena cava 7, 17, 51, 51f, 52f, 121, 196, 205f,
226f, 229f, 230, 230f, 231f, 235f, 253, 254f,
257f, 259f, 309f, 626f, 639, 655f, 657f, 665f,
672f, 1029, 1075
obstruction142
Supplemental oxygen 938
Supracardiac TAPVC 233
Supramitral ring 445t, 703f
Supravalvar aortic stenosis 173, 370t, 371, 374
Supravalvular
stenosing ring 380, 383
stenosis820
Supraventricular tachycardia 72, 416, 426, 821,
847, 848, 871
includes both atrioventricular 74f
Surgery for
double outlet right ventricle 601
dual orifices in left atrioventricular
valve304
heart defects 965
various age groups, indications for 279t
Surgery, indications for 326
Surgical
correction, objectives of 303
intervention in heterotaxy syndrome,
results of 159
management of single ventricle 651, 653f
procedures in vascular rings 537
repair
of congenital heart diseases 1022
results of305
septal myectomy 730, 731
techniques for intracardiac repair 557
Survival without treatment in patients with
Swan-Ganz catheter 359
Symmetrical liver 146
Symptoms of exercise intolerance and fatigue/
congestive heart failure 254
Syndromes with common atrium 639
Systemic
and pulmonary vasculature effects 1047
arterial saturations 400f
AV valve regurgitation 764
circulation184
collateral
arteries, characteristics of 567t
artery568f
disease44
inflammatory response syndrome 1010
lupus erythematosus 686
manifestations in heterotaxy 155
1107
1108
Transitional AVSD 293

care in congenital heart disease 745
Transport
and handover to pediatric intensive care
unit1034
of baby with duct-dependent congenital
heart disease 93
Transposition of great
arteries 22, 84, 87, 89, 105, 173, 198f, 297,
415, 519, 594, 618, 619, 621f, 763, 822
and ebstein anomaly of left
atrioventricular valve428f
vessels 61, 87f, 170
Transthoracic
2D echocardiography 256, 267
echocardiogram 215, 911, 998
of secundum atrial septal defect 257f
echocardiography 313, 350, 368, 388f, 451,
487f, 628, 702, 897, 899f, 1029
Transvenous
biopsy904
pacemakers without right-to-left
shunts804
Transverse scans 46
Traube sign 490t
Treadmill stress testing 814
Treatment in Eisenmenger syndrome,
recommendations for 941t
Treatment of pulmonary arterial
hypertension939f
Trebeculated ventricular chamber to
aorta428f
Treprostinil940
Triangular resection 496f
Tricuspid
annular plane systolic excursion 924
aortic valve 477t
atresia 45, 87, 90, 183, 397, 402f
classification of398
double inlet left ventricle 185
with PS89
regurgitation66f, 180f, 429, 634, 764
stenosis911
valve 268, 403f, 473f, 582, 632f, 686f, 767f,
964f
abnormalities59
prolapse951
repair or replacement of 424
stenosis429
valvular dysplasia 65
Triggered activity 847
Trilogy of Fallot 560
Trimethoprim-sulfonamide26
Tripartite RV 581
Trisomy 13 100, 112
Trisomy 18 100
Trisomy 21 99, 112
Trisomy period 112
Trucus asteriosus 103
True univentricular heart 646
Truncal
root
angiography612
dilatation616
valve605
regurgitation616
Truncus arteriosus 45, 62, 131, 183, 362,
604, 612f
with small pulmonary arteries 183
Tuberous sclerosis 44
Tubular hypoplasia 520f
Tumors in fetal life 906
Tunnel-like obstruction 367
Turners syndrome 63, 100, 112, 172, 488, 489,
505
with aortic ectasia 488
Twins35
Twin-twin transfusion syndrome 44
Types of
aorto-left ventricular tunnel 338
aortopulmonary window 333f
arrhythmias71
artificial valves 496
exercise 812, 813f
human heart 133f
interrupted aortic arch 519f
perimembranous ventricular septal
defect278f
pulmonary hypertension 929
systemic collateral arteries 568f
univentricular heart 649
Typical congenital mitral stenosis 385
U
Umbilical
arteries 12, 69
artery PI 68
cord blood sampling 111
vein7f, 213f, 224f
venous catheter 422f
Unbalanced with
left dominant type 295
right dominant type 295
Unconscious
competence182
incompetence182
Underdevelopment of right ventricle 9
Underestimation of gradient across AV 484
Underexposed or overexposed 190
Unfractionated heparin 796
Unicuspid
aortic valve 476, 477t
unicommissural aortic valve 477f
valve477f
Unified classification of tricuspid atresia 398
Unilateral pulmonary venous atresia 240
Unique
characteristics of pediatric cardiac
anesthesia1024t
features of pediatric cardiac
anesthesia1024
Uniqueness of fetal circulation 16
Univentricular
atrioventricular connection 645
connections53
heart 771, 792, 822
of left ventricular type 644
of right ventricular 644

with fontan operation 766
Unnoticed blood loss 1010
Unoperated valve disease 804
Unroofing of coronary sinus 183
Upper lobe branch 599f
Use of
hydroxyurea in hyperviscosity
syndrome774
pulse oximetry in routine screening for
congenital heart disease 90
V
Valsalva maneuver 725, 752
Valvar
aortic stenosis 366, 476
pulmonary stenosis 104, 357, 359f
in adults358
in children357
in neonate357
Valve leaflets
and valve orifice 414
Valve ring hypoplasia 359
Valve, morphology of 477t
Valvular
atresia 566f
defects 754, 755t
diseases820
heart disease 918f
Various
aortic valves for percutaneous
implantation498t
cardiac chambers, morphological features
of130
echocardiographic patterns in aortic arch
anomalies535
Vascular
anomalies of aorta 533f
channels932f
endothelial growth factor 896, 920f
injury1010
plug IV 249f
resistance1019
ring, classification of 526
rings525
smooth muscle cells 493
tracheoesophageal compressive
syndrome 542, 543f
tumor 44, 65
Vasoconstriction934
Vasodilator therapy 939
Vasular plug 249f
Vein of Galen 65
Velocardiofacial syndrome 101, 146, 184
Venoatrial connection 148
Venous
access1012
blood pressure 18
connection184
Doppler 66, 67
pressures184
discordance822
junction 132, 469
attachment of aortic root to heart 469
Ventriculography612
Vertical vein 234f, 382f
Viral cardiomyopathy 686
Virus negative inflammatory myocarditis 692
Visceral
heterotaxy145
situs137
Visceroatrial situs 190
Viscerocardiac heterotaxy 161
Vitamin31
A32
congeners971
congeners974
Vitelline vein 7f, 14, 213f
VSD type 597
Wave Doppler both mitral stenosis and

regurgitation392f
Westermark sign 200
Wheezing92
White blood cells 718
and platelets 772
Wide splitting 176
Widened superior mediastinum 533
Williams syndrome 171f, 173
William-Beuren syndrome 362
Williams syndrome 103, 172
Williams-Beuren syndromes 103, 371, 505
Wolf-Hirschhorn syndrome 103
Wolf-Parkinson-White syndrome 415, 756, 784,
791, 797, 821, 847, 852
Woods theory 549
Worsening cyanosis 657
index
Ventricles 126, 131, 459, 606

with dominant left ventricle 650f
Ventricular
arrhythmias 761, 822, 856
assist devices 1053
dimensions491
ejection73f
failure659
fibrillation730
function 184, 491, 657, 819
heart disease 918f
level, single ventricle 183
loop 147, 150
outflow tract 565
premature complexes 687, 729f, 794
septal defect 9, 21, 48, 57, 87f, 99, 138, 151,
171, 180f, 259, 266, 267, 273f, 276f, 279,
282f, 301f, 304, 310, 347, 348, 360, 366, 382,
406f, 415, 442, 461f, 470, 505, 547, 594,
595f, 598f, 604, 605, 610f, 611f, 613f, 618,
619, 625, 632f, 703f, 753, 754, 761, 787, 819,
848, 921, 965, 973, 995, 1009
absent pulmonary valve with 442
absent pulmonary valve without 442
closure576
septum98f, 459
tachycardia 72, 74, 730, 849f, 857
in postoperative tetralogy of Fallot 865
Ventriculoarterial
connections 54, 649
W
Wandering pacemaker 839
Warfarin795
aspirin recurrent stroke study 752
embryopathy795
Water chlorination byproducts 33
Waterson
Cooley shunt 406
groove124
shunt 557, 761
Yeast artificial chromsome 107

Young with congenital health disease,
informational needs for 747t
Youngs theory 549
Z
Zellweger syndrome 106
Z-score 53, 553, 571
charts641
1109

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A Comprehensive Approach to

Professor of Pediatric Cardiology

Professor of Pediatrics and Medicine

JAYPEE BROTHERS MEDICAL PUBLISHERS (P) LTD

Jaypee Brothers Medical Publishers (P) Ltd

Jaypee-Highlights medical publishers Inc.

Jaypee Brothers Medical Publishers Ltd

2013, Jaypee Brothers Medical Publishers

Consultant Pediatric Cardiologist

Consultant Pediatric Cardiologist

James R Bentham DPhil BM BCh BA

Chitra Narasimhan MD FICPC

Debasree Ganguly MD FNB(Ped Card)

Sree Chitra Tirunal Institute for Medical

Associate Professor of Pediatrics

A Comprehensive Approach to Congenital Heart Diseases

Krishnamoorthy KM DM DNB FACC

Gowrishankar MS MCh DNB

Kumsi Sridhar MS MCh

Harold N Bass MD FACMG

Maitri Chaudhuri MD FNB

Professor and Head

Marhisham Che Mood

MD DM FICC FIAMS FIAE FICP FCSI FAMS DSc

Professor of Pediatric Cardiology

Narendra Babu M MS MCh

PM Chandrasekhara MD FICC FIACTA

Associate Professor of Cardiology

Ramesh Santhanakrishnan MS MCh DNB

Professor of Pediatrics and Medicine

Satish Govindiah MS MCh

A Comprehensive Approach to Congenital Heart Diseases

Sridevi Hegde MBBS DCH PhD

Tracy Kustwan Livecchi

Shishu Shankar Mishra

Varsha Kaulgud Mokhasi MD

MD FAIMS MCAM DoCM FCCP FIAE FICC

Professor and Director

Streisand/American Heart Association

FRCP (Lond), FRCPE, FAMS, FACC, FAHA,

Founder-President, All India Heart Foundation

A Comprehensive Approach to Congenital Heart Diseases

3. Etiopathogenesis of Congenital Heart Diseases

5. Congenital Heart Diseases with Duct-Dependent Circulation

6. Genetics in Congenital Heart Diseases

8. Classification of Cardiovascular Anomalies and their Terminologies

10. Heterotaxy Syndrome

11. Bedside Diagnosis of Acyanotic Congenital Heart Diseases

12. Clinical Approach to Cyanotic Heart Diseases

13. Role of Radiography in Congenital Heart Diseases

14. Role of Newer Cardiac Imaging in Congenital Heart Diseases

A Comprehensive Approach to Congenital Heart Diseases

Section 3: Defects in Atriovenous and Pulmonary Arteriovenous Connections

16. Anomalies of Pulmonary Veins

17. Congenital Pulmonary Arteriovenous Fistula

Section 4: Shunt Defects

19. Ventricular Septal Defects

20. Atrioventricular Septal Defects

21. Patent Ductus Arteriosus

22. Aortopulmonary Window

23. Aorticocameral Tunnels

24. Aneurysm of Sinus of Valsalva

Section 5: Right and Left Ventricular Obstructive Lesions

26. Left Ventricular Outflow Tract Obstructions