A Comprehensive Approach To Congenital Heart Diseases PDF

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 James R Bentham DPhil BM BCh BA Charles W Hoopes
Assistant Professor of Cardiology Paediatric Cardiology Intervention Fellow Associate Professor of Surgery
Sree Chitra Tirunal Institute for Medical Yorkshire Heart Centre Director, Heart Lung Transplant and
Sciences and Technology Leeds General Infirmary Mechanical Cardiac Support Program
Trivandrum, Kerala, India Leeds, UK University of Kentucky College
abhispin@gmail.com bentham@well.ox.ac.uk of Medicine, Lexington, KY, USA
Bhanu Duggal MD DM Chitra Narasimhan MD FICPC
AM Jagadeesh MD Associate Professor of Cardiology
Professor and HOD Assistant Professor of Clinical
Grant Medical College and Pediatric Cardiology
of Cardiac Anesthesia Sir JJ group of Hospitals Sri Jayadeva Institute of Cardiovascular
Sri Jayadeva Institute of Cardiovascular Mumbai, India Sciences and Research
Sciences and Research medhawini2k@yahoo.com Bengaluru, India
Bengaluru, India
Bhushan Chavan chitradr@gmail.com
Anil Sivadasan Radha Junior Consultant in Pediatric Cardiology
Debasree Ganguly MD FNB(Ped Card)
MD DNB(Pediatrics) DNB(Cardiology)
Madras Medical Mission
Junior Consultant in Pediatric Cardiology
Consultant Pediatric Cardiologist Chennai, India
Rabindranath Tagore International Institute
Department of Pediatric Cardiac Sciences Biswajit Bandyopadhyay of Cardiac Sciences
Apollo Health City, Jubilee Hills Head of the Department Kolkata, India
Hyderabad, India Sr Consultant Pediatric Cardiologist debasreeganguly23@gmail.com
dranil.s.r@gmail.com Rabindranath Tagore International Institute
of Cardiac Sciences (RTIICS) Deborah J Kozik
Anita Shet MD Kolkata, India Assistant Professor of Surgery
Associate Professor bisban@rediffmail.com University of Kentucky College
Department of Pediatrics of Medicine
Brannon Hyde Pediatric Cardiac Surgery
St John’s Medical College Hospital
Fellow in Cardiothoracic Surgery Kentucky Children’s Hospital
Bengaluru, India
University of Kentucky Lexington, KY, USA
anitashet@gmail.com
College of Medicine
Lexington, KY, USA Devananda NS MS MCh
Anurakti Srivastava
Consultant and Head
MD(Pediatrics), Fellow (Pediatric Cardiology) Biswaranjan Mishra MD DM
Department of Cardiothoracic Surgery
Consultant Pediatric Cardiologist Chief Consultant Cardiologist
Manipal Heart Institute
Department of Pediatric Cardiac Sciences Eko Imaging Institute
Bengaluru, India
Apollo Health City, Jubilee Hills Medical Road, Mangalabag
devananda_ns@yahoo.com
Hyderabad, India Cuttack, Odisha, India
anurakti07@yahoo.co.in drbisumishra@yahoo.co.in Dinesh Choudhary
Chandrakant B Patil MD DM Fellow in Cardiac Electrophysiology
Arjun Kalyanpur ABR Professor and HOD of Cardiology Sree Chitra Tirunal Institute for Medical
Chief Radiologist St Johns Medical College Sciences and Technology
Teleradiology Solutions Bangaluru, India Trivandrum, India
Bengaluru, India drcbpatil@gmail.com drdineshchoudhary8@gmail.com
arjun.kalyanpur@telradsol.com
Chandrika YR MD Duraisamy Balaguru
Professor and HOD MBBS DCH MRCP (UK) FAAP FACC
Asha Moorthy MD DM
Pediatric Anesthesiology Associate Professor of Pediatrics
Professor of Cardiology
Indira Gandhi Institute of Division of Pediatric Cardiology
Sri Ramachandra University
Child Health UT-Houston Medical School
Chennai, India
Bengaluru, India Houston, Texas, USA
drashasrmc@yahoo.co.in
doctoryrc@gmail.com Duraisamy.Balaguru@uth.tmc.edu
English C Flack MD MS Kiron Varghese MD DM Mazeni Alwi
Clinical Fellow Professor of Cardiology Senior Consultant in Paediatric
Pediatric Heart Institute St Johns Medical College Cardiology Paediatric and
Monroe Carell Jr Children’s Hospital Bangaluru, India Congenital Heart Centre

at Vanderbilt drkiron@hotmail.com Institut Jantung Negara
Nashville, Tennessee, USA (National Heart Institute)
english.c.flack@vanderbilt.edu Krishnamoorthy KM DM DNB FACC Kuala Lumpu, Malaysia
Additional Professor of Cardiology muhaneeza@ijn.com.my
Girish Warrier MS MCh(CVTS)
Consultant Pediatric Cardiac Surgeon Sree Chitra Tirunal Institute for Medical Mitesh Shetty
Department of Pediatric Cardiac Sciences Sciences and Technology MBBS MS(Medial Genetics-UK) PhD
Apollo Health City, Jubilee Hills Trivandrum, India Consultant
Hyderabad, India kmkm@sctimst.ac.in Medical Genetics
Manipal Hospital
Gowrishankar MS MCh DNB Kumsi Sridhar MS MCh Old Airport Road
Associate Professor of Pediatrc Surgery Professor of CTVS Bengaluru, India
Indira Gandhi Institute of Child Health Sri Jayadeva Institute of Cardiovascular mitesh@manipalhospitals.com
Bengaluru, India Sciences and Research
bcgshankar@gmail.com Bengaluru, India Maddury Jyotsna MD DM FACC FESC FICC
Additional Professor of Cardiology
Harold N Bass MD FACMG Nizams Institute of Medical Sciences
Madhav Hegde MD
Department of Genetics Secunderabad, AP, India
Consultant Cardiothoracic Radiologist
Kaiser Permanente Medical Center mail2jyotsna@rediffmail.com
Bengaluru, India
Panorama City, California, USA
docmadhavhegde@gmail.com MN Krishnan
Clinical Professor of Human Genetics
and Pediatrics DM FRCP FACC FESC FSCAI FCSI
David Geffen School of Medicine Maitri Chaudhuri MD FNB Professor and Head
University of California, Los Angeles Consultant Pediatric Cardiologist Department of Cardiology
(UCLA) Los Angeles, California, USA Manipal Hospitals and Vikram Hospitals Government Medical College
Bengaluru, India Kozhikode, Kerala, India
IB Vijayalakshmi drmaitricee@gmail.com dr.mn.krishnan@gmail.com
MD DM FICC FIAMS FIAE FICP FCSI FAMS DSc
Professor of Pediatric Cardiology Marhisham Che Mood Mrutyunjaya Satpathy MD DM
Sri Jayadeva Institute of Cardiovascular Senior Registrar in Paediatric Cardiology Former Professor of Cardiology
Sciences and Research Paediatric and Congenital Heart Centre Haripur Road, Dolmundai
Bengaluru, India Institut Jantung Negara Cuttack, Odisha, India
docvj@yahoo.com (National Heart Institute) m_satpathy03@yahoo.co.in
Kuala Lumpur, Malaysia MS Aditya MD DM
Jain T Kallarakkal MD DM
dr.marhisham@ijn.com.my Assistant Professor of Cardiology
Professor and HOD
MBMM Hospital Nizams Institute of Medical Sciences
Mark D Plunkett MD Secunderabad, AP, India
Kochi, India
Associate Professor of Surgery aditya.ms11@gmail.com
doctorjain1973@yahoo.com
Chief, Division of Cardiothoracic Surgery
Munde K
Jaydeepa S University of Kentucky College
Assistant Professor of Cardiology
Consultant Radiologist of Medicine
Grant Medical College and
Teleradiology Solutions, Director, Pediatric Cardiac Surgery
Sir JJ group of Hospitals
Bangaluru, India Kentucky Children’s Hospital
Mumbai, India
Lexington, KY, USA
Jayashree Kharge MD DM drkalyanmunde@yahoo.com
mplun2@email.uky.edu
Assistant Professor of Cardiology
Nagamani AC MD DM
Sri Jayadeva Institute of Cardiovascular
Mary M Canobbio RN MN FAAN Associate Professor of Cardiology
Sciences and Research
Lecturer School of Nursing Sri Jayadeva Institute of Cardiovascular
Bengaluru, India
Clinical Nurse Specialist Sciences and Research
khargej@gmail.com
Ahmanson/UCLA Adult Congenital Heart Bengaluru, India
Kiran VS Disease Center drnagamani_c@yahoo.co.in
Consultant UCLA Transitional Care Program for
Nagesh CM MD DM
Pediatric Cardiology Adolescents with Congenital
Associate Professor of Cardiology
Narayana Hrudayalaya Institute Heart Disease
of Cardiac Sciences, University of California Los Angeles Sciences and Research
Bengaluru, India (UCLA)
viii Bengaluru, India
drkiranvs@gmail.com Los Angeles, CA, USA drnageshcm@yahoo.com
Narayanan Namboodiri KK Pamela D Miner RN MN NP Ramesh Arora
MD DM DNB FIC(Aus) Nurse Practitioner MD DM FICC FCSI FIMSA FACC
Associate Professor of Cardiology Adult Congenital Heart Disease Chief Cardiologist
Contributors
Sree Chitra Tirunal Institute for Medical Ahmanson/UCLA Metro Heart Institute
Sciences and Technology Adult Congenital Heart Disease Center Noida, NCR
Trivandrum, India University of California Los Angeles Ex-Director
kknnamboodiri@yahoo.co.in (UCLA) Professor and Head
Los Angeles, California, USA Cardiology Department
Narendra Babu M MS MCh
Maulana Azad Medical College and
Associate Professor of Pediatrc Surgery
PM Chandrasekhara MD FICC FIACTA GB Pant Hospital, New Delhi, India
Indira Gandhi Institute of Child Health
Professor and HOD yuktiarora@hotmail.com
Bengaluru, India
Anaesthesia and Pain Management
drnarendrababum88@gmail.com Ramesh Santhanakrishnan MS MCh DNB
Sagar Hospitals, Bengaluru, India
Neeraj Awasthy MD FNB pmc.cardiacanaes@gmail.com Professor and HOD of Pediatric Surgery
Associate Consultant Indira Gandhi Institute of Child Health
Department of Pediatric and Congenital Prabhat Kumar MD FSCAI Bengaluru, India
Escorts Heart Institute and Research Centre Professor and HOD of Pediatric Cardiology doctorsramesh@gmail.com
New Delhi, India Military Hospital (CTC)
Reema Chugh MD FACC
n_awasthy@yahoo.com Armed Forces Medical College
Consultant
Pune, India
Neeraj Raghani MD DM Cardiology/Adult Congenital Heart Disease
drprabhat_cardio@yahoo.co.in
Assistant Professor of Cardiology and Heart Disease in Pregnancy
Grant Medical College and Kaiser Permanente Medical Center
Sir JJ group of Hospitals Pradeep Vaideeswar Panorama City, California, USA
Mumbai, India Professor (Additional)
drnirajraghani@yahoo.co.in Department of Pathology R Suresh Kumar MD DM FSCAI
(Cardiovascular and Thoracic Division) Senior Consultant in Pediatric Cardiology
Neeru Kaushik MD Seth GS Medical College, Frontier Lifeline, Chennai and
Assistant Professor of Pediatrics Mumbai, India Dr KM Cherian Heart Foundation
Pediatric Heart Institute shreeprajai@yahoo.co.in Tiruvalla, India
Monroe Carell Jr Children’s Hospital r.sureshkumar.mmm@gmail.com
at Vanderbilt Prasanna Nyayadhish
Nashville, Tennessee, USA Professor of Cardiology Sanjay Khatri MD DNB(Ped) FDNB(Ped Card)
Seth GS Medical College and KEM Consultant
Nicholas Hayes MBChB MRCPCH
Hospital, Parel, Mumbai, India Department of Pediatric Cardiology
Locum Consultant in Paediatric Cardiology
prasannanyayadhish@hotmail.com Fortis-Escorts Heart Institute
Evelina Children’s Hospital
New Delhi, India
6th Floor, Westminster Bridge Road
London SE1 7EH, UK Prasanna Simha Mohan Rao MS MCh
Professor of CTVS Sanjeev Kumar Veeredddy
Nick.Hayes@gstt.nhs.uk Senior Resident in Cardiology
Nirav Panchani MD DM Sciences and Research Seth GS Medical College
Assistant Professor of Cardiology Bengaluru, India and KEM Hospital
Grant Medical College and prasannasimha@gmail.com Parel, Mumbai, India
Sir JJ group of Hospitals dr_rahulreddy@yahoo.co.in
Mumbai, India Praveen Jayan JP MD DM
drniravpanchani@yahoo.com Satish MD DM
Consultant Cardiologist Assistant Professor of Cardiology
Nolan Thompson MD Bharath Hospital Sri Jayadeva Institute of Cardiovascular
Chief of Service Kottayam, Kerala, India Sciences and Research
Department of Psychiatry praveenjayan@gmail.com Bengaluru, India
Kaiser Permanente Medical Center reddy7sathish7@yahoo.com
Panorama City, California, USA P Syamasundar Rao
MD DCH FAAP FACC FSCAI Satish Govindiah MS MCh
Sudhayakumar N MD DM Professor of Pediatrics and Medicine Professor of CTVS
Professor of Cardiology Emeritus Chief of Pediatric Cardiology Sri Jayadeva Institute of Cardiovascular
Amrita Institute of Medical Sciences UT-Houston Medical School Sciences and Research
Kerala, India Houston, Texas, USA Bengaluru, India
nsudhayakumar@gmail.com P.Syamasundar.Rao@uth.tmc.edu satishgovindaiah@yahoo.co.in
ix
Seema Thakur S Radhakrishnan MD DM Syed T Rizvi MD
Senior Consultant HOD and Director Consultant in Psychiatry
Genetic and Fetal Medicine Department of Pediatric and Congenital Child and Adolescent Psychiatry
Fortis Health Care, New Delhi, India Escorts Heart Institute and Research Centre Department of Psychiatry
New Delhi, India Kaiser Permanente Medical Center
Sejal Shah
samurai43@yahoo.com Panorama City, California, USA
Consultant
Pediatric Cardiology Thomas P Graham MD
Sridevi Hegde MBBS DCH PhD
Narayana Hrudayalaya Institute of Emeritus, Professor of Pediatrics
Head of Department and Consultant
Cardiac Sciences, Bengaluru, India Pediatric Heart Institute
Medical Genetics, Manipal Hospital
sejalshahsuresh@yahoo.com Monroe Carell Jr Children’s Hospital
Old Airport Road, Bengaluru, India
at Vanderbilt
Shada J Al-anani sridevi.hegde@manipalhospitals.com
Nashville, Tennessee, USA
Fellow in Pediatric Cardiology
Rush Center for Congenital and Srilatha Alapati MD Tracy Kustwan Livecchi
Structural Heart Disease Assistant Professor of Pediatrics Licensed Clinical Social Worker
Rush University Medical Center Division of Pediatric Cardiology Psychotherapist
Chicago, IL, USA Texas Tech Health Sciences Center Adult Congenital Heart Association
Amarillo, Texas, USA Mental Health Consultant
Shakeel Ahmed Qureshi
Westport, Connecticut, USA
Professor of Pediatric Cardiology
Evelina Children’s Hospital Shishu Shankar Mishra Varsha Kaulgud Mokhasi MD
6th Floor, Westminster Bridge Road MD FAIMS MCAM DoCM FCCP FIAE FICC Professor and HOD
London SE1 7EH, UK Professor and Director Department of Anatomy
Shakeel.Qureshi@gstt.nhs.uk Department of Cardiology Vydehi Institute of Medical Sciences
Hi-Tech Medical College Bhubaneswar Bengaluru, India
Shardha Srinivasan MD Sr Consultant Cardiologist varsha_mokhasi@yahoo.com
Associate Professor of Pediatrics Med ‘N’ Heart Clinic
Director of Fetal Cardiology Cuttack, Odisha, India Vimala J MD DM
Co-director of Echocardiography drssmishra@yahoo.com Senior Consultant Pediatric Cardiologist
American Family Children’s Hospital The Madras Medical Mission
University of Wisconsin, Madison, USA Sunita Maheshwari ABP ABPC(USA) Chennai, India
ssrinivasan3@pediatrics.wisc.edu Senior Consultant vimalajesudian@gmail.com
Pediatric Cardiologist Neil Wilson MB BS DCH FRCP FRCP(CH) FSCAI
Shilpa Suresh Mavanoor DNB MCh
Bengaluru, India Consultant Paediatric Cardiologist
Assistant Professor of CTVS
sunita.maheshwari@telradsol.com John Radcliffe and Children’s
Sciences and Research Hospital Oxford
Bengaluru, India Suresh G Rao MS MCh Dip.NB FIACS Honorary Senior Lecturer Dept Paediatrics
shilpa.suresh@gmail.com Pediatric and Congenital Heart Surgeon University of Oxford
Director, Children’s Heart Centre Oxford, UK
Smita Mishra Kokilaben Dhirubhai Ambani Hospital neilwil1@aol.com
Senior Consultant Mumbai, India
Pediatric Cardiology raosureshg@gmail.com Ziyad M Hijazi MD MPH FSCAI FACC FAAP
Escorts-Fortis Health Care James A Hunter, University Chair
New Delhi, India Swati Garekar Professor of Pediatrics
smi1@rediffmail.com American Board Certified and Internal Medicine
(Pediatric Cardiology) Director, Rush Center for Congenital
Spoorthi Anup Belludi BDS MDS Consultant Pediatric Cardiologist and Structural Heart Disease
Professor of Periodontics Children’s Heart Centre Section Chief, Pediatric Cardiology
Department of Periodontics Kokilaben Dhirubhai Ambani Hospital Rush University Medical Center
KLE Society’s Institute of Dental Sciences Mumbai, India Chicago, IL, USA
Bengaluru, India swatigar@gmail.com Ziyad_Hijazi@rush.edu
x
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 goal—IB 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 Children’s Hospital of
Philadelphia founded three years later. The Children’s 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? Osler’s Principles and Practice of Medicine devoted a scanty five pages to Congenital
Affections of the Heart. Holt’s Diseases of Infancy and Childhood devoted seven pages to Congenital Anomalies of the Heart.
In 1929, in Eberswalde near Berlin, Werner Forssman performed the world’s 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 chapters—Section 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 whole-
hearted 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 field—Dr 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 Lab—Paul Junkel, Sarah Phillips, Terri McAnallen, Albert Amoranto, and Janae Johnson—who 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 Martiniere’s
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 3

Varsha Kaulgud Mokhasi
2. Fetal Circulation 16
Chitra Narasimhan, Vijayalakshmi IB
3. Etiopathogenesis of Congenital Heart Diseases 25
Krishnamoorthy KM
4. Fetal Cardiology 43
Shardha Srinivasan
5. Congenital Heart Diseases with Duct-Dependent Circulation 84
Smita Mishra, Sanjay Khatri
6. Genetics in Congenital Heart Diseases 97
Sridevi Hegde, Mitesh Shetty
Section 2: Basics
7. Examination of the Heart—A Comparative External and Internal Anatomy 119

Pradeep Vaideeswar
8. Classification of Cardiovascular Anomalies and their Terminologies 129
Prabhat Kumar, Vijayalakshmi IB
9. Cardiac Malpositions 136
Sejal Shah
10. Heterotaxy Syndrome 145
Smita Mishra, Seema Thakur
11. Bedside Diagnosis of Acyanotic Congenital Heart Diseases 166
Vijayalakshmi IB, Satpathy M
12. Clinical Approach to Cyanotic Heart Diseases 183
Sudhayakumar N
13. Role of Radiography in Congenital Heart Diseases 190
Madhav Hegde, Vijayalakshmi IB
14. Role of Newer Cardiac Imaging in Congenital Heart Diseases 203
Sunita Maheshwari, Arjun Kalyanpur, Jayadeepa
Section 3: Defects in Atriovenous and Pulmonary Arteriovenous Connections
15. Anomalies of Systemic Veins 213

Jayashree Kharge, Vijayalakshmi IB
16. Anomalies of Pulmonary Veins 224
Prasanna Nyayadhish, Sanjeev Kumar
17. Congenital Pulmonary Arteriovenous Fistula 243
Chandrakant B Patil, Kiron Varghese
Section 4: Shunt Defects
18. Interatrial Defects 253

Shada J Al-anani, Ziyad M Hijazi
19. Ventricular Septal Defects 266
Vijayalakshmi IB, Chitra Narasimhan, Prasanna Simha Mohan Rao
20. Atrioventricular Septal Defects 292
Neeraj Awasthy, Radhakrishnan S
21. Patent Ductus Arteriosus 307
Ramesh Arora, Vijayalakshmi IB
22. Aortopulmonary Window 332
Vijayalakshmi IB, Praveen Jayan, Satish Govindaiah
23. Aorticocameral Tunnels 337
Vijayalakshmi IB, Chitra Narasimhan
24. Aneurysm of Sinus of Valsalva 347
Biswajit Bandyopadhyay, Debasree Ganguly, Kumsi Sridhar
Section 5: Right and Left Ventricular Obstructive Lesions
25. Right Ventricular Outflow Tract Obstructions 357

Suresh Kumar R
26. Left Ventricular Outflow Tract Obstructions 366
Vijayalakshmi IB, Vimala J
27. Left Ventricular Inflow Obstructions 380
Neeraj Awasthy, Radhakrishna S
Section 6: Congenital Valvar Lesions
28. Tricuspid Atresia 397

xviii P Syamasundar Rao
29. Diseases of the Tricuspid Valve 414
Duraisamy Balaguru, P Syamasundar Rao
30. Pulmonary Valve Diseases 434
Asha Moorthy, Jain T Kallarakkal
contents
31. Congenital Mitral Valve Diseases 445
32. Mitral Atresia 458
33. Aortic Valve Diseases 468
Smita Mishra, Neeraj Awasthy
Section 7: Diseases of the Aorta
34. Coarctation of the Aorta 505

Bentham J, Wilson N
35. Interruption of Aortic Arch 518
Vijayalakshmi IB, Prasanna Simha Mohan Rao
36. Vascular Rings, Slings and Other Anomalies 525
Maitri Chaudhuri
Section 8: Cyanotic Heart Diseases
37. Tetralogy of Fallot 547

Suresh Kumar, Vijayalakshmi IB, Bhushan Chavan
38. Pulmonary Stenosis with Interatrial Communication 560
Vijayalakshmi IB
39. Pulmonary Atresia with Ventricular Septal Defect 565
Anurakti Srivastava, Anil Sivadasan Radha, Girish Warrier
40. Pulmonary Atresia with Intact Ventricular Septum 580
Marhisham Che Mood, Mazeni Alwi
41. Double Outlet Right Ventricle 594
Vimala J, IB Vijayalakshmi, Prasanna Simha Mohan Rao
42. Truncus Arteriosus 604
Duraisamy Balaguru, P Syamsundar Rao
43. D-Transpostion of the Great Arteries 618
Suresh Rao, Swati Garekar
44. Congenitally Corrected Transposition of the Great Arteries 625
English C Flack, Neeru Kaushik, Thomas P Graham
45. Common Atrium 639
Kiran VS, Sunita Maheshwari
46. Single Ventricle 644
Devananda NS, Maitri Chaudhuri xix
47. Hypoplastic Left Heart Syndrome 665

P Syamasundar Rao, Srilatha Alapati
Section 9: Congenital Cardiomyopathies
48. Dilated Cardiomyopathy 685

Bhanu Duggal, Munde K
49. Non-compaction of the Ventricles 697
Vijayalakshmi IB
50. Restrictive Cardiomyopathy 712
Bhanu Duggal, Neeraj Raghani
51. Hypertrophic Cardiomyopathy 723
Krishnan MN
52. Endocardial Fibroelastosis 736
Mishra SS, Mishra BR
Section 10: Congenital Heart Disease in Adults
53. Transitional Care in Congenital Heart Disease 745

Mary M Canobbio, Reema Chugh
54. Management Issues in Adults with Congenital Heart Diseases 751
Reema Chugh
55. Caring for the Adults with Cyanotic Congenital Heart Diseases 771
Reema Chugh
56. Pregnancy, Contraception and Gynecological Issues in Women with
Congenital Heart Disease 783
Reema Chugh, Pamela D Miner, Mary M Canobbio
57. Exercise and Sports in Adolescents and Adults with Congenital Heart Disease 812
Reema Chugh
58. Psychosocial Challenges and Psychiatric Issues while Growing Up with
Congenital Heart Disease 827
Tracy Kustwan Livecchi, Reema Chugh, Nolan Thompson, Syed T Rizvi
Section 11: Electrophysiological Issues in Children
59. Congenital Heart Blocks and Bradyarrhythmias 839

Abhilash SP, Dinesh Choudhary, Narayanan Namboodiri
60. Tachyarrhythmias 847
Sathish S
61. Invasive Electrophysiology Testing and Devices in Children 870
Dinesh Choudhary, Abhilash SP, Narayanan Namboodiri
xx
Section 12: Miscellaneous
contents
62. Congenital Coronary Artery Anomalies 879
Nick Hayes, Shakeel Qureshi
63. Cardiac and Extracardiac Masses 894
Bhanu Duggal, Vijayalakshmi IB
64. Lutembacher Syndrome 908
Nagamani AC, Nagesh CM
65. Pulmonary Hypertension 917
Maddury Jyotsna, Madhavapeddi Aditya
66. Congenital Pericardial Diseases 944
Prasanna Simha Mohan Rao
67. Marfan Syndrome 946
Harold N Bass, Reema Chugh
68. Down Syndrome 960
Harold N Bass, Reema Chugh
Section 13: General Issues
69. Prevention of Congenital Heart Diseases 971

Sunitha Maheshwari, Kiran VS
70. Oral Health Care in Children and Adolescents with Congenital Heart Diseases 979
Sphoorthi Anup Belludi
71. Infective Endocarditis in Congenital Heart Diseases 995
Anita Shet
72. Noncardiac Surgery in Congenital Heart Diseases 1004
Ramesh Santhanakrishnan,Chandrika YR, Narendra Babu M, Gowrishankar
73. Anesthesia in the Catheterisation Laboratory 1009
PM Chandrasekhara, AM Jagadeesh
74. Anesthesia for Surgical Repair of Congenital Heart Diseases 1022
PM Chandrasekhara, AM Jagadeesh
75. Postoperative Issues in Congenital Heart Diseases 1061
Shilpa Suresh Mavanoor, Prasanna Simha Mohan Rao
76. Pediatric Heart and Lung Transplantation 1070
Brannon Hyde, Deborah J Kozik, Charles W Hoopes, Mark D Plunkett
Epilogue—IB Vijayalakshmi 1089

Index 1091
xxi
Sec t i on
Embryo to the Neonate
C hapter
Development of the
1 Cardiovascular System
Varsha Kaulgud Mokhasi
INTRODUCTION through the streak. The cells destined to form the cranial
segments of the heart, the outflow tract, migrate first and
Cardiovascular system begins to develop by the middle of the the cells forming the more caudal portions, right ventricle,
3rd week of intrauterine life. Functioning of the heart starts by left ventricle and sinus venosus respectively, migrate in a
early 4th week of intrauterine life. It develops mainly from the sequential order. The cells proceed toward the cranium and
splanchnic mesoderm, which forms the primordial heart. This position themselves rostral to the oropharyngeal membrane
is the first major system to start functioning. and neural folds. The primordial heart tube is formed by 18
days.
PRIMORDIAL HEART The primordial myocardium is formed from the splanchnic
mesoderm surrounding the pericardial coelom. The heart
Endothelial strands appear from the angioblastic cords in is now a thin endothelial tube and is separated from the
the cardiogenic mesoderm by about the 3rd week. These primordial myocardium by cardiac jelly. The endothelial
comprise of myoblasts and blood islands (Figures 1A to C). lining becomes the endocardium.
These arrange in the form of cords, which canalize to form The primitive myocardium develops into the muscular
two heart tubes. The two tubes unite with the lateral fold of wall. The mesothelial cells arise from the external surface of
embryo to form a single tubular heart (Figures 2A to C). Heart the sinus venosus and spread over the myocardium and form
begins to beat by the 22nd to 23rd day. The flow of blood the visceral pericardium.
begins by the 4th week.
Position of the Heart Tube
Development of the Heart
After the onset of formation of the head fold, the heart and
The cardiac progenitor cells lie in the epiblast, immediately the pericardial cavity, which were at the cranial end, come
lateral to the primitive streak and from there, they migrate to lie ventral to the foregut and caudal to the oropharyngeal
A C
Figures 1A to C: A. Dorsal view of the embryo; B. Transverse section on the embryo; C. Cephalocaudal section of the embryo
1
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. the yolk sac through the vitelline vein. The blood from the
Thus, the heart becomes a continuous expanded tube, consisting sinus venosus reaches the primitive atrium and is controlled
of an inner endothelial lining and an outer myocardial layer. by the sinoatrial valves. It passes through the atrioventricular
It receives venous drainage at its caudal pole and begins to (AV) canal and then into the primary ventricle, bulbus cordis,
pump blood out of the first aortic arch into the dorsal aorta at truncus arteriosus and finally into the aortic sac. Then through
its cranial pole. the aortic arches the blood reaches the dorsal aortae.
The tubular heart develops alternate dilatations and
constrictions. They are from the cranial to caudal – truncus Formation of the Cardiac Loop
arteriosus, bulbus cordis, ventricle, atrium and sinus venosus.
The truncus arteriosus is continuous cranially with the aortic sac The straight heart tube normally loops or folds to the right and
and aortic arches. The sinus venosus receives three paired sets of this occurs mostly during the fourth week and is completed
veins, the umbilical, vitelline and common cardinal veins from by day 28. The cephalic (ventricle) portion of the heart tube
the chorion, yolk sac and body wall of the embryo respectively. is displaced ventrally, caudally and to the right and the caudal
The arterial and venous ends of the heart are usually fixed. As the (atrium) portion of the tube is displaced dorsally, cranially and
bulbus cordis and venrticle grows faster, they form a U-shaped to the left. Hence, the looping of the bulboventricular tube
tube called the bulboventricular loop (Figures 3A to D). leads the bulbus cordis (prospectively, the right ventricle)
The sinus venosus develops lateral expansions, the right to the right (D-loop) of the initial caudal segment, which is
and left horns. The heart elongates bends and gradually the primitive ventricle (prospectively, the left ventricle).
invaginates into the pericardial cavity. The dorsal mesocardium Simultaneously, individual regions of the tube are expanding
suspends the heart and the central part disappears and forms and differentiating such that by the end of folding the region
the transverse sinus. of the future atria lies craniodorsal to the future ventricular
region. The cardiac looping is one of the first manifestations
Circulation through the Primordial Heart of right-left asymmetry in the developing embryo.
4
The myogenic contractions start at the end of 4th week in Abnormalities of Cardiac Looping
utero by coordinated contractions. The blood enters the sinus
venosus from the embryo through the common cardinal veins; Dextrocardia is a condition where the heart lies on the right
from the developing placenta through the umbilical vein; from side of the thorax instead of the left and is caused because the
1
DEvElopmENt oF thE CArDiovAsCulAr systEm

A B C
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 week and is completed by the 5th week. At the end of the 4th
with situs inversus, a complete reversal of the position of all week, the endocardial cushions from the dorsal and ventral
organs. Situs inversus, which occurs in 1/7,000 individuals, is wall of the AV canal begin to approach each other and fuse
usually associated with normal physiology, although there is a with the right and left AV canals. These are formed from
slight risk of cardiac defects. The patients with isomerism have the endocardial cushions and function as AV valves. The
replication of the right or left cardiac and visceral structures endocardial cushions are made of specialized extracellular
bilaterally. The spleen reflects the difference between right matrix or cardiac jelly.
and left isomerism with polysplenia occuring in left-sided
bilaterality, left isomerism and asplenia or hypoplastic spleen Partitioning of the Primordial Atrium
in right-sided bilaterality, right isomerism. These patients also
have increased incidence of other malformations, especially The atrial partitioning begins at the end of the 4th week of
heart defects. The genes regulating sidedness are expressed development. The septum primum, a thin crescent-shaped
during gastrulation. membrane descends from the roof of primitive atrium
towards the endocardial cushion. A gap, foramen primum,
Partitioning of the Primordial Heart appears between the free margin of the septum primum and
the endocardial cushion. The foramen primum acts as a shunt
The single heart tube now starts to partition to form chambers. for the oxygenated blood to pass through from the right to
The partitioning of the AV canal, the primordial atrium and the left atrium. The septum primum merges with the fused 5
the primitive ventricle begins around the middle of the 4th endocardial cushion to form the primordial AV septum.
1 The perforations produced by programed cell death appear between the atria and consequently an oval foramen or
in the central part of the septum primum, before the foramen foramen ovale is formed. The cranial part of the septum
primum disappears. As the septum primum fuses with the primum disappears and the remaining part forms a flap-like
endocardial cushions, the perforations coalesce to form the valve of the ovale foramen.
foramen secundum and the foramen primum obliterates Before birth, the foramen ovale transmits the oxygenated
(Figures 4A to F). blood from the right to the left atrium. The left to right flow
The foramen secundum ensures free flow of the oxygenated is prevented by the septum primum, closing on the septum
blood from the right to the left atrium. The septum secundum secundum (Figures 5A and B). After birth, the valve of the
grows from the ventrocranial wall to the right of the septum oval foramen fuses with the septum primum and closes the
primum. The septum secundum forms an incomplete partition ovale foramen. The oval depression in the lower part of
A B C
D E F
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

A 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 rise to the coronary sinus (drains blood from the coronary
remnant of the oval foramen or foramen ovale. circulation of the heart muscle) and the small oblique vein
of the left atrium The right horn is incorporated into the right
Changes in the Sinus Venosus atrium and the remainder of the right atrium forms the auricle.
The two parts are demarcated internally by a vertical ridge,
Initially the sinus venosus opens into the centre of the right the crista terminalis and externally by a shallow groove, the
atrium and its right and left horns are about the same size. sulcus terminalis (Figures 5A and B).
There is progressive enlargement of the right horn due to two • The cranial part of the crista terminalis forms the right
left to right shunts of blood. The first shunt is the transformation sinoatrial valve
of the vitelline and umbilical veins. The second shunt occurs • The caudal part forms the valves of the IVC and the
when the anterior cardinal veins become connected by an coronary sinus
anastomosis. This communication shunts blood from the left • The left sinoatrial valve is incorporated into the interatrial
to the right anterior cardinal vein. This shunt becomes the septum.
left brachiocephalic vein. The right anterior cardinal vein and
the right common cardinal vein become the superior vena Formation of the Left Atrium
cava (SVC). The right horn, by the end of the 4th week, is
noticeably larger than the left. The sinoatrial orifice moves to The left atrial wall is mostly smooth because it is formed by
the right and opens in the part of the primitive atrium that will the incorporation of the primitive pulmonary veins. The veins
become the adult right atrium. develop as an outgrowth of the dorsal atrial wall to the left
The consequence of the two left to right venous shunts of the septum primum. As the atrium expands, the primitive
causes the left horn of the sinus venosus to decrease in size pulmonary veins and its main branches are gradually
and its importance. The right horn enlarges and receives all incorporated into the wall of the left atrium.
the blood from the head and neck, through the SVC; and from
the placenta and caudal regions through the inferior vena cava Partitioning of the Primordial Ventricle
(IVC) (Figures 6A and B).
Initially, the sinus venosus is a separate chamber. The left The septum formation starts in the AV canal and by the end of the 7
horn of the sinus venosus ceases to grow and eventually gives fourth week two cushions of mesenchyme, the AV endocardial
1
A B C D
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 examples of cardiovascular teratogens include rubella virus
canal initially gives access only to the primitive left ventricle and thalidomide. Others include retinoic acid (accutane),
and is separated from the bulbus cordis by the bulbo (cono) alcohol and many other compounds. The cardiac defects have
ventricular flange. As the AV canal enlarges to the right, the been linked to maternal diseases such as the insulin-dependent
blood passing through the AV orifice, now has direct access to diabetes and hypertension. The chromosomal abnormalities
the primitive left as well as the primitive right ventricle. are associated with heart malformations and 6 to 10 percent
The two lateral AV cushions appear on the right and left of newborns with cardiac defects have an unbalanced
borders of the canal, along with the anterior and posterior chromosomal abnormality. Furthermore, 33 percent of
endocardial cushions. The anterior and posterior cushions children with chromosomal abnormalities have a congenital
project into the lumen and fuse, resulting in a complete heart defect, with an incidence of nearly 100 percent in
division of the canal into the right and left AV orifices, by the children with Trisomy 18. Finally, cardiac malformations are
end of the 5th week (Figures 7A to D). associated with a number of genetic syndromes, including
craniofacial abnormalities, such as DiGeorge, Goldenhar and
Development of the Atrioventricular Valves Down’s syndromes.
The genes regulating cardiac development are being
The AV endocardial cushions fuse and each AV orifice is identified and mapped and mutations that result in heart defects
surrounded by proliferations of mesenchymal tissue. The are being discovered. For example, mutations in the heart-
bloodstream hollows out and thins the tissue on the ventricular specifying gene NKX2.5 on chromosome 5q35, can produce
surface of these proliferations to form valves and they remain atrial septal defects (secundum type), tetralogy of Fallot, and
attached to the ventricular wall by muscular cords. The AV conduction delays in an autosomal dominant fashion. The
muscular tissue in the cords degenerates and is replaced by mutations in the TBX5 gene result in Holt–Oram syndrome,
dense connective tissue. The valves consist of connective characterized by preaxial (radial) limb abnormalities and
tissue covered by endocardium. They are connected to thick atrial septal defects. The defects in the muscular portion
trabeculae in the wall of the ventricle, the papillary muscles of the interventricular septum may also occur. Holt–Oram
by means of the chordae tendineae (Figures 8A to C). The two syndrome is one of the groups of heart-hand syndromes,
valve leaflets constituting the bicuspid (or mitral) valve forms illustrating that the same genes may participate in multiple
in the left AV canal and three valve leaflets constituting the developmental processes. For example, TBX5 regulates
tricuspid valve forms on the right side. forelimb development and also plays a role in septation of
the heart. Holt–Oram syndrome is inherited as an autosomal
Clinical Embryology dominant trait with a frequency of 1/100,000 live births.
Mutations in a number of genes regulating production
Heart Defects: The heart and vascular abnormalities is the of sarcomere proteins cause hypertrophic cardiomyopathy
largest category of human birth defects, accounting for 1 that may result in sudden death in athletes and the general
percent of malformations among live-born infants. The population. The disease is inherited as autosomal dominant
incidence among stillborns is 10 times as high. It is estimated and most mutations (45%) target the β-myosin heavy chain
that 8 percent of cardiac malformations are due to genetic gene (14q11.2). The result is cardiac hypertrophy due
factors, 2 percent are due to environmental agents while most to disruption in the organization of cardiac muscle cells
are due to a complex interplay between the genetic and the (myocardial disarray), which may adversely affect cardiac
8 environmental influences (multifactorial causes). The classic output and/or conduction.
1

A B C
Figures 8A to C: Formation of atrioventricular valves and chordae tendinae
Atrial septal defect is caused either by excessive cell The Ebstein’s anomaly is a condition where the tricuspid
death and resorption of the septum primum or by inadequate valve is displaced towards the apex of the right ventricle. The
development of the septum secundum. Depending on the valve leaflets are abnormally positioned and the anterior one
size of the opening, considerable intracardiac shunting may is usually enlarged. As a result, there is hypertrophy of the
occur from left to right. The most serious abnormality in this right atrium with a small right ventricle.
group is complete absence of the atrial septum. This condition
known as common atrium or cor-triloculare biventriculare, Septum Formation in the Truncus Arteriosus and
is always associated with serious defects elsewhere in the Conus Cordis
heart.
Occasionally, the oval foramen closes during prenatal life. In the truncus, pairs of opposing ridges appear by the fifth
This abnormality, premature closure of the oval foramen, leads week. These ridges called the truncus swellings or cushions,
to massive hypertrophy of the right atrium and ventricle and lie on the right superior wall (right superior truncus swelling)
underdevelopment of the left side of the heart. Death usually and on the left inferior wall (left inferior truncus swelling).
occurs shortly after birth. The right superior truncus swelling grows distally and to the
The endocardial cushions of the AV atrioventricular canal left and the left inferior truncus swelling grows distally and
not only divides this canal into a right and left orifice, but to the right. Hence, while growing toward the aortic sac the
also participates in formation of the membranous portion swellings twist around each other, making the spiral course
of the interventricular septum and in closure of the ostium of the future septum. Once the fusion is complete, the ridges
primum. This region has the appearance of a ‘cross’, with form the aorticopulmonary septum, dividing the truncus into
the atrial and ventricular septum forming the post and the AV an aortic and a pulmonary channel.
cushions forming the crossbar. The integrity of this ‘cross’ is At the same time similar swellings (cushions) develop
an important sign in ultrasound scans of the heart. Whenever along the right dorsal and left ventral walls of the conus
the cushions fail to fuse, the result is a persistent AV canal, cordis. These conus swellings grow towards each other and
combined with a defect in the cardiac septum. This septal distally to unite with the truncus septum. The fusion of the
defect has an atrial and a ventricular component, separated by two conus swellings causes the septum to divide the conus
abnormal valve leaflets in the single AV orifice. into an anterolateral portion (the outflow tract of the right
Occasionally, endocardial cushions in the AV canal ventricle) and a posteromedial portion (the outflow tract of
partially fuse. The result is a ostium primum defect but there the left ventricle) (Figures 9A and B).
is closure of the interventricular septum. This defect is usually The arterial outlet, at the same time, undergoes a process
associated with a cleft in the anterior leaflet of the mitral of leftward shifting and differential growth that leads to the
valve. disappearance of the bulboventricular flange; the resorption of
The tricuspid atresia, which involves obliteration of the the caudal extreme; and leftward shifting of the conus, closer
right AV orifice, is characterized by the absence or fusion of to the anterior AV canal cushion. The differences in cell growth
the tricuspid valves. It is always associated with: of the outlet septum lead to a lengthening of the segment of
a. Patency of the oval foramen. smooth muscle beneath the pulmonary valve (conus). This
b. Ventricular septal defect. process separates the tricuspid and pulmonary valves. In
c. Underdevelopment of the right ventricle. contrast, the segment beneath the aortic valve disappears, so 9
d. Hypertrophy of the left ventricle. that there is fibrous continuity of the mitral and aortic valves.
1 Neural crest cells, originating in the edges of the neural the subaortic and the subpulmonary conal free walls, that is,
folds in the hindbrain region, migrate through the pharyngeal failure of subsemilunar conal free wall resorption.
arches 3, 4 and 6 to the outflow region of the heart which
they invade. Here, they contribute to the endocardial cushion Semilunar Valves
formation in both the conus cordis and truncus arteriosus. The
abnormal proliferation, migration or differentiation of these As the completion of the partitioning of the truncus, primordia
cells results in congenital malformations in this region, such of the semilunar valves occurs, small tubercles become visible
as tetralogy of Fallot, pulmonary stenosis, persistent truncus on the main truncal swellings. One of each pair belongs to
arteriosus and transposition of the great vessels. Neural crest the pulmonary and the aortic channels, respectively. A third
cells also contribute to craniofacial development; hence it is tubercle appears in both channels, opposite the fused truncal
not uncommon to see facial and cardiac abnormalities in the swellings. The tubercles slowly hollow out at their upper
same patient. surface, forming the semilunar valves (Figures 10 and 11).
Recent evidence shows that neural crest cells contribute to the
Septum Formation in the Ventricles formation of these valves.
By the end of the 4th week, the two primitive ventricles Aortic Arch Derivatives
begin to expand. This also includes continuous growth of the
myocardium on the outside and continuous diverticulation The pharyngeal arches develop during the 4th week and
and trabecula formation on the inside. they are supplied by arteries directly from the aortic sacs.
The medial walls of the expanding ventricles become The aortic arches terminate in the dorsal aorta and six pairs
opposed and gradually merge and this forms the muscular of arch arteries are formed (Figure 12A). Among them, the
interventricular septum. If the two walls do not merge first 2 disappears, when the 6th artery appears. The remaining
completely, a deep apical cleft between the two ventricles arteries will arrange into its final fetal arterial arrangement,
appears. The space between the free rim of the muscular during the 8th week.
ventricular septum and the fused endocardial cushions permits The small portion of the first arch artery remains as maxillary
communication between the two ventricles. artery. The second pair of aortic arch arteries persists as stems
The interventricular foramen, above the muscular portion of the stapedial arteries. In the third pair of arch arteries, the
of the interventricular septum, decreases on completion of proximal part forms the common carotid arteries; distal part
the conus septum. On further development, the outgrowth of joins with the dorsal aorta to form the internal carotid arteries.
the tissue from the inferior endocardial cushion along the top The fourth arch artery on left side forms part of the arch
of the muscular interventricular septum closes the foramen. of aorta. The right fourth aortic arch forms the proximal part
This tissue fuses with the abutting parts of the conus septum. of the right subclavian artery. The distal part of subclavian
Complete closure of the interventricular foramen forms the artery is formed from the right dorsal aorta and the right 7th
membranous part of the interventricular septum (Figure 9C). intersegmental artery. The left subclavian artery develops
from the left 7th intersegmental artery. As there is differential
Abnormalities of Conotruncal Development growth, the subclavian artery comes to lie close to the left
common carotid artery.
The conotruncus is one of the most common sites of The fate of the fifth pair of aortic arches in 50 percent of the
cardiac abnormalities, as it requires normal development embryos is rudimentary and it soon degenerates. They do not
and proliferation of multiple cell types (secondary heart develop in the other 50 percent. The proximal part of the sixth
field, neural crest cells, myocardium , endocardium). There pair of arch artery on the left side persists as proximal part of
are many disorders involving the conotruncal region such left pulmonary artery. The distal part of this arch artery passes
as common arterial trunk, double outlet right ventricle, from the left pulmonary artery to the dorsal aorta to form the
interrupted aortic arch, transposition of the great arteries, arterial shunt called ductus arteriosus.
tetralogy of Fallot and ventricular septal defect. The tetralogy The proximal part of the right sixth arch artery persists as
of Fallot occurs due to an unequal division of the conus the proximal part of right pulmonary artery and the distal part
resulting from the anterior displacement of the conotruncal degenerates (Figures 12B and C). The transformation of the
septum. The persistent truncus arteriosus results when the sixth pair of aortic arches, determines the course of recurrent
conotruncal ridges fail to fuse and to descend toward the laryngeal nerves. On the right, because the distal part of right
ventricles. The transposition of the great vessels occurs sixth aortic arch degenerates, the right recurrent laryngeal
when the conotruncal septum fails to follow its normal spiral nerve hooks around right subclavian artery, a derivative
course and runs straight down. Van Praagh has said that of the fourth aortic arch artery. The left recurrent laryngeal
the growth of the subaortic conal free wall and resorption nerve hooks around the ductus arteriosus, formed by the distal
10 of the subpulmonary conal free wall results in transposition part of sixth arch artery on the left side. As the arterial shunt
of the great arteries. Also, double-outlet right ventricle is involutes after birth, the nerve hooks around the ligamentum
caused due to the continued persistence and growth of both arteriosum and the arch of the aorta.
1

A B C
Figures 9A to C: A and B. Development of the conotruncal ridges; C. Formation of the interventricular septal development
A B C
Figures 10A to C: Transverse section through the truncus arteriosus
A B C
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 The aortic sacs arise from aortic arches and terminate in dorsal
embryonic pharyngeal arch system of arteries into the adult aorta, by the fourth to fifth weeks. Initially aorta is paired
arterial pattern, anomalies occur. Anomalies result from either and run through the body. Soon, single dorsal aorta caudal to 11
disappearance or persistence of parts of the aortic arch arteries. aortic arches is formed.
1
A B
C
Figures 12A to C: A. Aortic arches and dorsal aortae; B and C. Final form of the aortic arch arteries
Intersegmental Arteries distal part gets obliterates and remains as medial umbilical
The dorsal intersegmental arteries carry blood to somites. ligaments.
The vertebral artery is formed from the dorsal intersegmental
artery in the neck and the intercostal arteries are formed by the Clinical Correlates
dorsal intersegmental arteries. The lumbar arteries are formed
by abdominal intersegmental arteries. The fifth pair of the Arterial system defects: Normally, the ductus arteriosus is
lumbar intersegmetal arteries forms the common iliac arteries. functionally closed through the contraction of its muscular
The lateral sacral arteries form the sacral intersegmental wall shortly after birth to form the ligamentum arteriosum.
arteries. The caudal end of the dorsal aorta forms the median The anatomical closure occurs by the proliferation of intima
sacral artery. by 1 to 3 months.
In the coarctation of the aorta, the aortic lumen below the
Fate of the Vitelline origin of the left subclavian artery is significantly narrowed.
Since the constriction may be above or below the entrance of
The vitelline arteries pass to the yolk sac and the primitive the two types (preductal and postductal) may be distinguished
gut. The three vitelline arteries that remain are the celiac trunk (Figures 13A and B). The cause of the aortic narrowing is
to the foregut, the superior mesenteric artery to the midgut and primarily an abnormality in the media of the aorta, followed
the inferior mesenteric artery to the hind gut. by intimal proliferations. In the preductal type, the ductus
arteriosus persists; in the postductal type, which is more
Umbilical Arteries common, this channel is usually obliterated. In the latter case,
collateral circulation between the proximal and the distal parts
12 The umbilical arteries pass through the connecting stalk and of the aorta is established by large intercostal and internal
carry poorly oxygenated blood. The proximal part forms the thoracic arteries. In this manner, the lower part of the body is
internal iliac arteries and the superior vesical arteries. The supplied with blood.
1

A B
Figures 13A and B: Coarctation of aorta. A. Preductal; B. Postductal
A B
Figures 14A and B: Abnormal origin of the right subclavian artery
The abnormal origin of the right subclavian artery occurs In a double aortic arch, the right dorsal aorta persists
when the artery is formed by the distal portion of the right between the origin of the seventh intersegmental artery and
dorsal aorta and the seventh intersegmental artery (Figures its junction with the left dorsal aorta (Figure 15A). A vascular
14A and B). The right fourth aortic arch and the proximal part ring surrounds the trachea and the oesophagus and commonly
of the right dorsal aorta are obliterated. With shortening of compresses these structures, causing difficulties in breathing
the aorta between the left common carotid and left subclavian and swallowing (Figure 15B).
arteries, the origin of the abnormal right subclavian artery
finally settles just below that of the left subclavian artery. Since Development of Veins Associated with the Heart
its stem is derived from the right dorsal aorta, it must cross the
midline behind the oesophagus to reach the right arm. This The three paired veins drain into the tubular heart. The
location does not usually cause problems with breathing and vitelline veins return poorly oxygenated blood from the
swallowing since neither the trachea nor the oesophagus is yolk sac. The umbilical veins carry well-oxygenated blood
severely compressed. from the primordial placenta. The common cardinal veins 13
1
A B
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
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 Figure 16: Main intraembryonic and extraembryonic vessels
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 derivative of posterior cardinal vein is the root of azygos
veins around the duodenum. vein and common iliac vein. The subcardinal veins connect
The right umbilical vein and the caudal part of the left through the subcardinal anastomosis. It forms the stem of
umbilical vein between the liver and the sinus venosus the left renal vein, the suprarenal vein, the gonadal veins
degenerates. The persistent left umbilical vein forms the and a segment of the IVC. The supracardinal veins in adult
ductus venosus which is large venous shunt that develops form the azygos and hemiazygos veins and part of the IVC
within the liver. (Figures 17A and B).
The cardinal veins are the main venous drainage system
of embryo. The anterior and posterior cardinal veins drain Development of the Inferior Vena Cava
from the cranial and the caudal part of embryo. They join the
common cardinal vein and enter into the sinus venosus. The IVC is composed of four segments: hepatic, suprarenal,
The anterior cardinal vein anastomosis forms the left renal, and infrarenal. The hepatic segment is formed from the
brachiocephalic vein. The caudal part of the left cardinal vitelline vein. The right subcardinal vein forms the suprarenal
vein disappears. The SVC is formed from the right segment by formation of the subcardinal-hepatic anastomosis.
anterior cardinal vein and the right common cardinal The renal segment develops from the right suprasubcardinal
vein. The posterior cardinal vein develops as vessels of and postsubcardinal anastomoses. It is generally accepted
mesonephros and the developing transient kidneys. These that the infrarenal segment formed by the right supracardinal
14 veins disappear with these kidneys. The remaining adult vein.
1

A B
Figures 17A and B: Development of inferior vena cava, superior vena cava and azygos veins
ANOMALIES OF THE VENA CAVAE isolated angiogenic cell islets into a complex, four-chambered
structure. The critical period for development of anomalies
The anomalies of the vena cavae are double SVC, left SVC, is 3–6 weeks. Hence, knowledge of cardiac embryology is
Absence of hepatic segment of IVC, double IVC, azygos necessary to understand the congenital heart defects and to
continuation of IVC etc. These anomalies have been discussed develop strategies for prevention.
in chapter 15.
The embryological record is almost always abbreviated in
FETAL CIRCULATION accordance with the tendency of nature (to be explained on
the principle of survival of the fittest) to attain her needs by
Fetal Circulation has been discussed in Chapter 2. the easiest means.
— Francis Maitland Balfour
CONCLUSION
SUGGESTED READING
The cardiovascular system is the first functional system in
1. Sadler TW. Langmans Medical Embryology 11th edition.
embryo. The single heart tube begins to beat at 23 days of
Chapter 12.
development. The entire process of formation of cardiovascular 2. Keith L Moore. The developing Human Clinically oriented
structures is completed within one month after the first 20 embryology, 8th edition.
days of embryogenesis. This amazing process transforms
15
C hapter
2 Fetal Circulation
Chitra Narasimhan, Vijayalakshmi IB
Introduction ventricles work in parallel instead of in series as in the adult,

though he denied the existence of any pulmonary circulation
The fetal circulation is the circulatory system of a human at all in the fetus. It was later in 1938, that Barcroft and Barron
fetus. It refers to a unique system of shunts and pressures united their experience of fetal physiology with Barclay,
that are present in the fetal circulatory system. It is the first Franklin and Prichard’s experience in radiography.6 They
functional system in the embryo at 21 days.1 The normal described the first records of the course of the circulation
growth and development of the fetus is dependent on an active, in the fetal lamb. The changes in circulation at birth were
independent metabolism and also on an efficient circulation. first described by Dawes and coworkers.7 Rudolph and co-
The circulation in the fetus differs from that in the adult. The workers in 1967 pursued their studies of the fetal circulation
human fetal circulation and its adjustments after birth are for in lambs and the changes at birth, by using more physiological
the most part similar to those of other large mammals, although methods.8-10 The lamb model appears to best reflect human
rates of maturation differ. Congenital heart disease (CHD) is physiology.11 In 1972, Winsberg was the first to demonstrate
being diagnosed with increasing frequency during fetal life. fetal echocardiography.12 In the 1980s, hemodynamic
Hence, it is important to know the course and distribution of evaluation by Doppler enabled assessment of the fetal
the fetal circulation as it enables one to understand the manner circulation and in the late 1990s tissue Doppler methods
in which various defects influence the normal circulation. opened up new possibilities to assess cardiac function. Three
dimensional echocardiography and tissue tracking analysis of
HISTORICAL REVIEW the fetal heart improved the ease and quality of the assessment
of the fetal circulation, particularly in the first trimester.13
The first recorded mention of the fetal cardiovascular
circulation was in the second century AD by Galen.2 He UNIQUENESS OF FETAL CIRCULATION
described what was later to become known as the foramen
ovale and its valve, as well as the ductus arteriosus. “Nature is The fetal circulation is unique. There are several anatomical
neither lazy nor devoid of foresight. Having given the matter differences between a placenta supported circulatory system
thought, she knows in advance that the lung of the fetus does and an independent postnatal circulatory system.
not require the same arrangements of a perfected lung. She has 1. The fetal circulation is an unique example of the economy
therefore anastomosed the pulmonary artery with the aorta, of nature. It is optimized to deliver highly oxygenated blood
and the left and right atria…”. He also gave some account from the placenta to the vital organs in greatest need (brain,
of their postnatal closure. In 1564, Vesalius, in a posthumous heart) and deliver the relatively desaturated blood to sup-
publication, described the first account of the ductus venosus.3 ply less essential fetal structures.14 The placenta receives
In 1626, Spigel, also in a posthumous publication, noted that the deoxygenated blood from the fetal systemic organs. The
both the fetal ventricles are of approximately equal thickness fetus circulatory adaptations are achieved by both the pref-
and also noted the absence of any direct communication erential streaming of oxygenated blood and the presence of
between the umbilical vessels of the fetus and the uterine intracardiac and extracardiac shunts. Thus, the fetal circula-
vessels of the mother.4 In 1628, William Harvey introduced tion can be defined as a ‘shunt-dependent’ circulation.15
his concept of the circulation of the blood and his account 2. The fetal circulation is arranged in parallel. The right
of the fetal circulation.5 He realized that in the fetus the two ventricle delivers majority of its output to the placenta for
oxygenation and the left ventricle delivers majority of its 2
output to the heart, brain and upper part of the body.
3. The oxygenation takes place at a site external to the
Fetal Circulation
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 Figure 1: Anatomy of the fetal circulation and the oxygen saturations
the adult, whereas fetal myocardial energy requirements in the various chambers and vessels. RV = Right ventricle; LV = Left
ventricle
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 passes through the direct shunt, the ductus venosus (DV).19,20
oxygen partial pressure, fetal hemoglobin can carry 20 to The fetal DV is a slender trumpet-like shunt, connecting into
30 percent more oxygen than the maternal hemoglobin. the inferior vena cava (IVC), near its junction with the right
In addition, the presence of fetal hemoglobin means that atrium (RA).18 The DV and the umbilical vessels are kept open
the organs in the fetus are able to extract oxygen at low by the mechanical effect of the flow through them. The better
saturations.15 oxygenated blood from the DV remains on the posterior and
leftward aspect of the IVC and tends to stream separately from
ANATOMY OF THE FETAL CIRCULATION the extremely desaturated systemic venous blood, which is
returning from the lower portions of the body.15,21
The fetal circulation works differently from that of the baby On reaching the heart, the IVC blood is effectively divided
after birth, mainly because the lungs are not in use in the into two streams. A highly oxygenated stream is preferentially
fetus. The fetus obtains oxygen and nutrients from the mother shunted through the next shunt in the fetal circulation, the
through the placenta and the umbilical cord, while a baby foramen ovale (FO), into the left atrium (LA). The other stream
after birth acquires oxygen from its lungs. The embryo/fetus passes into the RA where it is joined by the deoxygenated
is attached to placenta via the umbilical cord. The anatomy of stream from the superior vena cava (SVC) and this is directed
the fetal circulation is shown in Figure 1. through the tricuspid valve into the right ventricle (RV). The
The deoxygenated blood passes to the placenta via the two mechanical effect of the streaming of the IVC blood into the
umbilical arteries. These arteries arise from the right and left LA and the physical relationship of the IVC to the LA, keeps
internal iliac arteries. The fetal blood is oxygenated in the the FO patent in the fetus.
placenta and is returned to the fetus via the umbilical veins. The preferential shunting of the more highly oxygenated
Initially, there is a right and a left umbilical vein and they IVC blood through the FO appears to be due to various
empty into the hepatic venous sinusoids. The right umbilical reasons:
vein regresses completely, early in fetal life.18 1. The angle at which the DV inserts into the IVC–RA
The blood flow in the umbilical vein splits in the liver. Some junction, directs most of the richly oxygenated blood
of it goes into the hepatic veins and the portal system of the across the FO and into the LA.22
liver. In fetal lambs, the proportions vary and on an average 2. The crista dividens, forming the upper margin of the FO
about 55 percent (range 20–90%) passes through the ductus (free margin of the septum secundum) overrides the IVC.23
venosus. In the human fetus, 20 to 30 percent of the blood flow The free edge of the lower margin of the FO, formed by the 17
1 septum primum, is on the left side of the atrial septum and the undersurface of the liver, represents the obliterated
the FO is kept open by the IVC stream. umbilical vein.
3. The IVC valve or the Eustachian valve diverts the IVC 3. The ligamentum venosum, lying within its fissure on the
blood stream towards the atrial septum.24 undersurface of the liver, continuing as the ligamentum
4. It is likely that the higher velocity of the DV bloodstream teres and terminating at the IVC, represents the obliterated
(55 cm/s) as compared to the lower velocity of the distal DV.
IVC (15 cm/s) bloodstream contributes to maintaining the 4. The fossa ovalis on the interatrial septum, which is ‘probe
preferential distribution of DV blood across the FO.25 patent’ in about 10 percent of normal subjects, represents
The Eustachian valve and the lower portion of the atrial the FO.
septum move in unison during the phases of the cardiac cycle. 5. The ligamentum arteriosum, between the aortic arch and
They move either to the left to facilitate movement of blood the left pulmonary artery, with the recurrent laryngeal
through the FO or to the right to enhance flow through the nerve in close proximity, represents the DA.
tricuspid valve.26 This preferential streaming of the DV and
the left hepatic venous blood through the FO distributes the PHYSIOLOGY OF THE FETAL CIRCULATION
highly oxygenated blood to the LA and this mixes with the
small amount of deoxygenated blood from the lungs, draining The fetal circulatory physiology has been based on animal
through the pulmonary veins, before entering the left ventricle data. Ultrasound in obstetrics has been used increasingly to
(LV) through the mitral valve. From the LV, the ascending provide physiological data from human fetuses. There are now
aorta delivers this oxygen-rich blood to the coronary arteries, a growing number of human studies, which have investigated
the head and neck vessels and the upper extremities. Only a the human physiology, with results that are similar, but not
small portion of left ventricular cardiac output (10%) traverses identical to those from animal studies.17 The human fetus
the aortic arch and supplies blood flow to the thoracic aorta.27 seems to circulate less blood through the placenta, shunt less
The most deoxygenated blood returns to the heart from through the DV and FO, but directs more blood through the
the upper body through the SVC and from the myocardium lungs than the fetal sheep. There are also substantial individual
through the coronary sinus. This blood, in addition to the variations and the pattern changes with gestational age.17
IVC’s anteriorly streamed flow (venous return from the lower
body and hepatic circulation), is directed across the tricuspid Fetal Blood Volume
valve into RV and then ejected into pulmonary artery (PA).15
Only about 5 percent or less of the deoxygenated blood from The blood volume in the human fetus is between 10 and 12
the SVC flows through the FO into the left atrium in the percent of the body weight as compared with 7 to 8 percent in
normal fetus.25 the adults.28 This is mainly due to the large volume of blood
As the lungs of the fetus are inactive, most of the in the placenta, which decreases with gestation.
deoxygenated blood from the RV is diverted via the third shunt, Studies have indicated a volume of 110 to 115 mL/kg,
the ductus arteriosus (DA), from the PA into the descending which is comparable with experimental sheep studies.29 The
aorta, distal to the left subclavian artery. The muscular DA fetus, when compared with adults, is capable of much faster
is kept open by the active dilatation of both locally produced regulation and restoration of the blood volume due to the high
and circulating prostaglandins (PGE2 and possibly PGI2). In diffusion rates between the fetal compartments.28
the fetus the DA is as large as the aorta. Only a small amount
of the RV output enters the pulmonary circulation, while the Fetal Arterial and Venous Blood Pressure
remaining major portion crosses the DA and then into the
descending aorta. The reduced blood flow to the lungs is also The human fetal mean arterial pressure was measured to
reflected by the relatively smaller branch pulmonary arteries be 15 mm Hg during cordocentesis at the gestational age of
in utero and a large arterial ductus and descending aorta. 19 to 21 weeks.30 Intrauterine recordings of the human fetal
The lower half of the body is thus supplied with relatively intraventricular pressure suggest that the systemic systolic
desaturated blood. This blood supplies the abdominal viscera pressure increases from 15 to 20 mm Hg at 16 weeks to 30 to 40
and the lower limbs and is shunted, via the umbilical arteries, mm Hg at 28 weeks.31 The results did not show any substantial
which branch from the internal iliac arteries, to the placenta for difference between the two ventricles and in the diastolic
oxygenation.15,18 ventricular pressure. The umbilical venous pressure, recorded
In adult anatomy the following remains of the fetal during cordocentesis and corrected for amniotic pressure,
circulation can be readily recognized.18 increased from 4.5 mm Hg at 18 weeks to 6 mm Hg at term.32
1. The medial umbilical ligament on each side, passing from
the superior vesical branch of the internal iliac artery to the Fetal Cardiac Function
umbilicus, represents the obliterated umbilical arteries.
18 2. The round ligament or ligamentum teres, lying in the free The fetal myocardium is structurally and functionally immature
edge of the falciform ligament and then in its groove on compared with that of the older child or adult. The structural
details of the fetal heart are organized during the embryonic Table 1
 2
period. The fetal heart continues to grow and is dependent on Showing differences between fetal/neonatal and adult
the physical environment including blood flow for its normal myocardial physiology
Fetal Circulation
growth. In many ways, the fetal myocardium differs from the
Feature Fetus/Neonate Adult
adult myocardium. The fetal myocardium is composed of
nearly 60 percent of non-contractile elements as compared to Cardiac output HR dependent SV and HR
30 percent in the adult myocardium.33 Early fetal myocytes Starling response Limited Normal
can undergo replication with development of hyperplasia or Compliance Less Normal
an increase in cell number, whereas mature adult myocytes Afterload Limited Effective
undergo hypertrophy or increase in cell size. The myofibrils compensation
density increases in early pregnancy, but the contractility Ventricular High Relatively low
continues to improve during the second half of pregnancy.34 interdependence
The relaxation properties of the fetal myocardium differs from
HR = Heart rate; SV = Stroke volume
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 cytosolic-
calcium in the fetus.35 Fetal heart is much stiffer than the adult pressure can affect both the ventricles, but the RV is affected
heart, with impaired relaxation properties relative to the adult. to a greater degree than the LV in the developing fetus.41
The ‘stiffness’of the fetal myocardium is also partly due to Thus in situations of increased preload or afterload, the RV
the constraint of the pericardium, lungs and chest wall.36 The will manifest hypertrophy, dilatation or dysfunction before
stiffness and impaired relaxation of the fetal myocardium is the LV.
reflected by the Doppler echocardiography done across the In the fetal heart, due to the wide communication between
atrioventricular valves. In the fetus, E : A ratio will typically the atria, there is equalization of pressures. Also, due to the
be less than 1, as passive early filling is impaired and active patency of the DA, there is equalization of pressures in the
atrial contraction is primarily responsible for emptying the aorta and pulmonary artery. As the atrial and great vessel
atrium.37 The E : A ratio is usually >1 in adults. pressures are equal, in the absence of aortic and pulmonic
The fetal heart has a limited preload reserve and hence stenosis, the ventricular pressures are also equal with a systolic
a limited capacity to increase stroke volume by increasing pressure of approximately 70 mm Hg using amniotic pressure
diastolic filling pressure, the RV even less than the left. as zero.27
Though the Frank-Starling mechanism operates in the fetal
heart, it does so till a point is reached, after which any increase Fetal Cardiac Output and Distribution
in preload will result in a plateau without any further increase
in the stroke volume.38 Fetal cardiac output is controlled In adults, the circulatory system is in series and as there are no
entirely by the changes in the fetal heart rate in contrast to the shunts, the LV and RV stroke volumes are equal. In the fetus,
stroke volume changes in the adult. Thus, heart rate may be the the circulation is in parallel and as a result of the intracardiac
single most prominent means of increasing cardiac output in and extracardiac shunting, the stroke volumes of the fetal LV
the fetus. There is immaturity of the sympathetic innervations and RV are not equal. Even though the pressures are equal,
of the fetal heart as compared to the parasympathetic. Thus, the RV stroke volume is more. This could be explained due
under stress the fetal cardiac output favors maintenance of the to the differences in afterload of the two ventricles. The fetal
umbilical blood flow and support of the myocardium, adrenal aortic isthmus is narrower than the ascending and descending
and brain.39 The differences between the fetal and adult aorta and this may functionally separate the upper and lower
myocardial physiology is shown in Table 1. body circulation to some extent.25
The pressure difference between the ventricles is minimal The fetal circulation is shunt dependent and is much more
in the fetus as compared to that in postnatal life. This is complex and hence the cardiac output must be expressed as
because the ventricles in the fetus are pumping in parallel the combined cardiac output (CCO).25 The estimated cardiac
into the systemic circulation.31 In fetal circulation as the RV output of the human fetus (553 mL/kg/min−1) is higher than
handles 55 percent of the combined ventricular output, it is that of sheep (450 mL/kg/min−1). The CCO is reported to be
larger and more dominant than the LV. This is confirmed on 210 mL/min at midgestation and 1900 mL/min at 38 weeks
echocardiographic evaluation of the human fetal heart. The in human fetus (Table 2).42 In addition, the right and left
wall thicknesses of both the ventricles in the fetal heart are ventricular outputs are more similar in the humans (56/44)
approximately equivalent. As compared to the LV, the RV has when compared with that in sheep (66/34).25 Thus, the ratio
a greater wall stress, which is due to the greater radius to wall of right to left ventricular output, which is about 2 : 1 in the
thickness ratio. Hence, the RV exhibits greater sensitivity sheep is about 1.2 to 1.3 : 1 in the humans.37,43,44 This ratio of
to changes in the afterload such as an increase in vascular the right to left ventricular outputs decreases with advancing 19
resistance, than the LV.40 Any increase in systemic arterial gestation, from 1.3 at 15 weeks to 1.1 at 40 weeks. This is due
1 Table 2
 blood that is shunted through the FO.17 Oxygen saturations in
The combined cardiac output and its distribution in normal human different parts of the fetal circulation are shown in Figure 1.
fetuses during the second half of pregnancy42
Percentage of combined cardiac output Control of the Fetal Circulation

at gestational age
The control of the fetal circulation is extremely complex and
20 weeks 30 weeks 38 weeks
is poorly understood. There are multiple control processes,
Combined 210 mL/min 960 mL/min 1900 mL/min which mature and develop with gestational age. Circulating
cardiac output
catecholamines, other circulating hormones and locally
Left ventricle 47 43 40 released vasoactive substances, all play a part. The circulating
Right ventricle 53 57 60 catecholamines exert their effect through the activation of
Foramen ovale 34 18 19 both the α- and b-adrenergic receptors, which mature during
Lungs 13 25 21
early gestation, independent of the autonomic innervation
process.
Ductus 40 32 39
arteriosus
The fetal peripheral circulation appears to be under a
tonic adrenergic influence (predominantly vasoconstriction),
probably mediated by the circulating catecholamines and in
to the fact that the larger human brain requires a higher LV particular by norepinephrine. Other factors such as arginine
output than the brain of the sheep. vasopressin (AVP) and the renin-angiotensin system may
The RV during fetal life, is not only pumping against the also have a role.15 In situations of fetal hypoxia, the fetal
systemic blood pressure, but is also performing a greater circulation responds to the hypoxic insults through the neural
volume of work than the LV. The RV output is directed and endocrine responses and to the prominent direct effect
across the main pulmonary artery and the DA, with a small on the cardiac function.39,46 The fetal heart responds to the
portion going to the vasoconstricted pulmonary vascular bed. hypoxia with bradycardia, unlike tachycardia in adults. All
The human fetal pulmonary flow is larger (mean 13–25%) these responses orchestrate a circulatory redistributional
than that in the classical fetal lamb studies (≤ 10%).17 The pattern that maintains placental circulation and gives priority
remaining major part of the RV output perfuses the descending to the adrenal glands, myocardium and the brain.47
aorta, lower part of the body and the placental circulation. The fetal pulmonary vascular resistance (PVR) is high
The LV output is directed towards the coronary and cerebral and this is multifactorial in origin. In fetal life, the alveoli
circulations, with a small portion (10%) crossing the aortic are fluid filled and there is increased tortuosity, kinking, high
isthmus to perfuse the lower body. Thus, the high degree of muscle mass and the high vasomotor resting tone of the small
oxygenated blood returning via the DV and its preferential pulmonary vessels, all of which contribute to the high PVR. The
intracardiac streaming across the FO is directed to the organs collapsed fetal lungs have a low resting oxygen tension. The
in greatest need of oxygen delivery for their development i.e. PVR may also be influenced by the changes in the pH, PCO2
heart and brain. The placenta receives 50 percent of the CCO and by the autonomic nervous system.48-50 Many endogenous
of the fetal heart.45 and exogenous vasoactive materials also stimulate the fetal
pulmonary vasculature. The DA also contains muscle that is
Oxygen Saturation sensitive to the oxygen tension and vasoactive substances.
The patency of DA in utero is maintained by the low oxygen
The oxygen saturations and PO2 are lower in the fetus than that tension and the vasodilating effects of prostaglandin E2.15
in the neonates, infants and children.25 This may be due to the
lower efficiency of the placenta to transport oxygen than the Transitional Circulation
lungs. However, the fetus is able to adapt to these lower levels
due to the presence of fetal hemoglobin. The fetal hemoglobin As the fetus begins its transition to postnatal life, several
P50 in the sheep is considerably lower (~19 mm Hg) than that important changes occur as the cardiovascular and respiratory
of adult blood (~31 mm Hg) and this facilitates greater oxygen systems adapt to extrauterine life. The fetus has to transit from
uptake from the placenta. The distribution of the blood to the a parallel circulation to a neonatal circulation in series. The
various organs and the placenta is advantageous in that the major circulatory changes occurring at birth are the elimination
highly saturated blood goes to the heart and brain and the low of the placenta, closure of fetal circulatory pathways, increased
saturated blood goes to the placenta. The lowest saturation pulmonary blood flow and an increase in the LV output. There
is found in the abdominal IVC and SVC and the highest is an impressive immediate change at birth followed by a
saturation is found in the umbilical vein.14 The difference slow change until an adult type of cardiovascular system is
in the oxygen saturations between the blood leaving the achieved. This may occur over varying time periods.51
20 RV and the LV is only 10 percent, increasing to 12 percent At birth, with separation of the umbilical cord, lungs
during hypoxemia. This is mainly due to the large volume of must swiftly take over from the placenta as the site of gas
exchange. In order for this to occur, PVR must fall rapidly interatrial septum primum and septum secundum results in 2
and this occurs due to an interaction of a number of factors. formation of an intact atrial partition. Remnants of the closed
There is a gradual reduction in PVR in late gestation. umbilical vein are enclosed within the ligamentum teres.1
Fetal Circulation
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 Fetal Circulation in Congenital
The first breaths to inflate the lungs are thought to stimulate Heart Diseases25,53
pulmonary stretch receptors which mediate reflex dilatation
of the pulmonary vessels. Mechanical distention of the lungs Any development of a structural abnormality will modify the
also promotes local production of prostacyclin, a pulmonary fetal circulation. This will affect the development of other
artery vasodilator, further decreasing PVR. The improved components and can lead to other defects. The impact of the
oxygenation of the blood acts as a vasodilator both directly defect will depend on it’s severity and the time of gestation at
and through its ability to stimulate nitric oxide production.52 which it occurs. The fetal circulation is modified in many of the
The reduction in PVR leads to increase in pulmonary blood defects, but it will not significantly affect the fetal perfusion
flow and an increased venous return to the LA. and hence the fetal growth and development. This is because
As soon as the placenta is removed, there is a dramatic fall of the parallel fetal circulation and its connections at the atrial
in the flow through the DV and a significant fall in the venous and great arterial level. This allows adequate transport of
return through the IVC. The DV closes passively, 3 to 10 days blood to the placenta to pick up oxygen and deliver it to the
after birth. Thus, there is decrease in IVC flow, which results tissues. Thus, some CHDs are well-tolerated in utero, while
in a fall in venous return to the RA. This in turn means that others can result in severe compromise of the fetal circulation
less blood enters the RA causing right atrial pressures to fall. and early fetal death.
At the same time with an increase in pulmonary blood flow The fetal heart functions as a common mixing and pumping
due to the decrease in PVR, there is increase in the pulmonary chamber and hence many complex anomalies are compatible
venous return and subsequent elevation in LA pressures. with survival to term. Fetal shunt pathways play important
These two factors allow the pressures in the LA and RA to roles in the pathophysiology of many types of congenital
equalize. At this point the flap of the FO is pushed against the cardiac malformations. The defects associated with septal
atrial septum and the atrial shunt is effectively closed. This defects like atrial septal defect, ventricular septal defect (VSD)
initial ‘functional’ closure of the FO occurs within minutes rarely influence fetal cardiac development. In atrioventricular
to hours of birth. Anatomical closure occurs later via tissue septal defects, the obligatory flow from LV to RA will result
proliferation.15 in decrease in LV output and an increase in RV output. This
The shunt at the level of the DA becomes bidirectional will reduce the flow across the isthmus and can predispose to
with the reduction in the PVR. In addition, there is a dramatic coarctation. It is the degree of severity of the atrioventricular
reduction in the production of prostaglandin E2 (by the valve lesion and the regurgitation, which will determine the
placenta) and an increase in its metabolism (by the lungs).52 outcome.
This in combination with increased oxygen content in the Any interference with blood flow into or out of the LV or
blood provides the stimulus for the DA to constrict. The RV is known to interfere with its development. Premature
ductal tissue itself may become less sensitive to the dilating closure or restriction of the FO or mitral orifice results in LV
influences of the prostaglandins. Anything that increases the hypoplasia as a result of reduced blood flow, which decreases
PVR, such as acidosis, hypoxemia, polycythemia or lung the LV volume. In these fetuses with under development
disease, may keep the ductus patent. In healthy full term of the left side of the heart, the fetal RV and pulmonary
newborns, functional ductal closure occurs by 96 hours. artery are larger than usual reflecting flow redistribution.
This functional closure is followed by anatomical closure The compensatory dilation of the contralateral ventricle
via endothelial and fibrous tissue proliferation by 2 to 3 results in normalized CCO. In the fetus with mitral atresia
weeks.15,27 Once the DA closes, pulmonary artery pressures or aortic atresia, if the FO is sufficiently large and the
reduce significantly as the PVR decreases. The pulmonary DA accommodates the whole of the systemic blood flow,
artery pressures are approximately one-half of the aortic there will be no significant interference with intrauterine
pressures within the first 24 hours of life. Further decrease development and survival, but the problems will occur
in the PVR and involution of the pulmonary arteriolar after birth as the DA closes. Blood flows retrograde from
medial musculature occurs more gradually. The pulmonary the DA across the arch to the ascending aorta. The reduced
vasculature looks very similar to that of the adult by the age flow through the left heart in cases of atrioventricular valve
of 6 to 8 weeks.51 obstruction (atresia, stenosis) and in aortic atresia can result
Functional closure of the three shunts typically happens in in aortic hypoplasia and coarctation. The aortic isthmus is
the first 48 hours and is followed by tissue proliferation that especially vulnerable to small changes in intracardiac flow
results in anatomical closure and formation of the ligamentum from various congenital defects. This may account for the
arteriosus and ligamentum venosus, while fusion of the relatively high incidence of narrowing or atresia in this 21
1 region. The increased flow in the DA allows the substrate presence of the FO. Venous return is diverted away from the
for development of a posterior aortic wall ridge opposite ventricle with obstructed outflow and preferentially enters
the orifice and usually a narrowing results at this site. Other the ventricle with the greater diastolic compliance. In cases
CHDs may be associated with decreased flow into the aorta of critical aortic valve stenosis, congestive heart failure can
thus interfering with its development. Thus in the fetus with occur with hydrops fetalis.
tricuspid atresia with transposition, the aorta arises from the In the fetus, TOF, total anomalous pulmonary venous
RV. If only a small VSD is present, the RV is small and flow connection (TAPVC) and transposition of great arteries (TGA)
into the ascending aorta is restricted, resulting in hypoplasia. are well-tolerated. In TOF, depending on the severity of the
Infants with aortic atresia have been reported to show a obstruction to the pulmonary blood flow, the aorta will carry a
high incidence of neurodevelopmental problems due to the larger percentage of CCO. Hence, there is a larger amount of
reduced cerebral blood flow during fetal life. blood flow across the ascending aorta and the isthmus and they
The patency of the fetal flow pathways is very important for tend to be larger. If the obstruction to the pulmonary blood
fetal survival when the right side of the heart is underdeveloped, flow is very severe, blood flow to the lungs will be supplied
as in absent right atrioventricular connection with right via the DA from the descending aorta (i.e. the reverse of the
ventricular hypoplasia or with severe right ventricular outflow normal situation). In absent pulmonary valve syndromes,
obstruction (RVOTO), as in critical pulmonary stenosis or pulmonary artery branches are greatly dilated. Significant
atresia. The size of the FO and the flow through it is larger pulmonary regurgitation can seriously affect perfusion of the
than normal. All the venous blood returning to the heart is pulmonary vessels and cause abnormal development of the
directed through the FO to the LA and hence the LV provides intrapulmonary vessels.
the total output of the heart. Thus, due to the decreased venous In the fetus, TAPVC, may be masked as the pulmonary
filling into the RV and increased flow and volume into the LV, venous return is already low. If whole of the pulmonary
the LV size is more than the RV. The DA is smaller in caliber venous return drains into the SVC, LV will be totally free
than normal and is usually more vertically oriented than in the of pulmonary venous blood and hence will be of higher
normal fetus. This is due to the smaller than normal volume saturation. LA and LV will be relatively small in TAPVC.
of flow across the DA and then into the branch pulmonary In TGA, the aorta arises from the RV and the pulmonary
arteries. Also, as the total CCO is ejected into the ascending artery from the LV. The FO and DA develop normally and
aorta, there is higher flow across the aortic isthmus. The hence there are no major circulatory consequences of this
ascending aorta is large and the aortic isthmus is as wide as lesion in utero. Restriction of the FO and the DA is more
the descending aorta. These changes are also observed with likely to be observed in later gestation. The diameter of the
other malformations that reduce right ventricular output, such DA will be reduced as a result of both the lower flow through
as tricuspid atresia and tetralogy of Fallot (TOF) with severe it and the constrictor effect of the higher oxygen saturation.
pulmonary stenosis. The increased pulmonary blood flow will result in greater
In a fetus with rapidly developing RVOTO with intact return of blood to the LA and this tends to reduce the size
ventricular septum, RV and LV cannot compensate and the CCO of the FO. The presence of these changes in the fetus is
falls. But if the RVOTO develops slowly, both LV and RV can predictive of early severe hypoxemia postnatally.
compensate and CCO is maintained. If severe RVOTO develops Congenital cardiovascular malformations with valvar
early in gestation in the fetus with intact ventricular septum, regurgitation most often cause elevation in the systemic
the DA flow is reversed and carries only 8 to 10 percent of the venous pressure. The regurgitant atrioventricular valves
cardiac output. The DA will be narrower and will make an acute can lead to chamber dilation, hydrops fetalis and death.
inferior angle with the aorta. The DA will remain patent for a Atrioventricular valve regurgitation is noted in many fetuses
longer duration than normal. In these fetuses with RVOTO with with Ebstein malformation, some with atrioventricular septal
intact ventricular septum, if significant tricuspid regurgitation defect and in pulmonary regurgitation with absent pulmonary
(TR) develops, RV pressure remains low and myocardial valve syndrome. Some fetuses with obstruction to the LV,
sinusoids and coronary fistula do not develop. But if TR does such as with aortic atresia or to the RV output, such as with
not develop, then there is significant RV systolic pressure and if DA constriction, may develop increased venous pressure. The
this occurs early in gestation there is development of coronary manifestation of the elevated venous pressure is fetal hydrops.
fistula and intramyocardial sinusoids. In the fetus with Ebstein’s anomaly, severe TR can manifest
In the fetus with isolated aortic or pulmonary stenosis as cardiac failure especially if the FO is restrictive. There
there is interference with the outflow of the left or right is marked enlargement of the RA and the atrialized RV can
ventricle respectively and this restricts the stroke volume of cause septal displacement and compromise the LV output.
the affected chamber. Ventricular muscle mass increases in Functional pulmonary atresia can result and ductal flow
response to the increased systolic pressure. The left or right may be reversed. Marked enlargement of the RA can cause
atrial pressure does not increase significantly because of the pulmonary hypoplasia.
22
Pathologic Fetal Ductus Arteriosus25,53 References 2
In normal fetal circulation, as a large volume is ejected by 1. Berhrsin J, Gibson A. Cardiovascular system adaptation at
Fetal Circulation
the RV, the pulmonary trunk is large and due to the direction birth. Paediatr Child Health. 2011;21:1-6.
of flow through the ductus, the inferior angle between the 2. Galen. Opera Omnia IV:243. In Dalton JC (translator):
ductus and the descending aorta is oblique. In the fetus with Doctrines of the Circulation. Philadelphia: Lea’s Sons and Co;
1884:68.
RVOTO obstruction, either stenosis or atresia, RV output is
3. Vesalius A. De Humani Corporis Fabrica Libri Septem. Ex Off.
markedly reduced. This results in poor development of the Ioannis Oporim, Basileae, 1543.
main pulmonary artery and the ductus. Hence, due to the 4. Spigel A. Adriani Spigelii Bruxellensis equitis D. Marci,
direction of flow in the ductus, it results in an acute inferior olim in patavino Gymnasio Anatomiae et Chirurgiae Profess.
angle of the ductus with the descending aorta. In LV outflow Primarij, De Humani Corporis Fabrica Libri Decem. Tabulis
obstruction, as in aortic atresia, the RV output is increased XCIIX aeri incisis elegantissimis, nee ante hac visis exornati,
and the blood flow through the DA is markedly increased. The screnissimo Ioanni Carnelio Venetiarum Duci Dicati. Opus
ductus is large and connects with the descending aorta with a posthumum. Daniel Bucretius Vratislaviensis Philos. et Medic.
wide oblique inferior angle. D. Jussu Authoris in lucem profert. Venetiis MDCXXVII.
5. Harvey W. Movement of the heart and blood in animals. Franklin
Constriction of the DA in the fetus increases the smooth
KJ (translator). Oxford: Blackwell Scientific Publishers, 1957.
muscle development, which results in elevation of the PVR. 6. Barclay AE, Barcroft J, Barron DH, et al. A radiographic
This may interfere with the normal fall in PVR after birth. demonstration of the circulation through the heart in the adult
Constriction of the DA in utero may result from administration and in the foetus, and the identification of the ductus arteriosus.
of non-steroidal anti-inflammatory agents (prostaglandin Br J Radiol. 1939;12:505-18.
inhibitors) to the mother. Acute ductal constriction, may be 7. Born GV, Dawes GS, Mott JC, et al. Changes in the heart
associated with acute right ventricular dilation and TR due to and lungs at birth. Cold Spring Harb Symp Quant Biol.
‘afterload mismatch’, which is reversible with discontinuation 1954;19:102-8.
of the offending agent. A similar response may occur with 8. Rudolph AM, Heymann MA. The circulation of the fetus in
utero. Methods for studying distribution of blood flow, cardiac
acutely increased impedance to the RV due to marked
output and organ blood flow. Circ Res. 1967;21:163-84.
placental insufficiency, relating to vascular disease within the 9. Rudolph AM, Heymann MA. Circulatory changes during
placental circuit. These changes may result in irreversible RV growth in the fetal lamb. Circ Res. 1970;26:289-99.
pump failure. 10. Rudolph AM. Fetal and neonatal pulmonary circulation. Ann
Rev Physiol. 1979;41:383-95.
Conclusion 11. Rudolph AM. The changes in the circulation at birth: Their
importance in congenital heart disease. Circulation. 1970;41:
Fetal circulation is uniquely adapted to the intrauterine life 343-59.
of low oxygen saturation and non-functional lungs. The 12. Winsberg F. Echocardiography of the fetal and newborn heart.
Invest Radiol. 1972;7:152-8.
fetal circulatory pathways facilitate placental gas exchange
13. Matsui H, Gardiner H. Current aspects of fetal cardiovascular
and promote distribution of oxygenated blood to the vital function. Fetal Matern Med Rev. 2008;19:61-84.
organs of the fetus. The preparation for postnatal adaptation 14. Rudolph AM. Distribution and regulation of blood flow in the
occurs throughout fetal life. The postnatal circulatory changes fetal and neonatal lamb. Circ Res. 1985;57:811-21.
influences the clinical presentation and clinical course of the 15. Murphy PJ. The fetal circulation. Continuing education in
neonate with CHD. Congenital cardiac malformations may anesthesia, intensive care and pain. 2005;5:107-12.
fundamentally alter the circulatory pattern of the human fetal 16. Kent B, Whitaker. Fetal Circulation. Comprehensive Perinatal
cardiovascular system. Fetal echocardiography has enhanced and Pediatric Respiratory Care. Delmar Thomson Learning;
the early diagnosis of CHDs. The progression of the disease 2001;18-20.
17. Kiserud T. Physiology of the fetal circulation. Semin Fetal
processes and the physiological events need to be studied in
Neonatal Med. 2005;10:493-503.
more detail in humans. There is a possibility that prenatal 18. Ellis H. Anatomy of fetal circulation. Anesthesia and intensive
intervention may alter the development of detrimental care medicine. 2005;6:73.
physiological phenomenon/events, thereby improving both 19. Kiserud T, Rasmussen S, Skulstad SM. Blood flow and degree
fetal and mature adult outcomes. of shunting through the ductus venosus in the human fetus. Am
J Obstet Gynecol. 2000;182:147-53.
Natural forces within us are the true healers of disease. 20. Bellotti M, Pennati G, De Gasperi C, et al. Role of ductus
—Hippocrates venosus in distribution of umbilical flow in human fetuses
23
1 during second half of pregnancy. Am J Physiol Heart Circ
Physiol. 2000;279:H1256-63.
37. Reed KL, Meijboom EJ, Sahn DJ, et al. Cardiac Doppler flow
velocities in human fetuses. Circulation. 1986;73:41-6.
21. Sharma A, Ford S, Calvert J. Adaptation for life: a review of 38. Gilbert RD. Control of fetal cardiac output during changes in
neonatal physiology. Anaesthesia and intensive care medicine. blood volume. Am J Physiol. 1980;238:H80-H86.
2010;12:85-90. 39. Iwamoto HS. Cardiovascular effects of acute fetal hypoxia and
22. Szwast A, Rychik J. Current concepts in fetal cardiovascular asphyxia. In: Hanson MA, Spencer JAD, Rodeck CH (Eds). Fetus
disease. Clin Perinatol. 2005;32:857-75. and Neonate Physiology and Clinical Applications. 1. Circulation,
23. Barclay AE, Franklin KJ, Prichard MML. The foetal circulation vol. 1. Cambridge: Cambridge University Press, 1993.
and cardiovascular system and the change that they undergo at 40. Reller MD, Morton MJ, Reid DL, et al. Fetal lamb ventricles
birth. Oxford, Blackwell Scientific; 1944:275. respond differently to filling and arterial pressures and to in
24. Ho SY, Angelini A, Moscoso G. Developmental cardiac utero ventilation. Pediatr Res. 1987;22:621-6.
anatomy. In: Long WA (Ed). Fetal and Neonatal Cardiology. 41. Pinson CW, Morton MJ, Thornburg KL. Mild pressure
Philadelphia, WB Saunders Co; 1990:3-16. loading alters right ventricular function in sheep. Circ Res.
25. Rudolph AM. The fetal circulation. In: John Wiley and Sons. 1991;68:947-57.
Congenital Diseases of the Heart: Clinical-Physiological 42. Rasanen J, Wood DC, Weiner S, et al. Role of the pulmonary
Considerations. 3rd edition. UK; 2009. pp. 1-24. circulation in the distribution of human fetal cardiac output during
26. Schmidt KG, Silverman NH, Rudolph AM. Assessment of the second half of pregnancy. Circulation. 1996;94:1068-73.
flow events at the ductus venosus–inferior vena cava junction 43. De Smedt MCH, Visser GHA, Meijboom EJ. Fetal cardiac
and at the foramen ovale in fetal sheep by use of multimodal output estimated by Doppler echocardiography during mid and
ultrasound. Circulation. 1996;93:826-33. late gestation. Am J Cardiol. 1987;60:338-42.
27. Freed MD. Fetal and Transitional Circulation. In: Keane JF, 44. Sutton MG, Plappert T, Doubilet P. Relationship between
Lock JE, Fyler DC (Eds). Nadas’ Pediatric Cardiology. 2nd placental blood flow and combined ventricular output with
edition. Saunders, Pennsylvania; 2006:75-9. gestational age in normal human fetus. Cardiovasc Res.
28. Brace RA. Regulation of blood volume in utero. In: Hanson 1991;25:603-8.
MA, Spencer JAD, Rodeck CH (Eds). The circulation, Fetus 45. Rychik J. Fetal cardiovascular physiology. Pediatr Cardiol.
and neonate. Physiology and clinical application, Vol. 1. 2004;25:201-9.
Cambridge: Cambridge University Press; 1993. pp. 75-99. 46. Iwamoto HS, Kaufman T, Keil LC, et al. Responses to acute
29. Brace RA. Fetal blood volume response to intravenous saline hypoxemia in fetal sheep at 0.6-0.7 gestation. Am J Physiol.
solution and dextrane. Am J Obstet Gynecol. 1983;143:777- 1989;256:H613-20.
81. 47. Kiserud T, Jauniaux E, West D, et al. Circulatory responses to
30. Castle B, Mackenzie IZ. In vivo observations on intravascular acute maternal hyperoxaemia and hypoxaemia assessed non-
blood pressure in the fetus during mid-pregnancy. In: Rolfe invasively by ultrasound in fetal sheep at 0.3-0.5 gestation. Br
P, (Ed). Fetal physiological measurements. London, Boston, J Obstet Gynaecol. 2001;108: 359-64.
Durban, Singapore, Toronto, Wellington: Butterworths; 1986. 48. Reynolds SRM. Fetal and neonatal pulmonary vasculature in
pp. 65-9. guinea pig in relation to hemodynamic changes at birth. Amer
31. Johnson P, Maxwell DJ, Tynan MJ, et al. Intracardiac pressures J Anat. 1956;98:97-102.
in the human fetus. Heart. 2000;84:59-63. 49. Cassin S, Dawes GS, Mott JC, et al. The vascular resistance
32. Ville Y, Sideris I, Hecher K, et al. Umbilical venous pressure of the fetal newly ventilated lung of the lamb. J Physiol. 1964;
in normal, growth-retarded and anemic fetuses. Am J Obstet 171:61-79.
Gynecol. 1994;170:487-94. 50. Cook CD, Drinker PA, Jacobsen HN, et al. Control of pulmo-
33. Friedman WF. The intrinsic physiologic properties of the nary blood flow in the fetal and newly born lamb. J Physiol.
developing heart. Prog Cardiovasc Dis. 1972;15:87-111. 1963;169:10-29.
34. Thornburg KL, Morton MJ. Development of the cardiovascular 51. Rao PS. Perinatal circulatory physiology: Its Influence on
system. In: Thorburn GD, Harding R, (Eds). Textbook of fetal clinical manifestations of neonatal heart disease. Neonatology
physiology. Oxford: Oxford University Press; 1994. Today. 2008;3:6-12.
35. Artman M. Sarcolemmal sodium–calcium exchange activity 52. Zeltser I, Tabbutt S. Critical Heart Disease in the Newborn. In
and exchanger immunoreactivity in developing rabbit hearts. Pediatric Cardiology: The Requisites in Pediatric Cardiology.
Am J Physiol. 1992;263:H1506-H1513. Vetter VL (Ed). Mosby, Inc, US; 2006. pp. 31-3.
36. Grant DA, Fauche`re JC, Eede KJ, et al. Left ventricular stroke 53. Rudolph AM. Congenital cardiovascular malformations and
volume in the fetal sheep is limited by extracardiac constraint the fetal circulation. Arch Dis Child Fetal Neonatal (Ed).
and arterial pressure. J Physiol. 2001;535:231-9. 2010;95:F132-6.
24
C hapter
Etiopathogenesis of
3 Congenital Heart Diseases
Krishnamoorthy KM
Introduction There are six supposed pathogenetic mechanisms of CHD

as enumerated below:5
Congenital heart diseases (CHD) are the most prevalent and 1. Abnormal migration of ectomesenchymal tissue
serious of all recognized structural birth defects. Surviving 2. Abnormal intracardiac blood flow
infants often require surgery or interventions and lengthy 3. Abnormal cellular death (apoptosis)
hospitalizations, and will have a lifetime of disability that 4. Abnormalities of the extracellular matrix
imposes a significant burden on families. Costs associated with 5. Abnormal targeted growth
the care of a child with a CHD are significant even in developed 6. Abnormalities of situs and looping.
countries,1 particularly when lifetime costs of management This chapter reviews the etiopathogenesis of CHD and
are considered. Advances in medical diagnosis and treatment deals with etiologic factors, which are not genetic. Genetic
have certainly helped to improve the survival of patients with factors will be dealt within another chapter. Most of the causes
CHD. The burden of CHD can be further ameliorated through of CHD discussed occur within the fetal-placental-maternal
primary prevention, if the causes are known. ‘environment’. They are broadly classified into:
1. Infections
Prevalence of CHD 2. Maternal drug exposure
3. Parental medical conditions
The prevalence of CHD at birth in a population-based 4. Parental smoking
setting is 0.9 percent or one in 110 newborns.2 CHD are very 5. Parental alcohol intake
heterogeneous in anatomy, hemodynamics and recognition 6. Vitamins
rates. It is difficult to pinpoint one or even a multifactorial 7. Environmental factors
cause for etiopathogenesis in the majority of cases. An 8. Sociodemographic factors
estimated 15 percent of CHD can be traced to a known cause.3 9. Recurrences of CHD in families.
The remaining cases are thought to result from complex Studies done in such situations are reviewed. Wherever
interactions involving environmental exposures, maternal data is available, the pathogenesis of CHD is briefly reviewed.
lifestyle factors and genetic susceptibilities. Limitations of such studies are also discussed in the end.
Pathogenetic Mechanisms Infections

Pathogenesis during cardiac development varies between Exposure to teratogen produces an estimated 1 percent of CHD.6
the different types of CHD. Hence a particular teratogen will
not increase the risk of all defects. Between 5 to 8 weeks Maternal Rubella
of gestation, the primitive heart tube undergoes folding,
remodeling and septation that transforms its single lumen Maternal rubella was the earliest teratogen identified. This
into a four-chambered heart. By the 9th week, the outflow is discovery was important not only in itself, but by stimulating
divided into two. For a teratogen to act on the embryonic heart interest in the etiology of CHD. The rubella virus passes through
to produce CHD, it has to do so during the 14 to 60 days of the chorionic epithelium to the bloodstream of the fetus. It
gestation, which is the most vulnerable period.4 has a selective action on the heart and on the three epidermal
1 structures of the fetus. The cells are severely damaged, includes CHD ranging from ventricular and atrial septal
becoming swollen and vacuolated and sometimes destroyed. defects to complex conotruncal defects.21 Extensive review
Most offsprings (90%) have ‘flow’ defects, especially patent on this association is available.22
ductus arteriosus (20%) and peripheral pulmonic stenosis

(10–20%).7 Both occur more commonly in infants with Metronidazole
rubella syndrome than in those with non-rubella CHD.8 Other
defects noted are pulmonary valve abnormalities7, as well as In the Baltimore-Washington Infant Study, maternal use of
atrial and ventricular septal defects.7,9 Of particular note, there metronidazole during pregnancy was found to be associated
is a relative absence of conotruncal, atrioventricular canal, with an increased risk of outflow tract anomalies with normally
laterality and single-ventricle defects. related great arteries, as well as membranous ventricular
septal defects.8
Other Infections and Fever
Trimethoprim-sulfonamide
There are intriguing reports of association of CHD with
maternal fever in the first trimester, including influenza.8,10 An association with CHD was found, when trimethoprim-
A 40 to 80% increase in risk for CHD has been reported10-12 with sulfonamide was taken during the first trimester pregnancy
some degree of specificity in the outcomes. The association in a case-control study.23 Similar were the observations
with febrile illness appears to be more marked for tricuspid in the Hungarian case-control surveillance of congenital
atresia,8 atrial and ventricular septal defects8,10, as well as for abnormalities.24 Significantly, the risks were reduced if the
left-sided obstructive defects and transposition of the great mother also took folic acid supplementation.
arteries.10,11 Specific defects shown to be associated with
such febrile illness include pulmonic stenosis,8 all right-sided Isotretinoin
obstructive defects,10 coarctation of the aorta,10 d-transposition
of the great arteries8 and conotruncal defects.10,11 In a smaller This analogue of vitamin A, used to treat cystic acne, has been
cohort study, an infant exposed prenatally to high fever had associated with CHD.25 A characteristic pattern of malformation
transposition of the great arteries.13 Mothers with any febrile involving craniofacial, cardiac, thymic and central nervous
illnesses during the first trimester of pregnancy have a 2-fold system structures is seen. Conotruncal and aortic-arch
higher risk of CHD in the offspring.8,10 A case-control study abnormalities have been described.25 High maternal intake of
found an association of maternal fever with conotruncal retinol supplements is uniquely associated with transposition
defects among offspring born to mothers, who did not use of great arteries, according to one study.26 Like thalidomide,
multivitamins.14 it produces highly specific and time-dependent effects on
Hyperthermia in chick embryos causes malformations of cardiovascular development.27 It may have a deleterious
the outflow tract and stenosis of the ventral aorta and aortic effect on cephalic neural crest cell activity that results in the
arches.15,16 But in man, the exposure is febrile illness rather observed craniofacial, cardiac and thymic malformations.25
than hyperthermia. Both fever and infection have biological The frequency of CHD is reduced among offsprings of women,
effects on specific developmental pathways. Apoptosis is who discontinue therapy before conception.28
affected by both hyperthermia17 and viruses.18 Apoptosis is
involved in cardiac morphogenesis, e.g. in the development Antiepileptic Drugs
of the cardiac outflow tract.19 Distinguishing the effect of
hyperthermia from that of underlying infection may be Anticonvulsant drugs are strongly implicated as teratogens.
difficult. Most of the studies have not been able to distinguish Their use during pregnancy has been associated with
between independent and joint effects associated with CHD.29–34 Among 69 patients with valproate embryopathy, 26
maternal fever, maternal infection and use of medications to percent had CHD in a study.31 Ventricular septal defects, aortic
control the fever or infection. stenosis, pulmonary stenosis and patent ductus arteriosus
were observed. These lesions belong to the category of
Maternal Drug Exposure abnormalities resulting from altered embryonic blood flow.
Therapeutic Drug Exposure Fluconazole

An unusual pattern of CHD in offsprings of mothers treated
Thalidomide with high-dose of fluconazole for meningitis, during the first
Thalidomide was the second teratogen recognized after rubella. trimester has been noticed. One baby had tetralogy of Fallot,
It was shown to be involved in anomalies of the ventricular patent ductus arteriosus, pulmonary artery hypoplasia, patent
26 outflow tract more than 50 years back.20 The embryopathy foramen ovale, while the other had ventricular septal defect
and pulmonary artery hypoplasia.35 But prospective studies use of ibuprofen during pregnancy has been associated with 3
are not available to draw definite conclusions. The drug d-transposition of great arteries, membranous ventricular
inhibits cytochrome P450 as well as cytochrome c oxidative septal defects, atrioventricular septal defects and bicuspid
Etiopathogenesis of Congenital Heart Diseases

and peroxidative enzymes. This results in an increase in aortic valve.46 Ketoprofen47 has been associated with
intracellular peroxide generation, which is toxic to the CHD. Indomethacin has been similarly implicated.48,49
developing fetus. Two studies have associated indomethacin and patent
ductus arteriosus, the risk being maximum, when it is
Lithium given within 48 hours of delivery. Patent ductus arteriosus
was more common in infants after maternal indomethacin
Maternal treatment with lithium carbonate during pregnancy administration as a tocolytic. These neonates failed to
and the occurrence of Ebstein anomaly have been respond to postnatal indomethacin to close a patent ductus
associated.36,37 In a voluntary reporting registry, serious CHD arteriosus.50 Infants exposed to antenatal indomethacin
were observed in 8 percent of 225 infants born to mothers, had an increased incidence of patent ductus arteriosus,
who had taken lithium during the first trimester of pregnancy.38 were more symptomatic from the ductus, which was more
One-third of these infants had Ebstein anomaly. But current resistant to medical closure.51
data from retrospective, prospective and meta-analysis studies Case reports of persistent pulmonary hypertension and
suggest that lithium is not a known cardiac teratogen.39,40 premature closure of the ductus arteriosus in infants, whose
mothers took other non-steroidal anti-inflammatory drugs are
Hypnotics available like naproxen,52 diclofenac53 and sulindac.48
The incidence of CHD was increased among infants of Female Hormones

women, occasionally treated with amobarbital.41 The risk for
chronic or high-dose maternal use is unknown. Female sex hormones were found to be teratogenic to the fetus
during the period of cardiovascular embryogenesis, for any type of
Phenothiazine CHD and specifically for ventricular septal defects.54–57 Although
case-control studies58 suggested a risk of CHD in offsprings
One study mentions phenothiazine exposure as a risk factor from maternal use of oral contraceptives, later reports and meta-
for CHD in the offspring.41 analysis did not substantiate this association.59
Narcotics Clomiphene
Case-control studies29 reported an association of CHD in Maternal use of clomiphene was associated with coarctation of
offsprings with maternal codeine use during the first trimester the aorta and tetralogy of Fallot.8 Among 397 newborns from
of pregnancy, but with methodological limitations. Other women treated with clomiphene in a study, four had ventricular
studies failed to confirm this.42 septal defects.60 This was more than expected and the rate of
all CHD was significantly high. Atrial and ventricular septal
Sympathomimetics defects, as well as coarctation of aorta were observed in
another study.61 The same authors published their observations
There are conflicting reports of association of phenylephrine on the incidence of CHD among women, who conceived
with CHD: a case-control study with positive association43 after assisted reproductive technology.62 Studies that have
and a large cohort study with negative association.41 investigated the impact of clomiphene on fetal development
have been criticized for combining the use of clomiphene with
Corticosteroids assisted reproductive technology. In fact, the defect categories
that appear to be associated with both clomiphene and assisted
A similar conflicting data is available for the association reproductive technology are similar: septal heart defects and
of maternal corticosteroid use and CHD. The Baltimore- esophageal atresia.61,62 Further, the small number of cases,
Washington Infant Study showed a possible association by inconsistency of some findings with previous reports and the
univariate analysis, but not when other variables were taken inability to assess the clomiphene effect separately from that of
into account.44 infertility alert to a cautious interpretation.
Non-steroidal Anti-inflammatory Drugs Chemotherapy

A large registry study found a slightly high-risk of CHD for It is impossible to study the effect of chemotherapy during
these drugs, but no drug specificity for CHD.45 Maternal pregnancy. Studies on children of mothers, who received 27
1 chemotherapy for cancer in childhood, found CHD in 10 mellitus does not affect the risk of malformation in the fetus.
percent of such children.63 However, the duration of diabetes has a significant effect on
the malformation risk with higher incidence seen in infants of
Non-therapeutic Drug Exposure 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
Cocaine and Marijuana
metabolism, is the responsible factor for the increase of
Maternal: A case report suggested that single ventricle may malformations in the fetus.
result from maternal cocaine ingestion.64 Coronary occlusion
in the developing fetal heart due to coronary spasm could have Early Lesions
produced an infarct, which destroyed the right ventricle. This
fetal pathology may be one mechanism that leads to single The pattern of CHD encountered with an emphasis on
ventricle hearts. Data from a case-control study, the Atlanta abnormalities of laterality, looping and conotruncal septation
Birth Defects Case-Control Study, investigated the role of suggests that maternal diabetes affects cardiogenesis very early,
maternal cocaine ingestion in the induction of single ventricles prior to 7 weeks of gestation.73,74 Experimental embryogenesis
and found no association.65 In this study, even if maternal in a medium with high glucose concentrations, shows that the
cocaine ingestion during pregnancy was a purported cause of migratory and proliferative capacity of neural crest cells are
single ventricle, most cases appeared to be unrelated to this affected.75 ‘Early onset’ defects like conotruncal anomalies
exposure. An increased frequency of CHD was seen among are thus explained in diabetic pregnancies. The case of two
infants with neonatal toxicology screens showing the prevalence infants of diabetic mothers, with DiGeorge syndrome and
of cocaine in 1 study, with peripheral pulmonic stenosis as the normal chromosome 22q11, further illustrates that maternal
leading diagnosis and in far greater numbers than in the general diabetes may be a pathogenic factor in this anomaly.76 In the
population.66 Case-control studies have reported an association Baltimore-Washington Infant Study, only the ‘early’ CHD
of maternal cocaine abuse with increased risk of any CHD,67 (defects of primary cardiogenesis) were strongly associated
heterotaxy68 and membranous ventricular septal defects.8 with maternal diabetes, while those arising later in cardiac
Paternal: The Baltimore-Washington Infant Study reported development (obstructive and shunting defects in four-
an association of paternal cocaine use with an increased risk chambered hearts) were not significantly associated.77
of any CHD and with ventricular septal defects and tricuspid
atresia in particular.8 In this study, it was found that paternal Mechanism
marijuana use and use of cocaine among older fathers were
risk factors for isolated membranous ventricular septal defects It is believed that the abnormal glucose levels disrupt expression
in offspring.69 The evaluation of these drugs is hampered due of a regulatory gene in the embryo, leading to embryotoxic
to the concomitant use of tobacco and alcohol and therefore apoptotic cellular changes.78 Variations in glucose metabolism
individual effect is difficult to evaluate. In the Atlanta Birth and/or protein glycosylation, perhaps of genetic origin, affect
Defects Case-Control Study, risk of isolated simple ventricular the vascular complications of diabetes.79 Vascular alterations
septal defects doubled in offsprings with maternal self- and as a common pathway to cardiovascular maldevelopment
paternal-proxy reported marijuana use.70 Risk of isolated might be initiated by aneuploidy and by maternal diabetes.
simple ventricular septal defect increased with regular Both of these etiological factors would explain the occurrence
(3 day/week) marijuana use for both maternal self- and of early, rather than late CHD. Another postulated mechanism
paternal-proxy report. The association was significant for is an association between excess oxygen radical activity and
maternal self-report. Maternal use of marijuana was also disturbed embryogenesis in diabetic pregnancy.80 Adminis
found to be associated with a slight increase in risk for Ebstein tration of antioxidants to diabetic pregnant rodents can reduce
anomaly in the Baltimore-Washington Infant Study.8 the risk for diabetes-associated embryopathy.81 A higher
genetic susceptibility towards congenital malformations also
Parental medical conditions plays a role in diabetic women.82 Pregestational diabetes
increases the risk of CHD83 and is hypothesized to change the
Among CHD, 1 percent of CHD can be attributed to maternal expression of a regulatory gene important for the septation of
diseases, such as type I diabetes and phenylketonuria.42 the outlet tract of the heart.84
Diabetes Mellitus Defects

Diabetic mothers have offsprings with CHD.32,54,71 In the Laterality and looping defects,3,8 hypoplastic left heart
Atlanta Birth Defects Case-Control Study, the absolute risk syndrome,8 non-chromosomal atrioventricular septal defects,8
28 for CHD was 5.3 per 100 live births.72 Therapy of diabetes outflow tract anomalies, tetralogy of Fallot,72,85 transposition
of great vessels,8,72 patent ductus arteriosus8,72 and ventricular elevation for aggregate CHD among obese black women.94 3
septal defects8,72 are associated with maternal diabetes. There A 2-fold increase in risk of aggregate CHD with predilection
is a strong predilection for left atrial isomerism86 and visceral for truncus arteriosus and transposition of great arteries has

heterotaxia in transposition.87 In the Baltimore-Washington been reported95 and for a grouped category of defects of the
Infant Study, maternal diabetes was strongly associated with great vessels.96 Obesity is a complex condition and has to be
CHD with significant heterogeneity within these developmental studied carefully to minimize the possibility of associations
categories: among laterality defects, diabetes was associated due to chance and bias. The possibility of confounding by
only with cardiovisceral and atrioventricular discordance; among other factors such as type 2 diabetes, intake of micronutrients
outflow tract anomalies, the risk was strongly associated with or use of multivitamin supplements have to be borne in mind.
normally related great arteries but not with simple transpositions; This is because of a hypothetical explanation that undetected
and among atrioventricular septal defects, diabetes was diabetes type 2 may be associated with an increased risk for
associated with the complete but not with the partial forms.77 CHD.97
The association was strongest among infants with multisystem,
predominantly VACTERL association (vertebral anomalies, Parental Smoking
anal atresia, cardiac defect, tracheoesophageal fistula, renal
anomalies, limb defects). The mortality with CHD was more
Maternal
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 Lesions
and low birth weight. Three mothers with insulin-dependent Tobacco smoking is one of the major preventable causes of
diabetes mellitus had babies with isomerism. High glycated morbidity and mortality. Its use in pregnancy is a public health
haemoglobin levels made the authors implicate poor glycemic issue and is a human developmental toxicant and potential
control, although other teratogenic mechanisms associated with teratogen.98 Some studies have reported an adverse effect of
diabetes could not be excluded. Both right and left isomerism gestational smoking on the risk of CHD (as a group) in the
in different parts of the same patient were seen and suggested offspring99-102 or on specific heart defect subgroups,99,100,103
the model of random development of laterality following the though others have not found any relationship.89 A meta-
interruption of normal developmental processes.88 analysis of studies published between 1971 and 1999 (12
analyses of all CHD and 7 analyses of CHD groups or specific
Epilepsy phenotypes separately) found no association for CHD and
mixed results for analyses of specific groups or phenotypes.99
Pregnant women with epilepsy are at an increased risk for Reports of positive associations of maternal smoking with
CHD in their offsprings.89,90 Confounding factors like direct CHD combined100,101 and negative association are available
teratogenic effects of anticonvulsant drugs or their indirect (Baltimore-Washington Infant Study).8 A similar trend is
effect on folate metabolism prevent an objective analysis of seen for associations between maternal smoking and CHD
the impact of epilepsy on the causation of CHD. As already groups. Positive association has been suggested for atrial
mentioned, anticonvulsant drugs are known teratogens.29-34 septal defects, atrioventricular septal defects and tetralogy
No specific pattern of CHD seems to be closely related to of Fallot,100 while these were not corroborated by larger
these factors, with reported associations involving CHD as a studies such as the Baltimore-Washington Infant Study8 and
whole, as well as the common arterial trunk, transposed great a Swedish study.99 In the Swedish population-based study,
arteries and septal defects. unadjusted estimates revealed an increased risk of having an
infant with either truncus arteriosus or atrial septal defects
Phenylketonuria among women, who smoked.99 Analyses of small case groups
based on the Baltimore-Washington Infant Study data has
Untreated maternal phenylketonuria is associated with a > 6 shown associations of maternal smoking with single ventricle
fold increased risk of CHD.91 One study reports an increased and l-transposition of great arteries.68,103 Smoking in early
incidence of left-sided obstruction.92 Other defects described pregnancy was associated in a dose-dependent manner with
are tetralogy of Fallot, ventricular septal defects, patent ductus transposition of great arteries with ventricular septal defect
arteriosus and single ventricle. This can be reduced with strict and with pulmonic valve stenosis.8 The effects were seen in
diet control before conception and during pregnancy.8 certain, possibly susceptible subgroups, such as older mothers
and those with a history of miscarriages.
Obesity Among the congenital defects in a large cohort study on
congenital anomalies in relation to gestational smoking,
There is a modestly elevated risk among obese women for only CHD showed a significantly increased incidence in the
CHD in their offspring.32,93 Another study found a 6.5-fold risk tobacco exposed group.101 Maternal and infant characteristics 29
1 of neonates with CHD were compared with normal neonates exposed to the toxins. Both maternal and paternal exposure
in one study.104 More mothers of neonates with CHD smoked to toxins increased the CHD risk in children, who carried the
(40.8% vs 19.7%) during pregnancy. Logistic regression combined null GST genotypes. Polymorphisms in GST genes
analysis showed that periconceptional tobacco smoking can modify a person’s risk of toxicant exposure. It showed
was associated with increased risk of CHD in the offspring. that GST polymorphism might mediate the risks of parental
Incidence of neonatal CHD increased with the level of fetal exposure to toxin for CHD.
tobacco exposure, suggesting a dose effect too. Genetic polymorphisms in the nitric oxide synthase (NOS)
gene are associated with birth defects. In a population-based
Quantification registry, single nucleotide polymorphisms in the NOS3 gene
among infants with conotruncal defects were more likely to
Any-time smokers have babies with septal defects, the associ- carry the variant alleles for NOS3 (922A > G), NOS3 (298G
ation being stronger for mothers, who reported heavier tobac- > T) or both and to have mothers who smoked cigarettes
co consumption during pregnancy.105 This was independent periconceptionally compared with control infants.112 The
of potential confounding factors. Mothers, who smoked > 25 gene-environment interaction reported by this study illustrates
cigarettes/day more often gave birth to babies with right-sided the importance of the associations among CHD, maternal
obstructive lesions.105 The dose-effect relation for CHD was exposure and genetic variants that modify the effect of
confirmed in a case-control study.104 Maternal overweight and exposure on developing hearts.
smoking may have a synergistic adverse effect on the devel-
opment of the fetal heart and these women should be strongly Paternal
encouraged to stop smoking and to lose weight before becom-
ing pregnant.106 Father’s cigarette smoking has been shown to be more common
among children with ventricular septal defect.113 Other studies
Mechanism showed that parental smoking, particularly when both parents
were smokers, increased the risk of conotruncal defects.114
Smoking during pregnancy results in deposition of tobacco It is also believed that male exposure might exert a
constituents in the circulation of mother and hence the teratogenic effect through toxic nicotine compounds adsorbed
fetus. This serves as serious hazard at all stages of human to the sperm and transmitted to a woman in the ejaculate. The
development.98 Gestational smoking results in placental contaminant is absorbed by the woman, where it might reach
pathologies, preterm birth, low birth weight and structural and adversely affect a current pregnancy or may even remain
malformations in the offspring, abnormal somatic growth in the woman’s body to influence future pregnancies.108
and increased blood pressure in childhood.98 Nicotine and In all these studies, some residual confounding could
carbon monoxide have high placental permeability, resulting not be excluded. Exposure to environmental smoking was
in increased concentrations in the fetal circulation compared determined by maternal self-reports, without independent
to maternal levels.98 Nicotine constricts the uterine arteries, biochemical validation.
reducing placental blood flow.107 Carbon monoxide increases
fetal carboxyhemoglobin impairing fetal oxygenation.98 Both Parental alcohol intake
contribute to tobacco-associated fetal hypoxia, which exerts a
teratogenic effect.
Maternal
Environmental toxin can induce oxidative deoxyribonucleic
acid (DNA) damage, mutations and chromosomal aberrations, Alcohol abuse is known to be teratogenic and among the effects
such as DNA strand breaks and aneuploidy.108 They might act seen are CHD.115 Some studies could not find an association.33
in human seminal fluid as endocrine disrupting agents causing Ethanol produces fetal tissue edema and affects the turgor of
direct germ line DNA damage or epigenetic changes.108 the primitive cardiac loop. Alcohol intake is associated with
Smoking is associated with increased oxidative stress,109 increased oxidative stress109 that decreases the activity of
which can decrease the functional activity of methionine methionine synthase through limiting the availability of reduced
synthase through limiting the availability of reduced vitamin vitamin B12. Homocysteine and S-adenosylhomocysteine
B12. As mentioned in the section on alcohol, homocysteine are elevated. S-adenosylhomocysteine is a potent product
accumulates and produces its toxic effects.110 inhibitor of cellular methyltransferases, which during
Glutathione S-transferase (GST) polymorphisms were organogenesis can alter gene expression, cell differentiation
investigated in a study on mothers of affected children and apoptosis.110 Homocysteine has embryotoxic effect and
with CHD.111 The modification effect of susceptibility in leads to inhibition of DNA methyltransferase reactions, DNA
children, who lacked the genetic capacity to produce GSTM1 hypomethylation and altered gene expression.
and GSTT1 enzymes was explored. Paternal smoking The first description of fetal alcohol syndrome pointed
30 (>15 cigarettes/day) was found to be associated with CHD at alcohol, as a cardiac teratogen.116 Atrial, ventricular and
risk. An additive risk was present, when both parents were conotruncal defects are predominantly seen after maternal
alcohol consumption during pregnancy.117 In a case-control In a review125 of all major randomized trials and 3
study of patients with conotruncal abnormalities and observational studies from 1992 to 2000, three studies121-123
ventricular septal defects, the effect of maternal alcohol use showed an overall decrease in the risk of CHD in the range

was compared with controls.118 Maternal alcohol consumption of 25 to 50 percent. This was maximal for conontruncal and
during the first trimester of pregnancy was more common septal defects. A derangement of maternal homocysteine
among the mothers of infants with ventricular septal defects metabolism and a mutation in the methylenetetrahydrofolate
than among those of controls. These mothers consumed reductase gene termed C677T are more frequently seen
alcohol regularly every week and consumed more than 1 drink in selected populations with CHD.126,127 This mutation is
per occasion. Another case-control study examined sporadic associated with elevated homocysteine levels, which can be
and daily doses of alcohol consumption and reported an normalized by folic acid supplementation.
increased risk of CHD, as a group only with the highest level In a case-control design, biomarkers of the folate-dependent
of maternal alcohol consumption per day (> 92 g/day).119 methionine and homocysteine pathway were measured among
Increased risks of atrial septal defects118 and ventricular septal a population-based sample of women, whose pregnancies were
defects120 are associated with any maternal alcohol consumption affected by CHD.110 Case subjects had higher concentrations
in the first trimester, but the dose-response trends in risk have of homocysteine and S-adenosylhomocysteine and lower
been inconsistent with a causal association in these studies. In concentrations of methionine. Methionine is initially activated
the Baltimore-Washington Infant Study, heavy consumption by adenosine triphosphate (in presence of methionine
(5 drinks on a single occasion) was linked to increased risk for synthase) and converted to S-adenosylhomocysteine.
small muscular ventricular septal defects; but no statistically Homocysteine is elevated among women with a history of
significant associations were detected for atrial septal defect or adverse pregnancy outcomes including CHD.128 Increased
membranous ventricular septal defects.8 A similar study from S-adenosylhomocysteine is a potent product inhibitor of
Finland reported double the risk of atrial septal defects with cellular methyltransferases, which during organogenesis
maternal alcohol consumption during the first trimester.120 can alter gene expression, cell differentiation and apoptosis.
These alterations, if not causally related, are associated with
Paternal an increased risk of having adverse pregnancy outcomes,
including CHD. Possible causes for the altered biomarkers
Alcohol use by the father was positively related to the include deficiencies in folate or vitamin B12 or both. Possible
offspring’s risk of ventricular septal defects in one study.113 mechanisms by which homocysteine may have an embryotoxic
The authors admit that the data does not indicate strong effect include oxidative stress and secondary accumulation of
associations between paternal attributes and CHD. Because of S-adenosylhomocysteine, which leads to product inhibition of
this study’s imprecision and limited ability to isolate defects DNA methyltransferase reactions, DNA hypomethylation and
likely to be of paternal origin, further study is necessary. altered gene expression.
Vitamins Indirect Evidence

While the above studies directly tested the association
Folic Acid
between multivitamin use and risk for CHD, other studies
present ancillary evidence of a protective effect of folic acid-
Direct Evidence containing supplements on CHD. When pregnant women
A Hungarian randomized trial on birth defects showed that took folic acid antagonists, there was a two-fold increased
periconceptional use of multivitamin supplements containing risk of having babies with CHD. This was reduced among
folic acid had a 50 percent overall reduction in risk for CHD.121 those, who also took multivitamin supplements containing
It was 25 percent reduction in risk in the Atlanta population- folic acid.30 In a study on the effect of multivitamins in
based case-control study.122 Multivitamin use reduced the high-risk groups, the increased risk for CHD associated with
risk in case-control studies: 54 percent reduction in one122 febrile illness was reduced among women using multivitamin
and 30 percent in another.123 For ventricular septal defects, a supplements around the time of conception and during early
population-based case-control study122 showed a 40 percent pregnancy.10
reduction and the Hungarian randomized trial showed a 85 Associations with sulfasalazine given to pregnant
percent reduction in risk.121 There was a 30 percent reduced mothers and CHD was observed in a case-control study.23
risk for conotruncal defects in a population-based case-control These associations were not seen among mothers, who took
study.123 Heterogenecity in this favorable response also has supplemental folic acid. As already mentioned, maternal
been reported, with a more apparent trend in risk reduction for use of trimethoprim-sulfonamide has resulted in CHD
transposition of the great arteries than for other defects of the in offspring,23 the risk being reduced when folic acid was
cardiac outflow tract.124 supplemented.24 31
1 Vitamin A Washington Infant Study, maternal exposure to herbicides and
rodenticides were linked to an increased risk of transposition
The association between high vitamin A in the diet and/or of the great arteries and maternal exposure to pesticides with
supplements and neural crest cell defects (cardiac and non- total anomalous pulmonary venous return and membranous
cardiac defects) or outflow tract have been addressed in some ventricular septal defects.8 A recent case-control study
studies. An increased risk of CHD with an intake of more of various end-product uses reported an increased risk of
than 10,000 IU retinol in the form of supplements129,130 and conotruncal defects with maternal exposure to insecticides.132
occurrence of defects of the cardiac outflow tract at dosages The Baltimore-Washington Infant Study, a case-control
more than 18,000 to 25,000 IU/day in animals have been study of CHD in liveborn infants, revealed an association
described. of maternal exposure to herbicides and rodenticides during
the first trimester with transposition of great arteries in their
environmental factors 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
Organic Solvents
exposures were each compared with unexposed mothers. One
Maternal occupational exposure to organic solvents, chemicals, study has shown no association of maternal pesticide exposure
dyes and paints is a signifcant risk factor for CHD and specifically at work places with a risk for CHD.136
for ventricular septal defects.54,55,131 The Baltimore-Washington
Infant Study showed that maternal exposure to degreasing or other Air Quality
solvents was associated with an increased risk of hypoplastic
left heart syndrome, coarctation of the aorta, pulmonic stenosis, Studies have addressed the associations of ambient air
transposition of the great arteries with intact ventricular pollutants with CHD. A population-based case-control
septum, tetralogy of Fallot, total anomalous pulmonary venous study139 looked at risks of CHD associated with second
return, non-chromosomal atrioventricular septal defects and trimester exposure to carbon monoxide, sulfur dioxide,
Ebstein anomaly.8 Other associations are that of occupational nitrogen dioxide, ozone and particulate matter less than 10 µm
exposure to organic solvents and increased risk of ventricular in aerodynamic diameter. There were associations between:
septal defects;118,132 dyes, lacquers and paints with conotruncal 1. Carbon monoxide exposure and increased risk of
malformations;133 and mineral oil products with coarctation of ventricular septal defect and tetralogy of Fallot,
the aorta.134 Genetic susceptibility to the effects of solvents and 2. Ozone exposure and elevated risk of aortic artery and valve
paints has been suggested.135 Genetic polymorphisms in key defects, pulmonary artery and valve defects and conotruncal
solvent-metabolizing enzymes, glutathione S-transferases, were defects,
found to mediate the risks of solvents and paints for pulmonic 3. Particulate matter less than 10 µm in aerodynamic diameter
valve stenosis and atrial septal defect. and atrial septal defect,
4. Sulfur dioxide and ventricular septal defects.
Chemicals at Workplaces The difference is explained by the usage of a different
critical window of exposure in the analysis: gestational month-
Hazardous maternal occupation has been implicated in the specific exposures140 vs mean exposure for the entire period
causation of CHD in some studies.54 A study investigated the of susceptibility, from gestational weeks 3 through 8.139
possible associations between CHD and maternal occupational
exposure to various factors during the first trimester of Groundwater Contamination
pregnancy.136 The cases were taken from infants diagnosed with
CHD, while controls were randomly selected from all normal Contamination of public drinking water supplies by
births during the same period. Maternal overall exposure to chlorinated hydrocarbon solvents reportedly was associated
chemicals at work was more prevalent among the case group. with increased risks for CHD.141–143 The risk of CHD was
Among the specific chemical groups, maternal exposure to greater among children of parents, who had contact with areas
dyes, lacquers or paints was significantly associated with the that had groundwater contaminated with trichloroethylene
risk of CHD. Exposure to organic solvents during the first than among children of parents, who had no such contact.141
trimester increased the risk of ventricular septal defects. Work Another study after evaluating the actual maternal
at video display terminals was more prevalent among the consumption of home tap water during the first trimester of
case group. pregnancy found an increased risk of CHD.142
Herbicides, Pesticides and Rodenticides Ionizing Radiation

32 An increased risk of conotruncal defects was associated Ionizing radiation is implicated in the pathogenesis of CHD
with maternal employment in the agricultural industry with in a small study.54 The Baltimore-Washington Infant Study
exposure to chemicals used in agriculture.137 In the Baltimore- studied associations of CHD with maternal exposure to
ionizing radiation in occupational settings or for medical for maternal age.148 A matched case-control study showed 3
evaluations and found no evidence of any associations.8 that an older paternal age was a significant risk factor for
developing any CHD, atrial and ventricular septal defects and

Water Chlorination Byproducts pulmonary stenosis.54 Other epidemiological studies have
found an association between advanced paternal age and
Studies have linked maternal exposure to chlorination by- CHD.147 A prospective study32 and the Baltimore-Washington
products in municipal water supplies and CHD.144 Infant Study69 could not find an association between paternal
age and CHD.
Other Environmental Hazards
Gender and Race
Communities situated near hazardous waste sites or other
sources of environmental pollution had an increased risk of Increased prevalence of left-sided obstructive lesions,
CHD as a group,145 but the number of exposed cases were particularly coarctation of the aorta and aortic valve stenosis,
small (n = 3) to draw valid conclusions. Rural residence was among whites has been reported.149,151 White infants are also
associated with an elevated risk for CHD. This might be due to reported to have an increased prevalence of Ebstein anomaly,
the fact that, in this study, a considerable percentage of parents atrioventricular septal defects, atrial septal defects,149 truncus
living in rural areas were factory workers. Other possible arteriosus, transposition of the great arteries, tetralogy of
explanations might be exposure to pesticides or herbicides, Fallot,137,149 patent ductus arteriosus149,152 and hypoplastic
higher frequency of respiratory and other infectious diseases left heart syndrome.152 In the Baltimore-Washington Infant
implicated in the etiology of CHD.54 Study, significant association for membranous ventricular
septal defect was found with African-American race of the
sociodemographic factors 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
Age
great arteries among male infants in the Baltimore-Washington
Infant Study and of atrioventricular septal defects in females
Maternal with Down syndrome has been noted.8
Increased maternal age at conception was associated with
increased risk for CHD.131 Other studies reported that, after Maternal Psychology and Stress
excluding cases with chromosomal anomalies, maternal age
was not associated with CHD.4 In the Baltimore-Washington Maternal psychological stress was associated with an
Infant Study, maternal age was not associated with non- increased risk of conotruncal heart defects in one study.137
genetic CHD as a group.8 But analysis by specific defects A case-control study gave similar results with a stronger
found that maternal age of more than 30 years was associated effect among offspring of mothers, who were high school
with an increased risk of transposition of great arteries and dropouts.153 Experiencing at least one stressful event during
Ebstein anomaly. More advanced maternal age (> 34 year) the periconceptional period was associated with a high-risk of
was associated with an increased risk of bicuspid aortic valve delivery of infants with conotruncal heart defects. At least one
and atrial septal defects. Young maternal age (< 20 year) was study has ruled out mothers’ education level as an association
associated with an increased risk of tricuspid atresia. Analysis for CHD.136
of non-chromosomal birth defects of the Metropolitan Atlanta
Congenital Defects Program found associations of advanced Socioeconomic Deprivation
maternal age (35–40 year) with an increased risk of all CHD,
tricuspid atresia and right ventricular outflow tract defects.146 There was an increasing risk with increasing deprivation for
all CHD and for septal defects.154 Other studies have shown
Paternal socioeconomic trends of higher risks in lower social classes
for some specific cardiac defects149 and ventricular septal
With increasing paternal age, an increase in the risk in the defects.155
offsprings for atrial and ventricular septal defects and patent
ductus arteriosus has been in one study147 and for pulmonic Reproductive History
stenosis in another.113 Offsprings of men less than 20 years
of age were at higher risk for atrial and ventricular septal
Birth Order
defects. Data from Metropolitan Atlanta Congenital Defects
Program also found an increased risk for atrial and ventricular A birth order of more than the second increases the risk of
septal defects with increasing paternal age after adjustment having CHD.4,150,156,157 33
1 Bad Obstetric History recurrences of CHD in families
This is associated with an increased risk of tetralogy of Fallot, Family History as Risk Factor
non-chromosomal atrioventricular septal defects, atrial septal

defects and Ebstein anomaly in the Baltimore-Washington Family history of CHD is a known risk factor. Several studies
Infant Study.8 have reported a higher risk for CHD in first degree relatives of
patients. Offspring of patients with CHD are at a higher risk
Assisted Reproductive Technology of having CHD.161 The prevalence of CHD is 3.1 percent in
offspring of individuals with CHD and 1.3 percent in offspring
A rapidly developing field, this is associated with CHD as of individuals without CHD. The adjusted odds ratio for CHD
seen in meta-analysis158 and in a controlled, prospective to offspring of parents with CHD is 1.73 (95% CI 0.89–2.44,
cohort study.159 This association is observed particularly for p = 0.02).161 The risk is higher if the affected first-degree
septal defects in a population-based, multicenter, case-control relative is a parent rather than a sibling6 and if it is the mother
study.160 From the data of the Paris Registry of Congenital rather than the father with CHD.1 When the recurrence risk
Malformations, there was a 40 percent increase in the overall of CHD was examined using fetal echocardiography in 6,640
risk of CHD without chromosomal abnormalities in children consecutive pregnancies, where a first-degree relative had a
conceived following assisted reproductive technology after CHD, the rate of recurrence for all CHD was 2.7 percen, with
taking into account maternal age, socioeconomic factors and a high concordance for the specific type of CHD (37%), or for
year of birth.62 There were specific associations between CHD of the same group (44%).162
assisted reproductive technology and subcategories of A population-based study163 found that the same CHD
CHD. Significant increases in the odds of malformations of phenotype showed strong familial clustering in first-degree
the outflow tracts and ventriculoarterial connections and of relatives, ranging from a 3-fold to 80-fold compared with the
cardiac neural crest defects and double outlet right ventricle population prevalence. A family history of any CHD among
were seen. These results for CHD without chromosomal first-degree relatives accounted for 2.2 percent of CHD in the
abnormalities suggest that associations between CHD and population. This relative risk diminished, when the family
assisted reproductive technology are not due to the association history of CHD was in only second- and third-degree relatives.
of the latter with chromosomal abnormalities. This higher This suggests that gene mutations may be an underlying cause.
risk for CHD varied specifically, according to the method of In families where there were two or more recurrences, the exact
assisted reproductive technology and the type of CHD and concordance rate was 55 percent. Even in these families in
may be due to assisted reproductive technology per se and/or which there was a strong evidence for monogenic inheritance,
the underlying infertility of couples. the type of heart defect was not always predictable; over
The confounding factor of an additional mechanism came 40 percent of index and first affected pregnancy cases were
into play here. There was no adequate data for folic acid and/ discordant. Exact concordance rates were particularly high
or multivitamins intake for women in this population. Lack for isolated atrioventricular septal defects (80 percent) and
of adjustment for multivitamins use could have resulted laterality defects (64 percent). Minor CHD in the index case
in an underestimation of the risks associated with assisted does not exclude more severe disease in recurrences. Major
reproductive technology: CHD in the index case does not necessarily imply very severe
i. Multivitamins/folic acid intake lowers the risk of CHD in recurring cases. For non-syndromic hypoplastic left
CHD.122 heart syndrome, epidemiologic studies have demonstrated an
ii. A higher proportion of women, who conceived after increased recurrence risk in the family.163 From a population-
assisted reproductive technology may have had an based registry of adults, who survived surgery for selected
adequate multivitamins/folic acid intake.160 Another major CHD, the recurrence risk among offspring (4.1%) was
compounding factor is the difficulty in distinguishing significantly greater than among siblings (2.1%).165
between the effects of the underlying subfertility and the The risk of recurrence of CHD in a child having one parent
infertility treatments used. It is not decided if the history with CHD is reported to vary from a lowest of 2.5 percent
of reproductive problems is a proxy for teratogenic (atrial septal defect) to a highest of 4.3 percent (ventricular
exposures or is an inherent increased susceptibility septal defect).97 The abnormality in the child is often the
for CHD. Gestational losses has been described, both same as in the parent or a closely related variant. A parent
for general117 and specific defects.83 Further, women with pulmonary stenosis without a Mendelian syndrome,
undertaking assisted reproductive technology are likely who has a spouse with no CHD and no other children with
to have lower exposure to toxins such as alcohol and CHD, has a risk to a subsequent child of 3 percent. If the
cigarettes and to be of higher socioeconomic status, than mother has Noonan syndrome, half of her children will have
the general population of pregnant women. this dominantly inherited syndrome and half of those with
34
the syndrome will have 25 percent risk rather than 3 percent (based on the suspected pathogenic mechanism) for CHD was 3
recurrence risk. A mother with atrial septal defect, whose 100 percent. Dizygotic twins are siblings with different genes,
mother and only sibling also have atrial septal defects and carried together in the same womb. Genetically, they can be

her husband is free of CHD should be considered a high-risk considered as non-twin siblings. Thus, the higher occurrence
family until proved otherwise. Inspection of other family of CHD in dizygotic twins could depend on a non-identified
members would reveal a minor limb anomaly, which would environmental risk during pregnancy.
support dominant inheritance.
Consanguinity
Left vs Right-sided Lesions
A highly inbred population showed a much lower incidence of
Left-sided lesions predominate among relatives of patients CHD.173 Some studies found a relationship with consanguinity
with CHD. In the Baltimore-Washington Infant Study, the and CHD,54,174-177 but some of those studies were performed
sibling recurrence risks of CHD was 3.1 percent overall and in regions where endogamy is common.174-176 This association
highest among cases with left-sided obstructive heart defects, with consanguinity was higher for certain heart defects,
notably, hypoplastic left heart, with an 8.0 percent recurrence especially ventricular and atrial septal defects.174,175
rate and coarctation of aorta, with a recurrence rate of 6.3
percent.8 Familial aggregation of left-sided obstructive heart Mother or Father
defects, particularly coarctation and aortic valve stenosis, has
been reported.165,166 Relatives of children with hypoplastic The adjusted odds ratio for CHD is higher for offsprings of
left heart syndrome have a higher incidence of left-sided affected females than for offsprings of affected males (2.30 vs
lesions such as bicuspid aortic valve and aortic stenosis.167 1.31, respectively).161 The increased risk for the offspring of a
Concordant left-sided obstructive CHD (including bicuspid mother with CHD contrasted to a father with CHD is noted in
aortic valve) among siblings, parents and other relatives of other studies.164,178-181 This gender difference has been noted
affected probands has been reported in another study.168 Thus, even for specific CHD, as for example, in Ebstein anomaly.179
an apparent familial aggregation of left-sided obstructive Since the etiology of CHD is multifactorial, the threshold for
defects is seen and corroborated in studies of echocardiograms the penetrance in females could be higher. An affected female
on first-degree relatives.169,170 represents an increased genetic burden, transmitting the disease
more often to her offspring.178 Other possibilities could be a
Twins parent of origin effect due to maternally imprinted CHD genes
or involvement of mitochondrial genes in the etiology of CHD.
The relative risk for CHD in monozygotic twins was much
stronger than in unlike-sex twins, whereas the relative risks Limitations
in unlike-sex twins and in singletons with a family history of
any CHD in first-degree relatives were similar.163 The excess There are limitations in studies on the recurrence of CHD
relative risk of CHD in monozygous twins, also reported by in family. Patients with more severe CHD may not survive
others171 and not in unlike-sex twins indicates that twinning to adulthood or their handicap prevents them from having
per se predisposes to CHD, (omit plural) whereas the shared a child. Individuals with a milder defect might be included
in utero conditions do not appear to play a role. The relative more often in such studies. If more severe CHD are associated
risk for CHD in monozygotic twins is much stronger than the with a higher risk to offspring, the estimated relative risk
relative risk in unlike-sex twins, whereas the relative risks in could be underestimated. Misclassification bias could result
unlike-sex twins and in singletons with a family history of any from several factors. Some CHD, such as ventricular septal
CHD in first-degree relatives are similar. The excess relative defects, resolve spontaneously and are not diagnosed. Higher
risk of CHD in monozygous twins indicates that twinning proportion of offspring of patients with CHD may undergo
per se predisposes to CHD,171 whereas the shared in utero cardiac evaluation including echocardiography, while
conditions do not appear to play a role. offspring of individuals without CHD may not. Asymptomatic
In an elegant study on CHD in dizygotic twins,172 the potential CHD may be diagnosed in this group more often, resulting in
role of genetic and non-genetic factors in the development of an overestimated relative risk. Further, the group of unaffected
CHD was studied. Dizygotic twins were compared with non- parents may not undergo any cardiac evaluation and a few of
twin patients, who had a sibling with the same or similar CHD. them might have suffered from an undiagnosed 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 Interaction of genetic and non-genetic factors
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 The potential effects of parental exposures on etiopathogenesis
of twins in whom both siblings had CHD, the concordance of CHD are of great public and scientific concern. Both genetic 35
1 and non-genetic environmental factors play crucial roles in It requires fewer study subjects, since affected persons can
this. It is believed that CHD is caused by the interaction of be ascertained from a few sources; it is also more cost-
genetic and environmental factors182,183 and 30 percent of effective. Most of the data on risk factors come from case-
some CHD may be attributable to identifiable and potentially control studies and the best available information comes from
modifiable factors.46 After a teratogenic insult, fetuses may be two large population-based case-control studies specifically
unaffected, suggesting that only a subpopulation may be at risk. designed to investigate risk factors for CHD in an exploratory
In contrast, several syndromic and familial cases of CHD are manner. The Baltimore-Washington Infant Study conducted
caused by rare single-gene mutations that have major effects. in the Baltimore-Washington area between 1981 and 19898
The predisposition to CHD involves multiple factors, and the study conducted in Finland by the National Public
including different genetic loci, epigenetic factors (e.g. Heath Institute in Helsinki of cases and controls born during
DNA methylation or histone modifications that affect gene 1982 to 1984.131 These larger, population-based studies used
expression), environmental influences, subtle hemodynamic standardized methods for ascertaining and classifying CHD
factors during cardiac development or a combination of these and methods to minimize potential biases.
factors. The common forms of CHD that appear to be sporadic
may be caused by inherited genetic variants that affect protein Limitations of the Studies
expression or function and manifest, as disease only when
combined with additional genetic, epigenetic, environmental The disadvantages of case-control studies are the potential
or hemodynamic insults.128 A parent may harbor a genetic for selection bias in assembling the case population, such that
predisposition to a disease (susceptibility allele) and transmit the cases are not representative of all the patients with the
this genetic risk to the offspring. However, this would result disease. This bias may relate to non-participation in the study
in CHD only in conjunction with variants in other genetic loci or to incomplete participation and missing information on the
or with epigenetic factors, resulting in disease penetrance. exposure questions. It is possible that women, who conceive
The susceptibility allele alone may not be sufficient to cause after exposure are more likely to participate in the study.
disease in offspring (non-penetrance), but the individual Further, some studies focus on individuals with severe CHD,
would still be at risk for vertical transmission of increased some include all types of CHD.
risk. A potential disease-susceptibility allele could lead to Then there is the potential for recall bias. Maternal
disease penetrance or non-penetrance, depending on the size recollection of periconceptional events may be influenced by
of the effect of the susceptibility allele and the presence of the birth of a child with a congenital malformation, calling to
‘second hits’ that modify the phenotype. mind events and exposures suspected as being teratogenic.
In the Baltimore-Washington Infant Study, significant Assessment is based on parental recall after the birth of the child.
associations were found for membranous ventricular septal Most studies on non-genetic factors in the etiopathogenesis of
defects with paternal marijuana use, cocaine use among CHD suffer from recall and interviewer bias. They are based
older fathers and African-American race of the infant. These on retrospective interview data or questionnaires. This could
associations support a multifactorial etiologic hypothesis for very often be long after the birth of the infant. This method
isolated membranous ventricular septal defects.69 of data collection may carry the risk for recall bias and
when interviews are part of routine birth defect registration,
Studies on risk factors for CHD interviewer bias can also be involved.
Patients with more severe CHD may not survive to
While etiopathogenesis of CHD has been comprehensively adulthood or their handicap prevents them from having a
reviewed, it may be noted that there are controversies child. Individuals with a milder defect might be included
and conflicts too. Hence, it is appropriate to look into the more often in such studies. If more severe CHD are associated
methodology of collection of data in the various studies with a higher risk to the offspring, the estimated relative
described. risk could be underestimated. Some CHD may have subtle
symptoms or, for better or worse, be asymptomatic. Some
Study Designs are strongly age-dependent in manifestations, following the
natural history of the malformation. Some CHD (e.g. small
The ideal study design for the epidemiological approach ventricular septal defects) spontaneously resolve and are not
to CHD is a randomized clinical trial. Except for prenatal diagnosed. There is no universal coding or nomenclature
multivitamin supplements containing folic acid, which system, hampering communication among scientists.
reduce the occurrence of CHD,121,123 there are very few Further, CHD is not a single disease, but rather a spectrum
preventive strategies. Then there are case-control studies. encompassing many specific diagnoses, each of which may
They identify patients with CHD, select a comparison group be distinct in origin and risk factors. Many fetuses with CHD
and retrospectively evaluate the risk factors in the two groups. die in utero, resulting in a survival bias among the types of
36
CHD present among live births. Technological advances might be due to confounding by the condition for which the 3
in diagnosis (e.g. echocardiography) have increased the analgesic was taken (e.g. influenza or a febrile illness) and
sensitivity of diagnosis, which makes it difficult to compare the apparent protective effect of multivitamin supplement use

modern and historical studies. If there is a large increase in might be due not to the use itself, but to the behavior of the
the prevalence of any particular malformation in later studies user. The differences in the results of the different studies can
compared to older ones, it may entirely be due to better also be attributed to different methodologies used.
diagnostic methodologies. Higher proportion of offspring of
patients with CHD may undergo cardiac evaluation including Conclusion
echocardiography, while offspring of individuals without
CHD may not. Asymptomatic CHD may be diagnosed in this Congenital heart defects are a frequest cause of morbidity and
group more often, resulting in an overestimated relative risk. mortality in children and adolescents. They have an impact
Further, the group of unaffected parents may not undergo any on human suffering and economic costs. The challenge for
cardiac evaluation and a few of them might have suffered the future is to prevent CHD through primary prevention.
from an undiagnosed CHD. This can be done through genetic counseling and also health
The data in case control studies refer to the prevalence awareness of the various risk factors.
of a CHD at birth and may not reflect the true incidence, if
prenatal selection of malformed embryos or fetuses occurs We know a great deal more about the causes of disease than
through spontaneous or selectively induced abortions. For we do about the causes of health.
CHD, the true incidence would need to include occurrences —M Scott Peck, TRLT
among spontaneous abortions. A risk factor that causes a
selective loss of embryos with CHD may not be detectable in References
a study based on infants born. Therefore, some associations
might be missed in this study. The other alternative, the 1. Waitzman NJ, Romano PS, Scheffler RM. Estimates of
prospective studies, are known to detect stronger associations, the economic costs of birth defects. Inquiry. 1994; 31(2):
but there are difficulties in the case of CHD, since performing 188-205.
2. Botto LD, Correa A, Erickson JD. Racial and temporal
autopsy on stillborn and dead neonates is necessary to rule
variations in the prevalence of heart defects. Pediatrics.
out other causes of stillbirth or neonatal deaths (e.g. other 2001;107:E32.
congenital anomalies). But case-control studies identify risk 3. Botto LD, Correa A. Decreasing the burden of congenital heart
factors for CHD in fetuses that survive to birth, which is the anomalies: an epidemiologic evaluation of risk factors and
group representing the practically important problem. Taking survival. Progress in Pediatric Cardiology. 2003;18:111-21.
into consideration the relatively low prevalence rate of CHD 4. Nora JJ, Nora AH. The environmental contribution to
in livebirths, a whole population-based study is required to congenital heart disease. In: Nora JJ, Takao A (Eds). Congenital
obtain an adequate sample size that will not affect the power Heart Disease: Causes and Processes, Mount Kisko. New York:
of the study with such a multitude of associations. Future Publishing Co. 1984:15-27.
5. Clark EB. Pathogenetic mechanisms of congenital cardiovascular
Variations in live birth prevalence of CHD by time and
malformations revisited. Semin Perinatol, 1996;20: 465-72.
place can yield tentative clues about risk factors. Peak rates 6. Nora J, Nora AH. The evolution of specific genetic and envi-
of coarctation of aorta was seen in winter in one study,184 ronmental counseling in congenital heart diseases. Circulation.
plausibly suggesting an infectious source. But, variability 1978; 57:205-13.
in study designs and methods makes it extremely difficult to 7. Reef SE, Plotkin S, Cordero JF, et al. Preparing for elimination
compare prevalence rates taken from different reports and of congenital rubella syndrome (CRS): summary of a workshop
time periods. on CRS elimination in the United States. Clin Infect Dis. 2000;
The absence of demonstrable effects may have different 31:85-95.
explanations. Studies on the association between risk factors 8. Ferencz C, Loffredo CA, Correa-Villasenor A (Eds.). Genetic
and Environmental Risk Factors of Major Cardiovascular
and CHD may be limited by small numbers and lack of
Malformations: the Baltimore-Washington Infant Study: 1981-
an appropriate control group. A true association may be 1989, Perspectives in Pediatric Cardiology, vol. 5. Armonk,
missed, because of low validity in exposure information (e.g. New York: Futura Publishing; 1997.
occupational exposure, where only maternal and paternal 9. Stuckey D. Congenital heart defects following maternal rubella
occupation was known). Low validity of the exposure during pregnancy. Br Heart J. 1956;18:519-22.
information may also affect the results, as regular or heavy 10. Botto LD, Lynberg MC, Erickson JD. Congenital heart defects,
and temporary exposures may not be differentiated (e.g. maternal febrile illness, and multivitamin use: a population
alcohol abuse). Associations between risk factors and CHD based study. Epidemiology. 2001;12:485-90.
in observational studies may be the result of chance, bias or 11. Tikkanen J, Heinonen OP. Maternal hyperthermia during
pregnancy and cardiovascular malformations in the offspring.
confounding. Confounding is of concern in that an apparent
association between reported analgesic use and a heart defect
Eur J Epidemiol. 1991;7:628-35. 37
1 12. Zhang J, Cai WW. Association of the common cold in the
first trimester of pregnancy with birth defects. Pediatrics.
33. Bossi L. Fetal effects of anticonvulsants. In: Morselli PL,
Pippenger CE, Penry JK (Eds). Antiepileptic drug therapy in
1993;92:559-63. pediatrics. New York (NY): Raven Press; 1983. pp.37-64.
13. Chambers CD, Johnson KA, Dick LM, et al. Maternal fever 34. Bracken MB. Drug use in pregnancy and congenital heart
and birth outcome: a prospective study. Teratology. 1998; 58: disease in offspring [Letter]. N Engl J Med. 1986;314:1120.
251-7. 35. Pursley TJ, Blomquist IK, Abraham J, et al. Fluconazole-
14. Shaw GM, Nelson V, Carmichael SL, et al. Maternal induced congenital anomalies in three infants. Clin Infect Dis.
periconceptional vitamins: interactions with selected factors 1996; 22:336-40.
and congenital anomalies? Epidemiology. 2002; 13:625-30. 36. Moore JA. An assessment of lithium using the IEHR
15. Nilsen NO. Endothelial changes and microvascular leakage Evaluative Process for Assessing Human Developmental and
due to hyperthermia in chick embryos. Virchows Arch B Cell Reproductive Toxicity of Agents: IEHR Expert Scientific
Pathol Incl Mol Pathol. 1984; 46:165-74. Committee. Reprod Toxicol. 1995; 9:175-210.
16. Nilsen NO. Vascular abnormalities due to hyperthermia in 37. Llewellyn A, Stowe ZN, Strader JR Jr. The use of lithium and
chick embryos. Teratology. 1984; 30:237-51. management of women with bipolar disorder during pregnancy
17. Mirkes PE, Cornel LM, Park HW, et al. Induction of and lactation. J Clin Psychiatry. 1998;59(suppl 6):57-64.
thermotolerance in early post-implantation rat embryos is 38. Weinstein MR. Lithium treatment of women during
associated with increased resistance to hyperthermia-induced pregnancy and in the post-delivery period. In: Johnson N
apoptosis. Teratology. 1997; 56:210-9. (Ed). Handbook of Lithium Therapy. Lancaster, Pa: MTP
18. Roulston A, Marcellus RC, Branton PE. Viruses and apoptosis. Press. 1980. pp.421-9.
Ann Rev Microbiol. 1999; 53:577-628. 39. Warner JP. Evidence-based psychopharmacology, 3: assessing
19. Watanabe M, Choudhry A, Berlan M, et al. Developmental evidenceof harm: what are the teratogenic effects of lithium
remodeling and shortening of the cardiac outflow tract in- carbonate? J Psychopharmacol. 2000; 14:77-80.
volves myocyte programmed cell death. Development. 1998; 40. Jacobson SJ, Ceolin L, Kaur P, et al. Prospective multicentre
125:3809-20. study of pregnancy outcome after lithium exposure during first
20. Taussig HB. A study of the German outbreak of phocomelia.The trimester. Lancet. 1992; 339:530-3.
thalidomide syndrome. J Am Med Assoc. 1962;180:1106-14. 41. Heinonen OP, Slone D, Shapiro S. Birth defects and drugs in
21. Smithells RW, Newman CG. Recognition of thalidomide pregnancy. Littleton, Mass: Publishing Sciences Group Inc;
defects. J Med Genet. 1992; 29:716-23. 1977.
22. Lenz W. A short history of thalidomide embryopathy. 42. Shaw GM, Malcoe LH, Swan SH, et al. Congenital cardiac
Teratology. 1988; 38:203-15. anomalies relative to selected maternal exposures and conditions
23. Hernandez-Diaz S, Werler MM, Walker AM, et al. Folic acid during early pregnancy. Eur J Epidemiol. 1992; 8:757-60.
antagonists during pregnancy and the risk of birth defects. N 43. Rothman KJ, Fyler DC, Goldblatt A, et al. Exogenous
Engl J Med. 2000; 343:1608-14. hormones and other drug exposures of children with congenital
24. Czeizel AE, Rockenbauer M, Sorensen HT, et al. The heart disease. Am J Epidemiol. 1979; 109:433-9.
teratogenic risk of trimethoprim-sulfonamides: a population 44. Ferencz C, Rubin JD, McCarter RJ, et al. Congenital heart
based case-control study. Reprod Toxicol. 2001; 15:637-46. disease: prevalence at livebirth: the Baltimore-Washington
25. Lammer EJ, Chen DT, Hoar RM, et al. Retinoic acid Infant Study. Am J Epidemiol. 1985; 121:31-6.
embryopathy. N Engl J Med. 1985; 313:837-41. 45. Ericson A, Kallen BA. Nonsteroidal anti-inflammatory drugs
26. Botto LD, Loffredo CA, Scanlon KS, et al. Cardiac outflow in early pregnancy. Reprod Toxicol. 2001; 15:371-5.
tract defects in the offspring of mothers who took retinol 46. Wilson PD, Loffredo CA, Correa-Villasenor A, et al.
supplements. Proc Greenwood Genet Center. 1997; 16:146-7. Attributable fraction for cardiac malformations. Am J
27. Lynberg MC, Khoury MJ, Lammer EJ, et al. Sensitivity, speci- Epidemiol. 1998; 148:414-23.
ficity, and positive predictive value of multiple malformations 47. Ostensen M. Nonsteroidal anti-inflammatory drugs during
in isotretinoin embryopathy surveillance. Teratology. 1990; pregnancy. Scand J Rheumatol Suppl. 1998; 107:128-32.
42:513-9. 48. Lione A, Scialli AR. The developmental toxicity of
28. Dai WS, Hsu MA, Itri LM. Safety of pregnancy after discon- indomethacin and sulindac. Reprod Toxicol. 1995; 9:7-20.
tinuation of isotretinoin. Arch Dermatol. 1989; 125:362-5. 49. Norton ME. Teratogen update: fetal effects of indomethacin
29. Zierler S, Rothman KJ. Congenital heart disease in relation to administration during pregnancy. Teratology. 1997; 56:282-92.
maternal use of Bendectin and other drugs in early pregnancy. 50. Souter D, Harding J, McCowan L, et al. Antenatal indomethacin:
N Engl J Med. 1985; 313:347-52. adverse fetal effects confirmed. Aust N Z J Obstet Gynaecol.
30. Ardinger HH, Atkin JF, Blackston RD, et al. Verification of the 1998; 38:11-6.
fetal valproate syndrome phenotype. Am J Med Genet. 1988; 51. Hammerman C, Glaser J, Kaplan M, et al. Indomethacin
29:171-85. tocolysis increases postnatal patent ductus arteriosus severity.
31. Kozma C. Valproic acid embryopathy: report of two siblings Pediatrics. 1998; 102:E56.
with further expansion of the phenotypic abnormalities 52. Wilkinson AR. Naproxen levels in preterm infants after
and a review of the literature. Am J Med Genet. 2001; 98: maternal treatment. Lancet. 1980; 2:591-2.
168-75. 53. Zenker M, Klinge J, Kruger C, et al. Severe pulmonary
32. Cedergren MI, Selbing AJ, Källén BA. Risk factors for hypertension in a neonate caused by premature closure of the
cardiovascular malformation: A study based on prospectively ductus arteriosus following maternal treatment with diclofenac:
38
collected data. Scand J Work Environ Health. 2002; 28:12-7. a case report. J Perinat Med. 1998; 26:231-4.
54. Bassili A, Mokhtar SA, Dabous NI, et al. Risk factors
for congenital heart diseases in Alexandria, Egypt. Eur J
75. Siman CM, Gittenberger-De Groot AC, Wisse B, et al.
Malformations in offspring of diabetic rats: morphometric
3
Epidemiol. 2000; 16:805-14. analysis of neural crest-derived organs and effects of maternal

55. Hook EB. Cardiovascular birth defects and prenatal exposure vitamin E treatment. Teratology. 2000; 61:355-67.
to female sex hormones: A reevaluation of data reanalysis from 76. Wilson TA, Blethen SL, Vallone A, et al. DiGeorge anomaly
a large prospective study. Teratology. 1992; 46:261-6. with renal agenesis in infants of mothers with diabetes. Am J
56. Addis A, Impicciatore P, Miglio D, Colombo F, Bonati M. Med Genet. 1993;47: 1078-82.
Drug use in pregnancy and lactation: The work of a regional 77. Loffredo CA, Wilson PD, Ferencz C. Maternal diabetes: an
drug information center. The Ann Pharmacother. 1995; 29: independent risk factor for major cardiovascular malformations
632-3. with increased mortality of affected infants. Teratology. 2001;
57. Wiseman RA, Dodds-Smith IC. Cardiovascular birth defects 64:98-106.
and antenatal exposure to female sex hormones: A reevaluation 78. Phelan SA, Ito M, Loeken MR. Neural tube defects in embryos
of some base data. Teratology. 1984; 30:59-370. of diabetic mice: role of the Pax-3 gene and apoptosis. Diabetes.
58. Heinonen OP, Slone D, Monson RR, et al. Cardiovascular birth 1997;46: 1189-97.
defects and antenatal exposure to female sex hormones. N Engl 79. McCarter R, Hempe J, Gomez R, et al. Hemoglobin glycosyla-
J Med. 1977; 296:67-70. tion index is a precursor of complications in the DCCT (Diabe-
59. Bracken MB. Oral contraception and congenital malformations tes Control and Complications Trial). Diabetes. 2000; 49:A48.
in offspring: a review and meta-analysis of the prospective 80. Simán CM, Eriksson UJ. Vitamin E decreases the occurrence
studies. Obstet Gynecol. 1990; 76(pt 2):552-7. of malformations in the offspring of diabetic rats. Diabetes.
60. Tulandi T, Martin J, Al-Fadhli R, et al. Congenital malformations 1997; 46:1054-61.
among 911 newborns conceived after infertility treatment with 81. Cederberg J, Siman CM, Eriksson UJ. Combined treatment
letrozole or clomiphene citrate. Fertil Steril. 2006; 85:1761-5. with vitamin E and vitamin C decreases oxidative stress and
61. Reefhuis J, Honein MA, Schieve LA, et al. National Birth improves fetal outcome in experimental diabetic pregnancy.
Defects Prevention Study. Use of clomiphene citrate and birth Pediatr Res. 2001; 49:755-62.
defects, National Birth Defects Prevention Study, 1997-2005. 82. Nazer J, Ramírez R. Congenital malformations in the offspring
Hum Reprod. 2011; 26:451-7. of diabetic mothers.Rev Med Chil. 2000; 128:1045-52.
62. Tararbit K, Houyel L, Bonnet D, et al. Risk of congenital heart 83. Jenkins KJ, Correa A, Feinstein JA, et al. Noninherited risk
defects associated with assisted reproductive technologies: a factors and congenital heart defects: current knowledge: a
population-based evaluation. Eur Heart J. 2011; 32:500-8. scientific statement from the American Heart Association
63. Green DM, Zevon MA, Lowrie G, et al. Congenital anomalies Council on Cardiovascular Disease in the Young. Circulation.
in children of patients who received chemotherapy for cancer 2007; 115:2995-3014.
in childhood and adolescence. N Engl J Med. 1991; 325:141-6. 84. Morgan SC, Relaix F, Sandell LL, et al. Oxidative stress during
64. Shepard TH, Fantel AG, Kapur RP. Fetal coronary thrombosis as diabetic pregnancy disrupts cardiac neural crest migration and
a cause of single ventricular heart. Teratology. 1991; 43:113-7. causes outflow tract defects. Birth Defects Res A Clin Mol
65. Martin ML, Khoury MJ. Cocaine and single ventricle: a Teratol. 2008; 82:453-63.
population study. Teratology. 1992; 46:267-70. 85. Loffredo CA. Epidemiology of cardiovascular malformations:
66. Lipshultz SE, Frassica JJ, Orav EJ. Cardiovascular abnormali- prevalence and risk factors. Am J Med Genet. 2000; 97:319-25.
ties in infants prenatally exposed to cocaine. J Pediatr. 1991; 86. Splitt M, Wright C, Sen D, et al. Left-isomerism sequence and
118:44-51. maternal type-1 diabetes. Lancet. 1999; 354:305-6.
67. Shaw GM, Malcoe LH, Lammer EJ, et al. Maternal use of 87. Martinez-Frias ML. Heterotaxia as an outcome of maternal
cocaine during pregnancy and congenital cardiac anomalies. J diabetes: an epidemiological study. Am J Med Genet. 2001;
Pediatr. 1991; 118:167-8. 99: 142-6.
68. Kuehl KS, Loffredo C. Risk factors for heart disease associated 88. Slavotinek A, Hellen E, Gould S, et al. Three infants of diabetic
with abnormal sidedness. Teratology. 2002; 66:242-8. mothers with malformations of left-right asymmetry - further
69. Ewing CK, Loffredo CA, Beaty TH. Paternal risk factors for evidence for the aetiological role of diabetes in this malformation
isolated membranous ventricular septal defects. Am J Med spectrum. Clin Dysmorphol. 1996; 5:241-7.
Genet. 1997; 71:42-6. 89. Pradat P. A case-control study of major congenital heart defects
70. Williams LJ, Correa A, Rasmussen S. Maternal lifestyle factors in Sweden: 1981-1986. Eur J Epidemiol. 1992; 8:789-96.
and risk for ventricular septal defects. Birth Defects Res A Clin 90. Dansky LV, Finnell RH. Parental epilepsy, anticonvulsant drugs
Mol Teratol. 2004; 70:59-64. and reproductive outcome: epidemiologic and experimental
71. Rowland TW, Hubbell JP, Nadas AS.Congenital heart disease findings spanning three decades. II. Human studies. Reprod
in infants of diabetic mothers. J Pediatr. 1973; 83:815-20. Toxicol. 1991; 5:301-35.
72. Becerra JE, Khoury MJ, Cordero JF, et al. Diabetes mellitus 91. Rouse B, Azen C. Effect of high maternal blood phenylalanine
during pregnancy and the risks for specific birth defects: a on offspring congenital anomalies and developmental outcome
population-based case-control study. Pediatrics. 1990; 85:1-9. at ages 4 and 6 years: the importance of strict dietary control
73. Kousseff BG. Diabetic embryopathy. Curr Opin Pediatr. preconception and throughout pregnancy. J Pediatr. 2004;
1999;11: 348-52. 144:235-9.
74. Mills JL, Baker L, Goldman AS. Malformations in infants of 92. Levy HL, Guldberg P, Güttler F, et al. Congenital heart disease
diabetic mothers occur before the seventh gestational week. in maternal phenylketonuria: report from the Maternal PKU
39
Implications for treatment. Diabetes. 1979; 28:292-3. Collaborative Study. Pediatr Res. 2001; 49:636-42.
1 93. Watkins ML, Botto LD. Maternal prepregnancy weight and
congenital heart defects in offspring. Epidemiology. 2001; 12:
polymorphisms, and congenital heart disease. Am J Cardiol.
2011; 108:1625-31.
439-46. 112. Shaw GM, Iovannisci DM, Yang W, et al. Risks of human
94. Mikhail LN, Walker CK, Mittendorf R. Association between conotruncal heart defects associated with 32 single nucleotide
maternal obesity and fetal cardiac malformations in African polymorphisms of selected cardiovascular disease-related
Americans. J Am Med Assoc. 2002; 94:695-700. genes. Am J Med Genet. 2005; 138:21-6.
95. Queisser-Luft A, Kieninger-Baum D, Menger H, et al. Does 113. Savitz DA, Schwingl PJ, Keels MA. Influence of paternal age,
maternal obesity increase the risk of fetal abnormalities? smoking, and alcohol consumption on congenital anomalies.
Analysis of 20 248 newborn infants of the Mainz Birth Register Teratology. 1991; 44:429-40.
for detecting congenital abnormalities. Ultraschall Med. 1998; 114. Wasserman CR, Shaw GM, O’Malley CD, et al. Parental
19:40-4. cigarette smoking and risk for congenital anomalies of the
96. Waller DK, Mills JL, Simpson JL, et al. Are obese women at heart, neural tube, or limb. Teratology. 1996; 53:261-7.
higher risk for producing malformed offspring? Am J Obstet 115. Alpert JJ, Zuckerman B. Alcohol use during pregnancy: what
Gynecol. 1994; 170:541-8. is the risk? Pediatr Rev. 1991; 12:375-9.
97. Nora JJ, Nora AH. Recurrence risks in children having one 116. Clarren SK, Smith DW. The fetal alcohol syndrome. N Engl J
parent with a congenital heart disease. Circulation. 1976; 53: Med. 1978; 298:1063-7.
701-2. 117. Carmichael SL, Shaw GM, Yang W, et al. Maternal
98. Rogers JM. Tobacco and pregnancy: overview of exposures periconceptional alcohol consumption and risk for conotruncal
and effects. Birth Defects Res C Embryo Today. 2008; 84(1): heart defects. Birth Defects Res Part A Clin Mol Teratol. 2003;
1-15. 67:875-78.
99. Kallen K. Maternal smoking and congenital heart defects. Eur 118. Tikkanen J, Heinonen OP. Risk factors for ventricular septal
J Epidemiol. 1999; 15:731-7. defect in Finland. Public Health. 1991; 105:99-112.
100. Torfs CP, Christianson RE. Maternal risk factors and 119. Martinez-Frias ML, Bermejo E, Rodriguez-Pinilla E, et al. Risk
major associated defects in infants with Down syndrome. for congenital anomalies associated with different sporadic and
Epidemiology 1999; 10:264-70. daily doses of alcohol consumption during pregnancy: a case-
101. Woods SE, Raju U. Maternal smoking and the risk of congenital control study. Birth Defects Res A Clin Mol Teratol. 2004;
birth defects: a cohort study. J Am Board Fam Pract 2001; 70:194-200.
14:330-4. 120. Tikkanen J, Heinonen OP. Risk factors for atrial septal defect.
102. Hobbs CA, James SJ, Jernigan S, et al. Congenital heart Eur J Epidemiol. 1992; 8:509-15.
defects, maternal homocysteine, smoking, and the 677 CNT 121. Czeizel AE. Periconceptional folic acid containing multivi-
polymorphism in methylenetetrahydrofolate reductase gene: tamin supplementation. Eur J Obstet Gynecol Reprod Biol.
evaluating gene–environmental interactions. Am J Obstet 1998; 78:151-61.
Gynecol. 2006; 194:218-24. 122. Botto LD, Mulinare J, Erickson JD. Occurrence of congenital
103. Steinberger EK, Ferencz C, Loffredo CA. Infants with heart defects in relation to maternal mulitivitamin use. Am J
single ventricle:a population-based epidemiological study. Epidemiol. 2000; 151:878-84.
Teratology. 2002; 65:106-15. 123. Shaw GM, O’Malley CD, Wasserman CR, et al. Maternal
104. Karatza AA, Giannakopoulos I, Dassios TG, et al. Periconcep- periconceptional use of multivitamins and reduced risk
tional tobacco smoking and isolated congenital heart defects in for conotruncal heart defects and limb deficiencies among
the neonatal period. Int J Cardiol. 2011; 148:295-9. offspring. Am J Med Genet. 1995; 59:536-45.
105. Malik S, Cleves MA, Honein MA, et al. National Birth Defects 124. Scanlon KS, Ferencz C, Loffredo CA, et al. Preconceptional
Prevention Study; National Birth Defects Prevention Study. folate intake and malformations of the cardiac outflow tract.
Maternal smoking and congenital heart defects. Pediatrics. Epidemiology. 1998; 9:95-8.
2008; 121:e810-e6. 125. Botto LD, Olney RS, Erickson JD. Vitamin supplements and
106. Baardman ME, Kerstjens-Frederikse WS, Corpeleijn E, et al. the risk for congenital anomalies other than neural tube defects.
Combined adverse effects of maternal smoking and high body Am J Med Genet. 2004; 125C:12-21.
mass index on heart development in offspring: evidence for 126. Junker R, Kotthoff S, Vielhaber H, et al. Infant methylenetet-
interaction? Heart. 2012; 98:474-9. rahydrofolate reductase 677TT genotype is a risk factor for
107. Shi M, Wehby GL, Murray JC. Review on genetic variants and congenital heart disease. Cardiovasc Res. 2001; 51:251-4.
maternal smoking in the etiology of oral clefts and other birth 127. Wenstrom KD, Johanning GL, Johnston KE, et al. Association
defects. Birth Defects Res C: Embryo Today. 2008; 84:16-29. of the C677T methylenetetrahydrofolate reductase mutation
108. Gianicolo EA, Cresci M, Ait-Ali L, et al. Smoking and and elevated homocysteine levels with congenital cardiac
congenital heart disease: the epidemiological and biological malformations. Am J Obstet Gynecol. 2001; 184:806-12.
link. Curr Pharm Des. 2010; 16:2572-7. 128. Shieh JTC, Srivastava D. Heart Malformation. What Are the
109. Moller P, Wallin H, Knudsen LE. Oxidative stress associated Chances It Could Happen Again? Circulation. 2009; 120:269-
with exercise, psychological stress and life-style factors. Chem 71.
Biol Interact. 1996; 102:17-36. 129. Rothman KJ, Moore LL, Singer MR, et al. Teratogenicity of
110. Hobbs CA, Cleves MA, Melnyk S, et al. Congenital heart high vitamin A intake. N Engl J Med. 1995; 333:1369-73.
defects and abnormal maternal biomarkers of methionine and 130. Botto LD, Loffredo C, Scanlon KS, et al. Vitamin A and cardiac
homocysteine metabolism. Am J Clin Nutr. 2005; 81:147-53. outflow tract defects. Epidemiology. 2001; 12:491-6.
40
111. Cresci M, Foffa I, Ait-Ali L, et al. Maternal and paternal 131. Tikkanen J, Heinonen OP. Risk factors for cardiovascular
environmental risk factors, metabolizing GSTM1 and GSTT1 malformations in Finland. Eur J Epidemiol. 1990; 6:348-56.
132. Shaw GM, Nelson V, Iovannisci DM, et al. Maternal occupa-
tional chemical exposures and biotransformation genotypes as
152. Maron BJ, Applefeld JM, Krovetz LJ. Racial frequencies in
congenital heart disease. Circulation. 1973; 47:359-61.
3
risk factors for selected congenital anomalies. Am J Epidemiol. 153. Carmichael SL, Shaw GM. Maternal life event stress and

2003; 157:475-84. congenital anomalies. Epidemiology. 2000; 11:30-5.
133. Tikkanen J, Heinonen OP. Risk factors for conal malformations 154. Vrijheid M, Dolk H, Stone D, et al. Socioeconomic inequalities in
of the heart. Eur J Epidemiol. 1992; 8:48-57. risk of congenital anomaly. Arch Dis Child. 2000; 82:349-52.
134. Tikkanen J, Heinonen OP. Risk factors for coarctation of the 155. Olshan F, Baird PA, Lo KH. Socioeconomic status and the risk
aorta. Teratology. 1993; 47:565-72. of birth defects. Am J Epidemiol. 1991; 134:778-9.
135. Loffredo CA, Beaty TH, Silbergeld EK. Solvent and paint 156. Rothman KJ, Fyler DC. Sex, birth order and maternal age
exposures interact with polymorphisms in glutathione-S- characteristics of infants with CHD. Am J Epidemiol. 1976;
transferase genes to increase the risk of congenital heart 104:527-34.
defects. Teratology. 1997; 55:42A. 157. Tay SH, Yip WCL, Joseph R. Parental age and birth order in
136. Tikkanen J, Heinonen OP. Occupational risk factors for Chinese children with CHD. J Med Genet. 1982; 19:441-3.
congenital heart disease. Int Arch Occup Environ Health. 1992; 158. Hansen M, Bower C, Milne E, et al. Assisted reproductive
64:59-64. technologies and the risk of birth defects-a systematic review.
137. Adams MM, Mulinare J, Dooley K. Risk factors for conotruncal Hum Reprod. 2005; 20:328-38.
cardiac defects in Atlanta. J Am Coll Cardiol. 1989; 14:432-42. 159. Katalinic A, Rosch C, Ludwig M. Pregnancy course and
138. Loffredo CA, Silbergeld EK, Ferencz C, et al. Association outcome after intracytoplasmic sperm injection: a controlled,
of transposition of the great arteries in infants with maternal prospective cohort study. Fertil Steril. 2004; 81:1604-16.
exposures to herbicides and rodenticides. Am J Epidemiol. 160. Reefhuis J, Honein MA, Schieve LA, et al. Assisted
2001; 153:529-36. reproductive technology and major structural birth defects in
139. Gilboa SM, Mendola P, Olshan AF, et al. Relation between the United States. Hum Reprod. 2009; 24:360-6.
ambient air quality and selected birth defects, seven county 161. Romano-Zelekha O, Hirsh R, Blieden L, et al. The risk for
study, Texas, 1997-2000. Am J Epidemiol. 2005; 162:238-52. congenital heart defects in offspring of individuals with
140. Ritz B, Yu F, Fruin S, et al. Ambient air pollution and risk of congenital heart defects. Clin Genet. 2001:59:325-9.
birth defects in Southern California. Am J Epidemiol. 2002; 162. Gill JK, Splitt M, Sharland GK, et al. Patterns of recurrence
155:17-25. of congenital heart disease. An analysis of 6,640 consecutive
141. Goldberg SJ, Lebowitz MD, Graver EJ, et al. An association pregnancies evaluated by detailed fetal echocardiography. J
of human congenital cardiac malformations and drinking water Am Coll Cardiol. 2003; 42:923-9.
contaminants. J Am Coll Cardiol. 1990; 16:155-64. 163. Oyen N, Poulsen G, Boyd HA, et al. Recurrence of congenital
142. Shaw GM, Swan SH, Harris JA, et al. Maternal water heart defects in families. Circulation. 2009; 120:295-301.
consumption during pregnancy and congenital cardiac 164. Burn J, Brennan P, Little J, et al. Recurrence risks in offspring
anomalies. Epidemiology. 1990; 1:206-11. of adults with major heart defects: results from first cohort of
143. Dawson BV, Johnson PD, Goldberg SJ, et al. Cardiac British collaborative study. Lancet. 1998; 351:311-6.
teratogenesis of halogenated hydrocarbon-contaminated 165. Rose V, Gold RJM, Lindsay G, et al. A possible increase in the
drinking water. J Am Coll Cardiol. 1993; 21:1466-72. incidence of congenital heart defects among the offspring of
144. Shaw GM, Malcoe LH, Milea A, et al. Chlorinated water affected parents. J Am Coll Cardiol. 1985; 6:376-82.
exposures and congenital cardiac anomalies. Epidemiology. 166. Whittemore R,Wells JA, Castellsague X. A second-generation
1991; 2:459-60. study of 427 probands with congenital heart defects and their
145. Croen LA, Shaw GM, Sanbonmatsu L, et al. Maternal resi- 837 children. J Am Coll Cardiol. 1994; 23:1459-67.
dential proximity to hazardous waste sites and risk for selected 167. McBride KL, Garg V. Heredity of bicuspid aortic valve: is
congenital malformations. Epidemiology. 1997; 8:347-54. family screening indicated? Heart. 2011; 97:1193-5.
146. Reefhuis J, Honein MA. Maternal age and non-chromosomal 168. Boughman JA, Berg KA, Astemborski JA, et al. Familial
birth defects, Atlanta-1968-2000: teenager or thirty-something, risks of congenital heart defect assessed in a population-based
who is at risk? Birth Defects Res A Clin Mol Teratol. 2004; epidemiologic study. Am J Hum Genet. 1987; 26:839-49.
70:572-9. 169. Lewin MB, McBride KL, Pignatelli R, et al. Echocardiographic
147. Olshan AF, Schnitzer PG, Baird PA. Paternal age and the risk evaluation of asymptomatic parental and sibling cardiovascular
of congenital heart defects. Teratology. 1994; 50:80-4. anomalies associated with congenital left ventricular outflow
148. Lian ZH, Zack MM, Erickson JD. Paternal age and the occurrence tract lesions. Pediatrics. 2004; 114:691-6.
of birth defects. Am J Hum Genet. 1986; 39:648-60. 170. Loffredo CA, Chokkalingam A, Sill AM, et al. Prevalence of
149. Correa-Villasenor A, McCarter R, Downing J, et al. White- congenital cardiovascular malformations among relatives of
black differences in cardiovascular malformations in infancy infants with hypoplastic left heart, coarctation of the aorta, and
and socioeconomic factors: the Baltimore-Washington Infant d-transposition of the great arteries. Am J Med Genet. 2004;
Study Group. Am J Epidemiol. 1991; 134:393-402. 124A:225-30.
150. Torfs CP, Curry CJ, Harris JA. The descriptive epidemiology 171. Bahtiyar MO, Dulay AT, Weeks BP, et al. Prevalence of
of hypoplastic left heart, coarctation of the aorta, and aortic congenital heart defects in monochorionic/diamniotic twin
stenosis. Teratology. 1991; 43:448-9. gestations: a systematic literature review. J Ultrasound Med.
151. Storch TG, Mannick EE. Epidemiology of congenital heart 2007; 26:1491-8.
disease in Louisiana: an association between race and sex and 172. Caputo S, Russo MG, Capozzi G, et al. Congenital heart disease
41
the prevalence of specific cardiac malformations. Teratology. in a population of dizygotic twins: an echocardiographic study.
1992; 46:271-6. Int J Cardiol. 2005; 102:293-6.
1 173. Gatrad AR, Read AP, Watson GH. Consanguinity and complex
cardiac anomalies with situs ambiguus. Arch Dis Child. 1984;
cytoplasmic inheritance and vulnerability to teratogens. Am J
Cardiol. 1987; 59:459-63.
59:242-5. 179. Connolly HM, Warnes CA. Ebstein’s anomaly: outcome of
174. Becker SM, Al Halees Z, Molina C, et al. Inbreeding and pregnancy. J Am Coll Cardiol. 1994:23:1194-8.
congenital heart disease in Saudi Arabia. Am J Med Genet. 2001; 180. Emanuel R, Somerville J, Inns A, et al. Evidence of congenital
99:8-13. heart disease in the offspring of parents with atrioventricular
175. Yunis K, Mumtaz G, Bitar F, et al. Consanguineous marriage defect. Br Heart J. 1983; 49:144-7.
and congenital heart defects: A case-control study in the 181. Nora J, Nora AH. Update on counselling the family with a
neonatal period. Am J Med Genet A. 2006; 140:1524-30. first degree relative with a congenital heart defect. Am J Med
176. Gev D, Roguin N, Freundlich E. Consanguinity and congenital Genet. 1988:29:137-42.
heart disease in the rural Arab population in northern Israel. 182. Nora JJ. Multifactorial inheritance hypothesis for the etiology
Human Heredity. 1986; 36:213-7. of congenital heart diseases: the genetic-environmental
177. Jain VK, Nalini P, Chandra R, et al. Congenital malformations, interaction. Circulation. 1968; 38:604-17.
reproductive wastage and consanguineous mating. Aust NZ J 183. Ferencz C, Correa-Villasenor A. Epidemiology of cardiovascular
Obst Gynaecol. 1993; 33:33-6. malformations: the state of the art. Cardiol Young. 1991; 1:264-84.
178. Nora J, Nora AH. Maternal transmission of congenital heart 184. Miettinen OS, Reiner ML, Nadas AS. Seasonal incidence of
disease. New recurrence risk figures and the questions of coarctation of the aorta. Br Heart J. 1970; 32:103-07.
42
C hapter
4 Fetal Cardiology
Shardha Srinivasan
eOver the past two decades, rapid advances in the field of planning of pregnancy and delivery options and institution of
ultrasound, in conjunction with developments in surgery, appropriate fetal and neonatal management strategies.
invasive cardiology and intensive care has revolutionized
the field of pediatric cardiology. With this came the need IdentIFyIng the Fetus at rIsk For
for early diagnosis of congenital heart disease (CHD) in an CongenItal heart dIsease
effort to further improve morbidity and mortality. Ultrasound
has been increasingly applied to the evaluation of the fetal The incidence of congenital cardiac malformations in
cardiovascular system allowing for more detailed evaluation newborns is approximately 5 to 11/1,000 live births.1–5
of cardiac structure as well as its function. Over the past decade CHDs are 8 times more common than Down syndrome for
or so, fetal cardiology has evolved into a highly specialized which there are currently well-established prenatal screening
field, based on close collaboration between perinatology and protocols. Recent studies suggest that the overall incidence has
pediatric cardiology. been stable over the past decade.2,6 CHD may be attributed to
Ultrasound provides a unique ability for noninvasive various different etiologies, which can be stratified into three
assessment of fetal heart and cardiovascular system including: groups: fetal, maternal and familial risks as outlined in Table
1. The assessment of fetal cardiac anatomy and its alterations 1. However, there are currently no strong markers for fetal
2. The assessment of fetal cardiovascular physiology CHD with the highest yield being in the setting of abnormal
3. Assessment of fetal rhythm. cardiac screening views in 42 to 69 percent, followed by fetal
Advances in transducer technology and ultrasound machines chromosomal abnormalities in 47 to 50 percent and presence
and the resultant improvement in image resolution allows of other extracardiac abnormalities in 4.4 to 9 percent.7,8 A
for evaluation of anatomic details at much greater level and diagnosis of CHD is established in about 2.7 to 20 percent of
prenatal detection of most CHD. Early assessment of fetal heart cases referred for a fetal echocardiogram.8,9
and serial assessments have provided us with an understanding Maternal metabolic disorders such as pregestational diabetes
of the evolution of certain types of lesions; spurring the and phenylketonuria are associated with heart defects in fetus.
exploration of interventional strategies in some lesions in an Though a 3 to 5 times increase in risk for CHD is reported in
attempt to modify the evolution to more significant heart disease. maternal diabetes, recent data suggests that this higher risk is
Doppler evaluation of the fetal heart and fetal cardiovascular associated with poor control and higher hemoglobin A1c levels
system has provided us with unique insights into cardiovascular in the periconceptional period. Recent studies have reported
physiology and fetal compensatory mechanisms to both altered yields of 0 to 7 percent and are likely reflective of the setting
structure as well as in the setting of noncardiac pathologies and in which the study is performed.8,9 Other maternal risk factors
the pathophysiology of fetal heart failure. Ultrasound has also include exposure to either drugs or viral infections (Table 1)
contributed significantly to our ability to diagnose, monitor and that may damage the developing heart with resultant CHD and
manage fetal arrhythmias. Fetal echocardiography now has a myocarditis. Fetal dilated cardiomyopathy has been reported
significant role in the management of not just fetal CHD, but with maternal viral infections.10,11 Maternal autoantibodies
also in several noncardiac fetal pathologies. especially anti-Ro and anti-La antibodies can cross the placenta
Prenatal diagnosis of CHD allows for evaluation of between 16 to 18 weeks gestation with a risk for fetal heart
associated genetic or noncardiac lesions that can impact block and cardiomyopathy in about 1 to 3 percent cases, but
outcomes, better counseling and preparation of the family, the majority of these occur in asymptomatic women.
1  table 1
Indications for fetal echocardiography
Embryo to thE NEoNatE
Maternal Fetal Familial

1. Systemic disease 1. Abnormal cardiac screen 1. Paternal CHD
• Pregestational diabetes 2. Increased nuchal translucency 2. Prior child or fetus with CHD
• Phenylketonuria 3. Extracardiac anomaly 3. Familial syndromes/single gene defects
• Presence of anti-SSA/SSB • Omphalocele • Noonan
autoantibodies • Duodenal atresia • William
2. Teratogen exposure • Diaphragmatic hernia • DiGeorge
• Anticonvulsants • Tracheoesophageal fistula • Holt–Oram
• Lithium • Cystic hygroma • Marfan
• Paroxetine • Situs inversus • Tuberous sclerosis
• Retinoid • Abdominal wall defects
• NSAID • Single umbilical artery
3. Maternal infection 4. Chromosomal anomaly
• Parvovirus 5. Conditions with known risk for heart
• TORCH failure:
• Coxsackie • Vascular tumor
4. In-vitro fertilization • Arteriovenous malformation
5. Maternal CHD • Cystic adenomatoid malformation
• Absence of ductus venosus
6. Hydrops fetalis
7. Monochorionic twinning
8. Fetal arrhythmia
9. Polyhydramnios
CHD = Congenital heart disease; NSAID = Non-steroidal anti-inflammatory drugs; TORCH = Toxoplasmosis, rubella, cytomegalovirus and herpes
Fetal chromosomal abnormalities have a high association Abnormalities with a particular association with CHD are
with underlying congenital heart defects. 3,12 These include included in Table 1. CHD may rarely present with either
cases of trisomy 21, 13 and 18 and 22q11 deletion. An significant tachycardia or bradycardia in the setting of
elevated first trimester nuchal translucency (NT) is a marker complex congenital heart defects, though overall incidence is
for aneuploidy and in the setting of normal chromosomes for low. Recent publications indicate a higher risk for CHD in
other fetal malformations including CHD.13 In the study by conditions such as twin-twin transfusion syndrome (TTTS) and
Hyett et al the prevalence of major CHD increased with an in vitro assisted conceptions.21–23 Fetal echocardiograms are
increase in the NT, from 0.8 per 1000 live births for a NT also increasingly being used for assessment of cardiovascular
less than 95 percentile to 63.5 per 1000 live births for those status and function in noncardiac lesions such as TTTS as well
with a NT greater than 99 percentile or about 3.5 mm and 55 as conditions associated with altered loading conditions on
percent of cases with CHD had an elevated NT between 10 the heart such as vascular tumors, diaphragmatic hernia and
to14 weeks gestation.13 However, the diagnostic accuracy of congenital cystic adenomatoid malformation (CCAM).
increased NT as a predictor of CHD in the general population A family history of CHD remains an important indication
has been lower. Based on a meta-analysis, Makrydimas et al for fetal echocardiography not because of high yields, but for
concluded that approximately 30 percent of the major CHD the reassurance that a normal study provides to these families.
detected by specialist echocardiography in a chromosomally Single gene disorders such as microdeletion of chromosome
normal population, had a NT greater than 99 percentile, 22 (del 22q 11) have been associated with patterns of CHD
but sensitivity has been lower in other population based typically involving the conotruncus. Recurrence risks are
studies.14–17 Nonetheless, the prevalence of CHD is 3 to 4 higher for certain lesions such as heterotaxy syndromes and
folds higher in the fetus with a NT greater than 3.5 mm and it left heart obstructive lesions.24,25
serves as an important indication for fetal echocardiography. The majority of CHD occurs in the absence of clearly
Other markers such as abnormal ductus venosus flow patterns identifiable risk factors and ideally all pregnancies should
in very early pregnancy as well as the presence of tricuspid be screened for heart defects in conjunction with the
regurgitation in early gestation are being explored as potential midgestation anomaly scan.9,26–28 There are many published
markers for CHD.18–20 studies and commentaries outlining the wide variation in
Fetuses with extracardiac malformations merit a complete prenatal pickup of CHD variably attributable to differences
cardiac evaluation. Malformations in more than one in scanning protocol-4 chamber alone versus inclusion of
44 system may indicate a syndrome or chromosomal anomaly. outflow tract imaging, instrumentation and level of training
of sonographers.27,29–33 Inclusion of outflow tracts improves limitations of image resolution are particularly important in 4
detection of conotruncal lesions, which have a high likelihood these early scans and it is important to keep use of color and
of being ductal dependent.28,34 Improvement in pickup rates pulsed Doppler to the minimum necessary. Given potential
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with regional training programs is well-demonstrated in for evolution of certain lesions through gestation, it remains
several European countries.35,36 However, recent studies necessary to perform a follow-up scan between 24 to 28 weeks
continue to demonstrate a wide variability in referral patterns in these cases. Currently, these early scans are mostly limited
for fetal echocardiography as well as pick up of cardiac to select population at high-risk such as those with abnormal
abnormalities on routine scanning.30,31,37 Table 2 outlines the first trimester screening or where the reassurance is important
anticipated abnormality by different views. as in a family history for CHD.
Fetal eChoCardIogram technical Considerations

Timing of Scan: The best balance of image definition as well Though ultrasound techniques for fetal evaluation are well-
as timing for counseling is afforded between 18 to 20 weeks defined, the fetal heart poses several differences that make it more
gestation. This allows time for re-evaluation in the setting of challenging. Firstly, the fetal heart is small and often measuring
a difficult scan, evaluation of the fetus for possible associated only a centimeter or two. Thus, high image resolution is needed
chromosomal defects and other abnormalities, and time for the to enable visualization of the cardiac structures in enough
family to consider all options available without being rushed. detail. However, the fetus may be situated at varying depths
Most major CHD can be reliably diagnosed in this time from the maternal abdomen depending on maternal habitus,
frame; however, a small number of lesions may evolve later in amniotic fluid volume and gestation age, necessitating imaging
pregnancy. From the standpoint of general applicability, this in the far field in some instances. Secondly, the fetal heart is a
remains the most favorable time period for assessment of the dynamic structure with heart rates typically ranging from 120 to
fetal heart. 160 BPM, hence high frame rates (typically 50 to 100 Hz) are
Several studies have demonstrated the feasibility of necessary for optimal temporal resolution. Finally, the fetus by
obtaining diagnostic scans in the early fetus, as early as 11 virtue of its mobility frequently changes its presentation with
to 13 weeks of gestation in skilled hands for major CHD respect to the transducer and hence a good understanding of
such as ventricular hypoplasia, transposition of the great the cardiac anatomy in three dimensions is necessary for the
vessels as well as atrioventricular canal defects.20,38–40 The performance and interpretation of fetal echocardiography.
 table 2
Expected findings on screening images in different congenital heart diseases
Diseases Four chamber view Outflow tracts Three vessel/trachea view

TAPVR PA PA PA
Tricuspid atresia A A A
Ebstein anomaly/ TV dysplasia A PA PA
Mitral valve dysplasia A A A
AVSD (balanced) A N N
Primum atrial septal defect A N N
Hypoplastic left heart A A A
Aortic stenosis PA PA PA
Pulmonic stenosis PA PA PA
PA/IVS PA A A
Coarctation PA PA PA
Large perimembranous VSD PA PA N
Malalignment VSD N A PA
L-transposition of great vessels A A A
D-transposition of great vessels N A A
Tetralogy of Fallot N A A
Double outlet right ventricle N A A
Truncus arteriosus N A A
Vascular ring N PA A
Interrupted aortic arch/no VSD N PA A
Interrupted aortic arch/VSD N A A
A = Abnormal; AVSD = Atrioventricular septal defect; N = Normal; PA = Possibly abnormal indicating cases where in a subtle abnormality may be present, 45
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;
1 To achieve the above requirements a balance between evaluation of Fetal Position and right-left orientation
penetration and the maximal possible lateral resolution is
needed. Most current ultrasound machines used for fetal It is critical that all fetal cardiac assessments begin with
imaging provide transducers with a range of imaging evaluating fetal position and establishing fetal right versus
frequencies, with typical frequencies used being the 4 to 10 left. Once the fetal stomach is identified as being correctly
MHz range. Lower frequencies along with use of harmonic positioned to the fetal left, it then serves as a useful landmark
imaging may be needed in the setting of increased fetal depth to reorient oneself through the scan with fetal movements.
or poor insonation characteristics. Linear array transducers Though there are algorithms that have been outlined for the
or phased array transducers with dynamic focus may be same,46 the easiest method is to establish fetal lie and thus the
used. Postprocessing should be set to improve frame rates by fetal left and right. This is best done by identifying the fetal
judicious use of dynamic zoom and optimal depth with low head and aligning the transducer along the spine of the fetus
persistence and spatial averaging. Endocardial definition is to establish the craniocaudal axis of the fetus and then turning
enhanced by the use of relatively high dynamic contrast and the transducer 90 percent to obtain a transverse scan through
appropriate grayscale map. Use of color flow mapping tends the abdomen and thorax.
to drop frame rates and it is especially important to set a small
region of interest and optimize color scales. Finally, given transverse scans and the extended
the dynamic nature of the heart, the capacity to record and Cardiac screening Views
display real time images along with still frames of Doppler
and M-mode recordings, is critically important. A series of transverse scans starting from the upper abdomen
Four dimensional evaluation using spatiotemporal image to ascertain situs, to the chest outlining the four chambers of
correlation (STIC) technology is now possible. Inherent the fetal heart and then to the mediastinum visualizing the
limitations are imposed by the temporal resolution and motion outflow tracts and great vessels, provides for a comprehensive
artifact. With the inclusion of color flow information good screening technique (Figure 1). Initially advocated by Yagel
diagnostic accuracy for detection of major CHD has been et al, this provides a template for sequential segmental
demonstrated.41–44 The ability to analyze the data set offline, evaluation of cardiac anatomy as noted in Figure 2.47 It should
may have an important impact on improving accessibility of be noted that these imaging planes represent a continuum and
cardiac screening to remote sites. As with other techniques small movements separate one view from the other.
there is a learning curve to the process and often a 1. Abdominal situs: The transverse scan across the upper
combination of techniques and postprocessing is required abdomen of the fetus helps to establish the abdominal situs.
to achieve good diagnostic capability. Fetal movements and Normal landmarks (Figure 1: plane A and Figure 3A)
arrhythmia continue to be issues. Inter and intraobserver include:
variability approaching 96 percent has been demonstrated for • Spine posterior
the assessment of fetal cardiac volumes.45 • Stomach bubble to left
• Pulsatile descending aorta anterior to spine, slightly left
normal Fetal echocardiogram of midline
• Inferior vena cava slightly anterior to right of descending
It is important to evaluate the fetal heart in a segmental aorta
fashion with the goal towards establishing situs, segmental • Scanning cranially the cardiac mass is noted with apex
connections and alignments as well as functional assessment to left
(Figures 1 and 2). Fetal position, as well as motion may not • The inferior vena cava passes anteriorly to drain into the
allow for these to be assessed in a sequential fashion as in base of right atrium.
postnatal studies; hence, it is important to have a mental Besides this, the umbilical vein is noted looping
or written checklist to make sure that all components are away from the stomach and the ductus venosus can be
understood at the end of the study. Poor visualization or identified as a small vessel connecting the umbilical vein
incomplete visualization should prompt a repeat study. to the inferior vena cava. Color flow evaluation shows low
Scanning the fetal heart requires small controlled movements. velocity accelerated continuous flow pattern.
The importance of assessment in a segmental fashion as Alterations in abdominal situs or right/left symmetry
well as assessment of morphologic characteristics of various may be the first clue to associated heterotaxy. The presence
cardiac structures cannot be stressed enough; especially in of a prominent venous structure posterior to the aorta may
the diagnosis of congenital heart defects where in seemingly be seen in setting of interruption of the inferior vena cava
minor issues may alter prognosis and surgical approach, such with either an azygos continuation (right posterior vessel)
as associated obstructed total anomalous pulmonary venous (Figure 3B) or hemiazygos continuation (left posterior
return. vessel). In these cases, the flow in the vein is cephalic,
46
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E d
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 Figure 2: Segmental analysis of cardiac anatomy. A stepwise approach
in cases of situs inversus or heterotaxy. to the evaluation of the different cardiac segments is recommended in
2. Four chamber view: The four chamber view of the heart evaluation of the fetal heart. At each level it is important to evaluate
is visualized by obtaining a transverse scan of the fetal for the ‘presence or absence’ of a structure as well as ‘variations in
size and function’. For example, a small hypoplastic left ventricle, a
thorax just above the level of the diaphragm (Figure 1: well-developed but poorly contractile right ventricle in some cases
Plane B). It is important to train one’s eyes to recognize of pulmonary atresia with intact ventricular septum. In addition,
morphological characteristics of the different cardiac it is important to ascertain the connections between the different
segments. The fetal heart occupies about a third of the fetal segments in terms of ‘alignment’ as well as ‘function’. For example,
double inlet left ventricle, where in both atrioventricular valves are
thorax and is situated with the cardiac axis at about 45 ± 15 aligned to the left ventricle, discordant atrioventricular connections in
percent to the axis of the chest. The heart is situated more L-TGA or failure to demonstrate pulmonary venous connection in the
horizontal than in postnatal life, allowing for side-by-side four chamber view, etc. The extended cardiac screening as shown
visualization of the right and left inflows in the same plane in Figure 1 helps readily identify variations and further supportive
information is obtained from supplemental views in terms of the short-
(Figures 4A and B). axis and sagittal scans 47
1
a b
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.
Landmarks include: Early in gestation there is relative equality of the two sides
• Spine is posterior though there may be mild right sided prominence past
• Descending aorta is noted anterior to spine and slightly 28 – 30 weeks’ gestation and this becomes more prominent
to left of midline in late gestation. The four chamber view may be projected
• Anteriorly, the cardiac mass lies with apex to left and either horizontally or vertically depending on the angle
occupies about a third of the chest of imaging. The perimembranous septum is normally the
• Cardiac axis of about 45 degrees to the line bisecting the thinnest part of the interventricular septum and is prone
thorax to dropout on two dimensional imaging. In these cases,
• Four chambers with a intact crux in the center: right = assessing the septum in a horizontal orientation to maximize
left (in midgestation) lateral resolution of the transducer and use of color flow
• Right atrium is anterior and receives the superior and mapping will help resolve the issue (Figure 4B). However,
inferior vena cava given relatively equal pressures between the two ventricles
• Left atrium is posterior and receives the pulmonary and the limitations of resolution may result in missed
veins (The space between the left atrium and aorta is diagnosis of a ventricular septal defect (VSD), especially in
free of vascular structures at this level) early scans and with poor imaging windows. Abnormalities
• Foramen flap towards the left atrium in cardiac position may be noted in setting of extracardiac
• Right ventricle is anterior and is identified by the malformations with cardiac displacement, heterotaxy with
tricuspid valve and presence of moderator band at the or without associated cardiac displacement. A change in
apex cardiac axis is an important marker for associated cardiac
• Tricuspid valve is slightly offset towards the apex and defects as well as extracardiac malformations with resultant
has septal attachments cardiac shift. The differential features and common causes
• Left ventricle is posterior and receives the mitral valve are outlined in Table 3.
• Mitral valve is septophobic or lacks attachments to the 3. Outflow tract view: Scanning cephalic or towards the
septum and attaches slightly higher than the tricuspid fetal head from the four chamber view shows the origin of
valve the aorta from the left ventricle (Figure 1: Plane C). Slight
• Normal valve motion rotation of the transducer in such a way as to ‘lengthen’ the
• Normal myocardial squeeze and echogenicity interventricular septum will result in opening of the left
• Normal heart rate with atrioventricular synchrony ventricular outflow tract (LVOT) and better visualization
• Additional evaluation includes color flow and Doppler of the aortic valve (Figures 5A to C). Note is made of the
48 evaluation of the valves and septum. following:
4
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a b
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
a b C
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 4. The 3 vessel view (3VV) and the 3 tracheal view (3VT):
center of the heart Extending the scan further cranially into the mediastinum
• Aortomitral continuity is present of the fetus demonstrates the three vessel view and its
• Aortoseptal continuity is present continuation into the tracheal view. This view outlines the
• Interventricular septum appears intact great vessels and their relationship in the mediastinum.
• Cranial scanning opens the pulmonary valve and These are easily obtained by a slow cranial sweep from
pulmonary artery the four chamber view (Figure 1: Plane D and E). A slight
• Normal valve motion is noted rotation of the transducer will help lay out the vessels.
• Color and Doppler evaluation is performed. 49
1  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 45º ± 15%
• CA 1/3rd of TA
Mesocardia • Cardiac mass: Midline • Extrinsic shift: CHAOS

• Axis: ~90° • Abnormal looping: Atrioventricular
• Apex midline discordance
• Heterotaxia
Dextrocardia • Majority of cardiac mass in right thorax • Situs inversus totalis

• Apex to right • Heterotaxia
• Isolated dextrocardia
Dextroposition • All of cardias mass in right thorax • ↑ Mass in LEFT thorax with extrinsic
• Apex to front/left push: e.g. Left DH, left pleural effusion,
• Cardiac size often small CCAM
• ↓ Mass in right thorax: Right
lung agenesis or hypoplasia with
compensatory increase in left lung
Levoposition • All of cardiac mass in left thorax • ↑ Mass in RIGHT thorax with extrinsic
• Apex to front push: e.g. DH, pleural effusion, CCAM
• Cardiac size often small • ↓ Mass in left thorax: Left lung agenesis
or hypoplasia
Left axis shift • Majority of cardiac mass in left thorax • Shift of ventricular septum:
• Axis > 60° to midline Right ventricular enlargement/
• Cardiac size: Normal or enlarged hypertrophy
• Apex to left Left ventricular hypoplasia
• Milder forms of extrinsic shift
Right axis shift • Majority of cardiac mass in left thorax • Shift of ventricular septum:
• Axis < 30° to midline Right ventricular hypoplasia
• Size normal or increased Left ventricular enlargement
• Apex left or midline • Milder forms of extrinsic shift
50
CCAM = Congenital cystic adenomatoid malformation; CHAOS = Congenital high airway obstruction; DH = Diaphragmatic hernia
Landmarks include: abnormalities in number, size, alignment and flow in the 4
• Cranial sweep from the left outflow view opens the components of each of the views (Figures 6 and 7).
pulmonary valve and pulmonary artery
FEtal Cardiology
• Pulmonary valve is anterior and connects to the right sagittal Planes
ventricle
• Pulmonary artery gives off lateral branches 1. Aortic and ductal arch view: Scanning in the thorax
• There is a subpulmonary conus or muscle and lack of along the long axis or parallel to the spine provides the
continuity with the tricuspid valve sagittal images of the fetal heart. Due to the shadowing
• The two great arteries cross each other with the effects for the spine it is important to approach the heart
pulmonary valve being anterior and to the left of the slightly from the one side of the fetal spine. This window
aorta profiles the superior vena cava-inferior vena cava (SVC-
• The three vessels are seen from right to left: The right IVC) view, identifying the great veins as they enter the
superior vena cava, the ascending aorta and the main right atrium. Aortic arch forms a ‘candy cane’ with cranial
pulmonary artery head and neck vessels while the ductal arch is much more
• Ascending order in size with: The superior vena cava ≤ ‘shallow’ reminiscent of the American ‘hockey stick’
ascending aorta ≤ main pulmonary artery. (Figures 8A and B). Given embryologic origins the aortic
Scanning cephalic from here gives the tracheal view arch is slightly cranial to the ductal arch, though in cases
(Figure 1: Plane E): of severe arch hypoplasia this may be difficult to reliably
• Pulmonary artery continues into the ductal arch demonstrate. The right pulmonary artery can be seen
• Aorta continues to the aortic arch posterior to the ascending aorta and superior vena cava
• The aortic arch is slightly cephalic to the ductal arch (Figures 8A and 9A). The foramen ovale is well-profiled in
• The ductal arch and aortic arch come together to form a this view (Figure 9A). In the abdomen, the ductus venosus
‘V’ with apex at the descending aorta can be identified as it connects to the IVC in the liver.
• Three vessels are seen from right to left with ascending Short-axis images of the ventricles can be obtained and
order in size: The right superior vena cava ≤ the aortic the ventricular function and mitral valve papillary muscles
arch ≤ the ductal arch identified (Figure 9B).
• Trachea is noted slightly posteriorly between the 2. Short-axis images: Given horizontal positioning of the fetal
superior vena cava (SVC) and the aortic arch heart short-axis images of the ventricles can be obtained
• Further, cephalic innominate vein is noted crossing either from a relative fronto/sagittal position or from a
from left to right to join the SVC. transverse scan plane orthogonal to the four chamber view
Abnormalities in the 3 VV and 3 VT are important clues depending on fetal position. The mitral valve, papillary
for the presence of underlying conotruncal malformations muscles, function, pulmonary valve, branch pulmonary
and variations in arch anatomy. It is important to assess for arteries and the ductal arch are well seen.
a b C
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-right—cross-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. 51
Lt = Fetal left; S = Spine.
1
a b
C d
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 b
Figures 8a and b: Normal sagittal views of the fetal arches: A. Aortic arch (*) demonstrating a candy cane with presence of cranial directed
52 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
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a b
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 Fetal diagnosis of congenital heart defects is in general
that allows for qualitative assessment. However, in cases skewed towards more serious defects given that the majority
of doubt, formal measurements of various structures in the of defects are picked up on routine screening. Most significant
fetal heart can be performed. Routine measurements of cardiac defects can be reliably diagnosed prenatally with some
key structures has the advantage of allowing the operator limitations. It is very important to adopt a segmental approach
to become familiar with norms by experience and serial to the assessment of cardiac anatomy (Figures 1 and 2). In a
determination allows tracking of growth of structures in case simple fashion, this involves assessment of the following:
of abnormalities. Z score graphs for various fetal cardiac 1. Abdominal situs and atrial anatomy:
structures are now published.48–52 Several studies have a. Solitus: Normal atrial and venous arrangements. The
also demonstrated the utility of tracking Z scores or growth atrial appendage morphology may occasionally be
for predictive value in certain defects.53–56 However, it is seen well enough to aid in the diagnosis. Variations to
important that there be standardization of technique within the systemic and pulmonary venous return may be seen in
lab and for use of normative data.57 isolation in the absence of situs abnormalities.
b. Situs inversus: Mirror image arrangement.
Color and doppler evaluation c. Abnormal situs: Includes cases of right and left atrial
isomerism as well as situs ambiguous. There is a high
Color flow and Doppler evaluation are an important part of the association of complex congenital heart defects.
anatomic and functional assessment of the fetal heart (Figures 2. Atrioventricular connections:
4B and 10). As with postnatal assessment they are sensitive to the a. Concordant: Normal right atrium to right ventricle and
angle of insonation, gain, velocity settings. For pulse Doppler, left atrium to left ventricle.
it is important to use small sample volumes and low velocities. b. Discordant: Right atrium to left ventricle and left atrium
Color Doppler evaluation aids in anatomic assessment in some to right ventricle or inverted connections.
cases with poor 2D definition. Characteristic flow patterns are c. Univentricular connections: Where in there is connection
noted across the different valves and vascular structures and to one ventricular chamber and includes: Double inlet
are outlined in Figures 11A to I. (both atrioventricular valves aligned predominantly to
53
1
a b C
d E F
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
one ventricle), common inlet (common atrioventricular b. Discordant: Right ventricle to aorta and left ventricle
valve aligned to one ventricle) or single inlet (atresia of to pulmonary artery or transposed. As noted, this will
one valve either the mitral or tricuspid valve). result in a parallel orientation to the great vessels on
It is important to look carefully at the atrioventricular ultrasound (Figures 12A and B).
valves for presence of straddling attachments, which c. Double outlet: Where in the majority of both great
may change surgical management towards a single vessels arise from one ventricle, more commonly an
ventricle approach even though there are two effective anatomic right ventricle.
ventricles. Similarly, the size of the inflow may have a d. Single outlet: Where in there is only one outlet from the
significant impact on surgical approach. For example, ventricular mass. These include aortic atresia (small aorta
a small tricuspid valve annulus that is well below -3 Z and large pulmonary artery) and pulmonary atresia (small
scores may rule out a two ventricle repair even in the pulmonary artery and normal aorta) and a single large
presence of an otherwise reasonable sized right ventricle outlet as in cases of truncus arteriosus where in a single
in setting of severe pulmonary stenosis/atresia with an large outflow vessel gives rise to the coronaries, head
intact septum. and neck vessels as well as pulmonary arteries. A wide
3. Ventriculoarterial (VA) connections: variation in size and morphology of the atretic valve can be
a. Concordant: Normal, i.e. right ventricle to pulmonary seen and in some cases may hamper distinction between a
artery and left ventricle to aorta. true truncus and tetralogy of Fallot with pulmonary atresia.
In the normal heart, the great arteries cross each other Careful attention to the origin and relationships of the
and their relationship is such that visualization of one pulmonary arteries and head, neck vessels from the single
great artery in long axis will show a cross sectional view vessel is needed to make the diagnosis in these cases, to
of the other. The ability to show the long axis of both great help plan surgical intervention and outline prognosis.
54 arteries at the same time or parallel orientation of great Ultimately, the impact of complex heart defects depends on
vessels suggests abnormal connections and/or alignment. the ability of the fetus to tolerate the hemodynamic alterations
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a b
C d
E F
g h
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
1
a b
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
a b C
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
sPeCIFIC lesIons
in utero and its ability to have a successful transition to neonatal
circulation. In the fetal circulation, the right and left hearts are 1. Systemic venous abnormalities: Variations in systemic
working in parallel rather than in series as after birth. There venous anomalies can be easily detected on fetal
exists the potential for flow redistribution across the foramen echocardiograms. A dilated coronary sinus is often the clue
ovale as well as ductus arteriosus. Obstruction or resistance to look for an associated left superior vena cava (LSVC).
to flow through one ventricle allows for redistribution of flow The presence of a LSVC can be easily confirmed in the high
across the foramen and the ductus arteriosus to the other. mediastinal or 3 VV and tracheal views by the presence of a
Hence, right heart obstruction or high afterload states on the fourth vessel leftward to the pulmonary artery (Figure 13).
left ventricle may present with relative enlargement of the Though this variation has no hemodynamic significance,
right ventricle and vice versa. Similarly, one may see flow it is often noted as an associated finding in left heart
56 reversal in the ductus arteriosus with right heart obstructive lesions and should prompt a careful review of the left heart
lesions and flow reversal in the ascending aorta with lesions structures including the mitral valve and arch and may
that impact left ventricular output. prompt a follow-up evaluation to assess in utero growth of
the left heart. Systemic venous anomalies may be found in circulatory patterns. The normal atrial septum in the fetus 4
isolation, but are also often a part of more complex lesions is characterized by the presence of the foramen flap, which
as seen in heterotaxy (Figure 3B). A careful evaluation for opens towards the left atrium and demonstrates low velocity
FEtal Cardiology
situs abnormalities is warranted. flow from right to left with a transient left to right flow in
2. Pulmonary venous anomalies: Include variations in return late diastole.58 The foramen ovale also serves as an obligate
such as total anomalous pulmonary venous connection shunt in the setting of congenital heart defects such as right
(TAPVC) and partial anomalous pulmonary venous and left heart obstructive lesions, transposition of the great
connection (PAPVC) or pulmonary vein atresia. Pulmonary arteries and also total anomalous pulmonary venous return.
venous Doppler show characteristic changes in setting of Prenatal restriction of the foramen ovale has been reported
high left atrial pressures and have been well-characterized in 6 to 22 percent of cases in these settings and is associated
(Figures 15A to D). Obstructed total anomalous pulmonary with poorer outcomes both in fetal and postnatal life.59–61
venous drainage can be a true surgical emergency in the It can be a true emergency in the delivery room in some
delivery room. It is important to identify at least one vein cases and has important implications for delivery planning.
from each lung as entering the left atrium on screening scans The presence of restriction may be indicated by a bulging
to avoid missing diagnosis of total anomalous pulmonary tense appearing foramen with either restricted motion or
venous return. Subtle features suspicious for TAPVR hypermobile motion, straight septum with small opening
include mild right heart enlargement in setting of RV: LV by 2 dimensional imaging, the presence of turbulent flow
disproportion as well as the presence of a vascular structure across it by color Doppler and elevated velocities in excess
in the space between the left atrium and the descending of a 1 m/sec,62–64 (Figure 10). The appearance of the atrial
aorta on four chamber views (Figure 14). Rarely, a cor septum will vary depending on the underlying lesion.
triatriatum may mimic this picture. Pulmonary venous Left heart obstructive lesions are associated with a higher
anomalies are also often seen in the setting of heterotaxy incidence of left atrial hypertension.61,65
and may have a significant impact on outcomes in single Atrial septal defects: The presence of a normal foramen
ventricle physiology. Partial anomalous pulmonary venous ovale in fetal life precludes diagnosis of secundum atrial
return is often missed on prenatal scans unless an effort is septal defects in fetal life. Rarely, the absence of a foramen
made to delineate all four veins in each study. flap and a ‘T’ artifact may clue one to the presence of
3. Atrial and ventricular septal abnormalities: one. Sinus venosus defects are typically high or low in
Prenatal restriction of the foramen ovale: Patency of the proximity to the venous inflow and may be diagnosed in
foramen ovale is critical to the maintenance of normal fetal 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 VSD’s 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
Figure 14: Total anomalous pulmonary venous return: Four chamber underlying syndrome.
view showing presence of pulmonary vein confluence (arrows) in
the space between the left atrium (LA) and descending aorta (Ao).
Endocardial cushion defects: Complete endocardial
Note: The LA and left ventricle are well-developed in this case. cushion defect includes a primum atrial septal defect with
RA = Right atrium; S = Spine. (Image courtesy: Dr Bettina Cuneo) an inlet ventricular septal defect and a CAVV, however, 57
1
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)
incomplete forms may be present. This defect is easily as part of a more complex CHD in the setting of heterotaxy.
detected based on the absence of the ‘crux’ in the center The lesion may be balanced or unbalanced or favoring
of the heart in four chamber views. Presence of a CAVV one or the other ventricle with resultant hypoplasia of
results in the two atrioventricular valves being at the one ventricle and associated outflow abnormalities.66,67
same level and lack of apical offset of the tricuspid valve Significant atrio-ventricular valve insufficiency is
58 (Figure 16). Endocardial cushion defects are commonly associated with a higher risk for fetal hydrops and fetal
seen in the setting of aneuploidy especially trisomy 21 and demise especially in the setting of heterotaxy syndromes.
atrialization of the right ventricular inflow and right 4
ventricular hypoplasia. This is a lesion where in fetal
physiology is detrimental and is associated with a high
FEtal Cardiology
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
Figure 16: Balanced complete common endocardial cushion defect: by color Doppler, with or without elevation in Doppler
Note: Lack of ‘X’ at crux. The normal offset of atrioventricular valves
is lost and a common atrioventricular valve is noted separating the
velocities, may indicate the presence of an underlying
ventricular septal defect (arrow) from the primum atrial septal defect abnormality (Figure 6). In utero progression may result in
(dashed arrow). Note: Pulmonary vein draining into the left atrium severe stenosis or rarely atresia.
(arrow head). The ventricles are equal in size. DAo = Descending In pulmonary valve atresia, there is no demonstrable
aorta; LV = Left ventricle; RA = Right atrium; Rt = Right.
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
4. Tricuspid valve abnormalities: Tricuspid valve abnor- the pulmonary artery (Figures 17A and B). The branch
malities may range from subtle minor abnormalities with pulmonary arteries are typically small but confluent in
mild tricuspid insufficiency to significant abnormalities cases with an intact ventricular septum. Branch pulmonary
such as tricuspid valve dysplasia with thickened leaflets, artery abnormalities are in general more likely in the
Ebstein malformation with mild to severe downward setting of pulmonary atresia with a VSD, which falls in
displacement of the septal leaflet with associated stenosis the realm of tetralogy of Fallot and is discussed later.
and regurgitation, tricuspid valve hypoplasia and stenosis Pulmonary atresia with intact septum is associated with
to atresia.68 The tricuspid valve plays an important role in varying degrees of right ventricular and tricuspid valve
fetal circulation given that fetal right ventricle functions hypoplasia ranging from a very small hypoplastic right
against systemic pressures. The normal tricuspid valve ventricle along the lines of a single ventricle, to those
in the fetus is usually fully competent and any trivial where in a tripartite right ventricle is noted and prenatal
insufficiency is usually limited to early systole.69,70 decision making in terms of a two ventricle versus single
Pan-diastolic tricuspid regurgitation is abnormal and ventricle repair becomes challenging.53,54,72,73 Important
suggests either an underlying abnormality or an alteration issues in these cases include the morphology and size of
in right ventricular afterload. Significant right heart lesions the right ventricle as well as tricuspid valve growth. The
are often associated with abnormalities in venous flow range of surgical options are described in chapter 40 in this
patterns suggestive of elevated right atrial pressures and book. Coronary sinusoidal connections can be suggested
are not predictive of outcomes in this setting.71 prenatally by presence of to-fro flow along the surface of
Severe tricuspid valve stenosis or atresia is often seen the heart and presence of a dilated proximal coronary.
in the setting of a single left ventricle. As in cases of Rarely, a dysplastic pulmonary valve may be noted with
pulmonary stenosis, even cases that appear not quite severe a combination of severe stenosis and insufficiency. In these
in early second trimester, may progress in severity with lack cases there is right ventricular enlargement. As with other
of right ventricular growth and resultant single ventricular volume loading conditions there is a risk for hydrops and
physiology in late gestation and serial evaluation during fetal loss in these cases.
pregnancy is necessary.54,72,73 6. Mitral valve abnormalities: Isolated mitral valve abnor-
Ebstein malformation of the tricuspid valve involves malities are unusual and are usually seen in the setting of
varying degrees of apical displacement of the valve and associated abnormalities of the left ventricle and aortic 59
resultant enlargement of the right atrium secondary to valve. The combination of a dysplastic mitral valve with
1
a b
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
associated stenosis and severe regurgitation presenting These findings may be subtle in the early second trimester
with severe left ventricular and left atrial dilatation and scan and may be missed, especially on screening studies.
ineffective left ventricular ejection is usually associated More severe stenosis may be associated with altered flow
with poor outcomes.76,77 This lesion is characterized by a patterns across the distal arch with retrograde filling being
high risk for prenatal restriction at the level of the foramen noted in the transverse arch with or without associated arch
ovale given elevated left atrial pressures; associated right hypoplasia (Figure 10B).
heart failure due to impairment of right ventricular filling The combination of a hypoplastic left ventricle with
in the setting of a dilated hypocontractile left ventricle varying degrees of aortic valve stenosis/atresia and
(Figure 10). There is a high risk for hydrops in these cases. mitral valve stenosis/atresia with aortic arch hypoplasia
In utero intervention in terms of balloon dilatation of the constitutes hypoplastic left heart syndrome. However,
foramen ovale has been attempted in some cases. It is often many different combination of lesions may share the
difficult to distinguish this from severe aortic stenosis with physiology and surgical options. For example, a dysplastic
secondary mitral valve insufficiency. The aortic valve mitral valve may preclude a two ventricle repair even
though small will often show low velocity laminar forward though the left ventricle and aortic valve may be deemed
flow in these cases. In many situations associated with adequate.66,77–79 Significant aortic stenosis and variations
mild left ventricular hypoplasia, the mitral valve lesion is of hypoplastic left syndrome result in a ductal dependent
often the limiting factor for a two ventricle repair. A cleft systemic circulation (Figure 10B).
in the mitral valve may be seen in setting of an endocardial 8. Conotruncal lesions: Common lesions include tetralogy of
cushion defect and is best seen in the sagittal images of the Fallot, truncus arteriosus, transposition of the great vessels
left ventricle with the mitral valve ‘en-face’. and double outlet right ventricle amongst others. All of
7. Aortic valve disorders: Include stenosis, atresia and these lesions share defects in septation of the conotruncus
associated left ventricular abnormalities. The left ventricle or formation of the aorticopulmonary septum and are often
may be dilated or hypoplastic or may show evolution from associated with a malalignment type VSD (except simple
one to the other in later gestation. Isolated mild aortic D-transposition of great vessels). Interrupted aortic arch
valve stenosis in the setting of an otherwise normal left with a VSD falls in the same category, but is discussed
ventricle may be difficult to diagnose in fetal life. Clues with arch anomalies given that a VSD is not universally
include subtle dilation of ascending aorta, thickened aortic present. Associated chromosomal abnormalities, including
valve leaflets on 2D imaging and aliasing of color flow 22q11 deletions and aneuploidy, have been reported in
across the valve and elevated flow velocities across the 17 to 26 percent of cases and may affect counseling and
60 valve by Doppler or subtle right ventricular enlargement. outcomes.3,80–82 The outflow tract, 3 VV and tracheal
4
FEtal Cardiology
a b
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 lack of crossing of the aorta and pulmonary artery in the
and great vessels with supplemental information from the outflow views, along with a posteriorly placed pulmonary
sagittal and transverse scans.83–85 vessel that shows lateral branching (Figure 12).
Tetralogy of Fallot: It is associated with anterior D-transposition of the great vessels is characterized
deviation of the conal septum with resultant aortic override, by atrioventricular concordance and ventriculoarterial
malalignment VSD and varying degrees of sub- and valvar discordance. Four chamber views are normal however,
pulmonary stenosis. The right ventricular hypertrophy outflow tract views reveal parallel great vessels. The 3
is a normal feature in fetal life. This lesion is associated VV/tracheal views are abnormal as the ductal and aortic
with varying degree of hypoplasia of the pulmonary arch will superimpose and result in lack of the normal ‘V’
arteries (Figure 6C). With severe outflow tract obstruction seen in the tracheal view. Though well-tolerated in fetal
and with pulmonary atresia the pulmonary blood flow is life this results in significant desaturation after birth and
ductal dependent and there is reversed flow noted in the significant hypoxemia can result especially in the setting
ductus arteriosus.86 Rarely, in the setting of pulmonary of poor mixing at the atrial and ductal level. In about 13
atresia, the lesion may be mistaken for a truncus arteriosus percent of cases there can be in utero restriction at the level
(Figures 18A and B). Color flow evaluation of the arch in of the foramen ovale with resultant failure to resuscitate in
sagittal views may reveal the presence of aortopulmonary the delivery room or early neonatal death in unrecognized
collaterals. A variant of this defect is tetralogy of Fallot cases. A hypermobile foramen, restrictive foramen
with absent pulmonary valve syndrome. This lesion, flow and diastolic reversed flow in the ductus arteriosus
characterized by aneurysmal dilated branch pulmonary have been suggested as predictors for an urgent balloon
arteries and a dilated right ventricle in the setting of severe septostomy.64,88
pulmonary insufficiency, has poorer fetal and postnatal L-loop transposition of the great vessels is character-
outcomes.87 Severe air trapping may be seen in postnatal ized by the presence of atrioventricular and ventriculoarte-
period, in the setting of tracheobronchial compression rial discordance, which results in physiologically corrected
from the dilated pulmonary vessels and hence these fetuses flows. The clinical picture is dictated by the associated
are best delivered at a tertiary care center. lesions, which are reported in upto 85 percent of cases and
Transposition of the great vessels: These include D-loop include VSDs, left atrioventricular (tricuspid valve) ab-
transposition and L-loop transposition of the great vessels. normalities, pulmonary and subpulmonary stenosis, heart
From the standpoint of fetal echocardiogram both these block and arch abnormalities.89,90 There is an incremental
defects show a parallel orientation of the great vessels, with risk for complete heart block in this setting and this may 61
1 often be the presenting feature in fetal life. Echocardiogra- enlargement in the second trimester was associated with
phy reveals an abnormal four chamber view with the right arch abnormalities in 60 percent of fetuses in one series.93
ventricle being posterior and parallel outflows, with the Markers including the presence of isthmic hypoplasia or
aorta being situated anterior and to the left of the pulmo- a Z score of less than -2, presence of a posterior shelf and
nary artery. an isthmus to ductus diameter ratio less than 0.74.56,94
Double outlet right ventricle: In this defect both great Fetal diagnosis of a coarctation remains very challenging,
arteries arise from the right ventricle (Figure 17). The especially in the third trimester due to the normal presence
clinical picture is dictated by the variable relation of the of right ventricular prominence and tortuosity of the
great vessels to each other, the relationship of the VSD to ductus arteriosus in late gestation and variable postnatal
the great arteries and presence or absence of stenosis of presentation.95
one of the semilunar valves. Relative hypoplasia of one of The ductus arteriosus has a major role in fetal circulation
the ventricle may be seen. A systematic approach to outline acting as a conduit of most of the fetal systemic blood flow
the connections and alignment of the different cardiac to the lower body with aortic isthmus only seeing about 7
segments is needed to elucidate the physiologic effect of to 10 percent of the combined cardiac output. Inadequate
the lesion. It is particularly important on prenatal scans forward flow from the right heart results in flow reversal in
to identify the fetus at risk for ductal dependent systemic the ductus arteriosus from the aorta to the pulmonary artery
circulation as in the setting of aortic stenosis and arch and serves as a marker for ductal dependent pulmonary
hypoplasia or as is more commonly seen, ductal dependent blood flow in postnatal period (Figure 17B). Similarly, in
pulmonary circulation in the setting of severe pulmonary cases of inadequate left ventricular cardiac output there is
stenosis or atresia. Outcomes depend on the subtype and retrograde filling of aortic arch from the ductus arteriosus
association of chromosomal abnormalities.91 and hence a marker for ductal dependent systemic blood
Truncus arteriosus: It results from failure of aortico- flow (Figure 10B). Prenatal restriction of the ductus has
pulmonary septum to form completely. This is characterized been reported in the setting of both a normal heart as well
by the presence of a single large vessel that overrides the as setting of CHD.63 It may result from maternal exposure
ventricular septum and gives rise to both the aorta and to medications such as indomethacin and its analogues
the branch pulmonary arteries (Figure 18A). Important and has been reported with high dietary polyphenol
differential includes tetralogy of Fallot with pulmonary exposure.96–98 Narrowing may be noted on 2D imaging
atresia and aortic atresia with a VSD. 22q11 deletion along with turbulent color flow and elevated diastolic flow
may be found in 30 to 40 percent cases.92 Associated velocities across the ductus and results in right ventricular
abnormalities include a right aortic arch, interruption of hypertrophy, enlargement and progressive tricuspid
the arch, truncal valve stenosis and regurgitation. Inability regurgitation. If no correctable cause is noted then early
to document head and neck vessels from the only arch and delivery may be indicated with resultant improvement
the presence of a larger than normal first head and neck in right ventricular function. Elevated ductal flow may
vessel that is directed straight up should raise suspicion of be seen in high output states.99 Ductal constriction is
ductal continuation of the aorta. A dysplastic truncal valve associated with a decrease in pulsatility index (PI) of less
with severe stenosis or insufficiency may adversely affect 1.9, where as high output states result in as elevated PI. In
prognosis. utero ductal restriction in the setting of underlying CHD
9. Aortic arch and ductal abnormalities: The addition such as transposition of the great arteries is associated with
of the three vessel and tracheal views have significantly a poorer outcome and serial evaluation through pregnancy
added to the assessment of the variations in ductal and is recommended to adjust delivery management.
aortic arch anatomy including lesions such as interruption The ductus arteriosus is often smaller and curlicue in
of the aortic arch, aortic arch hypoplasia, variations in the setting of conotruncal lesions associated with severe
arch sidedness, variations in ductal morphology including right ventricular outflow tract obstruction (Figure 17B).
ductal aneurysm, and vascular rings (Figure 7). Diastolic flow reversal in the ductus arteriosus in setting
Type B interruption demonstrates ductal continuation of transposition of the great arteries may be a marker
of the descending aorta and a straight appearance to the for prenatal restriction of the atrial septum and has been
ascending aorta. There is a high association with a mal- associated with persistence of pulmonary hypertension in
alignment VSD, various degrees of subaortic obstruction the newborn.63,64
and 22q11 deletion. 10. Complex CHD: A segmental approach is critical to
Isolated coarctation of the aorta is difficult to reliably the diagnosis of complex CHD, with a view towards
diagnose in fetal life in the absence of arch hypoplasia. establishing the anatomic diagnosis along with the
The redistribution of flow results in relative prominence functional consequence. Heterotaxy syndromes are often
of the right ventricle. Though there are other causes for associated with significant cardiac defects that include
62 right ventricular prominence, presence of right heart variations in systemic and pulmonary venous return,
cardiac looping and outflow abnormities. In these cases, limitations of Fetal echocardiograms 4
the risk for associated rhythm abnormalities, malrotation
of the intestines and abnormal splenic function may Though a high degree of diagnostic accuracy has been
FEtal Cardiology
impact postnatal management and should be addressed at achieved with a comprehensive fetal echocardiogram,
the time of counseling. several lesions may be difficult to diagnose or missed in the
11. Miscellaneous heart defects: Intracardiac masses—A prenatal period given inherent limitations of fetal physiology
range of cardiac tumors may present in fetal life. and resolution by ultrasound. These include small VSDs,
Rhabdomyomas are the most common followed by isolated minor valvular lesions, secundum or sinus venosus
teratomas, fibromas and hemangiomas amongst others.100,101 atrial septal defects, partial anomalous pulmonary venous
Cardiac consequences may occur due to effects of the tumors return, isolated coarctation of the aorta and importantly late
on blood flow across the valves resulting in obstruction to gestational changes in form or function.
blood flow or regurgitation of the valve; local impact on
the myocardium resulting in poor contractility or irritability In utero Course and ImPlICatIons For
and cardiac arrhythmias; local effects such as development delIVery PlannIng
of pericardial effusions and tamponade. Serial monitoring
of cardiac function, tumor size and its hemodynamic impact The main goal of prenatal diagnosis is to afford adequate
is needed during pregnancy. Rhabdomyomas may regress counseling to families with regards to implications of the
after birth, but are associated with tuberous sclerosis in up cardiac lesion and to plan follow-up, delivery and neonatal
to 80 percent of cases and the postnatal course is dominated care. A positive impact on survival has been shown only in
by the neurologic consequences of the same.102 If identified certain lesions, however, several studies have shown an
prenatally, formal genetic counseling and evaluation for improvement in preoperative variables.106–109 Data suggests
tuberous sclerosis is indicated. that one in three infants with a potentially life-threatening
Echogenic foci appear as discrete ‘echo-bright’ or echogenic lesion leave the hospital undetected.110,111 Fetal diagnosis of
spots in the submitral or subtricuspid valvular apparatus and CHD in general, tends to be on the severe end of the spectrum
move with the cardiac valves, are often noted on routine scans. given that most are picked up on screening studies. There is in
They are thought to represent areas of ectopic calcification or general a higher risk for fetal loss in the setting of chromosomal
fibrosis. It is important not to mistake them for cardiac tumors. abnormalities especially with Turner’s syndrome.
These do not affect cardiac function. In general, fetal CHD is well-tolerated in fetal life given the
presence of shunts at the level of the foramen ovale and the
Cardiac diverticulum and aneurysms are rare lesions ductus arteriosus. Obstructive lesions involving one ventricle
affecting the ventricles or atria that may be noted on fetal are compensated by redirection of flow across the foramen
echocardiograms. Aneurysm are thin walled, lack myocardium, ovale to the other ventricle. As long as the combined cardiac
have a wide attachment to the ventricle and tend to fill with output is relatively maintained by the other ventricle the fetus
ventricular systole, while a diverticulum has a narrow neck, has does well. Congenital heart defects that are poorly tolerated in
myocardium and contracts in synchrony with the ventricle.103,104 fetal life include those associated with:
A ventricular diverticulum may be idiopathic or seen in the • Prenatal restriction at the foramen ovale with or without
setting of herniation of a part of the ventricle through an anterior associated CHD
chest wall defect as with pentalogy of Cantrell. It may be difficult • Prenatal restriction at the level of the ductus arteriosus with
to prenatally distinguish between the two. They may present in or without associated CHD
association with pericardial effusion, needing pericardiocentesis • Significant valvular insufficiency (e.g. Ebstein malforma-
in setting of cardiac dysfunction or if progressive, to prevent tion, absent pulmonary valve syndrome)
lung hypoplasia; cardiac arrhythmias or rupture with fetal death. • Poor myocardial function (e.g. myocarditis, myocardial
In utero as well as postnatal resolution has been described.105 non-compaction, heart failure)
• Arrhythmias: both tachy- and bradyarrhythmia, especially
Cardiomyopathy: Fetal cardiomyopathy may have a diverse in the setting of associated CHD
presentation and may result from many different causes • Associated placental insufficiency and intrauterine growth
as in postnatal life. Fetal anemia and myocarditis may retardation.
mimic dilated cardiomyopathy. A picture of hypertrophic
cardiomyopathy may be idiopathic or seen in the setting of Progression of lesions
Noonan syndrome in the fetus, severe uncontrolled diabetes
mellitus in mother, right ventricular hypertrophy in the The potential for progression of fetal heart disease has an
recipient twin in TTTS. Non-compaction cardiomyopathy important bearing on prenatal counseling with regards to
may coexist with arrhythmias and complex CHD in prognosis and planning of prenatal and neonatal management.
heterotaxy syndromes. This progression may happen at many levels such as: 63
1 • Progressive increase in degree of stenosis or resultant foramen ovale.55,79,113,115 There appears to be an improvement
atresia of valves in hemodynamics with growth of the inflow and outflow,
• Lack of growth of a chamber or vessel with resultant ductal but growth of the left ventricle itself is not as robust. Fetal
dependent systemic or pulmonary blood flow. This may mortality is about 10 percent. A threshold scoring system
ultimately change surgical options with potential need for for prediction of a biventricle outcome has been developed
a univentricular repair rather than biventricular repair. by the Boston group in an effort to predict a two ventricle
• Progressive regurgitation of a valve with risk for fetal outcome.55,116
hydrops and implications for delivery
• Development of significant restriction at the level of the Creation or Enlargement of Inter-atrial Communication
foramen ovale and/or ductus arteriosus with implications
for timing, type and place of delivery; given potential need In utero restriction of the foramen ovale is associated with
for urgent intervention and high risk for fetal and early poor postnatal outcomes secondary to poor oxygenation and
neonatal demise chronic left atrial hypertension with resultant pulmonary
• Myocardial dysfunction may develop with resultant fetal venous hypertension. Technically, this is more challenging
heart failure given the small atria. Though successful in utero stenting of the
• Development of fetal arrhythmias needing medical mana- atrial septum has been reported, however an improvement in
gement or impacting timing of delivery outcomes has not been clear, given the small numbers. Timing
• Progression or regression of a cardiac tumor. of intervention, size of defect created and relief of associated
significant aortic stenosis may all have an impact.114,116,117
Fetal Cardiac Interventions
Pulmonary Valvuloplasty
As our understanding of the in utero progression of certain
lesions evolve, there has been an attempt to alter or limit the Pulmonary atresia with intact septum or highly restrictive
progressive changes by in utero intervention. On a broader VSD is associated with varying degrees of right ventricular
slate, prenatal interventions include the use of transplacental hypoplasia and tricuspid valve involvement, which is often
antiarrhythmic medications in fetal arrhythmias or use of the limiting factor to a two ventricle repair. In utero dilatation
Digoxin for inotropy. However, in terms of progressive structural of the pulmonary valve has been successfully performed and
lesions most of the recent advances have been in the setting improvement in right ventricular growth demonstrated on
of percutaneous fetal cardiac interventional procedures. Fetal follow up.114,118,119 The procedure is technically challenging
‘open’ cardiac surgery has been limited by the high incidence and case selection and technological advances is a subject of
of preterm labor in these cases.112 With closed interventional current investigation.
approach, a high degree of technical success has been achieved
especially in left heart lesion. The success in prevention of a delivery Planning
single ventricle physiology is dependent on case selection,
timing of intervention and the underlying diagnosis and these In general, delivery is best done as close to term as possible
are evolving. Methodological advances are being made. A in the setting of complex congenital heart defect to avoid
handful of centers across the world are involved in a systematic complications of associated lung disease of prematurity.
approach to these lesions given ethical considerations. Several However, these decisions have to be made on a case by
recent publications have addressed the technical aspects, case case basis, weighing the risk benefit ratio of continuing the
selection as well as world-wide results.113–116 pregnancy to those of prematurity.
Interventional approach has been applied to primarily three Type of delivery is usually dictated by obstetric needs
subsets: except in certain situations such as:
• Concerns for poor myocardial reserve in the fetus in setting
Balloon Valvuloplasty of the Aortic Valve of heart failure or hydrops where in the stress of a vaginal
delivery may not be well-tolerated.
For aortic stenosis with a normal or large left ventricle and • Fetal arrhythmias such as complete heart block or tachy-
poor function, with a view towards promoting growth of arrhythmias where in monitoring of fetal well-being in
the left ventricle and thus prevent the need for a single labor may be difficult
ventricle repair. Inclusion criteria which reflect predictors for • Presence of anterior abdominal or chest wall defects.
development of HLHS includes: critical aortic stenosis as the • Significant prenatal restriction at ductal or atrial level
dominant lesion, presence of retrograde flow across the arch, where in immediate postnatal intervention is contemplated.
monophasic mitral inflow pattern, normal sized or dilated left An early delivery may be considered in some cases in
ventricle with diminished function, right to left flow at the the setting of progressive hydrops, especially in the setting
64
of right heart failure where in the fetal physiology is more combined cardiac output after midgestation; estimated to 4
detrimental to cardiac function as in Ebstein malformation be about 60 percent at about 38 weeks.120,121 The combined
or severe prenatal ductal constriction, intractable arrhythmias cardiac output in the human fetus is estimated to be about 425
FEtal Cardiology
not responsive to medical management, progressive placental to 550 mL/kg/min.122 Heart failure in the fetus manifests as
dysfunction and markers for poor fetal well-being or for features of increased central venous pressures characterized
maternal causes. by fluid accumulation and diminished cardiac output with
Factors predictive of the need for neonatal intervention and associated decentralization of flow. Hydrops fetalis is defined
planned delivery include: as the presence of two or more of the following: pleural or
• Prenatal restriction at the level of foramen ovale or ductus pericardial effusion, ascites or skin edema.
arteriosus
• Obstructed pulmonary venous return etiology of heart Failure
• Ductal dependent systemic or pulmonary circulation or
potential for the same Heart failure in a fetus may result from one or a combination
• Poor myocardial function and heart failure of physiologic factors in a variety of clinical settings both
• Presence of fetal hydrops cardiac and non-cardiac as outlined in Box 1.
• Uncontrolled arrhythmias: Tachyarrhythmia or bradyarr- Secondary cardiac dysfunction has now been recognized in
hythmia. a variety of extracardiac conditions. Volume overload occurs in
Most congenital heart defects are well-tolerated in the the setting of fetal anemia, arteriovenous malformations as in
delivery room and the stabilization of ductal dependent vein of Galen malformation, vascular tumors as in hemangiomas
lesions can be achieved with the use of prostaglandin E1 and sacrococcygeal teratomas, congenital absence of the
(PGE1) infusion. However, the presence of restrictive fetal ductus venosus when associated with an extrahepatic vascular
pathways, obstructed pulmonary venous return, airway shunt. Studies have shown that a combined cardiac output of
obstruction or severe myocardial dysfunction may present as greater than or equal to twice the normal indexed combined
true emergencies in the delivery room and arrangement for cardiac output result in the evolution of hydrops and this may
delivery at a tertiary care center with availability of immediate
interventional, surgical or ECMO support, depending on the
underlying issues is critical. box 1: Causes of fetal congestive heart failure
Other lesions that are not ductal dependent such as
a complete common atrioventricular canal that is well- 1. C
ongenital heart disease associated with valvular
balanced, VSDs or conotruncal lesions that are not clearly insufficiency:
ductal dependent are managed differently in different settings, • Ebstein malformation and tricuspid valvular dysplasia
depending on the standard of care available locally. The • Mitral valve dysplasia
• Absent pulmonary valve syndrome and severe pulmonary
availability of teleconferencing and the ability to read studies
stenosis
remotely and availability of PGE1 has made it easy to stabilize • Dysplastic common atrioventricular valve
neonates locally and allow for transport in a timely fashion if • In utero constriction of ductus arteriosus or foramen ovale
needed. • Dysplastic truncal valve
2. Fetal arrhythmias:
• Sustained tachyarrhythmia with HR > 220/min
• Sustained bradyarrhythmia with FHR < 55/min
FunCtIonal assessment oF Fetal CardIaC 3. High output states:
FunCtIon and Fetal heart FaIlure • Fetal anemia: Maternal parvovirus infection, immune medi-
ated
The systematic application of ultrasound and Doppler to • Vascular tumors: Sacrococcygeal teratomas, placental
the evaluation of the fetal circulatory state has provided us chorioangioma
• Arteriovenous malformation: Vein of Galen
with a unique insight into fetal circulatory system and its
• Agenesis of ductus venosus
compensatory mechanisms to conditions associated with 4. Extrinsic cardiac compression:
cardiovascular stress. Clinical features suggestive of congestive • Diaphragmatic hernia
heart failure after birth can be elucidated based on changes in • Congenital cystic adenomatoid malformation
cardiac function and Doppler parameters in the fetus. 5. Primary myocardial dysfunction:
The fetal circulation is a parallel circulation characterized • Fetal cardiomyopathy
• Fetal myocarditis
by the presence of shunts across the foramen ovale, ductus
• Intracardiac tumors (also cause valvular dysfunction)
arteriosus and the ductus venosus. Though early in gestation, 6. Recipient in twin-to-twin transfusion syndrome
the relative outputs of the two ventricles are similar, the 7. Severe uteroplacental insufficiency (IUGR)
right ventricle contributes to an increasing proportion of the
65
1
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.
influence decision to intervene.123–125 Cardiovascular findings evaluation of Fetal Cardiac Function and
include cardiomegaly, atrioventricular valve regurgitation and Changes in Fetal heart Failure
abnormal Doppler. Extrinsic compression on the heart may Evaluation of fetal heart function involves a comprehensive
impede venous return and affect myocardial contractility and systematic assessment of the fetal cardiovascular system
and result in heart failure as in diaphragmatic hernia and including the following:
CCAM.126 • Cardiac function
Conditions associated with a high afterload such as • Assessment of hemodynamic consequences:
placental dysfunction and the recipient twin in TTTS can result – Venous Doppler
in cardiac failure. In the fetal circulation, the right ventricle is – Arterial Doppler
particularly susceptible to the effects of high afterload imposed • Signs of congestive heart failure: Evaluation for hydrops
by placental insufficiency and this may result in ventricular Assessment of fetal cardiac function and myocardial
hypertrophy, altered diastolic function and systolic dysfunction. performance: Several parameters help in the assessment
TTTS complicates about 10 to 15 percent of all monoamniotic- of cardiac function (Figures 20A to E). Cardiac outputs
dichorionic (MoDi) pregnancies. It is characterized by a mixed can be calculated using Doppler data (Figures 21A and B).
picture of volume overload in the setting of a high afterload Atrioventricular valve inflow patterns in the fetus typically
in the recipient fetus (Figure 19). The presence of placental show ‘A’ wave dominance with an E/A ratio of less than 1.
vascular communications allows for the transmission of Increasing stiffness of the ventricle is reflected in the presence
vasoactive mediators secreted by the donor fetus in response of a ‘monophasic’ inflow pattern characterized by ‘A’ wave
to hypovolemia. Progressive right ventricular dysfunction alone. Elevated filling pressures result in increasing atrial flow
results, with associated left ventricular dysfunction, tricuspid reversal in venous Doppler. Vector velocity mapping has been
insufficiency with progression to hydrops consistent with an applied for assessment of fetal myocardial properties recently
acquired cardiomyopathy.123 In utero therapy with laser ablation and has the advantage of being angle independent though it is
of placental vascular connections can lead to stabilization and affected by frame rates.129 Myocardial performance index has
improvement in cardiac status and outcomes. Acquired sub- been used as a measure of global function and can be altered
pulmonary stenosis and evolution to pulmonary atresia has with systolic or diastolic dysfunction.130,131 Alterations in
been reported. Findings of right ventricular cardiomyopathy myocardial performance index (MPI) have been reported
are absent in stage 1 and 11 of the Cincinnati modification of in the setting of CHD, altered afterload as in diabetic
66 the Quintero classification and allows for a trial of expectant pregnancies and TTTS. Progressive ventricular dilatation
management with or without amnioreduction.22,127,128 and hypertrophy in the setting of elevated afterload, results
4
FEtal Cardiology
a
b C
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
Venous dopplers
in atrioventricular valve insufficiency. The presence of holo-
systolic tricuspid insufficiency is abnormal and merits close Studies in both animals and human fetuses have shown that
follow-up. Normalization of afterload as seen with reversal alterations in central venous blood flow patterns accurately
of ductal constriction with cessation of indomethacin therapy reflect changes in hemodynamics. Normal venous flow
or s/p laser ablation in setting of TTTS results in a prompt patterns in the systemic veins show biphasic forward flow; 67
improvement in degree of tricuspid regurgitation and can be corresponding to the ‘S’ wave with ventricular systole and ‘D’
used as a marker for improving hemodynamics. wave during early diastole followed by a transient negative or
1
a b
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 box 2: doppler indices
venosus, atrial contraction results in decreased flow velocity
but maintains forward flow. Normal umbilical vein shows Commonly used venous doppler indices:
non-pulsatile flow. Increasing central venous pressure leads 1. Preload index (IVC): Peak A velocity/peak S velocity
2. Pulsatility index for veins (DV): Systolic-diastolic (a) velocity/
to progressive increase in ‘a’ wave reversal starting from the
time averaged maximal velocity
hepatic veins and IVC through the ductus venosus and hence 3. Percentage reverse flow: Time velocity integral (S+D)/time
to the umbilical veins with increasing severity.132,133 Early velocity integral A reversal
venous Doppler changes indicative of high filling pressures
Commonly used arterial doppler indices:
may be seen normally in the setting of CHD associated 1. SD ratio: Systolic/diastolic ratio
with right heart obstructive disease, but should be non- 2. Pulsatility index (PI): Systolic velocity–diastolic velocity/
progressive in these states.134–136 Similarly, tachyarrhythmias mean velocity
result in abnormal venous Doppler tracing but should show 3. Resistive index (RI): Systolic velocity–diastolic velocity/
normalization during sinus rhythm. Persistence of abnormal systolic velocity
4. Cerebroplacental ratio: Middle cerebral artery PI/umbilical
venous Doppler tracings in sinus rhythm is thought to be
artery PI
indicative of underlying myocardial dysfunction. Doppler
D = Diastolic; DV = Ductus venosus; IVC = Inferior vena cava; S = Systolic.
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 including the middle cerebral artery (MCA) and the umbilical
venous flow shows low velocity forward flow with a ‘S’ and cord. Evaluation of the arterial Doppler patterns enables
‘D’ peak and cessation of flow in atrial systole. Increasing left the assessment of features of decentralization of flow and
atrial pressure results in flow reversal in the pulmonary veins assessment of the fetoplacental unit. Fetal hypoxia results in
with atrial contraction and a decrease in diastolic forward cerebral vasodilatation as a ‘brain sparing’ response, which
flow, ultimately resulting in a biphasic to-and-fro pattern results in a decrease in MCA PI due to increase in diastolic
with absent ‘D’ velocities.65,137,138 Left atrial hypertension flow velocity, in the setting of increased PI in the umbilical
and restriction at the level of the foramen ovale has been artery.139 This results in an increase in cerebroplacental index
associated with poor outcomes.59 (Box 2). Fetal anemia results in an increase in MCA peak
velocity. The healthy placenta is a low resistance circuit and the
arterial doppler umbilical artery shows a systolic peak with continued forward
68 flow in diastole. With progressive placental dysfunction, there
Arterial Doppler can be obtained at several sites including is initially a decrease in diastolic flow velocity followed by
the semilunar valves, great arteries and their branches cessation and then reversed flow in diastole implying a high
 table 4 4
Cardiovascular profile score.
Cardiovascular profile score (10 points = normal)
FEtal Cardiology
Feature Normal –1 point –2 points
Hydrops None (2 points) Ascites or pleural effusion or Skin edema
pericardial effusion
Venous Doppler
(Umbilical vein)
(Ductus venosus) UV UV UV pulsations
DV (2 points)
DV
Heart size (Heart area/chest ≤ 0.35 (2 points) 0.35 - 0.50 > 0.50
area) < 0.20
Cardiac function Normal TV and MV Holosystolic TR or Holosystolic MR or

RV/LV S.F. > 0.28 RV/LV S.F. < 0.28 TR dP/dt < 400 or
Biphasic filling (2 points) Monophasic filling
Arterial Doppler
(Umbilical artery)
UA (2 points) UA (AEDV) UA (REDV)
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 assessment of Fetal rhythm
arterial flow patterns especially in left heart obstructive lesions
and should be taken into account.141–143 Ultrasound is the mainstay in the clinical evaluation and man-
A fetal cardiovascular profile score has been proposed agement of rhythm disorders in the fetus. Fetal echocardio-
by Huhta and colleagues as outlined in Table 4.144 A normal graphy allows for a comprehensive assessment of the fetus
score would be 10 with a decrease in the score with each including:
additional abnormality. A decreasing score has been shown • Assessment of underlying rhythm and elucidation of
to be predictive of poor outcome in the setting of placental mechanism of arrhythmia
insufficiency and primary heart defects.145,146 • Evaluation for associated cardiac malformations
• Serial evaluation/assessment for evidence of heart failure
Fetal arrhythmIas and tolerance of arrhythmia
• Response to therapeutic intervention.
Fetal rhythm disturbances account for about 10 to 20 percent of The assessment of underlying rhythm by ultrasound
referrals to fetal cardiologists.147,148 Most of these are benign and depends on the extrapolation of electrical events based on its
consist of transient irregularity in rhythm and are well-tolerated. mechanical consequence in terms of myocardial contraction
However, persistent tachycardia and bradycardia may result (M-mode, tissue Doppler), its physiologic correlate by
in fetal heart failure and in utero demise. Transplacental drug assessing Doppler flow patterns or a combination of the
therapy has been used effectively, especially in the management two (color M-mode) (Figure 22). The goal is to establish
of fetal tachycardia, providing an impetus for comprehensive the chronologic relationship between atrial and ventricular
assessment of the fetal rhythm in an effort to improve outcomes contraction and their rates, thus inferring the underlying
in these fetuses. Normal fetal heart varies with gestational age, rhythm. Mechanical PR interval can be measured using
but in general ranges from 120 to 160 BPM. Normograms have Doppler techniques and helps to assess A-V conduction times. 69
been published and are available for reference.149,150 (Figures 22 A and B).
1
a b
C d
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 which result in fusion of E and A waves and also when atrial
contraction occurs simultaneous with ventricular contraction
Alignment of the M-mode along the atrium and ventricle allows or against a closed atrioventricular valve.
for simultaneous recording of the atrial and ventricular wall Simultaneous sampling of the ascending aorta and the SVC
motion. The quality of the tracings is significantly affected by as it enters the right atrium, demonstrates the relationship
maternal insonation characteristics, fetal position and motion, of the atrial contraction (A reversal in SVC) to ventricular
which may limit the ability to achieve proper alignment. It contraction (forward flow in aorta) (Figure 22B). Using
is often difficult to obtain good quality tracings of one or the this technique one can assess chronological relationships to
other chamber and atrial signals may be of low amplitude in ascertain the rhythm and measure ventriculoatrial (VA) and
setting of hydrops. Color encoded M-mode overcomes some atrioventricular (AV) time intervals to further characterize
of these issues. In this, the M-mode cursor is optimized to the tachycardia.151 It is important to optimize Doppler gate
record atrial signals. The color Doppler gate is set over aorta as well as gain settings to allow for visualization of buried
or the LVOT and flow in the aorta (from ventricular ejection) events or A waves superimposed on ventricular ejection. This
is superimposed on the M-mode. (Figure 22D). The ability to technique can be used from other sites such as the pulmonary
obtain dual anatomic M-mode tracings on the newer machines vein and pulmonary artery and descending aorta and IVC.
may circumvent some of these issues (Figure 22C). The transmission of the ‘A’ reversal to the ductus venosus and
hepatic veins helps to identify atrial contraction sequence.
doppler evaluation Tissue velocity imaging using either annular Doppler or
simultaneous sampling of an atrium and ventricle has been
Pulsed Doppler recording of simultaneous inflow and outflow shown to permit reliable arrhythmia assessment.
signals in the LVOT can be used for characterizing the rhythm. Ultrasound also plays an important role in the assessment
The mitral valve ‘A’ wave results from atrial contraction and of fetal compensation to the arrhythmia. Hydrops is easy to
is followed by the systolic ejection wave in the left ventricular recognize, however assessment of fetal well-being in the
outflow from ventricular contraction (Figure 22A). However, prehydropic state may be challenging as current methods of
70 this method is not usable in the setting of high heart rates, assessment for heart failure are heavily dependent on Doppler
evaluations, which show baseline abnormalities while in • Premature atrial contractions 4
tachycardia. Persistence of abnormal venous Doppler in sinus • Premature ventricular contractions
rhythm, progressive valvular insufficiency and decreased • Mobitz type I or intermittent type II second degree block.
FEtal Cardiology
myocardial contractility may all provide clues. Atrial premature beats are fairly common in the late
second trimester and third trimester of pregnancy and are
Fetal electrocardiogram (FeCg) and often self-limiting. They may be conducted to the ventricle or
magnetocardiogram (FmCg) blocked with a resultant extra beat or skipped beat on Doppler
(Figure 23B). Persistent blocked atrial bigeminy will present
Fetal electrocardiogram (ECG) recordings are hampered by as fetal bradycardia (Figure 24B). It is important to assess the
low amplitude signals, especially from the atrium, secondary A-V relationship closely to rule out underlying conduction
to the insulating properties of vernix. Recent publications have defects (Figure 24). Most are self-limiting, however, there
outlined its use in a clinical setting for rhythm analysis but in is a 2 to 3 percent risk for sustained tachycardia especially
limited settings.152,153 Fetal magnetocardiogram, which involves in those with multiple or frequent blocked extrasystoles with
processing of the magnetic signals that go hand in hand with a resultant low heart rate.157 Hence, management includes
electrical signals, has been successfully applied to the study weekly, auscultation of the fetal heart in an outpatient till
of fetal rhythm and has provided valuable insights into the resolution and for any tachycardia. If they persist to term,
electrophysiological assessment of fetal arrhythmias; especially then a neonatal EKG is recommended to assess for underlying
those associated with abnormal repolarization.154–156 However, pre-excitation.
it is currently available only at a few centers worldwide and its Ventricular premature beats are occasionally seen in fetal life
lack of portability and need for a magnetically shielded room, and are diagnosed by a premature contraction of the ventricle
limits its applicability in the clinical arena. in the setting of a regular atrial rate (Figure 23C). Though they
are often benign, they may occur in the setting of increased
types of arrhythmias 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
Irregular Rhythms
evaluation is recommended with a baseline ECG.
These are common and usually noted in the obstetric office as Disorders of A-V conduction may present with an irregular
either extra beats or skipped beats. Causes include: rhythm. In Mobitz type I block, there is gradual prolongation
a C
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 71
or early ventricular ejection
1
a b
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 non- accessory pathway (AVRT) or nodal re-entry (AVNRT)
conducted atrial impulse (Figure 24C). In intermittent Mobitz accounting for about 70 percent of cases. Heart rates are
type II second degree heart block, the baseline mechanical typically in the 220 to 280 BPM range, with sudden onset and
PR interval is stable (normal or prolonged) but occasional rapid termination of tachycardia. SVC/Ao tracings show a
atrial impulses are non-conducted. This should prompt an short VA interval due to rapid depolarization of the atrium via
evaluation for presence of maternal SSA/SSB antibodies and the accessory connection (Figure 25A). Medications that affect
for familial channelopathy. This has occasionally been reported the nodal refractory period or the pathway characteristics are
in otherwise normal pregnancies with a good prognosis in often effective in termination of tachycardia. At birth about 10
general.158–160 percent will have Wolff–Parkinson–White syndrome (WPW).
The presence of a long VA interval indicates either an ectopic
Fetal tachycardia atrial focus or permanent junctional reciprocating tachycardia
(PJRT) (Figure 25B). PJRT can be incessant and often requires
Fetal tachycardia is diagnosed at ventricular rates greater polydrug therapy for control.
than 180 to 200 BPM. Associated CHD may be seen in about Atrial flutter is characterized by much faster atrial rates in
10 to 12 percent cases. A broad classification based on A-V the range of 350 to 500 minute with ventricular rates in 180 to
relationships includes: 250 range in the setting of 2 or 3 : 1 conduction (Figure 25C).
• Sinus tachycardia Ventricular response may be irregular. Initiation of drug therapy
• Supraventricular tachycardia with 1 : 1 A-V relation may result in abrupt drop in fetal heart rate due to high grade
• Atrial flutter AV block and is often mistaken for fetal distress resulting in
• Ventricular tachycardia. an emergency cesarean or mistaken for sinus tachycardia
Sinus tachycardia with heart rates greater than 180 BPM depending on ventricular rates. A quick evaluation by bedside
may result from a variety of conditions such as maternal ultrasound will clarify the situation. A third of the cases may
pyrexia, hyperthyroidism, fetal anemia, etc. It is characterized coexist with supraventricular tachycardia (SVT) in the setting
by 1 : 1 A-V relationship, long VA interval and a variable heart of an accessory connection.161,162
rate that gradually increases and decreases. Ventricular tachycardia or junctional ectopic tachycardia
Supraventricular tachycardia includes different types of is characterized by a ventricular rate that is greater than the
tachycardia with 1 : 1 A-V relationship. The most common atrial rate. The atrial rate is usually normal with a ventricular
72 mechanism is atrioventricular re-entry either along an rate ranging from 160 to 300 BPM. These are rare, but
4
FEtal Cardiology
a
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 cardiac function in sinus rhythm and those with structural heart
channelopathy such as long QT syndrome (LQTS) as well as disease.165–167 Options include close observation, transplacental
immune-mediated heart block. It is not possible to characterize drug therapy and if that fails or in setting of hydrops, direct
ventricular repolarization abnormalities by ultrasound and this fetal therapy may be considered. Preterm delivery is avoided if
requires fetal ECG or magnetocardiography (MCG) to define the possible except if the fetus fails therapy and is of a sufficiently
fetal QTc.163–164 advanced gestational age and there is a clear advantage to
therapeutic options postdelivery.
management Medications that have been used for transplacental therapy
of tachyarrhythmia include digoxin, flecainide, sotalol,
The management of fetal tachycardia varies from center to amiodarone, propranolol, and propafenone, procainamide
center. General guidelines are presented here (Figure 26). and verapamil in the past.168 Most SVT can be successfully
Management options depend on the gestational age at diagnosis, managed by transplacental therapy. In the absence of hydrops
the frequency of tachycardia intermittent versus incessant, most centers will initiate therapy with digoxin which has
mechanism of tachycardia, presence or absence of hydrops and reported success rate of 60 to 80 percent in absence of hydrops
maternal and fetal well-being. Hydrops may result in upto 50 though therapeutic efficacy drops in setting of hydrops.169,170
percent of cases and risk increases with incessant tachycardia Digoxin is often used for its beneficial effects on fetal heart
(>50% time), younger gestation age at onset, diminished function. The second line of medications includes flecainide 73
1
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 tachycardia—implies absence or presence of.
or sotalol with success rates approaching 60 to 85 percent A cardiology assessment of the mother to look for contrain-
and in some centers amiodarone. Studies suggest comparable dications to therapy, as well as monitoring for adverse effects
efficacy of both with flecainide having better efficacy with of the medications is critical. This involves multidisciplinary
SVT and sotalol with flutter.171–178 Direct fetal therapy care involving the perinatologist, pediatric cardiologist and
is limited to fetuses with poor response to transplacental adult cardiologist to help coordinate care and monitoring of
medications in setting of heart failure and prematurity. The mother and fetus.
risk of adverse outcomes and fetal mortality approaches 15
to 30 percent167,171 in setting of hydrops and 0 to 10 percent Fetal BradyCardIa
without.167,170,179 Other morbidities include risk for cerebral
injury and also prematurity.167,176,180 Upto two-third of Fetal bradycardia is defined as a persistent fetal heart rate of
cases may have recurrence of arrhythmia in the neonatal less than 110 BPM. Transient fetal bradycardia is often seen
period. Cases of atrial flutter have low recurrence rates post during ultrasound evaluations and demonstrates a brisk return
cardio version in the neonatal period, unless associated with to normal heart rates with release of pressure. Differential
underlying pre-excitation.151,167 diagnosis of fetal bradycardia includes:
Ventricular arrhythmias are rare and when incessant • Sinus bradycardia
have been managed with transplacental administration of • Blocked atrial bigeminy
74 magnesium, lidocaine, mexiletine, beta-blockers and amiod- • 2 : 1 atrioventricular block
arone.148,181 • Complete heart block.
4
FEtal Cardiology
a b
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 evolved and suggests a generalized myocardial inflammation.
the setting of a slow atrial rate. Sinus bradycardia may be Findings reported include patchy areas of increased
seen in the setting of left atrial isomerism. In the setting of echogenicity, atrial endocardial fibroelastosis, valvular
a normal heart it may be associated with channelopathies insufficiency, chordal rupture, tachyarrhythmia including
as in SCN5A mutation, LQTS and in setting of maternal junctional tachycardia and torsade and sinus bradycardia
SSA/SSB antibodies, sick sinus syndrome and IUGR in and heart defects.186–189 Hydrops may result in setting of
fetus.148,159,182 Sinus bradycardia in setting of LQTS in fetus low non-reactive FHR below 50 BPM as well as myocardial
may be subtle with mean heart rates just below the 3 percent dysfunction.158,185,190 Once set CHB is generally thought to
in the 120 to 100 range in late gestation.183 In blocked atrial be irreversible even with steroid therapy with rare cases of
bigeminy (BAB) every other beat is an atrial ectopic beat that reversal being noted.191,192 In contrast, second degree heart
is non-conducted to the ventricles and the resultant ventricular block may show stabilization or rarely reversal.193 Recent
rate is usually slower than in sinus bradycardia (Figure 24B). data suggests that CHB may set in suddenly and the finding
It is usually associated with a good prognosis. of PR prolongation to ≥ 3 Z scores is not predictive for onset
Complete or third degree AV block presents with a of CHB.194,195
regular atrial rate and slow ventricular rate in the setting of
AV dissociation (Figures 27A and B). Second degree AV management oF autoImmune heart BloCk
block presents with a regular or irregular rhythm, while first
degree AV block manifests a regular rhythm with a prolonged Optimum evaluation schedule for fetuses at risk is not
mechanical PR interval. Isolated conduction abnormalities entirely clear. Many centers will offer weekly or biweekly
have been reported in setting of a normal heart.160 Complete monitoring of cardiac function and mechanical PR interval in
AV block is seen in the setting of CHD or with a structurally setting of maternal antibodies to SSA/SSB through 24 or 26
normal conduction system. Associated congenital heart defects weeks.196,197 Evaluation should include assessment for function
include left atrial isomerism and congenitally corrected and valvular insufficiency. Pharmacotherapy includes use of
transposition of the great vessels. Prognosis remains very poor beta- agonists such as terbutaline to augment fetal ventricular
in the setting of associated isomerism with only a 10 percent rates below 55 BPM, dexamethasone or beclomethasone to
survival in this setting.158,184 Therapy in these cases is generally limit inflammation and ongoing damage and intravenous IVIG
ineffective and includes use of beta agonists to increase fetal in an attempt to decrease circulating antibodies.168,189,190,193,
heart rate and also digoxin to improve contractility.185 196,198,199 Antenatal steroid therapy has associated risks of
The risk for immune mediated heart block is about 2 to oligohydramnios, neurologic concerns in the developing brain
3 percent in setting of maternal SSA and/or SSB antibodies. and maternal glucose intolerance. Indications are not clear, but
This risk increases to about 16 to 20 percent in setting of it is suggested that steroid therapy be reserved for cases with
a prior affected child suggesting that the cardiac effects are progressive heart block, evidence of endocardial fibroelastosis,
secondary to an interaction between environmental factors valvular insufficiency myocardial dysfunction or ongoing
with positive antibody status. The risk is highest between 16 features of heart failure. IVIG has been used in some fetuses
to 26 weeks of gestation, but CHB may be detected beyond non-responsive to steroids. Prophylactic IVIG given through
this time period and progression in postnatal period has been pregnancy in high-risk pregnancies did not prevent CHB in
reported. The spectrum of immune medicated disease has doses used.200–202 Survival in the setting of immune mediated 75
1
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 and it is important that regional programs dedicated to local
now greater than 90 percent on recent reports.196,203 Figure 28 sonographer training and support be developed. Hand-in-
outlines a general approach to the evaluation and management hand with the technological and therapeutic advances, it is
of fetal bradycardia. important to keep a focus on ethical issues, which are unique
in this setting, with the potential of harm not only to the
Future dIreCtIons mother and fetus, but in cases of twin gestation to all three of
them! 3D and 4D ultrasound will likely play a more prevalent
Ultrasound has significantly advanced our understanding of role in remote diagnosis of CHD and assessment of cardiac
fetal cardiovascular physiology. Recent work with the use of function.41,44
fetal ECG and MCG point towards the presence of possible
fetal repolarization changes and potential arrhythmias in the Medicine is a science of uncertainty and an art of probability.
stressed fetus with underlying CHD.154–156 Technological —Sir William Osler
advances resulting in improvements in the ability to obtain
fetal ECG and MCG at the bedside are needed. It is likely aCknowledgments
that assessment of fetal cardiovascular status by ultrasound
will play a more important role in several non-cardiac I would like to thank our sonographers Tim Heiser, Janet
conditions as well as providing guidance for invasive Klobuchar and Barb Trampe, for their dedication and help with
procedures. Prenatal detection rates for CHD remains poor the image acquisition.
76
reFerenCes 16. Jouannic JM, Thieulin AC, Bonnet D, et al. Measurement of
nuchal translucency for prenatal screening of congenital heart
4
1. Hoffman JI, Kaplan S. The incidence of congenital heart defects: a population-based evaluation. Prenat Diagn. 2011;
FEtal Cardiology
disease. J Am Coll Cardiol. 2002; 39:1890-1900. Epub 31:1264-9. Epub 2011/10/27.
2002/06/27. 17. Schwarzler P, Carvalho JS, Senat MV, et al. Screening for fetal
2. van der Linde D, Konings EE, Slager MA, et al. Birth aneuploidies and fetal cardiac abnormalities by nuchal translu-
prevalence of congenital heart disease worldwide: a systematic cency thickness measurement at 10-14 weeks of gestation as
review and meta-analysis. J Am Coll Cardiol. 2011; ; 58:2241- part of routine antenatal care in an unselected population. Br J
7. Epub 2011/11/15. Obstet Gynaecol. 1999; 106:1029-34. Epub 1999/10/16.
3. Pierpont ME, Basson CT, Benson DW Jr, et al. Genetic basis 18. Mogra R, Alabbad N, Hyett J. Increased nuchal translucency
for congenital heart defects: current knowledge: a scientific and congenital heart disease. Early Hum Dev. 2012; 88:
statement from the American Heart Association Congenital 261-7. Epub 2012/04/10.
Cardiac Defects Committee, Council on Cardiovascular Disease 19. Allan LD. The mystery of nuchal translucency. Cardiol Young.
in the Young: endorsed by the American Academy of Pediatrics. 2006; 16:11-7. Epub 2006/02/04.
Circulation. 2007; 115:3015-38. Epub 2007/05/24. 20. Bebbington M, Wilson RD, Johnson MP. Detection of
4. Reller MD, Strickland MJ, Riehle-Colarusso T, et al. Prevalence congenital heart disease in the first trimester of pregnancy.
of congenital heart defects in metropolitan Atlanta, 1998-2005. Progress in Pediatric Cardiology. 2006; 22:3-8.
J Pediatr. 2008; 153:807-13. Epub 2008/07/29. 21. Rychik J, Ayres N, Cuneo B, et al. American Society of
5. Bernier PL, Stefanescu A, Samoukovic G, et al. The challenge Echocardiography guidelines and standards for performance
of congenital heart disease worldwide: epidemiologic and of the fetal echocardiogram. J Am Soc Echocardiogr. 2004;
demographic facts. Seminars in thoracic and cardiovascular 17:803-10. Epub 2004/06/29.
surgery Pediatric cardiac surgery annual. 2010; 13:26-34. Epub 22. Pruetz JD, Sklansky M, Detterich J, et al. Twin-twin transfusion
2010/03/24. syndrome treated with laser surgery: postnatal prevalence of
6. Oyen N, Poulsen G, Boyd HA, et al. National time trends in congenital heart disease in surviving recipients and donors.
congenital heart defects, Denmark, 1977-2005. Am Heart J. Prenat Diagn. 2011; 31:973-7. Epub 2011/07/12.
2009; 157:467-73 e1. Epub 2009/03/03. 23. Manning N, Archer N. A study to determine the incidence of
7. Simpson LL. Indications for fetal echocardiography from a structural congenital heart disease in monochorionic twins.
tertiary-care obstetric sonography practice. J Clin Ultrasound. Prenat Diagn. 2006; 26:1062-4. Epub 2006/09/08.
2004; 32:123-8. Epub 2004/03/03. 24. Fesslova V, Brankovic J, Lalatta F, et al. Recurrence of
8. Friedberg MK, Silverman NH. Changing indications for fetal congenital heart disease in cases with familial risk screened
echocardiography in a University Center population. Prenat prenatally by echocardiography. Journal of pregnancy. 2011;
Diagn. 2004; 24:781-6. Epub 2004/10/27. 2011:368-067. Epub 2011/10/07.
9. Perri T, Cohen-Sacher B, Hod M, et al. Risk factors for cardiac 25. Oberhansli I, Extermann P, Jaggi E. Fetal echocardiography in
malformations detected by fetal echocardiography in a tertiary pregnancies of women with congenital heart disease-clinical
center. The journal of maternal-fetal and neonatal medicine : utility and limitations. Thorac Cardiovasc Surg. 2000; 48:323-
the official journal of the European Association of Perinatal 7. Epub 2001/01/06.
Medicine, the Federation of Asia and Oceania Perinatal 26. Cooper MJ, Enderlein MA, Dyson DC, et al. Fetal echocar-
Societies, the International Society of Perinatal Obstet. 2005; diography: retrospective review of clinical experience and an
17:123-8. Epub 2005/08/04. evaluation of indications. Obstet Gynecol. 1995; 86: 577-82.
10. Fishman SG, Pelaez LM, Baergen RN, et al. Carroll SJ. Epub 1995/10/01.
Parvovirus-mediated fetal cardiomyopathy with atrioven- 27. Stumpflen I, Stumpflen A, Wimmer M, et al. Effect of
tricular nodal disease. Pediatr Cardiol. 2011; 32:84-6. Epub detailed fetal echocardiography as part of routine prenatal
2010/10/12. ultrasonographic screening on detection of congenital heart
11. Ranucci-Weiss D, Uerpairojkit B, Bowles N, et al. Intrauterine disease. Lancet. 1996; 348:854-7. Epub 1996/09/28.
adenoviral infection associated with fetal non-immune 28. Achiron R, Glaser J, Gelernter I, et al. Extended fetal echocardio-
hydrops. Prenat Diagn. 1998; 18:182-5. Epub 1998/03/27. graphic examination for detecting cardiac malformations in low
12. Allan LD, Sharland GK, Chita SK, et al. Chromosomal risk pregnancies. BMJ. 1992; 304:671-4. Epub 1992/03/14.
anomalies in fetal congenital heart disease. Ultrasound Obstet 29. Sharland G. Routine fetal cardiac screening: what are we doing
Gynecol. 1991; 1:8-11. Epub 1991/01/01. and what should we do? Prenat Diagn. 2004; 24:1123-9. Epub
13. Hyett J, Perdu M, Sharland G, et al. Using fetal nuchal 2004/12/23.
translucency to screen for major congenital cardiac defects at 30. Pinto NM, Keenan HT, Minich LL, et al. Barriers to Prenatal
10-14 weeks of gestation: population based cohort study. BMJ. Detection of Congenital Heart Disease: A Population-Based
1999; 318:81-5. Epub 1999/01/08. Study. Ultrasound Obstet Gynecol. 2011. Epub 2011/10/15.
14. Makrydimas G, Sotiriadis A, Ioannidis JP. Screening perfor- 31. Friedberg MK, Silverman NH, Moon-Grady AJ, et al. Prenatal
mance of first-trimester nuchal translucency for major detection of congenital heart disease. J Pediatr. 2009; 155:26-
cardiac defects: a meta-analysis. Am J Obstet Gynecol. 2003; 31, e1. Epub 2009/04/28.
189:1330-5. Epub 2003/11/25. 32. Michelfelder EC, Cnota JF. Prenatal diagnosis of congenital
15. Simpson LL, Malone FD, Bianchi DW, et al. Nuchal heart disease in an era of near-universal ultrasound screening:
translucency and the risk of congenital heart disease. Obstet room for improvement. J Pediatr. 2009; 155:9-11. Epub
77
Gynecol. 2007; 109:376-83. Epub 2007/02/03. 2009/06/30.
1 33. Sklansky M. Current guidelines for fetal echocardiography:
time to raise the bar. J Ultrasound Med. 2011; 30:284-6; author
49. Schneider C, McCrindle BW, Carvalho JS, et al. Development
of Z-scores for fetal cardiac dimensions from echocardiography.
reply 6. Epub 2011/01/27. Ultrasound Obstet Gynecol. 2005; 26:599-605. Epub
34. Sklansky MS, Berman DP, Pruetz JD, et al. Prenatal screening 2005/10/29.
for major congenital heart disease: superiority of outflow tracts 50. Shapiro I, Degani S, Leibovitz Z, et al. Fetal cardiac measure-
over the 4-chamber view. J Ultrasound Med. 2009; 28:889-99. ments derived by transvaginal and transabdominal cross-
Epub 2009/06/24. sectional echocardiography from 14 weeks of gestation to term.
35. Sharland GK, Allan LD. Screening for congenital heart disease Ultrasound Obstet Gynecol. 1998; 12:404-18. Epub 1999/01/26.
prenatally. Results of a 2 1/2-year study in the South East 51. Lee W, Riggs T, Amula V, et al. Fetal echocardiography: z-score
Thames Region. Br J Obstet Gynaecol. 1992; 99:220-5. Epub reference ranges for a large patient population. Ultrasound
1992/03/01. Obstet Gynecol. 2010; 35:28-34. Epub 2009/12/17.
36. Hunter S, Heads A, Wyllie J, et al. Prenatal diagnosis of 52. Pasquini L, Mellander M, Seale A, et al. Z-scores of the fetal
congenital heart disease in the northern region of England: aortic isthmus and duct: an aid to assessing arch hypoplasia.
benefits of a training programme for obstetric ultrasonographers. Ultrasound Obstet Gynecol. 2007; 29:628-33. Epub 2007/05/04.
Heart. 2000; 84:294-8. Epub 2000/08/24. 53. Peterson RE, Levi DS, Williams RJ, et al. Echocardiographic
37. Chang RK, Gurvitz M, Rodriguez S. Missed diagnosis of predictors of outcome in fetuses with pulmonary atresia with
critical congenital heart disease. Arch Pediatr Adolesc Med. intact ventricular septum. J Am Soc Echocardiogr. 2006;
2008; 162:969-74. Epub 2008/10/08. 19:1393-400. Epub 2006/11/14.
38. Volpe P, Ubaldo P, Volpe N, et al. Fetal cardiac evaluation 54. Salvin JW, McElhinney DB, Colan SD, et al. Fetal tricuspid
at 11-14 weeks by experienced obstetricians in a low-risk valve size and growth as predictors of outcome in pulmonary
population. Prenat Diagn. 2011; 31:1054-61. Epub 2011/07/30. atresia with intact ventricular septum. Pediatrics. 2006;
39. Westin M, Saltvedt S, Bergman G, et al. Routine ultrasound ex- 118:e415-20. Epub 2006/08/03.
amination at 12 or 18 gestational weeks for prenatal detection 55. Makikallio K, McElhinney DB, Levine JC, et al. Fetal aortic
of major congenital heart malformations? A randomised con- valve stenosis and the evolution of hypoplastic left heart
trolled trial comprising 36,299 fetuses. BJOG: an international syndrome: patient selection for fetal intervention. Circulation.
journal of obstetrics and gynaecology. 2006; 113:675-82. Epub 2006; 113:1401-5. Epub 2006/03/15.
2006/05/20. 56. Matsui H, Mellander M, Roughton M, et al. Morphological and
40. Persico N, Moratalla J, Lombardi CM, et al. Fetal echocardi- physiological predictors of fetal aortic coarctation. Circulation.
ography at 11-13 weeks by transabdominal high-frequency ul- 2008; 118:1793-801. Epub 2008/10/15.
trasound. Ultrasound Obstet Gynecol. 2011; 37:296-301. Epub 57. Simpson JM, Cook A. Repeatability of echocardiographic
2011/01/14. measurements in the human fetus. Ultrasound Obstet Gynecol.
41. Yagel S, Cohen SM, Rosenak D, et al. Added value of three-/ 2002; 20:332-9. Epub 2002/10/18.
four-dimensional ultrasound in offline analysis and diagnosis 58. Feit LR, Copel JA, Kleinman CS. Foramen ovale size in
of congenital heart disease. Ultrasound Obstet Gynecol. 2011; the normal and abnormal human fetal heart: an indicator of
37:432-7. Epub 2010/10/30. transatrial flow physiology. Ultrasound Obstet Gynecol. 1991;
42. Goncalves LF, Lee W, Chaiworapongsa T, et al. Four-dimen- 1:313-9. Epub 1991/09/01.
sional ultrasonography of the fetal heart with spatiotemporal 59. Vida VL, Bacha EA, Larrazabal A, et al. Hypoplastic left
image correlation. Am J Obstet Gynecol. 2003; 189:1792-802. heart syndrome with intact or highly restrictive atrial septum:
Epub 2004/01/08. surgical experience from a single center. Ann Thorac Surg.
43. DeVore GR, Sklansky MS. Three-dimensional imaging of the 2007; 84:581-5; discussion 6. Epub 2007/07/24.
fetal heart: Current applications and future directions. Progress 60. Vlahos AP, Lock JE, McElhinney DB, et al. ME. Hypoplastic
in Pediatric Cardiology. 2006; 22:9-29. left heart syndrome with intact or highly restrictive atrial
44. Espinoza J, Lee W, Comstock C, et al. Collaborative study septum: outcome after neonatal transcatheter atrial septostomy.
on 4-dimensional echocardiography for the diagnosis of fetal Circulation. 2004; 109:2326-330. Epub 2004/05/12.
heart defects: the COFEHD study. J Ultrasound Med. 2010; 61. Divanovic A, Hor K, Cnota J, et al. Prediction and perinatal
29:1573-80. Epub 2010/10/23. management of severely restrictive atrial septum in fetuses
45. Messing B, Cohen SM, Valsky DV, et al. Fetal cardiac ventricle with critical left heart obstruction: clinical experience using
volumetry in the second half of gestation assessed by 4D ultra- pulmonary venous Doppler analysis. J Thorac Cardiovasc
sound using STIC combined with inversion mode. Ultrasound Surg. 2011; 141:988-94. Epub 2010/12/07.
Obstet Gynecol. 2007; 30:142-51. Epub 2007/06/15. 62. Donofrio MT, Bremer YA, Moskowitz WB. Diagnosis and
46. Cordes TM, O'Leary PW, Seward JB, et al. Distinguishing right management of restricted or closed foramen ovale in fetuses
from left: a standardized technique for fetal echocardiography. with congenital heart disease. Am J Cardiol. 2004; 94:1348-51.
J Am Soc Echocardiogr. 1994; 7:47-53. Epub 1994/01/01. Epub 2004/11/16.
47. Yagel S, Cohen SM, Achiron R. Examination of the fetal heart 63. Maeno YV, Kamenir SA, Sinclair B, et al. Prenatal Features of
by five short-axis views: a proposed screening method for Ductus Arteriosus Constriction and Restrictive Foramen Ovale
comprehensive cardiac evaluation. Ultrasound Obstet Gynecol. in d-Transposition of the Great Arteries. Circulation. 1999;
2001; 17:367-69. Epub 2001/06/16. 99:1209-14.
48. Sharland GK, Allan LD. Normal fetal cardiac measurements 64. Punn R, Silverman NH. Fetal predictors of urgent balloon atrial
derived by cross-sectional echocardiography. Ultrasound septostomy in neonates with complete transposition. J Am Soc
78
Obstet Gynecol. 1992; 2:175-81. Epub 1992/05/01. Echocardiogr. 2011; 24:425-30. Epub 2011/02/18.
65. Chintala K, Tian Z, Du W, et al. Fetal pulmonary venous
Doppler patterns in hypoplastic left heart syndrome:
80. Tometzki AJ, Suda K, Kohl T, et al. Accuracy of prenatal
echocardiographic diagnosis and prognosis of fetuses with
4
relationship to atrial septal restriction. Heart. 2008; 94:1446-9. conotruncal anomalies. J Am Coll Cardiol. 1999; 33:1696-701.
FEtal Cardiology
Epub 2007/10/10. Epub 1999/05/20.
66. Pitkanen OM, Hornberger LK, Miner SE, et al. Borderline left 81. Galindo A, Mendoza A, Arbues J, et al. Conotruncal anomalies
ventricles in prenatally diagnosed atrioventricular septal defect in fetal life: accuracy of diagnosis, associated defects and
or double outlet right ventricle: echocardiographic predictors outcome. Eur J Obstet Gynecol Reprod Biol. 2009; 146:55-60.
of biventricular repair. Am Heart J. 2006; 152:163 e1-7. Epub Epub 2009/06/02.
2006/07/11. 82. Sivanandam S, Glickstein JS, Printz BF, et al. Prenatal diagnosis
67. Huggon IC, Cook AC, Smeeton NC, et al. Atrioventricular of conotruncal malformations: diagnostic accuracy, outcome,
septal defects diagnosed in fetal life: associated cardiac and chromosomal abnormalities, and extracardiac anomalies. Am J
extra-cardiac abnormalities and outcome. J Am Coll Cardiol. Perinatol. 2006; 23:241-5. Epub 2006/04/21.
2000; 36:593-601. Epub 2000/08/10. 83. Yagel S, Arbel R, Anteby EY, et al. The three vessels and
68. Hornberger LK, Sahn DJ, Kleinman CS, et al. Tricuspid valve trachea view (3VT) in fetal cardiac scanning. Ultrasound
disease with significant tricuspid insufficiency in the fetus: Obstet Gynecol. 2002; 20:340-5. Epub 2002/10/18.
diagnosis and outcome. J Am Coll Cardiol. 1991; 17:167-73. 84. Vinals F, Heredia F, Giuliano A. The role of the three vessels
Epub 1991/01/01. and trachea view (3VT) in the diagnosis of congenital heart
69. Messing B, Porat S, Imbar T, et al. Mild tricuspid regurgitation: defects. Ultrasound Obstet Gynecol. 2003; 22:358-67. Epub
a benign fetal finding at various stages of pregnancy. 2003/10/07.
Ultrasound Obstet Gynecol. 2005; 26:606-9; discussion 10. 85. Wu Q, Li M, Ju L, et al. Application of the 3-vessel view
Epub 2005/10/08. in routine prenatal sonographic screening for congenital
70. Respondek ML, Kammermeier M, Ludomirsky A, et al. The heart disease. J Ultrasound Med. 2009; 28:1319-24. Epub
prevalence and clinical significance of fetal tricuspid valve 2009/09/26.
regurgitation with normal heart anatomy. Am J Obstet Gynecol. 86. Escribano D, Herraiz I, Granados M, et al. Tetralogy of
1994; 171:1265-70. Epub 1994/11/01. Fallot: prediction of outcome in the mid-second trimester of
71. Berg C, Lachmann R, Kaiser C, et al. Prenatal diagnosis of pregnancy. Prenat Diagn. 2011; 31:1126-33. Epub 2011/09/20.
tricuspid atresia: intrauterine course and outcome. Ultrasound 87. Wertaschnigg D, Jaeggi M, Chitayat D, et al. Prenatal
Obstet Gynecol. 2010; 35:183-90. Epub 2010/01/27. Diagnosis and Outcome of Absent Pulmonary Valve
72. Roman KS, Fouron JC, Nii M, et al. Determinants of outcome in Syndrome: Contemporary Single Center Experience and
fetal pulmonary valve stenosis or atresia with intact ventricular Review of the Literature. Ultrasound Obstet Gynecol. 2012.
septum. Am J Cardiol. 2007; 99:699-703. Epub 2007/02/24. Epub 2012/05/19.
73. Gardiner HM, Belmar C, Tulzer G, et al. Morphologic and 88. Jouannic JM, Gavard L, Fermont L, et al. Sensitivity and
functional predictors of eventual circulation in the fetus specificity of prenatal features of physiological shunts to
with pulmonary atresia or critical pulmonary stenosis with predict neonatal clinical status in transposition of the great
intact septum. J Am Coll Cardiol. 2008; 51:1299-308. Epub arteries. Circulation. 2004; 110:1743-6. Epub 2004/09/15.
2008/03/29. 89. Sharland G, Tingay R, Jones A, et al. Atrioventricular
74. Lasa JJ, Tian ZY, Guo R, et al. Perinatal course of Ebstein's and ventriculoarterial discordance (congenitally corrected
anomaly and tricuspid valve dysplasia in the fetus. Prenat transposition of the great arteries): echocardiographic features,
Diagn. 2012; 32:245-51. Epub 2012/03/21. associations, and outcome in 34 fetuses. Heart. 2005; 91:1453-
75. Barre E, Durand I, Hazelzet T, et al. Anomaly and Tricuspid 8. Epub 2005/03/12.
Valve Dysplasia: Prognosis After Diagnosis In Utero. Pediatr 90. Paladini D, Volpe P, Marasini M, et al. Diagnosis,
Cardiol. 2012. Epub 2012/05/29. characterization and outcome of congenitally corrected
76. Vogel M, McElhinney DB, Wilkins-Haug LE, et al. Aortic transposition of the great arteries in the fetus: a multicenter
stenosis and severe mitral regurgitation in the fetus resulting in series of 30 cases. Ultrasound Obstet Gynecol. 2006; 27:
giant left atrium and hydrops: pathophysiology, outcomes, and 281-5. Epub 2006/02/18.
preliminary experience with pre-natal cardiac intervention. J 91. Lagopoulos ME, Manlhiot C, McCrindle BW, et al. Impact
Am Coll Cardiol. 2011; 57:348-55. Epub 2011/01/15. of prenatal diagnosis and anatomical subtype on outcome in
77. Rogers LS, Peterson AL, Gaynor JW, et al. Mitral valve dysplasia double outlet right ventricle. Am Heart J. 2010; 160:692-700.
syndrome: a unique form of left-sided heart disease. J Thorac Epub 2010/10/12.
Cardiovasc Surg. 2011; 142:1381-7. Epub 2011/07/15. 92. Swanson TM, Selamet Tierney ES, Tworetzky W, et al.
78. Weber RW, Ayala-Arnez R, Atiyah M, et al. Foetal Truncus arteriosus: diagnostic accuracy, outcomes, and impact
echocardiographic assessment of borderline small left of prenatal diagnosis. Pediatr Cardiol. 2009; 30:256-61. Epub
ventricles can predict the need for postnatal intervention. 2008/11/19.
Cardiol Young. 2012. pp. 1-9. Epub 2012/04/06. 93. Jung E, Won HS, Lee PR, et al. Clinical implication of isolated
79. McElhinney DB, Marshall AC, Wilkins-Haug LE, et al. right dominant heart in the fetus. Prenat Diagn. 2007; 27:695-
Predictors of technical success and postnatal biventricular 8. Epub 2007/05/19.
outcome after in utero aortic valvuloplasty for aortic stenosis 94. Jowett V, Aparicio P, Santhakumaran S, et al. Sonographic
with evolving hypoplastic left heart syndrome. Circulation. predictors of surgery in fetal coarctation of the aorta. Ultrasound
2009; 120:1482-90. Epub 2009/09/30. Obstet Gynecol. 2012. Epub 2012/03/31.
79
1 95. Head CE, Jowett VC, Sharland GK, et al. Timing of
presentation and postnatal outcome of infants suspected of
112. Bacha EA. Impact of fetal cardiac intervention on congenital
heart surgery. Seminars in thoracic and cardiovascular
having coarctation of the aorta during fetal life. Heart. 2005; surgery Pediatric cardiac surgery annual. 2011; 14:35-7. Epub
91:1070-4. Epub 2005/07/16. 2011/03/30.

96. Respondek M, Weil SR, Huhta JC. Fetal echocardiography 113. Arzt W, Wertaschnigg D, Veit I, et al. Intrauterine aortic
during indomethacin treatment. Ultrasound Obstet Gynecol. valvuloplasty in fetuses with critical aortic stenosis: experience
1995; 5:86-9. Epub 1995/02/01. and results of 24 procedures. Ultrasound Obstet Gynecol. 2011;
97. Zielinsky P, Piccoli AL Jr, Manica JL, et al. Reversal of fetal 37:689-95. Epub 2011/01/14.
ductal constriction after maternal restriction of polyphenol-rich 114. Arzt W, Tulzer G. Fetal surgery for cardiac lesions. Prenat
foods: an open clinical trial. J Perinatol. 2011. Epub 2011/11/05. Diagn. 2011; 31:695-8. Epub 2011/06/15.
98. Auer M, Brezinka C, Eller P, et al. Prenatal diagnosis of 115. Pavlovic M, Acharya G, Huhta JC. Controversies of fetal
intrauterine premature closure of the ductus arteriosus cardiac intervention. Early Hum Dev. 2008; 84:149-53. Epub
following maternal diclofenac application. Ultrasound Obstet 2008/03/15.
Gynecol. 2004; 23:513-6. Epub 2004/05/11. 116. McElhinney DB, Tworetzky W, Lock JE. Current status of fetal
99. Tulzer G, Gudmundsson S, Sharkey AM, et al. Doppler cardiac intervention. Circulation. 2010; 121:1256-63. Epub
echocardiography of fetal ductus arteriosus constriction versus 2010/03/17.
increased right ventricular output. J Am Coll Cardiol. 1991; 117. Marshall AC, Levine J, Morash D, et al. Results of in utero
18:532-6. Epub 1991/08/01. atrial septoplasty in fetuses with hypoplastic left heart
100. Holley DG, Martin GR, Brenner JI, et al. Diagnosis and syndrome. Prenat Diagn. 2008; 28:1023-8. Epub 2008/10/18.
management of fetal cardiac tumors: a multicenter experience 118. Tworetzky W, McElhinney DB, Marx GR, et al. In utero valvu-
and review of published reports. J Am Coll Cardiol. 1995; loplasty for pulmonary atresia with hypoplastic right ventricle:
26:516-20. Epub 1995/08/01. techniques and outcomes. Pediatrics. 2009; 124:e510-8. Epub
101. Yinon Y, Chitayat D, Blaser S, et al. Fetal cardiac tumors: a 2009/08/27.
singlecenter experience of 40 cases. Prenat Diagn. 2010; 119. Tulzer G, Arzt W, Franklin RC. Fetal pulmonary valvuloplasty
30:941-9. Epub 2010/08/20. for critical pulmonary stenosis or atresia with intact septum.
102. Degueldre SC, Chockalingam P, Mivelaz Y, et al. Lancet. 2002; 360:1567-8. Epub 2002/11/22.
Considerations for prenatal counselling of patients with 120. Kiserud T. Physiology of the fetal circulation. Seminars in fetal
cardiac rhabdomyomas based on their cardiac and neurologic & neonatal medicine. 2005; 10:493-503. Epub 2005/10/21.
outcomes. Cardiol Young. 2010; 20:18-24. Epub 2010/01/23. 121. Mielke G, Benda N. Cardiac Output and Central Distribution
103. Conway J, Hancock Friesen C, Thompson D, et al. Fetal of Blood Flow in the Human Fetus. Circulation. 2001; 103:
diagnosis of an “extra cardiac chamber”. Pediatr Cardiol. 2008; 1662-8.
29:188-90. Epub 2007/10/04. 122. Rychik J. Fetal cardiovascular physiology. Pediatr Cardiol.
104. Williams JA, Collardey KR, Treadwell MC, et al. Prenatally 2004; 25:201-9. Epub 2004/09/14.
diagnosed right ventricular outpouchings: a case series and 123. Szwast A, Rychik J. Current concepts in fetal cardiovascular
review of the literature. Pediatr Cardiol. 2009; 30:840-5. Epub disease. Clin Perinatol. 2005; 32:857-75. Epub 2005/12/06.
2009/05/28. 124. Wilson RD, Hedrick H, Flake AW, et al. Sacrococcygeal
105. Cavalle-Garrido T, Cloutier A, Harder J, et al. Evolution of teratomas: prenatal surveillance, growth and pregnancy
fetal ventricular aneurysms and diverticula of the heart: an outcome. Fetal Diagn Ther. 2009; 25:15-20. Epub 2009/01/06.
echocardiographic study. Am J Perinatol. 1997; 14:393-400. 125. Byrne FA, Lee H, Kipps AK, et al. Echocardiographic risk
Epub 1997/08/01. stratification of fetuses with sacrococcygeal teratoma and twin-
106. Bonnet D, Coltri A, Butera G, et al. Detection of transposition reversed arterial perfusion. Fetal Diagn Ther. 2011; 30:280-88.
of the great arteries in fetuses reduces neonatal morbidity and Epub 2011/11/17.
mortality. Circulation. 1999; 99:916-8. Epub 1999/02/23. 126. Szwast A, Tian Z, McCann M, et al. Impact of altered
107. Mahle WT, Clancy RR, McGaurn SP, et al. Impact of prenatal loading conditions on ventricular performance in fetuses with
diagnosis on survival and early neurologic morbidity in congenital cystic adenomatoid malformation and twin-twin
neonates with the hypoplastic left heart syndrome. Pediatrics. transfusion syndrome. Ultrasound Obstet Gynecol. 2007;
2001; 107:1277-82. Epub 2001/06/05. 30:40-6. Epub 2007/05/30.
108. Tworetzky W, McElhinney DB, Reddy VM, et al. Improved 127. Michelfelder E, Gottliebson W, Border W, et al. Early mani-
surgical outcome after fetal diagnosis of hypoplastic left heart festations and spectrum of recipient twin cardiomyopathy in twin-
syndrome. Circulation. 2001; 103:1269-73. Epub 2001/03/10. twin transfusion syndrome: relation to Quintero stage. Ultrasound
109. Kipps AK, Feuille C, Azakie A, et al. Prenatal diagnosis of Obstet Gynecol. 2007; 30:965-71. Epub 2007/11/30.
hypoplastic left heart syndrome in current era. Am J Cardiol. 128. Habli M, Michelfelder E, Cnota J, et al. Prevalence and
2011; 108:421-7. Epub 2011/06/01. progression of recipient-twin cardiomyopathy in early-stage
110. Wren C, Reinhardt Z, Khawaja K. Twenty-year trends in twin-twin transfusion syndrome. Ultrasound Obstet Gynecol.
diagnosis of life-threatening neonatal cardiovascular malfor- 2012; 39:63-8. Epub 2011/10/15.
mations. Arch Dis Child Fetal Neonatal Ed. 2008; 93:F33-5. 129. Ishii T, McElhinney DB, Harrild DM, et al. Circumferential
Epub 2007/06/09. and longitudinal ventricular strain in the normal human fetus.
111. Kuehl KS, Loffredo CA, Ferencz C. Failure to diagnose J Am Soc Echocardiogr. 2012; 25:105-11. Epub 2011/10/29.
congenital heart disease in infancy. Pediatrics. 1999; 103:743- 130. Raboisson MJ, Bourdages M, Fouron JC. Measuring left
80
7. Epub 1999/04/02. ventricular myocardial performance index in fetuses. Am J
Cardiol. 2003; 91:919-21. Epub 2003/04/02.
131. Falkensammer CB, Paul J, Huhta JC. Fetal congestive heart
147. Hornberger LK, Sahn DJ. Rhythm abnormalities of the fetus.
Heart. 2007; 93:1294-300. Epub 2007/09/25.
4
failure: correlation of Tei-index and Cardiovascular-score. J 148. Fouron JC. Fetal arrhythmias: the Saint-Justine hospital expe-
FEtal Cardiology
Perinat Med. 2001; 29:390-8. Epub 2001/11/29. rience. Prenat Diagn. 2004; 24:1068-80. Epub 2004/12/22.
132. Baschat AA. Examination of the fetal cardiovascular system. 149. Serra V, Bellver J, Moulden M, et al. Computerized analysis of
Seminars in fetal & neonatal medicine. 2011; 16:2-12. Epub normal fetal heart rate pattern throughout gestation. Ultrasound
2010/09/25. Obstet Gynecol. 2009; 34:74-9. Epub 2009/06/03.
133. Baschat AA, Harman CR. Venous Doppler in the assessment 150. Park MI, Hwang JH, Cha KJ, et al. Computerized analysis of
of fetal cardiovascular status. Curr Opin Obstet Gynecol. 2006; fetal heart rate parameters by gestational age. Int JGynaecol
18:156-63. Epub 2006/04/08. Obstet. 2001; 74:157-64. Epub 2001/08/15.
134. Gembruch U, Meise C, Germer U, et al. Venous Doppler 151. Fouron JC, Fournier A, Proulx F, et al. Management of fetal
ultrasound in 146 fetuses with congenital heart disease. tachyarrhythmia based on superior vena cava/aorta Doppler
Ultrasound Obstet Gynecol. 2003; 22:345-50. Epub flow recordings. Heart. 2003; 89:1211-6. Epub 2003/09/17.
2003/10/07. 152. Fujimoto Y, Matsumoto T, Honda N, et al. Prenatal diagnosis of
135. Bianco K, Small M, Julien S, et al. Second-trimester ductus long QT syndrome by non-invasive fetal electrocardiography. J
venosus measurement and adverse perinatal outcome in fetuses Obstet Gynaecol Res. 2009; 35:555-61. Epub 2009/06/17.
with congenital heart disease. J Ultrasound Med. 2006; 25:979- 153. Graatsma EM, Jacod BC, van Egmond LA, et al. Fetal
82; quiz 83. Epub 2006/07/28. electrocardiography: feasibility of long-term fetal heart rate
136. Berg C, Kremer C, Geipel A, et al. Ductus venosus blood recordings. BJOG: an international journal of obstetrics
flow alterations in fetuses with obstructive lesions of the right and gynaecology. 2009; 116:334-7; discussion 7-8. Epub
heart. Ultrasound Obstet Gynecol. 2006; 28:137-42. Epub 2008/12/17.
2006/07/11. 154. Strasburger JF, Cheulkar B, Wakai RT. Magnetocardiography
137. Manning N, Archer N. Fetal pulmonary venous Doppler flow for fetal arrhythmias. Heart rhythm : the official journal of the
patterns in hypoplastic left heart syndrome. Heart. 2008; Heart Rhythm Society. 2008; 5:1073-6. Epub 2008/05/20.
94:1374-5. Epub 2008/10/22. 155. Zhao H, Strasburger JF, Cuneo BF, et al. Fetal cardiac
138. Michelfelder E, Gomez C, Border W, et al. Predictive value of repolarization abnormalities. Am J Cardiol. 2006; 98:491-6.
fetal pulmonary venous flow patterns in identifying the need for Epub 2006/08/09.
atrial septoplasty in the newborn with hypoplastic left ventricle. 156. Cuneo BF, Strasburger JF, Wakai RT. Magnetocardiography in
Circulation. 2005; 112:2974-9. Epub 2005/11/02. the evaluation of fetuses at risk for sudden cardiac death before
139. Baschat AA, Gembruch U, Harman CR. The sequence of birth. J Electrocardiol. 2008; 41:116 e1-6. Epub 2008/03/11.
changes in Doppler and biophysical parameters as severe fetal 157. Vergani P, Mariani E, Ciriello E, et al. Fetal arrhythmias:
growth restriction worsens. Ultrasound Obstet Gynecol. 2001; natural history and management. Ultrasound Med Biol. 2005;
18:571-7. Epub 2002/02/15. 31:1-6. Epub 2005/01/18.
140. Society for Maternal-Fetal Medicine Publications C, Berkley 158. Lopes LM, Tavares GM, Damiano AP, et al. Perinatal outcome
E, Chauhan SP, et al. Doppler assessment of the fetus with of fetal atrioventricular block: one-hundred-sixteen cases from
intrauterine growth restriction. Am J Obstet Gynecol. 2012; a single institution. Circulation. 2008; 118:1268-75. Epub
206:300-8. Epub 2012/04/03. 2008/09/04.
141. Guorong L, Shaohui L, Peng J, et al. Cerebrovascular blood 159. Lin MT, Hsieh FJ, Shyu MK, et al. Postnatal outcome of fetal
flow dynamic changes in fetuses with congenital heart disease. bradycardia without significant cardiac abnormalities. Am
Fetal Diagn Ther. 2009; 25:167-72. Epub 2009/03/19. Heart J. 2004; 147:540-4. Epub 2004/03/05.
142. Berg C, Gembruch O, Gembruch U, et al. Doppler indices 160. Chang YL, Hsieh PC, Chang SD, et al. Perinatal outcome of fetus
of the middle cerebral artery in fetuses with cardiac defects with isolated congenital second degree atrioventricular block
theoretically associated with impaired cerebral oxygen without maternal anti-SSA/Ro-SSB/La antibodies. Eur J Obstet
delivery in utero: is there a brain-sparing effect? Ultrasound Gynecol Reprod Biol. 2005; 122:167-71. Epub 2005/10/13.
Obstet Gynecol. 2009; 34:666-72. Epub 2009/12/03. 161. Jaeggi E, Fouron JC, Drblik SP. Fetal atrial flutter: diagnosis,
143. Kaltman JR, Di H, Tian Z, et al. Impact of congenital heart clinical features, treatment, and outcome. J Pediatr. 1998;
disease on cerebrovascular blood flow dynamics in the fetus. 132:335-9. Epub 1998/03/20.
Ultrasound Obstet Gynecol. 2005; 25:32-6. Epub 2004/12/14. 162. Simpson JM, Sharland GK. Fetal tachycardias: management
144. Huhta JC, Paul JJ. Doppler in fetal heart failure. Clin Obstet and outcome of 127 consecutive cases. Heart. 1998; 79:576-
Gynecol. 2010; 53:915-29. Epub 2010/11/05. 81. Epub 1999/03/17.
145. Wieczorek A, Hernandez-Robles J, Ewing L, et al. Prediction of 163. Cuneo BF, Ovadia M, Strasburger JF, et al. Prenatal diagnosis
outcome of fetal congenital heart disease using a cardiovascular and in utero treatment of torsades de pointes associated with
profile score. Ultrasound Obstet Gynecol. 2008; 31:284-8. congenital long QT syndrome. Am J Cardiol. 2003; 91:1395-8.
Epub 2008/02/07. Epub 2003/05/28.
146. Hofstaetter C, Hansmann M, Eik-Nes SH, et al. A cardiovascular 164. Cuneo BF, Strasburger JF, Wakai RT, et al. Conduction system
profile score in the surveillance of fetal hydrops. The journal of disease in fetuses evaluated for irregular cardiac rhythm. Fetal
maternal-fetal and neonatal medicine: the official journal of the Diagn Ther. 2006; 21:307-13. Epub 2006/04/08.
European Association of Perinatal Medicine, the Federation of 165. Cuneo BF, Strasburger JF. Management strategy for fe-
Asia and Oceania Perinatal Societies, the International Society tal tachycardia. Obstet Gynecol. 2000; 96:575-81. Epub
81
of Perinatal Obstet. 2006; 19:407-13. Epub 2006/08/23. 2000/09/27.
1 166. Naheed ZJ, Strasburger JF, Deal BJ, et al. Fetal tachycardia:
mechanisms and predictors of hydrops fetalis. J Am Coll
nationwide questionnaire survey in Japan. Circulation Arrhyth-
mia and electrophysiology. 2010; 3:10-7. Epub 2009/12/10.
Cardiol. 1996; 27:1736-40. Epub 1996/06/01. 184. Jaeggi ET, Hornberger LK, Smallhorn JF, et al. Prenatal
167. Moodley S, Sanatani S, Potts JE, et al. Postnatal Outcome in diagnosis of complete atrioventricular block associated with
Patients With Fetal Tachycardia. Pediatr Cardiol. 2012. Epub structural heart disease: combined experience of two tertiary
2012/05/29. care centers and review of the literature. Ultrasound Obstet
168. Strasburger JF, Wakai RT. Fetal cardiac arrhythmia detection Gynecol. 2005; 26:16-21. Epub 2005/06/07.
and in utero therapy. Nature reviews Cardiology. 2010; 7:277- 185. Zhao H, Cuneo BF, Strasburger JF, et al. Electrophysiological
90. Epub 2010/04/27. characteristics of fetal atrioventricular block. J Am Coll
169. Srinivasan S, Strasburger J. Overview of fetal arrhythmias. Cardiol. 2008; 51:77-84. Epub 2008/01/05.
Curr Opin Pediatr. 2008; 20:522-31. Epub 2008/09/11. 186. Cuneo BF, Strasburger JF, Niksch A, et al. An expanded
170. Krapp M, Kohl T, Simpson JM, et al. Review of diagnosis, phenotype of maternal SSA/SSB antibody-associated fetal
treatment, and outcome of fetal atrial flutter compared with cardiac disease. The journal of maternal-fetal and neonatal
supraventricular tachycardia. Heart. 2003; 89:913-7. Epub medicine: the official journal of the European Association
2003/07/16. of Perinatal Medicine, the Federation of Asia and Oceania
171. Jaeggi ET, Carvalho JS, De Groot E, et al. Comparison of Perinatal Societies, the International Society of Perinatal
transplacental treatment of fetal supraventricular tachyarrhyth- Obstet. 2009; 22:233-8. Epub 2009/03/31.
mias with digoxin, flecainide, and sotalol: results of a nonran- 187. Hornberger LK, Al Rajaa N. Spectrum of cardiac involvement
domized multicenter study. Circulation. 2011; 124:1747-54. in neonatal lupus. Scand J Immunol. 2010; 72:189-97. Epub
Epub 2011/09/21. 2010/08/11.
172. van den Heuvel F, Bink-Boelkens MT, du Marchie Sarvaas 188. Cuneo BF, Fruitman D, Benson DW, et al. Spontaneous rupture
GJ, et al. Drug management of fetal tachyarrhythmias: are we of atrioventricular valve tensor apparatus as late manifestation
ready for a systematic and evidence-based approach? Pacing of anti-Ro/SSA antibody-mediated cardiac disease. Am J
Clin Electrophysiol. 2008; 31:S54-7. Epub 2008/03/25. Cardiol. 2011; 107:761-6. Epub 2011/01/21.
173. Sonesson SE, Fouron JC, Wesslen-Eriksson E, et al. Foetal 189. Krishnan A, Pike JI, Donofrio MT. Prenatal Evaluation and
supraventricular tachycardia treated with sotalol. Acta Paediatr. Management of Fetuses Exposed to Anti-SSA/Ro Antibodies.
1998; 87:584-7. Epub 1998/06/26. Pediatr Cardiol. 2012. Epub 2012/05/23.
174. Shah A, Moon-Grady A, Bhogal N, et al. Effectiveness of sotalol 190. Fesslova V, Vignati G, Brucato A, et al. The impact of treatment
as first-line therapy for fetal supraventricular tachyarrhythmias. of the fetus by maternal therapy on the fetal and postnatal
Am J Cardiol. 2012; 109:1614-8. Epub 2012/03/27. outcomes for fetuses diagnosed with isolated complete
175. Oudijk MA, Michon MM, Kleinman CS, et al. Sotalol in the atrioventricular block. Cardiol Young. 2009; 19:282-90. Epub
treatment of fetal dysrhythmias. Circulation. 2000; 101: 2721- 2009/04/23.
6. Epub 2000/06/14. 191. Adams LL, Gungor S, Salim M, et al. Regression of fetal
176. Lulic Jurjevic R, Podnar T, Vesel S. Diagnosis, clinical features, heart block and myocardial echogenicity with steroid therapy
management, and post-natal follow-up of fetal tachycardias. in maternal Sjogren's syndrome. Ultrasound Obstet Gynecol.
Cardiol Young. 2009; 19:486-93. Epub 2009/08/20. 2008; 32:839-40. Epub 2008/10/08.
177. Krapp M, Baschat AA, Gembruch U, et al. Flecainide in the 192. Mevorach D, Elchalal U, Rein AJ. Prevention of complete
intrauterine treatment of fetal supraventricular tachycar- heart block in children of mothers with anti-SSA/Ro and anti-
dia. Ultrasound Obstet Gynecol. 2002; 19:158-64. Epub SSB/La autoantibodies: detection and treatment of first-degree
2002/03/06. atrioventricular block. Curr Opin Rheumatol. 2009; 21:478-82.
178. Ebenroth ES, Cordes TM, Darragh RK. Second-line treatment Epub 2009/07/09.
of fetal supraventricular tachycardia using flecainide acetate. 193. Hutter D, Silverman ED, Jaeggi ET. The benefits of
Pediatr Cardiol. 2001; 22:483-7. Epub 2002/03/15. transplacental treatment of isolated congenital complete
179. Hahurij ND, Blom NA, Lopriore E, et al. Perinatal management heart block associated with maternal anti-Ro/SSA
and long-term cardiac outcome in fetal arrhythmia. Early Hum antibodies: a review. Scand J Immunol. 2010; 72:235-41.
Dev. 2011; 87:83-7. Epub 2010/11/27. Epub 2010/08/11.
180. Lopriore E, Aziz MI, Nagel HT, et al. Long-term 194. Friedman DM, Kim MY, Copel JA, et al. Prospective
neurodevelopmental outcome after fetal arrhythmia. Am J evaluation of fetuses with autoimmune-associated congenital
Obstet Gynecol. 2009; 201:46 e1-5. Epub 2009/04/07. heart block followed in the PR Interval and Dexamethasone
181. Schleich JM, Bernard Du Haut Cilly F, Laurent MC, et al. Evaluation (PRIDE) Study. Am J Cardiol. 2009; 103:1102-6.
Early prenatal management of a fetal ventricular tachycardia Epub 2009/04/14.
treated in utero by amiodarone with long term follow-up. 195. Jaeggi ET, Silverman ED, Laskin C, et al. Prolongation of the
Prenat Diagn. 2000; 20:449-52. Epub 2000/06/22. atrioventricular conduction in fetuses exposed to maternal anti-
182. Eliasson H, Wahren-Herlenius M, Sonesson SE. Mechanisms Ro/SSA and anti-La/SSB antibodies did not predict progressive
in fetal bradyarrhythmia: 65 cases in a single center analyzed heart block. A prospective observational study on the effects of
by Doppler flow echocardiographic techniques. Ultrasound maternal antibodies on 165 fetuses. J Am Coll Cardiol. 2011;
Obstet Gynecol. 2011; 37:172-8. Epub 2011/01/26. 57:1487-92. Epub 2011/03/26.
183. Horigome H, Nagashima M, Sumitomo N, et al. Clinical char- 196. Cuneo BF, Lee M, Roberson D, et al. A management strategy for
acteristics and genetic background of congenital long-QT fetal immune-mediated atrioventricular block. The journal of
82
syndrome diagnosed in fetal, neonatal, and infantile life: a maternal-fetal and neonatal medicine: the official journal of the
European Association of Perinatal Medicine, the Federation of
Asia and Oceania Perinatal Societies, the International Society
200. Pisoni CN, Brucato A, Ruffatti A, et al. Failure of intravenous
immunoglobulin to prevent congenital heart block: Findings
4
of Perinatal Obstet. 2010; 23:1400-5. Epub 2010/04/14. of a multicenter, prospective, observational study. Arthritis
FEtal Cardiology
197. Jaeggi ET, Nii M. Fetal brady- and tachyarrhythmias: new Rheum. 2010; 62:1147-52. Epub 2010/02/05.
and accepted diagnostic and treatment methods. Seminars 201. Ostensen M. Intravenous immunoglobulin does not prevent
in fetal & neonatal medicine. 2005; 10:504-14. Epub recurrence of congenital heart block in children of SSA/Ro-
2005/10/11. positive mothers. Arthritis Rheum. 2010; 62:911-4. Epub
198. Breur JM, Kapusta L, Stoutenbeek P, et al. Isolated congenital 2010/02/05.
atrioventricular block diagnosed in utero: natural history and 202. Friedman DM, Llanos C, Izmirly PM, et al. Evaluation of
outcome. The journal of maternal-fetal and neonatal medicine: fetuses in a study of intravenous immunoglobulin as preventive
the official journal of the European Association of Perinatal therapy for congenital heart block: Results of a multicenter,
Medicine, the Federation of Asia and Oceania Perinatal prospective, open-label clinical trial. Arthritis Rheum. 2010;
Societies, the International Society of Perinatal Obstet. 2008; 62:1138-46. Epub 2010/04/15.
21:469-76. Epub 2008/06/24. 203. Jaeggi ET, Fouron JC, Silverman ED, et al. Transplacental
199. Miyoshi T, Maeno Y, Sago H, et al. Evaluation of Transplacental fetal treatment improves the outcome of prenatally diagnosed
Treatment for Fetal Congenital Bradyarrhythmia. Circulation complete atrioventricular block without structural heart
Journal. 2012; 76:469-76. disease. Circulation. 2004; 110:1542-8. Epub 2004/09/09.
83
C hapter
Congenital Heart Diseases with

5 Duct-dependent Circulation
Smita Mishra, Sanjay Khatri
Introduction is natural elimination of the role of the PFO and PDA in a

newborn baby.
Congenital heart diseases (CHDs) with major structural
alterations like pulmonary atresia or transposition of great Embryology
arteries (TGA) are usually compatible with fetal life. However,
these defects have serious manifestations once a baby is born. Embryologically, the DA is a remnant of the distal sixth aortic
To comprehend innate abnormality in a baby born with a arch and connects at the junction of the MPA and the left
certain heart defect, one has to understand fetal circulation pulmonary artery (LPA) to the proximal descending aorta.
and its disparity from postnatal circulation, which is described The left subclavian artery arises from the descending aorta
in detail in Chapter 2. near this junction.1–2
The ductus arteriosus (DA) or Botallo duct, is a normal
structure in the mammalian fetus, that diverts about 80 to Natural History of Ductus arteriosus
90 percent of the right ventricular output directly to reach
into the descending aorta.1,2 The DA is a large vessel in In the natural history of postnatal ductus, spontaneous closure
the fetus and its size is equal to the main pulmonary artery is the rule. Normally, in healthy term infants, the functional
(MPA) and the descending aorta. Typically, only about 9 to closure of the DA occurs in about 15 postnatal hours. However,
10 percent of the right ventricular (RV) output passes through true anatomical closure, in which the ductus loses the ability
the pulmonary vascular bed and 30 percent of the total right to reopen, may take several weeks.1–4
atrial (RA) inflow directly enters into the systemic circulation Cassels et al defined the true persistence of the PDA when
via the patent foramen ovale (PFO) into the left side of the it persists in an infant beyond 3 months of age.5 The ductus
heart to enter the ascending aorta and get distributed in the closure occurs by abrupt contraction of the muscular wall of
upper part of the body. The circulation of a smaller volume the DA secondary to increase in the partial pressure of oxygen
of blood in pulmonary circulation results in smaller branch (PO2), with the commencement of the first breath. This was
pulmonary arteries.1–3 The fetal circulation can be considered demonstrated by multiple experiments in the 1940s and
as parallel with two intertwining shunts through PFO and DA. subsequently was confirmed in clinical studies. Although the
Furthermore, the fetus enjoys the freedom from commitment neonatal ductus appears to be highly sensitive to the changes
of arranging gaseous exchange by active brea thing efforts in the arterial oxygen tension, the actual reasons for the
and has parasitic dependence on the placenta and maternal closure or persistent patency are complex. It involves perinatal
circulation for the oxygen.1–3 manipulation of ductal musculature by the autonomic nervous
With the onset of birth, a fetus becomes an independent system and chemical mediators.1,2,5
newborn. With the first few breaths, the inflated lungs start
functioning independently. The pulmonary and the systemic Morphology and Physiology of Ductus
circulations are now two distinct entities. Systemic venous Arteriosus
blood reaches the pulmonary vascular bed via the right atrium,
right ventricle, and the pulmonary artery, while the pulmonary Normally, the ductus is a muscular artery, which shows
venous blood reaches the left side of the heart, so that it can morphological variation in accordance to the gestational age of
be distributed into the systemic circulation. Therefore, there the fetus. Few reports based on the histology demonstrated that
the duct had a minimal thickening of the internal elastic lamina dependent CHDs (DDCHDs) must be ruled out before 5
and media in the first 3 to 6 months. Remarkable changes were attempting closure of PDA.
seen in structure after the seventh month of gestation.6,7
congenital heart diseases with duct-dependent circulation

The patency of the arterial duct is ensured by the low Patent Ductus Arteriosus Dependent
oxygen content of the fetal blood and the vasodilating action Congenital Heart Diseases
of the prostaglandins, mainly due to the prostaglandin E2.8
Takizava et al published an article about the role of nitric Ductus-dependent lesions are a special group of CHDs,
oxide and prostaglandin on ductal patency in fetus.9 They which have life-threatening propensities. These are either
concluded that endogenous nitric oxide has a major role in isolated severe obstructive lesions like coarctation of aorta
regulating the patency of the DA in earlier fetal stages, while or critical pulmonary stenosis or they can be more complex
dilator prostaglandins may play a role in the near-term fetus (Table 2). These defects are responsible for life-threatening
(Table 1). The duct is vulnerable to antenatal administration hemodynamic effects. The two shunts, PFO and PDA play
of prostaglandin inhibitors like indomethacin or other non- a unique role, since they do not have effective valves and
steroidal anti-inflammatory drugs (NSAIDs) which can cause depending on the pressure of the adjoining chambers or great
premature duct closure in fetus.1,2,4,10 arteries, they can shunt blood in either direction. Only the
duct-dependent lesions will be discussed in this chapter.
Role of Prostaglandins in Patency of Ductus:
Historical Review34–38,41 Classification of Duct Dependent Congenital
Heart Diseases1,2,4,31,32
Coceani and Olley et al established that the dilation of the
ductus is possible by infusion of prostaglandin (PGE1) in fetal The duct-dependent CHDs can be divided into three categories
lambs.19 The PGE1 was beneficial in opening the ductus and (Table 2, Figures 1A to C):
raising the systemic arterial oxygen saturation in neonatal
patients with duct-dependent congenital heart defects.22–24
Duct-dependent Pulmonary Circulation
Prolonged administration of PGE1 infusion provides a window
period before going for the surgical creation of a palliative The lungs are underperfused in these babies. The patent
systemic to pulmonary artery anastomosis or total correction. ductus diverts the partially saturated systemic blood towards
Clyman et al demonstrated that the PGE1 is effective as a duct the pulmonary circulation to improve the overall saturation.
dilator, even in the presence of normal arterial oxygen tension. Rarely, a widely open duct may raise the PaO2 above 49 mm
Subsequently, prostaglandins were used successfully to Hg. Therefore, the concentration of oxygen, to start ductal
achieve ductal patency in babies with interrupted aortic arch constriction, is seldom achieved by oxygen supplementation. It
and coarctation of aorta.26–27 In a study involving 56 centers, is observed that in babies with pulmonary atresia, who survive
PGE1, was used in 492 infants with ductus-dependent for several days or weeks, the PaO2 remains in the range of
CHDs. PGE1 provided effective palliation for the 385 35 to 40 mm Hg. It is not known whether it is related to this
infants out of which 107 babies were acyanotic and had left- physiological balance or whether it is due to poor development
sided obstructive lesions.28 Clinical improvement occurred of the ductus, so that it cannot accommodate a higher flow. The
in about 80 percent in both cyanotic and acyanotic babies. severely hypoxic babies who have very low pulmonary blood
In the infants with aortic coarctation and interruption, flow, are the least benefitted by oxygen administration.4,31
descending aortic blood pressures increased and the pressure Furthermore, the administration of 100 percent oxygen only
differences across the DA decreased markedly.28 increases the dissolved oxygen level. It is most unlikely that
According to McNamara, the period of 1946 to 1982 saw these babies can have their PaO2 level to the threshold level for
the revolution in pediatric cardiac care due to the evolution ductal constriction (Table 2 and Figure 1A).31
of the methods to keep open the PFO and PDA. Successful
medical manipulation of PDA also became the routine practice
Duct-dependent Systemic Circulation
in the same period.29
Obstructive left-sided lesions are responsible for the decreased
Dilemma of Managing Patent Ductus Arteriosus perfusion to the body. In the condition like critical aortic
in Sick Newborn Units stenosis, a generalized low perfusion pressure prevails leading
to hypoperfusion and acidosis of the vital organs including
Usually, babies born before achieving the desired gestational the brain and kidney. The aortic stenosis leads to pressure
age have patent ductus. These preemies have early congestive overload of the heart. The neonates of this group, who have
heart failure and become symptomatic. The prostaglandin PFO and duct, clinically present with hepatomegaly and right
inhibitors can be used to treat them medically. Some of ventricular dominance. The duct in such cases becomes not
them may need catheter or surgical intervention. The duct- only a decompressing channel, but also provides volume and 85
1 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.1,2,4,12–17
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.8–29
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.1–4,9
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 Possibly oxygen, via adenosine triphosphate (ATP) route, induc-
constriction es 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 anti- These agents are cyclo- Can cause premature ductal closure in fetus. Have therapeutic role
inflammatory drug (NSAID) oxygenase (COX 1 and in medical closure of duct in preterm newborns with PDA.1,2,4
2) inhibitors. Act as duct
constrictor.
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/ May have some supportive The role is not well defined.4
mono-oxygenase metabolite role in ductal constriction
86 of arachidonic acid induced by NSAID or O2
5

A B
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 Lesions which will depend on the flow Lesions where the systemic and
via the ductus arteriosus to maintain via the ductus arteriosus to maintain pulmonary circulations are separated so
pulmonary circulation (Figure 1A) systemic circulation (Figure 1B) that mixing site is needed (Figure 1C)
Pulmonary atresia with or without Critical aortic stenosis Transposition of the great arteries.
ventricular septal defect (VSD)
Critical pulmonary stenosis Coarctation of the aorta
Tricuspid atresia Interruption of aortic arch
Tetralogy of Fallot (severe form) Hypoplastic left heart syndrome
Few selected cases of Ebstein’s anomaly
of the tricuspid valve
perfusion pressure for the whole body. Echocardiographic reflected by the heightened blood pressure in the upper limb
evaluation shows characteristic reverse filling of the arch and and the head. This differential response of blood pressure is
ascending aorta. primarily due to the renal response to hypoperfusion. The
In interrupted aortic arch and severe coarctation of aorta, opening of the duct in such situations would provide perfusion
the perfusion is less in the lower part of the body and it is volume and pressure for the lower extremities. Furthermore, 87
1 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.30,33–35 The chemical
manipulation keeps the duct patent giving enough
opportunity to stabilize the baby before surgery, but it also Figure 2: Effect of hypoxemia in duct-dependent CHD31
makes patient vulnerable for unbalanced Qp : Qs and its
tribulations (Figure 1B and Table 2).
a. Modest rise in heart rate unlike in adults, where
Duct in Transposition Physiology: A Site for Mixing tachycardia is the rule.
b. ‘Hypoxic hypometabolism’ leading to decreased oxygen
Transposition of great vessels with intact ventricular septum consumption and core temperature.
is a common cyanotic CHD. In this condition, the aorta gets c. Lactic acidemia.
connected to right ventricle and pulmonary artery to the left d. Onset of hypoglycemia: Occurs secondary to increase in
ventricle leading to parallel circulation, where the systemic anaerobic glycolysis and can cause additional problem
venous blood would reenter into the systemic artery, bypassing of energy supply.
the lungs. Similarly, pulmonary venous blood evades systemic e. The PaCO2 does not rise. It can be related to the fact
circulation and reenters into the pulmonary artery. It leads to that CO2 readily diffuses across the alveolar-capillary
high oxygen saturation in the pulmonary arterial blood and membrane. Lactic acid metabolism is depressed and
severe systemic hypoxemia. A good sized PFO or atrial septal hence production of CO2 at tissue level is less.
defect is required to accomplish the proper mixing of blood The relative insensitivity of peripheral chemoreceptor in
at the atrial level. The balloon atrial septostomy in a tertiary the early postnatal period probably explains the fact that the
cardiac care center provides a non-surgical palliation for sick infants with cyanotic CHD with marked hypoxemia and who
neonates. However, ductus helps in oxygenation by redirecting do not have significant increase in respiratory efforts, do not
desaturated aortic blood towards the lungs. It also provides have bradycardia and may appear comfortable.
site for mixing, as bidirectional shunting occurs in presence
of pulmonary arterial hypertension.4,31,32 A restrictive PFO Differential Diagnosis1–4,30
may scuttle the advantage of patency of the duct in some cases
(Figure 1C and Table 2). We know that DDCHDs are associated with systemic
desaturation and central cyanosis. The central cyanosis can
EFFECT OF HYPOXEMIA SECONDARY TO DUCTAL be present clinically in conditions like persistent pulmonary
CONSTRICTION IN DUCT-DEPENDENT congenital hypertension of the newborn (PPHN), primary pulmonary
heart diseases30–31 disease, sepsis and methemoglobinemia. Many other
conditions can simulate DDCHDs like choanal atresia,
The mechanism responsible for the response to hypoxemia are Pierre Robin sequence, vascular ring, diaphragmatic hernia,
complex and the effects are the result of interacting influences acyanotic CHDs with shunt reversal, chest infections, neonatal
(Figure 2). The main mechanisms involved are: sepsis, hypothermia and hypoglycemia.
1. Chemoreflex responses.
2. Hormonal effects. Clinical Presentation
3. Direct local vascular responses.
4. Baroreflex response. The infants with duct-dependent circulation have imminent
88 The peculiarities of neonatal response to hypoxemia are: risk of life-threatening events. These events usually coincide
Table 3
 5
Clinical examination, X-ray chest and electrocardiogram (ECG) findings in duct-dependent congenital heart diseases (CHDs)1–4

Diagnosis Clinical findings X-ray chest ECG
Hypoplastic left heart Single S2, ↑breathing effort, Pulmonary arterial markings are ↓LV force usually, develops RAE,
syndrome ↓pulse amplitude, ↓perfusion, increased, cardiomegaly RAD
+/– SM
Transposition of great Split S2 +/–, murmur +/– ↑Pulmonary arterial markings, Develops RAE, RAD, RVH
arteries (IVS, VSD) +/– cardiomegaly with narrow
mediastinum (i.e. ‘egg on a
string’)
Tricuspid atresia Single S2, PSM/ESM ↓Pulmonary arterial Left axis deviation/LVH
with PS markings, +/– cardiomegaly
Tetralogy of Fallot
with severe PS Single S2, ESM +/– boot-shaped heart Develops RAE, RAD, RVH
or PA Single S2 continuous murmur, ↓ Pulmonary arterial markings
Left sternal edge, back and axilla and heart size
Pulmonary atresia Single S2, continuous murmur in ↓ Pulmonary arterial markings QRS axis 0° to 80°, RV forces may
intact ventricular axilla, back, front be absent
septum
Coarctation of aorta Feeble or absent lower limb ↑Heart size, Pulmonary venous RVH , LVH or Biventricular
pulses, decreased lower limb hypertension, pulmonary edema hypertrophy
blood pressure, soft ESM in
back +/–, click and S3 +/–,
differential cyanosis, shock like
picture mimicking sepsis
Critical aortic stenosis Shock like picture, poor pulses Heart size,
↑ QRS axis corresponds to +90 and
and perfusion, ESM +/-, click +/-, pulmonary edema +100 LVH, T-wave abnormalities
S3, single S2
Critical pulmonary ESM, click, single Normal or ↓ QRS axis 0° to 90°,
stenosis S2, most have pulmonary arterial develops RVH
cyanosis markings, RAE
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 to the morbidity and mortality. Hence a detailed examination
babies often present in the first few days of life with incremental and parental counseling is required.
cyanosis. The neonatal cyanosis becomes more conspicuous
due to their higher hemoglobin levels. The central cyanosis Management
is dependent on absolute concentration of deoxygenated Hb
and is more than 3 grams/L in arterial blood and more than 5
Assessment
grams/L in capillary blood. A polycythemic neonate with Hb
of >20 grams/L will have evident cyanosis at the saturation of The general condition of babies with DDCHD is so critical
85 percent. On the contrary a neonate with Hb of 8 grams/L that urgent resuscitation and stabilization becomes the
will show it only when saturations falls below 70 percent. Also primary goal. Nevertheless, once baby is stable one must try
babies with higher fetal Hb level will have late visible cyanosis. to confirm the diagnosis in the following steps:
Very sick babies usually have cyanotic spell or congestive heart 1. Confirmation of presence of central cyanosis: First of
failure and circulatory collapse without clinical cyanosis. An all, central cyanosis must be confirmed by monitoring
inaudible murmur must not be criteria for exclusion of CHD in saturation with pulse oximetry (PO) and subsequently with
these patients and some times, the deterioration of the clinical arterial blood gas analysis. A sample from the right radial
condition with disappearance of murmur is a pointer for an artery is preferable. Monitor pre- and postductal oxygen
urgent intervention. The patient may have additional clinical saturations. If there is a difference of saturation in upper
features. There is a probability of involvement of multiple and lower limb of more than 3 to 7 percent, the chances
organs like kidney, brain or skeletal system, which may add up of having ductal flow from the pulmonary artery to aorta 89
1 are high. In first few hours, differential saturation may be Without PO, discharge of apparently healthy infants with
fallacious due to high pulmonary artery pressure and patent unknown CHD was 5.5 times and 4.1 times more likely in
duct. cyanotic CHD and all serious CHD, respectively.
2. Applying hyperoxia test: The test is based on the

principle that in the absence of fixed cardiac shunts, 100 Pulse Oximetry: Implications of Differential
percent oxygen will increase alveolar PO2, leading to an Pre- and Postductal Saturation
increase in pulmonary venous and systemic arterial PO2.
In cyanotic CHD (e.g. decreased pulmonary blood flow or Pulse oximetry should be documented at preductal and
TGA), little or no rise in PaO2 would be expected after postductal sites to assess for differential or reverse differential
breathing 100 percent O2 (Table 4). However, the same cyanosis. If the preductal saturation is higher than the post-
finding may occur in infants with significant pulmonary ductal saturation (3 to 7% difference), differential cyanosis
hypertension, if significant right-to-left shunting persists exists. Oxygenated blood from the pulmonary circulation
through extrapulmonary shunts (ductus arteriosus and enters the descending aorta through PDA. In Sweden the use
foramen ovale). of PO and clinical examination led to an increased sensitivity
The baby must be kept in 100 percent oxygen for 10 of 82.8 percent and specificity of 100 percent for the duct-
minutes. Before and after the oxygen inhalation, an arterial dependent lesions.35
blood gas analysis must be done and saturations must be
tested. Usually the PO2 in arterial blood gas (ABG) is the best Goals of Management30–33
parameter to interpret the hyperoxia test, but many centers
may not be having facilities for ABG analysis (Table 5). One 1. To establish the diagnosis after initial stabilization, resusci-
can see for the rise in saturation by 10 to 20 percent and this tation with or without ventilator support.
can give a clue about the diagnosis. 2. Intubation is indicated when baby presents with apnea,
Validity of Use of Pulse Oximetry in Routine Table 5


Target arterial blood gas (ABG) analysis in hypoplastic left heart
Screening for Congenital Heart Disease34 syndrome38
Ten studies (44,969 newborns, 71 severe defects) evaluating pH* 7.25–7.35
the usefulness of neonatal PO screening in timely detection of PaO2* 35–45 mm Hg
CHD, were reviewed. PO showed a high specificity (99.99%)
PaCO2* 35–45 mm Hg
and the overall rate of detection of 15 individual defects with
PO was 72 percent (range 46–100%), exceeding that of the Target saturation 75–85%
clinical examination, 58 percent (9–86%). Similar results Fraction of inspired oxygen (FiO2) can be kept as low as 21 percent. If
were obtained for cyanotic CHD (89% vs 69%, respectively). saturation is < 70 percent then FiO2 can be increased. Avoid hyperventilation
and alkalosis.
Table 4

Interpretation of the hyperoxia test30–32
PaO2 (mm Hg) at FiO2 = 0.21 PaO2 (mm Hg) at FiO2 = 1.00
PaCO2 (mm Hg)
(% saturation) (% saturation)
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
#Cardiac disease
*Parallel circulation < 40 (< 75) < 50 (< 85) 35
**Mixing with restricted PBF < 40 (< 75) < 50 (< 85) 35
***Mixing without restricted PBF 40–60 (75–93) < 150 (< 100) 35
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 75–85%) will be observed when the PaO2 falls below 50 mm Hg. In contrast, if the baby has
90 mostly fetal hemoglobin, central cyanosis may not be observed, until the PaO2 drops 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.
shock or circulatory collapse, severe metabolic acidosis. f. The babies with transposition physiology are severely 5
Intubation in HLHS is done, if evidence of pulmonary hypoxemic and may have PO2 < 20 mm Hg, high PCO2
overcirculation are present like arterial saturation more in the absence of lung causes and severe metabolic

than 90 percent and systemic hypoperfusion. acidosis. They can be treated with emergency balloon
3. To minimize the hypoxemia: atrial septostomy and PGE1 infusion.1–4
a. Prostaglandin infusion: Prostaglandins have established 4. Finally, blood samples must be sent for blood counts, Hb,
role in maintenance of ductal patency. Prostaglandin E1 CRP, culture, electrolytes, sugar, urea, crea
tinine, liver
and E2 both can open up the closing duct. Routinely enzymes and screening for metabolic disorders to identify
PGE1 is used for pharmacological palliation of duct the co-morbid conditions.
dependent neonate (Table 6).8–29
b. To increase the fraction of inspired oxygen (FiO2) once CYANOTIC NEONATES WITH SPECIAL ISSUES
ductal patency is maintained. Moreover, PCO2 levels
should also be optimized between 35 to 45 mm Hg, with
Hypoplastic Left Heart Syndrome: Special Challenges of
or without ventilation, to achieve the balance between
Qp : Qs. (Table5)30–33
Preoperative Management
c. One must not try to achieve complete abolition of The HLHS is a fatal disease, with 90 percent of patients dying
cyanosis and a saturation of 75 to 85 percent can be within the first month of life without some sort of intervention.
adequate to avoid tissue hypoxemia and eventual lactic This is the group where special management strategies are
acidosis.30–33 Monitoring of babies on prostaglandin needed to control hyperoxia. A patient with mild to moderate
infusion is shown in Tables 6 and 7. restriction at PFO may have left atrial hypertension and hence
d. Intravenous fluid resuscitation, 10 ml/kg isotonic pulmonary venous and arterial hypertension leading to little
saline or colloid and then optimization of fluid therapy check on pulmonary overflow and hyperoxia. The group of
according to the status. If hemoglobin is less than 12 HLHS with no or severe restriction of PFO may present with
gm% blood transfusion can be given to improve the circulatory collapse and shock and might need resuscitation
oxygen carrying capacity. and medical or catheter intervention. The biggest task in
e. By maintaining the acid-base balance, one can correct a baby with HLHS is to keep the balance between the Qp :
acidosis. It has been established that PO2 less than Qs. Prostaglandins, vasoconstrictor drugs, oxygen inhalation,
32 mm Hg can be associated with severe metabolic all will decrease pulmonary vascular resistance and increase
acidosis due to hypoxemia at tissue level and onset of pulmonary blood flow (PBF) at the expense of systemic
anaerobic metabolism, which further deteriorates the circulation.
oxygen uptake and its release at tissue level. It also
leads to fall in core temperature, as thermogenesis is Strategies to Keep Qp : Qs Low36–40
affected. As we know that therapeutic goals vary in the
three categories of duct-dependent circulation, a fine 1. By keeping FiO2 low (21%).
tuning of systemic and pulmonary vascular resistance 2. By increasing PaCO2. It is well known that CO2 is a
must be achieved with the customized use of ventilatory potent pulmonary vasoconstrictor and it can be increased
parameters, vasodilators and vasoconstrictors. by giving supplemental inspired PaCO2. This approach
Table 6

Prostaglandin–doses, preparation, monitoring37
Drug Doses Preparation Monitoring

Prostaglandin E1 Starting dose: 0.05–0.1 500 µg in vial (1 ml) dissolved in 49 ml During the infusion close monitoring
Vial :1 ml (500 mcg/kg/min of 5% dextrose to make concentration of heart rate, oxygen saturation, blood
mcg) Maintenance: 0.002–0.05 10 µg/ml. In most infants, the ductus will pressure, respiratory rate, and core
mcg/kg/min reopen within 30 minute to 2 hour after body temperature is required.
starting PGE1. Once the ductus has a. Stable infants on PGE1: Side effects
opened, the maintenance doses can be like apnoea, profound bradycardia,
started. 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
1 Table 7

Side effects of prostaglandins48–56
Side effects Detailed description

Apnea Usually dose related. Less common if dose is < 0.01 mcg/kg/min.
Hyperthermia Occurs in 10–14% 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
Necrotizing enterocolitis In preterm, prolonged and higher doses > 0.5 mcg/kg/min
Hyperostosis 50–60%, if PGE2 used for prolonged period
Gastric outlet obstruction In 6–7% (after prolonged use)
Intimal tears within the pulmonary arteries and changes in These changes may be dose related, occurring more frequently
vessel muscularity. Aneurysmal dilatation and vessel wall when higher infusion rates are used to maximize pulmonary blood
edema flow
for increasing PaCO2 is preferred over hypoventilation, Ebstein’s anomaly is optimally stabilized on prostaglandin to
which may lead to atelectasis. It has been demonstrated support pulmonary blood flow. As PVR falls, a trial of wean-
that the hypercapnic acidosis (HCA) increases oxygen ing from prostaglandin must be done and the clinical pattern
delivery by 44 percent. Furthermore, there is evidence that of response must be assessed. Usually surgical management
HCA is a lung protective strategy that preserves pulmonary strategies are based on tricuspid valve regurgitation and de-
mechanics, attenuates lung protein leakage, reduces gree of cyanosis. If cyanosis alone is the dominant symptom, a
pulmonary edema and improves oxygen delivery in an systemic to pulmonary artery shunt alone is performed.
animal model of lung injury. However, when poor right ventricular function in association
3. PVR can be increased by decreasing the concentration of with severe tricuspid regurgitation is present, right ventricular
inspired oxygen and by adding supplemental nitrogen gas exclusion by patching the tricuspid valve is the best option.
to attain a FiO2 of 17 to 19 percent. Additionally, PVR can This is one condition where actively pulmonary vasodila-
also be increased by maintaining the hematocrit greater tation is attempted, if weaning of PGE1 fails. Trial of nitric
than 40 percent, a state that optimizes oxygen-carrying oxide has been attempted in many centers. Sildenafil also was
capacity and increases the viscosity of the blood. tried successfully in few case reports.45
Newborn with Severe Ebstein Anomaly of Tricuspid Total Anomalous Pulmonary Venous Connection:
Valve: Issue of PGE1 Infusion41–45 Effect of Prostaglandins46–48
The Ebstein anomaly is not only a tricuspid valve disease, but Routinely, cyanotic CHDs with severe hypoxemia can be put
also disease of the right ventricle and right atrium, or right heart on prostaglandin infusion without any harm before sending
disease. Of all neonates with the diagnosis of Ebstein anomaly, them to a tertiary cardiac care center, when facility for
20 to 40 percent will die in a month. Like in HLHS, the pre- echocardiography is not available and exact diagnosis cannot
surgical and surgical management of critically ill neonates and be made. However, there are some concerns regarding its use
young infants with Ebstein anomaly remains challenging. The in total anomalous pulmonary venous connection (TAPVC)
problems which can influence the overall outcome are diminu- espcially the obstructed type. PGE1 could produce adverse
tive and dysfunctional right ventricle, severity of tricuspid re- effects by two mechanisms:
gurgitation, severity of right ventricular outflow obstruction, 1. By increasing the cyanosis and hypoxemia of systemic
size of pulmonary arteries, severity of pulmonary hypertension circulation: When the pulmonary arterial pressure is higher
92 and dysfunctional left ventricle. The symptomatic neonate with than that in the aorta, dilatation of the DA may result in
an increase in right-to-left shunt and would increase in the systemic circulation, a ductal stenting or high-risk modified 5
degree of cyanosis. Norwood procedure is expected. In transposition physiology,
2. By direct pulmonary vasodilatation leading to altered Qp : if baby fails to stabilize, a balloon atrial septostomy could be

Qs: Usually it might be expected that the ductus response the first interventional procedure before the switch operation.
to PGE1 would predominate and cyanosis may be expected All of these methods, have some procedure related morbidity
to worsen. and mortality, as well as financial implications. The neonatal
Very rarely PGE1 has an ameliorating effect on infradia- transport from remote parts of India also has significant risk.
phragmatic TAPVC by relaxing the ductus venosus and thus Hence, besides securing intubation, central and peripheral
relieving the obstruction. line, prostaglandin, dextrose, electrolytes, fluid infusions,
temperature optimization, antibiotics coverage, one needs to
PROSTAGLANDIN E1: SIDE EFFECTS do detailed parental counseling before transporting the baby.
Prostaglandins are great rescuers for babies with duct- INTERVENTION IN DUCT DEPENDENT congenital
dependent circulation. However, PGE1 infusion is not totally heart diseases: DUCTAL STENTING
safe. The problems are associated with gestational age and
type of lesions. Mc Elhinney et al followed-up 643 babies With growing interest in catheter interventions and persistent
with complex congenital anomaly and they found 3.3 percent high mortality related to shunt surgery, efforts were made to
incidence of necrotizing enterocolitis and it showed high explore the new possibilities to maintain the ductal patency.
correlation with prematurity and little higher PGE1 infusion Moreover, arterial duct stabilization with a high-flexibility
rate (> 0.5 mcg/kg/min).51 There is risk of apnoea requiring coronary stent is an effective alternative in high-risk surgical
ventilation particularly in premature, low-birth-weight (LBW) candidates or whenever short-term pulmonary blood flow
newborn.48–56 support is anticipated. It seems highly logical to try to keep
the duct open rather than going for a surgical alternative
Transport of a Baby with Duct-dependent with prosthetic material. We know prostaglandins are highly
Congenital Heart Disease38,57 effective at maintaining duct patency medically in the short
term. They become less reliable and have more side-effects if
Early diagnosis and optimization of blood biochemistry, given long-term. Ductal stenting at cardiac catheterization was
adequate oxygenation, if required ventilation and prostaglandin first described in the early 1990s.58 Even though technique of
infusion to maintain the adequate Qp : Qs ratio is important. stenting has not changed appreciably in the past 15 years, stent
In tetralogy of Fallot (TOF) physiology, usual goal in a case and balloon technology is becoming better. With the future
of duct-dependent pulmonary circulation is to do modified advancement and training, one can think of better outcome of
Blalock-Taussig shunt or ductal stenting. In duct-dependent this promising and life-saving procedure (Table 8).
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 (3–6 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 93
heart surgeon (Level of Evidence: C).
1 Advantages of Ductal Stenting and radial force. The stent characteristics like larger metallic
cross-sectional area, thicker struts, and smaller cell area give
1. Eliminating the need for neonatal palliative surgery. good scaffolding with limited tissue prolapse. However, these
2. Reducing the number of operations required. properties reduce the flexibility and conformability of the
3. Optimizing the time of definitive surgical correction. stent, and are known to enhance in-stent restenosis rate in
coronary arteries. Balloon redilatation or additional stent can
Procedure59,60 be deployed to avoid residual stenosis. The radial force and
side-branch accessibility are no issue for a stent deployed in the
Ductal stenting is done in the catheterization laboratory under arterial duct. A thin but complete layer of endothelium forms
general anesthesia. Angiography is done to demonstrate the over the stent as early as 1 month. Neoendothelial proliferation
anatomy and to measure the length of the arterial duct. IV plays an important role in duct-dependent pulmonary blood
heparin (50 U per kg) must be given. Cefazolin 30 mg per kg flow. There could be gradual fall in oxygen saturation as the
is administered prior to stent implantation, followed by another duct becomes compromised by neoendothelium.
two doses at the interval of 8 hours. Prostaglandin infusion can Alwi and colleagues demonstrated that PDA stent
be stopped several hours before the procedure, so that duct can accelerates pre-existing stenosis of the pulmonary arteries,
have grip over stent. Prostaglandin inhibitors can be used in primarily in the LPA. They concluded that the stent metal
selected cases. grid provokes intense neointimal proliferation and fibrosis in
The antegrade approach through femoral vein or retrograde the ductal tissue encircling the pulmonary arteries.60 Because
approach through femoral artery can be used. For antegrade the pulmonary artery implants at the LPA origin, the higher
approach in a case of pulmonary atresia, perforation of incidence of stenosis in this branch can be explained by the
pulmonary valve would be required. concomitant effect of the pulmonary coarctation and the
The procedure for stent implantation has to be individuali neointimal hyperplasia. Fortunately there are attempts to evolve
zed, since origin and morphology of the duct varies in novel technologies. The innovative methods like rapamycin-
different CHDs. In patients with pulmonary atresia with coated drug eluting stents have been experimented in newborn
intact interventricular septum, the approach can be either pigs successfully.
antegradely through the pulmonary artery after the perforation The palliation obtained from ductal stenting, is less reliable
of atretic valve or it can be done retrogradely. In patients with and of shorter duration than that expected from a surgical
pulmonary atresia with VSD also, the approach has to be either aortopulmonary shunt. In HLHS, a more complex hybrid
antegrade or retrograde. For better support during delivery of approach (selective pulmonary artery bandings without
the stent, a 4F long sheath (Mullin) can be used. After entering cardiopulmonary bypass followed by percutaneous PDA stent
pulmonary artery, by using an end-hole catheter, a 0.014 implantation and balloon dilation of the atrial septum) was done
coronary wire is introduced via arterial route to cross the DA. by Akinturk et al in 2002 with little better results.61 However,
Over this wire, the delivery system with the coronary stent duct stenting in HLHS as a part of combined procedure, is still
may be advanced into the duct. After confirming the correct an unpredictable and technically demanding procedure and not
position of the stent across the duct, the balloon is inflated in recommended as Class I indication.
order to deploy the stent. Post stenting, anticoagulation and
prevention and management of the restenosis are important.
Bioengineering in Duct Patency
Acetylsalicylic acid, 1 to 3 mg/kg/day, is started for as long as
stent patency is required. Stent restenosis can be treated with Transfection is the delivery of DNA, RNA, proteins, and
ballooning and restenting. 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
Modifiers for Success of the Procedure59–61
for closure of the duct, the gene for a fibronectin 'decoy'
The success of procedure depends on the type and length of was introduced directly in utero in the ductal tissue to keep
PDA, type of stents and experience of operator. A stented duct is ductal patency in animal experiments. Percutaneous postnatal
more comparable with a central shunt, which has no restriction transfection of gene for PG in ductal tissue also ensured
at the aortic end. Usual size of surgical shunt in neonate is 3 prolonged patency of duct. These and several other projects
to 4 mm. The final lumen within the stent, will depend on the are underway to get the safest technique to keep duct open.2
stent diameter at the time of implantation. The diameter of
lumen decreases by contraction of the vessel wall leading to Conclusion
tissue prolapse through the stent struts. This process starts after
few hours of stent placement. Further decrease in size of lumen Duct-dependent congenital heart diseases are life-threatening
is secondary to endothelial hyperplasia. The stent’s design and cardiac emergencies and need to be recognized as early as
94 material determines the cross-sectional area, strut thickness possible. Medical intervention with prostaglandin infusion
provides time for referral and planned definitive repair. Many 15. Elliot RB, Starling MB, Neutze JM. Medical manipulation of
patent ductus arteriosus. Lancet. 1975; 1:140-2.
5
babies need to be supported with inotropes and ventilation,
which needs to be customized according to the type of 16. Heymann MA, Rudolph AM, Silverman NH. Closure of

lesion. Ductal stenting can obviate need for shunt surgery. the ductus arteriosus in premature infants by inhibition of
prostaglandin synthesis. N Engl J Med. 1976; 295:530-3.
Mostly such babies can undergo successful cardiac corrective
17. Silove ED. Pharmacological manipulation of the ductus
intervention at an appropriate time. arteriosus; Archives of Disease in Childhood. 1986; 61:827-29.
18. Nadas AS. Patent ductus revisited. N Engl J Med. 1976; 295:
They do certainly give very strange, and new fangled, names 563-5.
to diseases. 19. Coceani F, Olley PM. The response of the ductus arteriosus to
—Plato prostaglandins. Can J Physiol Pharmacol. 1973; 51:220-25.
20. Silove ED, Coe JY, Shiu MF, et al. Oral prostaglandin E2 in
References ductus dependent pulmonary circulation. Circulation. 1981;
63: 682-88.
1. Rudolph AM. The Ductus arteriosus and Persistent Patency 21. Silove ED, Roberts DGV, Giovanni JVD. Evaluation of oral
of the Ductus Arteriosus, in Congenital Diseases of the Heart: and low dose intravenous prostaglandin E2 in management of
Clinical-Physiological Considerations. Futura publishing ductus dependent congenital heart disease. Archives of Disease
house, UK. 2001:155-96. in Childhood. 1985; 60:1025-30.
22. Elliott RB, Starling MB, Neutze JM. Medical manipulation of
2. Benson LN. The arterial duct: its persistence and its patency.
the ductus arteriosus. Lancet. 1975; 1:140-42.
In Paediatric Cardiology, Third edition. Anderson RH, Baker
23. Heymann MA, Rudolph AM. Ductus arteriosus dilatation by
EJ, Penny DJ, Redington AN, Rigby ML, Wernovsky G (Eds).
prostaglandin E1 in infants with pulmonary atresia. Pediatrics.
London: Churchill Livingstone; 2010:875-93.
1977; 59:325-9.
3. Gray H. Peculiarities in the Vascular System in the Fetus. Gray’s
24. Heymann MA, Berman W Jr, Rudolph AM, et al. Dilatation
Anatomy of the Human Body, 20th edition. Philadelphia: Lea
of the ductus arteriosus by prostanglandin E1 in aortic arch
and Febiger; 1918.
abnormalities. Circulation. 1979; 59:169-72.
4. Corbet AJ. Medical manipulation of the ductus arteriosus.
25. Lang P, Freed MD, Rosenthal A, et al. The use of prostaglandin
In: Garson Jr A, Bricker JT, Fisher DJ, Neish SR (Eds) The
E1 in an infant with interruption of the aortic arch. J Pediatr.
Science and Practice of Pediatric Cardiology. 2nd edition. Vol 1977; 91:805-07.
II.Williams & Wilkins, Baltimore. 1998; 2489-2513. 26. Freed MD, Heymann MA, Lewis AB, et al. Prostaglandin E1
5. Cassels DE, Bharati S, Lev M. The natural history of the in infants with ductus arteriosus-dependent congenital heart
ductus arteriosus in association with other congenital heart disease. Circulation. 1981; 64:899-904.
defects. Perspect Biol Med. Summer. 1975; 18:541-72. 27. McNamara DG. Twenty-five years of progress in the medical
6. Melka J. Beitrage Zur Kenntnis der, Morphologic and treatment of pediatric and congenital heart disease. Journal of
Obliteration des Ductui Botalli. Anatomical Anzeles. 1926; 61: the American College of Cardiology. 1983; 1:264-73.
348-61. 28. Robin H, Steinhorn MD. Evaluation and management of the
7. Mujahid BM, Gaikwad PG. A Study of Histology of Human cyanotic neonate, Clin Pediatr Emerg Med. 2008; 9:169-75.
Ductus Arteriosus—Before and After Birth. J Anat Soc India. 29. Rudolph AM. Oxygen uptake and delivery. In Congenital
2000; 49:3-5. Diseases of the Heart: Clinical-Physiological Considerations.
8. Coceani F, Bodach E, White E, Bishai I, Olley PM.Prostaglandin Futura publishing House, UK. 2001; 85-119.
I2 is less relaxant than prostaglandin E2 on the lamb ductus 30. Marino BS, Fine KS. Cardiology. In Blueprints Pediatrics
arteriosus. Prostaglandins. 1978 ; 15:551-6. (Blueprints Series) 3rd edition. Marino BS, Fine KS, McMillan
9. Takizawa T, Kihara T, Kamata A, et al. Role of nitric oxide in JA (Eds). Blackwell publishing 2004; 16-26.
regulating the ductus arteriosus caliber in fetal rats. J Vet Med 31. Costello JM, Franklin WH. Preoperative and postoperative care
Sci. 2000; 62:707-10. of infants with critical congenital heart diseases. In Avery’s
10. Coceani F, White E, Bodach E, et al. Age-dependent changes neonatology: pathophysiology and management of the newborn
in the response of the lamb ductus arteriosus to oxygen and 6th edition. MacDonald MG, Seshai MMK, Mullett MD (Eds).
ibuprofen. Can J Physiol Pharmacol. 1979; 57:825-31. Lippincott Williams & Wilkins, Philadelphia, USA. 2005; 710-
11. Hammerman C, Aramburo MJ, Bui KC. Endogenous dilator 767.
prostaglandins in congenital heart disease. Pediatr Cardiol. 32. Valmari P. Should pulse oximetry be used to screen for
1987; 8:155-59. congenital heart disease? Arch Dis Child Fetal Neonatal Ed.
12. Clyman RI, Heymann MA, Rudolph AM. Ductus arteriosus 2007; 92:F219-F24.
responses to prostaglandin E1 at high and low oxygen concen- 33. Granelli A, Wennergren M, Sandberg K, et al. Impact of
tration. Prostaglandins. 1977; 13:219-23. pulse oximetry screening on the detection of duct dependent
13. Olley PM, Coceani F, Bodach E. E type prostaglandins. A congenital heart disease: a Swedish prospective screening
new emergency therapy for certain cyanotic congenital heart study in 39,821 newborns. BMJ 2009; 338:a3037.
malformations. Circulation. 1976; 53:728-31. 34. Liske MR, Aschner JL. Counterpoint: hypoxia is not the
14. Clyman RI, Sangstad D, Mauray F. Reactive oxygen optimal means of reducing pulmonary blood flow in the
preoperative single ventricle heart. J Appl Physiol. 2008;
metabolites relax the lamb ductus arteriosus by stimulating 95
prostaglandin production. Circ Res. 1989; 64:1-8. 104:1836-8.
1 35. Wernovsky G, Ades AM, Spray TL. Management of congenital
heart diseases in low birth weight infants; In Avery’s Diseases
49. McElhinney D, Hedrick H, Bush D, et al. Necrotizing
enterocolitis in neonates with congenital heart disease: risk
of the Newborn, 8th edition. Taeusch HW, Ballard RA, Glea- factors and outcomes. Pediatrics. 2000; 106:1080-87.
son CA (Eds), Elsevier 2004; 888-895. 50. Lewis AB, Freed MD, Heymann RA, et al. Side effects of
36. Shan F, Shekerdemian L, Millar J, et al. Early management of therapy with prostaglandin E1 in infants with critical congenital
infants with hypoplastic left heart syndrome. Hhs. 2008. doc; heart disease. Circulation. 1981; 64:893-98.
http://www.rch.org.au/emplibrary/picu/HLHS.pdf. 51. Sone K, Tashiro M, et al. Long-term low dose prostaglandin
37. Day RW, Barton AJ, Pysher TJ. Pulmonary vascular resistance E1 administration. J Pediatr. 1980; 97:866-67.
of children treated with nitrogen during early infancy. Ann 52. Kaufman MB, El-Chaar GM. Bone and tissue changes following
Thorac Surg. 1998; 65:1400-4. prostaglandin therapy in neonates. Ann Pharmacother. 1996;
38. Dessardo S, Ahe V. Preoperative management of hypoplastic 30:269-74,277.
left heart syndrome. SIGNA VITAE. 2009; 4:12-15. 53. Peled N, Dagan O, Babyn P, et al. Gastric-outlet obstruction
39. Kinouchi K, Okawa M, Fukumitsu K. Perioperative manage- induced by prostaglandin therapy in neonates. New Engl J
ment of two neonates with severe Ebstein’s anomaly with pul- Med. 1992; 327:505-10.
monary atresia. Masui. 2000; 49:1274-7. 54. Heffelfinger S, Hawkins EP, Nihill M, et al. Pulmonary vascular
40. Jaquiss RD, Imamura M. Management of Ebstein’s anomaly changes associated with prolonged prostaglandin E1 treatment.
and pure tricuspid insufficiency in the neonate. Semin Thorac Pediatr Pathol. 1987; 7:165-73.
Cardiovasc Surg. 2007; 19:258-63. 55. Transfer of Babies with Duct Dependent Congenital Heart
41. Bove EL, Hirsch JC, Ohye RG, et al. How I Manage Neonatal Disease. Neonatal transfer service. NHS. http://www.neonatal.
Ebstein’s Anomaly. Semin Thorac Cardiovasc Surg Pediatr org.uk/documents/1457.pdf.
Card Surg Ann. 2009; 12:63-65. http://cardiopedhnn. 56. Rosenthal E, Qureshi SA, Kakadekar AP, et al. Comparison
comfypage.com/site/UserFiles/Ebstein-Neonatal-Sx.pdf. of balloon dilation and stent implantation to maintain patency
42. Pham P, Hoyer A, Shaughnessy R. A Novel Approach Incorpo- of the neonatal arterial duct in lambs. Am J Cardiol. 1993;
rating Sildenafil in the Management of Symptomatic Neonates 71:1373-76.
with Ebstein’s Anomaly. Pediatric Cardiology. 2006; 27:614- 57. Gewillig M, Benson LN. Stenting the Neonatal Arterial Duct
17. in Duct-Dependent Pulmonary Circulation: New Techniques,
43. Aggarwal S, Chintala K, Humes RA. Sildenafil use in a Better Results. J Am Coll Cardiol. 2004; 43:107-12.
symptomatic neonate with severe Ebstein’s anomaly of the 58. Djer MM, Alwi M. Stent implantation into ductus arteriosus:
tricuspid valve. Am J Perinatol. 2008; 25:125-28. a new alternative of palliative treatment of duct-dependent
44. Chang AC, Burke RP. Anomalous pulmonary venous connec- pulmonary circulation. Paediatrica Indonesiana. 2004;
tion. In Pediatric cardiac intensive care, Chang AC, Hanlay 44(1-2).
FL, Wernovsky G, Wessel DL (Eds). Williams and Wilkins, 59. Boucek MM, Mashburn C, Kunz E, Chan KC. Ductal anatomy:
Toronto. 1998; 223-28. a determinant of successful stenting in hypoplastic left heart
45. Bullaboy CA, Johnson DH, Ajar H. Total anomalous syndrome. Pediatr Cardiol. 2005; 26:200-5.
pulmonary venous connection to portal system: A new role for 60. Alwi M. Initial results and midterm follow-up of stent
prostaglandin E1. Pediatric Cardiology. 1984; 5:115-16. implantation of patent ductus arteriosus in duct dependent
46. Product information. Prostin VR Pediatric. The Up John pulmonary circulation. J Am Coll Cardiol. 2004; 44:438-45.
Company; Kalamazoo, MI. January 1995. 61. Akinturk H, Michel-Behnke I, Valeske K, et al. Hybrid
47. Host A, Halken S, Kamper J, et al. Prostaglandin E1 treatment transcatheter-surgical palliation: basis for univentricular or
in ductus dependent congenital cardiac malformations: a biventricular repair: the Giessen experience Pediatr Cardiol
review of the treatment of 34 neonates. Dan Med Bull. 1988; 2007; 28:79-87
35:81-84. 62. Feltes TF, Bacha E, Beekman RH, et al. Indications for Cardiac
48. Kramer HH, Sommer M, Rammos S, et al. Evaluation of Catheterization and Intervention in Pediatric Cardiac Disease:
low dose prostaglandin E1 treatment for ductus dependent A Scientific Statement From the American Heart Association
congenital heart disease. Eur J Pediatr. 1995; 154:700-07. Circulation. 2011; 123:2607-52.
96
C hapter
Genetics in
Sridevi Hegde, Mitesh Shetty
The first reference in history to the presence of congenital techniques.3,4 Therefore, the number of adults with a CHD
heart disease (CHD) comes from a Babylonian tablet, which is on the rise. Once these patients enter the reproductive age
dates back to around 4,000 BC. The description mentions; group, knowledge of heritability of such defects is essential.
“When a woman gives birth to an infant that has the heart Isolated congenital heart defects are most frequently sporadic.
open and has no skin, the country will suffer from calamities”, Despite the sporadic nature, a genetic component is still very
which might refer to ectopia cordis (Figure 1). likely to contribute to the occurrence of these defects and there
Leonardo da Vinci, was the first to describe a congenital is a higher recurrence risk among siblings and offspring of
heart defect in humans in his Quaderni de Anatomia.1 patients with CHD.5,6 CHD, being a complex trait, is thought
Congenital heart disease is the leading cause of infant to be multifactorial.7 Even though, extensive knowledge of the
morbidity in the western world, but only in the past 10 years its genetic control of cardiogenesis in animals is available, this
etiology has been understood. Recent studies have uncovered has not been translated into an equivalent amount of clinical
the genetic basis for some common forms of the disease and knowledge of the genetic determinants of CHD in humans.
provide new insight into how the heart develops and how
dysregulation of heart development leads to disease.2 In this EmbryoloGy
day and age, about 85 to 95 percent of the children with CHD
survive into adulthood due to better surgical and non-surgical Congenital heart diseases arise from abnormal heart develop-
ment 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
Figure 1: Ectopia cordis posterior components (such as the atria).9
1
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
Human genetic studies have identified numerous genes allele have similar cardiac abnormalities to those seen in 6
that are responsible for inherited and sporadic congenital heart Holt–Oram syndrome, with septal defects and atrioventricular
diseases. Most of these genes encode transcription factors (AV) conduction block.12,14 Mouse TBX20 is expressed in the
GENEtics iN coNGENital hEart DisEasEs

that regulate specific events in heart development, such as cardiac crescent, and in some cells of the SHF. In the heart
ventricular septation or outflow tract morphogenesis. A core set tube, it is expressed in myocardium and in endothelial cells
of evolutionarily conserved transcription factors (NK2, myocyte associated with the endocardial cushions; this latter expression
enhancer factor 2 [MEF2], GATA, TBX and HAND) control persists with further development, as myocardial expression
cardiac cell fates, the expression of contractile protein-encoding weakens. TBX20 interacts directly with TBX5, NKX2-5, and
genes and cardiac morphogenesis.10 In turn, these transcription GATA4.14 TBX20 null mouse embryos have hypoplastic,
factors regulate one another and many other transcription factors unlooped hearts. Expression of TBX20 is required for normal
are involved. Of these, MEF2 is the key myogenic transcription levels of NKX2-5 expression.16 Notch signalling pathway,
factor, involved in the differentiation of all types of myocyte. In NOTCH1 is expressed in the endocardium of the great vessels
turn, it is under regulation by NK2 homeobox genes, particularly of the heart, where it is thought to be important for epithelial
tinman in Drosophila and its orthologous in mammals. The to mesenchymal transition and valve formation. Individuals
homeodomain factor NKX2-5 is a key transcription factor in with NOTCH1 mutations have a spectrum of defects, including
cardiac development.11 It is expressed in cardiac progenitor cells AS, ventricular septal defect (VSD), Tetralogy of Fallot (TOF)
of both the first and second heart fields. Expression continues in and, in one patient, mitral atresia, double outlet right ventricle
the primary heart tube and in the looping heart, in the outflow (DORV) and hypoplastic left ventricle. NOTCH1 also represses
tract, ventricles, common atrium and the proximal horns of a bone related pathway, which might explain calcifications in
the sinus venosus. Expression continues in muscular layers of the cardiac valves of patients with NOTCH1 mutations.2
the heart throughout the remainder of embryogenesis and into
postnatal and adult life.12 The absence of NKX2-5 is catastrophic EtioloGy
to heart development in the mouse embryo, resulting in complete
failure of cardiac morphogenesis, chamber formation and Most of the congenital heart defects are sporadic. The major
outflow tract development. NKX2-5 acts as a part of pathway, genetic cause for congenital heart defects includes the following:
in which it physically interacts with a set of other transcription a. Chromosomal disorders and single gene disorders
factors to activate target genes. For example, the zinc finger constituting eight percent.
transcription factor GATA4 (one of a group of genes named b. Two percent of environmental teratogens.
because their protein products bind to the nucleotide sequence c. Ninety percent multifactorial disorders.17
GATA) physically interacts with NKX2-5. When coexpressed, Multifactorial means both genetic and environmental
their effect on the transcription of some cardiac genes is factors interact, to interfere with the development of the heart.
synergistically augmented.12 GATA4 protein is regulated by Increased incidence of CHDs has been noted with intrauterine
other co-transcription factors including the friend of GATA (Fog) viral infections, maternal drug and alcohol consumption
proteins. GATA4 null mouse embryos have severely disrupted during first trimester of pregnancy and pregnancy-induced
cardiac development, with failure to form the primitive heart tube systemic maternal disease.18
among other severe developmental abnormalities.13
The T-box genes are a group of transcription factors, which Chromosomal Aberration
share a highly conserved 180 a-amino acid DNA-binding
domain called the T-box.14 Of the seven or more T-box genes The association of CHDs with chromosomal anomalies
expressed in the developing human heart, TBX1, TBX5 varies between 4 to 12 percent.19 The following are common
and TBX20 have been implicated in human CHD. TBX1 is chromosomal abnormalities associated with CHD.18,20
important in the SHF and subsequently the outflow tract,
consistent with its role as the major determinant of the cardiac Trisomy 21 (Down Syndrome)
phenotype in velocardiofacial syndrome (characterized by
conotruncal malformations).15 Down syndrome is also known as trisomy 21 because of the
There is evidence that TBX5 functions as part of the extra copy of chromosome 21. It was first described by John
NKX2-5 pathway.12,16 Mouse TBX5 associates directly with Langdon Down in 1866. It is the most common cause of
NKX2-5 and GATA4, synergistically stimulating chamber- human birth defects. It is associated with a delay in cognitive
specific genes in later stages of cardiac development. TBX5 ability, physical growth and a particular set of facial features.
is specifically expressed in the FHF, at the cardiac crescent At least 40 percent of children with Trisomy 21 will have
stage and later in the primary heart tube. TBX5 null mouse heart disease; furthermore, 50 percent of those children
embryos are severely dysmorphic and fail to undergo cardiac with heart abnormalities will specifically be affected with
looping. Interestingly, mice heterozygous for a TBX5 null atrioventricular septal defect (AVSD) (Figures 3A to D).
99
1
a b
c D
Figures 3a to D: Baby with Down syndrome and karyotype of Trisomy 21
Trisomy 18 (Edward Syndrome) meningomyelocele, cleft palate, polydactyly, overlapping

fingers, omphalocele, mental deficiency and CHD (Figures
Edward syndrome was first described by John H Edward in 4A and B). Common CHDs include atrial septal defect (ASD),
1960. This is the second most common autosomal aneuploidy VSD, patent ductus arteriosus (PDA) and cardiac malpositions
after Down syndrome. Majority of the fetus carried to the especially dextrocardia (6%).
term will be stillborn. Common features of trisomy 18
are strawberry-shaped head, microcephaly, micrognathia, 45, X (Turner Syndrome)
clenched hand, crossed leg, rocker bottom feet, renal problem,
mental deficiency and CHD. Common CHDs include VSD, Association between short stature and abnormal ovarian
AVSD, double outlet right ventricle and hypoplastic left heart. development was described by Rossle in 1922. This was
explained with webbed neck and cubitus valgus by Turner in
Trisomy 13 (Patau Syndrome) 1938. It is a chromosome abnormality in female, where one
of the sex chromosome is missing. Common CHDs include
Patau syndrome was first observed by Thomas Bartholin in VSD, coarctation of the aorta (COA), bicuspid aortic valve,
1657 but chromosomal defect was confirmed by Dr Klaus hypoplastic left heart, mitral valve prolapse and idiopathic
Patau in 1960. It is associated with holoprosencephaly, aortic root dilatation.
100
6

a b
Figures 4a and b: A. Baby with Trisomy 13 and B. Karyotype Trisomy 13
Tetrasomy 22q (Cat Eye Syndrome) Tetrasomy 12p (Pallister–Killian Syndrome)

Usually the result of additional copy of chromosome 22, Pallister-Killian syndrome is due to extra isochromosome
triplicate or quadruplicate of the critical region 22 pter→q11. It 12p, which is seen mainly in skin fibroblast. It is characterized
is characterized by coloboma of iris and anal atresia. The CHDs by hypotonia, skin pigmentary changes, diaphragmatic defect,
association is found to be 30 percent in patients with total mental deficiency and CHD. The CHDs association is found
anomalous pulmonary venous drainage as a major problem. to be in 25 percent of the patients that includes VSD, COA,
One of the patient at the time of anomaly scan showed PDA, ASD and aortic stenosis (AS).
marked hypoplasia of both ears with preauricular ear tags and
moderate degree of micrognathia (Figure 5). Detailed fetal Chromosome Deletion Syndrome
echocardiography showed slight discrepancy in the cardiac
ventricles. Based on this ultrasonography (USG) finding,
Deletion 22q11.2 Syndrome (OMIM: 611867)
amniocentesis was carried out, which revealed tetrasomy 22q
(Figures 6 and 7). After genetic counseling, the couple opted Deletion 22q11.2 syndrome comprises of three major
to terminate the pregnancy. Postnatal examination of the fetus syndromes: DiGeorge syndrome (DGS), Velocardiofacial
confirmed the ultrasound findings and in addition there was syndrome (VCFS) and conotruncal anomaly face syndrome
anal atresia. (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
1 be at least 1 in 4,000–6,000 livebirths, but this might be an
underestimation as many cases with mild features may remain
undiagnosed.21–23
In 1965, DiGeorge described a patient with hypoparathy-

roidism 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,
Figure 7: Mosaic trisomy 22q and tetrasomy 22q
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
Figure 8: Microdeletion of 22q11 region FISH report has been reported. Hypotonia in infancy is frequent. Speech
102 a b
Figures 9a and b: DiGeorge syndrome. A. Mother and B. Child
6

a b
Figures 10a and b: Children with Williams syndrome
development is often delayed and impaired with almost Wolf–Hirschhorn Syndrome (OMIM: 194190)
always hypernasal voice. Additionally, affected children are
more likely to have attention deficit hyperactivity disorder Wolf–Hirschhorn syndrome is due to deletion of the terminal
(ADHD) and developmental disorders such as autism that segment of chromosome 4p (Figures 12A and B). There is
affect communication and social interaction. Hypocalcemia an increased incidence of cleft lip, palate, seizures and heart
may present with seizure activity, but responds promptly to disease (30%).
replacement therapy and becomes less apparent with age. The
immune deficit also resolves with time and is often less evident Alagille Syndrome (OMIM: 118450)
than in the original case. Later in life, they are at an increased
risk of developing mental illnesses such as schizophrenia, Alagille syndrome is characterized by prominent forehead,
depression, anxiety and bipolar disorder. A variety of cardiac deep set eyes, thin nose, butterfly vertebrae, arcus juvenilis
malformations are seen particularly affecting the outflow with pulmonary artery stenosis (Figure 13). It is caused by
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.
Williams Syndrome (Williams–Beuren 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 103
from a specific region of chromosome 7q11.23 (Figure 11). Figure 11: Microdeletion at 7q11 FISH report
1
a 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 Holt–Oram Syndrome (OMIM: 142900)
Holt–Oram 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)

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.
104 It is caused by mutation of EVC gene, which is linked to
Figure 14: Hypertelorism, short-webbed neck, and low hairline
in a child with Noonan syndrome chromosome 4p16.
6

a b
Figures 15a and b: Holt–Oram syndrome familial ASD. A. Child with Holt–Oram 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)

Pompe disease is an inborn error of metabolism and is caused
by an accumulation of glycogen in the lysosome due to 105
Figure 17: Child with Ellis-van Creveld syndrome deficiency of the lysosomal acid alpha-glucosidase enzyme.
1 There is accumulation of glycogen in certain organs and NKX2–5 (omim: 600584) NK2 Homeobox 5/CSX
tissues. It is manifested as hypotonia, generalized muscle
weakness, feeding difficulties, failure to thrive, cardiomegaly Homeobox genes have been found to play a crucial
and hypertrophic cardiomyopathy. role in regulating tissue specific gene expression. The
cardiac homeobox protein NKX2-5 is essential in cardiac
Zellweger Syndrome (OMIM: 214100) development and mutations in CSX (cardiac-specific
homeobox which encodes NKX2-5) cause various congenital
Zellweger syndrome is characterized by hypotonia, high heart malformations. The earliest molecule marker of the
forehead, flat facies, hepatomegaly and CHDs like PDA cardiac lineage is NKX2-5 in vertebrates. It is one of the
and septal defect. It is caused by defects in number of PEX members of NK2 family of homeobox genes and a homolog
genes. of the Drosophila tinman.25 It has highly conserved regions
of DNA binding, protein-protein interactions, nuclear
Smith–Lemli–Opitz Syndrome (OMIM: 270400) translocation, and regulation of other transcription factors.
Their homeodomains have a tyrosine at position 54,
Smith–Lemli–Opitz syndrome is characterized by severe making it the most unambiguous feature of this class and
learning disability, failure to thrive, cleft palate, bitemporal is a useful classification tool.26 Mutations in this gene have
narrowing, anteverted nares and syndactyly. Fifty percent been reported to cause ASD, VSD with atrial ventricular
will have CHDs like AVSD or ASD. It is due to severe block, TOF and tricuspid valve abnormalities. Mutations in
defect in cholesterol biosynthesis resulting in deficiency this gene can also cause congenital hypothyroidism, non-
of 7-dehydrocholestrol reductase (DHCR7) gene, which is goitrous type 5, a non-autoimmune condition.27
mapped to chromosome 11q12–13. Turbay and group28 mapped the CSX gene to chromosome
5q35, close to the junction with band 5q34.
GEnES ASSoCiAtED witH CHD Pauli and group29 described a distal 5q deletion, with
karyotype del(5)(q35.1q35.3), in a 7½-year-old girl who, in
Most of the isolated congenital heart defects do not show addition to ASD and PDA, had ventricular myocardial non-
a typical Mendelian inheritance pattern, but as mentioned compaction. Fluorescent in situ hybridization (FISH) analysis
earlier a genetic component is very likely to contribute showed that this deletion included the locus for CSX. Thus,
(Table 1). they suggested that some instances of ventricular myocardial

table 1
Genes causing different types of CHDs with their chromosomal region in humans18
Gene Chromosome locus Type of defects
ASD, VSD, AV block, TOF, Ebstein malformation and

CSX / NK-X2-5 5q35
Tricuspid valve abnormalities
GATA4 8p22–23 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;
106 HLHS = Hypoplastic left heart syndrome; PDA = Patent ductus arteriosus; TOF = Tetralogy of Fallot; VSD = Ventricular septal defect
non-compaction may be caused by haploinsufficiency of mice, germline ablation of the gene encoding GATA4 results 6
CSX. They reviewed four other cases with deletions in the in abnormal ventral folding of the embryo, failure to form a
same region of 5q and pointed out that two of them had atrial single ventral tube and lethality. Besides heart development,

septal defects and one had a cardiomyopathy. Gibbons and GATA4 is involved in the formation of multiple organs, such
associates30 presented an infant girl with an interstitial deletion as intestine, liver, pancreas and swim bladder in zebrafish
of chromosome bands 5q33 to 5q35 inherited from a maternal as well as gastric epithelial development in mouse through
interchromosomal insertion ins(8;5)(p23; q33q35), which was interaction with factor of GATA (Fog) cofactors.36 The
confirmed by FISH. She had increased tone, microcephaly, mutation in GATA4 gene diminishes DNA-binding affinity
short neck, apparently low-set ears, micrognathia, campto- and transcriptional activity. GATA4 is capable of synergizing
dactyly, mild rocker bottom feet and hammer toe. Cardiac with other transcription factors such as NKX2-5, dHAND and
anomalies included a large VSD, PDA pulmonary hypertension TBX5 to activate cardiac-specific gene expression.
and hypoplastic right ventricle. Schafer and group31 described There are published deletions involving chromosome
two male sibs with partial monosomy of chromosome 5 8p23.1 range from large terminal deletions that are easily
[46,XY,der(5)inv ins(1;5)(p32;q35.4q34)]; maternally derived detectable by routine chromosome analysis and small
from a balanced insertion of 1 and 5 [inv ins (1;5) interstitial deletions that are best identified using FISH or
(p.32;q35.4q34)]. One sibling had microcephaly, cleft lip and molecular techniques such as array comparative genomic
palate, facial anomalies, ASD and VSD, camptodactyly the hybridization (aCGH). Lubs and Lubs described37 first case
4th and 5th fingers and developmental delay. The other sibling of an individual with a partial deletion of distal chromosome
showed microcephaly, facial anomalies, ASD, hypotonia, arm 8p and CHD. Bröcker-Vriends and group38 described
primary optic nerve hypoplasia and developmental delay. Both two patients with partial monosomy of the short arm of
had only one copy of the cardiac specific homeobox CSX gene. chromosome 8. The chromosomal abnormality of partial
Schiffer and group32 described a boy with complex heart monosomy of 8p was initially not considered. They stressed
defect, club feet, adducted thumbs and facial dysmorphic upon the importance of cytogenetic investigations in all infants
features. Karyotype identified an abnormal chromosome 5q with major congenital heart defect and facial dysmorphism or
suspected to be an interstitial deletion (5)(q33q35). Breakpoints microcephaly or both.
of the deleted segment were confirmed as del(5)(q33.3q35.2) Devriendt and group39 reported the prenatal diagnosis at
by multicolor FISH using two sets of combinatorially labeled 30 weeks of gestation of a del(8)(p21.3→pter) in a growth-
band specific yeast artificial chromsome (YAC) clones. retarded fetus with an unbalanced AVSD and a hypoplastic
Baekvad-Hansen and group33 described a 15-year-old boy right ventricle. Pehlivan and group40 provided evidence that
with Ebstein anomaly, ASD, AV conduction defect and GATA4 may be involved in the etiology of some congenital
microcephaly. He had an apparently balanced paracentric heart defects. They performed FISH analysis using a GATA4
inversion of chromosome 5, with the karyotype 46, XY, probe on five patients with interstitial deletions of 8p23.1.
inv(5) (q13q35) de novo. Further mapping of the chromosome Hemizygosity for GATA4 was seen in the four patients with
breakpoints using FISH revealed a 2.2 Mb microdeletion at CHD but not in the patient without known cardiac anomalies.
the 5q35 breakpoint, which spans 16 genes, including the The authors proposed that haploinsufficiency of GATA4 may
cardiac homeobox transcription factor gene NKX2-5. They contribute to the CHD observed in some patients with del(8)
also suggested presence of a new microcephaly locus within a (p23.1).
2.2 Mb region at 5q35.1-q35. 2. Rauch and Dorr34 described a Reddy41 described a case with del(8)(p23.1) in amniocyte
larger terminal deletions including chromosomal bands 5q35. culture with normal cardia. Similar deletion was revealed in
1 and 5q35. 2 cause a more severe phenotype significant CHD, father’s karyotype. The karyotype from the prenatal case was
microcephaly, profound developmental retardation or early compared with the previous four cases of 8p23.1 deletions in
death due to respiratory failure. A heart defect is explained by his laboratory to see if there was a discernible difference in
haploinsufficiency of the NKX2-5 gene at 5q35.1. the size of the deletion. The deletion in the proband seemed to
Bjørnstad and Leren35 have identified a mutation in the involve a more distal 8p23.1 breakpoint. In the father's high
NKX2-5 gene on chromosome 5q35 responsible for autosomal resolution chromosomes (550–850 band level), the breakpoint
dominantly inherited ASD in the oval fossa combined with appeared to be 8p23.1 approximately 23.2 and FISH studies
disturbances of AV conduction in seven patients spanning four using an 8p telomeric probe confirmed a terminal deletion.
generations. Interstitial deletion of sub-band 8p23.1 was associated with
phenotypic abnormalities and distal 8p23.2→pter deletion
GATA4 (omim: 600576) was found in apparently normal individuals, therefore, 8p23.1
appears to be the critical region for clinical abnormalities.
GATA4 is a transcription factor which is characterized by a Bhatia and group42 reported the prenatal diagnosis, at 18
highly conserved binding domain of two zinc fingers. It is week gestational age of a del(8)(p23.1→pter) in a fetus with
expressed in the heart and is essential for mammalian cardiac an AV canal, persistent left superior vena cava and hypoplastic 107
development, localized to chromosome region 8p23.1. In right ventricle detected by sonographic imaging. Some of the
1 common features reported with partial monosomy of 8p include hypoparathyroidism and three with DGS) and one patient
growth and mental retardation, impulsive and aggressive with VCFS and a large interstitial deletion. FISH analysis
behaviour, congenital cardiac defects, diaphragmatic hernia demonstrated that these patients had overlapping deletions at
and in males, genital abnormalities. Devriendt and group43 the 10p13/10p14 boundary. They concluded that the results
have performed genotype-phenotype correlations in nine strongly support the hypothesis that haploinsufficiency of a
unrelated patients with a de novo del 8p. In five patients, a gene or genes within 10p (DGSII locus) can cause the DGS/
uniform interstitial deletion of approximately 6 Mb in 8p23.1 VCFS spectrum of malformations.
was detected. One patient carried a large terminal deletion Schuffenhauer and group52 performed FISH and
encompassing this commonly deleted region. All these polymerase chain reaction (PCR) analyses in 12 patients with
patients have a similar phenotype, with a CHD, microcephaly, 10p deletions, nine of them with features of DGS and in a
mild developmental delay, intrauterine growth retardation, familial translocation 10p;14q associated with midline defects.
and a characteristic behavioral phenotype. Features that have The critical DGS2 region was defined by two DGS patients
been recognized more recently are a characteristic behavioral and mapped within a 1-cM interval including D10S547 and
phenotype, hypospadias, and seizures.44 The del(8p) D10S585. The other seven DGS patients were hemizygous
phenotype often is relatively mild, without associated facial for both loci. The breakpoint of the reciprocal translocation
dysmorphism or other major internal malformations.45-47 10p;14q mapped at a distance of at least 12 cM distal to
They defined an 8p heart defect—critical region spanning a the critical DGS2 region. Interstitial and terminal deletions
10-cM segment defined distally by D8S1706 and proximally described in these patients were in the range of 10 to 50 cM
by D8S1759 and they suggested the transcription factor and enabled the tentative mapping of loci for ptosis and hearing
GATA4 as a candidate gene. loss, features that are not part of the DGS clinical spectrum.
Giglio and group48 narrowed this region by studying Lichtner and group53 reported a new case with the high
12 del(8p) patients, including 6 new cases, 7 of whom had dynamic range (HDR) phenotype: hypoparathyroidism,
CHDs. Patients with 8p deletions distal to D8S1706, at deafness and renal dysplasia. They were found to have partial
approximately 10 cM from the 8p telomere, did not have monosomy for 10p due to terminal deletions with breakpoints
CHD, whereas patients with a deletion that included the more between D10S585 and D10S1720. By comparison with data
proximal region suffered from the spectrum of heart defects previously published on patients with DGS/VCFS associated
reported in patients with 8p distal deletions. The 5-cM critical with 10p monosomy, they concluded that this is a contiguous
region is flanked distally by D8S1706 and WI-8327, both at gene syndrome. Hemizygosity for a proximal region can cause
approximately 10 cM and proximally by D8S1825, at 15 cM. cardiac defects and T-cell deficiency; hemizygosity for a more
distal region can cause hypoparathyroidism, sensorineural
Second DiGeorge Syndrome locus (DGSii) deafness and renal dysplasia.
(omim: 601362) Berend and group54 tested 412 patients, 54 were found
to be deleted for the DGSI locus on chromosome 22 (13%),
The DiGeorge syndrome and velocardiofacial syndrome may and a single patient was found deleted for the DGSII locus on
present many clinical problems, including cardiac defects, chromosome 10 (0.24%). The patient with the 10p deletion
hypoparathyroidism, T-cell immunodeficiency and facial had facial features consistent with VCFS, plus sensorineural
dysmorphism. They are frequently associated with deletions hearing loss, and renal anomalies. Cytogenetic analysis
within 22q11.2, but a number of cases have no detectable showed a large deletion of 10p [46, XX,del(10)(p12.2p14)]
molecular defect of this region. Bourrouillou and group49 and FISH using a 10p telomere region-specific probe
described a case of monosomy 10p with microcephaly, confirmed the interstitial nature of the deletion.
antimongoloid slant of the palpebral fissures, low-set ears, Lichtner and group55 constructed a deletion map of partial
prominent anthelix, congenital heart disease and abnormalities monosomy 10p patients and narrowed the critical region
of the limbs. Schuffenhauer and group50 described a DGCRII to about 300 kb. The genomic draft sequence of this
20-month-old girl with DGS and a monosomy 10p13→pter region contains only one known gene, BRUNOL3 ( NAPOR,
and a trisomy 10q26→qter due to a meiotic recombination of CUGBP2, ETR3). In situ hybridization of human embryos and
a maternal inversion (10)(p13q26). The proposita's phenotype fetuses revealed as well as in other tissues a strong expression
demonstrates typical features of the del(10p) syndrome, of BRUNOL3 in thymus during different developmental
which include mental retardation, abnormally shaped skull, stages. BRUNOL3 appears to be an important factor for
hypertelorism, low nasal bridge, micrognathia, dysmorphic thymus development and is therefore a candidate gene for the
low set ears, short neck, foot abnormalities and cardiac defect. thymus hypoplasia or aplasia seen in partial monosomy 10p
Daw and group51 stated that a number of single case reports patients. Many patients with the mild end of the DGS/VCFS
with deletions of 10p suggested genetic heterogeneity of spectrum have been referred to the cytogenetics laboratory
DGS. They compared the regions of hemizygosity in four by the physicians for FISH for the deletion on 22q11.2 and
108 patients with terminal deletions of 10p (one patient with high resolution G-banded analysis has been requested for only
those patients with a more severe presentation, although the Greenberg and group62 observed partial monosomy due 6
most effective method for detecting all possible cytogenetic to an unbalanced 4;22 translocation in a two-month-old male
abnormalities would be to perform a complete chromosome with type 1 TA and features of DGS. The asymptomatic

analysis along with the FISH studies. Other chromosomal mother showed partial T-cell deficiency and the same
abnormalities can help in detecting new gene loci similar to unbalanced translocation with deletion of proximal 22q11.
all other genes, which were identified based on chromosomal The recognition of the importance of 22q11 deletion grew
abnormality. Even though the deletion on 10p is relatively rare with improving techniques. Greenberg and group63 found
deletions of DGSI and DGSII result in similar phenotypes, chromosome abnormalities in five of 27 cases of DGS, three
and hence, it is still beneficial to screen patients referred for with 22q11 deletion though only one of these was an interstitial
DGS and VCFS for both DGSI and the DGSII loci.54 deletion. Wilson and group64 reported high resolution banding
(more than 850 bands per haploid set) in 30 of 36 cases of
DiGeorge Syndrome locus (omim: 188400; 600237) DGS and demonstrated nine cases of interstitial deletion. All
other cases were apparently normal. Use of molecular dosage
Most cases of DGS result from a deletion of chromosome analysis and fluorescence in situ hybridization with probes
22q11.2 (DiGeorge syndrome chromosome region or DGCR). isolated from within the deleted area revealed deletion in 21
Several genes are lost including the putative transcription of the 22 cases with normal karyotypes65 giving pooled results
factor TUPLE1 (TUP-like enhancer of split gene-1), which is of 33 deleted among the consecutive series of 35 cases.
expressed in the appropriate distribution. Molecular biology Gowde and Patel66 screened families with congenital heart
studies revealed that approximately 90 percent of patients disease for chromosome 22 microdeletion; of the 105 patients
have a typically selected region of 3 Mb, which encompasses screened six had microdeletion.
an estimated 30 genes, whereas about 8 percent of patients The VCFS has an extremely expansive phenotypic
have a smaller nested deletion of 1.5 Mb, which encompasses spectrum. More than 180 clinical features, both physical and
24 genes.56 behavioral, have been described. No single clinical feature
Halford and group57 reported that TUPLE1 gene is an occurs in 100 percent of cases and there is no reported case of
attractive candidate for the central features of the syndrome. the syndrome that has all or even most of the clinical findings.
This putative transcription factor shows homology to the The phenotype therefore shows markedly variable expression.
yeast transcription factor TUP and to Drosophila enhancer The diagnosis is therefore defined by the deletion of DNA from
of split. It contains four WD40 domains and shows evidence chromosome 22 at the q11.2 band spanning the region that is
of expression at the critical period of development in the regarded as the critical region. Other molecular genetics tests
outflow tract of the heart and the neural crest derived aspects will clearly become widely available in the near future, such
of the face and upper thorax. Lamour and group58 isolated a as microarray analysis and Multiplex ligation dependent probe
cDNA that encodes a protein of 1,017 amino acids, designated (MLPA), but at the current time, FISH is widely available,
HIRA (histone cell cycle regulation defective, Saccharomyces relatively cost effective, and highly accurate.67
cerevisiae, homolog of, A) on the basis of its homology to Volpe and group68 reported 141 cases of malformations
the HIR1 and HIR2 transcriptional repressors of S. cerevisiae. of the outflow tracts or interrupted aortic arch (IAA) from
HIRA encompasses the entire TUPLE1 protein with an 1150 prenatal cases of heart defects diagnosed over a period
additional 207 internal amino acid residues and an extra 44 of 10 years. 22q11 microdeletion was detected in 28 out of
N-terminal residues, a result of an alternative start codon. 141 fetuses (19.8%). IUGR, additional aortic arch anomalies
Thus, TUPLE1 cDNA appears to represent a truncated version and thymic hypoplasia were significantly more frequent in
of the HIRA cDNA. Demczuk and group59 reported the fetuses with 22q11 microdeletion. Most often, intrauterine
isolation and cloning of a gene encoding a potential adhesion growth restriction (IUGR) appeared to be associated with the
receptor protein in the DGCR. They designated the gene worst prognosis. Prenatal ultrasound thymus examination,
DGCR2 and suggested DGCR1 as a symbol for the TUPLE1 showed 75 percent sensitivity and 94 percent specificity. The
gene. Haploinsufficiency of the TBX1 gene is also responsible combination of these two predictors, namely, thymus defects
for most of the physical malformations. There is evidence that and IUGR associated with additional aortic arch anomalies
point mutations in the TBX1 gene can also cause the disorder. was more than 90 percent sensitive and 100 percent specific.
De la Chapelle and group60 suggested that DiGeorge A wide variety of non-cardiac malformations such as overt
syndrome may be due to a deletion within chromosome 22 or cleft palate, renal and limb abnormalities, neural tube defects
partial duplication of 20p, based on finding the syndrome in and polyhydramnios are identifiable prenatally, and have
members of a family with a 20;22 translocation. Specifically, been reported to occur in association with 22q11.2 deletion
they observed DGS in four members of one family and syndrome.69,70 Few authors have raised the possibility of
demonstrated monosomy of 22pter-q11 and 20p duplication. considering prenatal 22q11.2 deletion studies in the event
Their interpretation that DGS might result from monosomy for of non-cardiac USG findings. In a recent review on genetic
22q11 was confirmed by Kelley and group61 in three patients counseling for 22q11.2 deletion syndrome, McDonald- 109
with translocation of 22q11-qter to other chromosomes. McGinn and Zackai71 argued that, such findings lead to
1 systematic prenatal diagnosis of aneuploïdies, the addition Flow chart 2: Genes on 22q11 and 22q13 regions
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
Source: Image from Kreatech website
leading to intrauterine growth retardation and congenital heart
malformation.78 Therefore, high-risk fetuses showing growth
retardation and malformation should receive screening for The genetic predisposition to cardiac malformation may be
22q11.2 microdeletion. FISH test of the key gene TUPLE1 is influenced by in utero environmental or genetic background.
still considered the gold standard for the diagnosis of 22q11.2 The importance of genetic factors in the cause of congenital heart
microdeletion syndrome.79 defects has been shown by previous studies.82,83 Microdeletion
Indian postnatal studies of chromosome 22 microdeletions of chromosomal region 22q11 is an important cause of
for isolated CHD showed the microdeletion in 6/105 selected conotruncal cardiac defects of the heart and account
(5.71%)80 and 4/23 (17%)81 patients. for about 6.9 to 68 percent of cases.84–88 Prenatal diagnosis
of chromosome 22q11.2 microdeletion by FISH analysis was
first reported in 1995.89 Since then, numerous studies have
Flow chart 1: Decisional chart proposal for prenatal 22q11.2 testing
according to ultrasound finding (US) and aneuploidy screening tests77
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
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
110 and Duchenne muscular dystrophy in 1964. Steele and Breg
very importantly demonstrated in their seminal paper in the and microglossia. It is therefore imperative that chorionic 6
Lancet in 1966 that cultured, amniotic fluid cells were suitable villus sampling is performed only after 11 weeks and before
for karyotyping.92 The year 1966 is an important milestone 15 weeks by appropriately trained operators.95

in prenatal diagnosis, as this year saw the introduction of
amniotic fluid cell culture. Geneticists could advise on the Amniocentesis
degree of risk and the avoidance of pregnancy, but it was an
evident that genetic counseling had little impact without fetal Amniocentesis is a prenatal procedure, in which small amount
diagnosis. The emergence of amniocentesis and amniotic of amniotic fluid, which contains fetal tissues, is extracted
cell culture for fetal chromosomal and metabolic disorders from the amnion or amniotic sac surrounding a developing
in 1966 changed this practice forever.93 In 1974, Hobbins fetus. Amniocentesis is performed between the 15 to 20
and Mahoney reported a technique for obtaining fetal weeks of pregnancy. Under aseptic precaution, with the aid of
erythrocytes for prenatal diagnosis of hemoglobinopathies.94 ultrasound guidance, a fetal medicine specialist punctures the
Important trends in practice are revealed by the survey, such sac in an area away from the fetus and extracts approximately
as the gradual change from transcervical to transabdominal 20 ml of amniotic fluid. Apart from a risk of miscarriage, there
chorionic villi sampling from 1982 to 1986. is a risk of infection, injury to the fetus and amniotic fluid
leakage. It is also possible at 10 to 14 weeks of gestation.
Chorionic Villi Sampling However, randomized studies have demonstrated that after
early amniocentesis the rate of fetal loss is about 2 percent
Chorionic villi sampling (CVS) is the removal of a small higher and the incidence of talipes equinovarus is 1.6 percent
part of placenta tissue (chorionic villi) from the uterus. CVS higher than after first-trimester CVS or second-trimester
can be done through the cervix (transcervical) or through the amniocentesis. Amniocentesis should not be performed before
abdomen (transabdominal) (Figure 19). The techniques are 15 weeks.95
equally safe, when done by an experienced fetal medicine
specialist, although miscarriage rates are slightly higher when Cordocentesis
done through the cervix. Prior to procedure, an abdominal
ultrasound is performed to determine the position of the Cordocentesis, also sometimes called percutaneous umbilical
uterus, the size of the gestational sac and the position of cord blood sampling (PUBS), is a highly specialized prenatal
the placenta within the uterus. Under aseptic precaution, test that examines blood from the fetal umbilical cord. An
the transabdominal procedure is performed by inserting a advanced imaging ultrasound determines the location for
needle through the abdomen and uterus into the placenta. needle insertion into the placenta and the needle is guided
Ultrasound is used to help guide the needle and a small through the mother’s abdomen and uterine wall into the
amount of tissue is drawn into the syringe. Apart from the fetal vein of the umbilical cord, where a fetal blood sample
risk of miscarriage, there is a risk of infection and amniotic is removed. It can be done at 18 week of pregnancy or
fluid leakage. Random studies have demonstrated that the rate later. This test carries a significant risk of complication and
of fetal loss following first-trimester transabdominal CVS is includes blood loss at the puncture site, infection, premature
the same as with second-trimester amniocentesis. There is rupture of membranes and the rate of fetal loss is higher than
an association between chorionic villus sampling, before 10 amniocentesis.96
weeks and fetal transverse limb abnormalities, micrognathia
Cytogenetics
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 ‘eras’—the
‘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 111
Figure 19: Transabdominal chorionic vill sampling. division. The ‘Hypotonic Era’—(started in 1952 by TC Hsu)
[Reproduced from counseling aids for geneticists, 3rd edn, GGC (1995)] denotes the use of a solution with a lower salt concentration
1 than the cells, it contains. This causes the cells to absorb the best possible amendment to the disorder in an affected
water through their membranes and swell (but not burst). member.101
The swollen cells allow the chromosomes to readily separate, During genetic counseling, emphasis is placed on respecting
making them easier to count. During the ‘trisomy period’: the experiences of the patients and/or family and on patient
Cytogeneticists discovered patients with an additional autonomy in decision making so that an informed decision is
copy of a small chromosome, e.g. Trisomy 21 (Down made. A psychotherapeutic component of genetic counselling
syndrome), Trisomy 13 (Patau syndrome) and Trisomy 18 is desirable as the occurrence of a genetic condition can have
(Edward syndrome). Numerical abnormalities involving a family-wide impact and the clinician or genetic counselor
sex chromosomes (the X and Y chromosomes) were also should provide acceptance and empathy, but should never
described for the first time and such as Turner syndrome ‘play God’. Genetic counselling should be non-directive,
and Klinefelter syndrome. Further advances in technology presenting all information to the patient in a non-judgmental
led to banding techniques (hence the ‘banding era’), which and neutral approach. This will enable the patient to make a
brought out horizontal bands of differential staining intensity. decision best suited to their situation.
The most recent developments in cytogenetics have led to In cases where congenital heart defects are picked up
the ‘molecular era’. Advances in the use of DNA probes prenatally, it is important to address the immediate concerns
have allowed cytogeneticists to hybridize these probes to of the couple. The most important issues to discuss during a
chromosomes and determine if a specific DNA sequence prenatal visit are accuracy of prenatal testing, risks of prenatal
is present on the target chromosome. This has been useful testing, recurrence risks for the couple and family and most
in detecting abnormalities beyond the resolution level of importantly, what to expect, when undergoing prenatal
studying banded chromosomes at the microscope, and also in diagnosis. It is easy to assume what needs to be addressed
determining the location of specific genes on chromosomes. during the session, however, it is important to identify
Recent advances in cytogenetic techniques made a valuable the expectations and issues, the patient is facing. In our
contribution toward the practice of modern medicine.97,98 experience, the least important issues during the initial genetic
The FISH is a molecular cytogenetics technique that allows counselling session with the couple are pregnancy termination
identification and detection of the gene of interest within its options, discussions as to whether the couple should have
natural environment of chromosomes, cells or tissues. The another child and other reproductive options. It is optimum if
basic principle involved in this technique is natural affinity of these issues are addressed during the follow-up session.
base pairing of nucleotide sequences with the complementary Testing in the form of prenatal diagnosis should be
sequences. Pardue and Gall99 reported the hybridization of offered for an etiological diagnosis and its implication in the
radioactive DNA probes for repetitive sequences to mouse management and prognosis of the condition. In cases where
and drosophila chromosomes. In 1981 Harper and Saundres the cardiac defect is not amenable to surgical correction, the
reported an improved technique for in situ hybridization investigations will help in providing information in the form
allowing detection of unique DNA sequence along human of recurrence risks for future pregnancies. In developing
metaphase chromosome spread.100 countries, where affordability of health care is an issue for
The FISH allows rapid analysis of chromosome copy number majority of the population, the genetic counselor should be
in interphase cells of amniotic fluid, chorionic villi, cord blood supportive of the couple’s decision to undergo termination
and peripheral blood samples. It has been extensively applied of pregnancy, where the long-term prognosis, in absence of
in cancer cytogenetics to confirm various translocations. It is appropriate medical intervention, is poor.
also used for detection of microdeletion (less than 5 million
base pairs size) syndromes like DiGeorge syndrome, Prader– SummAry
Willi Syndrome, etc. Various types of FISH probes such as
centromeric, α-satellite, locus specific, telomeric, subtelomeric Antenatally diagnosed cases of CHD should be investigated
and whole chromosome painting probes are available. for karyotyping and for 22q11.2 deletion syndrome. Increased
NT, IUGR and other non-cardiac malformations of 22q11.2
GEnEtiC CounSElinG deletion syndrome should be screened carefully for thymus
hypo or aplasia and fetal echo for cardiac defects including
Genetic counseling is a communication process to aid people vascular ring. Chromosome analysis along with the FISH
understand and adapt to the medical, psychological and studies to be carried out in patients with the DGS/VCFS
familial implications of genetic contributions to disease. This spectrum. Other chromosomal abnormalities can help in
process integrates the following-interpretation of family and detecting new gene loci similar to all other genes, which were
medical histories to assess the chance of disease occurrence identified based on chromosomal abnormality. Even though
or recurrence, understanding alternatives for dealing with the deletion on 10p is relatively rare deletions of DGSI and
recurrence risk, choosing a course of action best suited to the DGSII result in similar phenotypes, and hence, it is still
112 patient based on their values and family goals and to make beneficial to screen patients referred for DGS and VCFS for
DGSII loci, if DGSI is normal.54 Recent studies also suggest ACknowlEDGmEnt 6
that mutation in GATA4 and NKX2-5 are responsible for CHDs
and may not be the microdeletion. We wish to thank Dr I B Vijayalakshmi, Professor of Pediatric

Couples who decide not to undergo termination of Cardiology, for sharing some of her clinical images.
pregnancy should be informed of good neonatal care so they
can plan accordingly for treatment in a tertiary care centre both rEfErEnCES
for cardiac intervention and the management of associated
clinical features. 1. Rashkind WJ. Pediatric cardiology: A brief historical
In cases where CHD is identified postnatally, it is perspective. Pediatr Cardiol. 1979; 1:63-71.
imperative to discuss about available medical treatment/ 2. Bruneau BG. The developmental genetics of congenital heart
management, what exactly is wrong with the child, can the disease. Nature. 2008; 451:943-48.
3. Morris CD, Menashe VD. 25-year mortality after surgical
condition be cured, learning coping skills and the chance of
repair of congenital heart defect in childhood: A population-
recurrence and of the condition occurring in the parents. It is
based cohort study. JAMA. 1991; 266:3447-52.
best to avoid discussions about relationship with the partner, 4. Okita Y, Miki S, Ueda Y, et al. Early and late results of repair
plans for future pregnancies, availability of prenatal testing of tetralogy of Fallot with subarterial ventricular septal defect:
and alternative reproductive options. These issues are best A comparative evaluation of tetralogy with perimembranous
discussed during following sessions. ventricular septal defect. J Thorac Cardiovasc Surg. 1995; 110:
180-85.
ConCluSion 5. Sanchez-Cascos A. The recurrence risk in congenital heart
disease. Eur J Cardiol. 1978; 7:197-210.
Individual with congenital malformations place a heavy burden 6. Loffredo CA, Chokkalingam A, Sill AM, et al. Prevalence of
on the society and affected families. Primary prevention of congenital cardiovascular malformations among relatives of
infants with hypoplastic left heart, coarctation of the aorta and
genetic diseases is emerging as an important area to improve
d-transposition of the great arteries. Am J Med Genet. 2004;
quality of life and to prevent disease burden. Hence, the
124:225-30.
causes of birth defects and developmental disabilities should 7. Bruyere HJ Jr, Kargas SA, Levy JM. The causes and underlying
be found. The primary focus of antenatal care has been health developmental mechanisms of congenital cardiovascular mal-
of the mother during pregnancy and safe delivery of the child. formations: A critical review. Am J Med Genet. 1987; 3:411.
Fetal medicine is now emerging as an equally important 8. Deepak Srivastava. Genetic assembly of the heart: Implication
component of the antenatal care. Hence, the scope of antenatal of congenital heart disease. Annual Review of Physiology.
care needs to be enlarged to include fetal health. 2001; 63:451.
The completion of the human genome project has 9. Buckingham M, Meilhac S, Zaffran S. Building the mammalian
provided a range and depth of information. It has brought heart from two sources of myocardial cells. Nature Rev Genet.
lot of importance and challenge to understand the genetic 2005; 6:826-35.
10. Olson EN. Gene regulatory networks in the evolution and
disease. Further challenges include utilizing this information
development of the heart. Science. 2006; 313:1922-27.
to improve diagnosis and treatment of children with CHDs.
11. Dunwoodie SL. Combinatorial signaling in the heart orches-
We need to extend the ability of fetal medicine specialist to trates cardiac induction, lineage specification and chamber for-
find heart defects as early as possible so that, they can be mation. Seminars in Cell and Developmental Biology. 2007;
treated while the heart is still forming.18 In near future whole 18:54-66.
genome sequencing will not only be achievable, but also come 12. Prall OW, Elliott DA, Harvey RP. Developmental paradigms in
within reach for advanced clinical diagnostic testing. Whole heart disease: Insights from tinman. Annals of Medicine. 2002;
genome sequencing will generate a lot of new information and 34:148-56.
interpreting these results will be difficult. There is a need to 13. Molkentin JD, Lin Q, Duncan SA, et al. Requirement of the
identify approaches and means to translate knowledge into transcription factor GATA4 for heart tube formation and ventral
effective intervention. This information can be translated morphogenesis. Genes and Development. 1997; 11:1061-72.
14. Stennard FA, Harvey RP. T-box transcription factors and
through Preimplantation genetic diagnosis (PGD) and gene
their roles in regulatory hierarchies in the developing heart.
therapy. PGD will help in selecting the normal embryos and
Development. 2005; 132:4897-910.
prevention of the termination of the pregnancy and physical 15. Yagi H, Furutani Y, Hamada H, et al. Role of TBX1 in human
and emotional trauma associated with it. Gene therapy will del22q11.2 syndrome. Lancet. 2003; 362:1366-73.
help in correcting the defect at the gene level. 16. Dunwoodie SL. Combinatorial signaling in the heart orchestrates
cardiac induction, lineage specification and chamber formation.
If someone feels that they never made a mistake in their life, Seminars in Cell and Developmental Biology. 2007; 18:54-66.
then it means that they had never tried a new thing in their 17. Payne M, Johnson MC, Grant JW, et al. Towards a molecular
life. understanding of congenital heart disease. Circulation. 2003;
—Einstein 91:494-504. 113
1 18. Ramegowda S, Ramachandra NB. An understanding the genet-
ic basis of congenital heart disease. Indian Journal of Human
36. Reamon-Buettner SM, Cho SH, Borlak J. Mutations in the
3'-untranslated region of GATA4 as molecular hotspots for
Genetics. 2005; 11:14-23. congenital heart disease (CHD). BMC Med Genet. 2007; 8:38.
19. Chaoui R, Korner H, Bommer C, et al. Prenatal diagnosis of 37. Lubs ML, Lubs HA. Chromosome identification-techniques
heart disease and associated chromosomal aberrations. Ultra- and applications in biology and medicine. Nobel Symposia.
schall Med. 1999; 20:177-84. 1973; 8:241-50.
20. Burn J, Goodship J. Cong. heart disease. In Emery and 38. Bröcker-Vriends AH, Mooij PD, van Bel F, et al. Monosomy
Rimoin’s: Principles and Practice of Medical Genetics, Rimoin 8p: an easily overlooked syndrome. J Med Genet. 1986; 2:
DL, Connor MJ, Pyeritz RE, Korf BR (Eds), 4th edn, Churchill 153-54.
livingstone, Chapter 2002; 47,1:1239-72. 39. Devriendt K, Fryns JP, Mortier G, et al. The annual incidence
21. Tézenas Du, Montcel S, Mendizabai H, et al. Prevalence of of DiGeorge/velocardiofacial syndrome. J Med Genet. 1998;
22q11 microdeletion. J Med Genet. 1996; 33:719. 35:789-90.
22. Devriendt K, Fryns JP, Mortier G, et al. The annual incidence 40. Pehlivan T, Pober BR, Brueckner M, et al. GATA4
of DiGeorge/velocardiofacial syndrome. J Med Genet. 1998; Haploinsufficiency in Patients With Interstitial Deletion of
35:789-90. Chromosome Region 8p23.1 and Congenital Heart Disease.
23. Botto LD, May K, Fernhoff PM, et al. A population-based study American Journal of Medical Genetics. 1999; 83:201-06.
of the 22q11.2 deletion: phenotype, incidence, and contribution 41. Reddy KS. A paternally inherited terminal deletion, del(8).
to major birth defects in the population. Pediatrics. 2003; (p23.1) pat, detected prenatally in an amniotic fluid sample: a
112:101-07. review of deletion 8p23.1 cases. Prenat Diagn. 1999; 19:868-
24. Carelle-Calmels N, Saugier-Veber P, Girard-Lemaire F, et al. 72.
Genetic compensation in a human genomic disorder. N Engl J 42. Bhatia SN, Suri V, Bundy A, et al. Prenatal detection and
Med. 2009; 360:1211-16. mapping of a distal 8p deletion associated with congenital
25. Shiojima I, Komuro I, Inazawa J, et al. Assignment of cardiac heart disease. Prenatal Diagn. 1999; 19:863-67.
homeobox gene CSX to human chromosome 5q34. Genomics. 43. Devriendt K, Matthijs G, Van Dael R, et al. Delineation of
1995; 27:204-6. the critical deletion region for congenital heart defects, on
26. Harvey RP. NK-2 Homeobox genes and heart development. chromosome 8p23.1. Am J Hum Genet. 1999; 64:1119-26.
Dev Bio. 1996; 178:203-16. 44. Claeys I, Holvoet M, Eyskens B, et al. A recognizable
27. Dentice M, Cordeddu V, Rosica A, et al. Missense mutation behavioral phenotype associated with terminal deletions of the
in the transcription factor NKX2-5: A novel molecular event short arm of chromosome 8. Am J Med Genet. 1997; 74:515-
in the pathogenesis of thyroid dysgenesis. J Clin Endocrinol 20.
Metab. 2006; 91:1428-33. 45. Fryns JP, Kleczkowska A, Vogels A, et al. Normal phenotype
28. Turbay D, Wechsler SB, Blanchard KM, et al. Molecular and slight mental retardation in de novo distal 8p deletion
cloning, chromosomal mapping and characterization of the (8pter–8p23.1). Ann Genet. 1989; 32:171-73.
human cardiac-specific homeobox gene hCsx. Molec Med. 46. Hutchinson R, Wilson M, Voullaire L. Distal 8p deletion (8p23.
1996; 2:86-96. 1–pter): a common deletion. J Med Genet. 1992; 29:407-11.
29. Pauli RM, Scheib-Wixted S, Cripe L, et al. Ventricular non- 47. Wu BL, Schneider GH, Sabatino DE, et al. Distal 8p deletion
compaction and distal chromosome 5q deletion. Am J Med (8p23.1): An easily missed chromosomal abnormality that
Genet. 1999; 85:419-23. may be associated with congenital heart defect and mental
30. Gibbons B, Tan SY, Kee SK, et al. Interstitial deletion of retardation. Am J Med Genet. 1996; 62:77-83.
chromosome 5 in a neonate due to maternal insertion, ins(8; 5). 48. Giglio S, Graw SL, Gimelli G, et al. Deletion of a 5-cM
(p23; q33q35). Am J Med Genet. 1999; 86:289-93. region at chromosome 8p23 is associated with a spectrum of
31. Schafer IA, Robin NH, Posch JJ, et al. Distal 5q deletion congenital heart defects. Circulation. 2000; 102:432-67.
syndrome: phenotypic correlations. Am J Med Genet. 2001; 49. Bourrouillou G, Colombies P, Gallegos D, et al. Partial
103:63-68. monosomy 10p in a case investigated with tomodensitometry.
32. Schiffer C, Popp S, Moshir S, et al. Multicolor chromosomal Ann Genet. 1981; 24:61-64.
bar coding characterizes a de novo interstitial deletion (5) 50. Schuffenhauer S, Seidel H, Oechsler H, et al. DiGeorge
(q33.3q35.2) in a child with multiple congenital malformations. syndrome and partial monosomy 10p: case report and review.
Clin Dysmorphol. 2003; 12:129-31. Ann Genet. 1995; 38:162-67.
33. Baekvad-Hansen M, Tümer Z, Delicado A, et al. Delineation of 51. Daw SC, Taylor C, Kraman M, et al. A common region of
a 2.2 Mb microdeletion at 5q35 associated with microcephaly 10p deleted in DiGeorge and velocardiofacial syndromes. Nat
and congenital heart disease. Am J Med Genet. A. 2006; Genet. 1996; 13:458-60.
140:427-33. 52. Schuffenhauer S, Lichtner P, Peykar-Derakhshandeh P.
34. Rauch A, Dörr HG. Chromosome 5q subtelomeric dele- Deletion mapping on chromosome 10p and definition of
tion syndrome. Am J Med Genet C Semin Med Genet. 2007; a critical region for the second DiGeorge syndrome locus
145C:372-76. (DGS2). Europ J Hum. Genet 1998; 6:213-25.
35. Bjørnstad PG, Leren TP. Familial atrial septal defect in the 53. Lichtner P, Konig R, Hasegawa T, et al. An HDR
oval fossa with progressive prolongation of the atrioventricular (hypoparathyroidism, deafness, renal dysplasia). syndrome
conduction caused by mutations in the NKX2.5 gene. Cardiol locus maps distal to the DiGeorge syndrome region on
Young. 2009; 19:40-44. 10p13/14. J Med Genet 2000; 37:33-37.
114
54. Berend SA, Spikes AS, Kashork CD, et al. Dual-probe 72. Chen M, Hwu WL, Kuo SJ, et al. Subtelomeric rearrangements
and 22q11.2 deletion syndrome in anomalous growth-restricted
6
fluorescence in situ hybridization assay for detecting deletions
associated with VCFS/DiGeorge syndrome I and DiGeorge fetuses with normal or balanced G-banded karyotype.

syndrome II loci. Am J Med Genet. 2000; 91:313-7. Ultrasound Obstet Gynecol. 2006; 28:939-43.
55. Lichtner P, Attié-Bitach T, Schuffenhauer S, et al. Expression 73. Donnenfeld AE, Cutillo D, Horwitz J, et al. Prospective study
and mutation analysis of BRUNOL3, a candidate gene for of 22q11 deletion analysis in fetuses with excess nuchal
heart and thymus developmental defects associated with partial translucency. Am J Obstet. 2006; 194:508-11.
monosomy 10p. J Mol Med. 2002; 80:431-42. 74. Lautrup CK, Kjaergaard S, Brøndum-Nielsen K, et al. Testing
56. Shaikh TH, Kurohashi H, Saitta SC, et al. Chromosome 22 for 22q11 microdeletion in 146 fetuses with nuchal translucency
specific low copy repeats and the 22q11.2 deletion syndrome: above the 99th percentile and a normal karyotype. Acta Obstet
genomic organization and deletion end point analysis. Hum Gynecol Scand. 2008; 87:1252-55.
Mol Genet. 2000; 9:489. 75. Boudjemline Y, Fermont L, Le Bidois J, et al. Can we predict
57. Halford S, Wilson DI, Daw SC, et al. Isolation of a gene 22q11 status of fetuses with tetralogy of Fallot? Prenat Diagn.
expressed during early embryogenesis from the region of 2002; 22:231-34.
22q11 commonly deleted in DiGeorge syndrome. Hum Molec 76. Chaoui R, Kalache KD, Heling KS, et al. Absent or hypoplasic
Genet. 1993; 2:1577-82. thymus on ultrasound: A marker for deletion 22q11.2 in fetal
58. Lamour V, Lecluse Y, Desmaze C, et al. A human homolog cardiac defects. Ultrasound Obstet Gynecol. 2002; 20:546-52.
of the S. cerevisiae HIR1 and HIR2 transcriptional repressors 77. Bretelle F, Beyer L, Pellissier MC, et al. Prenatal and postnatal
cloned from the DiGeorge syndrome critical region. Hum. diagnosis of 22q11.2 deletion syndrome. Eur J Med Genet.
Molec Genet. 1995; 4:791-99. 2010; 53:367-70.
59. Demczuk S, Levy A, Aubry M, et al. Excess of deletions of 78. Aslan H, Karaman B, Yildirim G, et al. Prenatal diagnosis
maternal origin in the DiGeorge/velo-cardio-facial syndromes: of jumping translocation involving chromosome 22 with
A study of 22 new patients and review of the literature. Hum. ultrasonographic findings. Prenat Diagn. 2005; 25:1024-27.
79. Liu T, Liu Q, Wang YX, et al. Use of amniocytes for prenatal
Genet. 1995; 96:9-13.
diagnosis of 22q11.2 microdeletion syndrome: A feasibility
60. De la Chapelle A, Herva R, Koivisto M, et al. A deletion in
study. Chin Med J. 2010; 123:438-42.
chromosome 22 can cause DiGeorge syndrome. Hum. Genet.
80. Gawde H, Patel ZM, Khatkhatey MI, et al. Chromosome 22
1981; 57:253-56.
microdeletion by FISH in isolated congenital heart disease.
61. Kelley RI, Zackai EH, Emanuel BS, et al. The association of the
Indian J Pediatr. 2006; 73:885-88.
DiGeorge anomalad with partial monosomy of chromosome
81. Madon PF, Athalye AS, Sanghavi K, et al. Microdeletion
22. J Pediat. 1982; 101:197-200.
syndromes detected by FISH –73 Positive from 374 Cases. Int
62. Greenberg F, Crowder WE, Paschall V, et al. Familial DiGeorge
J Hum Genet. 2010; 10:15-20.
syndrome and associated partial monosomy of chromosome
82. Ferencz C, Neill CA, Boughman JA, et al. Congenital cardio-
22. Hum. Genet. 1984; 65:317-19. vascular malformations associated with chromosome abnor-
63. Greenberg F, Elder FFB, Haffner P, et al. Cytogenetic findings malities: an epidemiologic study. J Pediatr. 1989; 114:79-86.
in a prospective series of patients with DiGeorge anomaly. Am 83. Johnson MC, Hing A, Wood MK, et al. Chromosome
J Hum Genet. 1988; 43:605-11. abnormalities in congenital heart disease. Am J Med Genet.
64. Wilson DI, Cross IE, Goodship JA, et al. A prospective 1997; 70:292-98.
cytogenetic study of 36 cases of DiGeorge syndrome. Am J 84. Driscoll DA, Salvin J, Sellinger B, et al. Prevalence of 22q11
Hum Genet. 1992; 51:957-63. microdeetions in DiGeorge and velocardiofacial syndromes:
65. Carey AH, Kelly D, Halford S, et al. Molecular genetic study implications for genetic counselling and prenatal diagnosis. J
of the frequency of monosomy 22q11 in DiGeorge syndrome. Med Genet. 1993; 30:813-17.
Am J Hum Genet. 1992; 51:964-70. 85. Goldmuntz E, Driscoll D, Budarf ML, et al. Microdeletions
66. Gowde H, Patel ZM. Cytomolecular Approaches in congenital of chromosomal region 22q11 in patients with congenital
heart disease: A Review. ICMR Bulletin. 2007; 37:7-9. conotruncal cardiac defects. J Med Genet. 1993; 30:807-12.
67. Shprintzen RJ. Velo-cardio-facial syndrome: 30 Years of study. 86. Momma K, Kondo C, Matsuoka R. Tetralogy of Fallot with
Developmental Disabilities Research Reviews. 2008; 14(1): pulmonary atresia associated with chromosome 22q11 deletion.
3-10. JACC. 1996; 27:198-202.
68. Volpe P, Marasini M, Caruso G, et al. 22q11 deletions in 87. Alikaþifoðlu M, Malkoc N, Ceviz N, et al. Microdeletion of
fetuses with malformations of the outflow tracts or interruption 22q11 (CATCH 22) inchildren with conotruncal heart defect and
of the aortic arch: impact of additional ultrasound signs. Prenat eþtracardiacmalformations. Turk J Pediatr. 2000; 42:215-18.
Diagn. 2003; 23:752-57. 88. Giray O, Ülgenalp A, Bora E, et al. Congenital cardiac defects
69. Ryan AK, Goodship JA, Wilson DI, et al. Spectrum of with 22q11 deletion. The Turkish Journal of Pediatrics. 2003;
clinical features associated with interstitial chromosome 22q1 45:217-20.
deletions: A European collaborative study. J Med Genet. 1997; 89. Puder KS, Humes RA, Gold RL, et al. The genetic implication
34:798-804. for preceding generations of the prenatal diagnosis of inter-
70. Wu HY, Rusnack SL, Bellah RD, et al. Genitourinary malfor- rupted aortic arch in association with unsuspected DiGeorge
mation in chromosome 22q11.2 deletion. J. Urol. 2002; 168: anomaly. Am J Obstet Gynecol. 1995; 173:239-41.
2564-65. 90. Iserin L, de Lonlay P, Viot G, et al. Prevalence of the micro-
115
71. McDonald-McGinn DM, Zackai EH. Genetic counseling for deletion 22q11 in newborn infants with congenital conotruncal
the 22q11.2. Dev Disabil Res Rev. 2008; 14:69-74. cardiac anomalies. Eur J Pediatr. 1998; 157:881-84.
1 91. Fuchs F, Riis P. Antenatal sex determination. Nature. 1956;
177: 330.
96. Percutaneous umbilical cord blood sampling (2010). wikipedia.
org. <http://en. wikipedia. org/wiki/Percutaneous_umbilical_
92. Woo J (2002). “A short History of Amniocentesis, Fetoscopy cord_blood_sampling>[Retrived on 2012-30-06].
and Chorionic Villus Sampling”. ob-ultrasound. net. <http:// 97. Jung Mde P, Cardoso MH, Villar MA, et al. Revisiting
www. ob-ultrasound. net/amniocentesis. html> [Retrieved on establishments of the etiology of Turner syndrome. Hist Cienc
2012-30-06]. Saude Manguinhos. 2009; 16:361-76.
93. Ferguson-Smith M, Bianchi DW. Prenatal Diagnosis: past, 98. Wolstenholme J, Rooney DE. Cytogenetics in the 1970s and
present, and future. Prenat Diagn. 2010; 30:601-04. 1980s. Prenat Diagn. 2010; 30:605-07.
94. Hobbins JC, Mahoney MJ. In utero diagnosis of haemoglobino- 99. Pardue ML, Gall JG. Molecular hybridization of radioactive
pathies. Technique of obtaining fetal blood. N Engl J Med. DNA to the DNA of cytological preparations. Proc. Natl. Acad.
1974; 290:1065. Sci. USA. 1969; 64:600-04.
95. Alfirevic Z, Walkinshaw SA and Kilby MD (2010). Green-top 100. Harper ME, Saundres GF. Localization of single copy DNA
Guideline No. 8 Aminiocentesis and Chorionic Villus Sampling sequences on Gbanded human chromosomes by in situ
from Royal College of Obstetricians Guidelines,<http://www. hybridization. Chromosoma. 1981; 83:431-9.
rcog. org. uk/womens-health/clinicalguidance/amniocentesis- 101. Resta R, Biesecker BB, Bennett RL, et al. National society of
and-chorionic-villus-sampling-green-top-8>[Retrieved on genetic counselors' definition task force. J Genet Couns. 2006;
2010-20-10]. 15:77-83.
116
Sec t i on
Basics
Examination of the Heart—
C hapter
7 A Comparative External
and Internal Anatomy
Pradeep Vaideeswar
Understanding the normal anatomy of the heart forms an further dissection or operative techniques. The features to
important basis in the diagnosis of various congenital and be seen on external examination would be the orientation,
acquired diseases of the heart through investigative modalities. cardiomegaly, appearance of anterior and posterior surfaces,
Examination of the external surface of the heart often provides chamber and vascular morphology and appearance of the
clues to the inner pathology, which may alter the pattern of epicardial surface.
ORIENTATION (fIguRES 1A ANd B)
Figure 1A Figure 1B
Most pathologists or for that matter even anatomists are guilty within the thorax by the systemic and pulmonary venous
of using inappropriate descriptive terms in the gross analysis connections. The axis of the ventricles is tilted laterally
as we continue to orient the heart in an upright position like a to the left from base to apex, extending anteriorly and
‘valentine’ heart. slightly inferiorly; the atrioventricular junction follows the
This is the true anatomic position of the heart. The ventricular orientation.
atrial have an anteroposterior relationship and are fixed
2 EXTERNAL SuRfACES
Anterior (figure 2)
BAsics
Figure 2
The anterior surface of the heart shows the right and left atrial appendages (RAA, LAA) and the great arteries (Ao—Aorta,
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)
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
120 Figure 3 the crux of the heart.
Right Atrial Morphology (figures 4 and 5) 7
ExAminAtion oF thE hEArt—A compArAtivE ExtErnAl And intErnAl AnAtomy

Figure 4A Figure 4B
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.
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. 121
Figure 5
2 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.
There is no obvious demarcation between the LA chamber

and the entry of the pulmonary veins. On the posterior aspect,
122 Figure 7 LA appears like a pillow with veins entering into its corners.
7

Figure 8B
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 9
The above figure 9 shows the relationship of various structures at the base of the heart. 123
2 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)

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 rim—limbus 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
124 terminalis or terminal crest (TC). Figure 11
7

Figure 14
The internal anatomy of RA also provides the landmark of

Figure 12
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
The crista terminalis originates from the septal wall and of tricuspid valve [TV]) forms the anterior border. At the base
sweeps like a twisted ‘C’. It passes anterior to the opening of of this isosceles triangle is the CS opening and at the apex, the
the SVC, descending posterolaterally and then anteriorly to central fibrous body. Around the apex are present compact and
skirt the right side of the orifice of IVC. 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 15
In sharp contrast to RA, the topography of LA is almost

The distal ramification of TC towards CS is part of the lower featureless. The pectinate muscles are confined to LAA.
RA wall called ‘flutter isthmus’. It is quadrilateral in shape Remaining portion appears smooth with thick pearly white
bordered by the Eustachian valve and Eustachian ridge endocardium. The septal aspect is usually marked by shallow,
posteriorly, tricuspid annulus anteriorly and CS superiorly. 125
irregular pits.
2 Atrioventricular Valves (figures 16 and 17) Ventricles (figures 18 to 22)
The atrioventricular valves are described on the basis of their

BAsics
annuli, commissures, leaflets, chordae and papillary muscles.
Figure 16
Figure 18
The TV has three leaflets: anterior (ATL), septal (STL) and The RV is coarsely trabeculated with a thin compact portion
posterior (PTL) and hence three commissures: anteroseptal, that measures 0.5 to 0.7 cm. The trabeculation extends even
posteroseptal and anteroposterior. The leaflets are anchored to into the outflow tract.
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.
Figure 17
The mitral valve (MV) has two leaflets: anterior (AML) and
Figure 19
posterior (PML) and two commissures: anterolateral and
posteromedial. The AML has a greater width and appears a The LV is finely trabeculated with a thick compact portion
little tongue-shaped. The subvalvular apparatus is represented measuring about 1 cm. The septal surface is smooth and
by delicate chords attached to fairly constant anterior and covered by the thicker endocardium (Measurements: Usually
126 posterior group of papillary muscles. taken 1 cm below the arterial valves).
7

Figure 20
The morphology of the RV lends itself to subdivision into Figure 21

three components. The inlet component extends from
tricuspid annulus to attachments of the tendinous chords. The
trabecular or sinus portion extends from chordal attachments Similar subdivisions (inlet, trabecular and outlet) can be
to apex, while the outlet portion is present beyond the septal applied to the sigmoid muscular interventricular septum IVS.
band. The septal band or trabecula septomarginalis (TSM) Asterisk marks the membranous portion of the IVS. On the
is an important landmark in the RV. Note another muscular right side, the roof of this septum is formed by attachment of
band connecting the TSM to the base of the anterior papillary anteroseptal commissure.
muscle (APM). This is the moderator band (MB).
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. 127
Figure 22
2 Arterial Valves (figures 23 and 24)
The arterial valves are described with respect to their annuli,
BAsics
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
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).
Figure 23 A discontinuous ridge, seen above the arterial ostia, is called
as the sinotubular junction. On the left side, the membranous
In PV, the cusps are one anterior and two posterior. 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 apothecary’s shop.
—William Withey Gull
128
C hapter
Classification of Cardiovascular
8 Anomalies and their Terminologies
Prabhat Kumar, Vijayalakshmi IB
Introduction Cardiac position in the chest and visceral sidedness is

first defined, i.e. on the left or right side. Each region of the
Pediatric cardiology and management of congenital heart heart is then evaluated in the direction of blood flow, i.e.
diseases has seen a sea of change in the last 75 years. Since beginning with systemic and pulmonary blood flow, both
the time Dr Maude E Abbott categorized 1,000 malformed atria, atrioventricular valves, ventricles, semilunar valves and
hearts,1 different systems of classification and nomenclature great arteries. It is not as simple as it looks on description.
have been described. The variation is mainly based on the To diagnose the simplest lesions to the most complex
importance given by the researcher either to embryogenesis, lesions, all the chambers of the heart are to be recognized by
atrial sidedness, morphology and position of ventricles and their morphological features rather than according to their
great arteries or on surgical anatomy. Till date, there is no position, e.g. morphological left atrium in a normal heart can
uniform system of nomenclature because with the development be identified by pulmonary veins, while a right-sided atrium
of every new classification, newer terms have been added, but will have systemic veins draining into it, but that is not the case
older terms have not been dropped. The need for a commonly in malformed hearts. In case of total anomalous pulmonary
acceptable nomenclature cannot be underestimated. There are venous connection, left atrium has to be identified by the
many different combinations of lesions observed in pediatric other constant morphological features such as appendicular
cardiology practice where description and an individual place morphology. Similarly, ventricles are identified based on their
for them in the classification is a must. trabecular pattern, attachment of the valve leaflets, etc. Great
Earlier descriptions and classifications of congenital heart arteries are identified based on their branching patterns. Apart
diseases by Richard Van Praagh and Maria Victoria de la Cruz from the identification of individual chambers, their relations
were based on topographic arrangement of the atrium, ventricle with each other is to be identified. The major abnormality in
and great arteries, thus developing the concept of concordance several cardiac malformations is that the cardiac chambers are
and discordance. The concept of detailed description of the not present at their anticipated locations. Thus, each chamber
heart has revolutionized and has become more rational, since has to be identified on the basis of their morphological features
the development of cross-sectional echocardiography. The and then they are to be described as morphologically left or
system of sequential segmental analysis by Anderson et al now morphologically right, irrespective of their locations. Term
takes into consideration all possible variations of relations, not single is applied to a chamber or valve when the corresponding
only between the two atria, ventricles, great arteries, but also contralateral structure is totally absent, while the term common
between the atrioventricular and ventriculoarterial junctions.2 is used when bilateral components are present, but septation
It is important that the system we use for description should is absent, e.g. tricuspid atresia with single inlet ventricle,
have more clarity and the concept of sequential segmental common atrium, etc. Cardiac chambers are largely defined by
analysis appears very appropriate at this time. the anatomic landmarks on septal surfaces.
Sequential segmental analysis SITUS

In this system of analysis, heart is considered a segmented The situs or sideness or position, applies to structures/organ
structure represented by three building blocks or regions, i.e. systems that are not bilaterally symmetric. It describes the
atria, ventricles and great arteries. Each region is partitioned position of the cardiac atria and viscera in the system. The
into a left-sided component and a right-sided component. visceroatrial situs refers to the position of the atria in relation
2 to the nearby anatomy (including the stomach, liver, spleen, drain into both right and left atrium.3 In situs ambiguous the
and bronchi).3 Three different anatomic configurations may stomach can be either on the left, right or in the midline.
be observed: situs solitus (normal), situs inversus (inverted
Basics
or mirror image of normal), or situs ambiguous (ambiguus). Morphological features of various

Situs solitus is the normal anatomic configuration, with cardiac chambers
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
Atria
lung (Figure 1A). The morphologic right bronchus is short, Each atrium has three components, i.e. an appendage, a
wide and its first branch is eparterial (bronchus is above the venous component and a septum, which separates the two
right pulmonary artery). The morphologic left bronchus is atria. The appendage, because of its characteristic external
long, thin, curved and is hyparterial (bronchus is below the features distinguishes the morphological right and left atrium.
left pulmonary artery). The appendage is the only component, which is universally
Situs inversus is an exact inversion of anatomic configura present to determine the type of atrium. The appendage of the
tion that is seen in situs solitus (Figure 1B). The morphologic right atrium is triangular with a broad base. Internally, right
left atrium is to the right of the morphologic right atrium and atrium has numerous pectinate muscles and a terminal crest
the larger lobe of the liver is on the left, the stomach and spleen (crista terminalis). Left atrium has a pyramidal or finger-
are on the right side of the body. The left lung is trilobed with shaped, small appendage with several lobes. The main body
an eparterial bronchus and the right lung is bilobed with a of the left atrium is smooth walled.
hyparterial bronchus. The atrial situs always corresponds to In situs solitus, i.e. the left atrium is on the left of the right
the visceral situs with situs solitus and situs inversus. atrium. If there is a mirror image of this arrangement, it is
Situs ambiguous is when the situs is uncertain. It is called situs inversus. Rarely, the atria and appendage do not
neither situs solitus nor inversus. Situs ambiguous may have such lateralization and the two appendages are mirror
manifest with various abnormal visceroatrial configurations image of each other, thus both the appendages are either
that are associated with extracardiac anomalies (e.g. splenic morphologically left type or of right type. It is important to
abnormalities, biliary atresia, and intestinal malrotation) as note that the morphology of the appendages is closely related
well as cardiac anomalies. Two subsets of situs ambiguous are to the arrangement of the thoracic and abdominal organs.
well recognized: right isomerism (asplenia) and left isomerism Atrial isomerism is thus a part of heterotaxy syndromes in
(polysplenia). In right isomerism, bilateral trilobed lungs, which lungs and atria have isomerism, while the abdominal
a large symmetric liver, absence of the spleen (Figure 1C), structures are jumbled up. Generally, isomerism of left atrial
and total anomalous pulmonary venous return are frequently appendage is associated with polysplenia, interrupted inferior
observed. Left isomerism is usually indicated by bilateral vena cava, while right atrial isomerism is associated with
bilobed lungs (Figure 1D), interruption of the inferior vena absence of spleen. Though these associations are common,
cava, multiple spleens (Figure 2) and pulmonary veins that they are not the rule. Structure of the appendages, atria,
A B C D
130 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
When the morphologic right ventricle is on the right side 8
of the morphological left ventricle, the bulboventricular loop
is defined as ‘D’ (dextro) loop. When the morphological
Classification of Cardiovascular Anomalies and their Terminologies

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.
Great Arteries
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
Figure 2: Coronal image of computed tomographic angiogram in a comes when only one arterial trunk is identified. It could be
2-year-old girl with left isomerism shows bilateral long, thin, curved due to atresia of one of the major great vessels, i.e. aortic
left bronchus (2 black arrows) with polysplenia indicated by 3 white atresia or pulmonary atresia. Common arterial trunk or
arrows. (Image courtsey: Dr Madhav Hegde) 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
visceral situs and orientation of the vessels at the diaphragm the types of truncus (type IV), the pulmonary trunk is absent
should be clearly defined. and the pulmonary blood supply comes from the collaterals
arising from the descending aorta. Such a type of arterial trunk
Ventricles is called solitary arterial trunk.4
The characteristic differentiating features of right and
Normal ventricle has three parts: inlet, trabecular and outlet. left atrium, ventricles and the two great arteries are given in
Inlet portion has the atrioventricular valve, its tension apparatus Box 1.5
including the papillary muscles. Trabecular portion extends
from the papillary muscles to the apex. Outlet portion is the part Atrioventricular Junction and
of ventricle from apex to the valves leading to the great vessels. Atrioventricular Valves
Trabecular portion of the ventricles differentiates the two
ventricles for identification. The right ventricle has coarse Atrioventricular junction is the union of atrium and ventricle
trabeculations whereas left ventricle has got fine trabeculations and its analysis will involve atrial arrangement with respect
and is smooth walled. to left and right atrium, their connections to ventricles
Atrioventricular valves always go with the ventricles, i.e. and morphology of the valves. Morphological left and
tricuspid valve will always be with the right ventricle and right atrium in respect to each other may be lateralized-
mitral valve with the left ventricle. Identification of valves meaning morphological left atrium is located to the left and
helps in defining the morphology of the ventricle. Tricuspid morphological right atrium is on right side or they could be
valve is identified by typical attachment of the septal leaflet mirror image, where they are located on opposite sides or
to the interventricular septum. Mitral valve does not have any there may be isomerism.
attachment to the septum. Its anterior and posterior leaflets are The atrioventricular valve is formed of fibrous tissue and
attached with the two papillary muscles within the ventricle. connects the atrium to the ventricle. Valves tend to travel
At the atrioventricular level, tricuspid valve is positioned along with their respective ventricles, thus tricuspid valve will
more closer to the apex in comparison to the mitral valve. always be present with the morphological right ventricle and
This feature is very well-defined in the four chamber view of mitral valve will always be with morphological left ventricle. 131
echocardiography. If morphological left atrium is connected to the morphological
2 Box 1: Morphological features of various cardiac chambers and great arteries
Basics
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
Ventricles
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 More apical More basal (cranial)
valve
Chordal attachment to the IVS Yes No
Great Arteries
Aorta Main pulmonary artery
Course Long arching Branching
Branches Origin of coronary arteries Pulmonary arteries
Cephalic and other systemic arteries
IVS = Interventricular septum
left ventricle then this connection is called concordant, while tricuspid valve atresia and mitral valve atresia has evolved
if this connection is inappropriate, means left atrium is for malformed hearts where one of these valve is atretic. In
connected to the morphological right ventricle and vice versa, such univentricular hearts, the corresponding ventricle, i.e.
it is called discordant.6 in tricuspid atresia, right ventricle or in mitral valve atresia,
The morphology of atrioventricular valves should be the left ventricle may be hypoplastic. The connection can be
defined well. One of the two atrioventricular valves may be discordant also in cases where the atrium can be connected
absent, while in another situation there can be overriding and to a dominant left or dominant right ventricle. Rudimentary
straddling. Both straddling and overriding are associated with ventricles are usually malformed and their morphology
ventricular septal defects. In straddling, the atrioventricular is defined by explaining the morphology of the dominant
valve has part of its chordal apparatus attached across the ventricle. Thus, if the dominant ventricle is morphologically
ventricular septum into the other ventricle, while in overriding left ventricle, hypoplastic ventricle will be the right ventricle
only the opening of the valve sits across the septal crest. only.
Malformed hearts where both the atria connect with only
one ventricle is categorized under univentricular connections. Ventriculoarterial Junction
Most of such cases have two ventricles, but only one ventricle
is of normal size and has inlet, body and outlet components. Ventriculoarterial junction is the junction of ventricles and
In such cases, the other ventricle is hypoplastic and usually arterial segments, where the connections could be concordant
lacks the inlet portion. Larger ventricle may be morphological or discordant. Concordant connection is when the aorta is
right ventricle or morphological left ventricle and respectively arising from the left ventricle and the pulmonary trunk is
named as double-inlet right ventricle or double-inlet left arising from the right ventricle. Discordant connection is
ventricle. when these vessels are arising from the opposite ventricles.
Similarly in the group of univentricular connections, one Transposition is a term used when the great vessels have
132 of the atrioventricular valve may be atretic and thus one of discordant connection with regard to the ventricle. The
the atria is not connected with the ventricle. Thus, the term 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 two-
dimensional 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 1–4 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;116:1337–1350, with 133
permission)
2 discordant ventriculoarterial connection gives rise to complete Complete transposition of the great arteries in an abbreviated
transposition of great vessels. The combination of discordant form can be described as (S, D, D ), i.e. S = situs soilitus,
connection at atrioventricular junction and discordant D = D loop, D = D transposition. Similarly, after segmental
Basics
ventriculoarterial connection (double discordance) gives rise analysis, all types of segmental connections can be described
to congenitally corrected transposition. in an abbreviated form (Figure 3).9 It is important that the
When both the great arteries arise from one ventricular description of complex cardiac anomalies in whatever way we
chamber, the ventriculoarterial connection is considered do, should be easier to understand and describe.
as double outlet. It can be from right ventricle or from left
ventricle. Defining the associated malformations
Morphology of ventricular outflow tract is different in
left and right ventricle. Right ventricular outflow tract has Sequential segmental analysis defines the chambers of the
muscular infundibulum, while there is fibrous continuity heart and the connections of various segments of the heart,
between the arterial and atrioventricular valve in the left but many a times, associated malformations are the ones
ventricle. who have a major impact on the clinical presentation.10
The spatial relation of both the great vessels to each other Apart from defining the position of the heart in the chest and
also needs to be defined. Two trunks usually have spiral defining the apex pointing to left or right, pulmonary venous
relation, but can be parallel to each other in transposition anomalies, various types of atrial septal defects, anomalies of
physiology. Anteroposterior and right-left relation of aortic atrioventricular valves, ventricular septal defects, anomalies
and pulmonary valves to each other also requires to be defined, of aortic arch and coronary anomalies, etc. They also require
as this would help in surgical management. to be defined well for complete diagnosis and management.
SEGMENTAL TERMS DEFINED AS ABBREVIATIONS Conclusion

The segmental terms can either be defined in full or can be In routine practice, most of the hearts with congenital
written as abbreviations.7 The types of visceroatrial situs heart diseases will have usual location in the chest, the
are solitus (S), inversus (I), or ambiguous (A). The types of chambers will have normal relationships with concordant
ventricular situs are solitus or D-loop ventricles (D), or inverted atrioventricular and ventriculoarterial connections. Still in
or L-loop (L). The types of great arterial situs are solitus (S), all patients without making any assumptions, analysis should
as in solitus normally related great arteries and inversus (I) be made by segmental approach so as to make detailed and
as in inverted normally related great arteries. When the great correct anatomical delineation without missing any defect.
arteries are abnormally related, the right sided (dextro or D) Segmental analysis is quite helpful and is the most accepted
location of the aortic valve relative to the pulmonary valve method of analyzing complex cardiac defects in detail, which
is symbolized as D and the left-sided (levo or L) location of is understood by all concerned. This method overcomes the
the aortic valve relative to the pulmonary valve is symbolized older controversial nomenclature in most of the situations thus
as L. D-malpositions of the great arteries are considered to making description much simpler and practical.
be solitus or non-inverted malpositions, the aortic valve
normally being right-sided in situs solitus. L-malpositions of Science is the systematic classification of experience.
the great arteries are considered to be inverted or mirror image —George Henry Lewes
malpositions because the aortic valve is left-sided relative to
the pulmonary valve, as in situs inversus totalis. In anterior or References
A-malpositions of the great arteries, the right-left location of
the aortic valve (directly anterior to the pulmonary valve) is 1. Abbott ME. Atlas of congenital cardiac disease. New York:
equivocal (neither right nor left). Hence, A-malpositions may American Heart Association. 1936.
2. Anderson RH, Becker AE, Freedom RM, et al. Sequential
be regarded as of uncertain situs (situs ambiguous of the great
segmental analysis of congenital heart disease. Pediatr Cardiol.
arteries).8 1984; 5(4):281-7.
For example, a normal heart without abbreviations can 3. Lapierre C, Déry J, Guérin R, Viremouneix L, Dubois J, Garel
be defined as: situs solitus of the viscera and atria, D loop, L. Segmental approach to imaging of congenital heart disease.
solitus normally related great arteries. In an abbreviated Radiographics. 2010; 30:397-411.
form it will be represented as (S, D, S), i.e. S = situs solitus; 4. Ho SY. Cardiac morphology and nomenclature. In: Diagnosis
D = D loop; S = solitus normally related great arteries. A and Management of Adult Congenital Heart Disease
mirror image dextrocardia or an inverted normal heart in an Philadelphia: Elsevier; 2011, pp. 5-13.
abbreviated form will be described as (I, L, I), i.e. I = inversus, 5. Yoo Sj, MacDonald C, Babyn P. Sequential segmental
approach to congenital heart disease. In: Chest Radiographic
L = L loop, I = inverted normally related great arteries.
134 Interpretation in Pediatric Cardiac Patients, 1st edition. Yoo Sj,
MacDonald C, Babyn P (Eds). Thieme Medical publishers,
New York, 2010, pp. 22-30.
JF, Lock JE, Fyler DC (Eds). Nadas’ Pediatric Cardiology. 2nd
edition. Saunders, Pennsylvania. 2006, pp.39-46.
8
6. Edwards WD. Classification and terminology of cardiovascular 9. Foran RB, Belcourt C, Nanton MA, et al. Isolated

anomalies. In: Moss and Adams’ Heart Disease in Infants, infundibuloarterial inversion {S, D, I}: a newly recognized
Children, and Adolescents: Including the Fetus and Young form of congenital heart disease. Am Heart J. 1988; 116:
Adults, 7th edition. Lippincott Williams and Wilkins; 2001, 1337-50.
pp. 118-39. 10. Anderson RH. Terminology. In: Anderson RH, Baker EJ,
7. Van Praagh R. Terminology of congenital heart disease. Macartney FJ, Rigby ML, Shinebourne EA, Tynan M (Eds)
Glossary and commentary. Circulation. 1977; 56:139-43. Pediatric Cardiology, 3rd edition. Philadelphia, Churchill
8. Van Praagh R. Segmental Approach to Diagnosis. In: Keane Livingstone; 2010, pp.3-16.
135
C hapter
9 Cardiac Malpositions
Sejal Shah
Cardiac malposition is defined as the location of the heart The morphological right atrium is to the right and morpho-
anywhere other than its usual position in the left hemithorax logical left atrium is to the left or the morphological right
or location of the heart in the left hemithorax when other atrium is to the right and posterior and the morphological
organs are in an abnormal position such as situs inversus. left atrium is to the left and anterior, hence the term situs
Cardiac malpositions include dextrocardia, mesocardia, solitus, pivoted is used.2 The morphological left ventricle
isolated levocardia, pericardial defects and ectopia cordis. is relatively anterior and right ventricle lies to the right. It
is frequently associated with atrioventricular discordance.
Dextrocardia
Embryology
Incidence
At 22 to 23 days of gestation, the primitive cardiac loop normally
Dextrocardia is defined as a right-sided heart with a base bends towards the right forming a D-loop (the morphological
apex axis directed rightward resulting from a variation in right ventricle is to the right of morphological left ventricle)
cardiac development and not used as a general term indicating (Figure 1A). During the next 10 to 12 days, the apex of the
any heart in the right chest.1 The malposition is intrinsic heart gradually migrates from the right side of the thorax to its
to the heart and not caused by extracardiac abnormalities. normal location in the left hemithorax. Lack of this normal left
Dextrocardia should be differentiated from secondary cardiac ward migration of the cardiac mass explains the development
dextroposition, which is defined as displacement of the heart of dextrocardia with situs solitus (dextroversion). Conversely,
to the right secondary to extracardiac causes such as right lung in situs inversus with L-loop (Figure 1B), the apex of the heart
hypoplasia, right pneumonectomy or diaphragmatic hernia.2 swings from the left hemithorax to the right, which explains
Dextrocardia occurs in approximately 0.01 percent of live the development of dextrocardia with situs inversus. Failure of
births1 and 0.008 percent of pregnancies.3 In a retrospective the shift of the apex of the heart to right hemithorax in L-loop
review of all cases of dextrocardia, the number of cases of can result in the development of levocardia with situs inversus
situs solitus, situs inversus and isomerism were found to be (levoversion). If the shift of the apex remains incomplete, it
similar.3 Cardiac malformations were more common in the results in mesocardia.
situs solitus (96%) and isomerism group (100%) compared
to situs inversus group (25%).3 Cardiac malformations were Clinical Presentation
complex in the situs solitus and isomerism groups.3
Incidental detection is common with mirror image dextrocar-
Types dia in normal intracardiac anatomy on chest X-ray done as
a screening test or for other medical disorders. In rest of the
1. Dextrocardia mirror image: This is true dextrocardia situations, the intracardiac anatomy would decide the type of
occurring with abnormal situs (situs inversus or ambiguous), presentation.
most common of which is situs inversus totalis. Physical appearance: Poland syndrome is reported with
2. Dextroversion dextrocardia: This type of dextrocardia situs solitus dextrocardia. It has absence of a pectoralis major
occurs with situs solitus. Here, the cardiac apex fails to pivot muscle, ipsilateral syndactyly, brachydactyly and hypoplasia
to the left and the heart appears to have twisted to the right. of a hand.4 Goldenhar syndrome is reported with complete
9
Cardiac Malpositions
A B
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 Echocardiography

vertebral dysplasia and hemifacial microsomia.5
On examination, check for chest asymmetry with right This non-invasive and convenient technique would be the
chest bulge. On percussion, gastric tympany, hepatic dullness gold standard to determining the type of dextrocardia, the
and cardiac dullness will give a clue about the dextrocardia intracardiac anatomy and physiology.
and situs. On auscultation, if prominent sounds are in the right It is important to start the examination from subcostal
anterior hemithorax compared to the left, suspect dextrocardia. view.6 The segmental approach will enable us to understand
the cardiac position and the anatomy of major cardiovascular
Investigations segments (visceral situs, atrial situs, ventricular looping and
relationship of great arteries).
Chest Roentgenogram
Cardiac Position and Base to Apex Axis
Before reading the chest X-ray, it is important to check the
marker (L or R). Chest X-ray is useful in demonstrating the When the heart is located in the left chest, right chest or
position of the heart, location of liver and stomach to determine midline, it is said to have levoposition, dextroposition or
the visceral situs (Figures 2A and B). It is important to check mesoposition respectively. When the cardiac axis (from base
for a curvilinear shadow in the right lung resembling scimitar. to apex) is oriented to the left, right or inferior, it is levocardia,
Secondary dextroposition can be suspected if the right lung dextrocardia or mesocardia respectively. This base to apex
appears hypoplastic (Figure 2C). axis is best defined by subcostal view (Figures 4A to C).
Subcostal 4-chamber view, when the cardiac apex is to the
Electrocardiogram right of midline, major axis of the heart is aligned from the
left shoulder to right hip, the morphological right atrium is to
It will show the P vector directed leftward and inferiorly in the right of morphological left atrium (atria are in their normal
situs solitus of the atria and rightward in situs inversus. In situs position or shifted slightly to the right) it is dextroversion.7
inversus with dextrocardia (mirror image), there is reversal When the major cardiac axis is between the left shoulder
of the QRS pattern in lead aVR and aVL. Hence, the major and the right hip, with the cardiac apex in the right fifth or
QRS is negative in lead one and aVL. The septal “q” waves sixth intercostal space at anterior axillary line and the right
depend on the looping of the ventricles in dextrocardia. The atrium is to the left of left atrium, it is dextrocardia—situs
frontal QRS axis has a right ward shift or right axis deviation. inversus.7 Though the major cardiac axis in dextroversion
In left precordial leads, a gradual reduction in the height of and dextrocardia situs inversus is the same, the angle is
the R-wave voltage in QRS complex (Figure 3A). Hence, it is more shifted to the right in dextrocardia situs inversus. In
necessary to obtain additional right precordial leads (V3R to dextroposition, though the heart is shifted to the right of
V6R) (Figure 3B). midline or in the retrosternal area with morphological right 137
2 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
Basics
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 second-
third 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
A 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

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
B 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 well-
described 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
C widely varying degrees of hypoplasia); dextroposition
of the heart; hypoplasia of the right pulmonary artery
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
(60%); systemic arterial blood supply to the right lower
dextrocardia with situs solitus. Note that the lung fields are oligemic; lung from the infradiaphragmatic aorta (60%); secundum
B. With a midline liver, indicating dextrocardia with situs ambiguous; ASD (40% overall, 80–90 % in the infantile variant);
C. With the right lung hypoplastic and shift of trachea to the right side, right-sided diaphragmatic hernia (15%) and horseshoe
138 likely dextroposition
lung. The infantile Scimitar syndrome, in addition to its
9
A
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
A B C
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 Scimitar syndrome can present in infancy with severe
of cardiovascular anomalies including ventricular septal symptoms, i.e. respiratory distress and severe pulmonary
defect, patent ductus, hypoplastic aortic arch, coarctation, arterial hypertension and has worse prognosis or can 139
tetralogy of Fallot, anomalous origin of the left coronary present in older children with recurrent respiratory tract
artery and truncus arteriosus.11 infections and a murmur.
2
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
 situs solitus, though situs inversus and ambiguous has also 9
Clues to differentiate types of dextrocardia on echocardiogram been seen. The types of the heart found in mesocardia are
same as those found in dextrocardia and levocardia.17
Dextroposition Dextroversion Dextrocardia
RA, RV on right RA, RV on right LA on the right of Isolated levocardia
side of LA, LV side of LA, LV RA
Major axis of heart Major axis of heart Major axis of heart When there is situs inversus or heterotaxy with levocardia,
pointing left from left shoulder from left shoulder it is considered a malposition. Isolated levocardia is rare.
to right hip to right hip The morphological right atrium is to the left and posterior
Entire heart to Apex to right of Apex in right fifth and the morphological left atrium is to the right and anterior,
right of midline/ midline intercostal space hence the term situs inversus, pivoted is used.2 Most of these
retrosternal
cases have been found to have atrioventricular discordance,
Transducer to right, PLAX plane in PLAX and PSAX in ventriculoarterial discordance or double outlet right ventricle
usual orientation of mirror image, mirror image
and right anterior aorta.8,18
plane PSAX normal
orientation
LA = Left atrium; LV = Left ventricle; PLAX = Parasternal long axis view; PSAX
Congenital pericardial defects
= Parasternal short axis view; RA = Right atrium; RV = Right ventricle
Congenital defects of pericardium are uncommon and difficult
to diagnose clinically. They are commonly detected as an
2. Situs inversus with dextrocardia is known to have much unexpected finding during surgery or autopsy. The incidence
less incidence of intracardiac abnormalities. It usually was found to be 0.044 percent among patients who underwent
occurs without coexisting congenital heart disease.12 cardiovascular surgery.19 Pericardial defects are due to
Associated anomalies included ventricular septal defect, defective formation of the pleuropericardial membrane or
tetralogy of Fallot, pulmonary atresia, complete atrioven- septum transversum.20
tricular septal defect, secundum ASD and atrioventricular It could range from minor partial defects to total absence of
concordance with ventriculoarterial discordance.13 Atriov- the pericardium.20 Two types of congenital pericardial defects
entricular with ventriculoarterial discordance is rare, but have been described: a complete form where there is absence
when present is associated with ventricular septal defect of the pericardium on one side of the heart, left or right and
with pulmonary stenosis.13 Rarely, isolated ventricular a partial form, where the defect is localized to a certain area
inversion is seen (atrioventricular discordance with ven- of the heart. Complete agenesis is not compatible with life.
triculoarterial concordance).13 Left-sided pericardial defects are more common.20,21 Right-
However, they are at a greater risk for pulmonary sided defects, diaphragmatic defects and total absence are
diseases than the general population. The most common of rare. Pericardial defects have been described with congenital
these is ‘Kartagener syndrome’ (KS). KS is an autosomal cardiac defects,19,22–24 though it is unlikely that they share the
recessive disorder14 characterized by dextrocardia, same pathogenic mechanisms.
bronchiectasis, sinusitis15 and infertility.16 The genetic cause for abnormal development of pericardium
is not clear. GATA4 gene is considered a candidate gene for
Treatment pericardial defects.25
Treatment must depend on the associated lesion seen. Readers Symptoms

are requested to refer to the corresponding chapters for
management. Most of the defects are asymptomatic.19 Sometimes, there
may be associated symptoms, some of which may be life-
Mesocardia threatening. There can be chest discomfort, recurrent
respiratory tract infections, palpitations, dizziness, syncope,
When the heart and the cardiac base-apex axis is directed to dyspnea or dysrhythmias.19 Gatzoulis et al found the chest
the midline of the thorax or with ventricular apices equally pain commonly as paroxysmal, sharp, stabbing (mimicking
directed to both the right and left sides, it is called mesocardia. coronary artery disease), of short duration, commonly in left
In other words, mesocardia is defined as a condition in which precordium and sometimes postural in nature, i.e. the pain
the longitudinal axis of the heart lies in the midsagittal plane, increases in supine or left lateral recumbent position and is
with the heart possessing no distinct apex.17 The atria lie side- relieved in semi-upright position.26 Sensation of ‘shifting
by-side and posterior to the ventricles with the atrial septum heart’ was also noticed by Gatzoulis et al.26 Awareness of heart
in an anteroposterior plane. The ventricles are anterior, more beats have been noted especially when patients are lying on
or less side-by-side (Figure 4C). Most of the mesocardia have the left side.21 141
2 In partial left-sided defects, there can be herniation of with decrease in the severity and frequency of pain in all
the ventricles through the patent pleuropericardial foramen patients after surgery.26
resulting in strangulation of the ventricles and sudden death or
Basics
herniation of the left atrial appendage. In right-sided defects, EctopiA cordis

herniation of the right lung into pericardial space can cause
superior vena cava (SVC) obstruction. In diaphragmatic Ectopia cordis is a rare congenital malformation where there
defects, greater omentum can herniate into pericardial space is complete or partial displacement of the heart outside the
causing cardiomegaly. thoracic cavity. The estimated prevalence of ectopia cordis is
Cause of chest pain in congenital absence of pericardium 0.079/10,000 births and more frequently seen in females.27
is unclear. It has been suggested to be multifactorial.26 It Ectopia cordis may be classified into cervical (5%),
could be due to herniation of left atrial appendage, torsion thoracic (65%), thoracoabdominal (20%) or abdominal (10%)
of the great vessels due to increased heart mobility, lack of types.28–30 The thoracic and thoracoabdominal types are the
pericardial cushioning, tension on pleuropericardial adhesion, most common followed by abdominal and cervical types of
pressure on the pericardial rim or constriction of the coronary ectopia cordis.31 The heart is found completely uncovered,
arteries by fibrous bands. covered with a serous membrane or with skin.28
Ecopia cordis is usually associated with Cantrell pentalogy
Diagnosis or a variant of Cantrell pentalogy with sternal defect.32 Cantrell
pentalogy is characterized by a midline supraumbilical
Physical examination usually does not provide any evidence abdominal wall defect/omphalocele, a defect of the lower
for the diagnosis of pericardial defect. The apical impulse may sternum, a deficiency of the anterior diaphragm, a defect in
be hyperactive and displaced to the left. A systolic ejection the diaphragmatic pericardium and congenital intracardiac
murmur can appear at the left sternal border. defects.33
The electrocardiogram is usually normal, though in
complete defects may show a right axis deviation and Pathogenesis
clockwise rotation probably due to anomalous rotation of the
heart. Incomplete right bundle branch block pattern has also Complete or incomplete failure of midline fusion of lateral
been reported in complete form of absent pericardium.26 folds has been proposed to result into ectopia cordis. Early
Chest X-ray was found to be diagnostic in 90 percent of rupture of the chorion and/or the yolk sac causing compression
patients.26 With a complete left pericardial defect, the heart of the thorax and preventing midline fusion has also been
is shifted to the left resulting in loss of the right heart border proposed as mechanical cause for development of ectopia
and the left heart border has bulges at the aortic knob, the cordis.34 Early rupture of the amnion with formation of fibrous
pulmonary artery or the left ventricle. A part of the lung may amniotic bands also has been postulated.35,36
insert between the aorta and pulmonary artery or between the
diaphragm and the inferior border of the heart. With a partial Associated Anomalies
left defect, there may be prominence of the pulmonary artery
or the left atrial appendage. Variety of congenital heart diseases have been seen to be
In echocardiogram, the apical windows are laterally associated with ectopia cordis, though ventricular septal defect,
displaced. For parasternal views, lateral placement of the atrial septal defect, tetralogy of Fallot and diverticulum of the
transducer might be needed. ventricle are the most common.31,37 Other congenital anomalies
In the current era, computed tomography (CT) scan or like abdominal wall defects, cranial and facial malformations,
magnetic resonance imaging (MRI) of the chest can confirm cleft lip and palate, anencephaly, hydrocephaly, neural tube
the diagnosis and give information regarding the extent of the defects, pulmonary hypoplasia, genitourinary malformations
defect. and gastrointestinal defects are seen with ectopia cordis.38–40
The complexity of the associated congenital cardiac defect
Treatment contributes to poor prognosis.37 Trisomy 18 and Turner
syndrome have been reported with ectopia cordis.41–45
Asymptomatic complete absence of the pericardium and
small defects require no intervention. Partial forms of Management
pericardial defects may require surgical intervention,
especially when symptomatic. Surgery is indicated for As ectopia cordis can be detected antenatally and is commonly
debilitating symptoms and for herniation with parital absence opted for termination due to a low survival rate, it is becoming
of pericardium. Surgical options include enlargement of the uncommon in clinical practice. Surgical correction requires a
defect to avoid the risk of strangulation and closure with a staged approach including coverage of the heart, placement of
142 flap of mediastinal pleura. Symptomatic benefit is reported the heart into the thorax and sternal/thoracic reconstruction.37
Intracardiac repair is commonly performed after the first stage in einem falle familiarer Bronchiektasien. Beitr Klin Tuberk.
1935; 87:331-3.
9
operation.38 Operations for thoracoabdominal ectopia cordis
carry extremely high-risk with only few survivors of thoracic 16. Guerrant JL, Douty T, Tegtmeyer C, et al. Bronchiectasis in the
immotile cilia syndrome. New Eng J Med. 1978; 298:282.
ectopia cordis.46
17. Lev M, Liberthson RR, Golden JG, et al. The pathologic
anatomy of mesocardia. Am J Cardiol. 1971; 28:428-35.
Conclusion 18. Stanger P, Rudolph AM, Edwards JE. Cardiac malpositions:
An overview based on study of sixty-five necropsy specimens.
A sequential segmental approach with an understanding of the Circulation. 1977; 56:159-72.
possible malpositions with their associations would greatly 19. Vas Son JAM, Danielson GK, Schaff HV, et al. Congenital
facilitate the diagnosis of congenital heart disease. partial and complete absence of the pericardium. Mayo Clin
Proc. 1993; 68:743-7.
The doctor is often more to be feared than the disease. 20. Southworth H, Stevenson CS. Congenital defects of the
pericardium. Arch Intern Med. 1938; 61:223-40.
—French Proverb
21. Ellis K, Leeds NE, Himmelstein A. Congenital deficiencies
in the parietal pericardium: A review with 2 new cases
References including successful diagnosis by plain roentgenography. Am J
Roentgenol Radium Ther Nucl Med. 1959; 182:125.
1. Evans WN, Acherman RJ, Collazos JC, et al. Dextrocardia: 22. Nasser WK, Helmen C, Tavel ME, et al. Congenital absence
Practical clinical points and comments on terminology. Pediatr of the left pericardium. Clinical, electrocardiographic,
Cardiol. 2010; 31:1-6. radiographic, hemodynamic and angiographic findings in six
2. Bharati S, Lev M. Positional variations of the heart and its cases. Circulation. 1970; 41:469-78.
component chambers. Circulation. 1979; 59:886-7. 23. Skalski J, Wites M, Haponiuk I, et al. A congenital defect of the
3. Bohun CM, Potts JE, Casey BM, et al. A population-based pericardium. Throac Cardiovasc Surg. 1999; 47:401-4.
study of cardiac malformations and outcomes associated with 24. Drury NE, De Silva RJ, Hall RMO, et al. Ann Thorac Surg.
dextrocardia. Am J Cardiol. 2007; 100:305-9. 2007; 83:1552-3.
4. Fraser FC, Teebi AS, Walsh S, et al. Poland sequence with 25. Jay PY, Bielinska M, Erlich JM, et al. Impaired mesenchymal
dextrocardia: Which comes first? Am J Med Genet. 1997; 73:194. cell function in GATA4 mutant mice leads to diaphrag
5. Gorgu M, Aslan G, Erdooan B, et al. Goldenhar syndrome with matic hernias and primary lung defects. Develop Biol. 2007;
situs inversus totalis. Int J Oral Maxillofac Surg. 1998; 27:404. 301:602-14.
6. Snider AR, Serwer GA, Ritter SB. Diagnostic approach to 26. Gatzoulis MA, Munk MR, Merchant N, et al. Isolated congenital
Complex Congenital Heart Disease. In: Echocardiography in absence of pericardium: Clinical presentation, diagnosis and
Pediatric Heart Disease 2nd edition; 1997. p. 560. management. Ann Thorac Surg. 2000; 69:1209-15.
7. Calcaterra G, Anderson RH, Lau KC, et al. Dextrocardia: value 27. Khoury MJ, Cordero JF, Rasmussen S. Ectopia Cordis, midline
of segmental analysis in its categorisation. Br Heart J. 1979; defects and chromosome abnormalities: An epidemiologic
42:497. perspective. Am J Med Genet. 1988; 30:811-7.
8. Van Praagh R, Van Praagh S, Vlad P, et al. Diagnosis of anatomic 28. In: Skandalakis JE, Gray SW, Ricketts R, Skandalakis JE, Gray
types of Dextrocardia. Am J Cardiol. 1965; 15:234-43. SW, (eds). Embryology for surgeons. 2nd edition. Baltimore:
9. Lev M, Liberthson RR, Eckner FAO, et al. Pathologic anatomy Williams and Wilkins; 1994. pp. 552-9.
of dextrocardia and its clinical implications. Circulation. 1968; 29. Blatt ML, Zeldes M. Ectopia Cordis: Report of a case and
37:979-99. review of the literature. Am J Dis Child. 1942; 63:515.
10. Van Praagh R, Vlad P. Dextrocardia, mesocardia and 30. Byron F. Ectopia Cordis: report of a case with attempted
levocardia: The segmental approach to diagnosis in congenital operative correction. J Thorac Surg. 1949; 17:717-22.
heart disease. In: Keith JD, Rowe RD, Vlad P (Eds). Heart 31. Leca F, Thibert M, Khoury W, et al. Extrathoracic heart (ectopia
Disease in Infancy and Childhood. 3rd edition. New York: cordis). Report of two cases and review of the literature. Int J
Macmillan; 1978. p. 638. Cardiol. 1989; 22:221-8.
11. Gudjonsson U, Brown JW. Scimitar Syndrome. Semin Thorac 32. Cantrell JR, Haller JA, Ravitch MM. A syndrome of
Cardiovasc Surg Pediatr Card Surg Ann. 2006; 9:56-62. congenital defects involving the abdominal wall, sternum,
12. Merklin RJ. Cardiac lesions associated with visceral inversion: diaphragm, pericardium and heart. Surg Gynecol Obstet.
A study of 185 cases. J Int Coll Surg. 1964; 4:597. 1958; 107:602-14.
13. Van Praagh R, Weinberg PM, Smith SD, et al. Malpositions 33. Laberge JM. Defination of pentalogy of Cantrell. Commentary
of the heart. In: Adams FH, Emmanoulides GC, on Araujo Junior et al: diagnosis of pentalogy of Cantrell by
Riemenschneider TA, (Eds). Heart Disease in Infants, three-dimensional ultrasound in third trimester of pregnancy
Children and Adolescents. 4th edition, Baltimore: Williams (Fetal Diagn Ther 2006; 21:544-7). Fetal Diagn Ther. 2008;
and Wilkins; 1989. p. 530. 23:168.
14. Gorham GW, Merselis JG Jr. Kartagener’s triad: a family 34. Kaplan LC, Matsuoka R, Gilbert EF, et al. Ectopia cordis and
study. Bull Johns Hopkins Hosp. 1959; 104:11-6. cleft sternum: Evidence of mechanical teratogenesis following
15. Kartagener M, Horlacher A. Zur pathogenese der rupture of the chorion or yolk sac. Am J Med Genet. 1985;
Bronchiektasien; Situs viscerum inversus and polyposis nasi 21:187-99.
143
2 35. Van Allen MI, Myhre S. Ectopia Cordis thoracalis with
craniofacial defects resulting from early amnion rupture.
41. Bick D, Markowitz RI, Horwich A. Trisomy 18 associated with
ectopia cordis and occipital meningocele. Am J Med Genet.
Teratology. 1985; 32:19-24. 1988; 30:805-10.
Basics
36. Bieber FR, Mostoufi-zadeh M, Birnholz JC, et al. Amniotic 42. Fox JE, Gloster ES, Mirchandani R. Trisomy 18 with Cantrell
band sequence associated with ectopia cordis in one twin. J Pentalogy in a still born infant. Am J Med Genet. 1988; 31:
Pediatr. 1984; 105:817-9. 391-4.
37. Amato JJ, Zelen J, Talwalkar NG. Single stage repair of 43. King CR. Ectopia Cordis and chromosomal errors. Pediatrics.
thoracic ectopia cordis. Ann Thorac Surg. 1995; 59:518-20. 1980; 66:328.
38. Hornberger LK, Colan SD, Lock JE, et al. Outcome of patients 44. Soper SP, Roe LR, Hoyme HE, et al. Trisomy 18 with ectopia
with ectopia cordis and significant intracardiac defects. cordis, omphalocele and ventricular septal defect. Case report.
Circulation. 1996; 94:32-7. Pediatr Pathol. 1986; 5:481-3.
39. Hochberg J, Ardenghy MF, Gustafson RA, et al. Repair of 45. Garson A, Hawkins EP, Mullins CE, et al. Thoracoabdominal
thoracoabdominal ectopia cordis with mucocutaneous flaps ectopia cordis with mosaic Turner’s syndrome. Report of a
and intraoperative tissue expansion. Plast Reconstr Surg. 1995; case. Pediatrics. 1978; 62:218-21.
95:148-51. 46. Morales JM, Patel SG, Duff JA, et al. Ectopia cordis and other
40. Diaz JH. Perioperative management of neonatal Ectopia midline defects. Ann Thorac Surg. 2000; 70:111-4.
cordis: report of three cases. Anest Analg. 1992; 75:833-7.
144
c hapter
10 Heterotaxy syndrome
Smita Mishra, Seema Thakur
IntroductIon Box 1: Terminologies

Situs solitus (SS): The normal left-right anatomical arrange-
Visceral heterotaxy or heterotaxy syndrome (HS) results
ment recognized in relation to the visceroatrial position.
from embryological failure to establish normal left and
Situs inversus (SI): Complete reversal of asymmetrical struc-
right asymmetry. As a consequence, there is an unusual tures in the thorax and abdomen. It occurs in approximately 1
spatial arrangement of thoracic and/or abdominal organs in in 8,000–25,000 individuals.
relationship to each other and this does not predict a final Situs ambiguous (SA): If right and left patterns of ordinarily
clinical or physiological outcome. asymmetrical structures like liver, spleen, atrial appendage,
This chapter analyses the dilemma in nomenclature, bronchus, etc. are unidentifiable and discordant.
management options of diverse lesions, long-term management It is recently defined as ‘an abnormality in which, there
of asplenia and primary ciliary dyskinesia (PCD). It also deals are components of situs solitus and situs inversus in the
same person. Situs ambiguous, therefore, can be considered
with embryological and genetic aspect of the disorder.
to be present when the thoracic and abdominal organs are
positioned in such a way with respect to each other as to be not
IncIdence1–5 clearly lateralized and thus have neither the usual or normal,
nor the mirror-imaged arrangements’. (Nomenclature Working
In general, the incidence of HS is 1/10,000 to 20,000 Group, 2007).
livebirths. It usually occurs sporadically. Although familial, Heterotaxy (Synonyms: Heterotaxy syndrome (HS) or
X-linked, autosomal recessive and dominant occurrence visceral heterotaxy): Heterotaxy is defined as an abnormality
where the internal thoracoabdominal organs demonstrate
are reported in literature, the recurrence rate in the same
abnormal arrangement across the left-right axis of the body.
family is just below 5 percent.5 The incidence tends to
Isomerism of right atrial appendage (IRAA): When both
be as high as 3 percent in neonates with congenital heart atrial appendages are morphologically right atrial appendage
disease (CHD) and 30 percent in babies dying with cardiac and cardiac and non-cardiac thoracoabdominal viscera show
malposition.1–5 In a large cohort study at least 6.3 percent of abundance of right-sided morphological features like bilateral
patients with PCD had heterotaxy. The prevalence of CHD trilobed lung, eparterial bronchi or absence of spleen.
with HS is 200 fold higher in PCD than general population Isomerism of left atrial appendage (ILAA): When both
(1: 50 vs 1:10,000). Hence screening for PCD is required in atrial appendages are morphologically left atrial appendage
and cardiac and non-cardiac thoracoabdominal viscera show
the HS patients.7,8 abundance of left-sided morphological features like bilateral
bilobed lung, hyparterial bronchi or presence of multiple spleen.
termInologIes1–6 Polysplenia syndrome: It can be defined as a subset of
heterotaxy with components of bilateral left-sidedness, usually
The important terms related to heterotaxy syndrome are given associated with multiple spleens.
in Box 1. Asplenia syndrome: It can be defined as a subset of hetero-
taxy with components of bilateral right-sidedness, usually as-
sociated with an absence of the spleen.
embryology and genetIcs
Ivemark syndrome: It is a term that, historically, is synony-
mous with asplenia syndrome. Other synonyms have been
Embryologically, the timing of origin of the disorder can be used for HS with asplenia including asplenia syndrome, bilater-
ascribed to the 5th week of gestation or Streeter horizon.13 al right-sidedness sequence and splenic agenesis syndrome.
This is the time when important developmental events like
2 bending and septation of cardiac loop and conotruncus, cardiac development because development of spleen, division
growth of endocardial cushion, location of lungs, rotation of of atrioventricular canal and the conotruncus, somewhat
gut, pulmonary venous connection to the roof of left atrium coincide in fetal life.1–6,21–24 The polysplenia initially was
BASIcS
(LA) and development of spleen takes place.9,10 overlooked as a marker of one more subset of HS till Moller
Over 100 genes have been identified as important in left- et al (1967) published another breakthrough paper of their own
right asymmetry in animal models.11–17 The heterogeneity findings and correlated it with previously published literature.
of genes related to HS, combined with a prediction of They found that these polysplenic patients had a tendency for:
reduced penetrance and variable expressivity, makes clinical 1. Cardiac malposition.
molecular diagnostics challenging. Patients with Trisomy 2. Interruption of inferior vena cava (IVC) with azygos
13 or Trisomy 18 have been reported to have heterotaxy. A continuation.
number of submicroscopic chromosomal deletions, including 3. Partial or total anomalous pulmonary venous connection to
22q11.2 (DiGeorge/velocardiofacial syndrome [VCFS]), have the venous atrium.
been identified in patients with heterotaxy.11,12 The majority 4. Bilateral superior vena cava
of mutations identified have been shown to have reduced 5. Defects in the atrial and ventricular septa
penetrance and variable expressivity, indicating multifactorial Additionally, they reported presence of extracardiac
causation. Environmental modifiers such as maternal diabetes, abnormalities that was:
maternal cocaine use and monozygotic twinning have all been 1. Partial or complete abdominal heterotaxy
associated with heterotaxy spectrum defects.15 2. Abnormality of pulmonary lobulation
The X-linked form of heterotaxy, HTX-1 (OMIM# :306955) 3. Symmetrical liver.23
is caused by mutations in a zinc finger transcription factor, These evolutionary findings fueled further debate regarding
ZIC3. X-linked heterotaxy, caused by mutations in ZIC3, is the the terminology of HS and splenic morphology.
best understood genetic cause of heterotaxy.16,17 Interestingly, The terminological address of spectrum of HS evolved
mutations in this gene can cause classic heterotaxy or isolated slowly. Evidently it needed a large numbers of publications
congenital heart defects. In one family, three of nine female and extensive discussions to reach to a consensus so that
carriers exhibited situs inversus. Approximately, 1 percent of current nomenclature and terminology could prevail.1–6
sporadic heterotaxy cases (male and female) and greater than
75 percent in familial X-linked heterotaxy cases are due to controversies in nomenclature25–27
ZIC3 mutations.17
Heterotaxy patients without mutations in ZIC3 have been It had been the convention over the years to describe these
screened for mutations in genes involved in the conserved characteristic groups of HS in terms of asplenia and polysplenia.
nodal signal transduction pathway.18 The mutations have been Afterwards, it was clear that these splenic morphological
identified in genes encoding the ligand (NODAL), ligand abnormalities are vacillating, henceforth cannot be reckoned
coreceptor (CFC-1), receptor (ACVRIIB), transcriptional co- as a sole pennant of HS. Subsequently, attention was drawn
activator (FOXH1) and midline inhibitor (LEFTYA) within towards the unique morphological resemblance of two
the nodal signal transduction pathway.12,19 atrial appendages (Figures 1A to C). Umera and Anderson
The PCD disorders are characterized by abnormalities et al highlighted that description of the morphology of the
of ciliary structure and function and are most commonly appendages as well as the venoatrial connections, were more
autosomal recessive. Heterotaxy with PCD is caused by conclusive than anything else. As it was pointed out by Van
mutations in DNAH5 and DNAH11 genes.20 Praagh, Anderson’s group themselves changed their stand
later, by advocating the inner anatomy of appendages as the
HIstorIcal background and nomenclature basis of diagnosis rather than the outer morphology. Now
there is a consensus regarding the description of HS on the
“…asplenia, is a teratologic syndrome of visceral symmetry…” broader basis rather than diagnosing it as right atrial (RA) or
— Ivemark 195522 LA isomerism and isomerism of atrial appendages is to be
accepted as a real anatomic entity (See Box 1).
The first case on record of this combination of anomalies
is that of Martin (1826), who described the necropsy findings recommendations of nomenclature Working group for
of a case of septal defect, transposition of the great vessels Pediatric and congenital Heart disease (2007)6
and agenesis of the spleen. In 1955, Biorn Ivemark (1955)
published his landmark paper, which included analyses This group reviewed the nomenclature, definition and
of all the cases from the published literature, as well as his classification of heterotaxy and emphasized more on sequential
own 14 cases, in which he postulated that it was possible to segmental analysis (Table 1). The few of the recommendations
have teratogenic effect of some genetic factor on splenic and are as follows:
146
10
HeTeRoTAxy SyndRome
A B
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%, 50–90%, >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
2 1. Description of cardiac and non-cardiac thoracoabdominal either of the groups. Discordant ventricular apex and stomach
structures: The cardiac anatomy and associated cardiac relationship predicts a complex CHD.
malformations, as well as the relationship and arrangement
BASIcS
of the remaining thoracoabdominal organs, must be Venoatrial Connection5,6,28–33

described separately.
2. Splenic morphology: Less than perfect association between Systemic venoatrial connections: The most important clue
the state of the spleen and the form of heart disease implies of morphological RA is its connection with IVC or absence
that the splenic morphology should be investigated in all of it (IVC interruption), which can be delineated by various
the forms of heterotaxy. The splenic morphology should imaging modalities. We will see in further analyses that there
not be used to stratify the form of disease within the heart may be exceptions to this rule.
and the form of the cardiac disease should not be used to Isomerism of right atrial appendage: Abnormal systemic
stratify the state of the spleen. venoatrial connections are the integral part of the syndrome.
3. Malrotation of gut: Intestinal malrotation is another IRAA is usually associated with bilateral superior vena cava
frequently associated lesion that must be considered. (SVC). The coronary sinus (CS), which collects systemic
venous blood from the persistent left superior vena cava
abnormalItIes of tHoracoabdomInal (LSVC) and cardiac veins, is usually absent. The cardiac veins
organs In Heterotaxy syndrome and persistent LSVC directly drain into either of the atrium.
IVC can drain into either of the atrium or centrally. The IVC
As mentioned above, the HS needs to be evaluated based on and aorta tend to remain juxtaposed on either sides of the
segmental analysis of the heart and a individualized approach midline (Figure 3A). The hepatic veins may drain into the IVC
to other organs. To accomplish it, the ‘morphological or occasionally anomalously to either of the atrium. Usually
method’ described initially for cardiac evaluation by Lev the left hepatic vein drains into the left sided atrium, which
et al and subsequently by Van Praagh and his associates, represents the morphological left sided IVC (Figure 4A).
must be followed. This principle states that structures should Isomerism of left atrial appendage: Generally, isomeric
be identified according to the component part that is most hearts with ILAA are associated with bilateral SVC and
universally present.27–31 have interrupted IVC. The suprarenal (hepatic) part of IVC
The first step in the assessment of the cardiac anatomy is missing here and hepatic veins may form a confluence
is to locate and identify the LA and RA. Anatomically, the or drain individually into the either of the atrium. The
atrial chamber differentiation based on the morphology of infrahepatic part of the IVC remains intact. Moreover, sizeable
atrial appendages are not reliably identifiable at ultrasound or number of patients may have missing coronary sinus. The
radiologic imaging and the localization of non-cardiac organs echocardiographic diagnosis of ILAA is based on the absence
is more helpful in determining the atrial situs. These non- of hepatic portion of IVC in the subcostal transverse section
cardiac organs are: and demonstration of ascending dilated retroaortic venous
1. Thoracic level—right and left bronchus and lungs. channel (azygos/hemiazygos venous system). In ILAA, the
2. Abdominal level—liver, spleen, descending aorta and the hemiazygos vein is usually present bilaterally and may drain
inferior vena cavae (Figure 2). into the CS, RSVC or LSVC (Figures 3B and 4B). However,
It is apparent from the various analyses, (Table 2), that the interrupted IVC can be seen in the IRAA as well as in
none of the findings are sacrosanct for isomerism of right patients with normal or non-isomeric hearts. Figure 3C is
atrial appendage (IRAA) or isomerism of left atrial appendage demonstrating a rare case of ILAA with intact IVC draining
(ILAA) and can be shared by either of groups. In general, IRAA into the floor of the left-sided atrium.
group usually presents with severe cardiac malformations Pulmonary venoatrial connections33–35: In IRAA, any type
whereas ILAA present with extracardiac malformations. With of total anomalous pulmonary venous drainage or connection
this basic understanding now we precede to the rest of chapter (TAPVD or TAPVC) is common because true morphological
and analyze: LA is absent in this group. Commonly, this connection is
A. Cardiovascular system obstructed irrespective of the site of drainage.
B. Extracardiac thoracoabdominal organs. In ILAA, pulmonary veins try to drain to the respective
isomeric atrium and partial anomalous pulmonary venous
anatomical configuration of cardiovascular system drainage (PAPVD) or TAPVD due to malaligned interatrial
and segmental analysis5,6,28–31 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
Cardiac Position patient had a short obstructed channel draining the pulmonary
The cardiac position is variable and all kinds of cardiac posi- venous confluence to the atrium. In ILAA group 7 out of 11
148 tions—levocardia, dextrocardia or mesocardia, can be seen in 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 Anatomy1,5,6,21–31 has an extensive junction with the vestibule of the RA; the
later structure is the smooth-walled atrial myocardium that
The RA has three basic parts: the appendage, the vestibule inserts into the leaflets of the tricuspid valve. The most
and the venous component. The right atrial appendage has the characteristic and constant feature of the morphology of the
shape of a blunt triangle, with a wide junction to the venous RA is that the pectinate muscles within the appendage extend
component across the terminal groove. The appendage also around the entire parietal margin of the atrioventricular (AV) 149
2 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
BASIcS
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).
A 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 Valve4–6,23–31
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.1–6,23–31
B The right ventricle (RV) is described as tripartite structure
having three components—inlet, 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,
c this may not be easy in presence of common AV junction or
unbalanced ventricles. Also in presence of grossly unbalanced
Figures 3A to c: Computed tomography (CT) angiography: A. CT
angio at T12, L1 level. Isomerism of right atrial appendage; right juxta- ventricles, the inner morphology becomes difficult to decipher.
position of inferior vena cava (IVC)/Abdominal Ao. Central liver; B. However, the ventricular looping and morphology follow the
CT angio at T12, L1 level. Isomerism of left atrial appendage; azygos usual normal or abnormal pattern (D or L loop) of evolution
continuation of IVC behind the abdominal Ao. Central liver and; C. and morphologically ventricles are never isomeric. It is not
150 CT angio at T12, L1 level. Isomerism of left atrial appendage; intact
suprarenal IVC in left isomerism. Central liver. (Courtsey: Apoorva uncommon to find univentricular heart with indeterminate
Goyal, Francis A) ventricular morphology.
10
HeTeRoTAxy SyndRome
A B
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 In ILAA, partial or transitional AVSD with two distinct AV
AV junction or the so called atrioventricular canal defect orifices, is common. However, presence of normal AV junction
(AVCD). This has also been called endocardial cushion defect with or without shunt lesions is not uncommon in ILAA.
or atrioventricular septal defect (AVSD). These defects Cardiac structure in ILAA may be completely normal or may
have varying degrees of incomplete development of the AV have simple heart defects. VSD is the usual finding in HS.
septal tissue adjacent the AV valves along with spectrum In IRAA, preponderance of common AV junction
of abnormalities of the AV valves themselves. Partial predisposes for a true large inlet VSD, but other types of
AVSD or incomplete AVSD has an ostium primum ASD isolated or additional defect like, perimembranous, outlet,
and abnormal left AV valve. Typically the left AV valve doubly committed and muscular, can be present.
in this subset differs from the normal MV. It is guarded In ILAA, an inlet VSD may be present as a part of AVSD.
by three leaflets and has a cleft essentially facing the IVS. Because common AV junction in this group usually manifest
Complete AVSD (CAVSD) has both defects in the atrial as partial or transitional AVSD, inlet VSDs is less frequent in
septum just above the AV valves (ostium primum ASD) and comparison to the IRAA. Other varieties of VSD can be seen
defects in the ventricular septum just below the AV valves. in this group.
In CAVSD, the AV valve is one valve that bridges both the
right and left sides of the heart, creating superior (anterior) outflow in Heterotaxy5,23–25,36,37
and inferior (posterior) bridging leaflets. Transitional or
intermediate AVSD is in-between and has two distinct The conotruncal abnormalities are frequent associations of
orifices, but also has an ASD just above and a ventricular HS. The outflows can be obstructed, partially or completely in
septal defect (VSD) just below the AV valves. The VSD both IRAA and ILAA.
in this lesion is often restrictive. The AV valves in all the IRAA, is usually associated with right ventricular outflow
three forms may be grossly abnormal, often regurgitant and tract (RVOT) obstruction and pulmonary valve anomaly.
prognosticate a suboptimal surgical outcome. In ILAA, on the contrary, the left ventricular outflow tract
In IRAA, CAVSD and common AV valve with common (LVOT) obstruction is common.
orifice is frequently associated. The tethering and type of Besides, both the groups in HS may be associated with
straddling of the superior and inferior bridging leaflets abnormal ventriculoarterial connection like transposition and
forms the hemodynamic basis for complex AV connections, double outlet right or left ventricle (Table 2).
abnormal flow pattern, resulting in developmentally
unbalanced ventricles. Sometimes, in the absence of AVSD, Conduction System
various degree of overriding, straddling of AV valves may lead
to serious consequences. The aforesaid complex intracardiac Patients with IRAA may be associated with bilateral
anatomy is the substrate for univentricular or Fontan type sinoatrial (SA) node. However bilateral presence of SA node
repair in majority of cases of IRAA. is not a universal finding as was shown by Ware et al who
151
2 demonstrated the presence of bilateral sinus nodes in only AV node is seen or a sling of conduction tissue is seen along
54 percent of the cases.38 the crest of IVS, connecting an anterior and posterior AV node.
In ILAA, bilateral absence of sinus nodes is seen frequently. Pattern is almost same when RV is the dominant ventricle, but
BASIcS
Ware et al documented bilateral absence of SA node in if LV is dominant with RV as a small ventricle, the AVN is
25 percent of cases with left isomerism.38 anterior and lies in relation to the LVOT.4,5
The pathways for AV conduction in hearts with isomerism
of the atrial appendages are conditioned both by ventricular Coronary Arteries in Heterotaxy
topology and by the AV connections. No pathognomonic
variation is seen in HS. Umera et al reported abnormal patterns in branching of the
In D-loop ventricle, an AV node is in its regular position, coronary arteries, associated with abnormal ventricular
with a posteroinferior penetrating bundle, which is further architecture. The morphologically LV/RV arteries were
posteriorly deviated in presence of AVSD. In L-loop ventricle, frequently lacking in those hearts with a dominant ventricle
the conduction system simulates to that of congenitally and a rudimentary or incomplete ventricle. A solitary coronary
corrected transposition of great vessels, i.e. either an anterior artery was seen in 13 percent of cases.39

Table 2
Usual morphological features in heterotaxy
Clinical and morphological Isomerism of left atrial appendage Isomerism of right atrial appendage
features
Heart position Levocardia: 50–75% dextrocardia: 2–10% Levocardia: 63%, rest dextro or mesocardia
Systemic veins Absence of intrahepatic portion of IVC with Bilateral SVC: 50–60% 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 90–96% of cases.
Bilateral SVC: 40% cases and absent coronary
sinus in 30–55% cases.
Pulmonary veins PAPVC: 40–60% with ipsilateral veins draining TAPVC > 50%, up to 40% case have
into respective atrial chamber. TAPVC 10–12% obstructed vertical vain
usually due to malalignment of atrial septum.
Scimitar syndrome 1%
Atria Both atrial appendages are both atrial Both atrial appendages are both atrial
appendages are morphological LAA: Long appendages are morphological RAA: Broad
narrow and pectinate muscles restricted upto base, thumb like in little anterior plane and
the base of appendage and not going beyond. pectinate muscle extending beyond the base
No crista terminalis, fossa ovalis is often of appendage.
absent. Large ostium primum defect in 50–65% Bilateral crista terminalis, fossa ovalis is
cases. However, fenestrated fossa ovalis, intact often absent. Common atrium or large ostium
atrial septum, sinus venosus ASD also have primum defect in majority of the cases, isolated
been reported. or as a component of complete AVSD.
Atrial septum/atrioventricular Common AV junction, partial AVSD with two Common AV valve associated with complete
(AV) junction/valve distinct AV orifices and cleft in left component or partial AVSD 80–90%. Common atrium
of AV valve. Ostium primum ASD is frequent where single strand runs through cavity or a big
as a part of partial AVSD. Other kind of ASDs secundum ASD along with ostium primum ASD
(secundum/sinus venosus can also be seen. (like common atrium) has been reported.
AV connection Univentricular connection: 10–40% Univentricular connection > 72%
RVOT/LVOT Pulmonary stenosis/atresia: 28–30% Pulmonary stenosis/atresia: Up to 80–90%,
LVOTO: 40% (coarctation of aorta 16%; LVOTO uncommon
AS 10%)
VA connection Are abnormal in 50% patients. TGA: 16%, Abnormal ventriculoarterial connection—
DORV: 32%, DOLV: 7% discordant, double oulet or single outlet:
90–96%
Significant CHD Less frequent > 98%
Conduction system Sinus node may be absent There may be two sinus node
152
Contd...
Contd... 10
Clinical and morphological Isomerism of left atrial appendage Isomerism of right atrial appendage
HeTeRoTAxy SyndRome
features
Lungs and bronchi Symmetrical, left bronchus and left lung Symmetrical, right bronchus and right lung
morphology bilaterally (90%) (trilobed) morphology bilaterally (90%)
Congenital lobar pneumonia
Spleen Majority multiple (88%), absent (5%); single in Majority-absent (80%) few: single (17%)
few multiple (4%)
Liver Symmetrical (25–70%), right-sided Symmetrical (majority of cases)
or left-sided
Stomach May be placed in center, right or left May be placed in center, right or left
hypochondrium 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 Usually no biliary abnormalities
are seen like mirror image branching,
quadruplicating or ciliary atresia, cholelithiasis
Percentages listed are approximations based on review of references22,29–31,34,36–39,49,50,52,53
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 IRAA, the lungs are trilobed bilaterally and are connected
in Heterotaxy Syndrome to eparterial bronchi. Both the branches of pulmonary artery
show the morphological pattern of right PA as they travel
Many other cardio-pulmonary anomalies like pulmonary below and anteroinferior to the bronchus on both the sides to
hypertension and portopulmonary shunt, have been described enter into the respective hilum. The corresponding bronchus
but can not be associated consistently with HS. There are enters underneath the PA after giving rise to its first branch
isolated reports of association of pulmonary emphysema, (eparterial branch). The ratio of the length of bronchi measured
non-compacted LV, scimitar syndrome, isolated pulmonary from bifurcation of trachea to the origin of first branch from
sequestration and bronchomalacia, mostly in ILAA group.40–43 bronchus, remains <1.5.
In ILAA, both the bronchi have the same length and the
anatomical arrangement and structure of extracardiac first branch of both the bronchi arise most distally (hyparterial
thoracoabdominal organs in Heterotaxy 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.
Lungs and Bronchial Anatomy43–45 Van Meirope et al suggested that the chest roentgenogram
The ratio between left (bronchus sinister) and right in anteroposterior or posteroanterior view can be best way
bronchial (bronchus dexter) length is usually 2 : 1. Also the of knowing atrial situs, as it always corresponds to tracheo-
branch pulmonary arteries (PAs) are in a unique relationship bronchial tree.44 This conventional thinking is not valid
with the ipsilateral bronchi. Accordingly, the first branch of absolutely and evidences to contrary, i.e. atriobronchial
the right bronchus can be described as ‘eparterial or that discordances, are cropping up.44–47
of the left bronchus as hyparterial’.45–47 The lungs differ Yet, in clinical settings, loss of bronchopulmonary
from each other in the number of their lobes, consequently asymmetry is most easily discernible and useful clue to the
the bronchi differ in their mode of subdivision (Figures 5A diagnosis of HS.
to D). The right lung has three lobes, one oblique and one In a recent publication, the five thoracic features in 306
horizontal fissure. The left lung has two lobes, one major postmortem specimens were assessed to evaluate broncho-
oblique fissure. These features can be appreciated in plain atrial relationship and its validity as a marker of atrial situs. 153
chest roentgenogram.45–47 The results showed a good, but variable predictive value of
2
BASIcS
A B
c d
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 Morphology of spleen in ILAA5,6,48–54: The splenic mass
branch pulmonary artery are given in Table 3. is usually divided into fairly equally sized 2 to 6 masses or
splenules. Usually these splenules are 1 to 6 cm in diameter,
abdomen in Heterotaxy 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
Liver 5,6,24–26,49,50
these splenules may be along the greater curvature of the
The liver normally has two lobes. The right lobe is usually stomach, in the left or right upper quadrant of abdomen. A
approximately six times larger than the left. It occupies the single-bilobed spleen is a rare variant. The polysplenia results
right hypochondrium, The left lobe is smaller and more from incomplete fusion of the splenic mesenchymal tissue. We
flattened than the right. It is situated in the epigastric and left will discuss functional status of the spleen later in the chapter.
hypochondriac regions. The liver in HS, is often centrally
placed or may remain in right or left hypochondrium. malrotation of gut
Spleen Normally, in visceral situs solitus the duodenojejunal junction

(DJ) lies towards the left of midline, at the level of L1-L2.
The absence of spleen can be the indicator of IRAA and Essentially, the stomach and DJ junction are on the same side
presence of multiple spleens indicates ILAA. Nevertheless, of spine. Intestinal malrotation can be broadly defined as the
with the growing understanding of HS, we know that splenic congenital abnormal position of the DJ junction. It is usually
154 morphology may vary and cannot predict the presence of accompanied by abnormal bowel fixation by mesenteric
either types of isomerism accurately. bands or absence of fixation of portions of the bowel, leading

Table 3 10
Morphological features of bronchi, lungs and branch
pulmonary artery47
HeTeRoTAxy SyndRome
Morphological features Percentage of positive prediction
(Specimen: 306; heterotaxy: 56)
Lung lobation 77%
Lengths of main bronchi 77%
Ratio of left to right (L/R) 90%
bronchial lengths (<1.5)
Relationship of bronchi to > 95%
ipsilateral pulmonary artery
Number of cartilage rings in 77%
each main bronchus
to increased risks of bowel obstruction, acute or chronic

volvulus and bowel necrosis. This abnormal position is Figure 6: Computed tomography (CT) angiography: Isomerism of left
atrial appendage: Intact inferior vena cava (IVC) (rare) with multiple
because of failure of normal counterclockwise rotation of the
spleens (SPL) and ransverse liver. (Courtsey: Apoorva Goyal, Mr Francis)
midgut by 270°, during the embryologic development. The
rotational abnormality of gut can be best attributed to non-
rotation, 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 structural anomalies are also seen in either of heterotaxy
position of DJ junction will not be attained and cecum does groups.
not reach to the right lower quadrant. The mesentery in turn • Central nervous system (CNS)—encephalocele, neural
forms a narrow base as the gut lengthens on the SMA without tube defects, porencepalic cyst, cerebellar agenesis.
rotation and this narrow base may lead to midgut volvulus • Axial skeleton—hemivertebra, sacral agenesis.
in many patients (Figure 7A).5,51,55,56 Barium examinations • Genitourinary/adrenal—hypoplastic or absent kidneys,
under fluoroscopy and getting upper gastrointestinal series is cystic kidney, hydroureter, hypospadias, duplicated uterus,
helpful.6,56 vaginal atresia, bicornuate uterus, ovarian cysts.
• Craniofacial—cleft lip/palate agnathia, micrognathia,
Pancreas in Heterotaxy choanal atresia, laryngeal cleft
• Endocrinal—fused or horseshoe adrenal, absent adrenal.
Pancreas is a centrally placed single organ, which has three
distinct parts—the head, neck, body, and tail extends between clInIcal evaluatIon
the curves of duodenum to spleen. The abnormalities of
pancreas are seen in ILAA. In many cases, the tissue from Babies with HS present very early with critical illness and
the head of pancreas forms a semicircle around the duodenum are clinically unstable for various reasons like:
and is known as annular pancreas; pancreas is called truncated 1. Severe cardiac diseases presenting with congestive heart
when only head or head and small body is present (Figure failure or severe hypoxia due to association with obstructed
7B).51,57 TAPVC, outflow obstruction or large shunt lesions, AV
regurgitation.
Gallbladder and Biliary Atresia 2. Associated tachyarrhythmia or bradycardia (AV block).
3. Extracardiac problems like volvulus, biliary atresia.
Gallbladder is an unpaired organ, which is placed under the 4. Severe sepsis.
surface of the right lobe of liver. In heterotaxy it may be placed Clinical signs may include: abnormal heart rate and rhythm,
in the midline. In ILAA, it may be absent or can be associated low volume or differential pulses, abnormal or differential
with biliary atresia. Davit et al have described specific gene blood pressure in all four limbs, cyanosis, abnormal cardiac
mutations associated with ILAA and biliary atresia.5,51,54 apex, with or without cardiomegaly, single second heart
sound, with or without ejection or pansystolic or continuous
other systemic manifestations in Heterotaxy5,6,8,35–38 murmur. In older children with ILAA, second sound may be
wide, variable or fixed. Abnormal positioning of liver dullness
Besides the above mentioned structural and positional or stomach tympanic sound may occur. Also, there may be 155
abnormality of thoracoabdominal viscera, some other abdominal distention.
2
BASIcS
A 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 3. Abnormal left axis deviation.
number of intracardiac abnormalities are associated with the HS. 4. Abnormal Q waves (single ventricle or ventricular
According to intracardiac anomaly clinical findings will vary. inversion).
5. Accessory pathway.
routine Work-up The atrial situs, ventricular hypertrophy patterns can
be assessed by evaluating axis and voltage of P, QRS and
According to the severity of symptoms, a detailed clinical T waves. In postoperative period, one can see varieties of
as well as laboratory work-up must be planned to ascertain rhythm abnormalities (Figure 8A).
the cardiac diagnosis and to see the functional status of renal, The characteristic ECG of ILAA shows an aberrant P-wave
hepatic, splenic and other systems. axis, progressive slow heart rate, multiplicity of atrial rhythm,
AV block and junctional escape rhythm. Overall complete AV
chest radiograph: Predictors of asplenia syndrome block is observed in one-tenth of cases of left isomerism.5,60
Figure 8B shows low atrial focus in a patient with ILAA.
Besides providing the usual information on cardiopulmonary This patient underwent a double switch operation successfully,
status, there are certain findings in chest X-ray which suggests but had a slow junctional rate postoperatively. The patient
the presence of HS. needed a permanent pacemaker implantation.
Trinavarat et al evaluated six such findings in a series of In IRAA, ECG may show multiple atrial rhythms and
30 prediagnosed patients of asplenia syndrome and found a variable P-wave axis. The changing P-wave axis is due to
bilateral minor fissure in 53 percent, bilateral eparterial bilateral sinus node with switching over of pacemaker function.
bronchi in 53 percent, symmetrical transverse liver in 30 In few cases, there might be dual QRS axis due to the
percent, ipsilateral side of liver and stomach in 30 percent, presence of dual AV node and sling of conduction tissue. Re-
ipsilateral side of minor fissure or eparterial bronchus and entry tachycardia can be seen in these circumstances.
stomach in 33 percent, contralateral side of minor fissure or One of the case series consisting of cases with ILAA
eparterial bronchus and liver in 23 percent. They found atleast showed mean frontal P-wave axis of −30° to −90° in 70
two positive findings in 28 out of 30 patients.58 percent of subjects. Additionally, in half of the cases, atrial
rate was below the second percentile. Only 10 percent cases
electrocardiogram5,59,60 had it persistently low. About 40 percent of cases showed a
tendency for recurrence. The junctional escape rhythm was
Electrocardiogram in HS must be evaluated for rate, rhythm, seen in 42 percent.60
accessory pathways and AV conduction. The abnormalities in ECG may also be related to
Usual ECG abnormalities are: intracardiac defects and QRS axis may deviate superiorly with
1. Abnormal P-wave axis (bilateral SA node or absent SA a counterclockwise or clockwise loop and may show abnormal
node and position of atria). ventricular dominance. An abnormal cardiac rhythm can also
156 2. Bradycardia/junctional rhythm/blocks. be noticed in fetal life.61
10
HeTeRoTAxy SyndRome
A
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 The computed tomography (CT) scan and angiography
anatomical and hemodynamic effects of the prevalent are used routinely for complex HS. The radiation to the
structural heart diseases in HS. It can be done by transthoracic babies and children remains a constant worry. Otherwise, it
or transesophageal route. Numerous series of images can be requires less time for acquisition of images unlike magnetic
displayed through multiple windows. Since the orthogonal resonance imaging (MRI) or conventional angiography.
planes of the heart are different from the major axes of the Our own experience with this modality is excellent. CT
body, it is conventional to describe the window of access as gives outstanding 2D and 3D imaging of atrial appendages,
well as the reference plane. The availability of the subcostal systemic and pulmonary veins, aorta and its branches,
windows in babies and small children are a great advantage, collaterals and pulmonary arteries. Additional morphological
because they enable the examiner to produce innumerable information about the bronchial anatomy, lung lobulation and
sequential images in desired orthogonal planes and hence position of the abdominal viscera can be obtained accurately.
provide opportunity to follow the anatomical course of veins The abdominal contrast CT is also needed to understand gut
and arteries, to study atrial and ventricular septum despite morphology (Refer: Figures 1A to C; 3A and B; 4A and B; 6
their obliquity and to identify the diverse placement of the and 7A and B).64,65
cardiac valves.
The diagnosis of HS by echocardiography is based on the magnetic resonance Imaging
abnormal placement of the descending aorta and IVC in the
subcostal short-axis view. We have seen that this relationship MRI gives excellent images of the cardiovascular system. It
is unpredictable at times. The identification of morphology can create moving images of the heart throughout its pumping
of the atrial appendages is not possible always (Figures 9A cycle. Therefore, unlike the CT scan, MRI can do a functional
to F). assessment of the heart. It can demonstrate abnormalities
157
2
BASIcS
A B
c d e F
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 extrahepatic portosystemic shunt (CEPS) is another

and can help in delineation of visceral situs abnormalities. interesting entity found in ILAA with interrupted IVC. In this
Nevertheless, it cannot define extent of pectinate muscles condition, pulmonary hypertension often coexists, though
in atrial appendages. Perhaps MRI is the best modality for liver is functionally normal. The percutaneous closure of
better assessment of complex anatomical and functional abnormal channels in CEPS is possible.70 Neonatal catheter
abnormalities after surgery.5,66 interventions and palliative procedures are routine like balloon
atrial septostomy, ballooning of obstructive lesions, ductal
conventional angiography and catheter Intervention stenting.71 The systemic venous abnormalities may pose
special problems. Interrupted IVC in ILAA may complicate
As a diagnostic modality, conventional angiography is losing a simple ASD device procedure. The electrophysiological
its place. Still, this is the only modality, which gives triple procedures can also be difficult in operated and non-operated
opportunity to obtain the anatomical details, hemodynamic patients.
data and to intervene. One such catheter interventions is the
coiling of major aortopulmonary collaterals, usually done management
before or after the surgical intervention. The hypoplastic
branch pulmonary arteries can undergo balloon angioplasty The HS is associated with spectrum of malformation and
and stenting. Donna et al reported successful device malfunctioning of thoracoabdominal organs and needs
closure of post-fenestrated Fontan in 154 cases, out of customized management plan. The goals of management are:
158 which 14 patients were with HS (Figures 10A and B).68 1. Diagnosis and management of malformations.
The completion of Fontan with percutaneous intervention 2. Infection control.
is an attractive and upcoming possibility.69 The congenital 3. Parental counseling.
10
HeTeRoTAxy SyndRome
A B
Figures 10A and B: Post-extracardiac Fontan surgery: LPA stenting in a 13-year-old boy
medical management72–76 series of 9 patients,82 with previous Fontan procedure

Usually, the babies presenting early have severe malformations (n = 3) or bidirectional Glenn shunt (n = 6) with intent for
and need hospitalization and urgent intervention. Besides a later Fontan procedure. Five of them had one and half
clinical and routine bedside investigations, pulse oximetry ventricular repair and 4 had biventricular repair. Two early and
must be used to record basal saturation in both right upper and one late death were reported in the series at a median follow-
lower limbs (Table 4). up of 27 months (range, 3.3–99.8 months). All survivors were
in New York Heart Association functional class I. Another
InterventIon In Heterotaxy advancement reported recently is, early direct hepatic vein to
azygos anastomosis without cardiopulmonary bypass.83
catheter Intervention
Results of Surgical Intervention in Heterotaxy Syndrome
The catheter interventions can be done before or after the
surgical intervention, as diagnostic or palliative procedures. The outcome of HS in unoperated cases varies from early
Rarely catheter interventions can be definitive procedure. demise to prolonged and productive life. The surgery is the
most important tool to modify the natural history.
surgical Intervention5,34,77–85 By and large, IRAA is common in males and has high
mortality and morbidity.5,85 The patients with ILAA can be
Majority of cases with right isomerism need surgical associated with less severe cardiac malformation and have
intervention for their survival. Usual urgent surgical better prognosis.4,5,85–89 The adverse outcome patients with
interventions are required for TAPVC repair or for palliative ILAA, may be the result of severe extracardiac malformations.
procedure like pulmonary artery banding or modified Gilljam et al reported 18 percent mortality in babies with
Blalock- Taussig shunt. Majority of the patients with IRAA normal heart.77
need bidirectional Glenn shunt or total cavopulmonary Nonetheless, neonates requiring early surgery have over
connection (TCPC). For few patients with IRAA and majority all, poor outcome. Complete AV septal defect, AV valve
of the patients with ILAA, biventricular corrective procedures regurgitation are independent risk factor against favorable
like AVSD repair, double switch with or without conduit can short term and long term results.22,58,67 In IRAA, presence
be done.77–85 These interventions are age dependent and are of complex CHD in association of pulmonary stenosis/
usually done in stages. The ILAA group may require a late pulmonary atresia and extracardiac obstructive TAPVC,
intervention. Recently, with growing experience, surgeons invariably foretells poor survivability.85 Factually, all patients
are less inclined to do univentricular repair.77–81 Hence, may not be operated due to complexity of lesions or they die
many centers are opting for biventricular or one and half before any intervention can be planned.
ventricular repair for the patients who initially underwent However, the technical improvement in diagnostic 159
bidirectional Glenn shunt. Hoashi T et al published a case modalities and concomitant improvisation in surgical
2 
Table 4
Medical management of heterotaxy syndrome (cardiac disease*)72–76
BASIcS
critical with cyanosis (rule out obstructed Prostaglandin infusion

TAPVc**) 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 ventricle (DORV) (3/91), tetralogy of Fallot (TOF) in
either univentricular or biventricular repair. 3.2 percent (3/91) and hemitruncus in 2.1 percent (2/91).
Noritaka Ota et al reported a retrospective review of Operations included double switch repair, physiologic repair,
institutional database from 1997 to 2010 and recognized 60 arterial switch and the Rastelli procedure. Separation of
consecutive patients with IRAA having single ventricle. They systemic from pulmonary venous return included intra-atrial
found that 5-year survival was 53.8 percent before 2003 and baffle in 48/91 patients and extracardiac grafting in 2/91.
81.7 percent after 2004 (p = 0.035) and identified persistent Average follow-up was 44.9 plus or minus 57.5 months
AV valve regurgitation of more than moderate degree (p = (3 days–189.3 months). Kaplan-Meier estimated survival
0.04) as a factor associated with late mortality.86 was 93.4% at 10 years; unbalanced complete AV canal was
One of the recently published retrospective studies has shown the only risk factor for mortality (P = .006). Subsequent
increased postoperative morbidity and mortality in 87 patients procedures were common with a 10-year freedom from
with CHDs with HS in comparison to that of CHDs without reoperation or reintervention of 38% ± 7.5%. Arrhythmias
HS. They found prolonged postoperative hospital stay (17 : 11 occurred in 36 (39.6%) patients; bradyarrhythmia in 27
days), prolonged mechanical ventilation (11 : 4 days), increased (29.7%) and tachyarrhythmia in 15 (16.5%). Freedom from
number of tracheostomies (6.9% : 1.6%), increased use of any arrhythmia was 53.9% plus or minus 6.7% at 10 years.88
ECMO (12.6 : 4.9%) and postsurgical deaths (16.1 : 4.7%).87 These results are better than the previously published
series about surgical outcome in patients with ILAA. In
bIventrIcular rePaIr In Heterotaxy syndrome— the series published by Gilljam et al, 87 percent cases
a surgIcal cHallenge underwent biventricular repair and combined 15 years
survival was less than 50 percent.77 This difference may be
To achieve biventricular repair in IRAA is a surgical challenge. due to patient selection strategies because incriminated risk
Nevertheless, world over, the recent trend amongst the factors had been congenital AV block, aortic coarctation,
surgeons is to attain a biventricular repair, whenever possible. single ventricle, billiary atresia and other gastrointestinal
Lim et al reported the series of 371 patients with HS. malformations.77,79,84,88
91/371 (24.5%) patients underwent biventricular repair from
1990 to 2007. Median age at repair was 6.8 months with a PreventIve strategIes and Prenatal dIagnosIs
range of 5 days to 22 years. LA isomerism was present in
73% (66/91) and right atrial isomerism in 10 percent (9/91), The genetic testing and counseling has some role to play, but a
with indeterminate atrial anatomy in 17 percent (16/91). definitive primary preventive strategy is yet to be found. When
Combined lesions were common, occurring in 99 percent we discuss the outcome of HS, the possibility of diverse outcome
of patients, which included systemic venous anomalies always pre-exists. Additionally, the risk of sepsis in asplenic
in 82 percent (75/91), pulmonary venous anomalies in patients or abnormal ciliary system in ILAA may influence
160 28 percent (26/91), endocardial cushion defects in 39 the outcome. Antenatal fetal echocardiography is the solitary
percent (36/91), transposition complexes 16 percent (15/91), preventive strategy in routine use. The natural elimination by
AV discordance in 10 percent (10/91), double outlet right spontaneous abortion has been noticed in many studies.
Berg et al examined their database retrospectively and found Streptococcus pneumoniae is the most common patho- 10
that in 32 of 35 fetuses had prenatal diagnosis of cardiosplenic gen causing septicemia in asplenic children followed by
syndromes. 22 fetuses had left isomerism. Their main prenatal Haemophilus influenzae, Neisseria meningitidis, Staphyloco-
HeTeRoTAxy SyndRome
ultrasound features were interrupted IVC (n = 21), CAVSD ccus aureus and other streptococci.
(n = 15), viscerocardiac heterotaxy (n = 15), persistent The splenic malfunction is diagnosed by presence of target
bradyarrhythmia (n = 12) and fetal hydrops or nuchal edema cells, Howell-Jolly, Heinz, Pappenheimer bodies and pitted
(n = 12). 12 pregnancies were terminated, 2 fetuses were erythrocytes in peripheral smear. The pits or pox on the red
stillborn and 8 infants survived. 10 fetuses had right isomerism. cell surface, ability to clear 51Cr-labeled heat damaged red
Their main sonographic features were juxtaposition of cells, SPECT-CT done with 99mTc-labelled, heat altered
the descending aorta and IVC (n = 7), CAVSD (n = 7), left autologous erythrocyte scintigraphy are the advanced methods
persistent SVC (n = 6) and viscerocardiac heterotaxy (n = 6). In to know the functional status of spleen.96,97
this group there was 1 stillbirth, 5 infant deaths and 4 survivors.
They suggested that diagnosis of left isomerism should be long-term management of asplenia/Hyposplenia76–80
strongly suggested in the presence of a combination of at least
two of the following: The four component of medical management are:
1. Complete atrioventricular septal defect or other structural 1. Antibiotic prophylaxis.
heart disease. 2. Appropriate immunization.
2. Interruption of IVC with azygos continuation. 3. Very aggressive management of suspected infection.
3. Early fetal heart block. 4. Parent education.
4. Viscerocardiac heterotaxy. Identification notes and written instructions must be
Right isomerism should be suspected in the presence of a given to asplenic patients (Box 2). The recommendations are
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 Box 2: Asplenia or hyposplenia: Prophylaxis against
Lin et al reported a series of 25 fetal diagnoses who were bacterial infection97–101
diagnosed and managed on the basis of antenatal diagnosis.90,91
• Universal immunization of IRAA patients with the
However, in their series isomerism of left atrial appendage
pneumococcal conjugate (PCV7) below 2 years and/or
was twice as common as isomerism of right atrial appendage. polysaccharide vaccine (PPC23) above 2 years and influenza
vaccine can improve the morbildity.81 Reimmunization is
Heterotaxy In adultHood recommended for children who received pneumococcal
vaccine before 24 months of age
It is rare to have adult patients afflicted with HS probably • Children up to 5 years should also receive all doses of
Haemophilus influenzae type b vaccine. Unimmunized
because severity of malformations makes them less capable to children >5 years should receive 1 dose
endure life. However, few of case reports and small case series • Patients should also receive quadrivalent meningococcal
have been reported. Majority of these patients had ILAA and vaccine.
less severe cardiac malformations.49,92,93 Antibiotic prophylaxis
• Regardless of vaccination status, children with splenic mal-
functIonal status of sPleen In function must be on antibiotic prophylaxis before 2-month
Heterotaxy syndrome94–101 of age. Oral administration of penicillin V potassium is
recommended at a dosage of 125 mg twice a day until
The association of IRAA with asplenia leads to deficient 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
body defense mechanism. Besides, absence or inappropriate pneumococcal infection and have received recommended
functional abilities of spleen in ILAA are also known. pneumococcal immunizations may discontinue penicillin
Thus, functional evaluation of the spleen is mandatory in prophylaxis after 5-year of age.
heterotaxy syndrome for an appropriate management plan. • Some experts recommend that asplenic patients have
The functional evaluation of spleen, bacterial prophylaxis and access to ‘stand-by’ antibiotics (Amoxicillin with or without
infection control protocols are guided by experience gained in clavulanic acid), which can be initiated with higher doses
schedule at the first sign of infection (fever, chills or
splenectomized patients. malaise). The initiation of ‘stand-by’ antibiotics is not a
substitute for seeking immediate medical attention at the
effect of asplenia/Hyposplenia94–95 onset of an illness cannot be overemphasized.79–80
• Asplenic patients have a high-risk to develop severe
Risk of bacteremia is highest in absence of spleen. The bacteria malaria with very high peripheral blood parasite counts.
transmitted by human or animal bite, protozoal infestations They should be given appropriate prophylaxis if travelling 161
to endemic areas.
like malaria or babesiosis can be dangerous.
2 extrapolation of the guidelines for the patients who underwent 5. Steven A, Umera H, Anderson RH. Paediatric Cardiology,
Isomerism of atrial appendages. 3rd edition editors-Anderson
spleenectomy for some medical reasons.
RH, Baker EJ, Redington A, Rigby ML, Penny D, Wernovsky
BASIcS
G. Churchil Livingstone. 2010.p.46392.

conclusIon 6. Jeffrey P Jacobs, Anderson RH, Weinberg PM, et al. The
nomenclature, definition and classification of cardiac
Heterotaxy syndrome, also known as incomplete lateralization structures in the setting of heterotaxy, Cardiol Young. 2007;
disorder, is now a well known entity of cardiac and non-cardiac 17(Suppl.2):1-28.
positional and structural anomalies. Demonstration of isomeric 7. Brueckner M. Heterotaxia, Congenital Heart Disease, and
atrial appendages, the juxtaposed abdominal aorta and IVC or Primary Ciliary Dyskinesia. Circulation. 2007; 115:2793-5.
interrupted IVC, radiological evidence of isomeric bronchi 8. Kennedy MP, Omran H, Leigh MW, et al. Congenital heart
and numeric abnormalities of spleen, abnormal placement disease and other heterotaxic defects in a large cohort of patients
of liver, helps in clinching this diagnosis. The meticulous with primary ciliary dyskinesia. Circulation. 2007; 115:2814-21.
9. Phoon CK, Neill CA. Asplenia syndrome: Insight into
examination of all thoracoabdominal organs is essential before
embryology through an analysis of cardiac and extracardiac
making the management plan. The cardiac anomalies need anomalies. The American Journal of Cardiology. 15 March
to be described by unbiased segmental analysis to deal with 1994; 73(8):581-7.
the diversity of cardiac lesions. Identifying genetic etiology 10. Sutherland MJ, Ware SM. Disorders of left-right asymmetry:
will improve the overall management, prognostication and Heterotaxy and situs inversus. Am J Med Genet Part C Semin
recurrence risk assessment. Finally, functional assessment Med Genet. 2009; 151C:307-17.
of ciliary and splenic functions is essential to prevent life- 11. Bisgrove BW, Morelli SH, Yost HJ. Genetics of human
threatening infections. laterality disorders: Insights from vertebrate model systems.
Annu Rev Genomics Hum Genet. 2003; 4:1-32.
12. Ware S, Belmont J. ZIC3, CFC1, ACVR2B, LEFTY2 and the
Symptoms, then are in reality nothing but the cry from
visceral heterotaxies. In: Epstein C, Erickson R, Wynshaw-
suffering organs. Boris A, (Eds). Inborn errors of development: The molecular
—Jean Martin Charcot, translated from French basis of clinical disorders of morphogenesis. New York:
Oxford University Press. 2008.pp.373-82.
acknoWledgments 13. Watanabe Y, Benson DW, Yano S, et al. Two novel frameshift
mutations in NKX2.5 result in novel features including visceral
I want to express my special gratitude to Dr Rajesh Sharma, inversus and sinus venosus type ASD. J Med Genet. 2002;
Director and Head of Department of Pediatric Cardiac 39:807-11.
Surgery for allowing me to access the data of his patients, to 14. Kuehl KS, Loffredo C. Risk factors for heart disease associated
with abnormal sidedness. Teratology. 2002; 66:242-8.
Dr Aoorva Goyal, Sr Consultant and Mr Francis, Technician
15. Ferrero GB, Gebbia M, Pilia G, et al. A submicroscopic
from the Department of Radiology for helping me in retrieving deletion in Xq26 associated with familial situs ambiguus. Am J
the CT angiographic images and to Dr Sanjay Khatri, Dr Hum Genet. 1997; 61:395-401.
Ashish and Dr Maitri Chaudhary for giving me their collection 16. Gebbia M, Ferrero GB, Pilia G, et al. X-linked situs abnormali-
of information. I am thankful to Ms Paramita Mishra and Mr ties result from mutations in ZIC3. Nat Genet. 1997; 17:305-8.
S. Balakrishnan for their help in editing. 17. Ware SM, Peng J, Zhu L, et al. Identification and functional
analysis of ZIC3 mutations in heterotaxy and related congenital
heart defects. Am J Hum Genet. 2004; 74:93-105.
references
18. Zhou X, Sasaki H, Lowe L, et al. Nodal is a novel TGF-beta-
like gene expressed in the mouse node during gastrulation.
1. Van Praagh R, Weinberg PN, Smith SD, et al. Malpositions of Nature. 1993; 361:543-7.
the heart. In: Adams FH, Emmanouilides GC, Riemenschneider 19. Mohapatra B, Casey B, Li Hua, et al. Identification and
TA (Eds). Moss’ Heart Disease in Infants, Children, and functional characterization of NODAL rare variants in
Adolescents 4th edition Baltimore: Williams and Wilkins; heterotaxy and isolated cardiovascular malformations. Hum
1985.pp.530-80. Mol Genet. 2009; 18(5):861-71.
2. Rowe RD, Freedom RM, Mehrizi A, Bloom KR. The neonate 20. Kennedy MP, Omran H, Leigh MW, et al. Congenital heart
with congenital heart disease, Philadelphia: WB Saunders, disease and other heterotaxic defects in a large cohort of
1981.pp.484. patients with primary ciliary dyskinesia. Circulation. 2007;
3. Webber SA, Sandor GGS, Patterson MWH, et al. Prognosis in 115:2814-21.
asplenia syndrome. A population based review. Cardiol young. 21. Caruso G, Becker AE. How to determine atrial situs?
1992; 2:129-35.
consideration initiated by 3 case of absent spleen with a
4. The science and practice in pediatric cardiology. 2nd edition
discordant anatomy between bronchi and atria. BHJ. 1979;
(Eds) In: Garson A Jr, Bricker JT, Fisher DJ, Neish SR,
41(5):559-67.
Gutgesell HP. Cardiac malposition and heterotaxy. William and
22. Ivemark BL. Implications of agenesis of the spleen on the
Wilkins. 1998.pp.1539-54.
pathogenesis of cono-truncus anomalies in childhood: analysis
162
of the heart malformations in splenic agenesis syndrome, with 39. Uemura H, Yen SH, Anderson RH, et al. Ventricular morphology
and coronary arterial anatomy in hearts with isomeric atrial
10
fourteen new cases. Acta Paediatrica. 1955; 44(Suppl 104):1-110.
23. Moller JH, Nakib A, Anderson RC, et al. Congenital cardiac appendages. Ann Thorac Surg. 1999; 67:1403-11.
HeTeRoTAxy SyndRome
disease associated with polysplenia: a developmental complex 40. Brandenburg VM, Krueger S, Haage P, et al. Heterotaxy
of bilateral ‘left-sidedness’. Circulation. 1967; 36(5):789. syndrome with severe pulmonary hypertension in an adult.
24. Stanger P, Rudolph AM, Edwards JEZ. Cardiac malpositions: South Med J. 2002; 95(5).
an overview based on study of 65 necropsy specimens. 41. Mohan KK, Kramer N, Margolis ML, et al. Intralobar pulmo-
Circulation. 1977; 56:159-72. nary sequestration in conjunction with bronchial isomerism.
25. Van Praagh R, Van Praagh S. Atrial isomerism in the heterotaxy Thorax. 1983; 38:77-9.
syndromes with asplenia, or polysplenia, or normally formed 42. Cho YH, Jin SJ, Yoon YW, et al. A case of noncompaction of the
spleen: an erroneous concept. Am J Cardiol. 1990; 66:1504. ventricular myocardium combined with situs ambiguous with
26. Rubino M, Van Praagh S, Kadoba K, et al. Venoarterial polysplenia. Yonsei Med J. 2007 December 31; 48(6): 1052-5.
connections in visceral heterotaxy. J Thorac Cardiovasc Surg. 43. Bush A. Left bronchial isomerism, normal atrial arrangement
1996; 111:1107-9. and bronchomalacia mimicking asthma: a new syndrome?
27. Rubino M, Van Praagh S, Kadoba K, et al. Systemic and European Respiratory Journal. August 1999; 14(2):475-7.
pulmonary venous connections in visceral heterotaxy with 44. Van Mierop LHS, Eisen S, Schiebler GL. The radiographic
asplenia: Diagnostic and surgical considerations based on appearance of the tracheobronchial tree as an indicator of
seventy-two autopsied cases. Thorac Cardiovasc Surg. 1995; visceral situs. American Journal of Cardiology. October 1970;
110:641-50. 26(4):432-5.
28. Kearney D, Titus JL. Cardiovascular anatomy, Chapter 4; The 45. Partridge JB, Scott O, Deverall PB, et al. Visualization
science and practice of ped. cardiology, second edition, editors: and measurement of the main bronchi by tomography as an
objective indicator of thoracic situs in congenital heart disease.
Garson A Jr, Bricker JT, Fisher DJ, Neish SR, publishers:
Circulation. 1975; 51:188-96.
Wiliam and Wilkins, 1998; 1:127-55.
46. Henry Gray (1821-1865). Anatomy of the Human Body (online
29. Mc Artney FJ, Zuberbuhler JR, Anderson RH. Morphological
version). 1918. Henry Gray (1821-1865). Anatomy of the
considerations pertaining to recognition of atrial isomerism.
Human Body. 1918. http://is1.mum.edu/vedicreserve/bartleby/
Consequences for sequential chamber localization. Br Heart J.
more_about_charaka.pdf.
1980; 44(6):657-67.
47. Louise Calder A. Thoracic situs as an indicator of atrial
30. Macartney FJ, Shinebourne EA, Anderson RH. Connexions,
appendage morphology: a postmortem study of 306 specimens
relations, discordance and distorsions. British Heart Journal.
with situs solitus in 250 and heterotaxy in 56 cases. Pediatr
1976; 38(4):323-6.
Cardiol. 2011 May 26.
31. Umura H, Ho SY, Devine WA, et al. Atrial appendages and
48. Osman Ratib, Joseph K. Perloff, John S Child. Unique discord-
venoatrial connections in hearts from patients with visceral ance thoracic situs solitus with left isomerism. Circulation.
heterotaxy. Ann Thorac Surg. 1995; 60:561-9 (spleen). 2004; 109:2252-3.
32. Lucas RV, Krabill KA. Anomalous venous connections, 49. Fulcher AS, Turner MA. Abdominal manifestations of situs
pulmonary and systemic. In: Adams FH, Emmanouilides GC, anomalies in adults. Radiographics. 2002; 22:1439-56.
Riemenschneider TA (Eds). Moss’ Heart Disease in Infants, 50. Ticho BS, Goldestein AS. Extracardiac anomalies in the
Children, and Adolescents. Baltimore:Williams and Wilkins. heterotaxy syndromes with focus on anomalies of midline-
1989.pp.580-617. associated structures. American Journal of Cardiology. 15
33. Neill CA. Development of the pulmonary veins. With reference March 2000; 85(6):729-34.
to the embryology of anomalies of pulmonary venous return. 51. Rose V, Izukawa T, Moes CA. Syndromes of asplenia and
Pediatrics. 1956; 18:880-7. polysplenia, a review of cardiac and non-cardiac malformations
34. Van Praagh S, Carrera M, Sanders S, et al. Partial or total direct in 60 cases with special reference to diagnosis and prognosis.
pulmonary venous drainage to right atrium due to malposition BR Heart J. 1975; 37:840-52.
of septum primum: anatomic and echocardiographic findings 52. Gilljam T, McCrindle BW, Smallhorn JF, et al. Outcomes of left
and surgical treatment: a study based on 36 cases. Chest. 1995; atrial isomerism over a 28-year period at a single institution, J
107:1488-98. Am Coll Cardiol. 2000; 36:908-91.
35. Colvin EV. Cardiac embryology, Chapter 3, the science and 53. Ruttenburg HD, Neufeld HN, Lucan RV, et al. Syndrome
practice of ped. cardiology, second edition, editors: Garson A congenital heart disease with asplenia: distinction from other
Jr, Bricker JT, Fisher DJ, Neish SR, publishers: Wiliam and forms from other forms of cyanotic cardiac disease. Am J
Wilkins, 1998.p.1. Cardiol. 1964; 14:587-406.
36. Hashmi A, Abu-Sulaiman R, McCrindle BW, et al. Management 54. Peoples WM, Moller JH, Edwards JE. Polysplenia: a review of
and outcomes of right atrial isomerism: a 26-year experience. J 146 cases. Pediatr Cardiol. 1983; 4:129-37.
Am Coll Cardiol. 1998. 55. Snyder WH Jr, Chaffin L. Embryology and pathology of the
37. Van Praagh S, Geva T, Friedberg DZ, et al. Aortic outflow intestinal tract: presentation of 40 cases of malrotation. Ann
obstruction in visceral heterotaxy: a study based on twenty Surg. 1954; 140:368-79.
postmortem cases. Am Heart J. 1997 May; 133(5):558-69. 56. Applegate KE, Anderson JM, Klatte EC. Intestinal malrotation
38. Ware AL, Miller DV, Porter CB, et al. Characterization of in children: a problem-solving approach to the upper gastroin-
atrial morphology and sinus node morphology in heterotaxy testinal series. Radiographics. Sept 2006; 26:1485-1500.
syndrome: an autopsy-based study of 41 cases (1950-2008).
163
57. Kapa S, Gleeson FC, Vege SS. Dorsal pancreas agenesis and
Cardiovasc Pathol. 2012 Sep; 21(5):421-7. Epub 2012 Jan 28. polysplenia/heterotaxy syndrome: a novel association with
2 aortic coarctation and a review of the literature. JOP. 2007 Jul
9; 8(4):433-7.
75. Marino BS, Bird GL, Wernovsky G. Diagnosis and management
of the newborn with suspected congenital heart disease. Clin
58. Trinavarat P, Tantiprawan K, Khongphatthanayothin A. Chest Perinatol. 2001; 28:91.
BASIcS
radiographic findings in children with asplenia syndrome. 76. Browning Carmo KA, Barr P, West M, et al. Transporting
Asian Biomedicine. August 2010; 4(4):585-94. newborn infants with suspected duct dependent congenital
59. Wren C, Macartney FJ, Deanfield JE. Cardiac rhythm in atrial heart disease on low-dose prostaglandin E1 without routine
isomerism. Am J Cardiol. 1987; 59:1156-8. mechanical ventilation. Arch Dis Child Fetal Neonatal Ed.
60. Momma K, Takao A, Shibata T. Characteristics and natural 2007; 92(2):F117.
history of abnormal atrial rhythms in left isomerism. Am J 77. Gilljam T, McCrindle BW, Smallhorn JF, et al. Outcomes of left
Cardiol. 1990; 65:231-6. atrial isomerism over a 28-year period at a single institution. J
61. Swaminathan S, Parthiban A. Progressive fetal atrioventricular Am Coll Cardiol. 2000; 36:908-91.
block in heterotaxy syndrome. Cardiology in the Young. 2007; 78. Humes RA, Feldt RH, Porter CJ, et al. The modified fontan
17:432-4. operation for asplenia and polysplenia syndrome. J Thorac
62. Huhta JC, Smallhorn JF, Macartney FJ, et al. Cross-sectional Cardiovasc Surg. 1988; 96:212-8.
echocardiographic diagnosis of systemic venous return. Br 79. Kaan Kirali, Ahmet Sasmazel, Ilker Mataraci, et al.
Heart J. 1982; 48:388-403. Biventricular repair of right atrial isomerism with complex
63. Lai WW, Geva T, Shirali GS, et al. Writing Committee, New congenital anomalies. Tex Heart Inst J. 2010; 37(2):202-4.
York, New York Guidelines and Standards for Performance 80. Uemura H, Yagihara T, Kawahira Y, et al. Staged unifocalization
of Pediatric Echocardiogram: A Report from the Task and anatomic repair in a patient with right isomerism. Ann
Force of the Pediatric Council of the American Society of Thorac Surg. 2001; 71:2039-41.
Echocardiography; J Am Soc Echocardiogr. 2006; 19:1413-30. 81. Jonas RA. Surgical Management of the Neonate with
http://www.asefiles.org/pediatricechoguidelines.pdf Heterotaxy and Long-term Outcomes of Heterotaxy; World
64. Karadeniz A, Oysu AS, Sahin S. Polysplenia/heterotaxy Journal for Pediatric and Congenital Heart Surgery April 13,
syndrome associated with aortic coarctation and multiple 2011; 2(2):264-27469.
venous anomalies: multidetector computed tomography 82. Hoashi T, Bove EL, Devaney EJ, et al. Outcomes of 1½- or
findings. Vasc Endovascular Surg. July 2010; 44(5):381-4, first 2-ventricle conversion for patients initially treated with single-
published on May 18, 2010. ventricle palliation. J Thorac Cardiovasc Surg. 2011; 141:419-
65. Chen S, Li YW, Wang JK, et al. Usefulness of electron beam 24.
computed tomography in children with heterotaxy syndrome. 83. Burstein DS, Mavroudis C, Michael DP, et al. Pulmonary
American Journal of Cardiology. 15 January 1998; 81(2):188- Arteriovenous Malformations in Heterotaxy Syndrome
94. the Case for Early, Direct Hepatic Vein–to–Azygos Vein
66. Wang JK, Li YW, Chiu IS, et al. Usefulness of magnetic Connection; World Journal for Pediatric and Congenital Heart
resonance imaging in the assessment of venoatrial connections, Surgery. December 30, 2010; 2(1):119-28.
atrial morphology, bronchial situs, and other anomalies in right 84. Koh M, Yagihara T, Uemura H, et al. Biventricular repair for
atrial isomerism. Am J Cardiol. 1994 Oct 1; 74(7):701-4. right atrial isomerism. Ann Thorac Surg. 2006; 81(5):1808-
67. Elliott LP, Cramer GG, Amplatz K. The anomalous relationship 16.
of the inferior vena cava and abdominal aorta as a specific 85. Yildirim SV, Tokel K, Varan B, et al. Clinical investigations
angiographic sign in asplenia. Radiology. 1966; 87:859. over 13 years to establish the nature of the cardiac defects in
68. Donna A Goff, Elizabeth D Blume, Gauvreau K, et al. Clinical patients having abnormalities of lateralization. Cardiol Young.
outcome of fenestrated fontan patients after closure the first 10 2007 Jun; 17(3):275-82.
years. Circulation. October 24, 2000; 102(17):2094-9. 86. Ota N, Fujimoto Y, Murata M, et al. Improving outcomes of
69. Alsoufi B, Alfadley F, Al-Omrani A, et al. Hybrid management the surgical management of right atrial isomerism. Ann Thorac
strategy for percutaneous fontan completion without surgery: Surg. 2012; 93(3):832-9.
early results. Ann Thorac Surg. 2011; 91:566-73. 87. Swisher M, Jonas R, Tian X, et al. Increased postoperative
70. Newman B, Feinstein JA, Cohen RA, et al. Congenital and respiratory complications in patients with congenital heart
extrahepatic portosystemic shunt associated with heterotaxy disease associated with heterotaxy. J Thorac Cardiovasc Surg.
and polysplenia. Pediatr Radiol. 2010; 40:1222-3. 2011; 141:637-44. e383.
71. Cheatham JP. The transcatheter management of the neonate and 88. Lim G, Bacha EA, Marx GR, et al. Biventricular repair in
infant with pulmonary atresia and intact ventricular septum. J patients with heterotaxy syndrome. J Thorac Cardiovasc Surg.
Interven Cardiol. 1998; 11:363. 2009; 137:371-9.
72. Duff DF, McNamara DG. History and Physical Examination of 89. Berg C, Geipel A, Smrcek J, et al. Prenatal diagnosis of
the Cardiovascular System. In: Garson A Jr, Bricker TM, Fisher cardiosplenic syndromes: 10-year experience. Ultrasound Obstet
DJ, Neish SR (Eds). The Science and Practice of Pediatric Gynecol. 2003; 22:451-9.
Cardiology Baltimore Williams and Wilkins. 1998.p.693. 90. Lin AE, Ticho BS, Houde K, et al. Heterotaxy: associated
73. Lees MH. Cyanosis of the newborn infant. Recognition and conditions and hospital-based prevalence in newborns. Genet
clinical evaluation. J Pediatr. 1970; 77:484. Med. 2000 May-Jun; 2(3):157.
74. Jones RW, Baumer JH, Joseph MC. Arterial oxygen tension 91. Lin JH, Chang CI, Wang JK, et al. Intrauterine diagnosis of
and response to oxygen breathing in differential diagnosis heterotaxy syndrome. Am Heart J. 2002 Jun; 143(6):1002-8.
of congenital heart disease in infancy. Arch Dis Child. 1976; 92. Raman R, Al-Ali SY, Poole CA, et al. Isomerism of the right
164
51:667. atrial appendages: clinical, anatomical, and microscopic study
of a long-surviving case with asplenia and ciliary abnormalities.
Clin Anat. 2003 May; 16(3):269-76.
99. Update for guidelines for the prevention and treatment of
infection in patients with an absent or dysfunctional spleen.
10
93. Brandenburg VM, Krueger S, Haage P, et al. Heterotaxy Working Party of the British Committee for Standards in
HeTeRoTAxy SyndRome
syndrome with severe pulmonary hypertension in an adult. Haematology Clinical Haematology Task Force. 2001.
94. Nagel BHP, Williams H, Stewart L, et al. Splenic state in (Accessed Dec 2006, at http://www.bmj.com/cgi/elet-
surviving patients with visceral heterotaxy. Cardiology in the ters/312/7028/430.
Young. 2005; 15:469-73. 100. Price VE, Dutta S, Blanchette VS, et al. The prevention and
95. Waghorn D. Overwhelming infection in asplenic. J Clin Pathol. treatment of bacterial infections in children with asplenia
2001 March; 54(3):214-8. or hyposplenia: Practice considerations at the Hospital for
96. De Porto APN, Lammers JJ, Bennink RJ, et al. Assessment Sick Children, Toronto. Pediatric Blood and Cancer. 2006;
of splenic function. Eur J Clin Microbiol Infect Dis. 2010 46(5):597-603. http://emedicine.medscape.com/article/
December; 29(12):1465-73. 885226-treatment.
97. Styrt B. Infection associated with asplenia: risks, mechanisms, 101. Langley JM, Dodds L, Fell D, et al. Pneumococcal and
and prevention. Am J Med. 1990; 88(5):33N-42N. influenza immunization in asplenic persons: a retrospective
98. Davidson RN, Wall RA. Prevention and management of population-based cohort study 1990-2002. BMC Infect Dis.
infections in patients without a spleen. Clin Microbiol Infect. 2010; 10:219.
2001; 7(12):657-60.
165
C hapter
Bedside Diagnosis of Acyanotic

Vijayalakshmi IB, Satpathy M
Introduction eral examination, followed by detailed examination of

the cardiovascular system by inspection, palpation, per-
The bedside diagnosis and detailed evaluation of the congenital cussion and auscultation. The examination of the respira-
heart diseases (CHDs) in infants and children is an absolute tory system and abdomen should be done in a methodical
clinical necessity. Despite the tremendous advancement in manner.
the various interventional invasive procedures and complex 3. Electrocardiography (ECG)
cardiac surgeries for CHD, the success of these procedures 4. Chest X-ray
mainly depends on the early and precise diagnosis. Hence, the 5. Echocardiography
accurate bedside diagnosis is no longer an academic curiosity, 6. Computed tomography (CT) angiogram and cardiac mag-
as in the past, when there were hardly any treatment modalities netic resonance imaging (MRI) in selected cases
available. 7. Invasive procedures like cardiac catheterization and angio
There is a considerable variation in the presentation at cardiography, if needed.
different ages (newborn to late adulthood), because the The diagnosis of CHD represents the summary of applied
manifestations mainly depend on the severity of the basic clinical logic. Appropriate data should be extracted and
lesion or the associated lesions. With the advent of fetal analyzed. When correct inferences are drawn from accurate
echocardiography, CHD can be detected prior to birth thus history, close observations with sharp clinical acumen,
preparing not just the clinicians to manage these patients, but diagnosis emerges with gratifying frequency.
the family too. Congenital heart defects are classified into two broad
The newborn period extends up to the first month and categories: acyanotic and cyanotic congenital heart disease.
infancy up to the first year of life. When a clinician evaluates a The acyanotic defects may further be subdivided into shunt
newborn or an infant in distress, it is important to differentiate lesions and non-shunt lesions, which are further sub divided
between cardiac and non-cardiac causes. It is very important to into obstructive and regurgitant lesions (Table 1).
exclude non-cardiac causes having structurally normal heart, Acyanotic congenital heart diseases may present with signs
which can produce cardiorespiratory distress either during the of congestive heart failure and/or heart murmurs that are heard
newborn or infancy period. At the same time, the physician during physical examination and can manifest any time during
should not be complacent if a newborn is apparently normal, infancy or early childhood. Most of these patients present
because some complex cyanotic heart diseases remains during the first 6 months of life, when the shunt or obstruction
asymptomatic with no murmur for a brief period. overwhelms the cardiac compensation and function. The
For a reasonably good clinical diagnosis the clinician Nadas criteria can be applied for the diagnosis of CHDs
should pay careful attention to the traditional systematic (Table 2). Presence of one major and two minor criteria are
examination and must know the normal parameters and its essential for the diagnosis of CHDs.
variations, according to the age group of the patients, so that
the abnormal findings can be easily detected and analyzed HISTORY
methodically.
The systematic approach to CHD includes the following: Eliciting correct history or complaints from the parents or
1. Detailed antenatal and postnatal history. reliable attenders during infancy is essential and cannot be
2. Systematic physical examination: Which includes gen- overemphasized in the evaluation of infants and children with
Table 1
 11
Classification of acyanotic congenital heart diseases
Bedside Diagnosis of Acyanotic Congenital Heart Diseases

Lesion Types Defects
Shunt lesions Pretricuspid Atrial septal defect

– Secundum
– Sinus venosus
– Primum
– Coronary sinus type
Partial anomalous pulmonary venous drainage—one 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
Non-shunt lesions 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
Table 2
 Table 3

Nadas criteria for the diagnosis of congenital heart diseases Causes of congestive heart failure in acyanotic congenital heart
diseases according to age
Major criteria Minor criteria
1. Systolic murmur of grade Systolic murmur grade 2/6 Age Causes
3–4/6 1st day of life Large arteriovenous fistula, congenital
2. Diastolic murmur Abnormal second heart sound severe pulmonary regurgitation (volume
overload of right ventricle), premature infant
3. Congestive heart failure Abnormal chest X-ray having large PDA, pinpoint aortic stenosis
4. Cyanosis ECG abnormalities with hydrops fetalis
Abnormal BP 1st week of life Coarctation of aorta, critical aortic stenosis,
critical pulmonary stenosis
Presence of one major and two minor criteria are essential for diagnosis of
congenital heart diseases 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
suspected cardiovascular disorders. But, in our country due to or without PDA, anomalous origin of the
low literacy rate, eliciting proper history from the parents or left coronary artery from pulmonary artery,
relatives can be difficult for the clinicians. aortoventricular tunnels
1 year of life Large VSD, AV septal defect
Presenting Complaints AV = Atrioventricular; PDA = Patent ductus arteriosus; VSD =
Ventricular septal defect
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 5. Recurrent respiratory infections
of: 6. Growth impairment in the infant
1. Feeding difficulties 7. Exercise intolerance
2. Tachypnea 8. Easy fatigability or murmur in the older child.
3. Sweating The age of presentation with heart failure also gives a clue
4. Subcostal recession regarding the type of acyanotic CHD (Table 3). 167
2 Symptoms to thrive is defined as weight < 3rd percentile for age. Usually,
the rate of weight gain is more delayed than that of height
Feeding Difficulties gain. It is probably related to the inadequate caloric intake due
Basics
to breathlessness during feeding and to the excessive energy

Feeding difficulties is a common symptom in significant requirements of congestive cardiac failure. If weight is severely
acyanotic CHDs. In infants, feeding itself is a form of exercise affected, a more general dysmorphic condition should be
or effort. An infant with heart failure has the inability to suspected.
complete feeds within 15 to 20 minutes, sucks less volume
of milk (< 3.5 ounces per feeding), gets tired easily and takes Chest Pain
frequent feeds (less than 2 hours). The infant has increased
breathing or tachypnea and perspiration during feeds. As the Chest pain or angina is rare, but not unknown in infants and
feeds are inadequate they become irritable and cry excessively. children. Chest pain is a common and benign symptom in
This suck-rest-suck cycle continues round the clock. Children older children and adolescents, estimated to occur in around 70
with respiratory distress and poor cardiac output due to heart percent of school-going children. Chest pain may be the first
disease cannot be fed well, as it requires considerable effort to complaint that points to an unsuspected anatomic heart defect.
suck, resulting in easy fatigability and failure to thrive. Pain associated with palpitations, dizziness and panic attacks
may be the presenting symptoms in some patients, who have
Respiratory Distress mitral valve prolapse (Barlow syndrome). These patients are
usually associated with a midsystolic click and occasionally an
Respiratory distress is the most prominent sign of heart failure apical mid-to-late systolic murmur. In patients, who have left
caused by significant left-to-right shunting in infancy. Symp- ventricular outflow tract obstruction (LVOTO) in the form of
toms of respiratory distress include tachypnea or rapid breathing stenosis of the aortic valve, subaortic valve area, supra-aortic
(respiratory rate > 60/min in newborn and > 50/min in infants) valve area or coarctation of the aorta, may present with chest
and intercostal and subcostal chest retractions. In very sick pain and associated with dizziness and fatigue. It can occur
infants, grunting and nasal flaring can also be present. Dyspnea in severe aortic stenosis or possibly in pulmonary stenosis
is manifested in infants by rapid breathing with retractions and due to demand-supply mismatch resulting in myocardial
grunting. Older children may complain of shortness of breath. ischemia. Chest pain in association with exercise intolerance
and fatigue may be the initial presenting complaint of patients,
Easy Fatigability who have hypertrophic or dilated cardiomyopathy. Chest pain
due to myocardial ischemia can occur in patients, who have
Fatigue on exercise or exercise intolerance must be distin- abnormal coronary artery anatomy, including congenital
guished from dyspnea, as it has a different physiologic basis. anomalies of the coronary artery, coronary artery fistulas and
It is a difficult symptom to interpret because of other factors, stenosis or atresia of the coronary artery ostium and have been
such as motivation or amount of exercise an individual can per- recognized in infants with an aberrant left coronary artery. In
form. In an infant, it is seen as poor ability to suck and feed. infants, it can present with excessive crying or irritability
In older children, heart failure may be manifested as exercise associated with pallor or sweating. Chest pain can also occur
intolerance; difficulty in keeping up with peers during sports with very rapid paroxysmal tachycardia.
or need for a nap after coming home from school and poor
growth. Eliciting a history of fatigue in an older child requires Syncope
questions about age-specific activities, including stair climb- Syncope is a transient loss of consciousness due to general-
ing, walking, bicycle riding, physical and competitive sports. ized cerebral ischemia, which usually is followed by rapid
and complete recovery. In rare instances, anoxic seizures may
Repeated Lower Respiratory infections result. Syncope may be preceded by palpitations, lightheaded-
ness, dizziness, weakness, pallor, nausea, cold sweat, blurred
Recurrent pneumonia has been defined as two episodes of vision or hearing loss.
pneumonia in 1 year or three episodes in any time frame. Syncope may result from impaired response of the
Respiratory infections, particularly pneumonia, are frequently autonomic nervous system or from cardiac structural defects,
present in infants and less commonly, in older children with especially those obstructing blood flow, or from cardiac
cardiac anomalies, especially those associated with increased arrhythmias. History of syncope on mild to moderate exertion
pulmonary blood flow (PBF) or left-to-right shunt. indicates severe aortic stenosis, hypertrophic cardiomyopathy
(HOCM), severe pulmonary hypertension or complete
Growth Retardation or Failure to Thrive transposition of the great vessels (CTGV). In CTGV, syncope
is due to significant bradycardia. The relatively uncommon
168 Growth retardation is common in many children, who present long QT syndrome is an especially worrisome cause of
with other cardiac symptoms within the first year of life. Failure syncope. Non-cardiac mechanisms, which cause syncope
in school-going children are vasovagal (neurocardiogenic), Meticulous history is the corner stone for the diagnosis of 11
orthostatic, breath holding and hyperventilation. Other causes some diseases. The common symptoms of acyanotic CHD
of syncope are metabolic, neurological and psychological and their pathophysiological basis is given in Table 4. The

disorders. grading of severity of heart failure in adults as proposed by
the New York Heart Association Class (NYHA) is universally
Peripheral Edema accepted. However, it is difficult to grade or apply these
classifications in children, especially infants. A common
Pretibial and presacral edema are late developments in system followed is the one advocated by Ross (Table 5).
the child with congestive circulatory failure, apparently
due to the difference in tissue turgor. When peripheral Family History
edema due to heart failure does develop in an infant, it
first appears periorbitally, and is usually preceded by other A detailed family history at times is rewarding in CHD. If
manifestations such as tachypnea, tachycardia, dyspnea and one parent has a congenital heart anomaly, the risk of the
liver enlargement. 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. 169
Contd...
2 Contd...
Symptom Pathophysiology
Basics
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 struc-
tural 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
 Box 1: Risk factors for CHD
Modified classification of heart failure by Ross
Maternal History
Types Features Diseases
Class I No limitations or symptoms • Diabetes mellitus—VSD/hypertrophic cardiomyopathy,
pulmonary stenosis, PDA, TGA
Class II Mild tachypnea or diaphoresis with feeding in
• Systemic lupus erythematosus—complete heat block
infants
• Phenylketonuria—VSD, ASD, PDA
Dyspnea on exertion in older children
No growth failure Infections/Ingestions/Exposure
Class III Marked tachypnea or diaphoresis with feeds or Infections
exertion • Rubella—PDA, pulmonary artery branch stenosis, congeni-
Prolonged feeding times tal rubella syndrome
Growth failure from congestive heart failure • Mumps—endocardial fibroelastosis
• Coxsackie virus, Cytomegalovirus, herpesvirus (in late
Class IV Symptoms at rest with tachypnea, retractions, pregnancy)—myocarditis
grunting or diaphoresis
Drugs
• Amphetamines—VSD, PDA, ASD, TGA
• Phenytoin (Dilantin)—PS, AS, CoA, PDA
as 10 percent. When a first cousin has a congenital heart • Trimethadione—VSD, PS, TGA, TOF, HLHS
anomaly, the risk of a sibling having one is approximately 2 • Lithium—Ebstein’s anomaly
• Retinoic acid—conotruncal anomalies
percent. With no family history of CHD, if the firstborn has
• Valproic acid—ASD, VSD, AS, CoA, pulmonary atresia with
a congenital heart lesion, the risk of a second child having a intact IVS
congenital heart lesion is 2 to 3 percent, slightly higher than • Progesterone and estrogen—VSD, TOF, TGA
the risk for the general population. Ingestions/Exposure
• Alcohol (fetal alcohol syndrome)—VSD, PDA
Maternal History • Marijuana, cocaine—VSD
• Smoking—PDA, prematurity
A maternal history of acute illness or exposure to drugs
especially in the first trimester or any chronic illness in the AS = Aortic stenosis; ASD = Atrial septal defect; CoA = Coarctation of
aorta; HLHS = Hypoplastic left heart syndrome; IVS = Interventricular
mother may provide an etiological information. The history septum; PDA = Patent ductus arteriosus; PS = Pulmonary stenosis;
should include: TGA = Transposition of great vessels; TOF = Tetralogy of Fallot;
a. Exposure to drugs (lithium, phenytoin, thalidomide) VSD = Ventricular septal defect
b. Alcohol intake
c. TORCH infections especially rubella
d. Maternal diseases like diabetes mellitus, systemic lupus The most important contributory factors for development
170 erythematous, phenylketonuria of CHD are given in Box 1. In most instances, however, no
e. Exposure to radiation. specific contributory factors can be identified.
PHYSICAL EXAMINATION 11
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? A B
7. Is the patient developmentally delayed in motor skills, Figures 2A and B: A. Hypertelorism, distinctive webbed neck, low set
speech or cognition? ear, small chin, malocclusion of teeth and wide-spaced nipples in a
Noonan patient; B. Short neck with low set ears with abnormal auricle
The clinician must have a background knowledge of the and low hairline in a 3-year-old Down syndrome patient
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.
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 A B
are some of the features seen in Noonan’s syndrome (Figure
Figures 3A and B: A. Mongoloid facies in a 1-year-old with Down’s
2A). Short neck or with low hairline is seen in Down syndrome syndrome; B. Palm of a 3-year-old child with Down’s syndrome show-
(Figures 2B). Mongoloid facies with transverse simian crease ing transverse simian crease
on the palm, hypotonic and hyperflexible limbs are also other
features of Down syndrome (Figures 3A and B). Elfin facies
indicate William’s syndrome (Figure 4). Child having moon like
Figure 4: Elfin facies in a 12-year-old boy of William’s syndrome with

Figure 1: Hypoplastic radius with fingerization of thumb with, supra-aortic stenosis showing patulous lips and malocclusion of the 171
polydactyly and syndactyly in 12-year-old boy with atrial septal defect teeth
2
Basics
A B
C D
Figures 5A to D: Marfan’s syndrome: A. Steinberg thumb sign; B. Murdoch-Walker wrist sign; C. Arachnodactyly—Abnormally 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 Fanconi syndrome—PDA, VSD

Turner syndrome (XO)—Coarctation of aorta in females, PS in Thrombocytopenia—absent radius—ASD, TOF
males, AS Rubinstein-Taybi syndrome—PDA
Marfan syndrome—Dissection of aorta, aortic aneurysm, AR, Ellis-van Crevald syndrome—Single atrium
MVP Kartagener syndrome—Dextrocardia
Rubella syndrome—PDA, PS, pulmonary artery branch Williams syndrome—Supravalvular aortic stenosis, peripheral
stenosis PS
Noonan syndrome—PS, ASD with/without PS Laurence Moon Biedl syndrome—VSD, TOF
DiGeorge syndrome—Aortic arch anomaly, Conotruncal Carpenter’s syndrome—PDA, VSD
anomaly Smith-Lemili-Opitz—VSD, PDA
Holt-Oram syndrome—Familial ASD, VSD Goldenhar syndrome—TOF
Multiple lentigenes (Leopard)—PS
Fetal alcohol syndrome—VSD, ASD, TOF
172
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
facies indicates valvular pulmonic stenosis (PS). Musculoskeletal Table 6
 11
abnormalities can be seen in Marfan syndrome (Figures 5A Respiratory rate and heart rate at different age
to D). The common clinical syndromes in CHD are given in

Box 2. Age Respiratory rate Heart rate
group (per minute) Tachycardia Bradycardia
The height, weight, head circumference and chest circum
ference should be plotted on appropriate growth charts. In the Newborn 40–60 > 160 < 100
absence of specific genetic conditions, head circumference Infants up to 30 > 120 < 90
and length are generally spared in children with clinically
1–4 years 24–26 > 100 < 60
significant heart disease. The puffiness of the face, pitting
Adolescents 18–20 > 100 < 60
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. routinely examined. The carotid pulse is palpated for pulse
Sometimes infants of large birth weight may also have cardiac contour, the femoral pulse is palpated for pulsus paradoxus.
problems like cardiomyopathy (infants of diabetic mothers) or The information to be gained from the examination of arterial
cyanotic heart disease like transposition of the great arteries pulse includes rate, rhythm, character and symmetry (between
(TGA). Infants with low birth weight particularly premature left and right side).
infants (less than 1.5 kg of birth weight) have more chance On simultaneous palpation, if femoral pulse is delayed,
of CHD. weak or absent in comparison to the brachial or radial pulse
One should look for clubbing and any peripheral signs of (radio-femoral delay), it indicates coarctation of aorta (CoA)
infective endocarditis (IE). They are less common overall or interrupted aortic arch. Also, if there is any discrepancy in
in children than in adults.The peripheral signs of IE are (a) both radial pulses it indicates supravalvular aortic stenosis,
petechiae which are common but nonspecific; (b) subungual aortic isthmus stenosis or pre-ductal CoA with the left
(splinter) hemorrhages which are dark red linear lesions in subclavian arising below the coarctation and the aortoarteritis
the nailbeds; (c) Osler nodes are tender subcutaneous nodules with obstruction to left subclavian artery. The right arm pulse
usually found on the distal pads of the digits; (d) Janeway is usually better felt than the left arm pulse, because blood
lesions are nontender maculae on the palms and soles; (e) pressure is slightly higher in right upper limb (the difference
Rarely, Roth spots which are retinal hemorrhages with small is <10 mm Hg). If pulse in the right upper limb is much better
and clear centers. felt than the left upper limb, one should suspect supra-aortic
The vital signs like temperature, pulse, blood pressure, stenosis. The discrepancies occurs because the jet of blood flow
heart rate and respiratory rate should be documented and from supravalvular aortic stenosis (SVAS) has a preferential
interpreted in the light of the child’s general state at the time trajectory into the brachiocephalic (innominate) artery. This is
of examination (e.g. quiet and cooperative, febrile or crying). called the ‘Coanda effect’. Also, the blood pressure is more in
the right upper limb than in the left upper limb (the difference
Respiration being >10 mm Hg).
The character of the pulse can give a clue to some of
Respiratory distress is the most prominent sign of heart failure the acyanotic CHDs. Collapsing pulse (also known as a
caused by significant left-to-right shunting or obstructive ‘water-hammer’ pulse) is jerky, with a full expansion phase
lesions in infancy. In newborns and infants, it is diagnosed by followed by a sudden collapse upon raising the arm to the
tachypnea, altered depth of breathing, intercostal, subcostal level above the heart, as there is a rapid peripheral runoff
retraction, flaring of alae nasi, grunting, stridor and apneic of blood in addition to a large stroke volume from the left
spells. Apneic spells are more common if central nervous ventricle. It can occur in patent ductus arteriosus (PDA)
system (CNS) is involved. The respiratory rate and heart rates with normal pulmonary pressures, aortopulmonary window,
vary with age (Table 6). large arteriovenous fistula and bicuspid aortic valve with
severe aortic regurgitation. Pulsus parvus et tardus is a
Arterial Pulse pulse that is slow-rising with delayed upstroke, late-peaking,
low amplitude and is characteristic of severe valvular aortic
Palpating the pulse is one of the simplest, oldest and yet the stenosis. It is best palpated on the carotid artery. A delayed
most informative of all clinical examinations. The arterial peak and slower upstroke of the carotid pulse suggests a
pulse is the abrupt expansion of an artery resulting from the prolonged left ventricular ejection time. In patients with aortic
sudden ejection of blood into the aorta and its transmission stenosis with incompetence, there may also be a palpable
throughout the arterial system. Routine examination in vibration (thrill) on the ascending limb of the pulse (carotid
infants involves the brachial and femoral arteries. In the shudder). It is often difficult to palpate the carotid pulses of
adolescent, the carotid artery is added, in adults the radial, such patients, because of lower pulse pressure and lack of a
popliteal, posterior tibial and dorsalis pedis pulses are rapid rise on the upstroke of the pulse. 173
2 Blood Pressure Jugular Venous Pressure
Recording blood pressure (BP) is essential, when assessing Jugular venous pressure (JVP) is raised, when the mean right
Basics
the cardiovascular system. It is often difficult to measure exact atrial (RA) pressure increases indicating right-sided heart
blood pressure in the upper and lower limbs in newborns and failure. The JVP is difficult to interpret in newborns and infants
infants, more so when the neonate is a premature one. Blood (due to short neck and tachycardia). But in cases of younger
pressure is taken by different methods at different ages. The children and adolescence, JVP is easily studied. Prominent ‘a’
methods are: (i) Flush method, (ii) Doppler ultrasound wave indicates a forceful atrial contraction present in cases
method and (iii) Oscillometric (Dinamap) method (these of tricuspid atresia, pulmonary stenosis with intact ventricular
are mainly for infants) besides conventional methods like septum, right atrial myxoma and Eisenmenger syndrome due
palpation. to ASD or PDA. In Lutembacher syndrome left atrial ‘a’ wave
Blood pressure cuff of the sphygmomanometer should be is reflected in the JVP. The schematic representation of various
of appropriate size according to the arm circumference. The waves of the normal JVP correlating with heart sounds and
National Heart, Lung, and Blood Institute (NHLBI) has prepared electrocardiogram is illustrated in Figure 6.
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 Oxygen Saturation
based on percentiles. Hypertension is defined as either systolic
and/or diastolic blood pressure ≥ 95th percentile measured on Documentation of systemic oxygen saturation with pulse
three or more separate occasions. The normal range of blood oximetry is generally reserved for patients with active
pressure according to the age given in Table 7. respiratory issues or known cyanotic heart disease.
In all patients suspected of cardiac disease, one should Documentation of oxygen saturation of less than 94 percent
record accurately the BP in both arms and one leg. This helps in the lower extremity would alert the practitioner, either to
in diagnosis of conditions causing obstruction such as CoA, cyanotic CHD or to any condition in which there is right-to-
recognition of conditions with ‘aortic runoff,’ such as PDA, left shunting through the PDA into the descending aorta. This
aortopulmonary window and identification of conditions with differential cyanosis is seen in left heart obstructive lesions
reduced cardiac output. The patient should be in a quiet, resting such as CoA, interrupted aortic arch, hypoplastic left heart
state and appropriate sized BP cuff must be used. The “ideal” syndrome, critical aortic stenosis or pulmonary hypertension
cuff should have a bladder length that is 80 to 100 percent and with PDA.
a width that is at least 40 percent of the arm circumference.
In infants, placing the cuff around the forearm and leg rather Precordial examination
than around the arm and thigh is easier. A 2-inch-wide cuff
can be used for almost all infants.
Inspection
Upper extremity hypertension can be an important first sign
of CoA, but is often missed in children younger than 3 years The precordium is the front of the chest overlying the
if BP is not obtained. The CoA is suspected, when the systolic heart. One should look for abnormal chest shape, visible
pressure is < 20 mm Hg in the legs than in the arms. Pulse pulsations, operation scars and an implanted pacemaker.
pressure (the difference between the systolic and diastolic The left side of the thorax is prominent anteriorly or the
pressures) normally should be approximately one-third of precordial bulge is seen due to the left atrial enlargement,
the systolic BP. A narrow pulse pressure is associated with as in post-tricuspid shunts. The upper sternum may bulge
a low cardiac output or severe aortic stenosis. Pulse pressure in children with a large left-to-right shunt and pulmonary
widens in conditions with an elevated cardiac output (anemia hypertension or with elevated pulmonary venous pressure.
and anxiety) or with abnormal runoff of blood from the aorta As the left atrium is a posterior structure it has to enlarge
during diastole (PDA or aortic insufficiency). anteriorly and hence pushes the compliant sternum and
anterior ribs forward. This may not be evident in the first
Table 7
 month of life, but it certainly will be by 3 months of age.
Normal range of blood pressure values In older patients with right ventricular (RV) hypertrophy
secondary to pulmonary hypertension there can be a
Age group Systolic Diastolic
(mm Hg) (mm Hg) prominant precordium. Other types of chest deformities
are pectus carinatum, (Figure 7A) and pectus excavatum
1. Neonates 60–70 20–60
(Figure 7B). Subcostal indrawing is abnormal and usually
2. Infants 87–105 53–65 indicates stiff lungs from either cardiac or pulmonary
3. Toddler 95–105 53–66 causes. If the child has been symptomatic with respiratory
4. Children 97–112 57–71 distress due to heart failure for more than 2 months, bilateral
174 Harrison’s sulci may be seen. This is due to the increased
5. Adolescents 112–128 66–80
11

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)
Palpation
Apex Beat
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
A B sustained heaving apical impulse is seen in pressure overload
Figures 7A and B: A. Pectus carinatum and B. Pectus excavatum
conditions like in LVOTO.
Thrill
diaphragmatic contractions during respiration, which
produces a sulcus in the lower thorax, with outward flaring A thrill is a palpable vibration caused by turbulent blood
of the inferior ribs. flow and is always pathological. Thrills are best identified
The abnormal location of the apical beat for age indicates by palpation of the precordium with the palmar surfaces
cardiomegaly. The visible pulsations over the precordium or of the metacarpophalangeal and proximal interphalangeal
hyperdynamic precordium is mainly seen in volume overload joints. Thrills are coarse, low-frequency vibrations occurring
conditions like in post-tricuspid shunts. Left parasternal with a loud murmur and are located in the same area, as the
pulsations and lift can be seen in large atrial septal defects maximal intensity of the murmur. Thrills at the lower sternal
and in cases of RV hypertrophy. In patients with PDA, border are more likely to be associated with VSDs than mitral
aortopulmonary window, aortic insufficiency, aortic stenosis or tricuspid regurgitation. Thrills at the right upper sternal
and CoA, suprasternal pulsations can be visible. border (RUSB) or suprasternal notch are most likely to be due
175
2 to severe aortic stenosis. Other less common cause of thrill the young individual S3. Normally, mitral (M1) and aortic
in the suprasternal notch is pulmonary stenosis. Diastolic (A2) heart sounds are louder than and precede tricuspid (T1)
thrills are less common. Parasternal lift or heave is a forceful, and pulmonary (P2) heart sounds. In children, the individual
Basics
outward movement of the left lower parasternal region of the mitral and tricuspid components are usually indistinguishable,
precordium and it indicates RV hypertrophy. so the first heart sound is apparently single. Occasionally, two
components of this sound are heard. A loud S1 can occur with
Percussion increased flow across the AV valves from large left-to-right
shunts, such as ASD, VSD or PDA.
Percussion of the heart can substantiate estimation of cardiac Potain in 1866 recognized splitting of the two components,
size in addition, to that obtained by inspection and palpation. aortic (A2) and pulmonic (P2), of the second heart sound during
It is redundant now. normal inspiration. Splitting of S2 is physiological and normal
on inspiration, when the degree of splitting increases, whereas
Auscultation on expiration it decreases. Shaver et al in 1974 described this
‘Hangout interval’ as a time interval or gap between the arterial
For the auscultation of heart sounds in infants and small pressure curve and the respective pumping chamber pressure
children pediatric-sized bell and diaphragm should be used. curve (right or left ventricle) at the level of incisura. Incisura is
High-pitched murmurs, first and second heart sounds are the notch on the descending limb of the arterial pressure curve,
better heard with the diaphragm; low-pitched murmurs, third which coincides with the pulmonary or aortic valve closure.
and fourth heart sounds are most evident with the bell. The In the highly compliant (low-resistance, high-capacitance)
patient should be examined in a quiet area and in multiple pulmonary vascular bed, the hangout interval may vary from
positions such as supine, left lateral decubitus, upright and 30 to 120 msec contributing significantly to the duration of
leaning forward, as well as during inspiration and expiration. RV ejection. In the left side of the heart, because impedance is
The examiner should auscultate over the listening areas; 2nd much greater, the hangout interval between the aorta and left
RICS, 2nd LICS, 4th LICS and the apex. The carotids and ventricular pressure curve is negligible (less than or equal to 5
chest areas, both front and back, should also be included.The msec). The hangout interval therefore correlates closely with
auscultatory areas are shown in Figure 8. the impedance of the vascular bed into which blood is being
injected. Its duration appears to be inversely related to vascular
Heart Sounds impedance. Leatham in 1964 described the second heart sound
as the “key to the auscultation of the heart”. The S2 is of great
The first and second heart sounds are produced by the valve diagnostic significance and also helps in assessing the severity
closure of the atrioventricular (AV) and semilunar valves of the lesion.
respectively. The normal heart sounds include S1, S2 and in 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,
176 such that the separation of A2 and P2 remains unchanged
Figure 8: Standard auscultatory areas during inspiration and expiration.
In ASD the fixed nature of the split is due to approximately valve or deformity of the chest wall or lung. Loud A2 is due 11
equal inspiratory delay of the aortic and pulmonic components, to increased flow, increased pressure and dilatation of the
indicating that the two ventricles share a common venous root of aorta. It can also be appreciated in acyanotic CHDs

reservoir. In ASD the second heart sound is widely split like COA and in ascending aortic aneurysm. Soft A2 can be
because the pulmonary hangout interval is wide and fixed, as appreciated in valvular, supra valvular aortic stenosis and in
the RV stroke volume does not show the normal respiratory aortic regurgitation.
changes. This is due to the dynamic phasic shunting across The P2 is considered to be abnormally loud in a subject
the interatrial septum, which keeps the RV diastolic as well as over the age of 20, if it is greater than the aortic component
systolic volume relatively constant. The respiratory variation of in the second left ICS or if it is audible at the cardiac apex.
S2 splitting, immediately returns to normal following surgical The P2 is accentuated when PAH occurs, due to the elevation
repair of an ASD, although the pulmonic closure sound may of pulmonary vascular resistance (PVR) or due to increased
remain delayed for weeks or months. Fixed splitting is also pulmonary arterial blood flow. As the level of pulmonary
seen in severe right heart failure due to the relatively constant arterial pressure increases, the P2 becomes louder and closer
RV output as RV inotropism is not good enough to handle to the aortic component and there is a narrow split of the
the inspiratory augmentation of RV end diastolic volume. second sound. When the PVR is equal to or greater than
The RV fails to respond to the increased volume produced systemic vascular resistance, closure of A2 and P2 will be
by inspiration and the impedance to forward flow from the nearly simultaneous, resulting in an audible ‘single’ S2, as in
RV barely falls during inspiration due to the congested lungs. PAH and Eisenmenger syndrome. In cases of ASD, P2 may
In partial anomalous pulmonary venous return without ASD, be heard at the apex without PAH due to the RV dilatation.
fixed splitting is not usually seen. However, if P2 is very loud and increases with mild exercise,
Paradoxical splitting or reversed splitting is heard maximal then PAH with ASD can be diagnosed. The P2 is soft or muffled
during expiration and minimal or not in inspiration. Thus in acyanotic CHDs like pulmonary stenosis. Masking of P2
P2 precedes A2. Paradoxical splitting always indicates may be due to loud A2, early opening snap and holosystolic or
significant underlying cardiovascular disease and is continuous murmurs.
usually due to prolongation of left ventricular activation or
prolonged left ventricular emptying that may delay the aortic Third and Fourth Heart Sound
component, causing it to follow the pulmonary component.
Left ventricular ejection is prolonged in conditions in which The third heart sound (S3) and the fourth heart sound (S4)
the left ventricle ejects an increased volume of blood into occur in the ventricles and are low pitched and best heard
the aorta (e.g. PDA), in left ventricular outflow obstruction with the bell of stethoscope. They are heard loudest over the
(e.g. severe aortic stenosis) or in delayed depolarization of the ventricle in which they occur. The S3 is usually related to high
left ventricle (complete left bundle branch block). The most flow, whereas S4 reflects a poorly compliant ventricle. The S3
common cause of paradoxical splitting of the second sound is occurs due to rapid ventricular filling in early diastole. They
left bundle branch block. Thus, wide splitting and paradoxical are normal in children with hyperdynamic circulation and thin
splitting of the second heart sound occur from similar cardiac chest wall, but are usually abnormal in patients older than 30
abnormalities, but on opposite sides of the heart. Paradoxical years of age. It occurs at the peak of ventricular inflow into
splitting is associated with severe left-sided disorders. the compliant ventricle. The S3 may originate from the left or
When the A2-P2 interval is just more than 30 msec then right ventricle and is best heard at the cardiac apex or the left
narrow splitting is appreciated. This is seen in shunt lesion lower sternal border respectively. The S3 is prominent, when
with severe pulmonary artery hypertension (PAH) without there is increased volume of ventricular inflow (as is seen
RV failure. Patients with VSD, who develop PAH may no in lesions with left to right shunts causing increased PBF),
longer have splitting of S2. Patients with ASD and associated valvular regurgitation and high cardiac output (as is seen with
PAH maintain a wide and fixed split of S2. Splitting is narrow anemia). A gallop rhythm heard in congestive cardiac failure,
(less than 30 msec), but remains physiologic, in patients with often represents exaggeration of the third heart sound in the
PDA who develop PAH. In acyanotic CHD like severe aortic presence of tachycardia.
stenosis, due to the delayed aortic closure one can appreciate The S4 is never considered normal and is due to atrial
a single S2. contraction inducing ventricular filling late in diastole. They
The loudness of each component of S2 is proportional occur with the P wave of the ECG and is synchronous to the
to the respective pressures in the aorta and pulmonary atrial ‘a’ wave. They are found in conditions in which, either the
artery at the onset of diastole. Dilatation of the aorta or atrium forcefully contracts against a ventricle with decreased
pulmonary artery may also cause accentuation of the aortic compliance, as from fibrosis or marked hypertrophy, or when
and pulmonic components, respectively. Decreased intensity the flow from the atrium to the ventricle is greatly increased.
of either component of the second sound may be due to stiff The S4 may be audible as a presystolic gallop, particularly if
semilunar valve, decreased pressure beyond the semilunar tachycardia is present. 177
2 Ejection Clicks 2. Forward flow through a constricted or irregular orifice or
into a dilated vessel or chamber.
Clicks are classified as ejection or nonejection clicks. The 3. Backward or regurgitant flow through an incompetent
Basics
most common clicks occur in systole and are related to valve, septal defect or patent ductus arteriosus.
abnormalities of the aortic, pulmonic and mitral valves. A combination of these factors is frequent. Before laying
Systolic ejection clicks are abnormal and they mark the a stethoscope on the patient’s precordium, the physician must
transition from the isovolumetric contraction period, to the have a clear concept of what to listen and where to auscultate.
onset of the ventricular ejection. It can be heard shortly after The importance of listening with the child supine cannot
the opening of the semilunar valves and are sharp, high-pitched be over- stressed. Murmurs, which are frequently detected
sounds with a click-like or clicking quality. They are heard in children, may either be innocent (Still’s murmur) or
loudest over their respective valves, except the aortic click pathological and it is important for the clinician to decide the
that is usually well heard at the apex. These sounds have been category.
classified as valvular, originating from deformed aortic and The murmurs are classified by their timing as systolic
pulmonic valves or as vascular, due to the forceful ejection (occurring between the first and second heart sounds), diastolic
of blood into the great vessels. The vascular clicks indicate (between the second sound and the first sound) or continuous
dilatation of either ascending aorta or pulmonary trunk. The (present continuously throughout the cardiac cycle). Continuous
dilatation may be due poststenotic dilation secondary to either murmurs also includes the murmur that begins in systole,
aortic or pulmonary valvular stenosis or from conditions with marches over the second sound and ends in diastole. Other
dilated major arterial trunk, like in Marfan’s syndrome or characteristics of the murmur to be observed are the location,
pulmonary hypertension. The mechanism of valvular click shape (crescendo, decrescendo, diamond, plateau), character
is unknown. It occurs at the point of maximal opening of a or quality (e.g. harsh, soft, blowing, rumbling, vibratory),
stenotic valve suggesting a valvular origin. It may also result radiation (the general rule of thumb is that the sound radiates in
from tensing of the wall of a dilated great vessel in which the direction of the blood flow), intensity or grades, pitch (low,
there are degenerated elastic fibers and the wall is supported medium or high) and variation with maneuvers (inspiration,
by collagen, which is indistensible. standing, squatting).
Ejection clicks in patients with a stenotic semilunar valve The most popular classification of murmur intensity is
occurs more commonly in mild or moderate stenosis and is described by Freeman and Levine. The systolic murmurs are
absent with severe stenosis. The pulmonary ejection click is graded from 1 to 6 and the diastolic murmurs are graded from
unique in that it is loudest during expiration. It is heard best 1 to 4. The intensity of murmur varies with the velocity of
with the diaphragm, in the pulmonary area with the patient blood flow across the area, where murmur is produced. The
sitting. The aortic ejection clicks is widely transmitted and velocity, in turn, is directly related to the pressure that drives
heard best at the cardiac apex or over the left lower thorax the blood across the murmur producing area.
with the patient in a supine position. They do not vary with Grading of Murmurs
respiration. The aortic valvular ejection sound is found Grade 1—so faint that it can be heard only with special
in non-stenotic congenital bicuspid valves. Clicks are not effort.
associated with dysplastic pulmonary valves, which move Grade 2—faint, but can be heard easily.
poorly if at all, or with fixed subvalvular stenosis. Grade 3—moderately loud, but no thrill.
Midsystolic click or non-ejection clicks with or without Grade 4—loud with palpable thrill.
a late systolic murmur is heard at the apex in mitral valve Grade 5—extremely loud and can be heard if only the edge of
prolapse. They are sharp, high-pitched and best heard at the stethoscope is in contact with skin.
cardiac apex. They vary with maneuvers, which alter the left Grade 6— exceptionally loud and can be heard with
ventricular volume. They are louder, when patient is standing stethoscope just removed from skin contact.
or sitting as LV volume is small and softer when patient
reclines or squats, which results in larger LV volume. Age of Presentation of Murmur
Murmurs If a murmur is audible in the first few hours of life it is often

due to structural heart disease particularly outflow obstruction
A cardiac murmur is defined as ‘a relatively prolonged series of or valvular heart disease, as their flow characteristics is
audible vibrations of varying intensity (loudness), frequency independent of PVR changes. These murmurs are usually due
(pitch), quality, configuration and duration.’ Cardiac murmurs to tricuspid valve regurgitation, aortic or pulmonary valve
are generated by turbulence in the normal laminar blood stenosis or else subvalvular aortic or pulmonary stenosis.
flow through the heart. Leatham has attributed production of Frequently, the PDA murmur is not continuous in the first week
murmurs to three main factors: of life and may be loudest at the left sternal border in the third
178 1. High flow rate through normal or abnormal orifices. and fourth interspaces. Occasionally, a long, high-pitched,
blowing, ‘organic-sounding,’ systolic murmur is encountered, to the site of obstruction and the direction of the jet in the aortic 11
heard maximally in the axillae. Common in prematures, it root.
also can be heard in full term babies with an increased stroke In supravalvular aortic stenosis, the murmur may be loudest

volume. This murmur arises in the peripheral pulmonary at a slightly higher location than in valvular aortic stenosis. In
arteries and is usually innocent and should disappear by 2 addition, the intensity of the radiated murmur over the right
months of age. The murmur of a VSD is often not present in carotid may be greater than over the left carotid artery. In
the first week of life. As PVR drops in the first few days in a subvalvular left ventricular outflow obstruction (hypertrophic
variable manner and continues to decrease during the first few cardiomyopathy), the maximum intensity of the murmur is
months of life, murmurs of shunt lesions, such as VSD, AV usually located along the lower left sternal border or over the
canal (endocardial cushion) defect, PDA and ASD, become cardiac apex. It radiates poorly to the base and neck.
audible. It is usually not difficult to distinguish between fixed
(aortic stenosis) and dynamic (obstructive hypertrophic
Systolic Murmurs cardiomyopathy) LVOTO. The character of the carotid pulse
provides important clues. In aortic valve stenosis, the initial
Systolic murmurs are heard between S1 and S2. They can upstroke and the peak of the carotid pulse are delayed and
be classified according to the time of onset and termination the volume may be reduced. In obstructive hypertrophic
in systole: early systolic, midsystolic (ejection systolic), cardiomyopathy, the initial upstroke of the carotid pulse
late systolic and holosystolic (regurgitant) murmur (Figure is usually sharp and the volume is normal. The change in
9). An ejection systolic murmur (midsystolic) begins after intensity of the ejection systolic murmur in response to
the S1 and ends before A2 (left sided) or P2 (right sided). different maneuvers is also useful diagnostically. Assuming
An early systolic murmur starts with S1 and extends for a a standing position increases the intensity of the murmur
variable length in systole, but does not extend up to S2. A late in hypertrophic cardiomyopathy; it decreases the murmur
systolic murmur starts after S1 and extends to A2 (left sided) of aortic valve stenosis. The murmur of hypertrophic
or P2 (right sided). A holosystolic murmur starts with S1 and cardiomyopathy increases in intensity with the straining phase
extends up to A2 (left sided) or P2 (right sided). of the Valsalva maneuver and the carotid pulse decreases or is
The ejection systolic murmur or midsystolic murmur unchanged. Both the intensity of the murmur and the carotid
results from the turbulent blood flow across the semilunar pulse volume decline with the Valsalva maneuver in aortic
valves. Mid-systolic murmurs typically have a crescendo- stenosis; the heart rate increases and arterial blood pressure
decrescendo character, that is, they start softly and become falls.
loudest near midsystole, followed by a decrease in sound The murmur of valvular pulmonary stenosis is harsh and
amplitude. They are also called crescendo-decrescendo or best heard over the left second interspace. When the murmur
diamond-shaped murmurs. These murmurs are seen in fixed is loud it radiates to the left side of the neck and is frequently
or dynamic outflow tract obstruction, increased flow across accompanied by a palpable thrill. A pulmonary ejection sound
normal semilunar valves, dilatation of the aortic root or at the onset of the murmur may be heard and S2 is widely
pulmonary trunk and in anatomical changes in the semilunar split with a decreased intensity of P2. The murmur duration
valves without obstruction. correlates reasonably well with the severity.
A bicuspid aortic valve is a frequent cause of a ejection
systolic murmur; this diagnosis should be entertained if the Holosystolic Murmurs
murmur is brief with an aortic ejection sound. The murmur
is best heard over the right second interspace with little or no Holosystolic (pansystolic) murmurs begin with the first heart
radiation. In valvular aortic stenosis, the maximum intensity sound and extend through systole. The intensity of these
is appreciated over the right second interspace; the ejection murmurs is high immediately after the onset of S1 and it
systolic murmur is harsh and rough and a thrill may be palpable extends to just before the S2. Often the S1 and S2 sounds
over the same area. The murmur radiates up into the neck and are overwhelmed by the murmur and may be difficult to
over both carotid arteries. In patients with aortic stenosis, the hear. This type of murmur is typically heard in AV valve
longer and later peaking murmur is usually associated with regurgitation. Mitral and tricuspid regurgitation murmurs
hemodynamically significant obstruction; a brief and early are high pitched, with variable intensity and blowing quality.
peaking murmur indicates mild stenosis. The intensity of the The murmur of mitral regurgitation is accentuated when the
murmur is variable and may not correlate with the severity of patient is in the left lateral decubitus position and it classically
stenosis. In the presence of heart failure and a reduced stroke radiates to the axilla and left infrascapular region; its intensity
volume, the duration, configuration and intensity bear a poor does not change with respiration. The murmur of tricuspid
correlation to the degree of obstruction. The ejection sound regurgitation increases in intensity with inspiration. It tends
is usually absent in severe stenosis. The site of maximum to radiate to the xiphoid area or epigastrium and right sternal
intensity and direction of radiation of the murmur are related border, but not to the axilla. Tricuspid regurgitation is often 179
2
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
associated with pulmonary hypertension and hence signs such
Box 3: Classification of continuous murmurs
11
as a sternal heave (right ventricular hypertrophy) and a louder
P2 may provide additional clues.

Continuous murmurs caused by high-to-low pressure
shunts:
Diastolic Murmurs • Systemic artery to pulmonary artery (patent ductus arterio-
sus, aortopulmonary window, truncus arteriosus, pulmo-
Diastolic murmurs occur after S2 and are therefore associated nary atresia with collaterals, anomalous left coronary artery,
with ventricular relaxation and filling. Diastolic murmurs are bronchiectasis, sequestration of the lung)
also classified according to the time of onset and termination • Systemic artery to right heart (ruptured sinus of Valsalva,
of the murmur in diastole. Diastolic murmurs are usually coronary artery fistula)
abnormal and may be early, mid or late diastolic. They may be • Left-to-right atrial shunting (Lutembacher syndrome, mitral
atresia with restrictive atrial septal defect)
caused by aortic or pulmonic valve regurgitation or by mitral or
• Venovenous shunts (anomalous pulmonary veins, porto-
tricuspid valve stenosis. Early diastolic murmurs, immediately systemic shunts)
follow S2 and are seen in aortic and pulmonary regurgitation. • Arteriovenous fistula (systemic or pulmonary)
Mid-late diastolic murmurs occur due to stenosis or increased
Continuous murmurs secondary to localized severe
flow across the mitral or the tricuspid valves. These murmurs
arterial stenosis:
can occur in mitral stenosis, tricuspid stenosis, or as flow
• Coarctation of the aorta
murmurs of ASD, VSD and PDA. Late diastolic (presystolic) • Branch pulmonary artery stenosis
murmurs occur due to pathological narrowing of the AV • Carotid stenosis
valves. The pulmonary regurgitation murmur in patients with • Celiac mesenteric stenosis
normal pulmonary artery pressure, is low-pitched and early • Renal stenosis
diastolic because of the low-pressure gradient. In patients with • Femoral stenosis
pulmonary hypertension, the murmur, known as the Graham- • Coronary stenosis
Steell murmur is heard, which is also early diastolic but is high Continuous murmurs caused by rapid blood flow:
pitched and decrescendo, because of the high pressure gradient • Venous hum
between the pulmonary artery and the right ventricle in • Mammary soufflé
diastole. The murmur of pulmonary regurgitation increases in • Hemangioma
intensity during inspiration, unlike that of aortic regurgitation. • Hyperthyroidism
• Acute alcoholic hepatitis
• Hyperemia of neoplasm (hepatoma, renal cell carcinoma,
Continuous Murmurs Paget disease)
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 Abdominal Examination
murmurs result from blood flow from a higher pressure Normally liver is palpable (2–3 cm below costal margin) at
chamber or vessel to a lower system associated with a midclavicular line up to 4 to 5 years of the age, after that
persistent pressure gradient between these areas during systole it remains palpable up to 1 cm till late childhood. If liver
and diastole. These murmurs may occur due to aortopulmonary is palpable further downwards and the infant is irritable it
connections, arteriovenous communication and disturbances probably indicates presence of congestive heart failure. If the
in the flow patterns in the arteries or veins. The continuous liver is in midline and palpable symmetrically, it indicates
murmur from aortopulmonary communications is loudest cardiac malpositions and underlying complex heart disease.
around the S2. The arterial continuous murmur is characterized The site of the gastric fundus is detected by percussion, which
by a more pronounced systolic component while a venous determines visceral situs. Spleen is not normally palpable; if
continuous murmur is characterized by a more pronounced palpable it indicates possibility of infective endocarditis.
diastolic component. The differential diagnosis for continuous
murmurs is given in Box 3. Respiratory System Examination
The systolic-diastolic murmur or the so-called to-and-
fro murmur, is not a continuous murmur. It being different Apart from rate of respiration, it is important to auscultate both
through a small ‘silence’ separating the two murmurs. A to- lung fields. Bilateral crepitations is an important sign of left
and-fro murmur, involves two components: a systolic one in heart failure. Unlike adults, where crepitations is commonly
which the blood flows in one direction and a diastolic one in basal, in neonates and infants it is more diffusely heard and
which the blood flows in the opposite direction, while in those often associated with rhonchi. The clinical characteristics of
with true continuous murmur, the blood flows in the same common types of CHD are summarized in Table 8.
direction in both systole and diastole. 181
2 Table 8

Characteristics of common types of lesions
Basics
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 • N
o recurrent chest infections
infections
• P
ulsatile precordium (active • N
o precordial activity (silent • S
ilent precordium, but forceful RV/LV
precordium with or without precordial precordium) impulse
prominence)
• Cardiomegaly • N
o cardiomegaly • No cardiomegaly
• Shunt murmurs and flow murmurs (if • No shunt murmurs • H

arsh ejection systolic murmurs (may
shunt large) be with thrill)
• Increased pulmonary vascularity • D

ecreased pulmonary vascularity • Normal pulmonary vascularity
(plethoric lung fields) (oligemic lung fields)
• T
endency for CHF to occur at early • C
HF occurs in late phase • C
HF occurs in very late phase; rarely it
phase mainly during infancy occurs early in severe stenotic lesions
CHF = Congestive heart failure; LV = Left ventricle; RV = Right ventricle
conclusion
where learning begins and where the most judgments
Clinical assessment is a solid foundation for diagnosis and against self are formed. This is also the stage that most
management strategy for cases of CHD. Meticulous history is people give up.
the cornerstone of the diagnosis of some CHDs. 3. Conscious Competence: “I know that I know how to
Auscultation is an art. Never auscultate from the wrong side do this.” This stage of learning is much easier than the
of the bed. One should know, what to hear and where to hear. second stage, but it is still a bit uncomfortable and self-
One should find out the reason, if one does not hear what is conscious.
expected after analyzing the good history, thorough general and 4. Unconscious Competence: “What, you say I did some-
systemic clinical examination. The clinician should not leave thing well?” The final stage of learning a skill is when it
the bedside until systematic analyses has been done of what has become a natural part of us; we do not have to think
one has heard on auscultation. The clinician is the captain of the about it.
ship (patient). If he fails to detect the disease in time by clinical
examination then he will not get the relevant investigations Suggested Reading
done and the patient is denied the proper treatment.
1. Clinical Methods. In: Walker HK, Hall WD, Hurst JW (Eds).
The history, physical and laboratory examinations. 3rd edition.
Stages of Learning Boston: Butterworths; 1990.
2. Libby. Braunwald’s. In: Libby P, Bonow RO, Mann DL, Zipes
1. Unconscious Incompetence: “I do not know that I do
DP (Eds). A Textbook of Cardiovascular Medicine. 8th edition.
not know how to do this.” This is the stage of blissful Elsevier Saunders; 2007.
ignorance before learning begins. 3. Perloff JK, Marelli AJ. Clinical recognition of congenital heart
2. Conscious Incompetence: “I know that I do not know disease. 6th edition. Philadelphia: Saunders, an imprint of
how to do this, yet.” This is the most difficult stage, Elsevier Inc; 2012.
182
C hapter
Clinical Approach to
12 Cyanotic Heart Diseases
Sudhayakumar N
Cyanotic congenital heart disease (CCHD) can be defined as an PBF are usually complex lesions with bidirectional shunt
anatomical congenital cardiovascular birth defect, which results and hyperkinetic PAH; cyanosis in these situations is due
in systemic arterial desaturation due to right-to-left shunt. Review to intercirculatory mixing or because of a transposition like
of literature reveals a reported incidence of congenital heart physiology.
disease (CHD) varying between 1.2 and 17 per thousand live 1. CCHD with low PBF and no PAH
births (probably on an average 8 per 1,000), of which cyanotic i. Tetralogy of Fallot (TOF).
congenital heart disease (CCHD) may contribute to about ii. TOF equivalents (pulmonary stenosis with ventricular
one-fourth.1,2 With recent advances in diagnostic modalities septal defect like pathology).
and improvement in interventional and surgical management, a. Double outlet right ventricle (DORV) + VSD + PS.
the survival and quality of life of children with CCHD have b. D-transposition of great arteries (d-TGA) + VSD +
improved tremendously. Though technology has revolutionized PS.
the diagnostic tools, a clear understanding of pathophysiology c. L-transposition of great arteries (l – TGA) + VSD
along with meticulous clinical examination and analysis of + PS.
simple bedside investigations like 12-lead electrocardiogram d. Tricuspid atresia + VSD + PS.
and chest skiagram can contribute heavily to proper diagnosis e. Single ventricle + PS.
and management of even very complex CCHDs. f. Truncus arteriosus with small pulmonary arteries.
Cyanotic congenital heart disease includes a wide spectrum iii. Pulmonary atresia with intact interventricular septum.
of anatomical and physiological aberrations ranging from a iv. PS with atrial septal defect (ASD).
relatively simple lesion like mild tetralogy of Fallot to very v. Ebstein anomaly of tricuspid valve.
complex problems like hypoplastic left heart syndrome 2. CCHD with low PBF and PAH
(HLHS). Though there are different approaches to classification, Eisenmenger syndrome.
an initial basic approach is based on the pulmonary blood 3. CCHD with high PBF
flow (PBF), as the systemic arterial saturation is primarily i. Intercirculatory mixing (admixture physiology)
determined by the volume of oxygenated blood that comes a. Venous level—total anomalous pulmonary venous
to the systemic circulation from the pulmonary capillaries.3,4 drainage (TAPVD).
Thus, CCHDs can be classified as those with, b. Atrial level—single atrium, tricuspid atresia, HLHS.
1. Reduced pulmonary blood flow (Qp/Qs < 1). c. Ventricular level—single ventricle.
2. Increased pulmonary blood flow (Qp/Qs > 1). d. Arterial level—truncus arteriosus.
3. Near normal pulmonary blood flow. ii. Transposition physiology
Basic abnormality in this group is a very high resistance a. d-TGA.
to PBF either because of pulmonary stenosis or severe b. Taussig-Bing anomaly.
pulmonary arterial hypertension (PAH), so that the ventricles 4. CCHD with near normal PBF
find it easier to empty to the systemic circulation. Hence, i. Pulmonary arteriovenous fistula.
these entities can be subdivided into those with pulmonary ii. Anomalous drainage of vena cava to left atrium (LA).
stenosis (PS) and those with PAH. CCHDs with increased iii. Unroofing of coronary sinus into the LA.
2 CCHD can also be classified in a different approach as characteristically varying degrees of cyanosis depending on
follows: the severity of pulmonary stenosis and history of squatting.
1. TOF physiology. Cyanotic spell is almost diagnostic for this entity. Those with
basics
2. Transposition physiology. increased PBF will have features of heart failure (dyspnea,
3. Admixture physiology. interrupted feeding due to dyspnea, failure to thrive, etc.),
• Pretricuspid—TAPVD, HLHS, tricuspid atresia, single frequent respiratory tract infection and relatively lesser degrees
atrium of cyanosis. Acute pulmonary edema like presentation in the
• Post-tricuspid—single ventricle, truncus arteriosus. neonatal period in a cyanotic baby may indicate obstructed
4. Eisenmenger physiology. TAPVD or HLHS with restrictive interatrial communication.5
5. Ductus dependent physiology. Cyanosis in TOF typically appears a few weeks after birth;
• Ductus-dependent pulmonary circulation, e.g. pulmonary however, as the severity of Fallot increases, the cyanosis can
atresia appear earlier. Cyanosis on day 1 indicates either d-TGA or
• Ductus-dependent systemic circulation, e.g. HLHS. other complex situations. In Ebstein anomaly, a characteristic
6. Near normal physiology, e.g. pulmonary arteriovenous biphasic pattern is described—cyanosis at birth; disappears as
fistula. pulmonary resistance falls and reappears later as right heart
7. Miscellaneous, e.g. Ebstein anomaly, PS + ASD. failure ensues.6
Maternal history is also important; d-TGA may have
Approach to clinical diagnosis of a correlation with maternal diabetes though this has not
Cyanotic congenital heart disease been supported by recent observations. History of maternal
ingestion of teratogens can also be contributory to diagnosis—
Clinical approach to diagnosis of CCHD should aim at maternal consumption of alcohol has been correlated with
delineating the anatomical and physiological abnormalities occurrence of d-TGA, lithium with Ebstein anomaly and sex
and also the rhythm status of the child. Following aspects hormones with d-TGA and TOF.
have to be addressed.
Physical Findings
Physiology
Meticulous physical examination contributes greatly to arrive
• Pulmonary circulation—flow, pressure, resistance at a reasonable clinical diagnosis of the entity. Presence of
• Systemic circulation—oxygen saturation, cardiac output, dysmorphic or syndromic features gives us a clue to the
blood pressure, resistance underlying condition based on the established associations.6,7
• Ventricular function A few examples are given below:
• Venous pressures—systemic/pulmonary • Down syndrome—atrioventricular canal defects (AVCDs)
• Any obstruction to circulation • DiGeorge syndrome8,9—interrupted aortic arch, truncus
• Ductus dependent or not arteriosus, TOF
• Any compensatory mechanisms. • Laurence-Moon-Biedl syndrome—TOF
• Ellis Van Crevald—Common atrium
Anatomy • Alagille syndrome—TOF
• Velocardiofacial syndrome—conotruncal anomalies
• Visceral and cardiac situs • CHARGE syndrome—HLHS
• Visceroatrial/atrioventricular/ventriculoarterial connection Extracardiac anomalies are seen with a relatively higher
• Right ventricular/left ventricular/biventricular pattern frequency in certain CCHDs—48 percent in truncus arteriosus,
• Great artery relation—normal/transposed/malposed 30 percent in TOF, 20 percent in tricuspid atresia, 15 to 30
• Status of inflow tract and outflow tract of the ventricles percent in HLHS; but less frequent with d-TGA (< 10%).10
• Venous connection—pulmonary and systemic Differential cyanosis is diagnostic for Eisenmenger patent
• Coronary anatomy ductus arteriosus, whereas reversed differential cyanosis occurs
• Collaterals. in d-TGA with ductus and preductal coarctation or PAH.11
Symptomatology contributes to the assessment of physiology
and physical findings guide to anatomical status; radiology and Pulse, Blood Pressure and Jugular
electrocardiogram add to this. Venous pulse
Symptoms Bradycardia suggestive of complete heart block occurs

more frequently with l–TGA and atrioventricular (AV) canal
As outlined initially the main aim is to assess the pulmonary defects.12 High volume pulse with wide pulse pressure in a
184 blood flow. Reduced PBF group with TOF physiology has cyanotic indicates aortic runoff as in aortic regurgitation in TOF,
truncal regurgitation or aortopulmonary runoff through a ductus l–TGA and truncus or loud P2 in high PBF physiology or 12
or aortopulmonary collaterals in conditions like pulmonary PAH).Wide split S2 in a cyanotic patient in the absence of
atresia. It can also occur following a palliative aortopulmonary right ventricular failure indicates TAPVD or single atrium.
clinical approach to cyanotic heart diseases

shunt for pulmonary oligemic situations. Radiofemoral delay of Left ventricular third heart sound indicates a high pulmonary
coarctation of aorta occurs with a higher frequency in Taussig blood flow.
Bing anomaly (20%), tricuspid atresia (8%) and d-TGA (5%). Pulmonary stenosis murmur is heard in TOF physiology—
Prominent ‘a’ wave in a cyanotic is a clue for tricuspid atresia length of murmur being inversely related to the severity. In
or Ebstein anomaly; it is unusual in TOF. TOF, this murmur is best heard in third left intercostals space;
in DORV, it may be relatively higher. As the pulmonary
Precordium artery is vertically oriented in d-TGA, the pulmonary stenosis
murmur may be heard well in the upper midsternal or upper
Cardiac and visceral situs has to be assessed straightaway right sternal area. A loud VSD like murmur can be heard in
as cardiac malpositions and they have some specific truncus arteriosus and tricuspid atresia. Mitral mid-diastolic
associations e.g. higher incidence of l-TGA in dextrocardia murmur indicates increased pulmonary flow; in a low PBF
with situs solitus, very complex lesions in levocardia with group, it may indicate tricuspid atresia or pulmonary atresia
situs inversus. A normal cardiac size with quiet precordium, with intact IVS. Tricuspid mid-diastolic murmur in CCHD
absent pulmonary artery pulsation and murmur of PS is quite points to TAPVD, single atrium, AV canal defects or Ebstein.
characteristic of a TOF like physiology, whereas cardiomegaly Early diastolic murmur could be of aortic regurgitation
with dynamic precordium and features of PAH indicate a high in TOF, truncal regurgitation, pulmonary regurgitation in
pulmonary flow group. Assessment of ventricular dominance Eisenmenger syndrome or the normotensive pulmonary
is of importance as outlined below. regurgitation of absent pulmonary valve in TOF; the latter can
be heard following intracardiac repair of TOF also. Continuous
Right Ventricle Dominant murmur occurs in low PBF group (especially pulmonary
atresia)—in second left space due to patent ductus arteriosus
TOF, DORV + VSD + PS, d-TGA + VSD + PS, l–TGA + VSD and in lung fields due to aortopulmonary collaterals. Venous
+ PS, PS + ASD, HLHS. hum persisting despite occlusion of right jugular vein is
characteristic of the classical supracardiac variety of TAPVD
Left Ventricle Dominant due to the increased superior vena caval flow.
Tricuspid atresia, double inlet left ventricle (DILV), pulmonary Electrocardiogram

atresia with intact ventricular system (IVS), Ebstein anomaly
with hypoplastic right ventricle and non-restrictive ASD. In addition to assessment of cardiac rhythm status, ECG
contributes to evaluation of atrial situs, ventricular loop,
Biventricular—Indicates Increased Pulmonary Blood ventricular dominance and electrical axis, which aids in the
Flow (no Pulmonary Stenosis) clinical diagnosis; or it may have a typical diagnostic pattern
(Figures 1 and 2) as in the case of Ebstein anomaly (very tall
Double outlet right ventricle + VSD, d-TGA + VSD, tricuspid or Himalayan P wave suggestive of right atrial abnormality,
atresia with VSD, truncus arteriosus. polyphasic QRS in chest leads, delta wave of right-sided
accessory pathway) or tricuspid atresia (right atrial P wave,
Normal left axis deviation and absent right ventricular forces).13
Atrial tachyarrhythmias occur in conditions with dilated
Pulmonary AV fistula, vena caval drainage to LA, unroofing atrium as in Ebstein and AVCDs. In the case of Ebstein anomaly,
of coronary sinus. presence of a right-sided accessory atrioventricular pathway
Prominent pulsations in the second left intercostal space also contributes to the higher incidence of tachyarrhythmias.
occurs in high PBF group; however, in a case of high PBF, if Atrioventricular blocks occur more frequently in l–TGA and
pulmonary artery pulsations are not felt it may be a clue for AVCDs. Complete heart block in l–TGA may be present at
transposition. In l–TGA, the ascending aortic pulsation may birth or many times it will manifest only later. Prolongation
be strongly felt in second and third left space quite laterally. of PR interval is common in DORV also. Superior P axis may
indicate visceral heterotaxy.
Auscultation Absence of Q waves in V5, V6 in presence of LV dominance
indicates a possibility of ventricular inversion as in l–TGA or
A loud and split first heart sound is characteristic of Ebstein DILV of inverted type. Left axis deviation of QRS occurs in
anomaly of tricuspid valve. Second heart sound is single in presence of AV canal type of defects, tricuspid atresia and DORV
majority of the conditions and is often loud (loud A2 in TOF, without PS. Majority of cases of CCHD has right ventricular 185
2
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
hypertrophy or biventricular hypertrophy. Prominent left position of aortic arch can also be determined (Figures 3 to 12
ventricular forces and left atrial overload indicates enhanced 7). Many times, the radiology picture could be diagnostic
PBF. Paucity of right ventricular forces is a clue for tricuspid as in supracardiac TAPVC (snowman appearance), TOF

atresia, pulmonary atresia with intact IVS or DILV. (boot-shaped/coeur en sabot), d-TGA (egg on side) or
Ebstein anomaly (box shaped). Increased pulmonary
Radiology vascularity without prominent main pulmonary artery
segment may indicate malposition of aorta; a prominent
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
Figure 3: Classical lifted up right ventricular (RV) apex (coeur en Figure 5: Cardiomegaly, huge right atrium and reduced pulmonary
sabot), concave pulmonary bay, pulmonary oligemia and right aortic vascularity of Ebstein anomaly (box-shaped heart)
arch in tetralogy of Fallot
Figure 4: Cardiomegaly, increased pulmonary vascularity and narrow Figure 6: Classical figure of 8 appearance of total anomalous 187
vascular pedicle (absent visible main pulmonary artery) in d-TGA (egg pulmonary venous connection
on side appearance)
2
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
hump along the left upper border suggests L-posed aorta. in a neonate suggest the possibility of obstructed TAPVC
Right aortic arch is common with truncus arteriosus (pulmonary edema in neonate occurs in HLHS with
(40%), pulmonary atresia with VSD (30%) and TOF restrictive interatrial communication also).
(20–25%).14,15 A higher incidence of left superior vena Clinically, normal heart with normal ECG and chest X-ray
cava has been observed in AVCDs (19%), mitral atresia occur with pulmonary arteriovenous fistula, anomalous vena
(17%), TOF (10%) and truncus arteriosus (9%). Near caval connection to left atrium and unroofed coronay sinus in
188 normal cardiac silhouette with pulmonary edema pattern left atrium.
The overall flow chart for clinical approach to CCHD is 6. Schiebler GL, Adams P Jr, Anderson RC, et al. Clinical
study of 23 cases of Ebstein’s anomaly of the tricuspid valve.
12
illustrated in Flow chart 1.
Circulation. 1959;19:165-87.

7. Morris CD, Outclal J, Menashe VD. Hypoplastic left heart syn-
Conclusion drome: natural history in a geographically defined population.
Pediatrics. 1990;85:977-1000.
Systematic clinical evaluation of a cyanotic child with proper 8. Van Mierop LH, Kutsche LM. Cardiovascular anomalies
history and meticulous physical examination supported in DiGeorge syndrome and importance of neural crest as a
by a careful ECG and X-ray chest interpretation can give a possible pathogenetic factor. Am J Cardiol. 1986;58:133-37.
reasonable clue to the nature of the underlying heart disease 9. Goldmuntz E, Clark BJ, Mitchell LE, et al. Frequency of
(as shown in the flow chart), making echocardiographic 22q11 deletions in patients with conotruncal defects. J Am Coll
confirmation easier. Cardiol. 1998;32:492-98.
10. Glauser TA, Rorke LB, Weinberg PM, et al. Congenital brain
anomalies associated with hypoplastic left heart syndrome.
A doctor who cannot take a good history and a patient who
Pediatrics. 1990;85:984-90.
cannot give one are in danger of giving and receiving bad 11. Wernovsky G. Transposition of great arteries. In: Allen
treatment. HD, Shaddy RE, Driscoll DJ, Felters TF (Eds). Moss and
— Author Unknown Adams Heart Disease in Infants, Children and Adolescents,
7th edition. Philadelphia: Lippincott, William and Wilkins;
References 2008. pp. 1038-87.
12. Daliento L, Corrado D, Buja G, et al. Rhythm and conduction
1. Freed MH. The patholohy, pathophysiology, recognition disturbances in isolated, congenitally corrected transposition of
and management of congenital heart diseases. In: Fuster V, the great arteries. Am J Cardiol. 1986;58:314-18.
Alexander RW, O’Rourke RA (Eds). Hurst’s The Heart, 10th 13. Davachi F, Lucas RV Jr, Moller JH. The electrocardiogram
edition. Mc Graw Hill. 2001. pp. 1837-1905. and vectorcardiogram in tricuspid atresia. Correlation with
2. Ferencz C, Rubin JD, McCarter RJ, et al. Congenital heart pathologic anatomy. Am J Cardiol. 1970;25:18-27.
disease: prevalence at birth. The Baltimore-Washington Infant 14. Bharati S, Paul MH, Idriss FS, et al. The surgical anatomy of
Study. Am J Epidemiol. 1985;121:31-36. pulmonary atresia with ventricular septal defect: pseudotruncus.
3. Edwards WD. Classification and terminology of cardiovascular J Thorac Cardiovasc Surg. 1975;69:713-21.
abnormalities. In: Allen HD, Shaddy RE, Driscoll DJ, Felters 15. Butto F, Lucas RV, Edwards JE. Persistent truncus arteriosus:
TF (Eds). Moss and Adams Heart Disease in Infants, Children pathologic anatomy in 54 cases. Pediatr Cardiol. 1986;7:95-101.
and Adolescents, 7th edition. Philadelphia: Lippincott, William
and Wilkins. 2008. pp. 34-57. Suggested Reading
4. Perloff KJ. Introduction and formulation of the problem. In:
Perloff KJ (Ed). Clinical Recognition of Congenital Heart 1. Allen HD, Shaddy RE, Driscol DJ, Felters TF (Eds).
Disease, 4th edition. Philadelphia: WB Saunders Co. 1994. Moss and Adams Heart Disease in Infants, Children and
pp. 1-8. Adolescents, 7th edition. Philadelphia: Lippincott, William
5. Sudhayakumar N, Rajesh G. Hypoplastic left heart syndrome. and Wilkins; 2008.
In: Satpathy M (Ed). Clinical Diagnosis of Congenital Heart 2. Perloff KJ (Ed). Clinical Recognition of Congenital Heart
Disease, 1st edition. Jaypee Brothers; 2008. pp. 312-16. Diseases, 4th edition. Philadelphia; WB Saunders Co, 1994.
189
C hapter
Role of Radiography in
Madhav Hegde, Vijayalakshmi IB
IntRoDuCtIon BasIC InteRRogatIons on CHest X-Ray
The role of radiography especially chest X-ray (roentge- 1. Cardiac position.

nogram) has decreased as a tool of cardiovascular thoracic 2. Situs.
imaging, because of the widespread reach of antenatal 3. Bony cage.
(fetal echocardiography) and postnatal transthoracic 2D 4. Rotation.
echocardiography (TTE). The early detection of congenital 5. Cardiothoracic ratio.
heart disease (CHD) by TTE and its management, has in turn 6. Thymic shadow.
led to lessened ‘classical’ appearances on radiography. Still 7. Underexposed or overexposed?
it continues to play an important role in evaluation of both 8. Degree of inspiration.
pediatric and grown up congenital heart diseases (GUCH). 9. Pulmonary vascularity.
Today, chest X-ray (CXR) is not a main diagnostic tool 10. Cardiac silhouette.
for detection of CHD, however it is complimentary to clinical 11. Lung fields.
assessment and TTE. With its decreased importance over the 12. Cardiophrenic (CP) angles.
last two-three decades, the ability of interpreting X-ray has
also declined across the medical fraternity. Although diagnosis Cardiac Position
of CHD on CXR can be attempted, it is unfortunately less
accurate. Intricate anatomical and physiological phenomena Normally the major portion of the heart (2/3rd) lies to the left
make the interpretation of CXR a complex process compared to of the midline. Any position other than left is considered as
echocardiography. Echocardiography allows direct visualization malposition. The left sided heart with left ventricular apex on
of the cardiac structures and their functional profile, whereas the left side is called ‘levocardia’. When most of the heart is
CXR provides mere summation of these complex anatomic and in the right hemithorax and the base to apex axis points to the
pathophysiological processes. In most cases, cardiac pathology right, it is called ‘dextrocardia’. When the heart is in midline
is reflected in an abnormal CXR image. In few situations, it is it is termed as ‘mesocardia’.
easier to get and store data in terms of roentgenogram rather
than echocardiography, e.g. calcification of the patent ductus situs
arteriosus (PDA) and aortic knuckle, pulmonary arteriovenous
(AV) malformation, situs, pulmonary vasculature and laterality Situs is the site or position of the viscera. Situs solitus is
of the aortic arch. the normal position, in which the liver is to the right and
Chest X-ray needs to be regarded as a necessary tool with the fundal gas shadow is to the left. Dextrocardia with situs
limitations, with a specific role in the diagnosis of CHD. The solitus is called isolated dextrocardia (Figure 1). In mirror
gallery of images showing the few ‘current’ clinical scenarios, image dextrocardia there is situs inversus (Figure 2).
where CXR has a vital role is given in this chapter. Evaluation
of the quality of X-ray requires some understanding of the Visceroatrial Situs
technical factors involved in the production of an X-ray
image. Without such understanding, the risk of making an Visceroatrial situs means that the right atrium (RA), liver,
interpretive error is increased. inferior vena cava (IVC) and trilobed right lung are on one
13
Role of RadiogRaphy in Congenital heaRt diseases

figure 3: Schematic representation of bronchial morphology
LB = Left bronchus; RB = Right bronchus
figure 1: CXR image shows isolated dextrocardia with liver shadow to

the right and fundal gas shadow to the left (situs solitus, dextrocardia)
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. 191
figure 5: CXR image in right lateral view shows how
ii. Right bronchus is short, wide and straight. to identify the normal structures
2
BasiCs
figure 6: CXR image shows scoliosis
figure 7: Chest X-ray in a 2 years old child of patent ductus arteriosis

iii. Left bronchus is long, thin and curved. (PDA) with meningocoele, shows spina bifida, hemivertebrae (arrow)
iv. Measure the bronchus from the bifurcation, the longer of with splaying of left lower ribs and the PDA coil is in situ
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.
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 figure 8: CXR image with correct centering. There is equal distance
detected by simple X-ray. The children with Down syndrome between the medical end of clavicle and midline
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 be checked before reading it. The centering is checked by
is seen in subclavian pulmonary artery anastomosis as in clavicular symmetry. There should be equal distance between
Blalock-Taussig shunt. the medial end of the clavicle and midline (Figure 8). If the
distance between medial end of the clavicle and center line
Is there significant Rotation? is unequal then centering is not correct (Figure 9). If the
centering is not correct then the interpretation can go wrong
Rotation means that the baby was not positioned flat on the due to rotation. Rotation can make the lungs look asymmetrical
X-ray film and one plane of the chest is rotated in comparison and it can change the orientation of the cardiac silhouette. If
192 to the plane of the film. The centering of the CXR has to there is significant rotation, the side, which has been lifted
13

figure 9: CXR image with incorrect centering—unequal distance figure 10: The correct method of measuring the
between the medial end of clavicle and central line 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.
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. figure 11: CXR image in a patient epicardial fat in cardiophrenic
angle mimicking cardiomegaly
thymic shadow
(Figure 12A). The right lobe of the thymus can insinuate
The thymic shadow is usually prominent in the first few years into the minor fissure, causing a ‘sail’ sign (Figure 12B). The
of life. Thymic shadow should not be mistaken for mediastinal awareness of various apperances of thymus on CXR can bail
widening. The shadow of the thymus lies anteriorly in one out of a situation wherein thymus mimics a pericardial
relationship to the heart and great vessels. The relative size mass on echocardiography.
of the thymus increases with expiration and decreases with
inspiration. The thymus decreases in size during periods Is the X-ray underexposed or overexposed?
of stress, such as during sepsis. Because the thymus is a
soft organ, its lateral margin can have indentations caused A properly penetrated chest radiograph is one, in which the
due to the overlying costal cartilages, causing a ‘wave’ sign intervertebral bodies can be seen. Normally only the first four 193
2
BasiCs
a B
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 iii. Pulmonary venous hypertension (PVH) (ground glass
CXR, the vertebral bodies are visible clearly through the appearance).
cardiac shadow. In underpenetrated or underexposed film iv. Pulmonary edema (bat-wing appearance).
the vertebral bodies are not visible at all. An underpenetrated
chest CXR does not differentiate the vertebral bodies from Oligemia
the intervertebral spaces. An overpenetrated film shows the
intervertebral spaces very distinctly. An overpenetrated CXR In oligemia, vascular shadows are reduced. They are not seen
will be darker and the subtleties will be harder to see. An even in the intermediate lung zones. Main pulmonary artery
underpenetrated CXR will emphasize normal lung and make (MPA), left pulmonary artery (LPA) and right descending
it appear as if there are infiltrates. Hence it is important to pulmonary artery (RDPA) are of small size (normally RDPA
know whether the CXR is overexposed or underexposed. is of the same size as the right lower lobe bronchus). Oligemia
Overexposure causes the image to be dark. Under these occurs in critical pulmonary stenosis (PS) and in tetralogy
circumstances, the thoracic spine, mediastinal structures, of Fallot (TOF). In pulmonary valvular stenosis along with
retrocardiac areas, nasogastric and endotracheal tubes are oligemia there is poststenotic dilation of the MPA and the
well seen, but small nodules and the fine structures in the lung right ventricle (RV) and RA are enlarged (Figure 13A). In
cannot be seen. However, the widespread availabilty of digital TOF pulmonary bay is empty (MPA is small) and severe RVH
imaging (computed radiography, direct digital radiography) is seen without RA enlargement (as RV pumps into the over-
has reduced the importance of ‘optimal’ exposure as images riding aorta and the pressure is not transmitted to RA). Nearly
can be manipulted on viewing monitors. 25 percent of TOF can have right sided aortic arch (Figure
13B). The left or right aortic arch can be made out by the
Degree of Inspiration ipsilateral indentation of the trachea.
Normally, the right hemidiaphragm should be at the level of Plethora

6th rib anteriorly and the 9th rib posteriorly. If diaphragm is
below this level, it is a ‘hyperinflated’ film. Expiratory films In plethora (Figure 14) the vascular shadows are numerous and
produce apparent cardiomegaly and pseudotracheal deviation. vessels can be traced in the lateral one-third of the lung fields
The heart appears larger on anteroposterior (AP) than in PA also. The MPA, LPA and RDPA are large. End on vessels are
view. Expiratory film, simulates pulmonary edema and the more in number ( ≥ 3 in one lung field or ≥5 in both lung fields).
heart appears larger. 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
Pulmonary Vascularity 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
Pulmonary vascularity can be nicely made out on CXR and one lesion. In normal children diameter of RDPA is less than that
can know whether the patient has decreased pulmonary flow of trachea. If the ratio of RDPA to trachea is more than 1 it
(oligemia) or increased pulmonary flow (plethora). Abnormal indicates significant left to right shunt. Plethora occurs in left
pulmonary vascularity can be generally divided into four types: to right shunts, admixture lesions and transposition of the
i. Oligemia. great arteries (d-TGA) without PS. To have plethora left to
194 ii. Plethora. right shunts should be at least 1.5:1.
13

a B
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 figure 15: Fluroscopic image of 4 months infant tetralogy of Fallot
defect and atrial septal defect with pulmonary arterial hypertension, with absent left pulmonary artery, shows oligemia in right lung and
shows right atrium, right ventricle, main pulmonary artery dilated with absent vascular markings in left lung
plethora
Occasionally there can be unilateral plethora as in BT there is equalization of the vascularity. When there is severe
shunt and in unilateral major aortopulmonary collateral artery obstruction to the pulmonary veins, the CXR shows ground
(MAPCA). Asymmetry in lung vascularity can also occur glass appearance (Figure 16A). The ground glass appearance
after Glenn surgery and in pulmonary artery branch stenosis due to pulmonary venous hypertension is an important feature
or absent right pulmonary artery (RPA) or LPA (Figure 15). and should be distinguished from hyaline membrane disease.
The normal pulmonary capillary wedge pressure (PCWP) is
Pulmonary Venous Hypertension < 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
Normally the upper lobe veins are less prominent than the pulmonary veins in the upper lobe are more prominent than 195
lower lobe veins. In PVH or postcapillary hypertension, that in the lower lobe. This is cephalization of the veins and
2
BasiCs
a B
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. Cardiac silhouette

In stage II PVH, as PCWP increases to between 18-25 mm
Hg, interstitial edema occurs and causes perihilar haziness, In the frontal projection, the right border of the cardiac
peribronchial cuffing (increased thickness of the bronchial silhouette consists of the following structures from top to
walls seen end-on, usually near the hilum), subpleural bottom: superior vena cava (SVC), ascending aorta, right
effusion and the appearance of Kerley B lines (short, thin, 1 atrial appendage RA and IVC. The left border of the cardiac
to 2 cm long parallel lines seen at right angles to the pleura, silhouette is formed from top to bottom by the aortic knuckle
laterally at the lung bases). These lines represent fluid in the (aortic knob), pulmonary trunk, left atrial appendage and the
interlobular septa. In stage III PVH, the PCWP is > 25 mm LV. Any enlargement or hypoplasia of a particular component
Hg. There is frank pulmonary edema reaching to the hilum of the heart will alter the normal shape of the cardiac silhouette.
and a typical ‘bat-wing’ appearance on CXR (Figure 16B). An upturned apex without cardiac enlargement occurs in right
PVH and pulmonary edema occur in mitral valve disease, ventricular hypertrophy.
obstructed total anomalous pulmonary venous connection The features of LV enlargement (lateral (L) and frontal
(TAPVC), hypoplastic left heart syndrome (HLHS), dilated (F) views) are:
cardiomyopathy (DCM). Stage IV PVH is seen in chronic • Mild-obliteration of retrocardiac (prevertebral) space (L)
pulmonary hypertension and there is hemosiderosis and • Moderate-cardiac shadow overlies vertebral column (L)
ossification. • Marked-cardiac shadow overshoots vertebral column (L)
• Left cardiac border elongated and more convex (Figure 17)
Pulmonary Artery Hypertension (F)
• Left cardiac border dips below left dome of diaphragm (F)
The characteristic radiological features of pulmonary • Apex rounded off (F).
arterial hypertension (PAH) or precapillary hypertension are The features of RV enlargement are:
prominent central pulmonary arteries and with tortuosity, • Obliteration of retrosternal space.
deviation, diminution in the size of arteries in the middle and • Clockwise rotation of heart—apex moves posteriorly and
lateral thirds of the lungs (“Pruned-tree appearance”). Pruning RV comes to form the left cardiac border—rounded and
is defined as > 50% loss of vessel diameter at any degree elongated apex away from the left dome of diaphragm.
branching and is suggestive of PAH. With onset of PAH there The features of RA enlargement are:
RV and RA enlargement. The heart size tends to normalize • Right cardiac border becomes more convex and elongated
with the severe PAH, though in patients of ASD with PAH the • It forms greater than 50 percent of right cardiac border
right sided chambers remain enlarged. • Dilation of SVC
196
13

figure 17: CXR image in a 12 year old patient with Shone’s syndrome
showing cardiomegaly with left ventricular enlargement with pulmonary
venous hypertension 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)
• 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. valve instead of a empty pulmonary bay it is filled with
Increased height of the RA border occupying more than aneurysmally dilated MPA (Figure 19B) .
half of the vertical distance between medial end of right 2. Egg on side or egg on string: Transposition of great
clavicle and dome of right hemidiaphragm. vessels (TGA). The malposition of great vessles, in
association with stress-induced thymic atrophy and
The features of LA enlargement are: hyperinflated lungs, results in the apparent narrowing of
The LA is the uppermost and posterior most chamber in the superior mediastinum on radiographs, which is the
subcarinal angle. The first evidence of LA enlargement is the most consistent sign of TGA. The cardiovascular
the presence of a bulge, on the left heart border below the silhouette varies from normal in the first few days after
pulmonary artery, caused by the left atrial appendage, the ‘third birth to enlarged and globular, with the classic appearance
mogul sign’. The next evidence is a double density through described as an egg on a string (Figure 20).
the central heart shadow, followed by widening of the carinal 3. Figure-of-eight sign or snowman in snow storm: It is
angle with elevation or posterior displacement of the left main seen in supracardiac TAPVC (Figure 21). The pulmonary
bronchus. There is also posterior esophageal displacement in veins converge behind the heart to form a common
the right anterior oblique view. The displacement ends well pulmonary vein that connects to the dilated vertical vein
above the diaphragm. The LA shadow does not touch whereas on the left, which joins the left innominate vein on the top.
the RA shadow touches the right dome of the diaphragm. The This drains into the SVC on the right to form the head of
LA enlargement can be graded as follows. the snowman. The body of the snowman is formed by the
• Grade 1—double cardiac density (contour) enlarged RA along with cardiac shadow. Plethoric lung
• Grade 2—LA enlargement in flush with right cardiac with ground glass appearance looks like snow storm.
border 4. Scimitar sign: Scimitar is a Turkish sword with the curved
• Grade 3—oveshoots RA and itself forms right cardiac blade traditionally used by Persian and Turkish warriors.
border (Figure 18) The shadow resembling the shape of scimitar is produced
by an anomalous pulmonary vein that drains any or all of the
The characteristic cardiac contour in some anomalies are: lobes of the right lung (Figure 22). The so-called scimitar
1. Boot-shaped heart (couer en Sabot): Tetralogy of Fallot vein curves outward along the right cardiac border, usually
(Figure 19A): This deformity is due to the uplifting of the from the middle of the lung to the cardiophrenic angle and
cardiac apex because of RV hypertrophy and concavity usually empties into the IVC but also may drain into the
of the MPA. But in cases of TOF with absent pulmonary portal vein, hepatic vein or right atrium. 197
2
BasiCs
a 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)
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).
198 6. 3 sign: It is seen in COA. The number 3 is formed by the
figure 21: CXR image of posteroanterior view shows ‘snowman in snow
storm’ appearance in total anomalous pulmonary venous connection dilatation of the left subclavian artery and aorta proximal to
13

a B
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
a B
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 which are diagnostic, e.g. in cases with congenital corrected
of the aorta distal to the site (Figure 24A). transposition of great arteries (CTGV), the malposed ascending
7. Rib notching: It is seen in the lower margin of the third aorta produces a long convexity on the left upper mediastinal
to eighth ribs (Figure 24B) in aortic coarctation due to the contour and cardiomegaly with increased pulmonary vascular
enlarged, tortuous intercostal arteries supplying blood to markings secondary to a ventricular septal defect (Figure 25).
the descending aorta. The notching is not usually seen in The right pulmonary artery appears to have a high take off
children younger than 5 years. because of an absent aortic shadow and is also quite prominent
Apart from specific signs in some condition there are other indicating ventricular inversion. Also in tricuspid atresia, 199
conditions which have characteristic features on radiography, CXR shows a mildy enlarged LV with a gap between RA and
2
BasiCs
figure 25: CXR image of corrected transposition of great arteries. figure 27: CXR image of 32-year-old patient with large patent ductus
The ascending aorta producing a long convexity on the left upper arteriosus with severe pulmonary hypertension shows dilated right
mediastinal contour pulmonary artery and left pulmonary artery with peripheral pruning
figure 28: Fluroscopic image of 22-year-old patient with large

figure 26: CXR image of film of tricuspid atresia shows normal sized ventricular septal defect with severe pulmonary hypertension with
heart with mildly enlarged left ventricular configuration with a gap right to left shunt shows the classic ‘jug-handle appearance’ due to
between right atrium and the diaphragm, indicating hypoplastic right aneurysmally dilated main and right pulmonary artery. Note the normal
ventricle sized heart with peripheral pruning
the diaphragm, indicating hypoplastic RV (Figure 26). The

pulmonary artery can be enlarged as in shunt lesions with Lung Fields
PAH (Figure 27). In Eisenmenger’s, the classic ‘jug-handle Apart from the vascularity, the lung fields can give important
appearance’ due to aneurysmally dilated MPA and RPA can be clue for the diagnosis of pulmonary embolization of either
seen on CXR (Figure 28). There is a normal sized heart with thrombus or large vegetation from RV or pulmonary valve.
peripheral pruning. The CXR can be diagnostic in idiopathic The Fleischner lines are the linear shadows seen in the
200 dilatation of pulmonary artery where there is aneurysmally region of an embolus. The knuckle sign—Abrupt tapering or
dilated pulmonary artery with normal cardia and lung fields termination of a pulmonary vessel. The Westermark sign is
(Figure 29). the focal hyperlucency (Figure 30A). The Hampton’s Hump
is the classical peripheral wedge-shaped area of opacification 13
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 inter-
ventions 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.
Cardiophrenic angles
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
figure 29: CXR image shows aneurysmally dilated pulmonary artery
with normal cardia and lung field of 18-year-old girl with idiopathic heart failure along with the cardiomegaly the pleural effusion
dilatation of pulmonary artery can be detected on CXR as the costophrenic angle is obliterated.
a B
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
a B 201
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
2
BasiCs
a B
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 Correct interpretation of pulmonary vasculature requires

considerable experience and cannot simply be learned
Along with clinical evaluation CXR serves as a screening from a book.
tool for the detection of congenital cardiovascular diseases. —Kurt Amplatz
It is also a useful tool in short-term and long-term follow-
up of post-surgical and post-procedure cases especially BIBLIogRaPHy
device closures. It is simple documentation tool for situs,
cardiovascular silhouette, radio-opaque surgical and 1. Ahmed MZ, Gera R and Kailas L. Chest X-rays in pediatric
percutaneous interventional devices. All importantly CXR cardiology.
is a stimulating teaching tool and helps understanding the 2. Chokkalingam A, Chokkalingam V. Cardiac X-rays. Elsevier.
3. Sharada K and Gouthami V. Radiological Diagnosis of
complexity of CHD. CXR is not any more a primary diagnostic
Congential Heart Diseases.
tool in CHD but appreciating it as poor man’s CT will not be
202 4. Sutton D. Text Book of Radiology and Imaging, 7th edition.
overstating its utility in routine clinical practice. Churchill Livingstone.
C hapter
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

Role of Cardiac CT in Congenital Heart Disease
increasing number of patients surviving after therapeutic
intervention for congenital heart disease (CHD) has remarkably The role of CT in the evaluation of pediatric CHD is constantly
increased over the couple of decades. Echocardiography, evolving, refined and redefined with advances in the field and
either transthoracic or transesophageal, however, has been ever-expanding in its range of applications. There are many
the cardiologist’s eyes to the heart for this purpose, and will generally accepted clinical indications for evaluation of
probably uphold that status, at least in the diverse spectrum patients with CHD–either known or suspected on the basis of
of CHD. The accurate diagnosis and frequent follow-up of echocardiographic findings where in further imaging is needed
morphologic and functional cardiovascular status is required to characterize cardiac or extracardiac anomalies before
in CHD, preferably with a non-invasive imaging techniques intervention.2,3 Prime examples are described given below.
such as cardiac computed tomography (CT) and magnetic
resonance imaging (MRI) holds potential to replace many of Use of CT in Various Congenital Heart Diseases
the invasive angiograms done annually.1
Intracardiac Anomalies
need for Cardiac CT and MRI—Limitations of
echocardiography and catheter angiography 1. Tetralogy of Fallot (TOF) (Figure 1): The evaluation of
pulmonary arteries (PA’s) is the cornerstone of surgical
Although echocardiography and catheter-directed cardiac decision making in TOF (Figure 1). CT can provide
angiography are, by definition, regarded as the ‘cornerstones’ excellent delineation of PA’s–their confluence, size and
of primary imaging techniques for evaluation of CHD, CT and nature of the distal portion of branches. This information
MRI are rapidly emerging complementary diagnostic tools. may not be always evident on echocardiography. Other
In addition to being operator dependent, echocardiography valuable information that CT can provide in low pulmonary
may not be singularly sufficient for evaluating extracardiac blood flow situations like TOF is regarding the pulmonary
structures, such as the pulmonary arteries, pulmonary veins, venous drainage. It is possible that partial anomalous
and the aortic arch and great vessels due to acoustic window pulmonary venous drainage may be missed on echo, but
limitations. Catheter-directed cardiac angiography is limited can definitely be detected on CT.
by technical difficulties in evaluation in some situations, 2. Pulmonary atresia with ventricular septal defect (VSD):
e.g. of the pulmonary arteries in pulmonary atresia. Cardiac Detailed evaluation of PA’s and feeding vessels to PA’s
catheterization, in comparison to CT, also entails a higher is important for precise surgical planning. The branch
complication rate owing to its invasiveness, requirement PA’s may not have anatomical continuity (non-confluent).
of a larger volume of intravascular contrast material, more Pulmonary blood flow may be derived from a patent
frequent requirement of general anesthesia and risk of much arterial duct (PDA) or from aortopulmonary collaterals.
higher radiation exposure as compared to CT when appropriate CT can provide vital information on the issues related
pediatric CT protocols are used. to pulmonary arteries and its feeders and some pediatric
2
Basics
Figure 1: Confluent pulmonary arteries in tetralogy of Fallot. Figure 2: Oblique coronal maximum intensity projection (MIP)
LPA = Left pulmonary artery; PA = Pulmonary artery; reformat demonstrating coarctation of aorta (CoA).
RPA = Right pulmonary artery AAo = Ascending aorta; DAo = Descending aorta
cardiac surgeons consider it as the most useful investigation tracheal anomalies including tracheal bronchus, complete
for surgical planning. tracheal ring and localized tracheomalacia. CT scan and
3. Tetralogy of Fallot with absent pulmonary valve: CT also digital 3D reconstruction of the CT images can give an
plays an vital role in patients diagnosed as TOF with absent excellent recreation of the precise anatomy of this complex
pulmonary valve who are symptomatic not only because lesion and is the investigation of choice.6
of the cardiac problem, but also because of the inherent 8. Total anomalous pulmonary venous connection (TAPVC)
abnormalities in the lung parenchyma. Determining the PA (Figure 3): Although echocardiography can confidently
anatomy and its contribution to symptoms is of immense diagnose the condition in the vast majority, CT evaluation
importance in deciding the surgical management. Apart gives excellent anatomical data regarding the pulmonary
from defining the amount of bronchial compression, it also veins and should be considered in case of any doubt or
localizes areas of atelectasis or emphysema. when the echocardiographic data does not correlate with
4. Interrupted aortic arch (IAA): IAA represents a separation the clinical condition.7
between ascending and descending aorta. Evaluation of 9. Postoperative situations: An important and established
the distance between the proximal and distal segments, the role of CT in the follow-up of managed CHD is evaluation
size of the patent ductus arteriosus (PDA), the narrowest for successful surgical outcome and recognition of a
dimension of the left ventricular outflow tract and other variety of complications. CT angiography (CTA) can
cardiac structural abnormalities are important for surgical assess surgical conduits and intravascular stent patency,
planning. CT scan and digital 3D reconstruction of the CT wherein lack of central opacification in these structures
images can recreate the entire anatomy for the surgeon and suggests the presence of thrombosis that can have serious
simplify the surgical planning. clinical implications. CTA can also evaluate right ventricle
5. Coarctation of aorta (CoA) (Figure 2): CT scan can give an to pulmonary artery and modified Blalock-Taussig shunt
excellent delineation of the lesion to aid the management patency and stenosis. Similarly, CT can also assess
planning.4 patients previously treated with a surgical cavopulmonary
6. Aortopulmonary window (APW): Echocardiography may anastomosis, such as bidirectional Glenn shunt and Fontan
fail to pick up this lesion due to artificial dropouts and rapid procedures, where CT can establish pathway patency and
development of pulmonary hypertension. A great degree exclude abnormal pathway narrowing. Filling defects
of clinical suspicion needs to be exercised for the proper within the pathway suggest the presence of thrombus.
diagnosis. The role of helical CT has been well established
in the diagnosis of this condition.5 Disadvantages of Computed Tomography
7. Pulmonary artery sling: In this lesion, an aberrant left
204 pulmonary artery arises from the proximal right pulmonary CT has its inherent disadvantages, including the inevitable
artery, courses between the trachea and esophagus and radiation exposure and risks related to use of iodinated
extends to the left hilum. This may be associated with contrast material. Also, CT lacks in its ability at demonstration
Magnetic Resonance Imaging Sequences 14
and Techniques
Role of Newer Cardiac Imaging in Congenital Heart Diseases

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 high-
quality 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
Figure 3: Curved MIP reformat delineating the venous anatomy during image acquisition, which may not be possible with
in total anomalous pulmonary venous connection. SVC = Superior very young and sick patients. Respiratory motion can be
vena cava monitored using a bellows device around the body or by MRI
navigator echoes, which concurrently image the position of
of functional information such as right ventricular function, the diaphragm or heart.
pulmonary regurgitation fraction, etc. Additionally, in The pulse sequence specifies how the magnetic field
neonates and young infants, paucity of fat planes, tachycardia, gradients and radiofrequency pulses are applied and read during
tachypnea and motion-related artifacts can significantly affect image acquisition. In general, there are two major categories
the image quality. of pulse sequences—spin echo and gradient echo. A particular
pulse sequence can often be modified by adding preparatory
Cardiac MRI in the Current Day Scenario pulses that alter tissue contrast. In addition, there are numerous
user selectable imaging parameters that effect tissue contrast,
Magnetic resonance imaging (MRI) has been an established image quality and temporal and spatial resolution.9
high-resolution imaging modality for demonstration of
cardiovascular morphology. In contrast to CT, MRI allows Anatomic Imaging and Tissue Characteristics
functional evaluation in addition to morphologic detail in
CHD patients. Thus, in addition to anatomy, which can be Spin echo pulse sequences are usually used to produce images,
demonstrated by both techniques, cardiac MRI has the ability in which flowing blood has a low signal intensity and appears
to calculate ventricular function and assess valve regurgitation. dark (‘black blood’ imaging). Other tissues appear as varying
Right ventricular dilation and function assessment are shades of gray. Though cardiac-gated spin echo sequences
especially important in situations such as postoperative, produce only one image per location and thus provide only
TOF with pulmonary regurgitation, where worsening right static anatomic information, their advantages include high
ventricular (RV) function can necessitate pulmonary valve spatial resolution, excellent blood-myocardial contrast and
replacement. decreased artifact from metallic biomedical implants (e.g.
MRI with its advances in hardware design, new pulse sternal wires, stents, prosthetic valves). Spin echo sequences
sequences and faster image reconstruction techniques allows are also easily modified to alter tissue contrast and characterize
rapid high-resolution imaging of complex cardiovascular abnormal structures. Their clinical uses include evaluation
anatomy in 3D space, quantitative assessment of ventricular for arrhythmogenic right ventricular cardiomyopathy,
volumes, mass, stroke volume and ejection fraction, assessment cardiac tumors, constrictive pericardial disease, vessel wall
of myocardial function using tagging technique, quantification abnormalities and thoracic masses.
of blood flow rate and imaging of non-cardiac structures Cardiac-gated gradient echo sequences can be used to
such as the trachea and bronchi. A comprehensive cardiac produce multiple images over the cardiac cycle in each
MRI examination effectively characterizing cardiovascular anatomic location. These images can then be displayed in a
anatomy and physiology can now be performed in as little as cine loop format to demonstrate the motion of the heart and
60 minutes. vasculature over the cardiac cycle. On such cine MR images, 205
2 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
Basics
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

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
Figure 4: Bright blood MR imaging sequence demonstrating performed without cardiac gating using a 3D fast gradient
a large ostium secundum type of atrial septal defect (ASD)
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
flowing blood produces a bright signal and the myocardium and several acquisitions can be performed. The entire
and the vessel wall are relatively dark (‘bright-blood’ imaging) procedure takes only a few minutes to perform and yields a
(Figure 4).10 high-contrast and high resolution 3D data set depicting all or
Cine MRI is used to delineate cardiovascular anatomy part of the thorax (Figure 6).
and assess ventricular function, evaluating the systemic and MRA is ideally suited to illustrate the anatomy of the
pulmonary veins, atrial and ventricular septum, intracardiac aorta and its branches, PA’s, pulmonary veins and systemic
baffles and pathways (e.g. following Fontan, Mustard, veins. Although this technique is mostly used for imaging
Senning or Rastelli procedures), ventricular outflow tracts, of extracardiac anatomy, it is also useful in the evaluation of
ventricular arterial conduits, pulmonary arteries and the aorta. intra-atrial systemic and pulmonary baffles (such as in Mustard
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
Blood Flow Analysis

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 Figure 5: Velocity encoded MRI sequence demonstrating
206 is in proportion to blood velocity within that voxel. Using the bicuspid configuration of the aortic value
for planning of interventional catheterization or surgical 14
procedures (Figures 7A and B).14,15

Myocardial Ischemia and Viability
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

The indications for cardiac MRI are to evaluate the right
ventricle, valve regurgitation, surgical systemic and pulmonary
Figure 6: Contrast enhanced MRA with excellent delineation of venous pathways, Fontan pathways and the great vessels.
coronary collaterals in a case of Bland-White-Garland syndrome
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
or Senning operations and after Fontan procedures), as well operation, aortic arch anomalies and several other conditions.
as for imaging of the outflow tracts (such as in repaired TOF
and the arterial switch operation). In addition to volume Postoperative Tetralogy of Fallot
rendered CT angiogram, the MRA clearly delineates the spatial
relationships between vascular structures, the tracheobronchial In patients with repaired TOF, MRI is assuming an increasing
tree, chest wall, spine and other landmarks that may be useful role as the primary non-invasive modality. In the post-operative
207
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
2 detection of collateral vessels that bypass the coarctation site,
assessment of left ventricular mass, dimensions and function
and detection of any associated lesions.17
Basics
Fontan Circulation
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
Figure 8: Multiplanar true FISP axial image showing large aneurysm important investigational tool in the evaluation of myocardial
of the right ventricular outflow tract (RVOT) in a patient with post- mechanics in patients with a functional single ventricle and
tetralogy of Fallot repair Fontan circulation, demonstrating asynchrony and impaired
regional wall motion.18,19
follow-up of TOF, the patients often have residual anatomic The clinical utility of MRI in patients with the Fontan
and hemodynamic abnormalities such as chronic pulmonary circulation increases as the acoustic windows become more
regurgitation, residual ventricular septal defect, right restricted with growing years. The MRI examination in patients
ventricular volume overload and dysfunction, right ventricular with the Fontan circulation can assess the pathways from the
outflow tract obstruction, branch pulmonary artery stenosis, systemic veins to the pulmonary arteries for obstruction and
residual aortopulmonary collaterals and others. for a thrombus detection of Fontan baffle fenestration or leaks,
The goals of the MRI examination after TOF repair evaluation of the pulmonary veins for compression, systemic
include quantitative assessment of left and right ventricular ventricular volumes, mass and pump function, imaging of the
volumes, mass, stroke volumes and ejection fraction, imaging systemic ventricular outflow tract for obstruction, quantitative
the anatomy of the right ventricular outflow tract (Figure 8), assessment of the atrioventricular and semilunar valve(s) for
PA’s, aorta and aortopulmonary collaterals and to quantify regurgitation, the aorta for obstruction or an aneurysm and for
pulmonary regurgitation, tricuspid regurgitation, cardiac aortopulmonary, systemic venous or systemic to pulmonary
output and pulmonary to systemic flow.16 venous collateral vessels.19
Aortic Arch Anomalies Subpulmonic Ventricular septal defect

The use of MRI to image anomalies of the aortic arch is best MRI also aids in the diagnosis and management of supracristal
suited for non-invasive evaluation of congenital, acquired and VSD. Echocardiography, despite being the primary imaging
postoperative anomalies of the aorta in adolescents and adults. modality for the evaluation of cardiac shunts is less accurate
Certain diagnostic categories are known to have a higher for defining supracristal ventricular septal defect and cardiac
risk for aortic complications such as patients with Marfan angiography despite its accuracy in localizing the lesion,
syndrome and other connective tissue disorders who are at involves catheterization and ionizing radiation with attendant
risk for aortic aneurysm, dissection and rupture. Patients with risks to the patient. ECG-gated spin-echo MR imaging is an
a coarctation of the aorta comprise another high-risk group effective and non-invasive alternative, which can typically
for late development of aortic complications, including re- depict a characteristic defect between the base of the aorta and
stenosis of the repair site, transverse aortic arch hypoplasia, the right ventricular infundibulum and cine MR images can
progressive dilatation of the ascending aorta and aneurysm demonstrate a systolic flow jet from the left ventricle into the
formation. The objectives of the MRI evaluation of suspected right ventricular outflow tract, indicating a left-to-right shunt.
or repaired aortic coarctation include imaging of the aortic wall Shunt severity can be quantified by calculating the ratio of
at the coarctation site and any other abnormal aortic segment, pulmonary flow to systemic flow, with flow values obtained
dynamic imaging of blood flow throughout the thoracic from velocity-encoded cine MR planimetry. Additionally,
aorta to detect high-velocity flow jets suggestive of stenosis, MR imaging can diagnose complications of supracristal
208
ventricular septal defect, including aortic valve prolapse with specificity and range of indications for which each of them 14
resultant aortic regurgitation and secondary right ventricular can be customized. Patient’s clinical history is by far the most
enlargement or hypertrophy.20 important information and basis for choosing the appropriate

modality. As shown by many recent studies, cardiac CT
Disadvantages of Magnetic Resonance Imaging allows for a reliable morphologic evaluation in CHD and
enjoys constantly high negative predictive value, especially in
MRI has its own inherent limitations ranging from poorer assessment of postoperative assessment. MR is the modality
spatial resolution; image-degrading artifacts from implanted of choice in any functional aspect of cardiac imaging, whether
metal, such as intravascular stents and embolization coils; focusing on cardiac and valvular function or perfusion.
higher cost; limited availability to contraindications for
imaging of patients with pacemakers and increased need for Diagnosis is not the end, but the beginning of practice.
general anesthesia in younger children. MRI also takes longer — Martin H Fischer
than CT, possibly a relative contraindication for imaging the
critically ill, thermally unstable and uncooperative pediatric REFERENCES
patients and more often requires onsite physician monitoring
to assure diagnostic image quality and customized compatible 1. Haramati LB, Glickstein JS, Issenberg HJ, et al. MR imaging
monitoring equipment for the imaging per se. Finally, MRI is and CT of vascular anomalies and connections in patients with
limited in the evaluation of the airways and lungs, structures congenital heart disease:significance in surgical planning.
RadioGraphics. 2002;22:337-47; discussion, 348-49.
that CT smartly depicts well. The Box 1 compares the pros
2. Goo HW, Park IS, Ko JK, et al. CT of congenital heart
and cons of CT versus MRI in heart disease evaluation.
disease: normal anatomy and typical pathologic conditions.
RadioGraphics. 2003;23(Spec Issue):S147-65.
summary 3. Flohr T, Stierstorfer K, Raupach R, et al. Performance
evaluation of a 64-slice CT system with z-flying focal spot.
Both CT and MRI, in the context of congenital heart Rofo. 2004;176:1803-10.
disease have competed with each other in recent years to 4. Becker C, Soppa C, Fink U, et al. Spiral CT angiography
attain the ultimate goal: a one stop shop for comprehensive and 3D reconstruction in patients with aortic coarctation.
information on cardiac status. This has led to sophisticated EurRadiol. 1997;7:1473-77.
5. Sridhar PG, Kalyanpur A, Suresh PV, et al. Helical CT
technical innovations on both sides that have channelized the
Evaluation of Aortopulmonary Window. Ind J Radiol Imag.
2006;16:847-49.
6. Lee KH, Yoon CS, Choe KO, et al. Use of imaging for assessing
Box 1: Pros and cons of computed tomography anatomical relationships of tracheobronchial anomalies
versus magnetic resonance imaging in heart disease associated with left pulmonary artery sling. Pediatr Radiol.
evaluation 2001;31:269-78.
7. Kim TH, Kim YM, Suh CH, et al. Helical CT angiography
CT pros and three-dimensional reconstruction of total anomalous
• Short examination time pulmonary venous connections in neonates and infants. AJR
• Fewer requirements of sedation Am J Roentgenol. 2000;175:1381-86.
• Simultaneous evaluation of lung parenchyma 8. Mulkern RV, Chung T. From signal to image: magnetic
• High spatial resolution resonance imaging physics for cardiac magnetic resonance.
CT cons Pediatr Cardiol. 2000;21:5-17.
• Radiation exposure 9. Kerr AB, Pauly JM, Hu BS, et al. Real-time interactive MRI on
• Use of iodinated contrast material a conventional scanner. Magn Reson Med. 1997;38:355-67.
• Lack of functional information (e.g. right ventricular 10. Simonetti OP, Finn JP, White RD, et al. ‘Black blood’ T2-
function, pulmonary regurgitation fraction) weighted inversion-recovery MRI of the heart. Radiology.
MRI pros 1996;199:49-57.
• Multiplanar capability
11. Carr JC, Simonetti O, Bundy J, et al. Cine MR angiography of
• Wide field of view the heart with segmented true fast imaging with steady-state
• Lack of dependence on a rapid bolus of IV contrast precession. Radiology. 2001;219:828-34.
• No radiation 12. McVeigh ER, Atalar E. Cardiac tagging with breath-hold cine
• Can give valuable functional information MRI. Magn Reson Med. 1992;28:318-27.
13. Powell AJ, Geva T. Blood flow measurement by magnetic
MRI cons
resonance imaging in congenital heart disease. Pediatr Cardiol.
• Long scanning time, needs breath hold 2000;21:47-58.
• Difficult to scan intubated sick children
14. Neimatallah MA, Ho VB, Dong Q, et al. Gadolinium-enhanced
• Close monitoring
3D magnetic resonance angiography of the thoracic vessels. J
• Lower spatial resolution
Magn Reson Imaging. 1999;10:758-70. 209
2 15. Masui T, Katayama M, Kobayashi S, et al. Gadolinium
enhanced MR angiography in the evaluation of congenital
comparison between contrast-enhanced MR angiography and
fast spin-echo MRI. Eur Radiol. 2000;10:1847-54.
cardiovascular disease pre and postoperative states in 18. Mayer JE Jr. Late outcome after the Fontan procedure. Semin
Basics
infants and children. J Magn Reson Imaging. 2000;12: Thorac Cardiovasc Surg; Pediatr Cardiol Surg Annu. 1998;1:
1034-42. 5-8.
16. Helbing WA, de Roos A. Clinical applications of cardiac 19. Balling G, Vogt M, Kaemmerer H, et al. Intracardiac thrombus
magnetic resonance imaging after repair of tetralogy of Fallot. formation after the Fontan operation.
Pediatr Cardiol. 2000;21:70-9. 20. Holmqvist C, Hochbergs P, Bjorkhem G, et al. Preoperative
17. Bogaert J, Kuzo R, Dymarkowski S, et al. Follow-up of patients evaluation with MR in tetralogy of Fallot and pulmonary atresia
with previous treatment for coarctation of the thoracic aorta: with ventricular septal defect. Acta Radiologica. 2001;42:63-9.
210
Sec t i on
Defects in Atriovenous and

Pulmonary Arteriovenous
Connections
C hapter
15 Anomalies of Systemic Veins
Jayashree Kharge, Vijayalakshmi IB
INTRODUCTION posterior veins join before entering the sinus horn and form
the short common cardinal veins. During the fourth week,
The abnormalities of position and connection of the major the cardinal veins form a symmetrical system.
systemic venous channels draining to the heart are mostly Formation of the vena caval system is characterized by the
rare incidental findings with not much of hemodynamic appearance of anastomosis between the left and right sides in
significance, when visceroatrial situs is lateralized. In contrast, such a manner that the blood from the left side is channeled
the incidence of systemic venous anomalies in patients with to the right side (Figure 2). The anastomosis between the
heterotaxy syndrome exceeds 90 percent.1 However, even anterior cardinal veins develops into the left brachiocephalic
when not hemodynamically significant, they may complicate vein (Figures 2 and 3).
interventional procedures and cause arrhythmias. In some Most of the blood from the left side of the head and the left
cases it can cause cyanosis, polycythemia, paradoxical upper extremity is then channeled to the right. The terminal
embolism and even stroke. The relevant embryology portion of the left anterior cardinal vein entering into the left
and anatomy with individual anomalies and their clinical brachiocephalic vein is retained as a small vessel, the left
significance is discussed. superior intercostal vein (Figure 4). This vessel receives blood
from the second and third intercostal spaces. The superior
Classification of Systemic Venous Anomalies vena cava is formed by the right common cardinal vein and
the proximal portion of the right anterior cardinal vein.
1. Anomalies of the superior vena cava A left-sided superior vena cava is an abnormality caused
2. Anomalies of the inferior vena cava by the persistence of the left anterior cardinal vein and
3. Anomalies of the ductus venosus obliteration of the common cardinal and proximal part of the
4. Total anomalous systemic venous connection. 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 Figure 1: Cardinal veins. SV = Sinus venosus;
remaining part of the body of the embryo. The anterior and UV = Umbilical vein; VV = Vitelline vein
3
Subcategory of SVC Anomalies
Defects in Atriovenous and Pulmonary Arteriovenous Connections
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

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

There are no clinical manifestations when the persistent
Figure 4: Formation of the superior vena cava 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
the right is channeled towards the left by way of the right can facilitate development of systemic abscesses or emboli.
brachiocephalic vein. The left superior vena cava drains into When associated with other cardiac malformations there may
the right atrium by way of the left sinus horn, i.e. the coronary be diagnostic and technical difficulties during catheterization
214 sinus. and cardiac surgery.
15
Anomalies of Systemic Veins

Figure 5: Course of a left superior vena cava (LSVC) in presence Figure 7: Apical 4-chamber view by transthoracic echocardiogram with
of a brachiocephalic vein. Courtsey: Robert Anderson 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
Figure 6: Parasternal long axis view demonstrating marked dilation drainage. Rarer causes of dilated coronary sinus include
of the coronary sinus (CS) with no other apparent echocardiographic
postoperative obstruction, thrombosis or ventricularization,
abnormalities. LV = Left ventricle; RV = Right ventricle; Ao = Aorta;
LA = Left atrium and unroofing of the sinus. Extreme dilation of the coronary
sinus can cause substantial problems during septal puncture
in balloon mitral valvotomy.
Diagnosis Persistent LSVC can be diagnosed by magnetic resonance
imaging (MRI) either by spin echo or by gradient echo
Suspicion of LSVC may arise on the posteroanterior chest sequences. Magnetic resonance angiography (MRA) is
X-ray, where it may appear as widening of the aortic shadow, particularly suitable for rapid noninvasive delineation of
paramediastinal bulging, paramedian stripe, or a low-density systemic venous anatomy.
line along the upper left margin of the heart.12-14 Transthoracic By cardiac catheterization, LSVC can be suspected by
echocardiogram (TTE) is the main tool for diagnosing the presence of higher than expected coronary sinus oxygen 215
persistent LSVC (Figure 6).15-19 As demonstrated in the case, saturation. Left innominate vein angiography with balloon
3
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
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
Figure 8: Right heart catheter through right atrium (RA), coronary
sinus (CS) into left superior vena cava (LSVC). Hand injection of
death.
contrast shows LSVC draining to CS
Diagnosis
occlusion proximal to the injection site is diagnostic. The On the chest radiogram the LSVC may appear as a shadow
LSVC can be approached either through the right SVC (when along the left upper border of the mediastinum.
the innominate vein is present) or through the coronary sinus The electrocardiogram is similar to ostium secundum ASD.
(Figure 8). The diagnosis of systemic venous anomalies can However, in patients with visceral heterotaxy, the frontal axis
be reliably established by echocardiography and MRI, making of the P waves may be abnormal reflecting a left sinoatrial
cardiac catheterization unnecessary in most patients. node or an ectopic atrial rhythm.
The echocardiogram is the definitive imaging modality
Treatment with the subcostal or suprasternal window showing the LSVC
draining into the LA (Figures 9A to C).
No treatment is necessary when the LSVC is draining into an Flow mapping with color Doppler is useful in demons
intact coronary sinus. trating the flow from LSVC into the LA. A contrast injection
in the left arm vein demonstrates the appearance of the micro
Bilateral Superior Vena Cava with Unroofed bubbles in the left atrium before they appear in the right
Coronary Sinus atrium. CT angiogram and magnetic resonance imaging
is useful when the echocardiogram does not delineate the
Unroofed coronary sinus has been classified morphologically anatomy clearly (Figure 9D).
into four types by Kirklin and Barratt-Boyes, which are as Cardiac catheterization is diagnostic (Figure 10) and
follows:20 there is also step-down in the oxygen saturation between the
• Type I: Completely unroofed, with LSVC pulmonary veins and the left atrium. Also the LSVC can be
• Type II: Completely unroofed, without LSVC selectively cannulated.
• Type III: Partially unroofed mid portion
• Type IV: Partially unroofed terminal portion. Treatment
Raghib et al21 described eight cases with the following
findings: It is important to assess the size of the left innominate vein
1. Left superior vena cava drains into the left atrium. before any attempts to close the defect. If the LSVC is of small
2. An atrial septal defect is present. The defect lies in the size and the innominate vein is of adequate size, the LSVC
posteroinferior angle of the atrial septum and above the can be ligated and the interatrial communication closed. But
posteromedial commissure of the mitral valve. It is separated in the absence of an adequate sized innominate vein, it is
from the mitral valve by a small amount of septal tissue. prudent to “reroof” the coronary sinus22 which is achieved by
216 3. Coronary sinus is absent. baffling the coronary sinus along the posterior wall of the left
15

A B
C D
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

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
Figure 10: Fluoroscopic picture in a 6 years old girl, in frontal view, avoid difficulties during the interventional procedures such
shows right heart catheter through atrial septal defect into left
superior vena cava (LSVC). Selective contrast injection opacifies left
as transvenous permanent pacemaker implantation, venous
innominate vein (LIV), LSVC, left atrial appendage (LAA), left atrium cannulation for cardiopulmonary bypass or extracorporeal
(LA) and left ventricle (LV). The right superior vena cava (RSVC) and membrane oxygenator, pulmonary artery monitoring line 217
right atrium (RA) are also faintly opacified through the subclavian or jugular veins. And also prior to
3
surgery that includes cavopulmonary anastamosis and ortho As against this, reduced shortening of the aortic arch as
topic heart transplantation. It is not required to treat these seen in right aortic arch and high aortic arch may compress
patients when the physiology is normal. and prevent the further development of the superior transverse
venous plexus. Abnormal development of the pulmonary arte
Right Superior Vena Cava Draining into the Left Atrium ries, either pulmonary atresia or pulmonary stenosis, encou
rages the sparing of the inferior transverse plexus, possibly
The left atrial drainage of the right superior vena cava is a leading to formation of an anomalous course of the innominate
rare anomaly, manifesting as unexplained cyanosis and vein. This would explain frequent association of the retroaortic
clubbing.26 innominate vein with TOF and right aortic arch.29-31
This malformation probably represents a sinus venosus Usually, the retroaortic innominate vein in isolation has no
defect of the SVC type in association with atresia of the right clinical importance. The descending portion of the retroaortic
SVC orifice. There is unroofing of the right upper pulmonary innominate vein may be mistaken for persistent LSVC or
vein and its branches which drain into SVC and its left atrial an ascending vertical vein in a total anomalous pulmonary
orifice becomes the inter atrial communication. The left atrial venous connection on echocardiography.32 The retroaortic
blood can be shunted into the SVC-RA junction or the right segment may be misinterpreted as right pulmonary artery in
SVC blood can enter the left atrium depending on the pressure patients with hypoplastic or atretic central pulmonary arteries,
and the compliance differences between the two atria. or an early branching of right upper lobe pulmonary artery on
Cyanosis is the dominant clinical feature when the echocardiography.33,34
right SVC drains into the left atrium. The risks include In a retrospective analysis of echocardiograms the
polycythemia, systemic emboli, brain abscess, and other incidence of retroaortic innominate vein was found to be 0.55
cerebrovascular complications typically increasing with age. percent amongst children with congenital heart disease. It was
On the echocardiogram the common entrance site of right most commonly associated with tetralogy of Fallot and right
SVC and the right upper pulmonary vein in the roof of the left aortic arch.35
atrium can be demonstrated.27 It is widely considered to be anatomical variant without
Surgery is the treatment of choice where the right SVC clinical ramifications. However, knowing the precise
flow is diverted into the right atrium. The preferred surgical preoperative information about the anomaly can be critical in
approach involves transaction of right SVC above the right planning surgical procedure.
upper pulmonary vein and anastamosis of the transacted caval
end to the right atrial appendage.26 ANOMALIES OF THE INFERIOR VENA CAVA
Retroaortic Innominate Vein Anatomy

The left innominate (or brachiocephalic) vein is formed by The normal inferior vena cava (IVC) is composed of four
the left internal jugular and the left subclavian vein. In the segments: hepatic, suprarenal, renal, and infrarenal. The
situs solitus, its usual course is obliquely downward to the hepatic segment is derived from the vitelline vein. The right
right, passing superoanterior to the aortic arch. Anomalous subcardinal vein develops into the suprarenal segment by
course of the innominate vein is rare, being first described by formation of the subcardinal-hepatic anastomosis. The renal
Kershner more than 100 years ago.28 segment develops from the right supra-subcardinal and post-
Embryologically, the primordia of the systemic veins subcardinal anastomosis. It is generally accepted that the
first appear as paired anterior and posterior cardinal veins infrarenal segment derives from the right supracardinal vein,
that unite on each side to form a common cardinal vein (or although this idea is somewhat controversial.36 In the thoracic
Cuvierian duct) that opens into the primitive sinus venosus. region, the supracardinal veins give rise to the azygos and
During subsequent development, most of the left anterior car hemiazygos veins. In the abdomen, the postcardinal veins are
dinal vein disappears. The venous drainage from the left side progressively replaced by the subcardinal and supracardinal
of the head and neck and the left arm is then directed into veins but persist in the pelvis as the common iliac veins.
the right anterior cardinal vein by the development of new
transverse anastomotic channels above and below the fourth Interrupted Inferior Vena Cava
aortic arch (superior and inferior transverse capillary plexus)
by the eighth week. Normally, the aortic arch shortens during Moller et al in 1967 concluded that interrupted IVC represents
the embryological development and occupies the space of the one of the characteristics of the polysplenia syndrome.37
inferior transverse capillary plexus, thus causing its regression, However, interrupted IVC has also been reported in patients
while the rest of venous blood shunts into the superior with normal hearts38,39 and very rarely in asplenia.40
218 transverse capillary plexus. This facilitates the development Interrupted IVC is defined as the absence of the hepatic
of the normal supra-aortic course of the left innominate vein. segment of the IVC with azygos continuation into the right
15
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
Figure 11: Fluoroscopic image illustrates the interrupted inferior vena celiac and superior mesenteric arteries. When the renal-to-
cava with continuation through the azygos vein into the superior vena hepatic segment of IVC is absent, no IVC is seen below the
cava showing a candy cane apperance 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
or left superior vena cava. Infrahepatic interruption of the accurate in delineating normal and abnormal systemic venous
IVC with azygos continuation (Figure 11) is a rare congenital anatomy.
anomaly seen in 0.6–2% of patients with congenital heart
disease and in less than 0.3% of otherwise normal individuals.41 Treatment
Rarely, the infrahepatic segment of the IVC may continue to
both right and left SVC via bilateral azygos veins. The IVC interruption by a congenital membrane causing
Although the interrupted IVC does not result in physiologic distention of abdomen can be treated by transcatheter
abnormality, the clinical importance lies in its frequent intervention (Figures 12B and C). However, if patient is
association with the heterotaxy syndrome and polysplenia. asymptomatic no specific treatment is required. Inadvertent
Rarely, the IVC may be interrupted by a membrane causing ligation of azygos vein can lead to death.38
abdomonal distension and discomfort (Figure 12A). In
surgeries that require redirection of the systemic venous Inferior Vena Caval Drainage to the Left Atrium
return to the pulmonary arteries such as bidirectional Glenn
and modified Fontan, prior knowledge of the anatomical The inferior caval vein has been reported as connecting
abnormality helps in planning the surgery appropriately. directly to the LA both with an intact atrial septum and in
A B C
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 219
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
3
A B
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)
adenopathy.47 Transjugular access to the infrarenal IVC for

Figure 13: The cartoon shows a persistent Eustachian valve directing placement of an IVC filter may be difficult.
inferior venous caval flow into the left atrium. This should not be Hemiazygos continuation of a left-sided IVC has several
mistaken for connection of the inferior caval vein to the left atrium. variations.48-51 There are three likely routes for blood in the
Courtsey: Robert Anderson’s hemiazygos vein to reach the right atrium. In the first route,
the hemiazygos vein drains into the azygos vein at T8–T9. The
distal azygos and hemiazygos vein are enlarged. The second
association with an atrial septal defect. In this respect, it is route involves a persistent LSVC (Figure 14B). The blood
necessary to distinguish between direct connection to the LA flows from the hemiazygos vein into the accessory hemiazygos
and the arrangement in which an inferior caval vein overrides vein to the LSVC and then into the coronary sinus, all of which
a low-lying interatrial communication and allows functional are dilated. In the third route, the hemiazygos vein drains to the
drainage of inferior caval venous flow to the LA. The latter accessory hemiazygos vein, left superior intercostal vein, left
situation can be exacerbated by persistence of an unduly brachiocephalic vein and then into a normal right SVC.48,49
prominent Eustachian valve that directs the flow into the LA
(Figure 13). Bilateral Inferior Vena Cava
Clinical Features Bilateral suprahepatic IVCs, that is a normal IVC and a

contralateral hepatic vein, are frequently seen in cases of
The partial or complete drainage of the IVC into the LA visceral heterotaxy with asplenia. Bilateral infrarenal IVCs
results in cyanosis due to right-to-left shunting, including have also been reported but they too are of no hemodynamic
polycythemia, brain abscess, and paradoxical emboli. significance.
Treatment TOTAL ANOMALOUS SYSTEMIC VENOUS DRAINAGE

INTO THE LEFT ATRIUM
Inferior vena cava (IVC) blood is surgically redirected into
the right atrium.44,45 Total anomalous systemic venous drainage (TASVC)
including the hepatic veins and the coronary sinus draining
Left sided Inferior Vena Cava into the LA is extremely rare. It is thought to occur either
because of failure of regression of the right valve of the
A left sided IVC results from regression of the right systemic venous sinus (sinus venosus) or the systemic venous
supracardinal vein with persistence of the left supracardinal sinus being incorporated into the LA. It is usually associated
vein. The prevalence is 0.2–0.5 percent.46 The left IVC with other complex congenital heart diseases.
typically joins the left renal vein, which crosses anterior to There have been very few case reports of TASVC. In a case
the aorta in the normal fashion, uniting with the right renal report, an 11-year-old girl with heterotaxy syndrome presented
vein to form a normal right-sided prerenal IVC (Figure 14 A). with cyanosis.52 On echocardiography, and CT angiogram there
220 This anomaly can be misdiagnosed as left-sided paraaortic was an interrupted IVC with hepatic veins draining directly
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.
Treatment
Surgical correction to redirect the venous blood into the right
atrium.
Anomalies of Ductus Venosus
Figure 15A: Echocardiographic apical four-chamber view showing

Absent Ductus Venosus
ostium secundum atrial septal defect L-R shunt; dilated left atrium and
The absence of ductus venosus and abnormal termination
left ventricle; noncompaction of left ventricle; dilated superior caval
vein in cross-section in a 11 year old girl of total anomalous systemic of umbilical veins is a rare anomaly and do not produce any
venous drainage. ASD = Atrial septal defect; LA = Left atrium; LV = Left symptoms. However, there are a few reports of intrauterine
ventricle; SVC = Superior vena cava 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 pre-
natal 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 portal-
systemic 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 Conclusion

interruption of hepatic segment of inferior vena cava and hepatic
veins draining into the left atrium through a common channel45.
The anomalies of systemic venous return are rare and
Image Courtsey: Dr KS Ravindranath
usually missed by routine interrogation. They are usually
asymptomatic but may pose problem during surgery. Hence,
into the LA (Figures 15A and B). There was an associated detection of anomaly prior to surgery is pertinent. They can be
ostium secundum atrial septal defect and non-compaction of detected with gratifying results by segmental approach. These
the left ventricle. Oximetry revealed equal saturation in all the segments are SVC, LSVC, IVC, coronary sinus, hepatic veins
four cardiac chambers. CT angiography revealed polysplenia. and azygos veins.
The patient was treated surgically by redirecting the SVC into
the right atrium. Surgeons must be very careful
When they take the knife!
Clinical Significance of TASVC Underneath their fine incisions
Stirs the Culprit - Life!
It is one of the rare causes of cyanosis in cyanotic heart —Emily Dickinson
disease and yet another cause for equal oxygen saturations in 221
3
References 21. Raghib G, Ruttenberg HD, Anderson RC, et al. Termination
of left superior vena cava in left atrium, atrial septal defect,
1. Geva T, Van Praagh S. Abnormal systemic venous connections. and absence of coronary sinus; a developmental complex.
In: Allen HD, Driscoll DJ, Shaddy RE, Feltes TF (Eds). Moss Circulation. 1965;31:906-18.
and Adams’ Heart Disease in Infants, Children, and Adolescents: 22. Castaneda AR, Jonas RA, Mayer JE Jr, et al. Cardiac Surgery
Including the Fetus and Young Adults, 7th edn. Lippincott of the Neonate and Infant. Philadelphia: WB Saunders, 1994.
Williams and Wilkins, Philadelphia; 2008. pp. 792-817. pp. 152-3.
2. Sadler TW. Langman’s Medical Embryology. 7th edn. 23. Irlich TN, Herzer JA, Schulte HD, et al. Left persisting, singular
Baltimore: Williams and Wilkins, 1995. pp. 221-3. superior vena cava and pacemaker electrode implantation by
3. Marshall J. On the development of the great anterior veins in man right cephalic vein [in German]. Z Kardiol. 1976;65:575-82.
and Mammalia. Philos Trans R Soc Lond. 1850;140:133-70. 24. Lenox CC, Zuberbuhler JR, Park SC, et al. Absent right
4. McCotter RE. Three cases of persistent left superior vena cava. superior vena cava with persistent left superior vena cava:
Anat Rec. 1916;10:371-83. Implications and management. Am J Cardiol. 1980;45:117-22.
5. Meadows WR, Sharp JT. Persistent left superior vena 25. Bartram U, Van Praagh S, Levine JC, et al. Absent right
cava draining into the left atrium without arterial oxygen superior vena cava in visceroatrialsitussolitus. Am J Cardiol.
unsaturation. Am J Cardiol. 1965;16:273-79. 1997;80:175-83.
6. Sanders JM. Bilateral superior vena cava. Anat Rec. 1946;94: 26. Van Praagh S, Geva T, Lock JE, et al. Biatrial or left
657-62. atrial drainage of the right superior vena cava: Anatomic,
7. Geissler W, Albert M. Persistent left superior vena cava and morphogenetic, and surgical considerations report of three new
mitral stenosis [in German]. Z Gesamte Inn Med. 1956;11:865- cases and literature review. Pediatr Cardiol. 2003;24:350-63.
74. 27. Chin AJ. Subcostal two-dimensional echocardiographic
8. DeLeval MR, Ritter DG, McGoon DC, et al. Anomalous identification of right superior vena cava connecting to left
systemic venous connection—surgical considerations. Mayo atrium. Am Heart J. 1994;127:939-41.
Clinic Proc. 1975;50:599-610. 28. Kershner L. Morphologie der vena cava inferior. Anat Anz.
9. Nash EN, Moore GW, Hutchins GM. Pathogenesis of persistent 1888;3:808-23.
left superior vena cava with coronary sinus connection. Pediatr 29. Gerlis LM, Ho SY. Anomalous subaortic position of the
Pathol. 1991;11:261-9. brachiocephalic (innominate) vein: A review of published
10. Van Praagh S, O'Sullivan J, Brili S, et al. Juxtaposition of reports and report of 3 new cases. Br Heart J. 1989;61:540-5.
the morphologically right atrial appendage in solitus and 30. Konstantinov IE, Van Arsdell GS, O’ Blenes S, Roy N,
inversus atria: A study of 35 postmortem cases. Am Heart J. Campbell A. Retroaortic innominate vein with coarctation of
1996;132:382-90. the aorta: Surgical repair and embryology review. Ann Thorac
11. Cormier MG, Yedlicka JW, Gray RJ, Moncada R. Congenital Surg. 2003;75:1014-6.
anomalies of the superior vena cava: a CT study. Semin 31. Kim SH, Chung JW, Im JG, et al. Subaortic left innominate vein:
Roentgenol. 1989;24:77-83. Radiologic findings and consideration of embryogenesis. J
12. Cha EM, Khoury GH. Persistent superior vena cava: radiologic Thorac Imaging. 1999;14:142-6.
and clinical significance. Radiology. 1972;103:375-81. 32. Minami M, Noda M, Kawauchi N, Shirouzu I, Nakajima J,
13. Schummer W, Schummer C, Hoffmann E, Gerold M. Persistent Araki T, et al. Postaortic left innominate vein: Radiological
left superior vena cava: clinical implications for central venous assessment and pathogenesis. ClinRadiol. 1993;48:52-6.
cannulation. Nutr Clin Pract, 2002;17:304-8. 33. Choi JY, Jung MJ, Kim YH, Noh CI, Yun YS. Anomalous
14. Tak T, Crouch E, Drake GB. Persistent left superior vena cava: subaortic position of the brachiocephalic vein (innominate
incidence, significance and clinical correlates. Int J Cardiol. vein): An echocardiographic study. Br Heart J. 1990;64:385-7.
2002;82:91-3. 34. Chen SJ, Liu KL, Chen HY, et al. Anomalous brachiocephalic
15. Ratliff HL, Yousufuddin M, Lieving WR, et al. Persistent left vein: CT, embryology and clinical implications. Am J
superior vena cava: case reports and clinical implications. Int J Radiol. 2005;184:1235-40.
Cardiol. 2006;113:242-6. 35. Kulkarni S, Jain S, Kasar P, Garekar S, Joshi S. Retroaortic left
16. Troost E, Gewillig M, Budts W. Percutaneous closure of a innominate vein—Incidence, association with congenital heart
persistent left superior vena cava connected to the left atrium. defects, embryology, and clinical significance. Ann Pediatr
Int J Cardiol. 2006;106:365-6. Cardiol. 2008;1:139-41.
17. Ghadiali N, Teo LM, Sheah K. Bedside confirmation of 36. Phillips E. Embryology, normal anatomy, and anomalies. In:
a persistent left superior vena cava based on aberrantly Ferris EJ, Hipona FA, Kahn PC, Phillips E, Shapiro
positioned central venous catheter on chest radiograph. Br J JH, (Eds). Venography of the inferior vena cava and its
Anaesth. 2006;96:53-6. branches. Baltimore, Md: Williams and Wilkins, 1969. pp. 1-32.
18. Dearstine M, Taylor W, Kerut EK. Persistent left superior 37. Moller JH, Nakib A, Anderson RC, et al. Congenital cardiac
vena cava: chest X-ray and echocardiographic findings. disease associated with polysplenia: A developmental complex
Echocardiography. 2000;17:453-5. of bilateral left-sidedness. Circulation. 1967;36:789-99.
19. Sarodia BD, Stoller JK. Persistent left superior vena cava: case 38. Effler DB, Greer AE, Sifers AE. Anomaly of the vena
report and literature review. Respir Care. 2000;45:411-26. cava inferior: Report of fatality after ligation. JAMA.
222 20. Ootaki Y, Yamaguchi M, Yoshimura N, et al. Unroofed 1951;146:1321-3.
coronary sinus syndrome: diagnosis, classification, and surgical 39. Latimer HB, Virden HH. A case of complete absence of the
treatment. J Thorac Cardiovasc Surg. 2003;126:1655-6. inferior vena cava. J Kansas Med Soc. 1944;45:346-53.
15
40. Ruscazio M, Van Praagh S, Marrass AR, et al. Interrupted 50. Cohen MI, Gore RM, Vogelzang RL, et al. Accessory
inferior vena cava in asplenia syndrome and a review of the hemiazygos continuation of the inferior vena cava: CT

hereditary patterns of visceral situs abnormalities. Am J demonstration. J Comput Assist Tomogr 1984;8:777-9.
Cardiol. 1998;81:11. 51. Munechika H, Cohan RH, Baker ME, Cooper CJ, Dunnick
41. Matsuoka T, Kimura F, Sugiyama K, Nagata N, Takatani O. NR. Hemiazygos continuation of a left inferior vena cava: CT
Anomalous inferior vena cava with azygos continuation, appearance. J Comput Assist Tomogr 1988;12:328-30.
dysgenesis of lung, and clinically suspected absence of left 52. Khandenahally RS, Deora S, Math RS. Total anomalous
pericardium. Chest 1990;97:747-9. systemic venous drainage in left heterotaxy syndrome. Cardiol
42. Huhta JC, Smallhorn JF, Macartney FJ. Cross-sectional echo Young. 2012:1-3. [Epub ahead of print]
cardiographic diagnosis of azygous continuation of the inferior 53. White JJ, Brenner H, Avery ME. Umbilical vein collateral
vena cava. Cathet Cardiovasc Diagn 1984;10:221, 2321, 116. circulation: The Caput medusae in a newborn infant. Pediatrics.
43. Garris JB, Kangarloo H, Sample WF. Ultrasonic diagnosis of 1969;43:391-5.
infrahepatic interruption of the inferior vena cava with azygous 54. MacMahon HE. The congenital absence of the ductusvenosus:
(hemiazygous) continuation. Radiology. 1980;134:179-83. Report of a case. Lab Invest. 1960;9:127-31.
44. Licata RH. The human embryonic heart in the ninth week. Am 55. Hoffert PW, Strackman J. Intestinal obstruction due to an
J Anat. 1954;94:73-125. aberrant umbilical vein and hypertrophic pyloric stenosis in a
45. Yater WM. Variations and anomalies of the venous valves of 2-week old infant. Bull NY Acad Med. 1960;36:475-7.
the right atrium of the human heart. Arch Pathol. 1929;7:418- 56. Prust FW, Eskandari F. Intestinal obstruction due to
41. an aberrant umbilical vein: A case report. Ann Surg.
46. Phillips E. Embryology, normal anatomy, and anomalies. 1967;165:464-5.
In: Ferris EJ, Hipona FA, Kahn PC, Phillips E, Shapiro JH, 57. Svendsen LB, Johansen TS, Kristensen P. Intestinal obstruction
(Eds). Venography of the inferior vena cava and its branches. caused by an aberrant umbilical vein. Acta Chir Scand. 1977;
Baltimore, Md:Williams & Wilkins, 1969; 1-32. 143:191-2.
47. Siegfried MS, Rochester D, Bernstein JR, Milner JW. Diagnosis 58. Horiguchi Y, Kitano T, Imai H, et al. Intrahepatic portal-
of inferior vena cava anomalies by computerized tomography. systemic shunt: Its etiology and diagnosis. Gastroenterol Jpn.
Comput Radiol 1983;7:119-23. 1987;22:496-502.
48. Dudiak CM, Olson MC, Posniak HV. Abnormalities of the 59. Wittich G, Jantsch H, Dimiter D. Congenital portosystemic
azygos system: CT evaluation. Semin Roentgenol 1989;24:47- shunt diagnosed by combined real-time and Doppler
55. sonography. J Ultrasound Med. 1985;4:315-8.
49. Dudiak CM, Olson MC, Posniak HV. CT evaluation of 60. Neumaier CE, Cicio GR, Derchi LE, et al. The patent
congenital and acquired abnormalities of the azygos system ductusvenosus: An additional ultrasonic finding in portal
RadioGraphics 1991;11:233-46. hypertension. J Clin Ultrasound. 1983;11:231-3.
223
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 A B
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.
C D
Embryology 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
The knowledge of the pulmonary venous development is plexus of the foregut (the splanchnic plexus). A small evagination
essential to understand the anatomical abnormalities (Figures 1 can be seen in the posterior wall of the left atrium to the left of the
A to D). Recent work has demonstrated that they develop from developing septum secundum; B. By the end of the 1st month of
gestation, the common pulmonary vein establishes a connection
the dorsal mesocardium within the posterior mediastinum. between the pulmonary venous plexus and the sinoatrial portion of
They arise as a new channel and not as an outpouching from the heart; C. Next, the connections between the pulmonary venous
the sinus venosus that is forming the systemic veins that join plexus and the splanchnic venous plexus involute; D. The common
the right atrium. In the early part of the development, lungs pulmonary vein (CPV) incorporates into the left atrium so that the
individual pulmonary veins connect separately and directly to the left
get enmeshed by the vascular plexus from the foregut (i.e. atrium. LA = Left atrium; LCCV = Left common cardinal vein; LLB =
splanchnic). As the differentiation progresses these develop Left lung bud; RA = Right atrium; RCCV = Right common cardinal vein;
into the pulmonary vascular bed. At 25 to 27 days’ gestation, RLB = Right lung bud; UV = Umbilical vein
the developing pulmonary venous plexus retains connections PArtIAl AnomAlous PulmonAry VEnous 16
to the right superior vena cava (SVC), left SVC and portal ConnECtIon
system. No direct communication to the left atrium exists. At
AnomAlies oF PulmonAry Veins

the end of the first month of gestation, the common pulmonary In this anomaly, one or more of the pulmonary veins, but not
vein can be identified, draining the pulmonary venous plexus. all of them, connect abnormally to systemic venous system.
The origin (development) of the common pulmonary vein
is debated. Many believe that common pulmonary vein Key features
originates as an evagination from the left atrium (sinoatrial
region). Some believe that the common pulmonary vein starts Partial anomalous pulmonary venous connection (PAPVC)
from a confluence of vessels from the pulmonary plexus. results in atrial level left-to-right shunt and increased
The intraparenchymal pulmonary veins connect with the pulmonary blood flow (Qp : Qs > 1).
left atrium by establishing a connection with the common The first description of this anomaly was made by Winslow
pulmonary vein.3 in 1739; however Brody in 1942, more clearly summarized
Should the pulmonary venous channel fail to develop, these the condition.3 The advent of surgical correction of cardiac
anastomoses between pulmonary and systemic venous systems defects necessitated a more critical approach to diagnosis and
persist and enlarge. An anastomosis with the anterior cardinal resulted in the identification and description of hundreds of
systemic venous system then results in supracardiac anomalous cases. The reported incidence varies from 0.6-0.7 percent,
connection. Anastomosis with the systemic venous sinus or however most of them are autopsy studies and clinical
the left sinus horn, produces cardiac anomalous connection, incidence could be still lower.3
while the infradiaphragmatic connection is the consequence of
anastomosis with the omphalomesenteric system. Embryology
Anomalous connection always denotes anomalous blood
return or flow; however, anomalous drainage or return can occur The developmental basis (Figures 2A and B) for PAPVC could
without an anomalous connection. For example, in common be that the developing pulmonary vein might have made a
atrium, the right pulmonary vein may connect normally to the connection only with part of the developing pulmonary venous
left atrium, but functionally also enter the morphological right plexus. Anastomoses between the unconnected pulmonary
atrium, mixing with the systemic venous return. Likewise, with segments and systemic venous plexus persist and develop.
the malposition of the septum, the vein may connect normally
to the morphological left atrium, but malposition of the septum Anatomy
may cause anomalous drainage of the pulmonary venous
return, allowing it to mix with systemic blood. Thus we cannot Anatomic variants of PAPVC (modification of Kirklin and
interchange the terms return or drainage with connection. For Barrett-Boyes classification) (Figures 3A to D) are:
the purposes of this chapter we will use anomalous connections 1. Right pulmonary veins to the right SVC or azygos vein.
to imply abnormal anatomic attachments. This is the most common type. The anomalous pulmonary
A B
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 225
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
3 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
DeFeCts in AtrioVenous AnD PulmonAry ArterioVenous ConneCtions
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 B 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
C D veins.
A greater number of veins draining anomalously, results in
Figures 3A to D: Common forms of partial anomalous pulmonary more blood returning to the right side of the heart. The defect
venous connections (PAPVC): A. Anomalous connection of the right
clinically becomes significant when more than 50 percent of
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 the veins return anomalously. The source of the returning blood
IVC. The right lung commonly drains by 1 pulmonary vein without plays a role in determining the clinical effect of the defect.
its usual anatomic divisions. Parenchymal abnormalities of the right In the upright posture, individual blood flow to the lungs is
lung are common, and the atrial septum is usually intact. This type
directed primarily to the lower and middle lobes. Therefore,
of PAPVC is found in Scimitar syndrome; C. Anomalous connection
of the left pulmonary veins (LPV) to the left innominate vein (LIV) one would expect more blood to return to the right side of the
by way of a left vertical vein (LVV). An additional left-to-right shunt heart in individuals in whom the anomalous connection drains
may occur through the ASD; D. Anomalous connection of the LPVs either the right middle and lower lobes or the left lower lobe.
to the coronary sinus (CS). IVC = Inferior vena cava; LA = Left
Though the above mentioned factors influence the amount
atrium; LV = Left ventricle; RA = Right atrium; RV = Right ventricle;
SVC = Superior vena cava; VV = Vertical vein 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.
veins attach to the lower side of the SVC or the SVC–right PAPVC is often associated with an atrial septal defect (ASD),
atrium junction. especially of the sinus venosus type. Sinus venosus defects
2. Right pulmonary vein to the right atrium. The right physiologically allow an atrial level communication, but are not
pulmonary veins connect directly to the right atrium. true ASDs as they do not involve septum. In 20 percent of the
3. Right pulmonary veins to the inferior vena cava (Scimitar patients, the atrial septum is intact. PAPVC may also occur in
syndrome). The anomalous right pulmonary vein, generally patients with visceral heterotaxy and polysplenia.4
draining the entire right lung, descends in a cephalo-caudad
direction toward the diaphragm and then curves sharply to scimitar syndrome
the left to join the inferior vena cava (IVC) or IVC–right
atrium junction, superior to the hepatic vein orifices. Scimitar or pulmonary venolobar syndrome is a rare but
4. Left pulmonary veins to the left innominate vein. The left well known congenital cardiovascular defect that includes
pulmonary veins may connect to the left innominate vein a hypoplastic right pulmonary artery and right lung, which
by way of an anomalous vertical vein. leads to the displacement of the cardiac structures into the
5. Bilateral PAPVC. A rare form of PAPVC. Most commonly, right hemithorax, anomalous systemic arterial supply to the
the atrial septum is intact, the left superior pulmonary right lung and a characteristically curved anomalous right
vein attaches to the left innominate vein by way of an pulmonary vein that drains into the IVC. This resembles
226 anomalous vertical vein, and the right superior pulmonary the curved Middle Eastern Ottoman sword “Scimitar”5
vein attaches to the SVC–right atrium junction (Figures 4A to C). The Scimitar syndrome was first described
16

A B C
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 InVEstIgAtIons

all the CHDs. Isolated partially anomalous pulmonary
venous return to the IVC without the other components Chest radiograph
is known as “Incomplete Scimitar syndrome”. There are
two forms of Scimitar syndrome, the infantile form and The X-ray findings are similar to those of an ASD. A
the adult form. Infantile form is associated with multiple snowman appearance would suggest return to the left vertical
thoracic abnormalities and vascular malformations. Cardiac vein; in older patients with return to the inferior caval
malformations associated with this form include coarctation of vein, the anomalous pulmonary vein is always visible. The
aorta, tetralogy of Fallot, patent ductus arteriosus, ventricular other associated lung findings (pulmonary sequestration,
septal defects and other conoseptal anomalies.6 Adult form is hypoplasia) of Scimitar syndrome might be seen.
associated with a smaller shunt, minimal symptoms and lack
of other associated malformations. Electrocardiogram
Clinical manifestations The electrocardiogram (ECG) is identical to that of an ASD.

Specifically, V1 shows an rsr′ or rsR′, or rarely a QR pattern
The majority are asymptomatic in early life, regardless of in V1. Partial return to the IVC with intact atrial septum is
the presence of an associated ASD. Clinical symptoms are characterized by a terminal s or S wave in V1 (Figure 5). Most
similar to those of ASD. The most common manifestation ECGs in PAPVC are essentially normal.
in symptomatic children is exercise intolerance. Depending
upon the shunt volume, children are either asymptomatic or Echocardiography
have increased frequency of respiratory tract infections. Like
ASDs, symptoms usually appear in the late 20s to early 40s Echocardiography is the mainstay of diagnosis. Both
and consist of exertional dyspnoea and palpitations which transthoracic (TTE) and transesophageal echocardiography
are almost always supra-ventricular in origin. Physical (TEE) are commonly used in the diagnosis. Two dimensional
examination is often normal in those with single anomalous echocardiography with color Doppler is highly useful. The
pulmonary venous return. Peripheral oedema can occur subcostal and suprasternal view (so called crab view) allows
in adults with cardiac failure. Even in older, symptomatic visualization of all the pulmonary veins, SVC, aorta, right
patients, evidence of pulmonary artery hypertension with innominate vein and the right pulmonary artery. In the most
right-to-left atrial shunting manifested by reduced oxygen common form of PAPVC (right middle and upper pulmonary
saturations or overt cyanosis is unusual. In those with more vein to SVC) an abnormal color flow can be seen entering
than one anomalous pulmonary venous return, clinical the wall of the SVC. The spectral Doppler assessment of
findings are similar to those of ASDs like a soft systolic color flow will confirm the systolic and diastolic flow pattern
ejection murmur in the pulmonic area, wide fixed splitting typical of the pulmonary venous flow. The color flow mapping
of the second heart sound and hyperactive right ventricular allows rapid detection of small pulmonary veins and also the
impulse. possibility of stenosis in them. 227
3
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
A B
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 found the prevalence of previously undiagnosed PAPVC to
Scimitar syndrome. Majority of the patients with PAPVC be 0.2% in a general adult population. With advent of newer
have enlargement of right atrium and right ventricle. It is multi-slice CT machines, scan can be performed in few
recommended that TEE be performed in any patient with right seconds without the need for breath holding. Also images can
ventricular enlargement in whom transthoracic examination is be reconstructed in three dimensions with a better anatomical
inconclusive7 (Figures 6A and B). description. This helps the surgeon in deciding the technique
and approach8 (Figure 7).
ComPutEd tomogrAPhy
mAgnEtIC rEsonAnCE ImAgIng
Computed tomography (CT) is being increasingly used for
228 visualization of the anomalous connections of the pulmonary Cardiovascular magnetic resonance imaging (CMR) is an
veins since 1990. A recent retrospective series of CT scans 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
Figure 8: Contrast-enhanced volume-rendered magnetic resonance
tissue spatial relationship which is of extreme help in surgical image shows that left superior pulmonary vein drains to the left
planning. CMR has become an extremely valuable modality brachiocephalic vein (black arrowhead) via the vertical vein (VV).
for the diagnosis as well as the post-operative evaluation of Remaining pulmonary veins drain normally to the left atrium. Ao =
PAPVC9 (Figure 8). Ascending thoracic aorta; MPA = Main pulmonary artery; RBCV =
Right brachiocephalic vein; SVC = Superior vena cava
229
3 Cardiac Catheterization Prognosis
As non-invasive diagnostic modalities have increased the The prognosis of PAPVC is similar to an isolated ASD with
sensitivity and specificity of diagnosis of PAPVC, the need for a comparable left-to-right shunt. Patients with Scimitar
diagnostic catheterisation has decreased. The most definitive syndrome have a worse outcome than the other types of
technique for diagnosing PAPVC at cardiac catheterisation is PAPVC, especially those with early onset of symptoms. Of
to enter the right pulmonary vein directly with the catheter and those cases that require surgical repair, operative mortality
perform a selective angiogram in it or selective left pulmonary rates are low (under 1%). Systemic or pulmonary vein
artery angiogram in levophase illustrates the left pulmonary obstruction as well as sinus node dysfunction has been rarely
veins draining into vertical vein, then horizontal vein (left reported.10
innominate vein) and into right atrium (RA) at the superior
vena cava (SVC) and RA junction (Figure 9). This will totAl AnomAlous PulmonAry VEnous
help to demonstrate the venous drainage pattern, associated ConnECtIons
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
definition
streaming of the oxygenated blood from the renal vein. In this condition, all the pulmonary veins have abnormal
Inability to pass the catheter from the right atrium to the left connection to the systemic circulation. They do not connect
atrium or a difference in right atrial pressure and pulmonary directly to the left atrium.
wedge pressure is suggestive of PAPVC with intact septum. The term total anomalous pulmonary venous connection
(TAPVC) implies an absence of a direct connection between
management the pulmonary veins and the left atrium. The pulmonary
veins connect via systemic veins to the right atrium and are
Surgery is the definitive treatment. Infants with Scimitar often obstructed. This results in mixing of deoxygenated
syndrome may develop respiratory distress and need early and oxygenated blood in the right atrium. The reported
surgical treatment. Indications for surgery are Qp : Qs > 2, incidence for TAPVC ranges from 0.4 to 2 percent from
recurrent respiratory tract infections, Scimitar syndrome prior autopsy studies.11 Males and females are equally
and when surgery is being considered for other indications. affected, however few studies have demonstrated higher
Surgery is usually carried out between 2-5 years of age under incidence in males especially in the infracardiac type.12
cardiopulmonary bypass. Surgical mortality is less than 1 The non-cardiac conditions associated with TAPVC are
percent. Postoperative complications include SVC obstruction asplenia or polysplenia heterotaxy syndromes. There is no
and atrial arrhythmias. 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
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
Figure 9: Cardiac catheterization: Pigtail angiogram in LPA demon- venous connection
230 strating the anomalous drainage of the left pulmonary veins through
• Type 4 - Mixed type of total anomalous pulmonary venous
the vertical vein and horizontal vein (left innominate vein) into right
atrium (RA) at the superior vena cava (SVC) and RA junction connection
course of the vein is between the left pulmonary artery and the 16
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 2 (Cardiac) Total Anomalous Pulmonary

A B
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.
Type 3 (Infracardiac) Total Anomalous Pulmonary

C D
Venous Connection
The infracardiac or infradiaphragmatic type of TAPVC
represents 20 percent of all the cases. The anomalous
connection occurs at the infradiaphragmatic level and in 70-
Figures 10A to D: Types of TAPVC: A. TAPVC to the left innominate 80 percent cases they connect to the portal vein. This type
vein (LIV) by way of a vertical vein (VV); B. TAPVC to the coronary of TAPVC is almost always associated with obstruction.
sinus (CS). The pulmonary veins join to form a confluence designated
the common pulmonary vein (CPV), which connects to the coronary
Newborns have a stormy course with severe tachypnea and
sinus; C. TAPVC to the right atrium. The left and right pulmonary veins cyanosis. The pulmonary veins form a common chamber,
(LPV and RPV) usually enter the right atrium separately; D. TAPVC inferior and posterior to the left atrium. A common vessel
to the portal vein (PV). The pulmonary veins form a confluence from arises from this confluence and descends anterior to the
which an anomalous channel arises.This connects to the portal vein,
which communicates with the IVC by way of the ductus venosus (DV)
esophagus. The anomalous descending vessel then joins
or the hepatic sinusoids. IVC = Inferior vena cava; LA = Left atrium; the portal vein at the confluence of the splenic and superior
LH = Left hepatic vein; LP = Left portal vein; LV = Left ventricle; mesenteric veins. In the majority of the cases, this common
RA = Right atrium; RH = Right hepatic vein; RP = Right portal vein; pulmonary vein connects to the portal venous system, either
RV = Right ventricle; SMV = Superior mesenteric vein; SV = Splenic
vein; SVC = Superior vena cava
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 1 (Supracardiac) Total Anomalous Pulmonary
Venous Connection Type 4 (Mixed) Total Anomalous Pulmonary
Venous Connection
It is the most common subtype of TAPVC, representing
approximately 40 percent of all the cases. In this abnormality It is the rarest type, accounting for less than 5 percent of
the anomalous connection occurs at the supracardiac level. all cases. It is associated with other non-cardiac defects.
Two pulmonary veins from each lung converge behind the Mixed variant is often associated with other major cardiac
left atrium and form a pulmonary venous confluence. Then, structural defects and can have obstruction at several
an anomalous vertical vein arises from the left portion of the levels. The most common type of mixed connections has
confluence and courses toward the left innominate vein . The connection of the left pulmonary veins to a vertical vein
left innominate vein empties normally into the right SVC. leading to the left innominate vein along with connection
If the vein passes anterior to the left pulmonary artery, then of the right pulmonary veins to either the right atrium or
this course is not associated with obstruction. However, if the coronary sinus. 231
3 Pathophysiology in obstructed venous return. Rare manifestations (especially
in infracardiac TAPVC) include sudden death, unconjugated
TAPVC results in complete mixing of the systemic and hyperbilirubinemia and hematemesis. The infants with
pulmonary blood. There is an obligatory right-to-left shunt as large inter-atrial communication present at later age. They
the pulmonary venous return is to the systemic veins. Most often present with failure to thrive, tachypnea and frequent
of the times the right-to-left shunt occurs at the atrial level respiratory tract infections. On examination, neonates with
and rarely it has been reported at ventricular level or at ductal infracardiac TAPVC are sick, cyanosed with signs of poor
level with intact septum. Hence, the mixed venous blood may peripheral perfusion. Findings are similar to an ASD, with
enter the right ventricle and the pulmonary circuit or may a wide split second heart sound and mid systolic murmur.
pass through the obligatory right-to-left atrial communication Precordium is quiet. Sometimes there is a venous hum heard
and fill the left ventricle (LV) and the systemic circulation. A below the left clavicle especially in supracardiac TAPVC to
non-restrictive ostium secundum ASD is seen in 20% of the the left innominate vein. It differs from other venous hums in
patients with simple TAPVC.16 Remaining 80 percent of the that it persists even with compression of the neck veins and is
infants have PFO with restricted right to left shunt. As the not louder in diastole. P2 is loud. Hepatomegaly may be seen
neonates grow there is a decrease in the pulmonary vascular when the anomalous drainage is to the portal vein.18 Infants
resistance which further decreases the right to left shunt. without pulmonary venous obstruction present with typical
Most of the blood recirculates through the low resistance features of an ASD. The precordium is hyperdynamic with
pulmonary circulation resulting in increased pulmonary blood wide fixed splitting of the second heart sound.
flow and decreased systemic output. These neonates manifest
with respiratory distress and hypoxemia. They typically have Investigations
elevated right atrial pressures, pulmonary artery hypertension
and low cardiac output. When the shunt is at the level of the
Chest Radiography
atrium there is tendency for the fetal pattern of the circulation
to be maintained. In case of the infradiaphragmatic variant of In newborns with severe pulmonary venous obstruction,
TAPVC, the oxygenated blood ascending the inferior caval cardiac silhouette is normal or small with ground glass
vein towards the right atrium is directed towards the left appearance of the lung fields. Sometimes the findings may be
atrium. Accordingly, the systemic arterial oxygen saturation misinterpreted as RDS, which is more common in the newborn
is relatively higher than the pulmonary arteries. Conversely period. However, unlike obstructive TAPVC, in RDS usually
,in supracardiac TAPVC, oxygenated blood tends to be homogeneous patchy infiltrates along with air-bronchograms
directed down the SVC and through the tricuspid valve into are noted.19,20
the pulmonary circulation. Hence, the pulmonary oxygen In patients without the obstructive physiology, the X-ray
saturation is likely to be more than systemic. findings are similar to those with right-sided volume overload.
Obstruction to the pulmonary venous return results in the In older patients the pulmonary trunk may be prominent;
rise of the pulmonary capillary wedge pressure and rapid sometimes the left vertical vein may be prominent when that is
progression to pulmonary edema. With further rise of the the site of anomalous connection. This gives rise to snowman
pulmonary capillary pressure, the RV compliance decreases appearance also called WC Fields heart (Figures 11A and B).
leading to increase in the right atrial pressure and right-to-left
atrial shunt. This ultimately leads to systemic hypoxemia and Electrocardiography
metabolic acidosis. If the ductus is still open this will again lead
to increased right-to-left shunt and worsening of the systemic Right axis deviation with a clockwise frontal plane loop and
hypoxemia and pulmonary oligemia. The progressive rise in the right ventricular hypertrophy is seen. V1 usually shows an
metabolic acidosis leads to multiorgan failure. The outcome will rsR′ pattern, though a qR is seen in four-fifths of the patients,
be fatal without the relief of the pulmonary venous obstruction. which indicates severe pulmonary hypertension. By the age of
3 to 4 months most of the patients have features of right atrial
Clinical Presentation enlargement on ECG.
Two factors determine the severity of the symptoms in TAPVC. Echocardiography

One is the severity of the pulmonary venous obstruction and
other is the restriction of the inter-atrial communication. Echocardiography is the cornerstone investigation for
Neonates with infracardiac variant of TAPVC (commonly diagnosis of TAPVC. The accuracy of echocardiography in
associated with obstruction), present within 48 hours of birth, diagnosing TAPVC is 100%.21, 22 The key to the diagnosis of
with intense cyanosis and tachypnea. They are often treated as TAPVC is identifying the anatomic connections of all four
respiratory distress syndrome (RDS) of the newborn.17 Unlike pulmonary veins.23,24 Correlative anatomical studies suggest
232 RDS of the newborn, grunting respiration is very rarely seen that the subcostal and apical approaches image the normal left
16

A 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 Intracardiac TAPVC: The coronary sinus itself will be
approach, given a good window, can demonstrate all four. A dilated. It can be dilated because of a persistent left SVC
universal finding in TAPVC is right-sided volume overload, as well. Thus, delineating the connection of the confluence
with enlargement of the right atrium, right ventricle, and into the coronary sinus is imperative. The pulmonary venous
main pulmonary artery. The clue to diagnosis is the exclusive confluence is directly posterior to the left atrium. It is thus
right to left shunt at the atrial level. An essential element is well visualized in the parasternal, apical four-chamber and
identifying the size and location of each vein and how and subcostal views (Figure 12).
where they enter the heart. This is especially important Supracardiac TAPVC: The pulmonary venous confluence
because it has been shown that the sum of the individual is usually superior to the left atrium and is thus best visualized
vein sizes is an independent risk factor for postoperative in the parasternal views. It may also be seen from the subcostal
mortality. Specifically, small veins before surgery lead to long-axis views. Drainage to the SVC is either direct or
higher postoperative mortality.25 In patients who are difficult through the left vertical vein. Left vertical vein connects to
to image with TTE, TEE may provide better visualization of the brachiocephalic vein which is better visualized in supra-
the pulmonary veins and their site of drainage because of their sternal view (Figures 13A and B). An easy way to identify and
posterior location.26 trace the left vertical vein is to inject contrast bubbles into the
left arm.
Localizing the Confluence of Pulmonary Veins Infracardiac TAPVC: The pulmonary veins usually converge
just above the diaphragm. Therefore, the pulmonary venous
The suprasternal view or parasternal short axis view better confluence is often small and inferior to the left atrium or
demonstrates the venous confluence in TAPVC. Confluence may not exist as a distinct, separate chamber. The descending
is seen as an echo free non-pulsatile structure posterior to the vein is better demonstrated in the sub-costal long axis view
left atrium. It has a separate venous egress connecting to the (Figures14A and B). It should be differentiated from the aorta
systemic vein. Supracardiac TAPVC can generally be best and the IVC. It is non-pulsatile and doesn’t connect to either
seen from the parasternal imaging and infracardiac TAPVC atrium. Another easier way to differentiate it from the IVC is
is best visualized from subcostal views, however, multiple to inject contrast micro-bubbles into the leg veins.
views are often used. For obvious reasons, it is often difficult Mixed Form of TAPVC: This form of TAPVC is suspected
to localize the pulmonary venous confluence in neonates with when only two pulmonary veins are seen to enter the venous
RDS. Because of its size, shape and posterior location, the confluence in multiple views and planes. Special attention
pulmonary venous confluence can sometimes be difficult to should be paid to the coronary sinus and the innominate vein,
image directly, even by TEE. as potential sites of drainage. Echocardiography can be used
233
3
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
A B
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
to trace the final common pathway of pulmonary venous detection of obstruction by cross sectional imaging and color
drainage into the systemic vein. Obstruction in the pathway Doppler (Figure 15).
is recognized by the turbulent flow and pulse wave Doppler
234
offers an objective measure. The presence of a focal increase Computed Tomography and Magnetic Resonance Imaging
in flow velocity (~2 m/sec) with a continuous, non-phasic
flow pattern distally is a characteristic finding. A sensitivity These non-invasive modalities of imaging are of great help
of 100% and specificity of 85 percent have been claimed for in diagnosis and pre-operative work up. Considering the
16

A B
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
Figure 16: MRI 3D reconstructed image showing mixed total anom-
alous pulmonary venous connection (type IV). AA = Aortic arch;
CS = Coronary sinus; LIPV = Left inferior pulmonary vein; LPA = Left
complexity involved in understanding three dimensional pulmonary artery; RIPV = Right inferior pulmonary vein; RPA = Right
pulmonary artery; RSPV = Right superior pulmonary vein; SVC =
anatomical relationships between the pulmonary veins and Superior vena cava
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 within individual pulmonary veins and accurate chamber
in many implanted devices. As early as 1991, Masui and volumes and function.27
colleagues found MRI to be superior to both echocardiography
and conventional angiography in patients with TAPVC. Cardiac Catheterization
Magnetic resonance imaging and angiography (MRA) also
provides superb multiplanar imaging of these abnormal Catheterization for the diagnosis of TAPVC is obsolete
vascular structures (Figure 16). Additional advantages include these days. However, the diagnosis can be established by 235
its ability to obtain functional data, such as flow velocities entering the anomalous venous channel with the catheter and
3 performing the angiogram. The oximetry will demonstrate the umbilical vein is fully saturated, confirming the diagnosis.
step-up of the saturation to > 90 percent in the right atrium. The catheterization also gives the opportunity to perform the
Saturations in the right ventricle and pulmonary circulation interventions; however the catheter-based interventions are
are usually identical; however, it should be noted that because proved to be ineffective and are not typically undertaken.
of the streaming and incomplete mixing there could be a small Balloon or blade atrial septostomies were previously
difference in saturation. In TAPVC, the oxygen saturation in performed as a palliative measure, but they only delayed
the right atrium usually ranges between 80 percent and 95 definitive repair. The percutaneous stenting of the pulmonary
percent, and saturations in the right atrium, right ventricle, vein is largely ineffective and should not be undertaken.29,30
pulmonary artery, left atrium, left ventricle, and systemic
arteries are nearly identical. The right ventricular and differential diagnosis
pulmonary arterial pressures are usually suprasystemic with
obstructed TAPVC, but right atrial pressures are normal or Pulmonary venous atresia also presents as TAPVC with
nearly so. Pulmonary artery wedge pressure is elevated, severe pulmonary venous obstruction. Clinically, these two
whereas left atrial pressure is low. The size of the atrial conditions are indistinguishable. However, the unobstructed
communication is important for left heart preload and its size variant of TAPVC needs to be distinguished from other
can be determined at catheterization using an inflated balloon conditions like transposition of great vessels with ventricular
catheter. An interatrial communication less than 5 mm in septal defect. Atrioventricular septal defect with common
diameter is definitely restrictive.28 Selective pulmonary atrium can be distinguished from this condition on the basis
arteriography is usually diagnostic. Following injection and of ECG. Other conditions likely to cause mild cyanosis and
passage of the opaque dye through the pulmonary fields, the heart failure need to be distinguished.
dye collects in the pulmonary venous channels and clearly
outlines the anomalous connection. Rarely after selective management
left pulmonary artery angiogram in levophase we can see
the left pulmonary veins (LPVs) draining into azygos system Surgery is the only intervention with proven short and long-
(Figure 17A). Sometimes the right heart catheter through the term success for TAPVC. As a matter of fact, TAPVC is the first
azygos system can enter the right pulmonary veins (RPVs). condition in which neonatal open heart surgery was performed.
The hand injection of contrast can confirm the RPVs draining TAPVC with severe pulmonary venous obstruction requires
into azygos system (Figure 17B). If selective injection of urgent or emergent surgical intervention. Preoperatively
the contrast material into the anomalous venous channel is medical treatment needs to be started to stabilize the patient.
contemplated in the patient with TAPVC with obstruction, Neonatologists often start prostaglandin infusion in newborns
the injection should be done by hand. In a newborn with with respiratory distress and cyanosis considering the possibility
TAPVC to the portal venous system, blood obtained from the of ductus dependent circulation. It was considered dangerous
A B
236 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
in case of TAPVC with obstructive pulmonary circulation, as pulmonary tuberculosis or invasion by a tumor. Congeni- 16
it can increase the pulmonary blood flow and hence worsening tal pulmonary vein atresia is usually associated with other
the respiratory distress. However, Bullaboy et al argued that cardiac malformations. It may occur in either lung, with no

the PGE1 could be of benefit by maintaining the patency of right- or left-sided predominance.
the ductus venosus allowing for some decompression of the
obstructed infradiaphragmatic TAPVC. They do consider that Pathophysiology
there may be right-to-left shunting through the patent ductus
arteriosus, which could decompress the pulmonary circulation Severity of the manifestations depends upon the number of
and increase the systemic blood flow. Hence, PGE may be a the pulmonary veins affected, severity of the obstruction
reasonable medication during transport or until the diagnostic and other associated cardiac malformations. The pulmonary
evaluation has been completed.31 venous pressure on the affected side is elevated. This results
In most of the developing nations facilities for emergency in elevation of the pulmonary artery pressure.37 However, few
surgery are not available, hence an alternative approach of cases have been reported where pulmonary artery pressures
initial balloon septostomy followed by definitive surgery is are normal.38 The pulmonary artery hypertension causes
undertaken. Septostomy no longer seems appropriate because elevation of the right ventricular end-diastolic pressure
it delays the definitive procedure and is of little value when an which might cause right-to-left shunt through the foramen
anomalous venous channel is also obstructed.32,33 Preoperative ovale. It has been observed that the ipsilateral pulmonary
inotropic agents, diffuse pulmonary vein stenosis, emergency artery is hypoplastic, probably because of the preferential
surgery and postoperative pulmonary hypertensive events are pulmonary artery perfusion to the contralateral side, with
considered to be predictors of in-hospital mortality. In one resultant impaired growth of the affected pulmonary artery.
of the studies, the cardiac form of TAPVC was associated This pulmonary artery hypoplasia probably accounts for the
with higher mortality. The specific surgical technique used arterial systemic-to-pulmonary collateral vessels.39
is determined by the anatomy of the defect. Primary surgical
approach in many cases is creating an unrestrictive side-to- Clinical manifestations
side anastomosis between the pulmonary venous confluence
and the left atrium while resecting other means of egress from Clinical features depend upon the number of the veins affected
the confluence. In the cardiac TAPVC, surgeons can unroof and the severity of the obstruction. Most of the children
the coronary sinus to the left atrium and close the coronary with single pulmonary vein affection can be asymptomatic.
sinus orifice with a patch. However, the specific surgical However, most of the children present in early childhood with
technique and approaches are beyond the scope of this book. recurrent episodes of chest infections, dyspnea, failure to thrive,
hemoptysis and occasionally cyanosis. On auscultation, second
Prognosis heart sound is loud; however murmurs are usually absent.40
The prognosis in TAPVC is determined by the size of the Investigations

inter-atrial defect and by the presence of obstruction to the
anomalous venous pathways. Without surgery most of the
Chest X-ray
neonates do not see their first birthday. With improvements
in surgical techniques the operative mortality has decreased Cardiothoracic ratio on chest X-ray remains normal.
significantly. Currently, the operative mortality in the neonatal Pulmonary trunk might appear prominent. The affected
period is 0–5 percent.34,35 The anatomical type of TAPVC is lung may be hypoplastic with mediastinal shift (Figure 18).
less well correlated with the surgical outcome, however the Reticular opacities with septal lines are present in most of the
supracardiac TAPVC has a better outcome compared to other patients and are most marked in the lower lobes.41
forms.36 Rather than the anatomical subtype, it is the size of
the pulmonary veins and their confluence that determines Electrocardiogram
the outcome. The long-term outcome of the neonates with
surgical repair is excellent. However 10 percent of these cases Right ventricular hypertrophy and right atrial enlargement,
are known to develop pulmonary stenosis. The exact reasons without left-sided changes, is invariably found on the electro-
for this are unknown. Re-operation carries a high mortality cardiography.42
and a strong chance of recurrence.
Echocardiography
stEnosIs or AtrEsIA of IndIVIduAl
PulmonAry VEIns A diagnosis by standard echocardiography and Doppler
methods is made more difficult by the distance of the
Several acquired conditions can also be present with pulmo- pulmonary venous connection to the left atrium as measured 237
nary vein stenosis like constrictive pericarditis, mediastinitis, by the transducer of the surface echocardiographic acoustic
3
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 B
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 Figures 19A and B: A. Normal pulsed Doppler pulmonary vein flow
diastole and flow reversal after atrial contraction. However, pattern in a child. There are well-defined systolic and early diastolic
peaks of approximately 1 m/s and the flow reaches the baseline or
stenotic pulmonary veins have a pattern of continuous flow even reverses in late diastole; B. Typical pulsed Doppler flow pattern
that is disturbed without the normal phasic variation as well as of pulmonary vein stenosis. The flow pattern is turbulent, continuous
the turbulent flow (Figures 19A and B). A definitive diagnosis and has an abnormally high peak velocity
requires a cardiac catheterization.
Cardiac Catheterization
A pulmonary catheterization can be accomplished by the right
side venous or left side arterial approaches. Although, a trans-
septal 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 Figure 20: Pulmonary artery wedge angiogram of a patient with
severe left superior pulmonary vein stenosis caused by radiofrequency
venous stenosis. Pulmonary arterial wedge angiography ablation for atrial fibrillation. Note the balloon catheter wedged in the
238 (Figure 20) may be a better technique to demonstrate the precise superior segment of the left lung, which allows excellent visualization
anatomy of the pulmonary venous stenosis than pulmonary of the vein on levophase
arteriography, where selective pulmonary venous injection arteries, suggesting that the hemodynamic effect of unilateral 16
is preferred especially in cases with isolated pulmonary vein pulmonary vein stenosis is reflected in the caliber change in
stenosis.45 Pulmonary arteriography is often disappointing the branch pulmonary arteries. The computed tomography

in demonstrating the precise anatomy of pulmonary venous is also equally effective in delineating the pulmonary vein
stenosis. stenosis.
Computed Tomographic and Magnetic management

Resonance Angiography
Surgery is the definitive treatment. Advances in the technique
When pulmonary vein stenosis is suspected, MRA is performed of surgical repair of pulmonary vein stenosis have been based
as the initial MRI sequence. In a study by Valsangiacomo et on the concept of reducing trauma to the veins in the hope of
al, MRA visualized the central two-thirds of the pulmonary reducing any stimulus for regrowth of the obstructive tissue.
veins in 99 percent, while echocardiography was able to A technique by which the pericardium around the pulmonary
identify the pulmonary veins in only 89 percent.45 Contrast veins is attached to the left atrium avoids any stitches in the
enhanced MRA (Figures 21A and B) visualizes not only cut edges of the pulmonary veins and is now considered the
the stenotic lesion, but also the collateral venous channels best approach. Limited experience suggests that this sutureless
to the unobstructed pulmonary veins. The significance marsupialization may be superior to previous approaches that
of the stenosis can be evaluated by measuring flow in the used direct anastomosis after the resection of the stenotic
pulmonary veins and arteries in the affected and unaffected segments or patching of the stenotic vein. Overall, freedom
lungs. On the other hand, vessel caliber and blood flow profile from reoperation or death at 5 years, however, is still only
of the stenosed pulmonary vein do not necessarily reflect the ~50 percent. Patients with milder degrees of stenosis and
real severity of the stenosis, because redistribution of blood stenosis of only one or two pulmonary veins clearly have
flow to the unaffected lung areas results in reduced blood a better prognosis. Pneumonectomy may be necessary for
flow through the reduced caliber of the affected pulmonary hemoptysis. In a small number of patients with unrelenting
vein. Roman et al. demonstrated that unilateral pulmonary progression and development of severe pulmonary
vein stenosis was associated with reduced systolic forward hypertension, lung transplantation has been successful. Single-
flow and diastolic flow reversal in the ipsilateral branch catheter interventions for treatment of pediatric pulmonary
pulmonary artery.46 Furthermore, the cross-sectional area vein stenosis have also met with limited success. Immediate
ratio of the right and left branch pulmonary arteries correlated improvement is usually seen angiographically, but recurrent
well with the ratio of net forward flow through the pulmonary stenosis occurs in a large majority of patients.47
A B
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 239
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
3 Prognosis Echocardiography
Most patients will die before reaching adulthood, and It is very difficult to visualize the small pulmonary venous
frequently much sooner.37 The mode of demise is usually confluence. The features that should raise the possibility of
a pulmonary hypertensive crisis, intercurrent pulmonary presence of this condition include presence of right-to-left
infection, or hemoptysis. Breinholt et al found a mortality rate shunt through the foramen ovale, pulmonary hypertension
of 83 percent in patients with 3 or 4 stenosed pulmonary veins and inability to visualize the pulmonary vein or its confluence
versus zero percent in patients with 1 or 2 stenosed pulmonary entering the left atrium. The pulmonary venous return would
veins.38 More cases of mild forms of pulmonary vein stenosis not connect to right side structures.
are undoubtedly being diagnosed in relatively asymptomatic
patients as a result of increased awareness and improvements Cardiac Catheterization
in non-invasive imaging modalities. The precise natural
history of milder forms of pulmonary vein stenosis is therefore Cardiac catheterization might be required for accurate
not entirely clear. definition of the condition. However, catheterization can
be a high-risk procedure. During catheterization injection
AtrEsIA of thE Common PulmonAry VEIn of contrast material into the right ventricle causes the
persistence of the contrast in the pulmonary artery and non-
The common pulmonary vein is a transient structure normally opacification of the left atrium. Also there will be severe
identifiable only during the early stages in the development of pulmonary hypertension with desaturation in all chambers and
the pulmonary venous system. vessels.51
The term atresia of the common pulmonary vein refers to a
pattern of abnormal pulmonary venous development in which management
the individual pulmonary veins are formed, but no connection
exists between these veins and the heart or major systemic Surgery is the definitive treatment of this condition.
veins.49 Pulmonary veins converge behind left atrium and Previously, surgery carried a high mortality. But with advent
form a confluence without draining into it. of extracorporeal membrane oxygenation, its use in the
perioperative period has resulted in improved outcome.52
Pathophysiology
unIlAtErAl PulmonAry VEnous AtrEsIA
The proposed route by which blood reaches the systemic
circulation include: Unilateral pulmonary venous atresia is a rare condition carrying
1. Bronchopulmonary venous anastomoses → pleurohilar high mortality. Till now 30 cases have been reported.53 There
bronchial veins → azygos, hemiazygos and brachiocephalic is absence of the luminal continuity between the pulmonary
veins. venous drainage between one lung and the left atrium. Most
2. Pulmonary capillaries → pulmonary arteries → broncho- are diagnosed in the preschool period. It is usually diagnosed
pulmonary arterial into the systemic circuit. on lung perfusion studies. Often there is poor blood supply to
The pulmonary capillary pressure increases leading to the the affected lung. Pneumonectomy carries the better outcome
accumulation of fluid. However, there are reports of babies compared to other modalities of surgery.54
surviving for a month.49
ConClusIon
Clinical features
The abnormal embryonic pulmonary vein development may
The clinical features in the atresia of the common pulmonary result in a wide spectrum of congenital anomalies of the
vein resembles that in TAPVC. Respiratory distress and pulmonary veins. These conditions have traditionally been
cyanosis occurs in the first few hours after birth. The condition evaluated with echocardiography and angiography and now
is often misdiagnosed as RDS as there is no cardiomegaly they can be more accurately diagnosed with mutlidetector CT
and pulmonary parenchyma shows reticular pattern (due and MRI. The improved neonatal care and surgical techniques
to pulmonary venous hypertension). It can manifest as have reduced the perioperative mortality in most centers.
spontaneous pneumothorax.50
Reading a technically poor echocardiogram is like looking
Investigation at a polar bear in a snow storm.
—Lynn Y Zoiopoulos, DO
Electrocardiography reveals right ventricular hypertrophy.
240
rEfErEnCEs 20. Patton WL, Momenah T, Gooding CA, Silverman NH. The
vascular vise causing TAPVR type I to radiographically mimic
16
1. Healy JE, Jr. An anatomic survey of anomalous pulmonary TAPVR type III. PediatrRadiol. 1999;29:323-6.

veins: Their clinical significance. J ThoracCardiovasc Surg. 21. Van Hare GF, Schmidt KG, Cassidy SC, et al. Color Doppler
1952;23:433-44. flow mapping in the ultrasound diagnosis of total anomalous
2. Webb S, Kanani M, Anderson RH, Richardson MK, Brown pulmonary venous connection. J Am SocEchocardiogr. 1988;
NA. Development of the human vein and its incorporation in 1:341-7.
the morphologically left atrium. Cardiol Young. 2001;11: 632- 22. Sreeram N, Walsh K. Diagnosis of total anomalous pulmonary
42. venous drainage by Doppler color flow imaging. J Am
3. Hughes C, Rumore P. Anomalous pulmonary veins. Arch CollCardiol. 1992;19:1577-82.
Pathol. 1944;37:364-6. 23. Sahn DJ, Allen HD, Lange LW, et al. Cross-sectional
4. Xue JR, Luo Y, Cheng P, Cao RW. Diagnosis and treatment of echocardiographic diagnosis of the sites of total anomalous
partial anomalous pulmonary venous connection. Zhonghua Yi pulmonary venous drainage. Circulation. 1979;60:1317-25.
XueZaZhi. 2008;88:1066-8. 24. Snider AR, Silverman NH, Turley K, et al. Evaluation of
5. Woodring JH, Howard TA, Kanga JF. Congenital pulmonary infradiaphragmatic total anomalous pulmonary venous con-
venolobar syndrome revisited.Radiographics. 1994;14:349-69. nection with two-dimensional echocardiography. Circulation.
6. Vanderheyden M, Goethals M, Van Hoe L. Partial anomalous 1982;66:1129-32.
pulmonary venous connection or scimitar syndrome. Heart. Jul 25. Jenkins KJ, Sanders SP, Orav EJ, et al. Individual pulmonary
2003;89:761. vein size and survival in infants with totally anomalous
7. Wong ML, McCrindle BW, Mota C, Smallhorn JF. Echocardio- pulmonary venous connection. J Am Coll Cardiol. 1993;22:201-
graphic evaluation of partial anomalous pulmonary venous 6.
drainage. J Am Coll Cardiol. 1995;26:503-7. 26. Stumper O, Vargas-Barron J, Rijlaarsdam M, et al. Assessment
8. Greene R, Miller SW. Cross-sectional imaging of silent of anomalous systemic and pulmonary venous connections by
pulmonary venous anomalies Radiology. 1986;159:279-81. transesophageal echocardiography in infants and children. Br
9. Greil GF, Powell AJ, Gildein HP, et al. Gadolinium-enhanced Heart J. 1991;66:411-8.
3-dimensional MR angiography of pulmonary and systemic 27. Yoshioka K, Niinuma H, Kawakami T, Oyama K, Ishihara
venous anomalies. J Am Coll Cardiol. 2002;39:335-41. K, Kawazoe K. Three-dimensional demonstration of total
10. Hughes C, Rumore P. Anomalous pulmonary veins. Arch anomalous pulmonary venous return with contrast-enhanced
Pathol. 1944;37:364-6. magnetic resonance angiography. Ann Thorac Surg. 2004;
11. Mehrizi A, Hirsch MS, Taussig HB. Congenital heart disease 78:2186.
in the neonatal period: Autopsy study of 170 cases. J Pediatr. 28. Ward KE, Mullins CE, Huhta JC, et al. Restrictive interatrial
1964;65:721-6. communication in total anomalous pulmonary venous
12. Lucas RV Jr, Adams P Jr, Anderson RC, et al. Total anomalous connection. Am J Cardiol 1986;57:1131-6.
pulmonary venous connection to the portal venous system: A 29. Lock JE, Bass JL, Castaneda-Zuniga W, et al. Dilation
cause of pulmonary venous obstruction. AJR Am J Roentgenol. angioplasty of congenital or operative narrowings of venous
1961;86:561-75. channels. Circulation. 1984;70:457-64.
13. Solymar L, Sabel KG, Zetterqvist P. Total anomalous pul- 30. Wax DF, Rocchini AP. Transcatheter management of venous
monary venous connection in siblings. ActaPaediatr Scand. stenosis. PediatrCardiol. 1998;19:59-65.
1987;76:124-7. 31. Bullaboy CA, Johnson DH, Azar H. Total anomalous pulmonary
14. Kirklin JW. Surgical treatment of anomalous pulmonary venous connection to portal system: A new therapeutic role for
venous connection (partial anomalous pulmonary venous prostaglandin E1? PediatrCardiol. 1984;5:115-6.
drainage). Mayo Clin Proc. 1953;28:476-9. 32. Mullins CE, el-Said GM, Neches WH, et al. Balloon atrial
15. Darling RC, Rothney WB, Craig JM. Total pulmonary venous septostomy for total anomalous pulmonary venous return. Br
drainage into the right side of the heart: Report of 17 autopsied Heart J. 1973;35:752-7.
cases not associated with other major cardiovascular anomalies. 33. Bando K, Turrentine MW, Ensing GJ, et al. Surgical
Lab Invest. 1957;6:44-64. management of total anomalous pulmonary venous connection:
16. Burroughs JT, Edwards JE. Total anomalous pulmonary venous thirty year trends. Circulation. 1995;94:12-21.
connection.Am Heart J. 1960;59:913-31. 34. Raisher BD, Grant JW, Martin TC, Strauss AW, Spray TL.
17. Hastreiter AR, Paul MH, Molthan ME, Miller RA. Total Complete repair of total anomalous pulmonary venous connec-
anomalous pulmonary venous connection with severe tion in infancy. J Thorac Cardiovasc Surg. 1992;104: 443-8.
pulmonary venous obstruction: A clinical entity. Circulation. 35. Caldarone CA, Najm HK, Kadletz M, et al. Surgical management
1962;25:916-28. of total anomalous pulmonary venous drainage: impact of
18. Van Son JAM, Hambsch J, Kinzel P, et al. Urgency of operation coexisting cardiac anomalies. Ann Thorac Surg. 1998;66:1521-6.
in infracardiac total anomalous pulmonary venous connection. 36. Kirshbom PM, Myung RJ, Gaynor JW, et al. Preoperative
Ann Thorac Surg. 2000;70:128-30. pulmonary venous obstruction affects long-term outcome for
19. Lucas Jr RV, Adams Jr P, Anderson RC, et al. Total anomalous survivors of total anomalous pulmonary venous connection
pulmonary venous connection to the portal venous system: repair. Ann Thorac Surg 2002;74:1616-20.
A cause of pulmonary venous obstruction. Am J Roentgenol 37. Driscoll DJ, Hesslein PS, Mullins CE. Congenital stenosis
Radium TherNucl Med. 1961;86:561-75. of individual pulmonary veins: Clinical spectrum and
241
3 unsuccessful treatment by trans venous balloon dilation. Am J
Cardiol. 1982. p.49.
obstruction in children? A phase-contrast magnetic resonance
study. Pediatr Radiol 2005;35:580-6.
38. Cullen S, Deasy PF, Tempany E, Duff DF. Isolated pulmonary 47. Lock JE, Bass JL, Castaneda-Zuniga W, Fuhrman BP,
vein atresia. Br Heart J. 1990;63:350-54;1767-72. Rashking WJ, Lucas RV Jr. Dilation angioplasty of
39. Beerman LB, Oh KS, Park SC, et al. Unilateral pulmonary vein congenital or operative narrowings of venous channels.
atresia: clinical and radiographic spectrum. Pediatr cardiol. circulation.1984;70:457-64.
1983;4:105-12. 48. Breinholt JP, Hawkins JA, Minich L, Tani LY, Orsmond GS,
40. Shone JD, Amplatz K, Anderson RC, et al. Congenital stenosis Ritter S, Shaddy E. Pulmonary vein stenosis with normal
of individual pulmonary veins. Circulation. 1962;26:574-81. connection: associated cardiac abnormalities and variable
41. Heyneman LE, Nolan RL, Kevinharrison J, Page McAdams outcome. Ann Thorac Surg. 1999;68:164-8.
H. Congenital Unilateral Pulmonary Vein Atresia: Radiologic 49. Lucas Jr RV, Woolfrey BF, Anderson, et al. Atresia of the
Findings in Three Adult Patients. AJR 2001;177:681-5. common pulmonary vein. Pediatrics. 1962;29:729-39.
42. Bini RM, Cleveland DC, Ceballos R, et al. Congenital 50. Sharda JK, Kurlandsky LE, Lacina SJ, Radecki LL.
pulmonary vein stenosis. Am J Cardiol 1984;54:369-75. Spontaneous pneumothorax in common pulmonary vein
43. Samdarshi TE, Morrow WR, Helmcke FR, Nanda NC, atresia. J Perinatol. 1990;10:70-4.
Bargeron LM Jr, Pacifico AD. Assessment of pulmonary vein 51. Dudell GG, Evans ML, Krous HF, et al. Common pulmonary
stenosis by transesophageal echocardiography.Am Heart J vein atresia: The role of extracorporeal membrane oxygenation.
1991;122:1495-8. Pediatrics. 1993;91:403-10.
44. Bahl VK, Chandra S, Mishra S. Congenital stenosis of 52. Suzuki T, Sato M, Murai T, Fukuda T. Successful surgical
isolated pulmonary vein: role of retrograde pulmonary vein repair of common pulmonary vein atresia in a newborn.
catheterization. Int J Cardiol 1997;60:103-5. PediatrCardiol. 2001;22:255-7.
45. Valsangiacomo E, Levasseur S, McCrindle B, MacDonald C, 53. Shimazaki Y, Nakano S, Kato H, et al. Mixed type of total
Smallhorn J, Yoo S. Contrast-enhanced MR angiography of anomalous pulmonary venous connection with hemi-
pulmonary venous abnormalities in children. PediatrRadiol pulmonary vein atresia. Ann Thorac Surg. 1993;56:1399-401.
2003;33:92-8. 54. Kingston HM, Patel RG, Watson GH. Unilateral absence or
46. Roman KS, Kellenberger CJ, Macgowan CK, et al. How is extreme hypoplasia of pulmonary veins. Br Heart J. 1983;
pulmonary arterial blood flow affected by pulmonary venous 49:148-53.
242
C hapter
Congenital Pulmonary
17 Arteriovenous Fistula
Chandrakant B Patil, Kiron Varghese
Introduction successful surgical removal of a pulmonary hemangioma with

disappearance of the patient’s polycythemia and clubbing after
Pulmonary arteriovenous fistulas (PAVF) are rare pulmonary pneumonectomy. Surgical techniques were further refined to
vascular anomalies characterized by a direct communication lobectomy in 1950 and to local excision in 1959. In 1978,
between the branches of the pulmonary artery and the Taylor and coworkers reported the first case of successful
pulmonary veins, bypassing the capillary bed. They are also percutaneous catheterization and embolization of PAVM.2
named as pulmonary arteriovenous malformations (PAVM), After the initial description of telangiectasia and epistaxis
pulmonary arteriovenous aneurysms, pulmonary angiomatosis by Henry Joules Rendu in 1986, Sir William Osler reported a
and pulmonary hamartomas.1 family with HHT. In 1907, Frederick Weber described other
While more than half of the patients are asymptomatic, they manifestations of this disorder. Since then HHT has been
can manifest with dyspnea, fatigue, cyanosis and paradoxical known as Rendu-Osler-Weber syndrome. Approximately 70
embolization due to right to left shunting. Central nervous percent of arteriovenous fistulas are associated with HHT and
system (CNS) complications include stroke and brain abscess. about 15 to 30 percent of individuals with HHT have PAVF.4
There is a strong association between PAVF and hereditary Through refinements in interventional equipments and
hemorrhagic telangiectasia (HHT). Chest radiography and techniques, results have progressively improved to avoid
contrast enhanced computed tomography (CT) are essential device embolization. Transcatheter occlusion of the afferent
initial diagnostic tools, but pulmonary angiography is the gold artery or fistula is usually, accomplished using a coil umbrella
standard. Contrast echocardiography is useful for diagnosis or sack device rather than liquid adhesives or beads.5
and monitoring after treatment. Most patients, if symptomatic
need treatment. Therapeutic options include angiographic PREVALENCE, GENETICS AND ETIOLOGY
embolization with metal coils or balloon occlusion and if
needed be surgical excision.2 The PAVF are a result of an embryonic fault in the vascular
complex that is responsible for the development of pulmonary
Historical Background arteries and veins. It is a RASopathy. The fistulas can be solitary
or multiple, unilateral or bilateral or diffuse throughout both
Churton in 1897 first described PAVF in a 12-year-old the lungs.6 The PAVF may be single or multiple in occurrence
boy, who had episodes of epistaxis, hemoptysis and a loud and the incidence of single fistula ranges from 42 to 74 percent.
pulmonary systolic bruit. At postmortem examination he was Most solitary fistulas are seen in bilateral lower lobes, the left
found to have multiple bilateral PAVMs. In 1917, Wilkins lower lobe being the most common location followed by right
described the necropsy findings in a 23-year-old woman with lower lobe, left upper lobe, right middle lobe and right upper
cyanosis, clubbing, telangiectasia and bilateral axillary bruits, lobe. Majority of multiple PAVFs are also confined to bilateral
who died from hemothorax after rupture of a PAVF into the lower lobes, the incidence of which ranges from 8 to 20 percent.2
pleural cavity. In 1938, Rhodes recognized the association Approximately, 50 to 70 percent of these fistulas are situated in
between telangiectasias and PAVF.3 Smith and Horton in the lower lobes. The size of the lesions vary from microscopic to
1939 made the first clinical diagnosis of PAVF in a 40-year- 1 to 5 cm.7
old man who had cyanosis, clubbing, bruit and polycythemia. Approximately, 75 percent of congenital PAVFs involve the
In 1942, Hepburn and Dauphinee reported the first case of lower lobes or right middle lobe. They usually occur without
3 coexisting congenital heart disease (CHD). Isolated exceptions vascular channels or a tangle of smaller vessels instead of
have been reported with left isomerism and atrial septal defect capillaries. They attributed the aneurysmal connection to
(ASD). Estimated minimal prevalence rate is 1 per 10,000 the transmission of arterial pressure directly through the
births.6 The incidence is 2 to 3/100,000 population. The male connection with the veins. It is suggested that all PAVFs begin
to female ratio varies from 1: 1.5 to 1.8 in various series.2 as plexus type connection for unknown reasons; aneurysms
The PAVFs are usually congenital in origin. However, arise by progressive dilatation of one or several limbs of a
they may be acquired in a variety of conditions such as small plexus.9
hepatic cirrhosis, schistosomiasis, mitral stenosis, trauma,
actinomycosis and metastatic thyroid carcinoma and even Morphology
after cavopulmonary anastomosis.4,5
The HHT is an autosomal dominant disease with frequency Morphologically PAVFs are divided into two types:
estimated at estimated as 1-2 per 100,000 persons. A wide 1. Localized lesions commonly occurring in HHT or isolated
geographic variation in disease prevalence is reported. It is PAVF.
genetically heterogeneous disease with at least 3 abnormal 2. Diffuse lesions occurring in patients with CHD, liver
chromosomal loci (9q, 12q, and a third locus). HHT gene disease, portal vein thrombosis and Glenn shunts.
has been identified as endoglin, a transforming growth factor PAVFs range from small pinpoint lesions (1 mm) to huge
(TGF) beta binding protein. Mutations in endoglin may alter tubular or saccular, multilobulated structures occupying most
cellular ability to bind TGF beta 1 with significant potential of a lobe or an entire lung. Lesions may be single or multiple,
consequences in cell regulatory mechanisms. Presumably the unilateral or bilateral. Small lesions tend to be multiple,
vascular abnormalities seen in patients with HHT may arise diffuse and located deep within the parenchyma. Larger
from such aberrations in endothelial cell regulations and malformations are usually isolated involving the subpleural
functions.8 regions of the lower lobes (65%). The airways and lung
parenchyma surrounding the malformations are normal.5
PATHOLOGY, PATHOPHYSIOLOGY AND
MORPHOLOGY Physiology
Pulmonary arteriovenous fistulas do not affect cardiac
Pathology hemodynamics.2 The PAVF creates a right to left shunt from
Anatomically PAVFs are dilated and aneurysmal vessels the pulmonary arteries to the pulmonary veins, resulting in
that directly connect pulmonary arteries to pulmonary veins systemic arterial desaturation and secondary polycythemia. If
and thus bypass the normal capillary bed, which results in the channels are small there is no significant shunting, cardiac
two important physiological consequences. First, right to output (CO) is not increased, plasma volume remains normal
left shunting occurs with the degree of shunt related to the and the pulmonary blood flow and pressure are unchanged.
number of PAVFs and their size. Second, the pulmonary The total pulmonary vascular resistance is normal, resistance
capillary bed normally acts as a filter for venous blood, blood within the arteriovenous fistula is low, but resistance in the
flowing through the PAVM bypasses this filtering process other lung segments may be elevated two-fold. Since normal
and acts as a conduit through which paradoxical systemic pulmonary artery resistance is low, the arteriovenous fistula
embolism can occur. The abnormal vascular architecture shunt does not significantly reduce the overall pulmonary
of PAVMs, their resultant right to left shunting and the vascular resistance. Because emboli and bacteria can pass
associated impairment of pulmonary filtering capacity leads directly through the fistula in to the systemic circulation,
to recognized complications including pulmonary vascular stroke and brain abscess are well-known complications.5
hemorrhage, hypoxemia and neurological sequelae.8 The The degree of shunt determines the clinical effects on the
histopathology is structural heterogeneity in the arterial and patient. If shunting is minimal the symptoms are subacute
venous components. Degenerative changes and aneurysm or absent. If right to left shunt is greater than 20 percent of
formation may be associated with vessel wall rupture. systemic CO or there is reduced hemoglobin more than 50
Patients may have hemoptysis, hemothorax and pulmonary g/L the patient will have obvious cyanosis, clubbing and
hemosiderosis.5 In a case of a surgically resected PAVF, the polycythemia. In some cases of HHT cyanosis may be hidden
pathological findings were reported as lung tissue with focal by anemia caused by epistaxis or gastrointestinal bleed. The red
abnormal proliferation of vascular channels with thick walls, cell mass and blood volume are usually increased, while plasma
along with diffuse congestion and alveolar hemorrhage of volume is normal. The peripheral oxygen saturation is low and
surrounding lung tissue and diffuse interstitial angiomatosis.7 as expected does not normalize with 100 percent oxygen.2
Mayor et al after review of 7 out of 15 pathologic specimens A high percentage of patients with PAVFs demonstrate
described distended afferent and efferent arteries and veins orthodeoxia (greater hypoxemia, while in sitting or standing).
244 with either a direct connection through one or several large This is due to the basal location of most PAVFs, because of the
gravitational shifts of pulmonary blood flow to the base of the Physical Signs 17
lung, when assuming erect posture. The tendency for increased
shunting and cyanosis with age is not well-understood. Many Abnormal physical findings occur in 75 percent of patients.
Congenital Pulmonary Arteriovenous Fistula

factors have been implicated including an increased number Superficial telangiectasia can be seen in associated HHT. Groups
of intravascular communications, opening of previously of tiny ruby lesions on the nasal and oral mucous membranes,
unfilled channels, dilatation of existing communications or face, tongue, skin, retina, nail beds occur and they blanch with
progressive polycythemia.5 pressure and bleed with minor trauma. Examination of the
arterial pulse and precordium is unremarkable. Common signs
SIGNS and SympTOMS 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.
Symptoms
The bruit increases on inspiration and the Müller maneuver
Pulmonary arteriovenous fistulas may be asymptomatic in 13 and decreases on expiration and with the Valsalva maneuver2.
to 55 percent of patients. The classic triad of dyspnea, cyanosis The bruit may be absent if the lesion is deep inside or small
and clubbing is found in 10 to 30 percent of patients.5 In or diffuse.6 The accentuation of a bruit by deep inspiration is
asymptomatic patients PAVM can be less than 2 cm size and due to the increased blood flow through the lesion.5 Standing
the amount of right to left shunting is low. In early adult life increases the murmur of fistulas situated in the lower lobes and
cyanosis, clubbing and polycythemia appear. Cyanosis can be the lateral decubitus position decreases the murmur, because
present from infancy, but in HHT blood loss and the resulting of compression. Pregnancy also decreases the murmur by
anemia may mask the cyanosis. In asymptomatic patients the compression of the lower lobe fistulas. Cyanosis will be
diagnosis is often made by chest X-ray or abnormal oximetry.5 absent, when systemic arteries rather than pulmonary arteries
PAVF affects both the sexes equally6, but the association with feed the fistulas.6
HHT is more in women.8 Fistulas increase in size and number
as age advances. The mean age of presentation is 39 years (age Investigations
range 3–73 years).6 Symptoms include dyspnea (37%–67%),
hemoptysis (13%) and hemothorax (9%). Hemoptysis is due Many major complications of PAVF’s including stroke, brain
to the rupture of the thin-walled PAVF. Chest pain may be due abscess and hemoptysis can be prevented if detected early.
to the subpleural arteriovenous malformation rupture causing All persons of HHT should undergo screening for PAVF’s and
hemothorax. Associated HHT can lead to nose bleeds, hematuria, need monitoring and if the feeding vessel is more than 3 mm
vaginal and gastrointestinal bleeds.5 Dyspnea and fatigue may in diameter, in a symptomatic person, treatment is indicated.
be due to anemia secondary to bleeding telangiectasia. Because PAVF’s tend to grow overtime, rescreening is reco
Neurological symptoms occur in 43 to 67 percent2 and mmended every 10 years.8
include migraine headache (43%), seizures, speech disorders,
ocular disturbances and numbness. Transient ischemic attacks Chest Radiography
(TIA) occur in 37 percent and stroke in 18 percent due to
paradoxical embolism. The risk of stroke is 1.5 percent per Chest radiograph is an important diagnostic tool (Figures 1
year. Occasionally, cerebral abscess (9%) and seizures (8%) and 2A). If PAVF’s are small or microvascular, retrocardiac,
can occur.2 The causes are multifactorial and include systemic or at costophrenic angles, they may be missed on X-ray. It has
hypoxia, polycythemia, small vessel thrombosis and recurrent sensitivity of 83 percent and specificity of 92 percent and a
cerebral hemorrhage.5 Cerebral symptoms may be brief or low negative predictive value.8 The lesion is often seen as a
prolonged, isolated or recurrent and tend to have similar lobulated, round or oval sharp mass of uniform density, 1 to 5
pattern during subsequent attacks.6 cm in diameter, connected to the hilum and often situated in
Pregnancy can precipitate symptoms because of vasodilation lower lobes.2 About 50 percent of patients have 2 to 8 lesions
and they can resolve after delivery. Pregnancy can have favorable and may appear like lung nodules.4
effects by compressing lower lobe fistulas by elevation of Higgins and Waxier have classified PAVF’s radiographi-
diaphragm.6 Pulmonary hemorrhage is common during the 3rd cally as solitary, multiple of different sizes and diffuse (tel-
trimester of pregnancy. Platypnea (dyspnea in upright position) angiectatic), which appears to be appropriate in both children
and orthodeoxia (oxygen desaturation in upright position) are and adults.9
less common than exertional dyspnea and may be related to the
predominance of PAVF in basal portions of lungs.8 Pulse Oximetry
The severity of symptoms usually depends on the size of
the lesions. If the size is more than 2 cm, dyspnea, palpitations, Pulse oximetry is non-invasive, inexpensive, safe and useful
fatigue, epistaxis and hemoptysis can occur and cyanosis may to detect hypoxia and orthodeoxia. However, a normal result
be present.7 does not rule out PAVF.8 245
3 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
PAVF’s.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 PAVF’s. 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 Radionuclide Imaging
Radionuclide imaging is a useful adjunct in diagnosis
Electrocardiography and quantification of PAVF. Right to left shunting can be
demonstrated by ventilation perfusion scan of lung. Ordinarily,
Electrocardiography is usually normal because hemodynamic 95 percent of technetium labeled macroaggregated albumin is
burden is modest in PAVF.6 trapped in the pulmonary capillary bed. In right to left shunting
particles elude pulmonary microvasculature, with radio labeled
Arterial Blood Gas Analysis with Shunt Study macroaggregates subsequently appearing in the brain and
kidneys. Quantification of shunt fraction may also be done, but
Normally, less than 5 percent of the cardiac output bypasses does not differentiate intrapulmonary from intracardiac shunts.8
the pulmonary circulation. In PAVF’s the percentage of blood A positive result is not specific, but a negative result excludes the
shunted can be estimated using arterial blood gas (ABG) diagnosis. It is not employed routinely as it is expensive and has
measurement. In a sitting position patients are given 100 percent limited availability, which prohibits its widespread use.2
oxygen for 20 minutes through a mouthpiece. Normal persons
have arterial oxygen content (PaO2) of 600 mm Hg at the end of High Resolution CT Scan
20 minutes. In PAVF’s it decreases to less than 600 mm Hg. The
percentage of shunt can be calculated based on the measured High resolution CT scan is a non-invasive imaging modality.
arterial oxygen level. A shunt fraction of equal to or greater than It is useful for the structural description of PAVF’s like
A B C
246
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
morphology, size and number of vascular lesions. It is 17
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 PAVF’s8
and is significantly better than conventional angiography
in detecting PAVF’s (98 vs 60 percent).2 Contrast enhanced
CT can nicely illustrates the PAVF with its communication
(Figures 3A and B).
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 PAVF’s
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
Figure 3B: Contrast enhanced computed tomography showing
are difficult to interpret. Other limitations include limited
pulmonary arteriovenous fistula with its communication at the hilum
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 and it may reveal other unsuspected PAVF’s and intrathoracic
utilized. Phase contrast cine sequences are most accurate in and extrathoracic vascular communications. However, it is
detecting PAVF’s. MR Angiography may be used to define the an invasive procedure using contrast and should be done by
vascular anatomy of a PAVF.4 experienced hands. Super selective pulmonary angiography
should be performed to evaluate all segments of both lungs.
Angiography Angiography has high specificity, but lower sensitivity than
ultra fast CT or 3D CT and may miss smaller PAVF. However,
Despite its lower sensitivity, angiography is the gold standard most of smaller fistulas may be clinically insignificant. Digital
for the diagnosis of PAVF and is necessary in most cases to subtraction angiography (DSA) has to some extent, replaced
confirm the diagnosis. A detailed angiographic evaluation of conventional angiogram, but its sensitivity is lower than that
morphology of vascular lesions including the complexity and of contrast enhanced ultra fast CT scanning or 3D spiral CT
size of feeding vessels is useful prior to embolization or surgery scanning.4
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

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 PAVF’s and
who develop signs and symptoms of right to left shunting 247
Figure 3A: Contrast enhanced computed tomography showing
pulmonary arteriovenous fistula like dyspnea, fatigue, exercise intolerance or cyanosis and
3 who anticipate pregnancy, need treatment. Asymptomatic in isolated fistula, which is recommended in patients with
patients without hypoxia and with a feeding vessel diameter permanent bleeding secondary to intrapleural rupture or
less than 3 mm are usually monitored at least every 3 years. hemoptysis despite embolization. Morbidity, mortality and
Follow-up in this population is necessary as more than half of recurrences are low. Since most fistulas are subpleural, they
PAVF’s appear to increase in size over time. Pregnancy with are curable by resection.7
PAVF has high risk of maternal complications as the fistula Transcatheter coil/vascular plugs/and device embolization
size increases, because of vasodilatation or other hormonal has become the treatment of choice in multiple and bilateral
influences and hence increases risk of complications including arteriovenous fistulas, which are not suitable for surgery
worsening right to left shunt, pulmonary hemorrhage and (Figures 4A and B). This can also be done in patients as also in
stroke. Morbidity associated with untreated PAVF is up to 50 patients in whom thoracotomy and general anesthesia would
percent compared to about 3 percent in treated patients.10-12 carry a high risk due to massive shunting. In 1977, Portsman
Mortality figures range from 0 to 55 percent in various used home made metal coils, followed soon after by stainless
studies. The purpose of treatment is to reduce neurological steel coils and detachable balloons for embolotherapy.
complications, prevent progressive hypoxia and high output Through refinements in interventional equipment and techni
cardiac failure. Development of new symptoms at any time ques, embolization results have progressively improved. To
should prompt a re-evaluation.8 avoid device embolization (through the PAVF into systemic
circulation) transcatheter occlusion of the afferent artery or
TREATMENT fistula is done using an umbrella, coils or plugs rather than
liquid adhesives or beads. The Amplatzer vascular plug is a self-
Goals of therapy include relief of symptoms of dyspnea expandable, cylindrical device made from a nitinol wire mesh.
and fatigue, prevention of complications like hemoptysis The device is secured on both ends with platinum marker bands,
and hemothorax and prevention of sequelae of paradoxical especially designed for arterial and venous embolizations in
embolization including stroke and brain abscess. An attempt the peripheral vasculature. Various sizes of vascular plugs are
to raise the PaO2 to 60 mm Hg or higher, which represents available measuring from 4 to 16 mm (Figures 5A and B).
SaO2 of 90 percent. Excellent results have been achieved with embolotherapy and
Most patients with one or more PAVF’s are candidates the goal is to occlude all afferent arteries more than 3 mm in
for resection of the lesion. Asymptomatic patients or those diameter and to raise the systemic arterial oxygen saturation.
with small lesions (10–15 mm) or who have a small shunt The advantages of embolotherapy over surgery are that it avoids
are not treated, though their condition is followed regularly.7 thoracotomy and general anesthesia and multiple lesions can
An intervention is necessary in all symptomatic patients be embolized without significant loss of lung tissue. It appears
even with mild symptoms, whose lesions are visible in chest to be a durable form of treatment. In a series of 46 patients with
X-ray or CT scans. Excision is a highly successful procedure 82 PAVF’s followed for 2 to 4 years after embolotherapy, only
A B
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
248 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

A B C D
Figures 5A and B: A. Vasular Plug; B. Vasular Plug II; C. Vascular Plug IV; D. Diagrammatic representation of vascular plug in the vessel
Surgical Treatment
2 PAVF’s showed evidence of reperfusion. Even large PAVF’s
can be treated successfully with embolotherapy. In a series of The surgical treatment for PAVF’s is lobectomy, pneumon
45 patients with 52 PAVF’s with feeding arteries 8 mm or larger ectomy, subsegmental resection or ligation of the vascular
in diameter, all were successfully treated with embolization. pedicle feeding the PAVF. The first successful pneumonectomy
However, 15 percent required repeat embolotherapy for was performed in 1940 and the first segmental resection was
persistence of PAVF or recanalization after treatment.8 In 76 performed by Blalock in 1947. Current surgical treatment
adult patients, 276 PAVF’s were occluded providing persistent is segmental resection or lobectomy, removing the smallest
relief of hypoxemia, resolution of orthodeoxia and minimal amount of lung, while completely excising the PAVF. The
growth of small remaining PAVF’s. Some patients required operative mortality is 5 percent and the cure rate is 75 percent. In
multiple catheterizations.5 In another study done by White et infants or children surgical lobectomy may result in chest wall
al,9 patients with 91 PAVF’s were evaluated by super selective deformities, causing alterations in pulmonary mechanics. There
angiography and balloon embolotherapy was effective in is a long-term risk of developing arteriovenous malformation in
permanently obliterating the malformations in 14 patients contralateral lung.5
with rise in arterial PaO2 from 49 mm Hg to 65 mm Hg and Until 1978, surgical excision of solitary PAVF or the largest
in 3 patients it was not effective. Complex PAVF’s required PAVF’s in patients with multiple fistulas was considered the
occlusion of all feeding arteries.9 therapy of choice. Unfortunately in patients with multiple
Embolotherapy is successful in initially blocking the PAVF PAVF’s recurrences of symptoms occurred over 10 to 20
more than 95 percent of the time and has a low complication years as small PAVFs grew. In 1978, Tailor et al reported
rate. Depending on the size of the original PAVF, 5 to 15 successful embolotherapy using wool coils in a patient with
percent of the PAVFs may reopen over time and a new PAVF multiple PAVF’s. Despite complicating pulmonary infarction,
may grow. Therefore, it is very important to follow-up within 6 the patient recovered uneventfully with excellent results. In
months and then at least every 3 to 5 years to check the success 1980 additional PAVF’s were treated by coil embolotherapy
of the procedure.13 With the exception of diffuse PAVM’s, and balloon embolotherapy.9
embolotherapy results in improvement of oxygenation and Surgery is necessary in patients who fail to respond to
reduction in shunt fraction. Follow-up with chest X-ray/ embolotherapy, develop serious bleeding complications
CT scan, usually shows that lesions have disappeared in despite embolotherapy, have intrapleural rupture of the PAVF
1 year following embolotherapy. While a residual scar may or have untreatable contrast allergy and lesions not amenable
be seen in some patients, lack of radiological resolution to embolotherapy. Lung conservation resection, local resection
suggests recanalization of PAVM or inadequate embolization. or segmentectomy is the procedure of choice, whenever
Complications of embolotherapy are: possible. Staged bilateral thoracotomies were performed
1. Thrombosis, air embolism, arrhythmias. in a case of an extensive bilateral PAVF’s. Recently, video-
2. Pleurisy: It occurs in approximately 14 percent of patients. assisted thoracoscopy was employed in the resection of a
A delayed pleurisy 4 to 6 weeks later can also occur. small PAVF. Reported mortality is 0 percent after 1960.2 As
Paradoxical embolization occurs in less than 1 percent of with embolization it is important to follow-up these patients
patients.8 every 3 to 5 years to check for growth of new PAVF’s.13
In summary embolization has minimal morbidity and no
mortality and hence radiological intervention is the first choice CONCLUSION
of treatment in PAVF. Embolotherapy is a suitable alternative
to surgical interventions in the elderly, who are poor surgical Pulmonary arteriovenous fistula is an unusual clinical
candidates, in patients with multiple lesions and patients, who problem, which should be considered, when a suspected 249
decline surgery.2 case of cyanotic CHD is normal on clinical examination or
3 in symptomatic patients with the triad of exertional dyspnea, 3. Rodes CB. Cavernous hemangiomas of the lung with secondary
polycythemia. JAMA. 1938;110:1914-15.
cyanosis and clubbing with normal cardiac examination.
In such cases when cardiac findings are normal one should 4. SatSharma. Imaging in Artereovenous lung Malformations.
suspect PAVF. A diagnosis of HHT has to be kept in mind eMedicine.medscape.com/article/356824-overview.

5. Ronald GG, Preminger TJ. Vascular Anomalies: Pulmonary
in all PAVF’s with mucocutaneous telangiectasia. These
arterial malformations. In: Hugh DA, David JD, Robert
patients should be monitored and treated promptly to prevent ES, Timothy FF (Eds). Moss and Adams’ Heart Disease in
potential complications of paradoxical embolism, hemoptysis, Infants, Children, and Adolescents: Including the Fetus and
endocarditis and cerebral abscess. Once diagnosed, the lesion Young Adults. 7th edn, Lippincott Williams and Wilkins;
morphology and the degree of the shunt should be assessed by 2008;1:720-5.
appropriate imaging methods and treated with embolotherapy 6. Congenital Pulmonary AV fistula. In: Perloff JK, Marelli
or surgery wherever indicated. All patients with PAVFs who A (Eds). Perloff’s Clinical recognition of congenital heart
are symptomatic need intervention, the nature of which disease. 6th edition. Philadelphia: Saunders/ElsevierInc; 2012.
may depend on the morphological features of the lesions. pp.513-21.
7. Pelijan S, Rahmanijoo N, Farzanegan R, et al. Surgically treat-
Embolotherapy if available is a relatively safe and an effective
able pulmonary arteriovenous fistula. Ann Thorac Cardiovasc
procedure and preferred treatment for PAVF. Lung conserving Surg. 2012;18:36-38.
resection is an optimal treatment for symptomatic patients, 8. Lynn TT, White RI Jr. Pulmonary arteriovenous Malformations.
when embolotherapy is not feasible. Regular follow-up is PCCU (Pulmonary and Critical Care Update); A publication of
needed to detect recurrences of the lesions. American College of Chest Physicians; Lesson 10 Vol 13.http://
www.chestnet.org/downloads/education/online/Vol13_10_12.
Heart one of the most wonderous features of animate pdf.
nature is surely the most perfect harmony existing between 9. White RI Jr, Mitchell SE, Barth KH, et al. Angio architecture
structure and function. of pulmonary arteriovenous malformations: an important
consideration before embolotherapy. AJR Am J Roentgenol.
—John Hunter
1983;140:681-86.
10. Dines DE, Arms RA, Bernatz PE, et al. Pulmonary arteriovenous
Acknowledgment fistulas. Mayo Clin Proc. 1974;49:460-65.
11. Sluiter-Eringa H, Orie NG, Sluiter HJ. Pulmonary arteriovenous
We wish to thank Dr IB Vijayalakshmi, Professor of Pediatric fistula. Diagnosis and prognosis in noncomplaint patients. Am
Cardiology, for sharing some of her images. Rev Respir Dis. 1969;100:177-88.
12. Puskas JD, Allen MS, Moncure AC, et al. Pulmonary
arteriovenous malformations: therapeutic options. Ann Thorac
References Surg. 1993;56(2):253-7; discussion 257-58.
13. Gossage J. Overview Pulmonary (Lung) Arteriovenous Mal
1. Stringer CJ, Stanley AL, Bates RC, et al. Pulmonary
forma tions. 2012: Georgia Health sciences University. http://
arteriovenous fistula. Am J Surg. 1955;89:1054-80.
www.georgiahealth.edu/medicine/medicine/pulmonary/pvd/
2. Khurshid I, Downie GH. Pulmonary arteriovenous malfor
hht/pavm.html.
mation. Postgrad Med J. 2002;78:191-97.
250
Sec t i on
Shunt Defects
c hapter
18 interatrial Defects
Shada J Al-anani, Ziyad M Hijazi
introDuction flap to the crescent shaped septum secundum. Probe PFO is

known to occur in 25 percent of normal subjects beyond the
Interatrial defects are amongst the most common congenital 1st year of life.5
heart disease encountered at all ages. These defects are defined Secundum ASD occurs secondary to deficiency of the
as any opening between the two atria other than a competent septum primum (the valve of fossa ovalis) in the majority
foramen ovale.1 The true incidence of interatrial defects is of cases and rarely due to deficient septum secundum
underestimated due to high rate of early spontaneous closure counterintuitively. From this we can differentiate between
and the delay in presentation into adulthood due to subtle signs the PFO and secundum ASD with the latter being larger
and symptoms.2 Isolated secundum atrial septal defects (ASD) and unguarded by the valve effect of the septum primum
constitute 6 to 10 percent of all congenital heart defects, with apposition to the septum secundum. Secundum defects
a female preponderance of 2 : 1 ratio.3 There have been major comprise 70 percent of ASD and are seen at fossa ovalis
advances in the approach and management of such lesions in position (Figure 1).
the last decade. Septum primum is lined by endocardial cushion cells early
In this chapter, we will discuss pathology, natural history in fetal life and so primum ASD are acquired due to abnormal
and clinical presentation of such defects. In addition, relevant formation of the endocardial cushions. These are considered
investigation and management both surgical and catheter to be part of the atrioventricular (AV) canal defects and are
based interventions. associated with cleft mitral valve.6 They are usually located in
anteroinferior location relative to the fossa ovalis (Figure 1).
PAtHoLoGY Other less frequent types of ASD are sinus venosus
defects which include superior vena cava (SVC) and rarely
Anatomically the atrial septum not only separates the two inferior vena cava (IVC) type and coronary sinus defects.
atria ASD but in part separates the right atrium from the left These defects are not true ASDs, but rather a consequence of
ventricle. abnormal development of the embryologic venous tributaries;
Embryologically interatrial communication is vital for the right venous horn (sinus venosus defects) or the left sinus
survival during fetal life. Septum primum initially separates venous horn (coronary sinus defects).
both atria anteroinferiorly, lined by endocardial cushion cells. Sinus venosus defects (4–11%) SVC type is a result of
In order to maintain this mandatory interatrial communication, straddling of the right upper/middle pulmonary vein opening
cribriform perforations in the septum primum are later formed to the right atrium leading to a form of partial anomalous
joining together into ostium secundum (fossa ovalis). venous return ASD.7 This type of ASDs lack superior
Septum secundum, on the other hand, develops through boundaries and relates directly to the ostia of the SVC
enfolding of the roof of the atrium to the right of septum and the pulmonary veins. They are seen superior and posterior
primum, the leading margins of septum secundum constitutes to fossa ovalis. The IVC type of this defect is rarely seen
what is called the superior limbus of fossa ovalis.4 (Figure 1).
This embryological evolution of the atrial septum leads Coronary sinus defects are infrequent (< 1%) and they are
to a better understanding of the current classification of the due to defect in the wall that separates the coronary sinus from
interatrial communications. Patent foramen ovale (PFO) is the left atrium and ultimately leads to inter atrial mixing, this
the persistence of this fetal communication due to failure of is usually seen as dilated coronary sinus opening into the right
the functional and anatomic apposition of the septum primum atrium and is often associated with persistent left SVC.7
4 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
Shunt DefectS
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
figure 1: Different types of atrial septal defects from the right atrial ASD and younger age at diagnosis were both independent
view. Note: The position of each defect to fossa ovalis. AO = Aorta; predictors of spontaneous closure. ASDs 4 to 5 mm in diameter
CS = Coronary sinus; IVC = Inferior vena cava; PA = Pulmonary artery; at diagnosis showed spontaneous closure or regression to
RA = Right atrium; RPV = Right upper pulmonary vein; RV = Right a diameter less or equal to 3 mm in 86 percent of the cases
ventricle; SVC = Superior vena cava; SVD = Sinus venosus defect
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
GEnEticS device closure.14
Another question that was answered by a study by
The genetic basis of the ASD is not completely understood. McMahon et al15 whether ASD can with time enlarge in
In the majority of cases this is a sporadic lesion, yet some size or not. 104 children older than 4 years with ASD were
homebox gene defects have been found to explain some of followed up for 3 years. In 65 percent of patients the defects
the well-known familial cases with ASDs, such as NKX2- enlarged, some to the extent that they could not be closed by
chromosome 5, which has an autosomal dominant inheritance transcatheter techniques at that time.
and AV conduction defect.8 In summary, defects larger than 8 to 10 mm are less likely
Identification of ASD or other congenital heart defects to close spontaneously and most likely will require surgical
in more than one family member should prompt clinical or transcatheter closure, regardless of the age at diagnosis.
evaluation of all relatives.9 On the other hand, ASDs diagnosed after the first 4 years of
Other genetic syndromes with skeletal abnormality such life are less likely to spontaneously close and they can present
as Holt-Oram syndrome, which is caused by mutations in the later in life with several complications.
transcription factor TBX5, essential in the development of We will discuss below possible the complications that can
both the heart and upper limbs.10 ensue from interatrial communications.
Atrial septal defects can be part of many other syndromes
and more complex congenital heart diseases. Down syndrome complications
is associated with both primum and secundum ASD, while
Noonan syndrome most commonly is associated with
Symptoms of Exercise Intolerance and Fatigue/
secundum ASD and pulmonary valve stenosis.
Congestive Heart Failure
nAturAL HiStorY Although congestive heart failure is an uncommon presentation
in childhood, these symptoms are common among older
Secundum ASDs have been clinically described as early as patients. Craig and Selzer in an early series of adult patients
1900.11 Several studies were conducted to find the outcome of with ASD found that incidence of symptoms increases from
such common defects looking for the criteria that could predict 14 percent at 20 to 40 years to more than 24 percent between
spontaneous closure and the incidence of complications later 40 to 60 year. Exertional dyspnea can reach up to 75 percent
254 in life. in patients in their 6th decade.16,17
Atrial Arrhythmias dependent on not only the size of the defect, but also on the 18
relative difference in the gradient between the two atria, which
Right atrial dilation secondary to chronic stretching and volume is a mere reflection of the end-diastolic pressure difference
InteratrIal DefectS
overload predispose older patients to atrial arrhythmias such between the two ventricles when both AV valves open in
as atrial fibrillation and less commonly atrial flutter, this can diastole.
exacerbate sign and symptoms of heart failure. They are one This explains the timing of presentation for large shunts in
of the common presenting symptoms in the 4th to 5th decade infancy, which usually occurs between 6 to 8 weeks. At that
of life. Incidence can reach up to 52 percent in patients older point, the pulmonary vascular resistance drops to its normal
than 60 years of age.18,19 levels and the right ventricle becomes more compliant,
leading to increase pressure gradient between the two atria
Fixed Pulmonary Hypertension and subsequently a larger shunting volume. On the other
hand, later in life the left ventricle becomes more stiff perhaps
Pulmonary vascular disease is one of the most serious secondary to aging and ischemic changes and so the size of the
complications of ASDs, rendering the disease to be inoperable. shunt also increases, which might explain that most patients
Fortunately, this is not common at young age (14 to 18% with ASDs present in their 4th to 5th decade.16,17 Symptoms in
between 20–40 year of age)16 and occurs more frequently this age group include fatigue, dyspnea on exertion, peripheral
in female patients. It is still debatable whether this is caused edema and other symptoms of heart failure. This is rarely the
by the presence of large shunts or due to other predisposing case in children, where congestive heart failure or failure to
conditions such as thromboembolic phenomena.20 Severe form thrive are very uncommon.
of pulmonary hypertension leading to cyanosis as a result of Cyanosis as a result of right-to-left shunting can be due
reversal of the shunt (Eisenmenger syndrome) is infrequent and to high pulmonary vascular resistance (pulmonary vascular
usually present late in life. Konstantinides et al reported a mean obstructive disease) at an old age, but it also might be
age of 56 years.17 Sinus venosus defects patients are more prone secondary to direction of deoxygenated blood from the
to develop pulmonary hypertension at an earlier age, therefore, IVC through prominent eustachian valve or thebesian valve
close follow-up and early repair is warranted in this subset of through the defect to the left atrium. Differentiation between
patients.21 these two phenomena is crucial for future management.
Most of the time physical examination is unremarkable, typ-
Systemic Embolization ical physical findings include normal oxygen saturation, apart
from aforementioned conditions. Other findings include wide
The existence of a potential right-to-left shunt through fixed splitting of the second heart sound, which is an exaggera-
interatrial communication carries the risk of paradoxical tion of a normal phenomena that leads to delay in closure of the
embolization. This was confirmed by comparative studies pulmonary valve as a reflection of the dilation of the pulmonary
that found existing risk even in patients who do not have artery that warrants longer time to achieve adequate pressure to
atrial arrhythmias.17 The hazard of cardiogenic event such as close the pulmonary valve, other factors that explain this, is the
cryptogenic stroke increases dramatically in situations where prolonged emptying of the right ventricle.
the right atrial pressure increases such as in pregnancy and Auscultatory findings also include soft crescendo-
scuba diving. decrescendo ejection systolic murmur on the left upper sternal
border as a result of pulmonary blood overflow across that
Reduced Life Expectancy valve and a mid-diastolic murmur at the lower left sternal
border related to increased blood flow across the tricuspid
Secondary to pulmonary arterial thrombosis, congestive valve in larger shunts.
heart failure, paradoxical embolism and recurrent respiratory Once pulmonary hypertension develops these findings
infections. It is difficult nowadays to estimate age of survival completely change to a cyanotic patient with prominent
in patients with unrepaired ASDs in the modern era of surgical second heart sound, short systolic murmur and absent fixed
and catheter interventions. One study estimated the mortality splitting or diastolic murmur.
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 rELEvAnt invEStiGAtionS
cLinicAL PrESEntAtion chest X-ray

Patients with ASDs are usually asymptomatic early in life. Prominent pulmonary artery, hilar vessels and increased
In fact, most children present with a murmur on incidental pulmonary vascular markings point out to a large left-to-
cardiac examination or when they are referred for cardiology right shunt. Enlarged cardiac silhouette can also be seen as a
consultation for other purposes. Clinical characteristics consequence of prolonged volume overload to the right atrium 255
depend mainly on the magnitude of the shunt. Findings are and ventricle.
4 This indeed is not seen in case of pulmonary obstructive landmarks and other associated lesions should be also sought.
disease; on the contrary, the lung fields at that point would be In addition, looking for hemodynamic consequences of large
oligemic. shunts, mainly right atrial and ventricular dilation, flattening
Shunt DefectS
of the ventricular septum (Figures 3A to F).

Electrocardiogram It is prudent to avoid false drop out that may be confused
with a true ASD. This is achieved by finding the best view
Three points has to be kept in mind, while looking at an where the echo beam is perpendicular to the defect.
electrocardiogram in patients with ASDs: rhythm, AV The subcostal view is perfect for PFO and secundum atrial
conduction and signs of right-sided volume overload. defects using color Doppler for confirmation. Identification of
In most instances the rhythm is normal sinus, but sometimes the rims is very important for catheter-based interventions. For
and especially at an older age there might be evidence of atrial that, sagittal view provides good assessment for superior and
fibrillation or atrial flutter. Low atrial rhythm (negative P inferior rims. In this view also, close attention should be paid
wave) might point to a sinus venosus defect. to the insertion of the right upper pulmonary vein and SVC.
First degree AV block can be seen at older age secondary Absence of the wall between these two structures constitutes
mostly to interatrial delay. Occasionally complete heart block the major diagnostic finding in sinus venosus defect–superior
can be found in familial ASD. type (Figures 4A to C).
Peaked tall P wave as can be seen in right atrial dilation, Apical 4-chamber view, on the other hand, has a high rate
while right ventricular volume overload may manifest as of false drop out and is therefore inappropriate for diagnosis
rSR’ pattern (incomplete right bundle branch block) in leads of ASDs. However, it is appropriate for evaluation of right
V1 to V3. This is usually seen with right axis deviation ventricular dilation and estimation of right ventricular systolic
between 95 to 170°. If left axis deviation is found then primum pressure using tricuspid regurgitation jet.
ASD should be highly suspected (Figure 2). Parasternal short-axis view might offer an alternative
Exercise stress test are not required as part of a regular for the subcostal view in the adult population, high right
assessment of ASDs, unless there is inconsistency between parasternal view in right decubitus position is particularly
the symptoms and the clinical findings. Maximal exercise useful. PFO, sinus venosus defect can be readily identified in
testing is contraindicated in severe pulmonary hypertension.23 this position. In addition, parasternal short-axis view is the
proper view for evaluation of anterior (aortic) and posterior
Echocardiography 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
Transthoracic 2D Echocardiography
ventricle. Looking for the defect posteroinferiorly in the
Transthoracic 2D echocardiography (TTE) is the principal subcostal view shows the defect just above the right atrium and
tool in the diagnosis and follow-up of patients with interatrial IVC junction with intact foramen ovale. Sometimes mistaken
communication especially in children and thin adults where as septum primum defect, evidence of left SVC and absence
the acoustic windows are clear. Confirmation of location and of cleft mitral valve should prompt the diagnosis (Figures 5A
the size of the ASD from several views is necessary. Anatomic 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
256 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
a B c
D e f
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
a B c
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
4
Shunt DefectS
a B
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 required for TEE and provides high-resolution intracardiac
for accurate evaluation of the hemodynamics too determine images for the defect, its rims and adjacent structures.
the direction of flow of the shunt, mean gradient across the
septum between the left and right atrium, estimation of the 3D Echocardiography
right ventricular systolic pressure using tricuspid velocity jet
and the acceleration of pulmonary blood flow. 3D transesophageal echocardiography has an outstanding clear
image with spatial relationship to surrounding landmarks. It is
Contrast Echocardiography useful especially when attempting to close multiple defects
percutaneously (Figures 7A and B).
Verification of the presence of interatrial communication can
sometimes be challenging, particularly if the defect is small cardiac ct scan and cardiac Mri
or the acoustic windows are not optimal in older adults.
Peripheral intravenous line can be used to inject agitated The use of cardiac computed tomography (CT) and cardiac
saline using a three-way stopcock, while imaging the atria in magnetic resonance imaging (MRI) is not routine in evaluating
4-apical view. Air bubbles should opacify the right atrium, ASDs. These non-invasive techniques are reserved for complex
negative wash out will be seen in the case of left-to-right shunt. atrial defect anatomy. They provide wide field view with
This technique is used more frequently to look for presence of detailed resolution of the defect and the adjacent structures,
right-to-left shunt at rest or during Valsalva maneuver. It is specifically the pulmonary veins without the limitation of poor
confirmed by the passage of the micro-air bubbles into the left acoustic windows sometimes encountered in echocardiography.
atrium through a PFO. Cardiac MRI has the advantage of accurately estimating
right ventricle volume and even the shunt size (Qp : Qs ratio)
Transesophageal 2D Echocardiography thus offering better physiological understanding of the defect.
On the other hand, MRI cannot be performed in patients who
Transesophageal echocardiogram, is used in adult patients have pacemakers or coils and it also requires sedation in
whom the transthoracic acoustic windows are not optimal. It is young patients.
valuable in determining the ASD size, rims and the pulmonary
venous drainage. It is also used to guide transcatheter device cardiac catheterization
closure (Figures 6A to F).
The role of cardiac catheterization in ASD has changed
Intracardiac Echocardiography considerably over the past years from a diagnostic tool to
more of an interventional function.
Another valuable guiding tool for transcatheter device closure Nevertheless the indications for diagnostic cardiac
258 of ASD using a small disposable imaging catheters in the catheterization are to calculate pulmonary vascular resistance
interventional suite. It obviates the need for general anesthesia and to assess the reactivity of the pulmonary vascular bed
18
InteratrIal DefectS
a B c
D e f
figures 6a to f: 2D Transesophageal echocardiogram of secundum atrial septal defect: A and B. Mid-esophageal 4-chamber view (0°–20°) 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 (30°–40°) 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 (90°–100°): 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 • Equal pressure in both atria in large shunts
include partial anomalous pulmonary venous return where • Normal to mild elevation of right ventricular pressure
non-invasive data are nonconclusive for the course of these • Normal to mild elevation of pulmonary artery pressure
veins and their drainage.23 • Pulmonary vascular resistance should not exceed 4 Woods
Rarely, hemodynamic significance of atrial defects cannot units
be determined by echocardiography. Otherwise, hemodynamic • Unless there is pulmonary hypertension (Figure 8).
study is performed as part of an interventional procedure
during device closure of these defects. trEAtMEnt
Hemodynamic Changes Management questions arise when an ASD is found:

factors that should guide the decision to close such defects,
More than 5 percent (serial measurements) to 7-10 percent appropriate timing and the options for closure.
(one measurement) step up in the oxygen saturation is As it is the case in most congenital heart diseases, presence
expected from the SVC to the right atrium. of symptoms is certainly an indication for closure. This should,
however, be carefully understood in ASDs. Delaying closure
Differential Diagnosis until complications develops is not advisable. Thus, absence
of symptoms should not preclude closure, if other criteria are
Partial anomalous pulmonary venous return, left ventricle met.
to right atrial shunt (Gerbode defect), AV septal defects or Understanding the natural history of ASDs allows us to 259
ventricular septal defects (VSD) with tricuspid insufficiency. infer that size and age play major role in the management.
4
Shunt DefectS
a B
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
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.
figure 8: A diagrammatic view for oxygen saturation and pressure Patients with larger defects will suffer ultimately from
data of a 38-year-old patient found to have 27 × 29 mm ASD secundum complications later in their lives. For that reason, patients
260 defect. Qp : Qs ratio is 3.1 and pulmonary vascular resistance is 3.61
Woods units
who present with large defects (> 8 mm), large shunts (Qp : Qs
more than 1.5–2 : 1) or right ventricle volume overload with or explaining this phenomenon: one of which is right-to-left 18
without symptoms should be considered for surgical or device shunt secondary to redirection of the blood by the Eustachian
closure. valve and the thebesian valve into the left atrium through
InteratrIal DefectS
Clinical and laboratory findings of right ventricular volume PFO. This, however, should be confirmed with diagnostic
overload can manifest with physical findings of diastolic cardiac catheterization.
flow rumble due to tricuspid regurgitation, cardiomegaly and
increase pulmonary vascular markings on chest X-ray, signs- SurGErY
of right ventricular hypertrophy on electrocardiograms and
ultimately echocardiographic findings of right ventricular
History
hypertrophy with possible paradoxical wall motion of the
ventricular septum.23,24 Dennis et al25 in 1951 reported the first surgical attempt to
Unless the infant cannot be managed medically for signs close an ASD; although this was not a success story, dramatic
of congestive heart failure (which is quite unusual in this improvement in cardiopulmonary bypass technique later in
condition), closure is recommended after the 2nd year of life 1950s led to a safe surgical closure of ASDs in the current era.
in anticipation of spontaneous closure or decrease in size.
Development of inevitable sequelae of large shunts later in technique
life further complicates the management of older patients. Atrial
arrhythmias should not preclude the closure of large defects. This is achieved by direct closure of the ASD using pericardial
This, however, should be preceded by successful cardioversion or Dacron patches and sometimes stitch closure for PFO.
or ablation before the access to left atrium is closed.23 Associated anomalies should be identified prior to surgery:
A major complication, mainly encountered in adulthood is cleft in the mitral valve in septum primum defects should
pulmonary hypertension. Incidence of such complication is be repaired at the same time, while in sinus venosus defects,
variable among studies. Careful evaluation of these patients identification of right upper/middle pulmonary venous
should include cardiac catheterization to determine the drainage should be taken into consideration during surgery.
operability and risk of closure. It allows direct measurement of Transesophageal echocardiography in the operating room
the pulmonary arterial pressure and pulmonary vasoreactivity is mandatory to identify any residual shunt after closure and
test with oxygen or nitric oxide. to rule out any AV regurgitation prior to closure of the chest.
Balloon occlusion testing temporarily in the cardiac Minimally invasive surgeries nowadays avoid midster-
catheterization laboratory can provide insight to the risk of notomy approach using different less extensive incisions for
closure in patients with reversible pulmonary hypertension or cosmetic purposes.
bidirectional shunt or in patients whose response to medical
therapy for pulmonary hypertension is evaluated prior to Follow-up and outcome
closure of the defect.
Several studies tried to identify patients at high risk of Over the past decades several studies looked at the outcome
mortality and morbidity for shunt closure. Pulmonary vascular of patients with ASDs following surgical repair.One of the
resistance (PVR) of more than 15 Woods unit was found to be major findings was the excellent outcome and low operative
a strong mortality predictor by Steele and colleagues. Patients mortality especially at a younger age ranging between 0 to 1
with less severe hypertension (PVR of 7–9 Woods units) percent. Older patients (> 60 years) have, however, a higher
improved after surgery. General consensus is to avoid closure risk.26
in patients with PVR more than 8 Woods units or if pulmonary Operative morbidities include residual shunt due to
arterial pressure exceeds 2/3 systemic pressure, net right-to- incomplete closure of the defect. Postpericardiotomy
left shunt, no response to pulmonary vasodilator therapy and syndrome resulting in pericardial and pleural effusion.27 New
failed test occlusion.20,23 onset arrhythmia after surgical closure, stroke and acute left
Two points should be mentioned here. First: elderly patients heart failure in earlier series especially at old age.26,27 Sinus
who develop left ventricular diastolic dysfunction as a result venosus defect repair can be complicated by pulmonary
of ischemic heart disease, hypertension or acquired valvular venous or SVC obstruction. Sinus node dysfunction and AV
disease are considered a high risk for closure. Elevated left conduction delay requiring permanent pacemaker have been
ventricular end-diastolic pressure reflected by high pulmonary seen more in patients following sinus venosus repair (6%).28,29
wedge pressures should be anticipated. Adequate medical Childhood long-term outcome studies demonstrated no
treatment prior to closure of the defect and balloon test cardiovascular mortality, heart failure, stroke or pulmonary
occlusion before closing the defect are advised. hypertension in any patient for more than 25 years of follow-
Second: a rare condition is called orthodeoxia-platypnea. up. Risk of development of atrial arrhythmias was only 8
In this condition, despite the finding of cyanosis, closure of the percent. Long-term survival after surgical closure in childhood
defect is considered curative. There are different hypotheses showed that no change from the general population.30 261
4 This has not been the case in adult outcome series that lower mortality rate were noticed postoperatively in this group
showed higher incidences of adverse outcomes and decreased although they usually have an expected difficult immediate
life expectancy. Murphy et al31 in a follow-up study of postoperative course.20
Shunt DefectS
patients operated between 1956 to 1960 showed that survival

among patients younger than 24 years were no different from trAnScAtHEtEr cLoSurE oF AtriAL
rates among controls. Patients over 41 years of age, on the SEPtAL DEFEctS
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
History
main pulmonary artery before operation. Late heart failure, It has been more than 35 years since King and Mills33 first
stroke and atrial fibrillation were significantly more frequent described their double umbrella device closure of an ASD
in older patients thus requiring close follow-up.31 in 1976. Since then, major advancements in techniques,
Comparison between medical and surgical treatment in devices and outcomes were achieved. Currently, there are two
older individuals showed repeatedly better outcome in the devices approved for use by the United States Food and Drug
surgical arm of these studies improving survival, decreasing Administration (FDA) are the Amplatzer Septal Occluder
morbidity (recurrent pulmonary infection), increasing exercise device (St, Jude Medical, Plymouth, MN) (Figures 9A and
tolerance in this group of patients.17,32 B) and the Gore Helex Septal Occluder device (WL Gore and
This however has not been proven in preventing atrial Associates, Flagstaff, AZ), (Figures 10A and B).
arrhythmias. In fact, Berger et al19 showed atrial arrhythmias It was not until 2002 when the non-randomized multicenter
persisted in more than 48 percent after surgery in patients older study that compared percutaneous approach using Amplatzer
than 60 years which did not show significant improvement device in more than 400 patients to surgical approach
from incidence prior to surgery. They concluded that in this was reported. It demonstrated similar success rates, lower
group of high-risk patients (with atrial fibrillation) surgical complication rate and shorter hospital stay in the device
atrial closure should be combined with Cox-maze procedure. closure group versus the surgical repair group.34
Pulmonary vascular disease had been proven to be a strong Nowadays, transcatheter closure of septum secundum atrial
predictor of poor outcome after surgery. PVR higher than 15 defects and PFO is the mainstay of treatment for patients with
Wood units was shown to be associated with high mortality rate. suitable defects. Nevertheless, there are defects that are non-
Defects in patients with high PVR but less than 15 Wood units amenable to this approach in which surgery should be the
were partially closed, leaving a small residual shunt that allows appropriate option for closure. This includes, primum septal
decompression of the left atrium. Regression in symptoms and defects, sinus venosus and coronary sinus defects and defects
a B
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
262
Device Experience (MAUDE)/FDA have shown that mortality 18
with the Amplatzer device of less than 0.1 percent and rescue
operation was needed in 0.83 percent.35
InteratrIal DefectS
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
a 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
B
with impingement on surrounding structures, migration
figures 10a and B: Helex septal occluder device (WL Gore and after release, erosion to neighboring structures or cardiac
Associates, Flagstaff, AZ). The device can be seen mounted on the perforation are all rare incidents for which the patients are
preassembled delivery system. It is made of ePTFE patch material
supported by a single nitinol wire frame
observed for at least 24 to 48 hours after device closure.
The safe and effective nonsurgical option to close inter-
atrial defects should be assured by proper patient selection,
with associated anomalous pulmonary venous drainage. continuous assessment during device closure and close
Secundum atrial defects that are larger than 38 mm in diameter monitoring after deployment of the appropriate device.
or defects that have insufficient rims (< 5 mm) are also not
suitable for transcatheter device closure. concLuSion
Choice of the ASD that is amenable to transcatheter device
closure is a crucial step as is careful patient selection. High-risk Atrial septal defect is a common non-cyanotic congenital heart
patients include extremes of age: infants due to the need of large disease. Although usually carries benign course in childhood,
sheath size and risk of vessel injury and elderly patients with it has significant morbidity with advancing age. Closure of
left ventricular dysfunction. Other relative contraindications an ASD has certain indications. Safe non-surgical option via
include active infection, pregnancy, uncontrolled arrhythmias transcatheter closure is available for certain types of defects.
or conditions where antiplatelet therapy is not tolerated.
Genius is one percent inspiration and ninety-nine percent
technique perspiration.
—Aphorism
Technique of percutaneous approach includes hemodynamic
and echocardiographic assessment of the defect followed by AcknowLEDGMEntS
balloon sizing of the defect. Deployment of the device under
continuous echocardiographic guidance after selecting the The authors acknowledge Dr Qi-Ling Cao and John Bokowski,
appropriate type and size of the device. PhD, for their help in the echocardiography images in this
chapter.
Follow-up and outcome
rEFErEncES
Due to the relative short period, widespread use of
percutaneous approach of ASD closure follow-up data is 1. Porter C, Edwards W. Atrial Septal Defects. In: Moss and
limited. Nevertheless, the Manufacturer and User Facility Adams’ Heart Disease in Infants, Children, and Adolescent: 263
Lippincott Williams and Wilkins 2008:632-45.
4 2. Hoffman J, Kaplan S. The incidence of congenital heart
disease. J Am Coll Cardiol. 2002; 39:1890-1900.
21. Vogel M, Berger F, Kramer A, et al. Incidence of secondary
pulmonary hypertension in adults with atrial septal or sinus
3. Fyler DC. Atrial septal defect secundum. In: Nada’s Pediatric venosus defects. Heart. 1999; 82:30-33.
Shunt DefectS
Cardiology. Philadelphia: Hanley and Belfus; 1992:513-24. 22. Campbell M. Natural history of atrial septal defect. Br Heart J.
4. Anderson RH, Brown NA, Webb S. Development and structure 1970; 32:820-26.
of the atrial septum. Heart. 2002; 88:104-10. doi:10.1136/ 23. Warnes CA, Williams RG, Bashore TM, Child JS, Connolly
heart.88.1.104. HM, Dearani JA, del Nido P, Fasules JW, Graham TP, Hijazi
5. Hagen PT, Scholz DG, Edward WD. Incidence and size of ZM, Hunt SA, King ME, Landzberg MJ, Miner PD, Radford
patent foramen ovale during the first 10 decades of life: An MJ, Walsh EP, Webb GD, Smith SC Jr, Jacobs AK, Adams CD,
autopsy study of 965 normal hearts. Mayo Clin Proc. 1984; Anderson JL, Antman EM, Buller CD, Creager MA, Ettinger
59:17-20. SM, Halperin JL, Hunt SA, Krumholz HM, Kushner FG, Lytle
6. Van Mierop LHS. Embryology of the atrioventricular canal BW, Nishimura RA, Page RL, Riegel B, Tarkington LG, Yancy
region and pathogenesis of endocardial cushion defects. In: CW. Atrial septal defect. In: ACC/AHA 2008 guidelines for
Feldt RH, McGoon DC, Ongley PA (Eds). Atrioventricular the management of adults with congenital heart disease. Atrial
Canal Defects. Philadelphia; WB Saunders: 1976:1-12. septal defect. A report of the American College of Cardiology/
7. Weinberg P, Patel A, D’Alessandro L. Anatomy of the atrial American Heart Association Task Force on Practice
septum: transcatheterclosure of ASDs and PFOs. Minneapolis: Guidelines (Writing Committee to Develop Guidelines on the
Cardio text publishing; 2010:3-17. Management of Adults With Congenital Heart Disease). J Am
8. Schott JJ, Benson DW, Basson CT, Congenital heart disease Coll Cardiol. 2008; 52:e173-78.
caused by mutations in the transcription factor NKX2-5. 24. Driscoll, Allen HD, Atkins DL, et al. Guidelines for evaluation
Science. 1998; 281:108-11. and management of common congenital cardiac problems in
9. Benson DW, Sharkey A, Fatkin D, et al. Reduced penetrance, infants, children, and adolescents. A statement for healthcare
variable expressivity, and genetic heterogeneity of familial professionals from the Committee on Congenital Cardiac
atrial septal defects. Circulation. 1998; 97:2043-48. Defects of the Council on Cardiovascular Disease in the Young.
10. Li QY, Newbury-Ecob RA, Terrett JA, et al. Holt-Oram American Heart Association Circulation. 1994; 90:2180-88.
syndrome is caused by mutation in TBX5, a member of the 25. Dennis C, Spreng DS Jr, Nelson GE, et al. Development of
Brachyury (T) gene family. Nat Genet. 1997; 15:21-29. a Pump-oxygenator to Replace the Heart and Lungs: An
11. Bedford DE, Papp C, Parkinson J. Atrial Septal Defect. Brit Apparatus Applicable to Human Patients and Application to
Heart J. 1941;3:37. One Case Ann Surg. 1951; 134:709-21.
12. Cockerham JT, Martin TC, Gutierrez FR, et al. Spontaneous 26. Horvath KA, Burke RP, Collins JJ Jr, et al. Surgical treatment
closure of secundum atrial septal defect in infants and young of adult atrial septal defect: early and long-term results. J Am
children. Am J Card. 1983; 52:1267-71. Coll Cardiol. 1992; 20:1156-59.
13. Radzik D, Davignon A, Van Doesburg N, et al. Predictive 27. Ghosh S, Chatterjee S, Black E, et al. Surgical closure of atrial
factors for spontaneous closure of atrial septal defects septal defects in adults: effect of age at operation on outcome.
diagnosed in the first 3 months of life. J Am Coll Cardiol. Heart. 2002; 88:485-87.
1993; 22:851-53. 28. Jones DA, Radford DJ, Pohlner PG. Outcome following
14. Hanslik A, Pospisil U, Salzer-Muhar U, et al. Predictors surgical closure of secundum atrial septal defect. J Paediatr
of spontaneous closure of isolated secundum atrial septal Child Health. 2001; 37:274-77.
defect in children: a longitudinal study. Pediatrics. 2006; 118: 29. Attenhofer Jost CH, Connolly HM, Danielson GK, et al. Sinus
1560-65. venosus atrial septal defect: long-term postoperative outcome
15. McMahon CJ, Feltes TF, Fraley JK, et al. Natural history of for 115 patients. Circulation. 2005; 112:1953-58.
growth of secundum atrial septal defects and implications for 30. Roos-Hesselink JW, Meijboom FJ, Spitaels SEC. Excellent
transcatheter closure. Heart. 2002; 87:256-59. survival and low incidence of arrhythmias, stroke and heart
16. Craig RJ, Selzer A. Natural history and prognosis of Atrial failure long-term after surgical ASD closure at young age. A
septal defect. Circulation. 1968; 37:805. prospective follow-up study of 21-33 years: Eur Heart J. 2003;
17. Konstantinides S, Geibel A, Olschewski M, et al. A comparison 24:190-97.
of surgical and medical therapy for atrial septal defect in adults. 31. Murphy JG, Gersh BJ, McGoon MD, et al. Long-term outcome
N Engl J Med. 1995; 333:469-73. after surgical repair of isolated atrial septal defect. Follow-up
18. St John Sutton MG, Tajik AJ, McGoon DC. Atrial septal at 27 to 32 years. N Engl J Med. 1990; 323:1645-50.
defect in patients ages 60 years or older: operative results 32. Attie F, Rosas M, Granados N, et al. Surgical treatment for
and long-term postoperative follow-up. Circulation. 1981; secundum atrial septal defects in patients >40 years old. A ran-
64:402-09. domized clinical trial. J Am Coll Cardiol. 2001; 38:2035-42.
19. Berger F, Vogel M, Kramer A, et al. Incidence of atrial flutter/ 33. King TD, Thompson SL, Steiner C, et al. Secundum atrial septal
fibrillation in adults with atrial septal defect before and after defect. Nonoperative closure during cardiac catheterization.
surgery. Thorac Surg. 1999; 68:75-78. JAMA. 1976; 235:2506-09.
20. Steele PM, Fuster V, Cohen M, et al. Isolated atrial septal 34. Du ZD, Hijazi ZM, Kleinman CS. Comparison between
defect with pulmonary vascular obstructive disease: Long-term transcatheter and surgical closure of secundum atrial septal defect
follow-up and prediction of outcome after surgical correction. in children and adults: results of a multicenter nonrandomized
Circulation. 1987; 76:1037-42. trial. J Am Coll Cardiol. 2002; 39:1836-44.
264
35. DiBardino DJ, McElhinney DB, Kaza AK, et al. Analysis
of the US Food and Drug Administration Manufacturer and
37. Knepp MD, Rocchini AP, Lloyd TR, et al. Long-term follow
up of secundum atrial septal defect closure with the Amplatzer
18
User Facility Device Experience database for adverse events septal occluder. Congenit Heart Dis. 2010; 5:32-37.
InteratrIal DefectS
involving Amplatzer septal occluder devices and comparison 38. Al-Anani SJ, Weber H, Hijazi ZM. Atrioventricular block after
with the Society of Thoracic Surgery congenital cardiac transcatheter ASD closure using the Amplatzer septal occluder:
surgery database. J Thorac Cardiovasc Surg. 2009; 137:1334- risk factors and recommendations. Catheter Cardiovasc Interv.
41. 2010; 75:767-72.
36. Jones TK, Latson LA. Multicenter Pivotal Study of the 39. Krumsdorf U, Ostermayer S, Billinger K, et al. Incidence and
HELEX Septal Occluder Investigators, et al. Results of the US clinical course of thrombus formation on atrial septal defect
multicenter pivotal study of the HELEX septal occluder for and patient foramen ovale closure devices in 1,000 consecutive
percutaneous closure of secundum atrial septal defects. J Am patients. J Am Coll Cardiol. 2004; 43:302-09.
Coll Cardiol. 2007; 49:2215-21.
265
C hapter
19 Ventricular Septal Defects
Vijayalakshmi IB, Chitra Narasimhan, Prasanna Simha Mohan Rao
IntroDuCtIon is simple and is not accompanied by pulmonary stenosis; it

consists in patency of the septum between the ventricles in its
Ventricular septal defect (VSD) is a developmental defect of upper portion. It is revealed only by auscultation and shows
the interventricular septum (IVS) wherein a communication itself by a physical sign with quite distinctive characteristics:
exists between the cavities of the two ventricles.1,2 VSD is this is a loud, prolonged whirring sound; it is a single murmur,
a common congenital cardiac anomaly, occurring in both beginning with systole and continuing in such a way as to
children and adults. It can occur in isolation or as part of more entirely mask the normal rhythm; its maximum intensity is not
complex defects. Isolated VSDs are the second most common at the apex or at the right or left side of the base, but over the
congenital cardiac defect encountered after bicuspid aortic upper third of the precordial region; it is central like the septum
valves and this is also so in India.3, 4 The isolated VSDs can be itself and diminishes gradually from this central point the
repaired surgically with an acceptable mortality rate. Recently farther from it one listens; it is not transmitted; it corresponds
nonsurgical transcatheter device closure of VSD is in vogue. to no other sign of organic disease except the purring thrill.
Understanding the nature of the anomaly, clinical picture, the An abnormal murmur, which combines these characteristics
physiologic data and the natural history of VSD is important is the pathognomonic sign of patency of the ventricular
for planning the management strategy. septum”. His name is remembered by two eponymous terms:
About 20 percent of VSDs are associated with almost Maladie de Roger (Roger’s disease), which is a congenital
all forms of congenital heart disease (CHD).5,6 They occur asymptomatic VSD and Bruit de Roger (Roger’s murmur),
frequently as an integral part of other anomalies like tetralogy which is a loud pansystolic murmur of VSD.
of Fallot (TOF), truncus arteriosus, atrioventricular septal In 1898, Eisenmenger described a patient with VSD,
defects, double-outlet right ventricle (DORV) and transposition cyanosis and pulmonary hypertension (PH). This combination
of great arteries (TGA) or in association with coarctation of of VSD, pulmonary vascular disease and cyanosis has been
the aorta (COA), patent ductus arteriosus (PDA), atrial septal termed as ‘Eisenmenger complex’. Pulmonary vascular
defect (ASD), pulmonary stenosis (PS), etc. This chapter will disease and cyanosis in combination with any other systemic-
discuss only isolated VSDs. to-pulmonary connection has been called Eisenmenger
syndrome.8 In 1958, Heath and Edwards described the
HIStorICal reVIew morphologic changes associated with pulmonary vascular
disease and their 6 categories of vascular changes have
The first clinical description of VSD was made by Henri remained the standard of comparison to the present.9 The
Roger, a French pediatrician, at the age of 70 years, in 1879.1 earliest surgical treatment of VSD was pulmonary banding10
He described the clinical and auscultatory findings of six and subsequently Lillehei et al described the first successful
acyanotic patients and autopsy finding of a child with VSD.7 surgical closure.11 The anatomic assessment of VSD has
He described it as—“There is a malformation of the heart dramatically improved after the advent of 2D echocardiography
unaccompanied by cyanosis, in spite of the communication in 1979. Since the first successful percutaneous VSD device
between the ventricles and in spite of the free admixture closure in 1987 by Lock et al with the Rashkind double
of venous and arterial blood; this malformation, which is umbrella,12 there have been several reports of transcatheter
compatible with life and even with prolonged existence, closure of the VSD using different devices.13,14 Amplatzer
muscular VSD device was employed by Thonopoulos et al 
table 1 19
and Tofeig et al to close muscular VSDs.15,16 Catheter closure Aneuploid syndromes associated with ventricular septal defect
of perimembranous VSD using Amplatzer membranous VSD
ventricular septal defects

Syndrome CCVM Type of CCVM
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. Del 4q, 21, 32 60 VSD, ASD
There are case reports of the use of Amplatzer duct occluder Del 5p 30–60 VSD
II for closure of VSDs.20 The Amplatzer perimembranous Trisomy 13 80 ASD, VSD, TOF
ventricular septal occluder device (pmVSO2 device) is under Trisomy 18 100 VSD, TOF,
trial.21 In recent years, with the advent of new devices and (Edward’s syndrome) DORV
refinement of techniques, a number of reports on percutaneous Trisomy 21 40–50 VSD, AVCD
closure of VSD have been published with encouraging results. (Down syndrome)
Del 22q 11 50 Truncus
epIDemIology (DiGeorge syndrome) arteriosus, TOF,
VSD, interrupted
Ventricular septal defects occur either as an isolated defect aortic arch
or as a component of a more complex lesion. It occurs in 50 CCVM = Congenital cardiovascular malformation; AVCD = Atrioventricular
percent of all children with CHD and in 20 to 30 percent as canal defect; ASD = Atrial septal defect; DORV = Double-outlet right
ventricle; TOF = Tetralogy of Fallot; VSD = Ventricular septal defect
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 InHerItanCe
infants and those born with low weight.24 The advent of
transthoracic 2D echocardiography (TTE) has demonstrated Siblings of patients with VSD have three times the incidence
the higher incidence of VSDs, especially the small muscular of VSD, as compared to the general population.32 VSDs are
type in newborns to be 5 to 50 cases per every 1,000 live found in 3.3 percent of the first degree relatives33 and in nearly
births.25 The lower prevalence in adults is due to spontaneous 30 to 60 percent of siblings of the index case.34 Maternal
closure of many defects. VSDs are slightly more common in VSDs have a recurrence risk of 6 to 10 percent, whereas
females (56%).26 The doubly committed subarterial or juxta- with paternal VSDs, the recurrence risk in the offspring is 2
arterial defect is more common, about 30 percent in Asian percent.35 VSDs have been reported in identical twins, but the
populations, whereas muscular and multiple defects are less frequency of discordance is high.32
common in the same population.27
embryology
etIology
The normal development of the IVS is a complex process and
Congenital heart defects are believed to be multifactorial, in depends upon the endocardial cushions, conotruncal ridges,
which the interaction between hereditary predisposition and growth of tissues at the crest of the IVS and the muscular
environmental influences result in the defect.3 The definitive septum. The VSDs result from a deficiency of growth or a
cause of any individual CHD is rarely determined. Genetic failure of alignment or fusion of the component parts of the
risk factors include the presence of certain chromosomal IVS beyond the first 7 weeks of intrauterine life. The reason
syndromes like Trisomy 13, Trisomy 18, Trisomy 21, for this delayed or incomplete closure is still unknown. The
Del 22q 11, Del 4q, 21, 32 and Del 5p.28 Further studies membranous VSD occurs as a result of failure of fusion of the
have shown an interaction between TBX5, GATA4 and endocardial cushions, the conotruncal ridges and the muscular
NKX2.5, suggesting that transcriptional activation may septum. The outlet VSD may occur because of failure of
be responsible for septal defects.29 Aneuploid syndromes fusion of the conal septum. The inlet VSD may occur due to
associated with VSD are shown in Table 1.3 In the majority the incomplete fusion of the right endocardial cushion with
of the patients (95%) with an isolated VSD, the defect is the muscular septum. Muscular defects may occur because
not associated with a chromosomal abnormality and the of lack of merging of the walls of the trabecular septum or
cause is unknown. excessive resorption of muscular tissue during ventricular
The VSDs may be associated with exposure to certain growth and remodeling.36 The fetal circulation is not altered
environmental factors during pregnancy, especially within the significantly in uncomplicated VSDs.37
first 8 weeks of gestation. Some of the environmental factors
are maternal phenylketonuria, diabetes or exposure to febrile anatomy
illness, especially rubella, influenza or teratogens like alcohol,
cocaine, marijuana, ibuprofen, anticonvulsants (hydantoin, The IVS is a complex curvilinear, non-planar intracardiac 267
carbamazepine) or organic solvents.30,31 partition. Soto et al divided IVS into four regions by its
4 landmarks on its right ventricular aspect.38 The normal 3. Parietal band or distal conal septum (outlet septum).
ventricular septum is mostly muscular with a small fibrous 4. Septal band or proximal conal septum (conoventricular
portion, the membranous septum. septum).
shunt defects
The four regions are the inlet septum, trabecular septum, The atrioventricular node located in the triangle of Koch
outlet or infundibular septum (together making up the (formed by the tendon of Todaro, the coronary sinus ostium
muscular septum), and the membranous septum. and the septal leaflet of the TV) gives rise to the atrioventricular
The inlet septum is smooth walled and extends from the bundle (Bundle of His).40 The atrioventricular septum is itself
septal attachment of the tricuspid valve (TV) to the distal pierced by the atrioventricular bundle as it passes from the
attachments of the tricuspid tensor apparatus. The inlet septum apex of the triangle of Koch to reach the crest of the muscular
separates the septal cusps of the mitral and tricuspid valves. septum.41 At this point, the bundle is on the posteroinferior
The apical trabecular zone separates the coarse trabeculations margin of the membranous septum, which lies just posterior
of the right ventricular from the fine ones seen in the left to the commissure of the septal and anterior leaflets of the
ventricular apical septum. The trabecular portion separates TV. The right bundle branch traverses along the anteroinferior
the body and apices of the two ventricles. It extends from the border of the membranous septum to then enter the right
attachments of the tricuspid leaflets outward to the apex and ventricle (RV). Sometimes in inlet defects, the bundle of His
upwards to the crista supraventricularis. The smooth-walled passes anterosuperiorly to the defect.
outlet or infundibular septum, extends from the crista to the
pulmonary valve. The outlet septum separates the outlets ClaSSIfICatIon
of the ventricles. The supraventricular crest is an extensive
ledge in the muscular zone in the normal heart that separates Many classifications of VSDs have been proposed. Soto et al
the tricuspid from the pulmonary valves and the pulmonary classified VSDs depending on their location in the IVS as seen
from the aortic valves. The three muscular components of from the right ventricular side.38 They are divided into four
the ventricular septum fan out from the small membranous types of defects: 1. Perimembranous, 2. Muscular, 3. Outlet
septum, which lies under the commissure of the anterior and 4. Inlet.
and the septal tricuspid leaflets and below the right and the Anderson et al42 classified the VSDs according to the
noncoronary cusps of the aortic valve. The membranous relation of the defect to the atrioventricular conduction axis,
septum is further divided by the septal leaflet of the TV into i.e.
atrioventricular and interventricular components.38 Schematic i. The membranous septum.
diagram of the location of various types of VSD is given in ii. The relation of the defect to the atrioventricular valves.
Figure 1. iii. The relation of the defect to the arterial valves.
The four main anatomic components that make up the iv. The position of the defect within the ventricular septum,
normal IVS as described by Van Praagh et al39 are as follows: i.e. the inlet, trabecular or outlet part of the septum.
1. Atrioventricular canal septum (inlet septum). They have classified VSDs into four types: perimembra-
2. Muscular septum or ventricular sinus septum (trabecular or nous, muscular defects, doubly committed juxta-arterial and
muscular). juxtatricuspid (non-perimembranous) defects.
anatomical Classification
I. Perimembranous defects (infracristal, subaortic, mem-
branous, 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 be-
tween 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
Praagh’s classification considers that ‘perimembranous’
is a misnomer for this VSD as ‘peri’ is the Greek pre-
figure 1: Schematic diagram of the anatomical position of various fix meaning ‘around’. They suggest that the appropriate
types of ventricular septal defects. Source: The Lancet, 377 (9771), terminology should be ‘paramembranous’ VSD as the
268 Penny DJ, Vick GW 3rd; Ventricular Septal defect 1103-12 Copyright
(2011), with permission from Elsevier defect lies beside the membranous septum.39
In paramembranous defect, there can be a variable de- Kirklin’s Classification47 19
gree of anterior malalignment between the infundibu-
lar septum and the anterior ventricular septum such Type I: VSDs are termed as supracristal, infundibular,

that the aortic valve appears to override the defect.38 juxtaarterial or conal. This defect lies caudal to the
Posterior or leftward malalignment also occurs, produc- pulmonary valve in the infundibular portion of the
ing subaortic stenosis. Anterior malalignment of the right ventricular outflow tract.
conal septum is seen in TOF and posterior malalignment Type II: VSDs are termed as perimembranous or paramem-
is seen in interrupted aortic arch (IAA). branous and are located adjacent to the membranous
II. Muscular defects (trabecular): They account for 5 to 20 portion of the ventricular septum and the septal leaf-
percent of all the VSDs. They are entirely bounded by the let of the TV.
muscular septum and are often multiple, when viewed Type III: VSDs are termed as inlet or atrioventricular canal
from the right side. VSDs and are located posteriorly at the inlet portion
Kirklin et al43 further subclassified them depending on of the right ventricular septum (corresponding to the
their location in the muscular septum as: (a) anterior, (b) outlet portion of the left ventricular septum).
midmuscular, (c) apical, (d) posterior. An anterior or Type IV: VSDs are muscular defects and include a variety
marginal muscular defect is anterior to the septal band. of single and multiple defects in the muscular
A central midmuscular defect is posterior to the septal septum.
band. Apical defects are inferior to the moderator band
and the posterior defects are beneath the septal leaflet of HemoDynamICS
the TV.
When multiple muscular defects are seen, it is often re- The most important variables that determine the hemo-
ferred to as ‘Swiss cheese’ type of VSDs. Some believe dynamics in a patient with VSD are the size of the VSD,
that a Swiss cheese septum is actually an entity distinct pulmonary vascular resistance (PVR), systemic vascular
from multiple VSDs. The morphology of the Swiss resistance (SVR) and the presence of associated defects such as
cheese septum is believed to originate from septal non- ASD, PDA, right and left ventricular outflow tract obstruction
compaction during embryologic development. Thus, and arch obstruction. The location of the VSD is irrelevant.
unlike a group of muscular VSDs, Swiss cheese defects The pathophysiologic effects of VSD are secondary to the left
cannot close spontaneously.42,44,45 to right shunt and changes in the pulmonary vasculature. A left
III. Subarterial or Outlet defects (supracristal, conal, to right shunt at the ventricular level has three hemodynamic
infundibular, subpulmonary, doubly committed consequences:
subarterial, doubly committed juxta-arterial): They 1. Increased LV volume load.
occur in 5 to 7 percent of VSDs. They are situated just 2. Excessive pulmonary blood flow (PBF).
beneath the pulmonary valve and communicate with the 3. Reduced systemic cardiac output.48
right ventricular outflow tract above the supraventricular As cardiac output decreases, compensatory mechanisms
crest. The incidence is as high as 30 percent in Asian are stimulated to maintain adequate organ perfusion. These
populations.27 This defect frequently leads to prolapse mechanisms include increased catecholamine secretion and salt
of the right coronary cusp or less likely the noncoronary and water retention by means of the renin-angiotensin system.
cusp of the aortic valve causing aortic regurgitation The ventricular level shunts occur primarily during
(AR). In the perimembranous outlet defects there may be ventricular systole, in contrast to atrial level shunts, which
considerable degree of malalignment of the ventricular occur primarily during ventricular diastole and the arterial
with the infundibular septum.46 The conduction system level shunts which typically occur both during systole and
is remote to the outlet defects. diastole. The left to right shunting across the VSD occurs
IV. Inlet defects (canal type, endocardial cushion type, mainly during systole, and is determined by the relative
atrioventricular septum type, juxtatricuspid): These pulmonary and systemic vascular resistances. The shunting
VSDs account for about 8 percent of all the VSDs. is increased during the early phase of contraction, as LV is
They are located posteriorly and inferior to the activated before RV and the LV pressure rises faster than the
membranous septum. A muscular inlet defect can be RV pressure. Shunting continues from this early phase of
remote or have the conduction system bordering the systole till the semilunar valves open. During the early stages
defect superiorly. In the perimembranous inlet defects of diastole (isovolumic relaxation), the LV relaxes more
there may be some degree of malalignment of the quickly than RV, resulting in a transient pressure gradient
ventricular and the atrial septum.46 There can then favouring a right to left shunt across a moderate or a large
be overriding or straddling of the tricuspid or mitral VSD. The right to left shunt across the VSD is significant with
valve. marked elevation of PVR.
269
4 VSDs may be classified into small, moderate and large the pulmonary capillary pressure and there is elevated, but
based on the size of the defect and also based on the subsystemic PVR, which is variable. Therefore, in a large VSD
hemodynamics.2,48,49 both pulmonary arterial and venous pressures are elevated.
shunt defects
During the second year of life, the manifestations of

Small or restrictive Defects (maladie de roger) congestive heart failure (CHF) decreases as the pulmonary
artery pressure increases. As PVR increases and exceeds
The small VSD is less than one-third of the size of the aortic root SVR, right to left shunt occurs. Initially it is mainly during
or the orifical area is <0.5 cm2/m2. It is also called restrictive exercise, due to the fall in SVR. Later, the right to left shunt
as the size of the defect limits the left to right shunt and there occurs at rest with persistent cyanosis. There is marked
is a significant pressure gradient between the LV and RV. The fall in PBF with persistent hypoxemia. RV failure finally
pulmonary/aortic systolic pressure ratio is <0.3 with a small supervenes.
shunt (Qp/Qs < 1.4:1).The degree of LV volume overload is
minimal. There is no tendency to develop increased PVR. But eisenmenger VSD
they can develop AR or bacterial endocarditis.
A large VSD, if left untreated, can result in irreversible
moderate or moderately restrictive Defects damage to the pulmonary arterial tree with development
of pulmonary vascular obstructive disease (PVOD) and
The VSD size is said to be moderately restrictive, when it is 1/3– Eisenmenger’s syndrome. The systolic pressure ratio is 1 and
2/3 of the size of the aortic root or the orifical area is > 0.5 to 1 Qp/Qs is less than 1 : 1, with a net right to left shunt. There
cm2/m2. They are large enough to permit a moderate shunt, yet is identical RV and LV systolic pressures and suprasystemic
small enough to offer some resistance to flow. The pulmonary/ PVR.
aortic systolic pressure ratio is < 0.66 with a moderate shunt
(Qp/Qs > 1.4–2.2:1). The peak systolic pressure difference ClInICal featureS
is ≥ 20 mm Hg between the two ventricles. They develop
moderate left to right shunt leading to volume overload of the
History
left sided cardiac chambers causing LV and left atrium (LA)
dilatation and hypertrophy. The RV is not dilated and RV and The clinical manifestations of isolated VSDs have a wide
pulmonary artery pressures may remain low or be moderately spectrum, which varies depending upon the size of the defect
elevated. The PVR is low, but variable and rarely progresses and the magnitude of the shunt. It may range from being
to PH. asymptomatic to severe heart failure. The signs and symptoms
begin to develop, when the fetal PH starts declining sufficiently
large or nonrestrictive to permit left to right shunting.
The infants with large VSDs present with symptoms due to
The VSD is large, when it measures more than 2/3 of the size CHF by 4 to 6 weeks, as the PVR decreases. The symptoms are
of the aortic root or the orifical area is ≥1 cm2/m2. It is also increased respiratory rate (tachypnea), chest retractions, feeding
called nonrestrictive VSD as there is no resistance to flow difficulties with suck-rest-suck cycle, excessive sweating of
across the defect. The pressures in the ventricles are equal forehead, repeated respiratory infections and failure to thrive.
and they function as a common pumping chamber with two In infants with moderate VSD, the parents may observe
outlets. The degree of left to right shunt is dependent on the pulsations over the precordium or feel a thrill. Child may have
relationship between the pulmonary and systemic vascular mild tachypnea, cough during feeding and fatigue. Sweating
resistance. The pulmonary/aortic systolic pressure ratio is especially during feeding is frequent in infants below 6
>0.66 with a large shunt (Qp/Qs > 2.2:1). months. They may also present with lack of adequate growth
In infants with moderate or large VSDs the decline in and with one or more episodes of pneumonia. Older children
the PVR may be delayed for several months. At about 4 to may present with effort intolerance and fatigue.
6 weeks of life, the large left to right shunt causes increased The children with small VSDs are asymptomatic and may
PBF and subsequently increases pulmonary venous return be detected, because of the murmur on a routine health check-
into the LA and ultimately into the LV. This leads to dilatation up. Older asymptomatic children may be detected during
of LA and LV and increased LV end-diastolic pressure. routine school health check-up.
This is reflected in increased LA pressure and consequently The older children seen for the first time may be referred
in increased pulmonary venous pressure. The pulmonary by pediatricians for bacterial endocarditis, CHF, and rarely
overcirculation leads to increase in the pulmonary interstitial arrhythmia. Patients with large VSD with high PVR may
fluid and in severe forms may manifest as pulmonary edema. not have much symptoms at rest, but with exercise may have
The RV pressure increases and this causes RV dilatation and symptoms, which include exertional dyspnea, cyanosis, chest
270 hypertrophy. The increased pulmonary blood flow raises pain, syncope and hemoptysis.50
physical examination less, as the defect practically closes during systole. The murmur 19
in moderately large defects are long, low pitched decrescendo
The infants with large shunts with CHF are malnourished with murmur best heard in LSB. The systolic mumurs in outlet

poor growth and development. These infants are tachypneic defects are heard in the second ICS and may radiate upwards
with chest retractions and there is precordial bulge with to the left into the suprasternal notch and into the left side of
bilateral Harrison sulcus. If CHF is severe or if there is added neck. In outlet defects, the holosystolic murmur is crescendo or
pneumonia, there may be retractions and grunting. Infants cresendo-decresendo. When the shunt is large (Qp/Qs > 2:1),
with nonrestrictive VSDs with balanced shunts may become a short mid-diastolic murmur is heard at the apex due to the
cyanotic on crying or exercise. Cyanosis and clubbing are increased flow across the mitral valve. The soft blowing early
seen in adolescent and adults with large VSD with high diastolic decrescendo murmur in the left second and third ICS
PVR/Eisenmenger syndrome. Peripheral edema is unusual in could be due to associated AR and peripheral signs are present
infants. The VSDs can be associated with various syndromes if the AR is significant.
like Trisomy 18, 13, 21, Del 22q 11, Del 4q, 21, 32 and Del 5p. In patients with large VSDs with high PVR, the LV
precordial impulse is replaced by the RV impulse. There is a
Arterial Pulse very short soft decrescendo murmur or rarely no murmur in
balanced shunts. The ejection click may be heard due to the
Pulse is normal in small VSDs. In moderate VSDs, the pulse is flow in the dilated hypertensive pulmonary trunk. Second
brisk due to the vigorous LV ejection. In nonrestrictive defects sound is quite loud, palpable with narrow splitting. The third
with large left to right shunts and CHF there may be low sound of RV origin may be present along the LSB. There is no
volume pulse. The pulse is normal in Eisenmenger syndrome, diastolic rumble at apex, but a short early diastolic murmur of
as the systemic stroke volume is maintained. pulmonary regurgitation (Graham Steell murmur) may be heard
in the left upper parasternal area.
Jugular Venous Pulse
natural History
The jugular venous pulse (JVP) is not raised in VSD. So much
so if JVP is raised it indicates intact IVS and clinically rules The natural history of the patient with VSD has a wide spectrum,
out VSD. In Eisenmenger’s syndrome it is usually normal or ranging from spontaneous closure to CHF to death in early
with a small dominant ‘a’ wave. infancy. The natural history is influenced by its position, size,
number of defects and association of other malformations.
Precordial Movement and Palpation Small defects remain asymptomatic but are predisposed to
endocarditis and AR. Large defects often develop LV failure,
In moderate to large VSDs, precordial pulsations are visible PH (Eisenmenger syndrome) and eventually RV failure. Thus,
due to LV volume overload. The apical impulse is LV type, in the natural history of VSDs there may be:
hyperdynamic, displaced downward and outwards. In small 1. Spontaneous diminution in size or closure.
and moderate VSDs a precordial thrill is best felt in the third 2. Development of right ventricular outflow tract obstruction
and fourth intercostal space (ICS) at the left sternal border (Gasul’s effect).
(LSB). In cases with subarterial VSD the thrill maybe palpated 3. Development of AR.
in the second or first ICS and may radiate upwards to the left 4. Development of left ventricular outflow tract obstruction.
into the suprasternal notch and into left side of neck.51 In large 5. Development of pulmonary vascular obstructive disease.
VSDs with high PVR a left parasternal lift may be present. In 6. Infective endocarditis.
patients with severe PH, there is a left parasternal heave with With the advent of surgical closure and nonsurgical device
a palpable P2 in the left second ICS. 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) Henri Roger did not anticipate spontaneous closure of
is normal with normal split. Sometimes A2 may be obscured VSD. But in 1918, in the reports “the possibility of a loud
by the long murmur in small VSDs. Pulmonary component is congenital heart murmur disappearing when a child grows
normal or mildly increased in moderate VSDs. In large VSDs, up”52 and “can the clinical manifestation of congenital heart
the pulmonary component of the second sound is usually loud disease disappear with the general growth and development
with a narrow split. LV S3 can be prominent in large shunts or of the patient?”53 speculated spontaneous closure of VSD.
RV S3 may be present in large VSD with severe PH. The impact of these two reports are so dramatic and
The murmur in small VSDs is grade 4/6, harsh long systolic, vociferous that even after decades many clinicians advice
crescendo-decrescendo best heard along the lower LSB. In very the parents “Do not worry, the hole will close”. As a 271
small apical or muscular defects the murmur is soft, grade 2/6 or result many children grow up and develop Eisenmenger’s
4 syndrome. Hence it is very important to know, when and
how the VSDs close spontaneously.
Spontaneous closure occurs frequently in children and
shunt defects
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 figure 2: Transthoracic echocardiography in apical four-
60 percent close before 3 years and 90 percent by 8 years of chamber view shows large subaortic VSD (12 mm) with septal
age.24,57,58 Therefore, blanket advice by the pediatrician that aneurysm with a 6 mm opening and a small subaortic membrane.
VSD will close should be avoided, unless the size and site LA = Left atrium; LV = Left ventricle; RA = Right atrium; RV = Right
ventricle
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).
figure 3: Transthoracic echocardiography in parasternal long axis
rIgHt VentrICular outflow obStruCtIon view shows small ventricular septal defect with cusp prolapse and
severe aortic regurgitation. Ao = Aorta; LA = Left atrium; LV = Left
Right ventricular outflow obstruction occurs secondary to VSD ventricle
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.
aortIC regurgItatIon
272 figure 4: Transthoracic echocardiography in parasternal long axis
The incidence of aortic cuspal prolapse in outlet VSDs has view shows large vegetation on the right ventricular (RV) side literally
been shown to be as high as 73%. They can progress to AR closing the small VSD. Ao = Aorta; LA = Left atrium; LV = Left ventricle.
19

a B c
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 52–78% of the patients. In perimembranous VSDs, aortic postnatal fall, but there is a small risk of increase, usually
cuspal prolapse has been shown to be 14% with progression beyond 20 years of age. In patients with pulmonary artery
to AR in 6%.62 In infancy and early childhood only aortic cusp systolic pressure >50 percent of the systemic arterial systolic
prolapse without AR may be present, but progressive AR may pressure, there is significant risk for the development of
develop. The cause of the aortic cusp prolapse and AR in the pulmonary vascular changes.23 Measured PVR falls to high
doubly committed subarterial VSD is due to the unsupported normal levels in infancy and gradually rises in the ensuing years
right coronary cusp with the combined Venturi effect produced if the defect does not become smaller. The risk of development
by the VSD jet. In early systole, blood is ejected from the of permanent pulmonary vascular disease is very rare before
LV and is also shunted through the VSD. The anatomically the first year of life.66,67 Hence, prompt diagnosis and closure
unsupported coronary cusp and aortic sinus are driven into the of these defects at least prior to 18 months of age is likely to
RV due to the Venturi effect. The Venturi effect is caused by reduce the incidence of development of pulmonary vascular
the high velocity jet passing through the small VSD causing disease. If untreated these large or non-restrictive VSDs will
negative pressure. In diastole the intra-aortic pressure forces have a progressive rise in pulmonary artery pressure and a fall
the aortic valve leaflet to close, but the unsupported cusp in left to right shunting. In turn, eventually this leads to higher
(right or noncoronary) is pushed down into the left ventricular PVR and to Eisenmenger syndrome.
outflow tract away from the opposed coronary cusp, resulting
in AR (Figures 5A to C).63 In perimembranous defects, the InfeCtIVe enDoCarDItIS
AR is more due to the prolapse of the noncoronary cusp. The
AR is mainly as a result of the structural abnormality due to Infective endocarditis (IE) is an uncommon risk occurring in
the maldevelopment of the aortic commissure (between non- <1 to 3 percent of patients with VSD.67,68 A small peri-
coronary and right cusp) and is aggravated by the Venturi membranous VSD that does not close spontaneously is
effect of the VSD jet.64,65 Occasionally, the deformity of the generally associated with a good prognosis, but is at risk for
aortic cusps themselves can cause the AR, this is mostly seen development of IE. The vegetation is usually located on the
with perimembranous defects. 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
Subaortic Stenosis RV cavity. The site of the vegetation can occasionally be on
the aneurysm of the ventricular septum. Rarely, an acquired
Patients with membranous VSDs can occasionally develop left ventricular to right atrial shunt, Gerbode defect, can occur
discrete fibrous or fibromuscular subaortic stenosis, which is due to the perforation of the septal tricuspid leaflet secondary
generally progressive and there is potential for damage to the to endocarditis.
aortic valve resulting in AR.
gerboDe DefeCt
pulmonary Vascular obstructive Disease
A Gerbode defect is a rare type of VSD communicating
Pulmonary vascular obstructive disease may develop in 10 between the LV and RA. The LV–RA communications were
percent of the large VSDs. In patients with pulmonary artery first described in the 19th century by Thurman.69 It was not
and RV systolic pressure < 50 percent of the systemic arterial until 1958, however, that interest in this lesion was renewed
systolic pressure there is moderate left to right shunt with following the publication by Gerbode et al. of a series of 273
possible CHF. The PVR does not increase after the initial five patients who underwent successful surgical repair.70
4 The defect is usually congenital, but rarely is acquired. They 3. The third is the combined supravalvular and infravalvular
account for approximately 0.08% of all congenital cardiac defect or also called as Type III.
anomalies.71 Associated abnormalities occur in about 1/3 The physiological consequences of the Gerbode defects
shunt defects
of cases, of which ASD is the most common.72 An acquired depends upon the magnitude of the shunt which is dependent
Gerbode defect has been described following ventricular on the size of the defect and PVR.79 The shunting from the
septal perforation in the setting of bacterial endocarditis,73 LV to RA is predominantly systolic due to the large systolic
trauma,74 myocardial infarction,75 valve replacement76 and gradient between these chambers. The small gradient which
following surgical closure of VSD.77 exists during diastole produces negligible shunting. Smaller
The Gerbode defects result from a defect in the defects result in small size shunts and they can remain
membranous septum. The TV is normally more apically clinically silent. In the presence of large defect, the entire shunt
displaced than the mitral valve. Riemenschneider and Moss72 flow is returned to both ventricles during diastole, causing
classified LV–RA communications into supravalvular biventricular volume overload and enlargement of all four
and infravalvular types (Figure 6). It was based on the chambers. This is contrary to VSDs, where only LV volume
insertion of the septal leaflet of the TV, which divides the overload and in ASDs where RV volume overload occurs.73
membranous septum into atrioventricular (supravalvular) Significant PH can occur, but is not common.
and interventricular (infravalvular) portions. Sakakibara The clinical picture of Gerbode defect varies with mixed
and Konno have classified the LA-RA communications as symptoms related either to the LV to RA shunt or the underlying
Types I, II and III.78 The types of Gerbode defects are: etiology. In small defects, the shunt is well tolerated and there
1. The supravalvular defect, which accounts for 1/3, occurs may be no characteristic symptoms or clinical signs. These
in the atrioventricular septum. The shunt occurs between defects can remain clinically silent. In larger defects there
the LV and RA above the septal leaflet of the TV, which may be significant symptoms like failure to thrive, or exercise
remains intact. It is also called as direct type or Type I. It is intolerance and CHF. Physical findings are similar to VSD
the less common form and is usually acquired, more often with a loud harsh holosystolic murmur often associated with a
due to IE. thrill at the left sternal margin in the fourth or fifth intercostal
2. The more common infravalvular defect, which accounts space.73
for the remaining 2/3, occurs in the interventricular
membranous septum. This shunt produces a communication InVeStIgatIonS
between the two ventricles and the shunted blood entering
the RV is in turn diverted to the RA through associated
electrocardiogram
defects in the TV. There may be a variety of forms of
which septal leaflet perforation(s) are the most common. Electrocardiogram (ECG) is a useful mirror of the physiologic
This defect is found inferior to the insertion of the TV and changes and not the anatomical location of the VSD. The
is also called as indirect type or Type II. 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
figure 6: Schematic diagram showing the anatomic position of
the Gerbode defects. A. Direct or supravalvular type B. Indirect or
precordial leads as large equiphasic RS complexes (> 50 mm),
274 the “Katz-Wachtel phenomenon” (Figure 7). There is usually
infravalvular type. The combined type is a combination of A and B.
19

figure 7: 12 lead ECG (½ 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 the combination of right atrial P waves with left ventricular
tall ‘R’ wave in lead V1, deep Q waves, tall R and peaked, tall hypertrophy.70,72
‘T’ waves in V5 to V6 (Figure 8). In Eisenmenger complex,
the ‘P’ waves are peaked with right sided axis. There is a tall Chest X-ray
monophasic ‘R’ preceded by small ‘q’ or followed by small ‘s’
wave in V1. In 1913, Vaquez and Bordet described the radiological features
In Gerbode defects there is both biatrial and biventricular of VSD.82 Chest X-ray is practically normal in small VSDs.
enlargement. The tall peaked right atrial P wave in Lead II may Moderate VSDs show cardiac enlargement of varying severity
be present from infancy. There is rSr in V1, and prominent left and increased pulmonary vascular markings (PVM) or plethora
precordial q waves, tall R waves, upright T waves indicating (Figure 9A). The downward and leftward displacement of 275
biventricular volume overload. The hallmark in the ECG is the cardiac silhouette is due to LV enlargement. The PVMs
4
shunt defects
a B c
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 figure 10: Transthoracic echocardiography in apical four chamber
the MPA and its adjacent vessels with decreased pulmonary view with color Doppler shows midmuscular ventricular septal defect
with septoparietal bands in right ventricle
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
echocardiography
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 figure 11: Transthoracic echocardiography in inverted apical four
the VSD’s. Apical four chamber view is helpful in diagnosing chamber view shows large perimembranous ventricular septal defect
276
inlet VSD’s, mid muscular and apical muscular defects. trans VSD jet velocity is high with restrictive defects, reflecting 19
Parasternal long axis view demonstrates the perimembranous normal pulmonary and RV systolic pressure. The trans VSD
defects with or without formation of septal aneurysms. gradient of >64 mm of Hg indicates a restrictive VSD with

Parasternal short axis view at the semilunar valve level images a normal pulmonary artery pressure. The RV pressure can be
defects in the outlet septum at the 1 o’clock position, defects in also assessed from the velocity of the regurgitant tricuspid jet.
the subaortic septum at the 11 o’clock to 12 o’clock positions, Serial echocardiograms are performed to monitor defect size
and perimembranous defects at the 10 o’clock to 11 o’clock and development of PH. Also one needs to assess for potential
positions. In the parasternal short axis view at the level of the complications such as aortic cusp prolapse or AR.
mitral valve, the anterior defects of the trabecular septum are In Gerbode defects, Dzwonczyk et al. suggested that color
imaged between 12 and 1 o’clock position, mid muscular defects flow imaging in the parasternal short-axis, apical short-axis,
between 9 and 12 o’clock position and the inlet defects between and subcostal projections is useful to confirm the diagnosis
7 and 9 o’clock position. Multiple defects and any associated and eliminate the other possibilities like rupture of a sinus of
cardiovascular anomalies can be recognized (Figure 12). The Valsalva aneurysm, endocardial cushion defect and tricuspid
rare Gerbode defects are suspected on echocardiography when regurgitation.83 They also indicated that a disturbed color
there is an unusually dilated RA and a high Doppler gradient signal in the RA not originating from the TV and with a velocity
between LV and RA. The TTE with color Doppler can make of 4.0 m/sec or more should suggest a LV-RA communication.
out the type of defect and the presence of TR (Figure 13). The
physiologic consequences can be assessed by the amount of Transesophageal and 3D Echocardiography
LV and LA dilatation, as well as RV hypertrophy. The Doppler
method of recording the maximal velocity of the shunt allows Transesophageal echocardiography (TEE) is occasionally
estimation of the systolic pressure gradient across the defect. used. In the pediatric age group, it is used most often
If this value is subtracted from the measured arterial systolic intraoperatively to assess the completeness of the repair.
blood pressure, it is possible to obtain an estimate of the right Three-dimensional echocardiography has proved accurate for
ventricular pressure. This reflects the pulmonary artery systolic quantifying shunt and can provide accurate visualization of
pressure if there is no right ventricular outflow obstruction. The defects that otherwise are difficult to evaluate by TTE.20,84,85
magnetIC reSonanCe ImagIng

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 well-
validated 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 heart’s volumes and of the
associated anomalies that are sometimes difficult to diagnose
figure 12: Modified two chamber view with color Doppler in post- by echocardiography.42
surgical residual shunt shows hyperechogenic surgical patch with re-
sidual and Swiss cheese ventricular septal defects
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
figure 13: Transthoracic echocardiography in apical four chamber
echocardiography sometimes cannot identify.87
2. Interventional device closure of one or more defects. 277
view with color Doppler shows type II Gerbode defect (arrow)
4 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.
shunt defects
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:
Mean PA pressure – Mean LA pressure
PVR =
Pulmonary blood flow (Qp)
a B
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 c d
ventriculography into four types88 (Figures 14A to D). figures 14a to d: Left ventricular angiogram in the left anterior
1. Tubular type: The shunt jet is long and the diameter in the oblique view shows the various types of perimembranous ventricular
left and right sides of the septum is the same. septal defect
2. Window-like type: The shunt jet is scattered immediately
after crossing the septum.
3. Aneurysmal type: The shunt jet has an aneurysmal shape. ed, and some experimental protocols have demonstrated acute
4. Conical type: The shunt jet is wide on the left side of the benefit of digoxin on hemodynamic measurements.93
septum and narrow on the right side. 1. Diuretics (e.g. furosemide) may be used to relieve
pulmonary congestion. Furosemide is usually given in a
meDICal management dosage of 1 to 3 mg/kg/day in 2 or 3 divided doses.
2. Captopril is the most frequently used ACE inhibitor in
The children with small VSDs are asymptomatic and have children, especially in neonates and infants where usage
excellent long-term prognosis. The parents need to be given of enalapril may induce renal dysfunction. The intitial
reassurance, advise on subacute bacterial endocarditis prophy- starting dose is 0.1 mg/kg/dose; it is gradually increased
laxis and periodic clinical follow-up. Medical therapy is required to 0.5-1 mg/kg/dose three times a day. Maximum dose is
for patients with moderate to large VSDs till any intervention 2 mg/kg/dose. Blood pressure and renal parameters should
is done to close the defect. Patients will also require nutritional be monitored when up titrating the dose. Enalapril is
support with increased caloric density of feeds to ensure ad- commonly prescribed in older children. The initial dosage
equate weight gain.The drugs are usually a combination of is 0.1 mg/kg/24 hours divided twice daily, gradually
diuretics (i.e. furosemide), afterload-reducing agents angio- increasing to 0.5 mg/kg/24 hours divided into twice daily
tensin-converting enzyme (ACE) inhibitors and digoxin.89,90 dose.
Many studies have shown that the contractile function of the 3. Digoxin in a dose of 5 to 10 mcg/kg/day may be indicated
LV is normal or increased, casting doubts on the usefulness of if diuresis and afterload reduction do not relieve symptoms
278 digoxin.91,92 However, symptomatic relief has been document- adequately.
approaCHeS to VentrICular 19
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 figure 15: Subaortic VSD being closed with interrupted sutures
through the tricuspid valve
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. conduction system. Outlet VSDs can be approached through
the pulmonary artery. Subarterial VSDs can be approached
table 2 through the aorta or pulmonary artery. An RV approach can
The indications for surgery at various age groups be used as an alternate approach for VSDs depending on the
site. Apical VSDs can be done through the RA or at times
S. No. Age Indication for surgery
through a limited left ventriculotomy, though this can lead to
1. < 6 months Uncontrolled congestive heart failure, left ventricular dysfunction.
failure to thrive
Patients with high PVR pose a considerable problem as they
2. 6–24 months Pulmonary hypertension, symptomatic can have pulmonary hypertensive crises postoperatively. This
3. 2–5 years Qp/Qs > 1.5 : 1, aortic regurgitation can be managed by using pulmonary vasodilators like nitric
4. > 5 years Aortic regurgitation oxide and at times extracorporeal membrane oxygenation
(ECMO). Another option is flap valved VSDs closure,
Surgery for VSDs are done through median sternotomy which allows temporary right to left shunting preventing
using conventional hypothermic cardiopulmonary bypass suprasystemic RV pressures. This is at the cost of systemic
with bicaval cannulation. Rarely in small infants, deep desaturation, but it allows the patient’s left sided cadiac output
hypothermia with circulatory arrest may be used. The aim to be maintained.95
of closure is to have a secure and complete closure without Postoperative problems include residual VSDs, conduction
damaging adjacent structures, depending on the anatomy. disturbances (varying degrees of heart block), which may
The conduction tissue and the aortic valve are particularly in need pacemaker insertion, TR and persistant PH.
danger in perimembranous VSDs. The conduction system is The mortality for elective VSDs closure is ever diminishing
related to the posteroinferior margin and the region adjacent (less than 1%). Incremental risk factors include multiple VSDs,
to the septal leaflet and upto the papillary muscle of Lancisi, severe PH and associated cardiac anomalies. Late presentation
represents the danger zone, where the conduction system with PH and severe cardiac cachexia are particular problems
may be damaged. Muscular VSDs have adequate muscle in developing countries.
protecting the conduction system and do not pose a danger to
the conduction system. Devices for percutaneous Closure of Ventricular
Closure of VSDs are based on the type of the VSDs Septal Defect
and ease of access. The current trend is to try to avoid a
ventriculotomy as far as possible. Perimembranous and inlet Transcatheter closure of VSDs in animal models was described
VSDs are exposed through the RA and everting the TV leaflets for the first time by Rashkind in 1975.96 He used hooked
by appropriately placed traction sutures. Closure may be done single-disc and double-disc devices. Subsequently Lock et
by using interrupted or continuous sutures taking care to avoid al12 and Goldstein et al97 performed transcatheter closure
the conduction system (Figure 15). Sutures are placed on the of VSDs using Rashkind double-umbrella and Clamshell
base of the septal leaflet in the area adjacent to the triangle of devices. The transcatheter device closure of muscular VSDs 279
4 have been in vogue for the past 15 years. Although relatively is 4 mm larger and the proximal disc is 3 mm larger than
common, perimembranous VSDs can be difficult to close the diameter of the waist. To achieve immediate complete
percutaneously. Previous devices (e.g. Rashkind or button closure, three Dacron polyester patches are sewn securely
shunt defects
devices) have been unsuccessful in attempts to close these with polyester thread into the two discs and the waist of the
VSDs, because of the proximity of the defects to the aortic device. The device size corresponds to the diameter of the
valve and the potential for aortic valve damage. waist. The mechanism of closure involves stenting of the VSD
Now many varieties of new devices like muscular septal by the device and subsequent thrombus formation within
occluder for muscular VSDs, asymmetrical and symmetrical the device with eventual complete neoendothelialization.
perimembranous septal occluder and Amplatzer duct The device is available in sizes from 6 to 24 mm and these
occluder II (ADO II) are available to close perimembranous are delivered through 6 to 9 French sheaths. The delivery
VSDs and rarely Gerbode shunts. The Amplatzer devices system is prepackaged with a long Mullins type sheath,
(St. Jude Medical, Plymouth, MN) are made up of Nitinol, loader, diaphragm with side arm flush, delivery cable and
an alloy of 55 percent nickel and 45 percent titanium and pin vise. The Amplatzer membranous VSD occluder, is an
this has superelastic properties.98 It also has been proven asymmetric, self-expandable, double-disc device, unlike the
to have excellent biocompatability. The muscular VSD muscular septal occluder. Current recommendations are to
occluder (AVSDO) is a double-disc device. The thickness use this device in older patients, who weigh > 8 kg and who
of the nitinol wire is 0.004″ for devices 10 mm and smaller have a subaortic rim >2 mm. The various types of devices
and 0.005″ for larger devices. The leading retention disc with their characteristics are shown in Figures 16A to E.
a B c
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
280 d e
reCommenDatIonS for DeVICe CloSure delineation of anatomic details of the number and location of 19
of muSCular VSDs99 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
Class IIa transcatheter therapy. For apical muscular VSD, the anatomy
Class IIA is reasonable for infants who weigh ≥ 5 kg, children in the apical region is also important for the choice of device
and adolescents with hemodynamically significant (left and implantation route.
ventricular or left atrial volume overload or pulmonary to
systemic blood flow ratio ≥ 2:1) muscular ventricular septal Procedure
defect (MVSD) to undergo percutaneous VSD device closure
(level of evidence: B). Most procedures are performed with the patient under general
anesthesia and with either TEE guidance. The complications
Class IIb encountered in transcatheter closure of muscular VSD using
an AVSDO are arrhythmias occurred during or soon after
Neonates, infants who weigh < 5 kg and children with the procedure. Fortunately all the reported arrhythmias were
hemodynamically significant (left ventricular or left atrial transient. Reported complications have included aortic and
volume overload or pulmonary to systemic blood flow ratio tricuspid regurgitation, device embolization, complete heart
> 2 : 1) MVSD and associated cardiac defects requiring block, transient left bundle-branch block, hemolysis and small
cardiopulmonary bypass may be considered for performance of residual shunts.
hybrid perventricular closure of the VSD off bypass, followed In our experience perimembranous VSDs can be closed with
by surgical repair of the remaining defects or device placement asymmetrical or symmetrical perimembranous VSD occluders
during cardiopulmonary bypass (level of evidence: B). depending on the length of the septal tissue below the aortic
valve, (Figure 17A) so that there is no impingement of the
Class III aortic valve leading to AR (Figure 17B). If perimembranous
VSDs are small (<6 mm) with adequate aortic rim one can use
1. Neonates, infants and children with hemodynamically ADO II with excellent results (Figures 18A and B). The ADO
significant (left ventricular or left atrial volume overload II is also useful in closing fenestrated septal aneurysm (Figures
or pulmonary to systemic blood flow ratio >2 : 1) inlet 19A and B).
MVSDs with inadequate space between the defect and Spontaneous closure of Gerbode defects is very rare and
the atrioventricular or semilunar valves should not closure of essentially all Gerbode defects is recommended to
undergo device closure (hybrid or percutaneous) (Level of avoid progression of TR and occurrence of IE. Surgical closure
Evidence: B). remains the mainstay of treatment, yet transcatheter device
2. Neonates, infants and children with a small to moderate- closure is shown to be an effective alternative. There are a few
sized MVSD (without symptoms or evidence of pulmonary reports of successful transcatheter closure of congenital and
hypertension) in whom there is a reasonable expectation acquired Gerbode defect.100 The ADO II meant for closing long
that the defect will become smaller over time should be ducts in infants is very handy in closing these rare Gerbode
followed up expectantly and do not need closure of the VSDs (Figures 20 A and B).The major concerns during device
VSD (Level of Evidence: B). closure of these defects include alignment of the device,
conduction disturbances, and worsening TR. Transcatheter
patient Selection device closure of Gerbode defect is safe and effective. The TTE
can demonstrate the well-positioned device between the LV and
Patients are selected for transcatheter occlusion based on the RA space (retention disc below the TV) with disappearance of
presence of a hemodynamically significant VSD with left to TR (Figures 21A and B).
right shunt. The patients are evaluated with history, physical Unlike the regular ventricular septal occluder, the
examination, ECG and TTE. deployment of ADO II is done from the aortic end without
Exclusion criteria include: Weight less than 3.0 kg (unless making an arteriovenous loop. Hence, the fluoroscopic and
the hybrid perventricular approach is used); distance of less procedure time is shorter. As the cost of ADO II is lesser
than 4 mm between the VSD and the aortic, pulmonic, mitral compared to regular ventricular septal occluders, it is also
or tricuspid valves; PVR greater than 7 indexed Wood units; very useful in the closure of multiple VSDs, especially post
sepsis and patients with conditions that would be expected to surgical residual shunts (Figures 22A and B).
be exacerbated by the use of aspirin unless other antiplatelet In a case with ASD and VSD, simultaneously VSD and
agents could be used for 6 months.99 then ASD can be closed in the same setting (Figure 23). The
Prior to the transcatheter closure procedure, a alternative routes are either jugular or rarely through an ASD
comprehensive TTE study is of critical importance. Accurate (Figures 24A and B). 281
4
shunt defects
a B
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 B
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

a B
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
a B
figures 20a and B: A. Left ventricular angiogram in anteroposterior view shows the ventricular septal defect jet opacifying right atrium (RA) in 283
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
4
shunt defects
a B
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.
a B
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
There is not much literature on device closure of large mm Hg and PVRI decreased from 13.8 to 7.7 after 100 percent
midmuscular VSDs with severe PH. The surgery carries high- O2 inhalation. The QP: QS increased from 1.2 to 2:1 after O2
risk in such patients. However in selected cases, akin to flap inhalation and the right to left shunt disappeared, SaO2 increased
surgery, the fenestrations can be done with large dilator prior from 90 to 98 percent. This patient underwent device closure
to deploying the device. A 12-year-old girl had previously with 24 mm VSD muscular septal occluder after 2 fenestrations
undergone PDA ligation 4 years years back. Her aortic pressure were iatrogenically created with 7F dilator (Figures 25A
284 was 110/70 m 83 and pulmonary artery pressure was 92/60 m 71 and B). After deploying the fenestrated device, one can
mm Hg (PCW pressure was 22), which dropped to 76/46 m 56 check with either RV or LV angiogram (Figures 26A and B).
The position of the device and residual shunt can be assessed 19
by either TTE or TEE with color Doppler. On one year follow-
up, 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 27A 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
figure 23: Fluoroscopy shows atrial and ventricular done with systemic heparinisation. The pericardium is opened.
septal devices in situ Purse string is taken over the anterior surface of the RV. The RV
a B
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
4
shunt defects
a B
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
a B
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
puncture is done with a 18 gauge needle (modified Seldinger) since it is accomplished on the beating heart. The position of
under TEE guidance. 0.038″ × 95 cm diagnostic guide wire is the device can be checked by both LV angiogram and TEE
introduced through the needle and through the VSD into LV. (Figures 29A and B).
A 10 F sheath is passed over guidewire into LV (Figure 28A).
Through the sheath, the Amplatzer VSD occluder is passed future Direction
and the LV disc deployed in LV and the device is deployed by
releasing the proximal disc in the RV (Figure 28B). The major The interventional treatment of VSD is much more
286 advantage of this procedure is avoidance of cardiopulmonary complicated than closure of secundum ASD or PDA. There
bypass, less blood loss and speedy postoperative recovery, are mitral and tricuspid valve apparatus in both ventricular
19

a B
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
a B
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 by catheters or guide wires. Therefore, most of the defects
in the right ventricular cavity. The chordae tendinae and targeted for closure are muscular defects, which are at least
papillary muscle of septal leaflet of TV sits on the septum 4 mm away from any cardiac valve. The closure results and
and come in the way of making an arteriovenous loop. safety depends on the device used and also on the location
Perimembranous VSD is usually located in an area quite of the defects. With AVSDO, the complete closure rate is as
near the aortic and tricuspid valves. Encroaching any of these high as 100 percent. Besides, ADO and ADO II are also used 287
structures would cause severe complications. In addition, the in selected cases. ADO II has simple and smaller delivery
position and orientation make the defect, difficult to be passed system and can be effectively repositioned or retrieved
4
shunt defects
a B
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 referenCeS

end, without making an arteriovenous loop. Thus, with the 1. Roger H. Clinical researches on the congenital communication
newly designed devices like AVSDO II, transcatheter closure of the two sides of the heart by failure of occlusion of the
of perimembranous VSD in selected patients can be done interventricular septum. Bull de l’ Acad de Med. 1879; 8:1074-
as an alternative to surgical closure. Hybrid device closure 94, 1189-91.
has further brought down the lower limit of age and weight 2. Perloff JK, Marelli AJ. Ventricular septal defects. In: Perloff
criteria for the device closure. JK, Marelli AJ (Eds). Clinical recognition of congenital heart
disease. 6th edition. Philadelphia Saunders, an imprint of
Elsevier Inc, 2012.
ConCluSIon 3. McDaniel NL, Gutgesell HP. Ventricular Septal Defects. In:
Allen HD, Driscoll DJ, Shaddy RE, Feltes TF (Eds). Moss and
Ventricular septal defect is one of the most common CHDs. Adams’ Heart Disease in Infants, Children, and Adolescents:
It may be small, medium or large. The defect may be located Including the Fetus and Young Adults. 7th edition. Philadelphia
in the membranous or muscular portion of the ventricular Lippincott Williams and Wilkins, 2008, pp. 667-82.
septum. The good clinical, echocardiographic assessment is 4. Suresh V, Rao AS, Yavagal ST. Frequency of various congenital
important for timely management. The transcatheter closure heart diseases: analysis of 3790 consecutively catheterised
of VSDs in selected patients has been very encouraging with patients. Indian Heart J. 1995; 47:125-8.
the specially designed Amplatzer VSDO. Many common 5. Glen S, Burns J, Bloomfield P. Prevalence and development
types of muscular VSDs can be effectively occluded with the of additional cardiac abnormalities in 1448 patients with
congenital ventricular septal defects. Heart. 2004; 90:1321-5.
device. The spectacular results with device closure makes
6. Pyles LA, Steiner ME, Gustafson RA, et al. Ventricular septal
the various devices important in the armamentarium of the defect. In: Moller JH (Ed.). Surgery of Congenital Heart
interventional cardiologist caring for patients with VSD. Disease: Pediatric Cardiac Care Consortium 1984–1995.
Device closure of VSD could be an attractive alternative to Armonk, NY: Futura Publishing Company; 1998. pp. 45-66.
traditional surgery. The surgery is the age old time tested 7. Allwork SP. Maladie du Roger 1879: A New translation for the
method of management offered for large VSDs, not suitable centenary. Am Heart Journal. 1979; 98:307-11.
for device closure and for subpulmonic VSDs. In this modern 8. Wood P. The Eisenmenger syndrome or pulmonary hyper-
era no patient of VSD should be allowed to develop IE or tension with reversed central shunt. Br Med J. 1958. pp.
Eisenmenger’s complex. 755-62.
9. Heath D, Edwards JE. The pathology of hypertensive pulmonary
288 vascular disease; a description of six grades of structural
The patient does not care about your science; what he changes in the pulmonary arteries with special reference to
wants to know is, can you cure him? congenital cardiac septal defects. Circulation. 1958; 18(4 Part
— Martin H Fischer 1):533-47.
10. Müller WH Jr, Danimann JF Jr. The treatment of certain 26. Hoffman JLE, Rudolph AM. The natural history of ventricular 19
congenital malformations of the heart by the creation of septal defects in infancy. Am J Cardiol. 1965; 16:634-53.
pulmonic stenosis to reduce pulmonary hypertension and 27. Wilkinson JL. Ventricular septal defect. In: Moller JH,

excessive pulmonary blood flow; a preliminary report. Surg Hoffman JIE (Eds.) Pediatric Cardiovascular Medicine. New
Gynecol Obstet. 1952; 95:213-9. York: Churchill Livingstone; 2000. pp. 289-309.
11. Lillehei CW, Cohen M, Warden HE, et al. The results of direct 28. Nora JJ, Fraser FLC. Medical Genetics. Philadelphia: Lea and
vision closure of ventricular septal defects in eight patients by Febiger; 1974. p. 334.
means of controlled cross circulation. Surg Gynecol Obstet. 29. Garg V, Kathiriya IS, Barnes R, et al. GATA4 mutations cause
1955; 101:446-66. human congenital heart defects and reveal an interaction with
12. Lock JE, Block PC, McKay RG, et al. Transcatheter closure of TBX5. Nature. 2003; 424:443-7.
ventricular septal defects. Circulation. 1988; 78:361-8. 30. Jenkins KJ, Correa A, Feinstein JA, et al. Noninherited risk
13. Rigby ML, Redington AN. Primary transcatheter umbrella factors and congenital cardiovascular defects: current knowl-
closure of perimembranous ventricular septal defect. Br Heart edge: a scientific statement from the American Heart Associa-
J. 1995; 73:585-6. tion Council on Cardiovascular Disease in the Young: endorsed
14. Sideris EB, Walsh KP, Haddad JL, et al. Occlusion of by the American Academy of Pediatrics. Circulation. 2007;
congenital ventricular septal defects by the buttoned device. 115:2995-3014.
“Buttoned device” Clinical Trials International Register. Heart. 31. Lacro RV. Dysmorphology and Genetics. In: Keane JF, Lock
1997; 77:276-9. JE, Fyler DC (Eds). Nadas’ Pediatric Cardiology. Philadelphia,
15. Tofeig M, Patel RG, Walsh KP. Transcatheter closure of a mid- PA: Saunders; 2006. pp. 49-72.
muscular ventricular septal defect with an Amplatzer VSD 32. Newman TB. Etiology of ventricular septal defects: an epide-
occlusion device. Heart. 1999; 81:438-40. miologic approach. Pediatrics. 1985; 76:741-9.
16. Thanopoulos BD, Tsaousis GS, Konstadopoulou GN, et al. 33. Czeizel A, Mészáros M. Two family studies of children with
Transcatheter closure of muscular ventricular septal defects ventricular septal defect. Eur J Pediatr. 1981; 136:81-5.
with the Amplatzer Ventricular Septal Defect Occluder: Initial 34. Nora JJ, Nora AH. The genetic contribution to congenital heart
clinical applications in children. J Am Coll Cardiol. 1999; disease. In: Nora JJ, Takao A (Eds). Congenital Heart disease
33:1395-99.7. Mount Kisco. New York: Futura Publishing Company, 1984.
17. Hijazi ZM, Hakim F, Haweleh AA, et al. Catheter closure 35. Nora JJ, Nora AH. Update on counseling the family with a
of perimembranous ventricular septal defects using the first-degree relative with a congenital heart defect. Am J Med
new Amplatzer membranous VSD occluder: initial clinical Genet. 1988; 29:137-42.
experience. Catheter Cardiovasc Interv. 2002; 56:508-15. 36. Goor DA, Edwards JE, Lillehei CW. The development of
18. Marshall AC, Perry SB. Cardioseal/Starflex devices, In: Rao the interventricular septum of the human heart; correlative
PS, Kern MJ (Eds). Catheter Based Devices for the Treatment morphogenetic study. Chest. 1970; 58:453-67.
of Noncoronary Cardiovascular Disease in Adults and 37. Friedman AH, Fahey JT. The transition from fetal to neonatal
Children. Philadelphia Lippincott, Williams & Wilkins. PA; circulation: normal responses and implications for infants with
2003. pp. 253-8. heart disease. Semin Perinatol. 1993; 17:106-21.
19. Le T, Vassen P, Freudenthal F, et al. Nit-Occlud (Nickel- 38. Soto B, Becker AE, Moulaert AJ, et al. Classification of
Titanium Spiral Coil). In: Rao PS, Kern MJ (Eds). ventricular entricular septal defects. Br Heart J. 1980; 43: 332-43.
Catheter Based Devices for the Treatment of Noncoronary 39. Van Praagh R, Geva T, Kreutzer J. Ventricular septal defects:
Cardiovascular Disease in Adults and Children. Philadelphia: how shall we describe, name and classify them? J Am Coll
Lippincott,Williams & Wilkins, PA; 2003. pp. 259-64. Cardiol. 1989; 14:1298-9.
20. Ergene O, Nazli C, Kocabas U, et al. Percutaneous closure of 40. Truex RC, Bishof JK. Conduction system in human hearts
perimembranous ventricular septal defect with an Amplatzer with interventricular septal defects. J Thorac Surg. 1958; 35:
Duct Occluder in a dextrocardia patient. Int J Cardiol. 2011; 421-39.
150:e77-80. 41. Anderson RH, Ho SY, Becker AE. Anatomy of the human
21. Bass JL, Gruenstein D. Transcatheter closure of the per- atrioventricular junctions revisited. Anatomical Record. 2000;
imembranous ventricular septal defect-preclinical trial of a 260:81-91.
new Amplatzer device. Catheter Cardiovasc Interv. 2012; 42. Benson LN, Yoo SJ, Habshan FA, et al. Ventricular septal
79:1153-60. defects. In: Anderson RH, Baker EJ, Macartney FJ, Rigby ML,
22. Minette MS, Sahn DJ. Ventricular septal defects. Circulation. Shinebourne EA, Tynan M (Eds). Paediatric Cardiology. 2nd
2006; 114:2190-7. edition. London: Churchill Livingstone; 2002. pp. 591-624.
23. Rudolph AM. Ventricular septal defect. In: Rudolph AM (Ed). 43. Kirklin JK, Castaneda AR, Keane JF, et al. Surgical
Congenital Diseases of the Heart: Clinical-Physiological management of multiple ventricular septal defects. J Thorac
Considerations. 3rd edition. John Wiley and Sons UK; 2009. Cardiovasc Surg. 1980; 80:485-93.
pp. 148-78. 44. Seddio F, Reddy VM, McElhinney DB, et al. Multiple ven-
24. Moe DG, Guntheroth WG. Spontaneous closure of uncompli- tricular septal defects: How and when should they be repaired?
cated ventricular septal defect. Am J Cardiol. 1987; 60:674-8. J Thorac Cardiovasc Surg. 1999; 117:134-9.
25. Roguin N, Du ZD, Barak M, et al. High prevalence of muscular 45. Agmon Y, Connolly HM, Olson LJ, et al. Noncompaction of
ventricular septal defect in neonates. J Am Coll Cardiol. 1995; the ventricular myocardium. J Am Soc Echocardiogr. 1999;
26:1545-8. 12:859-63.
289
4 46. Hagler DJ, Edwards WD, Seward JB, et al. Standardized no-
menclature of the ventricular septum and ventricular septal
64. Van Praagh R, Mcnamara JJ. Anatomic types of ventricular
septal defect with aortic insufficiency. Diagnostic and surgical
defects, with applications for two-dimensional echocardiog- considerations. Am Heart J. 1968; 75:604-19.
shunt defects
raphy. Mayo Clin Proc. 1985; 60:741-52. 65. Tatsuno K, Konno S, Ando M, et al. Pathogenetic mechanisms
47. Kirklin JW, Harshbarger HG, Donald DE, et al. Surgical of prolapsing aortic valve and aortic regurgitation associated
correction of ventricular septal defect: anatomic and technical with ventricular septal defect. Anatomical, angiographic, and
considerations, J Thorac Surg. 1957; 33:45-59. surgical considerations. Circulation. 1973; 48:1028-37.
48. Gumbiner CH, Takao A. Ventricular septal defect. In: Garson 66. Nadas AS, Ellison RC, Weidman WH. Pulmonary stenosis,
A Jr, Bricker JT, Fisher DJ, Neish SR (Eds). The Science aortic stenosis, ventricular septal defect: clinical course and
and Practice of Pediatric Cardiology. Williams and Wilkins indirect assessment. Circulation. 1977; 56:(Suppl 1-1).
Baltimore, Md; 1998. pp. 1119-40. 67. van Hare GF, Soffer LJ, Sivakoff MC, et al. Twenty-five-
49. Specific cardiac defects. In Libby: Braunwald’s Heart Disease: year experience with ventricular septal defect in infants and
A Textbook of Cardiovascular Medicine, 8th edition. Libby children. Am Heart J. 1987; 114:606-14.
P, Bonow RO, Mann DL, Zipes DP (Eds). Elsevier Saunders 68. Kidd L, Driscoll DJ, Gersony WM, et al. Second natural
2007. history study of congenital heart defects. Results of treatment
50. Ellis JH 4th, Moodie DS, Sterba R, et al. Ventricular septal of patients with ventricular septal defects. Circulation. 1993;
defect in the adult: Natural history and unnatural history. Am 87:138-51.
Heart J. 1987; 114:115-20. 69. Thurman J. Aneurysms of the heart. Med Clin Trans R Med
51. Farru O, Duffau G, Rodriguez R. Auscultatory and phonocardio- Clin Soc (Lond) 1838; 21:187.
graphic characteristics of supracristal ventricular septal defect. 70. Gerbode F, Hultgren H, Melrose D, Osborn J. Syndrome of
Br Heart J. 1971; 33:238-45. left ventricular-right atrial shunt: successful surgical repair of
52. French H. Possibility of loud congenital heart murmur disappear- defect in 5 cases, with observations of bradycardia on closure.
ing when child grows up. Guys Hospital Reports. 1918; 32:87. Ann Surg 1958; 148:433-46.
53. Weber FP. Can the clinical manifestation of congenital heart 71. Laurichesse J, Ferrane J, Scebat L, et al. Communication
disease disappear with the general growth and development between the left ventricle and the right auricle. Arch Mal Coeur
of the patient? British Journal of Children’s Diseases. 1918; 1964; 57:703-24.
15:113. 72. Riemenschneider TA Moss AJ. Left ventricular–right atrial
54. Syamasundar Rao P. Diagnosis and management of acyanotic communication. Am J Cardiol 1967; 19:710-8.
heart disease: part II - left-to-right shunt lesions. Indian J 73. Wasserman SM, Fann JI, Atwood JE, Burdon TA, Fadel
Pediatr. 2005; 72:503-12. BM. Acquired left ventricular-right atrial communication:
55. Lin MH, Wang NK, Hung KL, et al. Spontaneous closure of Gerbode-type defect. Echocardiography 2002; 19:67-72.
ventricular septal defects in the first year of life. J Formos Med 74. Olsovsky MR, Topaz O, DiSciascio G, Vetrovec GW. Acute
Assoc. 2001; 100:539-42. traumatic ventricular septal rupture. Am Heart J 1996;
56. Hiraishi S, Agata Y, Nowatari M, et al. Incidence and natural 131:1039-41.
course of trabecular ventricular septal defect: two dimensional 75. Newman JN Jr, Rozanski L, Kreulen T. Acquired left ventricular
echocardiography and color Doppler flow imaging study. J to right atrial intracardiac shunt after myocardial infarction: a
Pediatr. 1992; 120:409-15. case report and review of the literature. J Am Soc Echocardiogr
57. Alpert BS, Mellits ED, Rowe RD. Spontaneous closure of 1996; 9:716-20.
small ventricular septal defects: probability rates in the first 76. Katz ES, Tunick PA, Kronzon I. To-and-fro left ventricular-
five years of life. Am J Dis Child. 1973; 125:194-6. to right atrial shunting after valve replacement shown by
58. Collins G, Calder L, Rose V, et al. Ventricular septal defect: transesophageal echocardiography. Am Heart J 1991; 121:
clinical and hemodynamic changes in the first five years of life. 211-4.
Am Heart J. 1972; 84:695-705. 77. Kudo T, Ryo S, Shimakura T, Imamura E, Imai Y. LV-RA
59. Weidman WH, Blount SG Jr, DuShane JW, et al. Clinical shunt developing after repair of VSD. Kyobu Geka 1974;
course in ventricular septal defect. Circulation. 1977; 56 27:93-8.
(1 Suppl):156-169. 78. Sakakibara S, Konno S. Left Ventricular-Right Atrial
60. Corone P, Doyon F, Gaudeau S, et al. Natural history of Communication. Ann Surg. 1963; 158:93-9.
ventricular septal defect. A study involving 790 cases. 79. Silbiger JJ, Kamran M, Handwerker S, Kumar N,
Circulation. 1977; 55:908-15. Marcali M. The Gerbode defect: left ventricular to right
61. Gasul BM, Dillon RF, Vrla V, et al. Ventricular septal defects; atrial communication-anatomic, hemodynamic, and
their natural transformation into the cyanotic or noncyanotic echocardiographic features. Echocardiography. 2009; 26:
type of tetralogy of Fallot. J Am Med Assoc. 1957; 164: 993-8.
847-53. 80. Thery C, Lekieffre J, Dupuis C. Atrioventricular block
62. Saleeb SF, Solowiejczyk DE, Glickstein JS, Korsin R, Gersony secondary to a congenital aneurysm of the membranous
WM, Hsu DT. Frequency of development of aortic cuspal septum. Histological examination of conduction system. Br
prolapse and aortic regurgitation in patients with subaortic Heart J. 1975; 37:1097-100.
ventricular septal defect diagnosed at < 1 year of age. Am J 81. Gersony WM, Nugent EW, Weidman WH, et al. Report from
Cardiol. 2007; 99:1588-92. the Joint Study on the Natural History of Congenital Heart
63. Ando M, Takao A. Pathological anatomy of ventricular septal Disease. Circulation. 1977(Suppl 1):24.
290 defect associated with aortic valve prolapse and regurgitation. 82. Vaquez H, Bordet E. Le Coeur et al.’Aorte, Etudes Radio-
Heart Vessels. 1986; 2:117-26. graphiques. Paris, JB Bailliere et Fils. 1913.
83. Dzwonczyk T, Davidson WR, Jr. The spectrum of left
ventricular-right atrial communications in the adult: Essentials
92. Kimball TR, Daniels SR, Meyer RA, et al. Effect of digoxin on
contractility and symptoms in infants with a large ventricular
19
of echocardiographic assessment. J Am Soc Echocardiogr septal defect. Am J Cardiol. 1991; 68:1377-82.

1995; 8:263-9. 93. Stewart JM, Hintze TH, Woolf PK, et al. Nature of heart failure
84. Ishii M, Hashino K, Eto G, et al. Quantitative assessment of in patients with ventricular septal defect. Am J Physiol. 1995;
severity of ventricular septal defect by three-dimensional 269:H1473-H1480.
reconstruction of color Doppler-imaged vena contracta and 94. Surgery for Congenital defects. In: JF Stark, MR De Leval,
flow convergence region. Circulation. 2001; 103:664-9. Tsang VT (Eds). John Wiley and Sons; 2006. pp. 354-71.
85. Kardon RE, Cao QL, Masani N, et al. New insights and obser- 95. Rao PS, Raju V, Narayana M. Flap valved closure of ventricular
vations in three dimensional echocardiographic visualization of septal defects with increased pulmonary vascular resistance.
ventricular septal defects. Circulation. 1998; 98:1307-14. Interact Cardiovasc Thorac Surg. 2010; 11:577-80.
86. Keane JF, Fyler DC. Ventricular septal defect. In: Fyler DC. 96. Rashkind WJ. Experimental transvenous closure of atrial and
Nadas’ Pediatric Cardiology. Philadelphia, Pa: Hanley and ventricular septal defects. Circulation. 1975; 52:II-8.
Delfus, Inc; 1992. pp. 435-7. 97. Goldstein SAN, Perry SB, Keane JF, Rome J, Lock JE.
87. Morales DL, Fraser CD Jr. Ventricular Septal defects. In: Transcatheter closure of congenital ventricular septal defects. J
Yuh DD , Vricella LA, Baumgartner W(Eds). Johns Hopkins Am Coll Cardiol. 1990; 15:240A.
Manual of Cardiothoracic Surgery. McGraw Hill Companies 98. Liu X, Stice JD. Shape-memory alloys and their applications. J
US; 2007. pp. 1077-89. Appl Manufactur Syst. 1990; 3:65-72.
88. Yang J, Yang L, Wan Y, et al. Transcatheter device closure 99. Feltes TF, Bacha E, Beekman RH 3rd, et al. Indications for
of perimembranous ventricular septal defects: mid-term cardiac catheterization and intervention in pediatric cardiac
outcomes. Eur Heart J. 2010; 31:2238-45. disease: a scientific statement from the American Heart
89. Artman M, Graham TP Jr. Congestive heart failure in infancy: Association. American Heart Association Congenital Cardiac
recognition and management. Am Heart J. 1982; 103:1040-55. Defects Committee of the Council on Cardiovascular Disease
90. Montigny M, Davignon A, Fouron JC, et al. Captopril in infants in the Young; Council on Clinical Cardiology; Council on
for congestive heart failure secondary to a large ventricular Cardiovascular Radiology and Intervention; American Heart
left-to-right shunt. Am J Cardiol. 1989; 63:631-3. Association. Circulation. 2011; 123:2607-52.
91. Berman W Jr, Yabek SM, Dillon T, et al. Effects of digoxin in 100. Arora R, Trehan V, Kumar A, Kalra GS, Nigam M. Transcatheter
infants with a congested circulatory state due to a ventricular closure of congenital ventricular septal defects: Experience
septal defect. N Engl J Med. 1983; 308:363-6. with various devices. J Interv Cardiol 2003; 16:83-91.
291
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 from an infant with complete

atrioventricular septal defect showing discrepancy in left ventricular
inflow (line-a) and outflow (line-b) measurements. Ao = Aorta;
DA = descending aorta; LA = Left atrium; LV = Left ventricle;
RV = Right 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
Incidence of AVSD varies from 1.4 to 10.8 percent (4–5%)
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
Figure 1: Subcostal short-axis view at the level of the common AV
non-invasive method (Alberta heritage study). The incidence
valve showing the components of the common AV valve. Ao = Aorta;
IBL = Inferior bridging leaflet; LV = Left ventricle; PA = Pulmonary of CHD in offspring of female with AVSD is 9.6 to 14.3
artery; RV = Right ventricle; SBL = Superior bridging leaflet. percent.
20
AtrioventriculAr SeptAl DeFectS

Figure 3: 2D echocardiography in apical four-chamber view showing Figure 4: Subcostal coronal view with anterior tilt (modified view) in
loss of offsetting with inlet ventricular septal defect in a case of diastole showing ‘gooseneck deformity’ of left ventricular outflow tract,
common. AV valve LA = Left atrium; LV = Left ventricle; RA = Right i.e. left ventricular outflow tract in elongated with anterior unwedged
atrium; RV = Right ventricle. position of aorta. Inferior bridging leaflet is seen (arrow). Ao = Aorta;
LV = Left ventricle; RA = Right atrium; RV = Right ventricle.
A B c D
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 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
Classification I
valve has a single annulus.
Patients with AVSD are classified into the following groups 3. Transitional AVSD: Subtype of partial AVSD. Additional
(Figures 5A to D): finding is a small inlet VSD that is partially occluded by
1. Partial AVSD: When the two bridging leaflets are joined dense chordal attachment to the septum.
to each other, by a tongue of tissue dividing the AV valve 4. Intermediate AVSD: Subtype of complete AVSD that has
into two separate orifices. Thus, partial AVSD has primum distinct right and left AV valve orifices despite having only
defect, two distinct mitral and tricuspid AV valve annuli one common annulus.
and cleft mitral valve is present invarably. Cleft anterior mitral leaflet (AML): Cleft is actually the
2. Complete AVSD is when the bridging leaflets are free, meeting point of left halves of anterior and posterior 293
guarding the opening of both the atria to the respective bridging leaflets. It is a type of commissure. The cleft
4
Shunt DeFectS
A B c
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.
A B
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 • Interatrial shunt only (primum ASD)
septum. The isolated cleft in the AML is directed towards • Interventricular shunt only (AV canal VSD) (Figures 7A
aortic valve annulus. and B)
• AVSD with intact interatrial and interventricular septum.
Classification II Rarely with complete AVSD, there will be absence of any
interatrial shunt when the superior bridging leaflet is attached to
Rarely AVSD is classified depending on level of shunting of the the lower end of atrial septum and absence of VSD when it is
294 blood in the cardiac chambers (Figures 6A to C): firmly attached to the ventricular septum as described with partial
• Interatrial and interventricular shunts AVSD.
20

A B
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
A B
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 • Unbalanced with left dominant type (Figures 9A and B): It
This type of classification depending upon the size of the is usually associated with pulmonary stenosis/pulmonary
ventricular chambers has practical importance as it helps in atresia.
deciding the modality of treatment for AVSD (univentricular The decision between balanced and unbalanced ventricles
versus biventricular pathway). in borderline cases is best done using AV valve index (AVVI).
• Balanced type
• Unbalanced AVSD: Unbalance in AVSD refers to two Method
distinct but related anatomical features:
1. Ventricular hypoplasia. Tracing the circumference of the common AV valve orifice
2. Malalignment of the AV valve junction. Latter may during end-diastole, averaged over three cardiac cycles using
affect ventricular size developmentally. a subcostal view on 2D echocardiography. This circumference
• Unbalanced with right dominant type (Figures 8A and is then divided by a line drawn over the place of intact
B): This is the common type, usually associated with arch ventricular septum (IVS) from the tip of the infundibuluar 295
hypoplasia, coarctation of aorta. septum to the crest of the muscular septum, thus dividing AV
4
Shunt DeFectS
A B
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
A B c
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
valve into left and right components. For a balanced AVVI Classification IV/Rastelli Classification
should be between 0.4 and 0.6 (Figures 10A and B).
When the right-sided component is small, the right ventricle It is more of historical importance. Complete AVSD is divided
is hypoplastic, the tricuspid valve overrides a malaligned inlet into type A, B, C based on extent of straddling of anterior
ventricular septum and the right AV valve has attachments that bridging leaflet into right ventricle (RV) (Figures 11A to C).
straddle the VSD. When the left-sided component is small, • Type A: It is seen in 50 to 70 percent of patients. Anterior
296 the morphological left ventricle is hypoplastic, but straddling bridging leaflet (ABL) is completely committed to left
does not occur despite AV malalignment because straddling is ventricle and there is minimal bridging of leaflet into
reserved for conoventricular malalignment. RV. Chordae are attached to the crest of the ventricle.
This type is the most common type associated with of the superior and inferior endocardial cushions. Complete 20
Down’s syndrome. AVSD: Lack of fusion between the superior and inferior
• Type B: More bridging of ABL into RV and chordae are cushions resulting in the formation of separate anterior and

attached into the papillary muscle of RV. It is least common posterior bridging leaflets.
type seen in 3 percent of patients of AVSD. It is almost Failure of the endocardial cushions to fuse results in defect
always associated with unbalanced AVSD with right in the AV septum. Recent work has shown that the lesion should
dominance. be considered as defect of dorsal mesenchymal protrusion
• Type C: It is seen in 30 percent of patients of AVSD. and inadequate development of vestibular spine rather than
Maximal bridging of ABL into RV with chordal attachment endocardial cushion defect. Additional experimental work has
into RV free wall. It is commonly associated with complex shown that the ingrowth through this vestibular spine/dorsal
anomalies like tetralogy of Fallot (TOF), double outlet mesenchymal protrusion is derived from the second heart
right ventricle (DORV), transposition of the great arteries stage being regulated by islet-1 gene.
(TGA) and in hetrotaxy syndromes. 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
SpeCIAl foRmS of AVSD from apex to aortic valve is increased. LVOT and aorta are
unwedged from their normal position—‘sprung aorta’ giving
malaligned Atrial Septum or Double-outlet Right Atrium the appearance of ‘gooseneck’ deformity.
AVSD may be associated with conotruncal anomalies like
The atrial septum is deviated to the left of the AV junction. TOF and DORV. Dextrodorsal conus cushions contribute to
Both right and left AV valves are visualized from right atrium, the development of right AV valve and the outflow tracts lie
which is connected to both ventricles through primum ASD. adjacent to their inflow tracts. Shift of the AV valve orifice to
Pulmonary veins may be isolated and obstructed if deviation either side results in disproportionate or unbalanced ventricle.
to the left is extreme.
nAtuRAl HIStoRy
AVSD with Intact Ventricular Septum
With improved diagnostic modalities and surgical advances,
This rare condition was first described by Anderson RH in more and more cases of AVSD are being diagnosed antenatally
1984 in two cases diagnosed on postmortem examination. (Figures 12A to D) and are successfully living normal adult
JP Kaski has described five cases of complete AVSD with intact lives. Factors on which fetal outcome depends are:
septum diagnosed by echocardiography. They were diagnosed 1. Morphology of the defect
as AVSD because they had the essential morphologic features 2. Size of VSD
which include: 3. Degree of ventricular hypoplasia
1. Disproportion between inlet and outlet portions of 4. Degree of AV valve regurgitation (most important for
interventricular septum. intrauterine survival)
2. Malorientation of the aortic valve relative to the AV valve. 5. Associated LVOT obstruction
3. Common AV junction guarded by common AV valve. 6. Associated coarctation and syndromes.
Such an entity is being described also in relation to the Outcome of the non-surgical patients of complete AVSD
spontaneous closure of AVSD. may be extrapolated from the 1979 study of Bollinger et al.
They had 54 percent survival at 6 months, 35 percent at 12
Common Atrium months, 15 percent at 24 months, 4 percent at 5 years. Most
patients die by 2 to 3 years of age without surgery. Patients
Common atrium is characterized by the near absence of of partial AVSD and minimal AV regurgitation do well.
the atrial septum and in the presence of two ventricles, it Atrial fibrillation is an important cause of late morbidity and
is always associated with an AVSD. In these cases TGA, mortality.
DORV, univentricular AV connection and anomalous venous The risk of infective endocarditis coincides with the
connections, asplenia syndrome are frequently encountered. regurgitation and not with the abnormal structure of a
The radiological and electrocardiographic characteristics of functionally competent valve. Paradoxical emboli are rare
the patients are indistinguishable from AVSD. with ostium primum ASD in contrast to ostium secundum
ASD, because emboli that originate in the lower extremities
embRyology are carried by inferior vena caval blood towards the midportion
of the atrial septum. Superior vena caval streaming targets the
It is characterized by the faulty development of the endocardial lower atrial septum, but emboli rarely originate in the upper
cushions and AV septum. Partial AVSD: Incomplete fusion extremity. 297
4
Shunt DeFectS
A B
c D
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 physical examination

moDAlItIeS foR AVSD
In the setting of pulmonary vascular obstructive disease, there
Clinical manifestations may be baseline systemic desaturation. A small water hammer
pulse is due to the rapid ejection of the large left ventricular
These are related to degree of the shunt and AV valve stroke volume of severe left AV valve regurgitation. The ‘v’
regurgitation. In complete AVSD, tachypnea and failure to wave is dominant in the jugular venous pulse especially in the
thrive occurs in view of congestive heart failure virtually in presence of left AV valve regurgitation being transmitted across
all patients by 1 year of age as a result of the large shunt and the ASD. The presence of congestive heart failure elevates
AV valve regurgitation further compounds this problem. If both ‘a’ and ‘v’ waves. The physical examination shows
these patients do not develop symptoms one should suspect hyperactive precordium, an accentuated first heart sound and
early development of pulmonary vascular obstructive disease. wide split second heart sound with P2 increased in intensity.
Patients of partial form have a presentation similar to large A loud holosystolic murmur of AV valve regurgitation may be
298 ASD. The phenotypic features of associated syndromes heard at the apex. Findings of AV valve regurgitation in the
particularly Down’s syndrome should be looked for. presence of a pretricuspid shunt strongly favors the clinical
diagnosis of AVSD. The mid-diastolic flow murmurs occurs that there will be a common valve orifice. Counterclockwise 20
across the AV valves. They can heard at the left lower depolarization results in q waves in leads I and aVL (Figure
parasternal border and may be also heard at the apex. 13). The S waves in leads II, III and aVF are characteristically

notched on their upstrokes because of a change in the direction
electrocardiography and electrophysiology of the terminal force of QRS (better seen on vector loop). In
few of the patients, the initial portion of the QRS is directed
Atrioventricular node is displaced posteriorly near the orifice downward and to the right.
of the coronary sinus and the His bundle is displaced inferiorly.
In conjunction with the ventricular septal myocardium, the Chest X-ray
His bundle is shorter than normal and is posteriorly placed,
the left bundle branch is displaced posteriorly and arises from The X-ray in isolated primum ASD is similar to any other
the common bundle immediately after it enters the ventricular pretricuspid shunt or secundum ASD. When left AV valve
septum. The left anterior division of the left bundle branch regurgitation is present, the right atrium is especially enlarged
has fewer fibers than normal and is increased in length, the because regurgitation flow is directed into the right atrium.
left posterior division is shorter than normal and provides The left cardiac border is straightened by a prominent right
small branches to the posterobasal wall of the left ventricle. ventricular outflow tract. In Down’s syndrome, the lateral
The right bundle branch is abnormally long and this results in chest X-ray may show a double manubrial ossification
characteristic features of AVSD on electrocardiogram (ECG). center and the posterioanterior projection may show absent
Sinus rhythm is seen in most patients of primum ASD. or rudimentary 12th rib. Hyperinflation of the lung may be
Prolongation of PR interval in relation to the patient’s age present because of upper airway obstruction in patients with
and heart rate is seen in 18 to 70 percent of the patients, due Down’s syndrome.
to increased intra-atrial conduction time. P wave changes
indicating right or left or biatrial enlargement are seen in 54 echocardiography
percent of the patients. Superiorly directed p wave axis may be
seen in cases of left isomerism. The assessment of the AV junction is readily achieved by
The mean QRS axis ranges from –30° to –120° degrees, two-dimensional echocardiography and since AVSD are
most commonly between –30° and –90° in partial form and primarily an abnormality of this region, reliable delineation
between –90 and –120 in complete form, due to specific of their detailed morphology is possible. Color flow Doppler
anomaly of the conduction system. Extreme left axis deviation interrogation compliments the anatomical investigation by
is a feature seen commonly in Down’s syndrome. The demonstrating the sites of intracardiac shunting and AV
superiorly oriented frontal QRS axis is manifested by dominant regurgitation, as well as defining any obstruction in the LVOT
S waves in leads III and aVF and prominent R wave in aVR. if present. Pulsed and continuous wave Doppler is used for
Further the frontal axis is deviated upwards and to the right, the quantitative measurements to assess pulmonary artery pressure,
deeper the scooping of the ventricular septum and more likely 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
299
leads III and aVF and prominent R wave in aVR and counter clockwise depolarization results in q waves in I and aVL
4 Various views may be used for defining various
Box 1: Two-dimensional echocardiographic findings
echocardiographic features common to AVSD (Box 1).
common to AvSD patients
Subcostal coronal view shows common AV junction, loss of
Shunt DeFectS
1. Loss of offsetting of atrioventricular valves.

offsetting of AV valves, scooped out inlet septum and inferior
2. Deficiency of inlet portion of ventricular septum.
bridging leaflet of AV valve (Figures 1 to 4). Subcostal sagittal 3. Presence of common atrioventricular valve fibrous orifice.
view shows common AV junction and in addition to that both 4. Abnormal morphology of atrioventricular valve cusps.
superior and inferior bridging leaflets and anterior unwedged 5. Abnormal position of papillary muscles.
position of aorta can be very well profiled. Parasternal short- 6. Longer left ventricular outflow and anterior unwedged
axis view shows trileaflet left AV valve, presence of cleft position of aorta.
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) Box 2: checklist for echocardiographic
and presence of LVOTO obstruction. Subcostal long-axis evaluation of AvSD
view LVOT shows ‘gooseneck’ deformity (long left ventricle 1. Type of defect, partial or complete atrioventricular septal
outflow with anterior position of aorta) (Figure 4). While defect.
evaluating a patient with AV septal defect, the things that need 2. Extent of atrial shunting.
to be addressed are tabulated in Box 2. 3. Extent of ventricular shunting.
Straddling of AV valve is also an issue, which needs 4. Presence and degree of atrioventricular valve regurgitation.
5. Commitment of atrioventricular valves to respective
to be defined. Straddling of left AV valve is defined in the ventricles, is there balanced atrioventricular connection or
parasternal long-axis view, while for right AV valve the four- unbalanced atrioventricular connection, degree of ventricular
chamber view and subcostal enface view are required to hypoplasia if present.
profile the chordal attachment (Figure 1). 6. Presence of straddling.
Color flow mapping is required to define presence and 7. Potential for left or right ventricular outflow obstruction.
8. Pulmonary artery pressures.
direction of shunting across interatrial or interventricular septum
9. Associated lesions.
(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 ventricle-right atrial shunt or right ventricle-left atrial shunt.
four chamber and parasternal short axis views are required to Right ventricle-left atrial shunt could be a cause of cyanosis in a
look for presence of AV valve regurgitation, presence of left 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

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
Figure 14: Echocardiography from a 4 years old child with partial mapping shows turbulence starting in the subaortic area.
300 atrioventricular septal defect showing trileaflet left atrioventricular
valve, and presence of cleft (arrow). LV = Left ventricle; RV = Right
Careful Doppler interrogation shows the site of the obstruction
ventricle. and severity of LVOTO.
Box 3: Causes of left ventricular outflow tract
20
obstruction in AvSD

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.
CompleX AtRIoVentRICulAR SeptAl DefeCt

Complex AVSD can be defined as AVSD morphology, which
precludes two-ventricle correction. The following conditions
Figure 15: Apical four-chamber with color flow mapping in a child with can be the cause of such a situation.
partial atrioventricular septal defect showing intact interatrial septum,
common atrioventricular junction, and small inlet ventricular septal
1. The most frequent is the association of AVSD with hetrotaxy/
defect with left-to-right shunt. Ventricular septal defect is small due to isomerism. Anomalous systemic/pulmonary venous
attachment of superior bridging leaflet to crest of ventricular septum connection, hypoplasia of ventricles and abnormalities
(arrow). LA = Left atrium; LV = Left ventricle; RA = Right atrium; RV = of ventricular arterial connection frequently precludes
Right ventricle.
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 AVSD—Because 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.
ASSoCIAtIon
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 Down’s 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.
Figure 16: Subcostal sagittal view with color flow mapping from a child The presentation of the defect ranges from fetal life to those
with partial atrioventricular septal defect showing left atrioventricular with partial forms presenting even in later age group.
valve regurgitation through cleft (arrow). LV = Left ventricle; RV = Right
ventricle; 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
Right Ventricular outflow tract obstruction especially in setting of isomerism. With unbalanced AV
connection leading to hypoplastic left ventricle, aortic arch
Pulmonary stenosis can occur at subvalvular (malalignment should be well profiled in suprasternal long axis view to rule
of outlet septum, infundibular hypertrophy), valvar or sup- out arch anomalies like coarctation of aorta and aortic arch 301
ravalvular levels and can also be well profiled on echocardio- interruption. With hypoplastic RV, pulmonary stenosis and
graphy. pulmonary atresia may be the associations.
4 CARDIAC CAtHeteRIzAtIon AnD AngIogRApHy
As discussed, preoperative assessment can now generally
Shunt DeFectS
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.
Figure 17: Left ventricular angiogram in left anterior oblique view
ASSeSSment of opeRAbIlIty shows the typical gooseneck deformity. Courtsey: Dr IB Vijayalakshmi
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 1. If the leaflets are not attached to atrial and ventricular
right ventricular outflow tract obstruction is clearly inoperable. level then potential for shunting is there at both atrial
What is required is the assessment of patients with borderline and ventricular level. The extent of ventricular shunting
operability. This is further analyzed by echocardiography and depends upon the proximity of the bridging leaflets to
cardiac catheterization. the septal crest. If there is free-floating leaflets then there
Echocardiographic features of inoperability are hugely will be large ASD and VSD. When cords from septal crest
dilated pulmonary arteries, a dominant RV, a compressed tether to one or both of the bridging leaflet than ventricular
appearing LV (not a small LV of unbalanced AVSD) and chest shunting can be limited.
X-ray showing absence of plethora. 2. When both the superior and inferior bridging leaflets are
Cardiac catheterization is useful in borderline cases. A raised attached to septal crest then shunting occurs only at atrial
and fixed pulmonary vascular resistance (> 8 Wood units/m2) level.
with little or no fall after 100 percent oxygen administration, 3. Sometimes, the bridging leaflets and a tongue, if present
indicates inoperability. An important precaution in these attached to the under surface of the atrial septum, this
patients is that the venous sample should be obtained high up arrangement permits shunting to occur only at the
in superior vena cava because of the atrial level of shunt. ventricular level.
In a hypothetical situation of a complete AVSD with a large 4. The degree of LV outflow obstruction augments left-to-
ventricular component, on room air the response to oxygen to right shunt and also augments AV valve regurgitation.
help to decide operability should have a large quantam of rise 5. Paradoxical embolization seen with ASD secundum is rare
in Qp : Qs (beyond 5 : 1) than just a smaller rise (2 : 1). with ostium primum defects.
LV angiogram in left anterior oblique (LAO) position gives
an important guide to the relation of the pulmonary to aortic Without pulmonary Stenosis
blood flow. If the dye appears earlier in pulmonary artery and
the density is more than aorta, it indicates a significant left-to- Partial Atrioventricular Septal Defect
right shunt and points to operability.
Partial atrioventricular septal defects behave like ASD. In
HemoDynAmIC ASSeSSment of AtRIoVentRICulAR the absence of significant AV valve regurgitation and normal
SeptAl DefeCt pulmonary artery pressure, the lesion is well tolerated and
patients may present late like fossa ovalis ASD. Significant
Hemodynamics of AVSD essentially depend upon the potential AV valve regurgitation, however may cause early congestive
for shunting and AV valve regurgitation. The degree of the former heart failure. Accurate assessment of pulmonary artery
depends upon the relationship of the bridging leaflets and of the pressure and AV valve regurgitation is critical in decision
connecting tongue if present, to the lower edge of atrial septum making in timing of surgery. Doppler assessment of
and to the crest of the scooped out ventricular septum. pulmonary artery pressure is usually performed by assessing
302
tricuspid regurgitation velocity. Care should be taken in not weight of 5 kg or an age of 6 months, is only possible at the 20
confusing left ventricle-right atrial shunt (LV-RA shunt) for cost of more complications and a higher rate of reoperation.
tricuspid regurgitation as the former invariably produce high- Severely symptomatic patients may benefit from earlier

velocity signals and will wrongly overestimate pulmonary operative repair because of failure to thrive and to prevent
artery pressure. secondary changes accompanying a large shunt and/or severe
AV valvar regurgitation. In these patients, the AV valve
Mechanism of Atrioventricular Valve Regurgitation annulus may dilate as a result of the large shunt and valvular
tissue may fibrose at the site of regurgitation, factors that may
In the majority of cases, the AV valve regurgitation occurs complicate a repair if postponed for too long.
through the cleft in the left AV valve (Figures 15A and B). Factors that increase surgical risk are:
Atrioventricular valve regurgitation can also occur through a. Young age.
the commissures of the left AV valve or through the right AV b. Severe AV valve regurgitation.
valve also. c. Hypoplasia of LV.
d. Increased/fixed pulmonary vascular resistance
Complete Atrioventricular Valve Septal Defect e. Severe preoperative regurgitation.
f. Associated defects viz double orifice mitral valve, single
Complete AVSD is associated with large VSD and pulmonary left papillary muscle, additional VSD.
arterial hypertension. Thus, congestive heart failure develops
in the first few months of life. Also rapid progression of objectives of Surgical Correction
pulmonary vascular disease, within 6 months of life, occurs
in this condition. Thus, there is an urgent need to correct these Repair of complete AVSD must be done prior to the
lesions early in life. development of irreversible pulmonary vascular obstructive
disease, preferably before 6 months of age. Surgical correction
With pulmonary Stenosis aims at closure of all septal defects, maintenance of competent
AV valves and repair of associated defects.
Patients with pulmonary stenosis present physiologically as
TOF. However, the morphology is much more complicated. Closure of the Septal Defect
The VSD, which is predominantly of the inlet type, also
extends into the outlet. Anterior malalignment of the outlet Methods of repair can be categorized classically as use of
septum causes right ventricular outflow obstruction and other one or two patches for closure of the entire defect, presuming
morphological abnormality associated with tetralogy. there are atrial and ventricular components to close. A further
categorization is whether or not bridging valvar leaflets are
mAnAgement of AVSD cut in order to expose the AV valvar annulus at the ventricular
septal junction. The cutting of bridging leaflets can be applied
With the exception of those rare patients with small septal to both the superior and inferior bridging leaflet, depending on
defects and competent AV valves, the treatment for all patients their extent of bridging. A further variable is provided by the
with an AVSD will be surgical correction. Medical therapy possibility of attaching one or both bridging leaflets directly
with digoxin and diuretics serves to stabilize the patients with to the septal crest. The various surgical strategies used in the
a large shunt and cardiac failure during early infancy. Feeding surgical repair of AVSD are enumerated in Box 4.
by gastric tube is sometimes necessary to provide adequate
caloric intake. The only aim of medical therapy is to postpone Repair of the left Atrioventricular Valve
surgery in symptomatic infants, preferably until the age of 6
months. In young infants with a very high pulmonary vascular Two schools of approach has evolved in the past decade for
resistance, oxygen is occasionally given continuously during repair of the left AV valve depending upon whether to leave
the last weeks prior to surgery in an attempt to reduce the the left AV valve bifoliate or trifoliate.
incidence of postoperative pulmonary hypertensive crises.
Normally, in the absence of congenital cardiac disease, Surgery for Dual orifices in the left
pulmonary vascular resistance drops and remains fairly Atrioventricular Valve
constant after 1 month of age. In the presence of AVSD with
interventricular shunting, resistance may increase following Dual orifices in the left or right ventricular components of
the initial drop. In some infants, resistance may even never the AV valve occur in about one-twentieth of patients, more
show the anticipated initial drop. This rise in pulmonary often in the setting of separate left and right valvar orifices. It
vascular resistance has served as a strong incentive to operate is an abnormal and incomplete connection between two of the
earlier in life. It is generally observed that repair below a body leaflets that forms the anatomical basis for the extra orifice, 303
4 Box 4: permutation of these strategies results in at
Left atrioventricular valve stenosis: It can result from
excessive suture closure of cleft, congenital anomaly of
least eight possible combination of techniques
AV valve or inappropriate surgical division of common
Shunt DeFectS
1. Using one patch and cutting the bridging leaflets. atrioventricular valve between the two ventricles. Doppler
2. Using one patch, but leaving the bridging leaflets intact,this
is only possible with minimal bridging of both bridging echocardiography helps in assessment of severity and need
leaflets and constitutes a numerically minor subset. for reintervention.
3. Using one patch in which a cut is made to accommodate Right atrioventricular valve stenosis or regurgitation: It is
one of the bridging leaflets, this is applicable when one of less common and has less serious hemodynamic consequences
the bridging leaflets bridge minimally, as in the Rastelli A than left AV valve regurgitation. It can be accurately diagnosed
malformation.
by careful Doppler evaluation.
4. Using one patch, having sutured the bridging leaflets
directly to the ventricular septal crest.
5. Using two patches and attaching the inferior bridging Left Ventricular Outflow Tract Obstruction
leaflet to the ventricular septal crest, while inserting a patch
between the septal crest and the superior bridging leaflet, Subaortic stenosis occurs more frequently after repair of the
which is left intact. partial AVSD. Underlying mechanisms producing stenosis
6. Using two patches, attaching the inferior bridging leaflet
to the ventricular septal crest, while cutting the superior
include, adherence of anterior bridging leaflet to the crest of
bridging leaflet. ventricular septum, membranes or chordae crossing LVOT or
7. Using two patches and cutting the bridging leaflets. redundant atrioventricular valve tissue protruding into LVOT.
8. Using two patches, leaving the bridging leaflets intact. Echocardiography helps in identifying the cause and severity
of obstruction.
which in the setting of the left valve is usually committed postoperative management
to a inferomural or superomural papillary muscle and most
significantly, is usually not regurgitant. Any annuloplasty will After the operation, the patient is kept intubated and ventilated
reduce even further the effective area of the valvar orifice. If until the hemodynamic situation is stable. Because of the
possible, these extra orifices are best left alone. known tendency of these postoperative patients to develop
pulmonary hypertensive crises, it is wise to prevent acidosis
Intraoperative Assessment and to avoid other precipitating factors, such as overly vigorous
intratracheal suction. Monitoring of pulmonary arterial
Because of the complexity of the repair, echocardiographic pressure is advantageous in patients known to have pulmonary
assessment in the immediate postoperative period and in long hypertension. The presence of a conspicuous left atrial ‘v’
term is mandatory to detect any important imperfections in the wave on left atrial pressure tracing, both before and after the
repair. Following lesions should be sought for in the patients procedure, is a good indication for regurgitation. The absence
following AVSD repair. of a ‘v’ wave, unfortunately, is not a fool proof indicator that
the valve will be competent immediately after repair, possibly
Residual Atrial or Ventricular Septal Defects because of the altered hemodynamics due to anesthesia or
through the damping effect of a large atrium. Presence of
Doppler color flow mapping is particularly useful as a rapid substantial ‘v’ waves, nonetheless, is an indication for further
screening technique for residual septal defects and to look for investigation and usually, further attempts at repair of the valve.
their location, size and hemodynamic impact.
ReSultS of SuRgICAl RepAIR
Inadequate Repair of Common Atrioventricular Valve
The function of the left AV valve, ventricular imbalance and
Inadequate repair of common atrioventricular valve is by far pulmonary hypertension are the sole incremental surgical risk
the most common postoperative problem. This will result in factors for death. Results of surgical repair have improved
left/right AV valve regurgitation or left/right AV valve stenosis. steadily over the decades, concomitant with developments
Left atrioventricular valve regurgitation: This is more in medical therapy, more appropriate criteria for selection
common in patients with complete form of AVSD than partial. and improvements in myocardial preservation, surgical skill
Most commonly it occurs at the commissure between anterior and postoperative care. The function of the left AV valve has
and posterior bridging leaflets—cleft mitral valve. Large determined the operative result, in both the short and the long
mural leaflet is also more common in patients with significant term. Late reoperations for left AV valvar dysfunction have been
residual left AV valve regurgitation. Echocardiography helps a source of considerable morbidity and indeed also mortality.
in assessment of severity of regurgitation and its hemodynamic At least 25 percent of patients require reoperation, most
304 significance. commonly because of progressive left AV valve regurgitation
or for relief of LVOTO. The results published to date include bridging of both inferior and superior leaflets, rather than one or 20
the follow-up over a period of 43 years of surgical corrections both leaflets being committed primarily to the LV, is more usual
between 1958 and 2000 of 133 patients with shunting in children with trisomy 21. Accordingly, the angle of the zone

exclusively at atrial level. Actuarial survival was 78 percent. of apposition between the inferior and superior leaflets is usually
Mortality at 30 days was about 7 percent, which currently perpendicular to the ventricular septum in children with Down’s
could be expected to be no more than 1 percent. Extrapolating syndrome, while this angle is often crooked and deviated from
from this premise would make predicted actuarial survival for perpendicular, in those with normal chromosomes. Recently
current patients about 84 percent. Survival of an age- and era- published series show that Down’s syndrome is not a risk factor
matched population without any congenital cardiac anomaly for surgical repair. If anything, anatomy is more favorable in
was about 90 percent. Subtraction of these two figures leads us those with trisomy 21. It is pulmonary vascular resistance, itself
to predict an excess mortality of just 6 percent, 43 years after related to age and other associated problems, that determine the
the surgical correction. Similar results have been reported risk for these patients.
elsewhere, but it is impossible to predict with total accuracy
the outcomes for correction at the present time, albeit that ConCluSIon
results are anticipated to be excellent for those with shunting
exclusively at atrial level, presuming it is possible to create a AVSD is characterized by the anatomical hallmark of a
competent left AV valve. Long-term results for repair of those common AV junction coexisting with deficient AV septation.
having a common AV valve are well-documented in analysis The components of AVSD includes a common AV valve ring
of 801 children in Sweden born alive between 1973 and 1997. with five leaflet valve that guards a common orifice, unwedged
Mortality at 30 days for the 502 patients undergoing surgical LVOT, an aortic orifice that is anterosuperior to the common
correction over the last 5 years of the study was 1 percent. AV junction, disproportion of the left ventricular mass. There
The actuarial survival curve flattens off after 1 or 2 years, and are a number of classifications based upon the morphological
shows a loss of lives of about 10 percent in 30 years. How characteristics and hemodynamic features of the lesion.
this compares to an age- and era-matched population is not Clinical features and presentation of AVSD depend on degree
known. Although similar results have been published, there of AV valve regurgitation and magnitude of left to right shunt.
are not many papers on results over the long term. An associated pretricuspid shunt in combination with a post
tricuspid shunt has a presentation of exaggerated pretricuspid
DoWn’S SynDRome shunt lesion. Jugular venous pulse exhibits a dominant ‘V’
wave (not only with the presence of tricuspid regurgitation)
Discussion of surgical treatment of AVSD cannot be concluded also as right atrium receives the regurgitate jet also from the
without consideration of the problems created by coexisting left ventricle. Precordial examination and palpitations are
Down’s syndrome. Children with Down’s syndrome are more similar to ostium secundum defect with the addition of the
likely to have AVSD than children without Down’s syndrome. apical systolic murmur that radiates towards the sternum as
Rastelli type A are more common in Down and are more likely far as the right sterna border. A fixed splitting of the second
to have associated TOF. Sidedness and splenic anomalies are heart sound (as for the pre-tricuspid shunt) may be associated
less common. LVOTO, left ventricular hypoplasia, coarctation with mid-diastolic flow murmur because of the flow across
of aorta and additional muscular VSD are less common. the right sided AV valve associated with systolic flow
Three principle issues are at stake. First, it is often claimed murmur across the pulmonary valve. The electrocardiogram
that children with Down’s syndrome have a higher incidence of typically shows a left axis deviation with counterclockwise
pulmonary hypertension. Second, the anatomical spectrum is depolarization. The chest X-ray shows increased pulmonary
different in children with Down’s syndrome, when compared vascularity with dilated right atrium and right ventricle. The
with their chromosomally normal peers. Third, there has been features are altered with the of degree of pulmonary artery
some controversy on the perceived benefit of surgical repair. hypertension and AV valve regurgitation. Echocardiography
Pulmonary hypertension is about 10 times more prevalent is the investigative modality of choice and would even
in patients with Down’s syndrome and has an earlier onset. decide the type of surgical intervention and modification of
Those patients with Down’s syndrome, therefore, must the surgical intervention if required. Long term outcomes
undergo surgery at a very young age, preferably before 6 are generally good and depend on the residual defects, left
months, while some argue for even earlier repair. Pulmonary ventricular outflow tract obstruction and degree of AV valve
hypertension has been reported to be more prevalent in those regurgitation.
having the Rastelli A configuration.
Obstruction to the left ventricular inflow and outflow, in Medicine is the only profession that labours incessantly to
contrast, is said to be far less frequent in the setting of Down’s destroy the reason for its own existence.
syndrome. This probably reflects the more frequent existence of —James Bryce, 1914
common valvar orifice in association with trisomy 21. Extensive 305
4 SuggeSteD ReADIngS 11. Reeder GS, Danielson GK, Seward JB, et al. Fixed subaortic
stenosis in atrioventricular canal defect: a Doppler
1. Anderson RH, Ho SY, Falcao S, et al. The diagnostic features echocardiographic study. J Am Coll Cardiol. 1992;20:
Shunt DeFectS
of atrioventricular septal defect with common atrioventricular 386-94.

junction. Cardiol Young. 1998;8:33-49. 12. Shrivastava S, Radhakrishnan S, Tomar M. Atrioventricular
2. Allwork SP. Anatomical-embryological correlates in septal defects in Echocardiography in congenital heart diseases,
atrioventricular septal defects. Br Heart J. 1982;47:419-29. A practical approach. 1st edition. 2008. pp. 42-51.
3. Cetta F, Minich L, Edwards W, et al. Arioventricular septal 13. Silverman NH, Zuberbuhler JR, Anderson RH. Atrioventricular
defect. In: Allen HD, Shaddy RE, Driscoll DJ, Feltes TF septal defects: cross sectional echocardiographic and
(Eds). Heart Diseases in Infants, Children and Adolescents, 7th morphologic comparison. Int J Cardiol. 1986;13:309-31.
edition. Lippincort Williams and Wilkins; 2008. pp. 647-67. 14. Sigfússon G, Ettedgui JA, Silverman NH, et al. Is a cleft in
4. Chan KY, Redington AN, Rigby ML. Color flow mapping in the anterior leaflet of an otherwise normal mitral valve an
atrioventricular septal defects: Does it have an important role in atrioventricular canal malformationt? J Am Coll Cardiol.
diagnosis and management? Cardiol Young. 1991;1:315-23. 1995;26:508-15.
5. Defects in cardiac septation. Snider AR, Serwer AG, Ritter 15. Smallhorn JF, Tommasini G, Anderson RH, et al. Assessment
SB (Eds). Echocardiography in Pediatric Heart Disease. 2nd of atrioventricular septal defects by two dimensional
addition. Mosby. 1997. pp. 235-97. echocardiography. Br Heart J. 1982;47:109-21.
6. Ebels T, Anderson RH. Atrioventricular septal defect. In: 16. Wenink AC, Ottenkamp J, Guit GL, et al. Correlation of
Anderson RH, Macartney RF, Shinebourne EA, Baker EJ, morphology of the left ventricular outflow tract with two-
Rigby ML, Tynan M (Eds). Paediatric, Cardiology. 2nd edition. dimensional Doppler echocardiography and magnetic
Churchill Livingstone: Har Court Publishers Limited. 2002.pp. resonance imaging in atrioventricular septal defect. Am J
939-81. Cardiol. 1989;63:1137-40.
7. Kaski JP, Wolfenden J, Josen M, et al. Can atrioventricular 17. Welke KF, Morris CD, King E, Komanapalli C, Reller MD,
septal defects exist with intact septal structures? Heart. Ungerleider RM. Population-based perspective of long-term
2006;92:832-35. outcomes after surgical repair of partial atrioventricular septal
8. Mehta S, Hirschfeld S, Riggs T, et al. Echocardiographic defect. Ann Thorac Surg. 2007;84:624-8.
estimation of ventricular hypoplasia in complete atrioventricular 18. Frid C, Björkhem G, Jonzon A, Sunnegårdh J, Annerén G,
canal. Circulation. 1979;59:888-93. Lundell B. Long-term survival in children with atrioventricular
9. Minich LA, Snider AR, Bove EL, et al. Echocardiographic septal defect and common atrioventricular valvar orifice in
evaluation of atrioventricular orifice anatomy in children with Sweden. Cardiol Young. 2004;14:24-31.
atrioventricular septal defect. J Am Coll Cardiol. 1992;19:149-53. 19. Talwar S, Singh V, Chandra N, Marwah A, Sharma R.
10. Rastelli GC, Kirklin JW, Titus JL. Anatomic observations on Challenges in Delayed Repair of Atrioventricular Septal
complete form of persistent common atrioventricular canal Defects. World Journal for Pediatric and Congenital Heart
with special reference to atrioventricular valves. Mayo Clin Surgery. 2010;1:87-90.
Proc. 1966;41:296-308.
306
C hapter
21 Patent Ductus Arteriosus
Ramesh Arora, Vijayalakshmi IB
IntroDuCtIon lesion.8 In 1907, John Munro first suggested the surgical

ligation of the PDA.9 In 1938, Robert Edward Gross from
Patent ductus arteriosus (PDA) is a common congenital heart Boston performed the first successful closure of PDA
disease (CHD), in which there is a persistent communication in a 7-year-old girl with intractable heart failure.10 This
between the descending aorta and the pulmonary artery that surgery introduced an amazing era of progress in the field
results from the failure of the normal physiologic closure of of surgery of congenital malformations of the heart. In
the fetal ductus arteriosus. PDA closes spontaneously in the 1991, the next surgical modification was introduced when
vast majority of infants and persists into later life in some. PDA closure was done by video-assisted thoracoscopic
PDA is defined as persistent patency in term infants even after surgery.11
three months.1 PDA may be isolated or may be an essential Porstmann et al in 1967 reported the first successful
component of a complex lesion or may also coexist with other attempt of non-surgical closure of PDA using an Ivalon
cardiac anomalies. PDA is critical for survival in neonates plug.12 In 1979, Rashkind reported the use of a foam covered
with severe obstructive lesions to either the right or left side wire hook device for closure of PDA, but the results were
of the heart and this has been dealt in the chapter on Duct less encouraging in the initial human studies.13 Subsequently
Dependant Circulation (Chapter 5). his group in 1987 described the successful deployment of a
percutaneously delivered double umbrella device in an 3.5
HIStorICAL rEVIEW kg infant.14 Lock-Clamshell device was used for occlusion
of large ducts.15 Sideris introduced a self-adjustable PDA
The ductus arteriosus and the foramen ovale has been described device and this was followed by its modification into a
as early as in 181 AD by the Greek physician and philosopher buttoned device in 1991.16 In 1992, Cambier et al reported
Galen in his original descriptions of the fetal circulation.2 the use of Gianturco coils to occlude small PDA.17 In
Karl von Rokitansky, a professor of pathology from Vienna, 1998 worldwide, the Amplatzer duct occluder (ADO)
recognized PDA as a congenital malformation and illustrated was introduced and later its subsequent modifications
it in his monograph in 1852.3 William Harvey, proposed the like Amplatzer duct occluder II (ADO II).18-20 The recent
concept of active circulation of the blood. He stressed on the Amplatzer duct occluder II additional size (ADO II AS) are
large size of the arterial ductus and the fact that during fetal currently being used for infants below 6 kg and premature
life blood flowed from right to left through it.4 Highmore, neonates.21
a friend of Harvey, described closure of the oval foramen Closure of PDA in preterm babies, with drugs like
and arterial ductus to occur with the onset of respiration.5 indomethacin, a non-selective prostaglandins (PG)
He rightly believed that the arterial ductus collapsed as a inhibitor, was first reported in 1976.22 The first large and
consequence of blood being diverted to the lungs. Virchow6 comprehensive randomized controlled trial evaluating
was the first to suggest that closure of the arterial ductus the role of indomethacin and establishing its role in the
results from contraction of its mural smooth muscle, while management of PDA was published in 1983.23 In 2000,
Gerard7 introduced the concept of two-stage closure, in which it was proved that ibuprofen therapy is as efficacious as
functional constriction is followed by anatomic obliteration. indomethacin for the treatment of PDA in preterm babies
In 1898, George Alexander Gibson described the with respiratory distress syndrome and is significantly less
classic continuous murmur and other features of this likely to induce oliguria.24
4 EMBrYoLoGY A decreased incidence of PDA is seen in those neonates
whose mothers received prenatal steroids at least 24 hours
The ductus arteriosus is derived from the sixth aortic arch. In before delivery or who had prolonged rupture of membranes
Shunt DefectS
human beings, it develops by about the 6th week of embryonic of more than 72 hours duration. Decreased incidence is
development from the distal portion of one of the sixth paired also seen in neonates with intrauterine growth restriction.42
aortic arches.25 The left, right or both ductus can sometimes Antenatal steroids inhibit PG production and increase the
persist.26,27 The proximal portion of the sixth pair of embryonic responsiveness of the ductus to the constricting effect of
aortic arches usually persist as the proximal branch pulmonary oxygen and decrease its sensitivity to the dilating effects of
arteries and the distal portion of the left sixth arch persists as prostaglandins.42
the ductus arteriosus. In the typical left aortic arch, the aortic Most cases of PDA are sporadic and many are believed to
end of the ductus arteriosus arises distal to the origin of the be due to multifactorial inheritance.43 The recurrence rates
left subclavian artery and inserts at the junction of the main are between 1 to 5 percent among siblings of individuals with
and left pulmonary arteries. The distal right sixth aortic arch isolated PDA.44-48 The mechanism of the genetic inheritance
loses its connection to the dorsal aorta and degenerates. This is not yet known. It occurs with increased frequency in
transformation is complete by 8 weeks of fetal life.28 In the several genetic syndromes with chromosomal abnormalities
fetus, the ductus is about the same diameter as the descending such as trisomy 21 and 18, deletion syndromes 4q, 16p13.3
aorta and at term this is about 10 mm.29 The ductus arteriosus (Rubinstein-Taybi) and 9p (CHARGE), single-gene mutations
usually is functionally closed within 48 hours of birth in full- (such as Carpenter’s syndrome and Holt-Oram syndrome)
term neonates and is considered abnormal if it is patent in and X-linked mutations (such as incontinentia pigmenti).28,49
full-term infants older than 3 months.1,30 The major factors Familial patent arterial ductus can be either isolated or part
influencing its closure after birth are the increased production of a syndrome like Char syndrome, familial thoracic aortic
of local vasoconstrictors (like endothelin) in response to higher aneurysm/dissection and with bicuspid aortic valve with hand
arterial oxygen tension. Also the levels of the vasodilators, anomalies.49
PGE2 and PGI2 (prostacyclin), fall due to the metabolism in A number of teratogens are known to influence the develop-
the now functioning lungs and elimination of the placental ment of the ductus, including rubella, alcohol, amphetamines,
source.28 anticonvulsants like hydantoin and valproate. The ductus is
most sensitive from 18 to 60 days of gestation.50,51 Rubella in-
InCIDEnCE fection, especially in the first 4 weeks of gestation, has a high
occurrence of PDA. The incidence in these rubella affected in-
Isolated PDA accounts for 9 to 12 percent of all CHDs with fants is as high as 85 percent, when associated with other cardi-
a higher incidence in females, with a female to male ratio of ac defects and is about 50 percent when it occurs as an isolated
2 : 1.31,32 The estimated incidence of isolated PDA is 1 in lesion.52,53
2,500 to 1 in 5,000 live births.33-35 If all children with PDA
including those with ‘silent PDA’ (only echocardiographic AnAtoMY
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 In a patient with a normal left-sided aortic arch, the PDA
population.36 connects the main pulmonary artery near the origin of the left
pulmonary artery (LPA) with the descending aorta, 5 to 10 mm
EtIoLoGY distal to the origin of the left subclavian artery. The anatomy
is more varied in the presence of a right-sided aortic arch. In
In premature infants, the PDA is due to immaturity rather the neonatal period, the size and shape varies greatly from
than a developmental anomaly. In the premature neonate, case to case. The PDA is most commonly left sided and is less
the occurrence of PDA is inversely related to the gestational frequently right sided and arises distal to the right subclavian
age and maturity. The incidence is 8 per 1,000 live births artery and inserts near the proximal right pulmonary artery. In
and ranges from 20 to 42 percent.37,38 In preterm neonates, rare instances, there is a bilateral PDA.54 The right-sided PDA
weighing less than 1,000 g, the incidence can be as high as is especially associated with aortic arch anomalies.55-57
80 percent.39 The patency of the ductus after birth in preterm The proper knowledge of anatomy is needed for the cardiac
babies is due to the fact that the immature ductal tissue is surgeon doing the surgical ligation. The PDA passes from the
less sensitive to oxygen-mediated constriction and more anterior aspect of the pulmonary artery to the posterior aspect
sensitive to PG-mediated vasodilation.40 The incidence of the aorta (Figure 1). The anatomic marker of the ductus is
of PDA is higher in neonates with persistent low oxygen the recurrent laryngeal nerve, which typically arises from the
tension in the blood like respiratory distress syndrome, vagus nerve just anterior and caudal to the ductus and loops
acute intrapartum stress, asphyxia and in those born at high posteriorly around the ductus to ascend behind the aorta en
308 altitudes.41 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 figure 2: Illustrates the schematic and angiographic types of the
The type A or conical type of PDA has a narrow end at the configuration of the ductus based on Krichenko et al classification.62
pulmonary insertion with a well-defined ampulla at the aortic Ao= Aorta; MPA = Main pulmonary artery; PA = pulmonary artery;
PDA = Patent ductus arteriosus
end. The type B or window type of PDA is short and wide. It
309
4 may be narrow at the aortic insertion. The type C or tubular end of the ductus; it may remain incomplete and dilated at the
type of PDA is tubular without any constriction. The type D or aortic end and is known as ductus ampulla or ‘ductus bump’.
complex type of PDA has multiple constrictions. The type E or The histopathology of a normal ductus, not yet closed and
Shunt DefectS
elongated type of PDA has a bizarre shape with an elongated a persistently patent ductus is different, thus suggesting a
conical appearance and the constriction being remote from primary anomaly and not a secondary effect.68,69 The ductus
the anterior border of the trachea. Within the types A and is a muscular artery with a thicker intima, less elastic tissue,
B, it is further classified into three subgroups depending on spirally arranged smooth muscle fibers and more hyaluronic
the relationship of the site of insertion of the PDA at the acid than the adjacent pulmonary trunk and aorta. The media
pulmonary end to the tracheal shadow.62 of the other arteries is composed mainly of circumferentially
arranged elastic fibers.68-70
Abnormal Anatomy The mechanism of ductal closure involves a complex
interaction of the level of arterial oxygen, circulating PGs,
In the presence of complex CHD, the usual anatomy of the genetic predetermination and unknown factors.71 The rise in
ductus may not be present. In the duct dependant cyanotic systemic oxygen saturation with the onset of ventilation, after
CHDs, the ductus is markedly varied with regards to its birth, causes active constriction in the ductus. Simultaneously,
origin from the aorta, size and shape, length, tortuosity and its there is a decrease in the level of circulating PGs due to
insertion onto the pulmonary artery.63 There are four groups both factors, i.e. reduced production following removal of
seen.64 In the first group A, the PDA arises from the proximal the placenta and increased metabolism in the pulmonary
descending aorta and resembles Krichenko type A PDA. It circulation resulting from the increase in pulmonary flow.
is seen in pulmonary atresia with intact ventricular septum Removal of the strong vasodilatory effect of the PGs promotes
(PAIVS), critical pulmonary stenosis (PS) and tricuspid further constriction of the ductus.72,73 Other vasoactive
atresia. In the second group B, the PDA arises from the substances (such as acetylcholine, bradykinin and endogenous
proximal or middle part of the aortic arch (‘vertical’ ductus catecholamines or variations in pH) may be involved in this
arteriosus). These ducts are most commonly seen in tetralogy dynamic process of ductus closure.72-75 Response to PGs and
of Fallot-pulmonary atresia (TOF-PA), transposition of great oxygen varies with ductal maturity: in the full-term infant the
vessels, ventricular septal defect (VSD) with pulmonary ductus is sensitive to oxygen, while in the premature infant
atresia and in single-ventricle physiology. In the third group the PGs have a dominant effect. Consequently, in premature
C, there is intermediate origin of the PDA. The PDA arises infants failure of ductal closure results from incomplete ductal
more proximally than those in group A, but not as extreme development, whereas in full-term infants, PDA results from
as seen in group B. PDA arises from the opposite side of structural abnormalities of ductal tissue.
the origin of the left subclavian artery (LSCA). In the fourth
group D, the PDA arises from the subclavian artery. It is the HEMoDYnAMICS
least common type, comprising less than 5 percent and this
PDA has the peculiar appearance of a Blalock-Taussig (BT) The persistent patency of the ductus causes left-to-right
shunt. The long tubular ductus arises from the LSCA (or from shunting of the high aortic pressure blood into the low-
the right subclavian artery in a right aortic arch) and joins the pressure pulmonary artery, in both systole and diastole.
pulmonary artery in a roughly perpendicular fashion.64 The magnitude of the left-to-right shunt in the PDA
depends on:76,77
MECHAnISM of DuCtAL CLoSurE 1. The size and length of the PDA (directly proportional to the
diameter, inversely proportional to the length).This governs
As soon as the baby is born and starts crying and taking breath, the resistance offered to flow. In a small or restrictive PDA,
the collapsed lungs expand and the pulmonary circulation the magnitude of the left-to-right shunt is determined by
starts functioning. The ductus arteriosus, which was essential the resistance offered by the ductus.
for fetal circulation, starts closing. The postnatal closure 2. The ratio between the systemic vascular resistance (SVR)
of the ductus occurs in two stages. In the first stage within and the pulmonary vascular resistance (PVR). The pressure
12 to 15 hours after birth (in full-term infants), there is difference between the aorta and the pulmonary artery
contraction of the medial smooth muscle in the wall of the is dynamic and is dependent on the SVR, PVR and the
ductus, which leads to shortening and increased wall thickness. cardiac output. In a large PDA, the magnitude of shunting
There is also protrusion of the intimal cushions into the lumen is determined by the relationship of the SVR and PVR.
and all this results in functional closure.65,66 In the second stage, Hence, the left-to-right shunting through PDA has been
2 to 3 weeks after birth, there is infolding of the endothelium defined as dependent shunting.77
with necrosis and proliferation of subintimal layers which leads In the early weeks of life in term infants, significant
to fibrosis and permanent sealing of the lumen to produce the shunting is unusual because a high PVR limits the
310 ligamentum arteriosum.67 Closure begins at the pulmonary development of a large aorto-pulmonary pressure gradient.78
After a few weeks, volume overload of the left heart develops activity and circulating catecholamines.28 These mechanisms 21
with chamber enlargement as seen in VSD. Therefore, the are responsible for the rapid heart rate and sweating often seen
onset of congestive heart failure (CHF) with PDA is similar in infants with heart failure. The diastolic ‘runoff’ through

to that in a VSD. The pulmonary vascular bed, left heart and the PDA decreases the diastolic blood pressure in the aorta.
ascending aorta dilate proportionately to the net shunt.79 The Along with this the shorter diastolic time due to tachycardia,
chambers that enlarge are the same as those in VSD, except increased intramyocardial tension from left ventricular
for an enlarged aorta, at the level of the PDA (i.e. enlarged dilatation and increased myocardial oxygen demand may
ascending aorta and transverse arch), which also handles an result in subendocardial ischemia.84
increased amount of blood flow. The physiological consequences of significant PDA in
Isolated PDAs are classified80 hemodynamically according preterm babies may include pulmonary overcirculation and/
to the degree of left-to-right shunting into: or systemic hypoperfusion. Both the increased pulmonary
1. Silent: Tiny PDA detected only by non-clinical means blood flow and the increased lung interstitial fluid contributes
(usually echocardiography). to decreased lung compliance and pulmonary hemorrhage.85
2. Small: Continuous murmur common; Qp/Qs < 1.5/1. The increased capillary penetration of serum proteins to the
3. Moderate: Continuous murmur common; Qp/Qs = 1.5 to lung tissue leads to the inactivation of surfactant and this
2.2/1. increases the risk of respiratory distress syndrome in the
4. Large: Continuous murmur present; Qp/Qs > 2.2/1. newborn.86 Systemic hypoperfusion can occur with large
5. Eisenmenger: Continuous murmur absent; substantial pul- ductal shunts, where over 50 percent of the flow can go
monary hypertension (PH), differential hypoxemia and backwards, up into the aorta. This may result in significant
differential cyanosis (pink fingers, blue toes). hypoperfusion to the brain, kidneys and gastrointestinal tract
The physiologic features of PDA depends on the magnitude even before a hemodynamically significant ductus is clinically
of the left-to-right shunt and the ability of the infant to handle suspected. This organ hypoperfusion can result in renal
the extra volume load.81 The shunting results in increased dysfunction, necrotizing enterocolitis, feeding intolerance and
pulmonary flow and left heart volume overload. intraventricular hemorrhage in the brain.87-89
In patients with moderate or large shunts, the left ventricular The premature infants develop left ventricular failure on the
dilatation increases the left ventricular end-diastolic pressure second or third postnatal day itself, even with a small ductus.
and in turn the left atrial pressure leading to left atrial This is because the compensatory mechanisms are not well
dilatation. The increased pulmonary fluid causes decreased developed. This may lead to low cardiac output syndrome and/
lung compliance, which results in increased work of breathing. or alveolar edema.90 The immature myocardium contains fewer
Later there is overt left heart failure and rarely pulmonary contractile elements, sympathetic innervation is not adequate
edema. A stretched, incompetent foramen ovale secondary to and the left ventricle is less compliant in preterm than in term
left atrial dilation is a fairly common association.81 If the PDA babies.91,92 Preterm babies with a symptomatic PDA may
is large with PH, right heart failure can occur. frequently have ST-segment depression on an electrocardiogram
In a large PDA, due to the long-standing left-to-right (ECG), suggestive of subendocardial ischemia that normalizes
shunting, the pulmonary vascular bed is exposed to high- after the surgical closure of PDA.93 The subendocardial
pressure and increased pulmonary blood flow. This leads ischemia is as a result of aortic run off to the low resistance
to progressive morphological changes in the pulmonary pulmonary circulation, which reduces the diastolic pressure and
vasculature. These changes, including arteriolar medial flow particularly to the coronary circulation.
hypertrophy, intimal proliferation, fibrosis and eventual
obliteration of the pulmonary arterioles and capillaries. These CLInICAL fEAturES
changes results in progressive increase in PVR. When PVR
approaches and exceeds SVR, there is reversal in the ductal The clinical history of patients with PDA varies from those
shunting and it becomes right to left.28 The pathophysiological who present with CHF in infancy to those who are completely
mechanisms for this are not completely understood, but there asymptomatic upto adulthood. The clinical status is dictated
is evidence that microvascular injury stimulates production of largely by the size of the left-to-right shunt, which depends on
growth factors and enzymes that result in intimal proliferation the size of ductus and age of the patient. Infants with moderate
and medial hypertrophy.82 Endothelial dysfunction and to large PDA may present with symptoms of CHF, including
platelet activation may also play a role in the obliteration of poor feeding with failure to thrive, tachypnea and diaphoresis,
pulmonary arterioles.83 within the first few weeks of life as the left-to-right shunt
Several compensatory physiologic mechanisms help to increases with the falling PVR. More commonly, many PDAs
improve myocardial performance and thereby maintain a are detected during evaluation of an asymptomatic heart
normal systemic output. The left ventricle compensates by murmur.94 Others are detected incidentally by echocardiograms
increasing stroke volume and eventually may hypertrophy. The performed for unrelated reasons in patients without symptoms
neuroendocrine adaptation causes increase in the sympathetic or clinical manifestations. Some older children may be 311
4 healthy, but report exercise intolerance or carry the diagnosis incidentally discovered ‘silent’ PDAs have normal cardiac
of asthma. The clinical course of prematures is different from examination.
that in full-term born babies. An untreated large PDA can also produce pulmonary
Shunt DefectS
vascular obstructive disease, with a resulting bidirectional

Physical Examination shunt at the ductus level. The bidirectional shunt may produce
cyanosis only in the lower half of the body (i.e. differential
On examination, the patient may have stunted growth, cyanosis). Auscultation no longer reveals the continuous
precordial bulge (pigeon chest), bilateral Harrison sulcus. murmur or the apical rumble as a result of the shunt reduction.
Differential cyanosis and clubbing are important to detect The S2 is usually narrowly split with loud P2 due to PH.
severe PH, as desaturated blood from the pulmonary artery is
shunted to the descending aorta. Clinical findings in Preterms
Arterial Pulse Premature infants can have a unique presentation. Clinical

signs of hemodynamically significant PDA (hsPDA) usually
The radial pulse is typically bounding (collapsing or high appear between days 3 and 4 of life and may include a general
volume, water–hammer). The carotid, brachial, femoral deterioration in the status with multiple episodes of apnea,
and even the dorsalis pedis pulses are bounding. The blood increasing oxygen requirements with ventilator dependence
pressure typically shows wide pulse pressure. and poor perfusion with cardiopulmonary deterioration.80
They can also present with necrotizing enterocolitis. CHF
Inspection and Palpitation often occurs earlier as compared to term infants. This is
because they have a significant left-to-right shunt due to the
On inspection jugular venous pulse is normal, but hopping immature pulmonary arteries and decreased PVR. Persistent
carotid pulsations are seen. The precordium is hyperdynamic tachycardia and tachypnea are frequently seen. There may be
with hyperdynamic left ventricular apex on palpation. There increase in the precordial activity with bounding pulses and a
is a systolic or continuous thrill in the left second intercostal wide pulse pressure (> 25 mm Hg). ‘Palmar pulses’, which are
space on palpation in small to moderate-sized PDA. palpable pulses in the palms of the hands, may be present. A
gallop rhythm may be heard. A systolic murmur at the left mid
Auscultation to upper sternal border is more common than a continuous
murmur, which is less frequent. An enlarged liver can often
The characteristic physical finding is a continuous murmur be appreciated.
heard at the upper left sternal border or the left infraclavicular Clinical diagnosis of hsPDA needs at least two of the
area, often referred to as a ‘machinery’ murmur.95 This murmur following findings like heart murmur, persistent tachycardia
is also called as Gibson murmur and is the hallmark of PDA. (heart rate > 160/min), active precordium, bounding pulse
This murmur typically accentuates in late systole and marches or pulse pressure > 25 mm Hg, hepatomegaly, pulmonary
over the second sound without change in the character of the hemorrhage (defined as blood or blood-stained fluid aspirated
murmur. The loudness of the murmur depends largely on from the endotracheal tube in association with a respiratory
the magnitude of shunting. The left-to-right shunt occurs in deterioration and radiographic evidence of pulmonary
both phases of the cardiac cycle, producing the characteristic hemorrhage), increasing respiratory support by 20 percent
continuous murmur. In patients with high PVR (newborns) a increase in oxygen supplementation or in pressure support and
murmur may not be present. In the early weeks of life, only chest radiographic evidence of cardiomegaly or pulmonary
systolic murmur may be present and the diastolic component congestion.96 The physical examination may not rule out PDA
becomes apparent as the PVR falls and the diastolic shunting in the very low birth weight preterm on mechanical ventilation
increases. The murmur is often heard in the back, particularly and an echocardiography is necessary to confirm the presence
on the left.94 If the shunt is large, a thrill may be present and a of PDA.
diastolic rumble may be audible at the cardiac apex, due to the
increased flow across the mitral valve. In patients with high InVEStIGAtIonS
PVR, there may be no murmur during systole or diastole, as
shunting may be minimal. The Eddy sounds may be heard.
Chest X-ray
These sounds are produced due to the turbulent flow inside
the ductus, which is caused by the head on collision of the The findings on chest X-ray are proportionate to the degree
diagonally opposite flows from the aorta and pulmonary artery. of shunting. The chest radiograph may be completely normal
The intensity of the pulmonic component of the second heart in a small PDA. The chambers enlarged in moderate to large
sound may be increased in large PDA and paradoxical splitting PDAs are the left atrium (LA), left ventricle (LV), pulmonary
312 of the second heart sound can occur. Patients with tiny, artery (PA) and the ascending aorta with plethoric lung fields
21

a B
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 figure 5: PDA measurements to be made on echocardiography.
PH. Calcified ductus arteriosus calcifications (‘railroad track’ A = Minimal diameter; B = Ampulla length; C = Ampulla diameter
sign) can be seen in adults. (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.
Electrocardiogram 2002;15:1155 with permission from Elsevier)
Electrocardiogram findings are proportionate to the degree

of shunting. In patients with small PDA, the ECG is often It is classified as silent, small, moderate or large. TTE done in
completely normal. In patients with moderate sized PDA, high parasternal short-axis view (ductal view) can delineate
ECG may show volume overload of LV and LA, Those with further, the PDA characteristics that can be used to select
larger shunts may demonstrate sinus tachycardia, LVH and candidates for coil or device closure in the catheterization
LAH. The free transmission of the aortic pressure to the laboratory (Figures 4A and B). Therefore, measurement of
PA produces PH, resulting in right ventricular hypertrophy the minimal diameter and the ampulla size are of extreme
(RVH). Therefore, the ECG shows biventricular hypertrophy importance. The minimal diameter of the PDA is the
and LAH in a large PDA with elevated PA pressure. The narrowest inner echocardiographic dimension measured.
ECG in a patient with large PDA and irreversible PH shows The ductal ampulla is the vascular structure between the
pure RVH because the LV is no longer volume overloaded. narrowest diameter and the ductal aortic end. The ductal
ampulla length is the distance between the mid-position of
Echocardiography the narrowest diameter and the mid position of the ductal
aortic end. The ampulla diameter, which is the diameter of
The diagnosis of PDA is usually made on clinical grounds the ductal end at the descending aorta, is visualized from the 313
and confirmed by transthoracic echocardiography (TTE). long-axis suprasternal or high parasternal views (Figure 5).97
4 The greatest value of TTE and Doppler evaluation in the (approximately Qp : Qs > 2) and this had more than 90 percent
diagnosis of PDA is to exclude other significant intracardiac specificity and sensitivity.101
lesions.
Shunt DefectS
In a patient with moderate to large PDA, the LA and LV Magnetic resonance Imaging and
are enlarged, while in a small PDA chamber sizes are usually Computed tomography
normal. The ratio of the LA size to the aortic root size (both
measured in systole) can be used to estimate the degree of Computed tomography (CT) can assess the degree of
ductal shunting. If this ratio is greater than 1.2 (normal is 0.8– calcification in adults.102 Volume rendered (VR) CT image
1.0), it suggests a significant shunt.94 can define the anatomy of the PDA well (Figure 6). Magnetic
Doppler echocardiography reveals continuous flow from resonance imaging and computed tomography is used to
the aorta into the MPA. If the magnitude of the left-to-right define anatomy in a PDA with unusual geometry and with
shunt is large, continuous flow around the aortic arch into associated abnormalities of the aortic arch.103 Cardiac
the ductus arteriosus in diastole and flow reversal in the magnetic resonance imaging may be useful to evaluate the
descending aorta are evident.98 There may be also variable anatomy, if a ductus arteriosus aneurysm is suspected.104
levels of continuous flow in the branch pulmonary arteries
related to the magnitude of shunt. As the shunt magnitude nAturAL HIStorY
increases, increased flow in the pulmonary veins is evident.
Color Doppler is a very sensitive modality in detecting the The functional closure of the PDA occurs in 20 percent of the
presence of PDA and is used to estimate the degree of ductal term infants at 24 hours after birth, 82 percent at 48 hours and
shunting. Color flow signal can detect an extremely tiny 100 percent by 96 hours of life.105 The term ‘winking ductus’
patent ductus entering the PA near the origin of the LPA. In a was coined in a study that showed that in healthy newborns
patient with large PDA with PH, with low velocity or right-to- up to day 5, there could be intermittent shunting even when
left flow, it may be difficult to demonstrate even a large PDA. the PDA seems to have closed.106 Even after functional
Associated findings such as septal flattening, unexplained ductal closure, the potential to reopen exists for the next 7 or
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.
Echocardiography in Preterm Neonates

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
figure 6: Volume rendered (VR) computed tomography image
velocity more than 0.42 m/s or LPA diastolic velocity more illustrates a large window type of patent ductus arteriosus (PDA). Ao =
314 than 0.2 m/s, all predicted an LV output: SVC ratio more than 4 Aorta; MPA = Main pulmonary artery;
8 days especially in preterms.107 In preterm babies, patency been reported in adults.112,113 The true incidence of aneurysm 21
of ductus arteriosus is common, as due to immaturity they of the PDA is unclear, although it has been reported to be as
lack the normal mechanisms for postnatal ductal closure. high as 8 percent.114 It is incidentally discovered and can

Delayed spontaneous closure of the ductus may be anticipated resolve spontaneously without sequelae. The etiology may
if the preterm baby does not succumb to other problems.80 be genetic or it may develop after IE, surgical closure or
Premature babies who had a significant PDA are more likely transcatheter coil occlusion.115-117 Arterial duct aneurysms
to develop bronchopulmonary dysplasia. are classified into:
The natural history of PDA is determined by the size a. The spontaneous infantile type that is present at birth
and magnitude of the shunt and the status of the pulmonary and grows rapidly.
vasculature. Patients with small PDA will have a normal b. The adult type that grows during childhood or
prognosis with only the risk of infective endarteritis. Patients adulthood.58
with small to moderate PDA are asymptomatic during Falcon et al118 classified this disorder into three types: (1)
infancy and childhood. Infants with large PDA presenting aneurysms that are patent on both the aorta side and pulmonary
with CHF may not survive without intervention, succumbing artery side of the arterial ductus, (2) those that are patent on
to poor nutrition and respiratory failure. In many infants, the pulmonary artery side, and (3) those after operation for
the PVR remains modestly elevated but in rare instances it PDA. Type 1 is frequently observed in children/infants and
never falls significantly after birth and the child may remain type 2 in adults.
asymptomatic or minimally symptomatic despite the presence The ductus arteriosus aneurysm may present with
of a large PDA. In theses patients even with the timely symptoms due to compression of the adjacent nerves or
intervention of closure of PDA, pulmonary vascular disease pulmonary structures.119,120 They usually have a benign
may progress and eventually prove fatal, suggesting that the course; but surgical resection is indicated if there is functional
PH may be primary rather than secondary to the PDA.108,109 compromise of the adjacent structures, persistent patency of
At present, with widespread use of echocardiography, the the ductus beyond the neonatal period, thrombus extending
diagnosis is being made at a younger age and virtually all cases into adjacent vessels, evidence of thromboembolic events,
are being closed either with devices or surgically. It is now or underlying connective tissue disease.121 The role of
extremely rare to encounter a patient with pulmonary vascular transcatheter occlusion with aneurysm obliteration has not
obstructive disease. This can occur by age of 2 years in an been established for ductus arteriosus aneurysm, but one
untreated large PDA. Rarely irreversible pulmonary vascular promising technique is placement of a covered stent in the
disease or Eisenmenger syndrome may occur gradually over aorta to simultaneously exclude the aneurysm and occlude the
time in patients with untreated, large, non-restrictive PDA.94 PDA.122
CoMPLICAtIonS DIffErEntIAL DIAGnoSIS

Patients with PDA have increased morbidity and mortality, The differential diagnosis for PDA are aortopulmonary window
primarily due to the development of CHF and infective (APW), VSD with aortic regurgitation, rupture of sinus of
endocarditis (IE).40 Pulmonary hypertension is a less common Valsalva, coronary arteriovenous fistula, systemic arteriovenous
problem. fistula, branch pulmonary artery stenosis, coarctation of aorta
1. Congestive heart failure—CHF occurs in the preterms, young (COA) with collaterals and rarely venous hum.
infants and in adults with large PDA. In the adult, atrial
arrhythmias (fibrillation or flutter) frequently accompany the MAnAGEMEnt
heart failure.110
2. Infective endocarditis—routine treatment of PDA with tran-
Medical Management
scatheter or surgical closure and antibiotics has decreased the
IE. The vegetations usually accumulate at the pulmonary end Medical therapy for CHF due to large PDA should be short term,
of the PDA. The IE associated with PDA remains a significant until definitive surgical or transcatheter closure is performed.
health problem in underdeveloped countries with limited Acute medical treatment for PDA before definitive closure
health resources and access to health care.111 is usually not necessary as most term babies and children
3. Pulmonary vascular disease—an isolated large PDA, as are asymptomatic. Symptomatic patients usually improve
with any large left-to-right shunt, can result in PH and with a standard regimen of diuretics and afterload reduction.
eventual irreversible vascular disease. It is now extremely Patients who are considered unacceptable candidates for
rare to encounter a patient with pulmonary vascular definitive closure of PDA, due to pulmonary vascular disease
obstructive disease due to the early diagnosis and timely may be managed with pulmonary vasodilating agents, such as
intervention. chronic oxygen therapy, prostacyclin, nifedipine, bosentan or
4. Aneurysm of PDA—the PDA aneurysm is a rare com- sildenafil.94 Recent guidelines do not recommend endocarditis 315
plication and commonly presents in infancy, but has also prophylaxis for patients with isolated PDA.
4 Preterm Infants symptomatic or give targeted presymptomatic or prophylactic
treatment. None of these approaches has shown unequivocal
Treatment of PDA in preterms varies with the magnitude of benefits in terms of outcomes.128
Shunt DefectS
shunting and the severity of hyaline membrane disease. The

PDA may contribute to the mortality in these preterms with Interventions
respiratory distress syndrome. Intervention is required in
preterm babies, who demonstrate signs of a significant left-to- Technical advancements in device design coupled with
right shunt and who are unresponsive to the medical measures improvements in quality of catheters, delivery sheaths, wires,
to control the CHF. Medical management in premature retrieval equipments and superior non-invasive imaging
babies consists of pharmacologic closure using inhibitors of modalities for identifying anatomical variations in ductus
the arachidonic acid metabolism pathways. The commonly anatomy have resulted in evolution of device closure of PDA
used drugs to constrict and close the PDA are indomethacin as a preferred modality of management in most interventional
or ibuprofen. Both these drugs inhibit PG synthesis. Fluid cardiology centers.129,130 Currently the benefits of transcatheter
restriction and diuretic therapy are also required in these closure of PDA compared to surgical closure seem obvious in
preterms to treat CHF. Surgical ligation is required in terms of short hospital stay, no thoracotomy scar, comparable
about 10 percent of these babies who are unresponsive to success rate and very minimal morbidity.129-132
indomethacin.80
Indomethacin has been used for many years to successfully InDICAtIonS for PDA CLoSurE
close PDA. The medication is contraindicated in patients
with active bleeding, low platelet count, intracranial hemor-
Premature Infants
rhage, renal insufficiency or necrotizing enterocolitis.23
Ibuprofen has been studied extensively as an alternative to PDA closure is indicated in all patients less than 10 days of age
indomethacin. It has less side effects on organ blood flow than with symptomatic PDA, who had no response to indomethacin
indomethacin.123,124 The parenteral preparations of ibuprofen and for those who are more than 10 days old. Symptomatic
are more expensive than indomethacin and not available in PDA is defined as respiratory rate of more than 70 per minute,
many places. A study with oral ibuprofen administration has heart rate more than 160 per minute, liver enlargement more
suggested that the oral route of administration can achieve than 3 cm below costal margin and cardiomegaly more than
PDA closure with similar efficacy as compared to the 60 percent on chest X-ray.133
intravenous indomethacin.125
The dosage of indomethacin is an initial dose of 0.2 mg/kg Children and Adults
stat followed by two additional age adjusted doses given at 12
to 24 hours intervals. It is given as an infusion over 30 minutes, Symptomatic and even asymptomatic PDA should be closed
with a usual maximum of two courses (Box 1).99 Some studies to avoid CHF, pulmonary vascular disease, IE and aneurysm
have shown that 0.1 mg/kg daily of indomethacin for 6 days formation.112,133,134
achieved similar closure rates with fewer side effects.126,127
Ibuprofen is usually given at 10 mg/kg stat followed by 2 Silent Patent Ductus Arteriosus
doses of 5 mg/kg/dose × 2 doses at 24 hour intervals.24
There have been several approaches to the timing of With the widespread use of echocardiography and Doppler
treatment of PDA in preterms. The unresolved issues are color flow imaging, silent PDA has been shown to be
whether to treat these infants when they become clinically 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
Box 1: Dosage of indomethacin and ibuprofen for ductus in preterm babies with respiratory distress syndrome.
closure of patent ductus arteriosus Management of these silent ducts is controversial. Balzer
indomethacin et al135 published a case report of silent PDA presenting
Initial dose as endarteritis and recommended ductal closure, whereas
0.2 mg/kg stat followed by age adjusted doses others clearly opposed it because of the potential mortality,
Subsequent dose morbidity and expense.36,133 Bennhagon and Benson in
their analysis of hemodynamics and angiographic study
< 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 found that the PDA murmur becomes silent probably due
> 7 day-0.25 mg/kg/dose 12 hourly for 2 doses to the direction of the jet across the ductus arteriosus not
reaching the anterior wall of the main pulmonary artery.136
ibuprofen
Considering the findings with no difference in ductal size
316 10 mg/kg stat followed by
and consequently no difference in clinical importance
5 mg/kg/dose 24 hourly for 2 doses
between silent and audible PDA, these authors drew the
conclusion that silent PDA, when diagnosed should be In almost all patients echocardiographic assessment of the 21
recommended for surgical or transcatheter closure. ductus can be obtained by using high parasternal duct and
suprasternal views, which can be confirmed by angiography

recommendations for transcatheter PDA occlusion137 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
Class I
0.038″ coils are usually selected, but for large PDA 0.052″ are
1. Transcatheter PDA occlusion is indicated for the treatment more advantageous. There are no specific guidelines available
of a moderate-sized or large PDA with left-to-right shunt for coil sizes (thickness, diameter and length).
that results in any of the following: Congestive heart Several techniques have evolved following the first
failure, failure to thrive, pulmonary overcirculation (with successful use of standard coil by the antegrade route for
or without pulmonary hypertension), or an enlarged occlusion of small PDA (< 2.5 mm). The retrograde approach
left atrium or left ventricle, provided the anatomy and was described for closure of small PDA (< 3.3 mm)141 and
patient size are suitable (Level of Evidence: B). encouraged by these results, with antegrade technique
delivery of multiple coils to close the larger size PDA was
Class IIa attempted.142 The immediate success rate using single or
multiple coils ranges from 67 to 95 percent, almost invariably
1. Transcatheter PDA occlusion is reasonable in the presence related to ductus size.139,140,143 Although ducts as large as
of a small left-to-right shunt with normal-sized heart 7 mm have been closed with coils, a larger ductus diameter is
chambers when the PDA is audible by standard an unfavorable factor.140 In addition, the success and occlusion
auscultation techniques (Level of Evidence: C). rate are also related to type and number of coils used (Figures
7B to D). The accurate placement of coils in a PDA, specially
Class IIb if large, can be technically challenging.
The most common complication is embolization to the
1. In rare instances, transcatheter PDA occlusion may be distal pulmonary arteries (6–20%).140 Embolization is another
considered in the presence of a bidirectional PDA shunt inherent complication even with the use of bioptome- assisted
due to pulmonary hypertension and obstructive pulmonary technique.139 Retrieval of coil mass is at times difficult,
vascular disease but reversible to pure left-to-right shunting requires placement of larger sheath and adds to the expense of
with pulmonary vasodilator therapy (Level of Evidence: the procedure. There is very little margin for error in infants
C). less than 5 kg with large ductus, where use of multiple coils
2. Transcatheter PDA occlusion may be considered in a PDA and a coil turn left in the LPA may lead to progression of
associated with a small left-to-right shunt with normal stenosis in the LPA.138 Lastly, the occlusion rates are still
heart size and an inaudible murmur (Level of Evidence: C). lower than other occlusive devices and surgery.129,139,144
Class III Sideris Buttoned Device

1. Transcatheter PDA occlusion should not be attempted in Regular buttoned device introduced in 1990 was used
a patient with a PDA with severe pulmonary hypertension for occluding PDA of all types and sizes upto 15 mm by
associated with bidirectional or right-to-left shunting that transvenous route through 7-8 F long sheath during a 6
is unresponsive to pulmonary vasodilator therapy (Level year period ending in August 1996 in 284 patients with 98
of Evidence: C). percent success rate. But, residual shunt was high (40%) at
implantation, which decreased with time to 0 percent at the
Catheter Interventions end of 5 years, yet the risk of IE continued.145 For that reason,
modified devices-folding plug, infant buttoned device and for
Transcatheter closure of small PDA using coils (single or adults wireless devices particularly the transcatheter patch for
multiple) has become an accepted alternative to surgical large PDA 12 to 22 mm have undergone clinical trials.146,147
closure in most cardiac centers specially in developing
countries.138-140 Gianturco coils are small coiled spring wires Gianturco-Grifka Vascular Occlusion Device
with fabric strands woven into springs (Figure 7A). They are
available as standard 0.035″, 0.038″ and 0.052″ with 3 to 15 Gianturco-Grifka vascular occlusion device is a fabric sac into
mm helical diameter. The size of the ideal coil for a given which a long coil is extruded, which confirms to the size and
ductus is not clear. The minimum PDA diameter, configuration shape of the large PDA with controlled delivery system.148
of the entire ductus, size of the ampulla and the age/weight It is ideal for long tubular PDA and should not be attempted
of the patient determines the coil size and combination.138 in window type PDA, as there is not enough vessel length 317
4
Shunt DefectS
a B
c D
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 closure rates.150 A modification of the duct-occlud device is the
device is not technically suitable for PDA more than 6 mm in reinforced device that has a cone-shaped appearance instead
size and for infants less than 3 kg as the delivery sheath is 8 of hourglass and achieves denser coil looping in the PDA
F. Using strict criterias for its use, only one-third of the cases facilitating total occlusion. Nit-occlud device is a modification
were found suitable by Ebeid et al.149 The prospective larger of the reinforced device and has same clinical configuration
clincial trials have not been done. but is made of nitinol-titanium alloy, which has higher shape
memory than steel coils and is suited for Type A conical
Duct-occlud and Nit-occlud Device PDAs (Figures 8A to C). The European registry and United
States Food and Drug Administration (US-FDA) trial reported
The duct-occlud device was developed to have a proper match successful implants in 90 percent and 77 percent respectively. In
318 with the size and shape of the PDA with a high stability during the former trial, there was a report of rupture of PDA that needed
and after closure, as well as for achieving higher complete surgical intervention and pulmonary artery embolization in 3.4
21

a B c
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 a B
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 c D
Calibrated angiography is done to select the specific occluder figures 9a to D: A. Amplatzer duct occluder with the retention disc
for a given PDA. In general, a device is chosen so that the on aortic end; B. Amplatzer muscular ventricular septal occluder with
retention disc on both the sides; C. Amplatzer duct occluder II with
diameter of the pulmonary arterial end of the device is 2 to 3
two retention discs of 3 mm on either side with central cylinder with no
mm larger than the narrowest diameter of the ductus (usually polyester material; D. Amplatzer duct occluder II AS is additional size
the pulmonary end of the ductus) (Figures 10A and B). with a bigger central cylinder
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 to device implantation. The most concerning morbidity was
suggesting high level of safety and efficacy of ADO.129,151 Pass aortic obstruction in 1 and LPA stenosis in 2 (gradient > 20
et al in their multicenter USA trial performed to obtain FDA mm Hg) at 1 year. Device embolization occurred in one case
approval, included 439 patients with exclusion criteria of those requiring surgery, as retrieval is not always possible. Amongst
less than 5 kg, PVR more than 8 Wood units, inferior vena the devices currently available, ADO has the highest efficacy
cava thrombosis and sepsis.129 The procedure was successful and safety in closing PDA more than 5 mm.130
in 435 (99%) with PDA size of 0.9 to 11.2 mm. The efficacy Occasionally, large PDA may be encountered, which are
rate (echocardiographic complete occlusion of PDA) was not amenable to closure even with the largest available ADO.
99.7 percent at one year. Additionally, virtually every shape Such ductus have been closed with Amplatzer ventricular
of the ductus was closed using the ADO. The complication septal occluder and no pulmonary or aortic obstruction was
rate was 2.3 percent with a single death that was unrelated observed on follow-up.130,152 Angiographic ventricular 319
4
Shunt DefectS
a B
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.
assessment in adults with large PDA may be potentially of the occluding device. Since PDA is a remnant of the sixth
imprecise due to the overlap between large aorta and aortic arch, it results in an acute angle with the descending
pulmonary artery. A compliant balloon may be used to assess aorta of 31.6 to 34.4 degree. For this, ADO with a 32 degree
the minimum diameter, configuration and distensibility of the angled retention disc was specially designed and its initial
PDA or intravascular ultrasound imaging can be done.153 human experience confirms it to be safe and efficacious for
Kinking of the delivery sheath commonly occurs and it infants having small PDA ampulla/window type ductus
mandates selection of kink resistant sheath with optimal shape (Figures 11A and B).19,157
and length.154 Fischer et al evaluated the role of ADO in eleven 3. Amplatzer plug device: Amplatzer vascular plug without
infants with PDA measuring angiographically 1.5 to 5 mm.155 retention disc can be deployed in very small children to avoid
The procedure was successful in 82 percent and residual obstruction in aorta and pulmonary artery. Thanopoulous
flow was seen in one patient at 24 hours, which subsequently et al attempted it in nine children, aged 0.5 to 3 years, PDA size
disappeared at 45 days follow-up. But technical problems 1.5 to 10.5 mm.158 Success rate was 100 percent but one patient
in advancing the device through sheath at right ventricular with large PDA had residual shunt with hemolysis and required
outflow tract (RVOT) occurred in 75 percent. The closure of two coils for complete occlusion. This experience is however
large PDA in very small infants was considered challenging in limited and larger clinical trials are needed.
the past and not recommended by the device manufacturers. 4. Amplatzer duct occluder II (ADO II): Recently,
But a recent study shows device closure of large PDA, in ADO II is a specially designed for long ducts in infants
infants weighing ≤ 6 kgs was successful in 60/61 infants has become available for transcatheter closure of PDA.
(98.4%). The age, ranged from 9 days–12 months (mean 8.9 This newer generation device, ADO II, is a self expanding
months), weight ranged from 2.2 to 6 kg (mean 5.3 kg), and device with 2 retention discs (at both aortic and pulmonary
PDA measured 3.2 to 8.7 mm (mean 4.8 mm). The largest ends) that articulate with a central plug, which is sized to
device used was 12 × 10 mm. Mild aortic obstruction occurred the diameter of the midpoint of the PDA and is composed
in 2 cases (3.3%), as the device got displaced towards the small of fine Nitinol wire mesh with no polyester fabric (Figure
aorta after release. The device embolized in 2 cases (3.3%). 9 C). The advantage of the ADO II is that it has a very low
In one it was retrieved by a novel method like fastening the profile and can be easily delivered through a 4 or 5 F sheath
screw in the aorta and was subsequently closed with a 4 × 6 in infants. As it has a retention skirt on either side, it can
Amplatzer duct occluder II. Left pulmonary artery obstruction be delivered either from the pulmonary or the aortic end,
occurred in one case (1.6%). Four cases (6.6%) had minor which is especially useful in infants with severe pulmonary
vascular complications.156 hypertension. The ADO II with its thin delivery cable and
2. Angled Amplatzer duct occluder: Regular ADO however more flexible kink-resistant sheath makes the crossing of
was not found very suitable for infants and small children due the RVOT very easy in infants. The ADO II is delivered
to the possibility of encroachment into LPA or aorta causing through a TorqVue low profile catheter (St. Jude Medical,
320 significant hemodynamic obstruction as a result of protrusion Plymouth, MN), which comes in 4 and 5 French sizes.
21

a B
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
a B
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 c D
approach may be preferable in some cases. Echocardiographic
figures 12a to D: A. Aortic angiogram in right anterior oblique view
guided intervention is a new concept and may be appealing, illustrates 3 x 4 Amplatzer duct occluder (device) II in situ, deployed
logistically easier but more precise assessment is needed. from the aortic end in a nine day old neonate with biventricular
6. Lifetech duct occluder: It is the replica of Amplatzer duct dysfunction; B. Check angiogram after release of the device shows no
occluder with ceramic coating to prevent nickel toxicity.The 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
devices are available up to 26 × 24 mm to close very large PDA. cylinder in the ductus and the two retention discs of 5 x 4 ADO II on
The custom made devices can be obtained up to 30 × 28 mm. either end of the ductus (pulmonary and the aortic end)
321
4 Special Situations 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
Pulmonary Artery Hypertension
Shunt DefectS
outcome and long-term results after PDA closure.159

The feasibility of temporary balloon occlusion of PDA in Thanopoulus et al evaluated the use of ADO in seven
the catheterization laboratory allows assessment of the size patients. Device delivery was successful in all without
and hemodynamic parameters in patients with systemic complications with a fall in mean PA systolic pressure from
or near systemic pulmonary artery pressures (Figures 13A 106 ± 13 to 61 ± 6 mm Hg.160 To prevent embolization into
to C). Although fall in systolic pressure of 20 percent aorta, the Amplatzer muscular VSD occluder also seems to
after O2 inhalation and tolazoline was being considered be more ideal in severe PH patients (Figures 14A and B).
a B c
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
a B
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
322 mm Hg. The oxygen saturation (SaO2) preprocedure in upper limb—92%, lower limb—84% 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.
Retrieval of embolized device could be tricky and Adult Patients 21
challenging. At times the embolised device caught by With advancing age, the morphologic characteristics of
the regular snare, if not coaxial with the sheath, wrinkles the ductus changes, altering the success of any procedure

making it impossible to retrieve the device (Figure 15A). for their closure. In the surgical series, the incidence of
The basket snare cannot catch the device sometimes (Figure calcification or aneurysmal changes ranges from 6 to 33
15B). Hence all types and sizes of retrieval basket, goose percent.161 Conventional methods of division and ligation
neck snares and large sheaths must be available in the can be difficult, incomplete or even hazardous. In particular,
catheterisation laboratory. The ADO was retrieved in two severe calcification makes the ductus too fragile for standard
patients by a very novel and unique method by fastening clamping thereby mandating the use of more invasive total
the screw to the device inside the aorta in one and in the cardiopulmonary bypass (CPB) with transaortic patch closure
left common iliac artery in another case. Then device was or may require the use of hypotensive anesthesia for easier and
pulled into the 7 F sheath like loading the device (Figures more effective surgical manipulation.161,162 Thus, morphologic
16A and B). changes necessitate the need for a more complex procedure
and its associated morbidity and mortality. Not only that one-
fifth 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
Associated Coarctation of Aorta

a B Associated COA is a challenging situation and strategy
figures 16a and B: A. 8 x 6 Amplatzer duct occluder (device) embolised depends on the age of the patient, size of PDA and aorta. If
into the aorta; B. The screw is fastened in aorta and the device is being the patient is suitable for stent, a device (ADO) may initially
pulled into the sheath be placed in the ductus and subsequently the coarctation can
a 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
4
Shunt DefectS
a B
c D
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 (pleural effusion, chylothorax, bleeding, pneumothorax, etc)
both to close the PDA and to repair the coarctation.166 PDA can result in prolonged mechanical ventilation and intensive
can be closed by using ADO with concomitant dilatation of care stay.131 Encouraged by the successful coil closure of
the coarcted segment (Figures 17A to D). large ducts especially with the availability of 0.052″ coils,138
the procedure has been attempted for five small sick ventilated
Sick Ventilated Small Infants infants, weighing 0.960 to 4.0 kg.170 Bioptome-assisted coil
delivery was done and PDA closure was achieved in all. There
Large PDA in full-term/premature babies is known to cause were two instances of embolization of coils with successful
CHF early in life.167 Superadded respiratory infections are not retrieval and redeployment. All infants could be weaned
uncommon and can result in respiratory insufficiency requiring off mechanical ventilation over the next 24 to 72 hours and
ventilatory support. When medical therapy with indomethacin remained asymptomatic at 3 months follow-up. But only ducts
(for preterms), fluid restriction and diuretics fails, closure of the with adequate ampulla are suitable and the procedure needs
PDA becomes a necessity. Surgical ligation by open thoracotomy certain degree of expertise.
is the standard treatment.144 This can be done even on site in the
neonatal intensive care units, avoiding the risk of transferring Marfan Syndrome
unstable neonates.168 Moreover, video-assisted thoracic surgery
has been proved to be effective and minimally traumatic in Younger patients with connective tissue abnormalities may also
324 premature infants with very low birth weight.169 This facility be at risk for development, progression and rupture of ductal
is not however uniformly available. Surgery related morbidities or aortic aneurysms after device closure. Marasini et al171
with coil occlusion.131,138,139,173 Residual shunts129 are 21
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
figure 18: Transthoracic echocardiography in parasternal short axis
The cause of the residual shunt was incomplete coverage
view shows large mobile vegetation (VEG) in the main pulmonary of the polyester patch on the pulmonary end in a large, but
artery (MPA) in a 9-year-old boy with patent ductus arteriosus (PDA) short and wide PDA. The hemolysis was controlled by
placing a coil inside the device.
2. Coils: Residual flow and hemolysis are the inherent
reported the development of giant aneurysm in a patient with limitations of using coils. If after implanting the coils,
Marfan syndrome after coil occlusion of PDA, the explanation immediate angiogram displays a residual jet of flow
for which remained speculative, as trauma from catheter or through the PDA, a second coil should be deployed. If not,
wire manipulation increased radial forces of the coils inside the persistent PDA keeps the patient at risk for endocarditis
the ductus or caused spontaneous dissection. In such cases, a and hemolysis due to high velocity flow. Proper hydration
careful manipulation of catheters/wires inside the ductus, and and observation should be done as hemolysis resolves
regular follow-up with radiography plus echocardiography is spontaneously, but if it persists for more than 24 hours,
recommended. immediate closure is needed by another coil or referral
for surgery.176 On follow-up if the leak does not close
Infective Endarteritis spontaneously after 1 year or there is recanalization, repeat
catheterization should be performed to implant another coil
Patients presenting with IE need to be hospitalized and to achieve complete closure.177
treated with appropriate antibiotics in adequate dosages for a
period of 4 to 6 weeks. Echocardiographic evaluation usually Surgery
reveals vegetations on the pulmonary artery and rarely on the
pulmonary valve or PDA (Figure 18). In hemodynamically Since the initial report by Gross et al10 in 1939, surgical
stable patients, after 8 weeks of stopping the antibiotics,172 repair has become a routine and relatively safe procedure,
if blood culture is negative and there is no other evidence but it carries the potential risk of morbidity and rarely
of infection, elective closure of the PDA can be considered. mortality associated with thoracotomy specially in infants
Sadiq et al attempted device occlusion in 8 and surgical and adults.131,144,161 Degenerative changes like calcification,
ligation in 5 children, without CPB.111 But, great caution friability and aneurysm formation with advancing age make
should be taken in adults with degenerative changes, as the conventional procedure of division and ligation difficult
the ductus may be fragile, due to the superadded infection and may mandate the use of more invasive approach including
(although treated). Even in the absence of mycotic aneurysm, total CPB and transaortic patch closure.131,161 Significant
where device closure is not possible, surgical ligation appears advances in technology over the past decade have allowed the
to be a better choice on/standby CPB.131,161 development of minimally invasive video-assisted thoracic
surgery, which has been found to be safe and effective not
Residual Shunts only in older children, but even in premature infants with
very low birth weight, when medical treatment fails.9 But this
Residual shunts have been observed after transcatheter has limitations in patients with calcified ducts, severe pleural 325
closure and surgical ligation and rarely after recanalization scarring and short, wide window like ducts. Also, robotically
4 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
Shunt DefectS
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.
figure 19: Operative image shows the exposed patent ductus
4. Recurrent ductus, giant ductus. arteriosus (PDA), just before ligation
5. PDA with complex CHD.
Contraindications
and lower borders of the ductus. Hemostasis is checked, pleura is
1. Severely elevated PVR (> 8 Wood units). covered and the chest is closed. In small children an extra pleural
2. Failure of PVR to fall (< 8 Wood units) with isoproterenol approach can also be attempted.
during cath study at 0.14 mg/kg/min. Closure from the midline sternotomy approach is done in
3. Qp:Qs of 1.5 to 1.8 at rest that becomes < 1 during exercise. cases where ligation is being done along with concomitant
4. Ductal dependent lesions. repair of the cardiac lesions, difficult ductus arteriosus and
residual ductus. It is also required to be done after device
Procedure embolization.The procedure is done by applying traction to
the MPA and the PDA appears like a ‘continuity’ of the MPA.
The PDA has to be controlled in all patients undergoing The right and left pulmonary arteries are noted and ligation
surgery under CPB as the presence of an open PDA during of the ductus is done before CPB or at the initiation of CPB.
CPB can cause flooding of the lungs and distention of the LV In case of a complicated ductus, the ductus is temporarily
in the arrested heart on CPB. The PDA is ligated or divided. interrupted by invaginating the MPA with a finger to occlude
Cardiopulmonary bypass is required in special circumstances the ductal orifice, while CPB is established. A balloon
like a calcified ductus, ductal aneurysm or a friable ductus with catheter may be placed to occlude the PDA after opening the
endarteritis. The usual approach is through the fourth intercostal MPA during a period of temporary low flow. After cooling
space through a posterolateral thoracotomy. A video-assisted the patient to the required temperature, head low position
thoracoscopic approach can also be used. Some surgeons ligate is given and under low flows, the orifice of the PDA is
the ductus through a minithoracotomy incision. The lung is gently closed with a patch or directly depending on the size of the
retracted and the ductus and the posterior pleura is incised. The ductus.
superior intercostal vein is divided and stay sutures are placed. It
is ensured that there is adequate blood present in the operating Complications
room, suction apparatus is functioning and the ductus clamps
are checked. Under hypotensive anesthesia, sharp and blunt Bleeding is a major complication and can occur during
dissection of the ductus arteriosus is done and the aorta above looping the ductus and also during division of the ductus.
and below the ductus are defined. The pericardial lappet needs Recanalization can occur both after ligation and even rarely
to be dissected and lifted off to allow definition of the ductus after division. Device closure of a residual ductus can be
(Figure 19). The ligatures are passed around the ductus and under done. Chylothorax due to division of lymphatics or thoracic
controlled hypotension the ductus arteriosus is ligated. In case duct, hematomas and recurrent laryngeal nerve injury can also
of a hypertensive ductus, a trial clamping may be done initially occur after ductal ligation through a thoracotomy.
and if there is any bradycardia and hypotension after clamping In premature infants, the operative mortality is related more
the ductus, the clamps may be released. If division is planned, due to the associated comorbid conditions and associated medical
ductus clamps are placed and the ductus is divided and running problems and can be as high as 10 to 15 percent. Uncomplicated
326 sutures are placed over both ends and clamps are removed. In ductal ligation is associated with minimal mortality. The
neonates, a large hemoclip can be placed after defining the upper recanalization can occur in upto 0.5 percent of cases.
ConCLuSIon
16. Rao PS, Wilson AD, Sideris EB, et al. Transcatheter closure of 21
The ductus arteriosus is an important and essential normal patent ductus arteriosus with buttoned device: first successful
structure during fetal development and usually undergoes clinical application in a child. Am Heart J. 1991;121:1799-

spontaneous closure during the early neonatal period. Persistent 802.
patency is abnormal and if not treated may result in significant 17. Cambier PA, Kirby WC, Wortham Dc, et al. Percutaneous
closure of small (less than 2.5 mm) patent ductus arteriosus
cardiac and pulmonary problems. The benefit of interventional
using coil embolization. Am J Coll Cardiol. 1992;69:815-6.
closure of tiny clinically silent PDAs remains controversial, but 18. Masura J, Walsh KP, Thanopoulos B, et al. Catheter closure of
for clinically significant PDA, routine transcatheter or surgical moderate- to large-sized patent ductus arteriosus using the new
closure is recommended to prevent long term complications Amplatzer duct occluder: immediate and short-term results. J
even in asymptomatic patients. Am Coll Cardiol. 1998;31:878-82.
19. Vijayalakshmi IB, Chitra N, Rajasri R, et al. Initial clinical
The best physician is the one who is able to distinguish experience in transcatheter closure of large patent arterial
between the possible and the impossible. ducts in infants using the modified and angled Amplatzer duct
occluder. Cardiol Young. 2006;4:378-84.
20. Bhole V, Miller P, Mehta C, et al. Clinical evaluation of the new
—Herophilus
Amplatzer duct occluder II for patent arterial duct occlusion.
Catheter Cardiovasc Interv. 2009;74:762-9.
rEfErEnCES 21. Agnoletti G, Marini D, Villar AM, et al. Closure of the patent
ductus arteriosus with the new duct occluder II additional sizes
1. Cassels DE, Bharati S, Lev M. The natural history of the ductus
device. Catheter Cardiovasc Interv. 2012;79:1169-74.
arteriosus in association with other congenital heart defects.
22. Friedman WF, Hirschklau MJ, Printz MP, et al. Pharmacologic
Perspect Biol Med. 1975;18:541-72.
closure of patent ductus arteriosus in the premature infant. N
2. Dunn PM. Galen (AD 129-200) of Pergamun: anatomist and
Engl J Med. 1976;295:526-9.
experimental physiologist. Arch Dis Child Fetal Neonatal Ed.
23. Gersony WM, Peckham GJ, Ellison RC, et al. Effects
2003;88:F441-F443.
of indomethacin in premature infants with patent ductus
3. Fejfar Z, Hlavàckova L. Karl Rokitanski. Clin Cardiol. 1997;
arteriosus: results of a national collaborative study. J Pediatr.
20:8,816-8.
1983;102:895-906.
4. Harvey W. Exercitatio Anatomica de Motu Cordiset Sanguinis
24. Van Overmeire B, Smets K, Lecoutere D, et al. A comparison
in Animalibus. Frankfurt: William Fitzer; 1628.
of ibuprofen and indomethacin for closure of patent ductus
5. Highmore N. Corporis Humani Disquisitio Anatomica. The
arteriosus. N Engl J Med. 2000;343:674-81.
Hague: Samuel Broun; 1651.
25. Congdon ED. Transformation of the aortic-arch system during
6. Virchow R. Die thrombosen der neugeboren. In: Gesamnelte
the development of the human embryo. Contrib Embryol.
Abhandlungerzur Wissenschafthchen Medicin. Frankfurt:
1922;14:47-110.
Maidinger; 1856. p. 591.
26. Barger JD, Bregman EH, Edwards JE. Bilateral ductus arterio-
7. Gerard G. De l’obliteration du canal arterial, les theories et les
sus with right aortic arch and right-sided descending aorta. Am
faits. J Anat. 1900;36:323-57.
J Roentgenol Radium Ther Nucl Med. 1956;76:758-61.
8. Gibson GA. A Clinical Lecture on Persistent Ductus Arteriosus.
27. Steinberg I, Miscall L, Goldberg HP. Congenital absence of left
Medical Press and Circular. 1906;pp. 572-4.
pulmonary artery with patent ductus arteriosi; treatment by closure
9. Munro JC. III Ligation of the ductus arteriosus. Ann Surg.
of ductus and left pulmonectomy. JAMA. 1964;190: 394-6.
1907;46:335-8.
28. Schneider DJ, Moore JW. Patent ductus arteriosus. Circulation.
10. Gross RE, Hubbard JP. Surgical ligation of a patent ductus
2006;114:1873-82.
arteriosus: A report of first successful case. JAMA. 1939;112:
29. Rudolph AM. The ductus arteriosus and persistent patency
729-31.
of the ductus arteriosus. In: Rudolph AM (Ed). Congenital
11. Laborde F, Noirhomme P, Karam J, et al. A new video-assisted
Diseases of the Heart: Clinical-Physiological Considerations.
thoracoscopic surgical technique for interruption of patent
3rd edition: John Wiley and Sons: UK; 2009. pp. 115-47.
ductus arteriosus in infants and children. J Thorac Cardiovasc
30. Cassels DE. The Ductus Arteriosus. Springfield, IL: CC Thomas:
Surg. 1993;105:278-80.
1973. p. 91.
12. Porstmann W, Wierny L, Warneke H. Closure of a persistent
31. Mullins CE, Pagotto L. Patent ductus arteriosus. In The Science
ductus arteriosus without thoracotomy. Ger Med Mon.
and Practice of Pediatric Cardiology. Garson AJ, Bricker JT,
1967;12:259-61.
Fisher DJ, Neish SR (Eds). Baltimore, Md: Williams & Wilkins;
13. Rashkind WJ. Transcatheter treatment of congenital heart
1998. pp. 1181-97.
disease. Circulation. 1986;67:711-6.
32. Record RG, Mckeown T. Observations relating to the aetiology
14. Rashkind WJ, Mullins CE, Hellenbrand WE, et al. Nonsurgical
of the patent ductus arteriosus. Br Heart J. 1953;15:376-86.
closure of patent ductus arteriosus: clinical application of
33. Anderson RC. Causative factors underlying congenital heart
the Rashkind PDA Occluder System. Circulation. 1987;75:
malformations. Patent ductus arteriosus. Pediatrics. 1954;14:
583-92.
143-51.
15. Bridges ND, Perry SB, Parness I, et al. Transcatheter closure
34. Carlgren LE. The incidence of congenital heart disease in
of a large patent ductus arteriosus with the clamshell septal
children born in Gothenburg 1941-1950. Br Heart J. 1959;21:
umbrella. J Am Coll Cardiol. 1991;18:1297-302. 327
40-50.
4 35. Mitchell SC, Korones SB, Berendes HW. Congenital heart
disease in 56, 109 births. Incidence and natural history.
57. Kanamaru H, Karasawa K, Miyashita M, et al. Successful
multiple coils embolization for bilateral patent ductus arterio-
Circulation. 1971;43:323-32. sus with isolated subclavian artery. Pediatr Int. 2006;48:510-3.
Shunt DefectS
36. Lloyd TR, Beekman RH 3rd. Clinically silent patent ductus 58. Kirklin JW, Barratt-Boyes BG. Cardiac Surgery. 2nd edn. New
arteriosus. Am Heart J. 1994;127:1664-5. York: Churchill Livingstone; 1993. p. 841.
37. Benson LN, Cowan KN. The arterial duct: its persistence and its 59. Hoffman J. Patent Ductus Arteriosus. In: Hoffman J (Ed). The
patency. In: Anderson RH, Baker EJ, Macartney FJ, Rigby ML, Natural and Unnatural History of Congenital Heart Disease.
Shinebourne EA, Tynan M (Eds). Paediatric Cardiology. 2nd USA: John Wiley and Sons Ltd; 2009. pp. 79-92.
edition. London: Churchill Livingstone. 2002. pp. 1405-59. 60. Basave M, Rangel A, Albarran H, et al. Unusual giant patent
38. Brook MM, Heyman MA. Patent ductus arteriosus. In: ductus arteriosus associated with ventricular septal defect and
Emmanouilides GC, Riemenschneider TA, Allen HD, et al. discrete aortic coarctation. A case report. Arch Cardiol Mex.
(Eds): Heart Disease in Infants, Children and Adolescents. 2001;71:146-50.
Baltimore. Williams and Wilkins; 1995. pp. 746-63. 61. PS Rao. Management of Patent ductus Arteriosus with
39. Evans N. Diagnosis of patent ductus arteriosus in the preterm emphasis on Transcatheter Therapy. 4th International Congress
newborn. Arch Dis Child. 1993;68:58-61. of Cardiology on the internet 2005.
40. Campbell M. Natural history of persistent ductus arteriosus. Br 62. Krichenko A, Benson L, Burrows P, et al. Angiographic
Heart J. 1968;30:4-13. classification of the isolated persistently patent ductus arteriosus
41. Clyman RI. Ductus arteriosus: Current theories of prenatal and and implications for percutaneous catheter occlusion. Am J
postnatal regulation. Semin Perinatol. 1987;11:64-71. Cardiol. 1989;63:877-80.
42. Eronen M, Kari A, Pesonen E, et al. The effect of antenatal 63. Abrams SE, Walsh KP. Arterial duct morphology with reference
dexamethasone administration on fetal and neonatal ductus to angioplasty and stenting. Int J Cardiol. 1993;40:27-33.
arteriosus: A randomized double blind study. Am J Dis Child. 64. Alwi M. Stenting the ductus arteriosus: Case selection,
1993;147:187-92. technique and possible complications. Ann Pediatr Cardiol.
43. Nora JJ. Multifactorial inheritance hypothesis for the etiology 2008;1:38-45.
of congenital heart disease: the genetic-environmental 65. Gittenberger-de Groot AC, Van Ertbruggen I, Moulaert AJ,
interaction. Circulation. 1968;38:604-17. et al. The ductus arteriosus in the preterm infant: histologic and
44. Nora JJ, Nora AH. Update on counselling the family with clinical observations. J Pediatr. 1980;96:88-93.
first degree relative with a congenital heart defect. Am J Med 66. Rudolph AM, Drorbraugh JE, Auld PA, et al. Studies on
Genet. 1988;29:137-42. the circulation in the neonatal period. The circulation in the
45. Zetterquist P. A Clinical and Genetic Study of Congenital Heart respiratory distress syndrome. Pediatrics. 1961;27:551-66.
Defects. Sweden: University of Uppsala; 1972. pp. 1-80. 67. Fay FS, Cooke PH. Guinea pig ductus arteriosus. II. Irreversible
46. Wilkins J. Risks of offspring of patients with patent ductus closure after birth. Am J Physiol. 1972;222:841-9.
arteriosus. J Med Genet. 1969;6:1-3. 68. Gittenberger-de Groot AC. Persistent ductus arteriosus: most
47. Polani PE, Campbell M. Factors in the causation of persistent probably a primary congenital malformation. Br Heart J. 1977;
ductus arteriosus. Ann Hum Genet. 1960;24:343-57. 39:610-8.
48. Lamy M, de Grouchy J, Schweisguth O. Genetic and non- 69. Gittenberger-de-Groot AC, Strengers JL, Mentink M.
genetic factors in the etiology of congenital heart disease: a Histologic studies on normal and persistent ductus arteriosus
study of 1188 cases. Am J Hum Genet. 1957;9:17-41. in the dog. J Am Coll Cardiol. 1985;6:394-404.
49. Forsey JT, Elmasry OA, Martin RP. Patent arterial duct. 70. Langer C. Zuranatomie der fotalenkreislaufsorgane. Z Ges
Orphanet J Rare Dis. 2009;4:17. Wien Arzte. 1857;13:328-38.
50. Nora JJ, Nora AH. The evolution of specific genetic and 71. Olley PM, Coceani F. Lipid mediators in the control of the
environmental counselling in congenital heart disease. ductus arteriosus. Am Rev Respir Dis. 1987;136:218.
Circulation. 1978;57:205-13. 72. Nguyen M, Camenisch T, Snouwaert JN, et al. The prostaglandin
51. Anoop P, Sasidharan CK. Patent ductus arteriosus in fetal receptor EP4 triggers remodelling of the cardiovascular system
valproate syndrome. Indian J Pediatr. 2003;70:681-2. at birth. Nature. 1997;390:78.
52. Gibson S, Lewis K. Congenital heart disease following maternal 73. Segi E, Sugimoto Y, Yamasaki A, et al. Patent ductus arteriosus
rubella during pregnancy. Am J Dis Child. 1952;83:117-9. and neonatal death in prostaglandin receptor EP4-deficient
53. Swan C, Tostevin AL, Black GHB. Final observations on mice. Biochem Biophys Res Commun. 1998;246:7.
congenital defects in infants following infectious disease 74. Smith GC. The pharmacology of the ductus arteriosus.
during pregnancy with special reference to rubella. Med J Aust. Pharmacol Rev. 1998;50:35.
1946;2:889-908. 75. Heymann MA, Rudolph AM. Control of the ductus arteriosus.
54. Knight L, Edwards JE. Right aortic arch. Types and associated Physiol Rev. 1975;55:62.
cardiac anomalies. Circulation. 1974;50:1047-51. 76. Kozik D, Ivy D, Ibrahim J, et al. Patent Ductus Arteriosus.
55. Carr MR, Neish SR, Leonard GT. Successful transcatheter In: Munoz R, Morrell V, da Cruz E, Vetterly C (Eds). Critical
coil occlusion of a right-sided patent ductus arteriosus Care of Children with Heart Disease: Basic Medical and
with aberrant left subclavian artery. Tex Heart Inst J. Surgical Concepts. Springer-Verlag London Limited; 2010.
2006;33:365-7. pp. 145-57.
56. Vida VL, Veras O, Leon-Wyss J, et al. The right-sided window 77. Rudolph AM. Congenital Diseases of the Heart: Clinical-
ductus: a rare anatomical entity. Ann Thorac Surg. 2006;81: Physiologic Considerations in Diagnosis and Management.
328
1126-7. Chicago: Year Book Medical. 1974.
78. Barnes N, Archer N. Understanding congenital heart disease.
Current Paediatrics. 2005;15:421-8.
98. Serwer GA, Armstrong BE, Anderson PA. Noninvasive
detection of retrograde descending aortic flow in infants using
21
79. Vijaya MJ, Sepehr S. Acyanotic Congenital heart defects. In continuous wave Doppler ultrasonography. Implications for

Pediatric Cardiology: The Requisites in Pediatric Cardiology. diagnosis of aortic run-off lesions. J Pediatr. 1980;97:394-400.
Mosby, Inc US: 2006. p. 87. 99. Agarwal R, Deorari AK, Paul VK. Patent ductus arteriosus in
80. Specific cardiac defects. In: Libby P, Bonow RO, Mann DL, preterm neonates. Indian J Pediatr. 2008;75:277-80.
Zipes DP (Eds). Libby: Braunwalo’s Heart Disease: A Textbook 100. Evans N. Diagnosis of the Preterm Patent Ductus Arteriosus:
of cardiovascular Medicine, 8th edn. Elsevier Saunders; 2007. Clinical Signs, Biomarkers, or Ultrasound? Semin Perinatol.
81. Rudolph AM, Mayer FE, Nadas AS, et al. Patent ductus 2012;36:114-22.
arteriosus. A clinical and hemodynamic study of 23 patients in 101. El Hajjar M, Vaksmann G, Rakza T, et al. Severity of the ductal
the first year of life. Pediatrics. 1958;22:892-904. shunt: A comparison of different markers. Arch Dis Child Fetal
82. Perkett EA, Lyons RM, Moses HL, Brigham KL, et al. Neonatal Ed. 2005;90:F419-F422.
Transforming growth factor-beta activity in sheep lung lymph 102. Morgan-Jughes GJ, Marshall AJ, Roobottome C. Morphologic
during the development of pulmonary hypertension. J Clin assessment of patent ductus arteriosus in adults using
Invest. 1990;86:1459-64. retrospectively ECG-gated multidetector CT. Am J Roentgenol.
83. Celermajer DS, Cullen S, Deanfield JE. Impairment of 2003;181:749-54.
endothelium-dependent pulmonary artery relaxation in 103. Brenner LD, Caputo GR, Mostbeck G, et al. Quantification of left
children with congenital heart disease and abnormal pulmonary to right atrial shunts with velocity encoded cine nuclear magnetic
hemodynamics. Circulation.1993;87:440-6 resonance imaging. J Am Coll Cardiol. 1992;20:1246-50.
84. Hoffman JIE, Buckberg GD. Regional myocardial ischemia: 104. Taneja K, Gulati M, Jain M, et al. Ductal arteriosus aneurysm
causes, prediction, and prevention. Vasc Surg. 1974;8:115-31. in the adult: role of computed tomography in diagnosis. Clin
85. Kluckow M, Evans N. Ductal shunting, high pulmonary blood Radiol. 1997;52:231-4.
flow, and pulmonary hemorrhage. J Pediatr. 2000;137:68-72. 105. Hammerman C. Patent ductus arteriosus. Clinical relevance
86. Robertson B. Surfactant inactivation and surfactant therapy in of prostaglandins and prostaglandin inhibitors in PDA
acute respiratory distress syndrome (ARDS). Monaldi Arch pathophysiology and treatment. Clin Perinatol. 1995;22:457-79.
Chest Dis. 1998;53:64-9. 106. Lim MK, Hanretty K, Houston AB, et al. Intermittent ductal
87. Jim WT, Chiu NC, Chen MR, et al. Cerebral hemodynamic patency in healthy newborn infants: demonstration by colour
change and intraventricular hemorrhage in very low birth Doppler flow mapping. Arch Dis Child. 1992;67:1217-8.
weight infants with patent ductus arteriosus. Ultrasound Med 107. Barst RJ, Gersony WM. The pharmacological treatment of
Biol. 2005;31:197-202. patent ductus arteriosus. A review of the evidence. Drugs.
88. Baptista MJ, Correia-Pinto J, Areias JC, et al. Patent ductus 1989;38:249-66.
arteriosus in neonatal intensive care. Rev Port Cardiol. 108. Bessinger FB Jr, Blieden LC, Edwards JE. Hypertensive pul-
1999;18:1095-1100. monary vascular disease associated with patent ductus arterio-
89. Bertino E, Giuliani F, Prandi G, et al. Necrotizing enterocolitis: sus: Primary or secondary? Circulation. 1975;52:157-61.
risk factor analysis and role of gastric residuals in very low birth 109. Yamaki S, Ishidoya T, Osuga T, et al. Progressive pulmonary
weight infants. J Pediatr Gastroenterol Nutr. 2009;48:437-42. vascular disease after surgery in a case of patent ductus
90. Baylen BG, Ogata H, Oguchi K, Ikegami M, Jacobs H, Jobe arteriosus with pulmonary hypertension. Tohoku J Exp Med.
A, et al. The contractility and performance of the preterm 1983;140:279-88.
left ventricle before and after early patent ductus arteriosus 110. Marquis RM, Miller HC, McCormack RJ, et al. Persistence of
occlusion in surfactant-treated lambs. Pediatr Res. 1985;19: ductus arteriosus with left to right shunt in the older patient. Br
1053-8. Heart J. 1982;48:469-84.
91. Friedman WF. The intrinsic physiologic properties of the 111. Sadiq M, Latif F, Ur-Rehman A. Analysis of infective endarteritis
developing heart. Prog Cardiovasc Dis. 1972;15:87-111. in patent ductus arteriosus. Am J Cardiol. 2004;93: 513-5.
92. Appleton RS, Graham TP Jr, Cotton RB, et al. Altered early left 112. Rutishauser M, Ronen G, Wyler F. Aneurysm of the nonpatent
ventricular diastolic cardiac function in the premature infant. ductus arteriosus in the newborn. Acta Pediatr Scand. 1977;66:
Am J Cardiol. 1987;59:1391-4. 649-51.
93. Way GL, Pierce JR, Wolfe RR, et al. ST depression suggesting 113. Cruickshank B, Marquis RM. Spontaneous aneurysm of the
subendocardial ischemia in neonates with respiratory distress ductus arteriosus. Am J Med. 1958;25:140-9.
syndrome and patent ductus arteriosus. J Pediatr. 1979;95:609-11. 114. Jan SL, Hwang B, Fu YC, et al. Isolated neonatal ductus
94. Schneider J. The Patent ductus arteriosus in term Infants, arteriosus aneurysm. J Am Coll Cardiol. 2002;39:342-8.
children and adults. Semin Perinatol. 2012;36:146-53. 115. Kerwin AJ, Jaffe FA. Post-operative aneurysm of the ductus
95. Gibson GA. Diseases of the Heart and Aorta. Edinburgh, arteriosus with fatal rupture of a mycotic aneurysm of a branch
Pentland, 1898. of the pulmonary artery. Am J Cardiol. 1959;3:397-403.
96. Nuntnarumit P, Khositseth A, Thanomsingh P. N-terminal 116. Ross RS, Feder FP, Spencer FC. Aneurysm of the previously
probrain natriuretic peptide and patent ductus arteriosus in ligated patent ductus arteriosus. Circulation. 1961;23:350-7.
preterm infants. J Perinatol. 2009;29:137-42. 117. Marasini M, Rimini A, Zannini L, et al. Giant aneurysm
97. Ramaciotti C, Lemler MS, Moake L, et al. Comprehensive following coil occlusion of patent ductus arteriosus. Cathet
assessment of patent ductus arteriosus by echocardiography Cardiovasc Intervent. 2000;50:186-9.
before transcatheter closure. J Am Soc Echocardiogr. 118. Falcon MW, Perloff JK, Roberts WC. Aneurysm of the
329
2002;15:1154-9. nonpatent ductus Arteriosus. Am J Cardiol. 1972;29:422.
4 119. Berger M, Ferguson C, Hendry J. Paralysis of the left
diaphragm, left vocal cord, and aneurysm of the ductus
in the Young; Council on Clinical Cardiology; Council on
Cardiovascular Radiology and Intervention; American Heart
arteriosus in a 7-day-old infant. J Paediatr. 1960;56:800-02. Association. Circulation. 2011; 123: 2607-52.
Shunt DefectS
120. Roughneen PT, Parikh P, Stark J. Bronchial obstruction 138. Kumar RK, Krishnan MN, Venugopal K, et al. Bioptome-
secondary to aneurysm of a persistent ductus arteriosus. Eur J assisted simultaneous delivery of multiple coils for occlusion
Cardiothorac Surg. 1996;10:146-7. of the large patent ductus arteriosus. Cathet Cardiovasc Interv.
121. Dyamenahalli U, Smallhorn JF, Geva T, et al. Isolated ductus 2001;54:95-100.
arteriosus aneurysm in the fetus and infant: a multi-institutional 139. Kumar RK, Anil SR, Kannan BRJ, Philip A, Sivakumar K.
experience.J Am Coll Cardiol. 2000;36:262-9. Bioptome-assisted coil occlusion of moderate-large patent
122. Roques F, Hennequin JL, Sanchez B, et al. Aortic stent-graft arterial ducts in infants and small children. Catheter Cardiovasc
for patent ductus arteriosus in adults: the aortic exclusion Interv. 2004;62:266-71.
technique. Ann Thorac Surg. 2001;71:1708-09. 140. Wang JK, Liau CS, Huang JJ, et al. Transcatheter closure of
123. Mosca F, Bray M, Lattanzio M, et al. Comparative evaluation patent ductus arteriosus using Gianturco coils in adolescents
of the effects of indomethacin and ibuprofen on cerebral per- and adults. Cathet Cardiovasc Interv. 2002;55:513-8.
fusion and oxygenation in preterm infants with patent ductus 141. Moore JW, George L, Kirkpatrick SE, et al. Percutaneous
arteriosus. J Pediatr. 1997;131:549-54. closure of small patent ductus arteriosus using occluding
124. Pezzati M, Vangi V, Biagiotti R, et al. Effects of indomethacin spring coils. J Am Coll Cardiol. 1994;23:759-65.
and ibuprofen on mesenteric and renal blood flow in preterm 142. Galal MO, Bulbul Z, Kakadekar A, et al. Comparison
infants with patent ductus arteriosus. J Pediatr. 1999;135:733-78. between the safety profile and clinical results of the Cook
125. Chotigeat U, Jirapapa K, Layangkool T. A comparison of detachable and Gianturco coils for transcatheter closure of
oral ibuprofen and intravenous indomethacin for closure of patent ductus arteriosus in 272 patients. J Interven Cardiol.
patent duct arteriosus in preterm infants. J Med Assoc Thai. 2001;14:169-71.
2003;86:S563-9. 143. Hijazi ZM, Geggel RL. Results of anterograde transcatheter
126. Hammerman C, Aramburo MJ. Prolonged indomethacin closure of patent ductus arteriosus using single or multiple
therapy for the prevention of recurrences of patent ductus Gianturco coils. Am J Cardiol. 1994;74:925-9.
arteriosus. J Pediatr. 1990;117:771-6. 144. Mavroudis C, Backer CL, Gevitz M. Forty-six years of
127. Rennie JM, Cooke RW. Prolonged low dose indomethacin for patent ductus arteriosus division at Children’s memorial
persistent ductus arteriosus of prematurity. Arch Dis Child. Hospital of Chicago: Standards for comparison. Ann Surg.
1991;66:55-8. 1994;1220:402-9.
128. Knight DB. The treatment of patent ductus arteriosus in 145. Rao PS, Kim SH, Choi JY, et al. Follow-up results of
preterm infants. A review and overview of randomized trials. transvenous occlusion of patent ductus arteriosus with the
Semin Neonatol. 2001;6:63-73. buttoned device. J Am Coll Cardiol. 1999;33:820-6.
129. Pass RH, Hijazi ZM, Hsu DT, et al. Multicenter USA Amplatzer 146. Sideris EB, Rao PS, Zamora R. The Sideris buttoned devices
patent ductus arteriosus occlusion device trial. J Am Coll for transcatheter closure of patent ductus arteriosus. J Inter
Cardiol. 2004;44:513-9. Cardiol. 2002;14:239-46.
130. Arora R. Transcatheter devices for large patent ductus arterio- 147. Wilson NJ, Occleshaw CJ, O’Donnell CP, et al. Subclinical
sus. Cardiology Today. 2004;8:121-3. aortic perforation with infant double-button patent ductus
131. LeBlanc JG, Russell JL, Sett SS, Potts JE, Human DG, Culham arteriosus occluder. Catheter Cardiovasc Interv. 1999;48: 296-8.
JA. The evolution of ductus arteriosus treatment. Int Surg 148. Grifka RG, Miller MW, Frischmeyer KJ, et al. Transcatheter
2000;85:1-5. occlusion of patent ductus arteriosus in a Newfoundland puppy
132. Leon-Wyss J, Vida VL, Veras O, et al. Modified extrapleural using the Gianturco-Grifka vascular occlusion device. J Vet
ligation of patent ductus arteriosus: a convenient surgical Intern Med. 1996;10:42-44.
approach in a developing country. Ann Thorac Surg. 149. Ebeid MR, Gaymes CH, Smith JC, et al. Gianturco-Grifka
2005;79:632-5. vascular occlusion device for closure of patent ductus
133. Rao PS. Transcatheter occlusion of patent ductus arteriosus: arteriosus. Am J Cardiol. 2001;87;657-60.
which method to use and which ductus to close. Am Heart J. 150. Moore JH, Schneider DJ, Dimeglio D. The duct-occlud device:
1996;132:905-09. design, clinical results and future directions. J Interv Cardiol.
134. Schrader R, Kadel C. Persistent ductus arteriosus–is closure 2001;14:231-8.
indicated also in asymptomatic adults with small ductus and 151. Faella HJ, Hijazi ZM. Closure of the patent ductus arteriosus
minor shunt? Z Kardiol. 1993;82:563-7. with the amplatzer PDA device: immediate results of the
135. Balzer DT, Spray TL, McMullin D, et al. Endartiritis associated international clinical trial. Catheter Cardiovasc Interv
with a clinically silent patent ductus arteriosus. Am Heart J. 2000;51:50-4.
1993;125:1192-3. 152. Pedra CA, Sanches SA, Fontes VF. Percutaneous occlusion of
136. Bennhagen RG, Benson LN. Silent and audible persistent the patent ductus arteriosus with the amplatzer device for atrial
ductus arteriosus. An angiographic study. Pediatr Cardiol. septal defects. J Invasive Cardiol. 2003;15:413-7.
2003;24:27-30 153. Hijazi ZM, Ahmad WH, Geggel RL, et al. Intravascular
137. Feltes TF, Bacha E, Beekman RH 3rd, et al. Indications for ultrasound during transcatheter coil closure of patent ductus
cardiac catheterization and intervention in pediatric cardiac arteriosus: comparison with angiography. J Invasive Cardiol.
disease: a scientific statement from the American Heart 1998;10:251-4.
330
Association. American Heart Association Congenital Cardiac 154. Duke C, Chan KC. Aortic obstruction caused by device
Defects Committee of the Council on Cardiovascular Disease occlusion of patent arterial duct. Heart. 1999;82:109-11.
155. Fischer G, Stieh J, Uebing A, et al. Transcatheter closure of arteriosus using a covered stent. Cathet Cardiovasc Interv.
2003;59:387-90.
21
persistent ductus arteriosus in infants using the Amplatzer duct
occluder. Heart. 2001;86:444-7. 167. Alter BP, Czapek EE, Rowe RD. Sweating in congenital heart

156. Vijayalakshmi IB, Chitra N, Praveen J, Prasanna SR. Chal- disease. Pediatrics. 1968;41:123-9.
lenges in Device Closure of a Large Patent Ductus Arteriosus 168. Gould DS, Montenegro ZM, Gaynor JW, et al. A comparison
in Infants Weighing Less Than 6 Kg. J Interven Cardiol . Pub- of on-site and off-site patent ductus arteriosus ligation in
lished online on 27th September 2012. premature infants. Pediatrics. 2003;112:1298-1301.
157. Vijayalakshmi IB, Chitra N, Rajasri R, et al. Amplatzer 169. Hines MH, Raines KH, Payne RM, et al. Video-assisted
angled duct occluder for closure of patent ductus ductal ligation in premature infants. Ann Thorac Surg.
arteriosus larger than the aorta in an infant. Pediatr Cardiol 2003;76:1417-20.
2005;26:480-3. 170. Kannan BRJ, Anil SR, Padhi S, et al. Transcatheter management
158. Thanopoulos BD, Tsaousis GS, Papadopoulos GS, et al. of patent ductus arteriosus in sick ventilated small infants.
Transcatheter closure of patent ductus arteriosus using the Indian Heart J. 2004;56:232-4.
swivel disk and plug occluders (abstract). Cath Cardiovasc 171. Marasini M, Rimini A, Zannini L, et al. Giant aneurysm
Intervent. 2002;57:99. following coil occlusion of patent ductus arteriosus. Cathet
159. Francis E, Anil SR, Sivakumar K, et al. Trial balloon occlusion Cardiovasc Interv. 2000;50:186-9.
for large patent ductus arteriosus with elevated pulmonary 172. Wilson WR, Giuliani ER, Danielson GK, et al. General
vascular resistance. Indian Heart J. 2002;54,E-57:499. considerations in the diagnosis and treatment of infective
160. Thanopoulos BD, Tsaousis GS, Djukic M, et al. Transcatheter endocarditis. Mayo Clin Proc. 1982;57:81-5.
closure of high pulmonary artery pressure persistent ductus 173. Daniels CJ, Cassidy SC, Teske DW, et al. Reopening after
arteriosus with the Amplatzer muscular ventricular septal successful coil occlusion for patent ductus arteriosus. J Am
occluder. Heart. 2002;87:260-3. Coll Cardiol. 1998;31:444-50.
161. Wright JS, Newman DC. Ligation of the patent ductus. 174. Ebeid MR, Masura J, Hijazi ZM. Early experience with the
Technical consideration at different ages. J Thorac Cardiovasc Amplatzer ductal occluder for closure of the persistently patent
Surg. 1978;75,695-8. ductus arteriosus. J Interv Cardiol. 2001;14:33-6.
162. John S, Muralidharan S, Jairaj PS, et al. The adult ductus: 175. Joseph G, Mandalay A, Zacharias TU, et al. Severe
review of surgical experience with 131 patients. J Thorac intravascular hemolysis after transcatheter closure of a large
Cardiovasc Surg. 1981;82:314-9. patent ductus arteriosus using the Amplatzer duct occluder:
163. Arora R, Singh S, Dalra GS. Patent ductus arteriosus: successful resolution by intradevice coil deployment. Cathet
catheter closure in the adult patient. J Interv Cardiol. Cardiovasc Interv. 2002;55:245-9.
2001;14:155-9. 176. Wang LH, Wang JK, Mullins CE. Eradicating acute hemolysis
164. Rogues F, Hennequin JL, Sanchez B, et al. Aortic stent-graft following transcatheter closure of ductus arteriosus by
for patent ductus arteriosus in adults: the aortic exclusion immediate deployment of a second device. Cathet Cardiovasc
technique. Ann Thorac Surg. 2001;71:1708-09. Diagn. 1998;43:295-7.
165. Hakim F, Hawelleh AA, Goussous Y, et al. Simultaneous stent 177. Grifka RG. Transcatheter closure of the patent ductus
implantation for coarctation of the aorta and closure of patent arteriosus. Catheter Cardiovasc Interv. 2004;61:554-70.
ductus arteriosus using the Amplatzer duct occluder. Catheter 178. Bret EL, Papadatos S, Folliquet T, et al. Interruption of patent
Cardiovasc Interv. 1999;47:36-8. ductus arteriosus in children: robotically assisted versus video
166. Sadiq M, Malick NH, Qureshi SA. Simultaneous treatment of thoracoscopic surgery. J Thorac Cardiovasc Surg. 2002;123:
native coarctation of the aorta combined with patent ductus 973-6.
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C hapter
22 Aortopulmonary Window
Vijayalakshmi IB, Praveen Jayan, Satish Govindaiah
INTRODUCTION CLASSIFICATION
Aortopulmonary window (APW) or aortopulmonary septal Aortopulmonary window, a defect in the aortopulmonary
defect is a rare congenital heart disease occurring in 0.2 to septum, is classified into various types by different authors.
0.6 percent of all patients with congenital heart disease.1 Mori et al classified the APW into three types3:
APW was first described by John Elliotson in 1830.1 APW Type I or proximal defect is the most common (70–96% of
represents a communication between ascending aorta and cases) and occurs in the proximal part of the aortopulmonary
pulmonary trunk. It is characterized by the presence of well- septum. They are located just above the semilunar valves.
defined and separate aortic and pulmonary valves, unlike in Type II or distal defect (14–25%) occurs in the distal part of
truncus arteriosus, where only an isolated truncal valve is aortopulmonary septum adjacent to the right pulmonary artery
noted.2 Half of the patients with APW are associated with (RPA). They involve the pulmonary bifurcation at the level of
other cardiac defects. The most common associated defect is the RPA. This form may be associated with type A IAA.8
the type A interrupted aortic arch (IAA). The other associated Type III or total defect (5%) is a large confluent defect
cardiac defects includes aortic origin of right pulmonary where there is total absence of the aortopulmonary septum.
artery, anomalous origin of right coronary or left coronary Later Ho et al9 modified the above classification of APW
artery from pulmonary artery, tetralogy of Fallot, patent ductus into four types according to its morphologic features:
arteriosus (PDA) and right aortic arch. It is rarely associated 1. Proximal defect is between the ascending aorta and the
with ventricular septal defect (VSD).3-5 main pulmonary artery, having little inferior rim separating
the APW from the semilunar valves.
Synonyms 2. Distal defect is between origin of the RPA and ascending
aorta having a well-formed inferior rim, but little superior
The synonyms like aortopulmonary septal defect, aortopul- rim. This defect is associated with aortic origin of the RPA.
monary fenestration or aortopulmonary fistula are not com- 3. Confluent defect, is a combination of the first and second
monly used. types with little superior and inferior rims.
4. Intermediate type is characterized by adequate superior and
EMBRyOLOGY inferior rims. It is the intermediate type of defect, which is
best suited for device closure (Figure 1).
The aortopulmonary septum is formed during early em- Kutsche and Van Mierop described three types of aorto-
bryogenesis by the opposing truncal cushions which fuse pulmonary defect:
to divide the truncus arteriosus into aortic and pulmonary 1. A defect with a circular border located between the
channels.6 Maldevelopment of this aortopulmonary sep- semilunar valves and pulmonary bifurcation.
tum leads to the development of APW. Unlike truncus 2. A similarly located fenestration in which the border
arterious, APW is not associated with DiGeorge syndrome.7 represents a helix.
22
Aortopulmonary Window
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 resistance, and the presence of associated defects. Clinical
to the author the first type may reflect non-fusion of features of APW are those of a large left-right shunt. Clinically
aortopulmonary septum and truncal septum. The second APW is indistinguishable from PDA. Signs of congestive heart
type suggests malalignment of the aortopulmonary septum failure (tachypnea, diaphoresis, failure to thrive and recurrent
and truncal septum, while the third type result from total respiratory infections) develops during first week of life. If
absence of embryonic aortopulmonary septum.1,6 associated with aortic arch anomalies, the patient can present
in the neonatal period with metabolic acidosis and cardiogenic
Natural History and Hemodynamics shock following the closure of PDA.
Clinical examination reveals tachypnea and intercostal
There is neither the tendency for APWs to close spontaneously retraction, a bounding arterial pulse and wide pulse
nor does the defect size decrease with time and growth pressure similar to nonrestrictive PDA with low pulmonary
of the patient. The defect is variable in size, but all defects vascular resistance. On auscultation second heart sound
result in a large and generally continuous left-to-right shunt, is accentuated and narrowly split indicating pulmonary
when the pulmonary vascular resistance falls, similar to hypertension.3,12 Large nonrestrictive APW generates a
other interarterial communications such as PDA or truncus loud systolic ejection murmur at the third left intercostal
arteriosus.7 After the immediate perinatal period there is space along with eddy sounds. Apical mid-diastolic murmur
enlargement of left atrium and left ventricle. The pulmonary is heard which represents increased flow across the mitral
arteries are dilated due to the increased pulmonary blood flow. valve.
The ascending aorta can be small in patients with APW with Moderately, restrictive APW generates a continuous
proximal defects or with associated arch anomalies.10 Without murmur in the upper left sternal border. Large APW associated
corrective surgery, irreversible obstructive changes in the with severe pulmonary arterial hypertension (PAH) and
pulmonary vascular bed develop early, followed by death in reversed shunt presents with Graham Steell murmur due to
the second decade, although patients surviving into the 4th the marked dilatation of hypertensive pulmonary trunk.
decade have been reported.5,11 There is an interesting report
of a patient with Eisenmenger syndrome secondary to a large Differential Diagnosis
unrepaired APW who gave birth to three children in her 30s,
survived into her 50s with relatively preserved quality of life, The signs and symptoms mimics large PDA and truncus
and died at age 60 years.12 The defect is small in about 10 arteriosus (Type I). In APW associated VSD and right-sided
percent of patients and they usually present late in childhood aortic arch are extremely rare.
like any other moderate sized left-to-right shunt.
ELECTROCARDIOGRAPHY
CLINICAL FEATURES
There is no characteristic electrocardiography (ECG) finding
The clinical presentation is determined by the size of the defect, in patients with APW. Large APW is characterized by
the relationship between systemic and pulmonary vascular biventricular hypertrophy (Figure 2). 333
4
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.
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
Figure 3: X-ray chest posteroanterior (PA) view shows cardiomegaly pulmonary artery (Figures 5A and B) and demonstrates arch
with biventricular hypertrophy with prominent MPA with plethora
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
Radiological Features
demonstrated.
The chest X-ray shows cardiomegaly with left ventricular
contour, LA enlargement and plethoric lung fields are seen TREATMENT
in patients with large APW (Figure 3). The aortic knuckle
is not prominent in contrast to PDA. Peripheral pruning of World literature on transcatheter closure of APWs is limited
pulmonary vessels with prominent main pulmonary artery to closure of restrictive defects, that too in adults or older
indicates severe pulmonary artery hypertension. children. Different operators have used different types of
devices for percutaneous closure of APWs including umbrella
Echocardiography device, Amplatzer septal occluder and duct occluders.
Intermediate type defect, which has adequate superior and
Two-dimensional echocardiography reveals dilatation inferior rims is best suited for device closure. There are few
of the left atrium and left ventricle. The right ventricle case reports of device closure of non-restrictive APW in
334 may be hypertrophied with significant dilatation of infants.14-16 Depending on the PA pressure either Amplatzer
pulmonary arteries. APW is usually seen as a dropout in the duct occluder or Amplatzer septal muscular occluder is
22
Aortopulmonary Window
A B
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.
A B
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, without extracorporeal circulation, through a transaortic or
then balloon sizing can be done. The standard arteriovenous transpulmonary approach, and with or without the use of a
loop is made and then selected device is introduced from patch. Transaortic approach allows close inspection of the
the venous end. The successful closure can be checked with coronary ostia, correction of arch anomalies and coronary
angiogram and also transthoracic echocardiogram (Figures anomalies.8 Recent revisions have used a pulmonary artery
6A to C). flap to close the defect and this technique avoids the use of
prosthetic material.
Surgery
Conclusion
Gross first successfully ligated an APW in 1948.17 This
technique was associated with distortion of the semilunar The survival of an infant with large APW, presenting with
valves and distortion of the left coronary artery. Several surgical congestive heart failure is poor. Approximately 20 to 30
techniques and modifications have been described, with or percent of large APW, patients die within 1 year. Early 335
4
Shunt Defects
A B C
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 7. Marmon LM, Balsara RK, Chen R, et al. Congenital cardiac
of treatment. It has to be done before the child develop anomalies associated with the DiGeorge syndrome: A neonatal
severe PAH. Early detection of APW is very important as experience. Ann Thorac Surg. 1984;38:881-4.
they develops severe PAH very early in life. Transthoracic 8. Pillekamp F, Hannes T, Koch D, Brockmeier K, Sreeram N.
echocardiogram and and magnetic resonance imaging are Transcatheter closure of symptomatic aortopulmonary window
in an infant. Images Pediatr Cardiol. 2008;35:11-7.
useful for diagnosis. Transcatheter non-surgical device
9. Ho SY, Gerlis LM, Anderson C, Devine WA, Smith A. The
closure is useful in small restrictive APW.
morphology of aortopulmonary window with regard to their
classification and morphogenesis. Cardiol Young. 1994;4:146-55.
A smart mother makes often a better diagnosis than a poor 10. Moguillansky D, Munoz R, Morell VO. Aortopulmonary Window.
doctor. In Critical Care of Children with Heart Disease: Basic Medical
—August Bier and Surgical Concepts. Munoz R, Morrell V, da Cruz E, Vetterly
C (eds). Springer-Verlag London Limited; 2010: 191-197.
REFERENCES 11. LC Blieden and Moller JH. Aorticopulmonary septal defect.
An experience with 17 patients. Br Heart J. 1974;36:630-5.
1. Kutsche LM, Van Mierop LH. Anatomy and pathogenesis of 12. Su-Mei AK, Ju-Le T. Large unrepaired aortopulmonary
aorticopulmonary septal defect. Am J Cardiol. 1987;59:443-7. window—survival into the seventh decade. Echocardiography.
2. Mert M, Paker T, Akcevin A, et al. Diagnosis, management, 2007;24:71-3.
and results of treatment for aortopulmonary window. Cardiol 13. Balaji S, Burch M, Sullivan ID. Accuracy of cross-sectional
Young. 2004;14:506-11. echocardiography in diagnosis of aortopulmonary window.
3. Mori K, Ando M, Takao A, et al . Distal type Aortopulmonary Am J Cardiol. 1991;67:650-3.
window. Report of 4 cases. Br Heart J. 1978;40:681-9. 14. Atiq M, Rashid N, Kazmi KA, Qureshi SA. Closure of
4. Redington AN, Rigby ML, Ho SY, Gunthard J, Anderson RH. aortopulmonary window with Amplatzer duct occluder device.
Aortic atresia with aortopulmonary window and interruption of Pediatr Cardiol. 2003;24:298-9.
the aortic arch. Pediatr Cardiol. 1991;12:49-51. 15. Rohit M, Nandakumar S, Bahl A, Kubba S, Talwar KK.
5. Meisner H, Schmidt-Habelmann P, Sebenning F, Klinner Transcatheter closure of aortopulmonary window. Indian Heart
W. Surgical correction of aorto-pulmonary septal defects. A J. 2005;57:161-3.
review of the literature and report of eight cases. Dis Chest. 16. Sivakumar K, Francis E. Transcatheter closure of distal
1968;53:750-8. aortopulmonary window using Amplatzer Device. Congenit
6. Van Mierop LH S, Kutsche LM. Embrology of the Heart. In: Heart Dis. 2006;1:321-3.
Hurst JW, (Ed). The Heart. (6th edn) New York: McGraw-Hill, 17. Gross RE. Surgical closure of an aortic septal defect.
1986. Circulation. 1952;5:858-63.
336
C hapter
23 Aorticocameral Tunnels
Vijayalakshmi IB, Chitra Narasimhan
Aorticocameral tunnels are extremely rare congenital extra Historical Review

cardiac vascular channels or communications, which connect
the ascending aorta above the sinotubular junction to any of The ALVT was originally described by Edwards and
the chambers of the heart. The ascending aorta is reported to Burchell6 who considered the malformation as a ‘separation
be the most common site of origin for aorticocameral tunnels between the aorta and the heart’ or a type of aneurysm, which
but rarely tunnel arising from the descending thoracic aorta lay against the outflow tract of the right ventricle and origin
has also been reported.1,2 of the pulmonary trunk’. The ‘aortico-left ventricular tunnel’
More than 90 percent of the aorticocameral tunnels was described by Levy and colleagues in 19637 and the term
communicate with the left ventricle, occasionally with the ‘aorto-left ventricular tunnel’ was introduced about 10 years
right ventricle, rarely with the atria.3 The most common of later by Ross and colleagues.8 The more general designation
these infrequent conditions is the aorto-left ventricular tunnel 'aorto-ventricular tunnels' has recently been applied to this
(ALVT), followed in frequency by the aorto-right atrial tunnel, group of malformations, as they may extend to either the left
aorto-right ventricular tunnel (ARVT) and the aorto-left atrial or the right ventricular cavity.9
tunnel. All of these conditions produce the physiology of
congenital aortic insufficiency, but when the tunnel connects Incidence and Etiology
to a right heart chamber, an important left-to-right shunt is
also produced.4 The incidence of ALVT varies between 0.05 to 0.46 percent
as reported in a clinicopathological series.5 Although, more
Aortoventricular Tunnel 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
Introduction more common in males than in females, and is seldom seen
in patients of Asian, Oriental or African descent. The etiology
Aortoventricular tunnel is a congenital extracardiac channel of aortoventricular tunnel is uncertain. It appears to result
that connects the ascending aorta above the sinotubular from the abnormal development, which involves failure of the
junction to the cavity of left ventricle or (less commonly) right outflow cushions to properly seperate from the arterial sinuses,
ventricle. The aortoventricular tunnel differs from ruptured the valvular leaflets and the fibrous interleaflet triangles.
sinus of Valsalva aneurysm in having its vascular orifice in the The cushions, which form the facing aortic and pulmonary
tubular aorta, rather than in the sinus of the aortic valve and sinuses with their respective valvar leaflets normally become
in passing outside the heart into the tissue plane between the separated by an extracardiac tissue plane due to the regression
muscular subpulmonary infundibulum and the aortic valvar of the surrounding muscle. The coronary arteries, which are
sinuses.5 The tunnel bypasses the normal ventriculoarterial initially encased by this cuff of myocardium, grow through it
junction but does not penetrate the septal musculature. The to connect with the aortic sinuses. If this tissue plane fails to
aortoventricular tunnel is the most common cause of abnormal develop normally it may then result in a tunnel above one of the
blood flow from the aorta to a ventricle in infancy. facing aortic sinuses and also is the reason for the associated
4 involvement of the proximal coronary arteries and valve Schematic representation of the most common type of ALVT
leaflets. Thus, this is one of the few congenital malformations is shown in Figure 1.
which may simultaneously involve both the pulmonary and Anomalies of the aortic root are present in about half of
Shunt Defects
aortic valves.7,27 Nearly half of the aorticocameral tunnel these patients with tunnels.7,9,32,33 Aortic regurgitation is the
patients suffer from other cardiac defects particularly aortic most common association, probably due to the weakness of
valve and/or coronary artery anomalies.28,29 the aortic sinus wall, especially the unsupported right coronary
cusp with resultant aortic root ectasia.33,34 Aortic valve stenosis
Pathological Anatomy has been reported with bicuspid or unicuspid aortic valves.27,32
Severe aortic dysplasia or atresia can also occur.35,36
The aortoventricular tunnel is an abnormal channel that Valvular pulmonary stenosis37,38 occurs less frequently
connects the lumen of the ascending aorta to the cavity of (around 5%), while compression of the right ventricular out
either the left or right ventricle. The aortic opening of most flow tract by the tunnel may produce subpulmonary obstruc
tunnels lies above the right coronary sinus of Valsalva. The tion.27,39 Rarely, both semilunar valves are stenotic.7,27 An as
tunnel courses in the tissue plane between the free-standing sociated ventricular septal defect is rare,28,40 but there can be
muscular subpulmonary infundibulum and the aortic sinus an associated sinus of Valsalva aneurysm.33,41
and communicates with the left ventricle in the fibrous Aortoventricular tunnels have important relationships to
interleaflet triangle between the right and left coronary aortic the proximal portions of the coronary arteries.42 The ostium
leaflets or the right ventricle immediately above or below of a coronary artery may lie within an aortoventricular tunnel.
the subpulmonary infundibulum.30 Tunnels lying above Atresia of the left11,43 or right8,15,28,31,32,44,45 have both been
the left sinus of Valsalva or the intercoronary commissure observed with this anomaly.
have less uniform morphology and they virtually never
enter this fibrous triangle.9 The tunnel itself may be dilated Pathophysiology
aneurysmally through part or the entirety of its course.
The origin of the tunnel from the tubular aorta is above the The pathophysiological effect depends on the size of the
sinotubular junction, which differentiates it from the rupture tunnel and the amount of regurgitation. Interference with
of an aneurysm of sinus Valsalva. The ruptured sinus of coronary blood flow may be a contributing factor. Fetal
Valsalva aneurysm originates below the sinotubular junction hydrops or death has occurred when the tunnel has been large,
and remains completely within the heart. The differentiation antenatally.46 The large tunnels cause severe congestive heart
of the tunnel from the coronary-cameral fistula is less clear failure and most patients are symptomatic in infancy and most
as a coronary arterial orifice may arise above the sinotubular often under a month of age.32,33,40,44,47,48 Patients with smaller
junction and the coronary arteries have been found to arise tunnels are asymptomatic and present between 1 and 15 years
from within the aortoventricular tunnel.9 But the coronary- of age. But almost all have aortic valve regurgitation or signs
cameral fistula passes through the myocardium to enter the of left ventricular dilatation and hypertrophy. The oldest
cardiac chamber and does not involve the hingepoint of an patient presented at 63 years of age with multiple tunnels.3
aortic valvular leaflet. Histologically, the arterial end of the In one patient the tunnel closed spontaneously.28 Infective
tunnel resembles the aorta with fibrous tissue, elastic fibers endocarditis has been reported in one case.49
and smooth muscle cells, while the ventricular end contains
hyalinized collagen and muscle. This reflects that the ‘walls’ Clinical Presentation
of the tunnels incorporate the structures through which they
pass.5 The onset, severity and progression of symptoms are variable.
While many patients may have no symptoms, others may pre
Types of Aorto-left Ventricular Tunnel sent with rapid progression or sudden death. Death in utero
may also occur. The symptoms are dependant on the size of
Hovaguimian et al31 have proposed an anatomic classification tunnel, its hemodynamic influence and the associated cardiac
of ALVT based on morphology. They classified them as defects.3 Congestive heart failure may occur at any age due to
Type I A simple tunnel with a slitlike opening at the aortic severe AR.50,51
end and no aortic valve distortion The signs may include bounding pulses, a wide pulse pressure
Type II A large extracardiac aortic wall aneurysm of the and a loud 'to-and-fro' systolic and diastolic murmur. It is usually
tunnel with an oval opening at the aortic end, with or accompanied by systolic and diastolic thrills felt on a wide area on
without ventricular distortion the precordium. In patients with ALVT with pulmonary stenosis,
Type III
Intracardiac aneurysm of the septal portion of the the onset of heart failure is delayed. In those with a tunnel, with
tunnel, with or without right ventricular outflow tract associated severe aortic valve obstruction, heart failure occurs
obstruction early, with or without low cardiac output and nearly one third of
338 Type IV Combination of type II and III reported cases having died before birth or on the first day of life.19
23
Aorticocameral Tunnels
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
the diagnostic investigation of choice.40,53-55 The apical five
Chest X-ray shows cardiac enlargement with uniform chamber view provides the clear anatomic picture of the tun
dilatation of the ascending aorta. The dilated aorta is not nel arising from the aorta (Figures 3A and B). Apical four
infrequently mistaken for the thymus gland. In some patients, chamber view with color Doppler shows the dilated tunnel
the tunnel itself can be seen as a leftward prominence of the entering the RV (Figures 4A and B).
aortic root in the area of the pulmonary trunk.8 The tunnel The subcostal or apical four chamber view can demonstrate
itself can be seen as a right border on chest X-ray in ARVT the device in situ after the transcatheter closure of the tunnel
(Figure 2). The electrocardiogram typically shows left or (Figures 5A and B). The aortic origin of the tunnel as well as its
biventricular hypertrophy with a ‘strain pattern’ of inverted T course and opening into the left ventricle can be demonstrated
waves seen in the precordial leads. The electrocardiogram can in a parasternal long-axis view with color Doppler (Figures 6A
be occasionally normal.52 and B) sometimes with clockwise rotation of the probe.28,56
The two-dimensional transthoracic echocardiography The device in situ can be nicely demonstrated in the same 339
(TTE) with cross-sectional and color Doppler imaging is view (Figure 6C). Tunnels which open into the right ventricle
4
Shunt Defects
A B
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
A B
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.
A B In the occasional patient in whom the diagnosis is difficult,

magnetic resonance imaging (MRI) or computed tomographic
Figures 3A and B: Echocardiogram with color Doppler in an 11 (CT) angiography can be done, especially to delineate the
month infant with aorto-right ventricular tunnel: A. Apical five-chamber
view shows the dilated tunnel arising from the right aortic sinus;
coronaries (Figures 7A and B) or cardiac catheterization
B. Parasternal short-axis view shows normal sized left and right may be helpful to know the anatomy for device closure.
coronary arteries arising from left coronary sinus. Ao = Aorta; LA = Left Magnetic resonance angiography (MRA) also has been used
atrium; LCA = Left coronary artery; LV = Left ventricle; RCA = Right to demonstrate tunnels to the left55 and right19 ventricles,
coronary artery; RV = Right ventricle.
but is not widely available in clinical practice. Cardiac
catheterization with angiography is now indicated only
when associated lesions or coronary arterial origins cannot
are visualized in the apical four-chamber view. The parasternal be evaluated with certainty on non-invasive studies or when
short-axis view helps to distinguish the coronary AV fistula percutaneous intervention is planned.
from the tunnel by delineating normal sized coronaries Of all these features, extensive and uniform dilation of
separately from the tunnel. the ascending aorta may be the best non-invasive clue to
On color Doppler studies, diastolic flow is seen passing the diagnosis of aortoventricular tunnel, for this is hardly
from the aorta to the left ventricle and systolic from the ever present early in life with other cardiac malformations.
ventricle to the aorta. In ALVT, the ventricular function, which Extremely rarely enlargement of the aorta is not present,
may be variably impaired with hypertrophy and dilatation, is specifically when there is critical obstruction of both the aortic
assessed in short-axis views.5 The fetal diagnosis can also be valve and within the tunnel.59
340 reliably done with both two-dimensional and real-time three- The most common diagnostic errors from echocardiography
dimensional echocardiography.48,57,58 have been to confuse the ventricular end of the tunnel with
23
A B C
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;
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
A B regurgitation, sometimes with left ventricular dysfunction and
hydrops.46 There are no known molecular markers for aorto-
Figures 7A and B: A. Computed tomography angiogram shows the ventricular tunnel at present and it is not associated with any
dilated tunnel arising from right sinus with right coronary artery and left
coronary artery (branching into left anterior descending and circumflex recognized genetic syndrome.5
arteries) arising from left coronary sinus (three white arrows) B. Shows
tunnel encircling the right atrium and opening into the right ventricle. Natural History
Ao = Aorta; LV = Left ventricle; RV = Right ventricle.
The anomaly can be detected in utero and if the tunnel is large,
a ventricular septal defect7,27 or to mistake displacement of it causes left ventricular dysfunction.9,48 One intrauterine
the subpulmonary infundibulum for Fallot’s tetralogy.29 Flow death has been attributed to the tunnel but several fetuses
of blood through the tunnel has also been misinterpreted as had congestive heart failure.46 Nearly 60 to 70 percent of
valvular aortic regurgitation29 or a ruptured aneurysm of the these patients present in infancy. If they present in infancy in
sinus of Valsalva.46 congestive heart failure, medical management results in almost
100 percent mortality, usually soon after presentation.33 A 63
Differential Diagnosis years old patient has been reported with multiple aortic cameral
tunnels.3
The differential diagnosis include lesions, which cause rapid
aortic run-off and produce cardiac failure. These include rupture Management
of sinus of Valsalva aneurysm, truncus arteriosus with valvular
regurgitation, aortopulmonary window, ventricular septal defect Surgical correction of tunnel carrying significant blood flow
with aortic regurgitation, patent ductus arteriosus, coronary- should be undertaken without delay, even in asymptomatic
cameral fistula, valvar aortic stenosis and regurgitation, tetralogy patients, as only those repaired in the first 6 months of life
of Fallot with absent pulmonary valve and cerebral arterio- have been shown to have subsequent normalization of
venous malformation.9 ventricular size and function.44 Moreover, lack of support for
the right or left coronary aortic leaflet invariably results in
Antenatal Diagnosis progressive aortic regurgitation,60 often necessitating repair
or replacement of the valve. Observation may be appropriate
The most consistent echocardiographic feature on antenatal for the occasional asymptomatic patient with a very small (2
examination between 18 and 33 weeks gestation is dilatation millimeter) ALVT.28 341
4 Surgery
Repair consists of closing the tunnel such that the

Shunt Defects
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 A B
tunnel itself to close the ventricular orifice and support the
Figures 9A and B: A. Aortic root angio in left anterior oblique (LAO)
aortic valve.5 The tunnel wall itself can be used alternatively
view shows the aorto-right ventricular tunnel with aneurysmally dilated
to achieve an equivalent anatomical result.61 The aortic proximal portion before opening into the right ventricular outflow
orifice can be closed by direct suture,28,41,62 but more tract. Both the left and right coronaries are seen arising from the left
often, the tunnel recurs or progressive aortic regurgitation coronary sinus; B. Check angiogram in LAO shows complete closure
of the tunnel with no residual shunt. Amplazter duct occulder II (device)
through an unsupported or distorted right coronary leaflet
is seen as two hyperechogenic points in the retention discs.
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 if percutaneous interventions can achieve long-term outcomes
not closed.39 In ARVT, it is less certain that the ventricular equivalent to those of current surgical techniques, for which
orifice needs to be closed but in most reported cases this has operative mortality approaches zero.28,44
been done, either with a patch or direct suture, through a
right ventricular incision.5 Associated lesions like aortic or Aortoatrial tunnels
pulmonary stenosis are treated as indicated either separately
or at the time of tunnel repair. Aortoatrial tunnel is a very rare congenital anomaly. There is
an abnormal tunnel-like vascular extracardiac communication
Non-Surgical arising from the aortic root and terminating in either the right
(Figures 10A and B) or left atrium. The tunnels between the
Transcatheter closure of an ALVT with an Amplatzer duct aorta and the left atrium is extremely rare and is more often
occluder has been reported in two patients (Figures 8A associated with complications of infective endocarditis65 and
and B).63,64 Transcatheter closure of ARVT has been done in paravalvular abscess, aortic dissection66 and after surgery
two patients, one with a duct occluder22 and another at our affecting the valve or aortic root.
institution using Amplatzer duct occluder II in an eleven month
infant26 (Figures 9A and B). Due to the benefit of providing Aorta-Right Atrial Tunnel
support for the aortic valvar leaflets, as well as the spectrum
of associated coronary arterial anomalies, it seems likely that The aorta-right atrial tunnel was first described in 1980.67
repair of the aortoventricular tunnels should remain largely, if It is a vascular channel that originates from any of the three
not exclusively, within the surgical domain as it is questionable 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
A B type of atrial septal defect and persistence of the left
superior vena cava.72
Figures 8A and B: A. Aortic root angiogram shows dilated aortic
root with moderate aortic regurgitation and aneurysmally dilated The embryologic background and pathogenesis of this
extracardiac portion of tunnel entering the left ventricle; B. Check anomaly are not clear. These are attributable either to an
angiogram shows the 16 X 14 Amplatzer duct occulder (device) device aneurysmal dilation of the sinus nodal artery or to a congenital
with residual shunt weakness of the elastic lamina in the aortic media.68,72 Due to
342
23
A B
C D
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 10B). Rupture of sinus of Valsalva can be differentiated
forms an extracardiac tunnel, leading to gradual enlargement by demonstrating a tunnel with an extracardiac course.68
and rupture into the RA because of its anatomic proximity and Aortography also helps to differentiate it from coronary
low filling pressure. cameral fistula and to delineate the tunnel and to assess the
tortuosity and suitability for transcatheter interventions
Symptoms and Signs (Figures 10C and D).
Electron beam tomography or MRA might might
This aorto-right atrial communication behaves like a be additional non-invasive tools for diagnosis. The CT
left-to-right shunt at the atrial level. Most patients may angiography is an additional non-invasive diagnostic tool.
be asymptomatic or they may present with exertional Electron beam tomography can be a good diagnostic tool,
breathlessness, palpitations or recurrent respiratory tract showing the tunnel taking its origin from the aortic root and
infections.72 On physical examination, a continuous murmur entering the right atrium through a tortuous communication.71
at the right parasternal border is present.
Management
Diagnosis
Closure of an aorta-right atrial tunnel is recommended even
The tunnel can be readily identified by TTE. The apical in asymptomatic patients69 as there is only a low rate of
four chamber view shows the tunnel opening into the right procedural complications. Moreover, the continued patency
atrium and the color Doppler also delineates the extracardiac of the tunnel leads to risk for biventricular volume overload,
portion of the tunnel (Figure 10A). Retrograde aortography bacterial endocarditis, pulmonary vascular disease, aneurysm
combined with selective coronary angiography is essential for formation, calcification of the wall, aortic regurgitation and 343
the demonstration of its course and the coronary ostia (Figure spontaneous rupture.67-69,72
4 Treatment options are available according to the type of lian. The Natural and Modified History of Congenital Heart
tunnel/fistula, its caliber, tortuosity, calcification, course and Disease. (Eds) Robert M. Freedom, Shi-JoonYoo, HaverjMi
relation of the coronary ostia to the aortic orifice of the tun kailian. William G Williams Copyright @ 2004 Futura.
Shunt Defects
nel/fistula. They include transcatheter closure, ligation under 5. McKay R. Aorto-ventricular tunnel. Orphanet J Rare Dis.
2007;2:41.
controlled hypotension or repair with the patient under under
6. Edwards JE, Burchell HB. The pathological anatomy of
cardio pulmonary bypass.72,73
deficiencies between the aortic root and the heart, including
Surgical options include plication of the tunnel or patch aortic sinus aneurysms. Thorax. 1957;12:125-39.
closure of aortic origin with direct closure of the atrial 7. Levy MJ, Lillehei CW, Anderson RC, et al. Aortico-left
opening. The ligation for anteriorly located aorta-right atrial ventricular tunnel. Circulation. 1963;27:841-53.
tunnel includes ligation near the aortic end, and for posteriorly 8. Somerville J, English T, Ross DN. Aorto-left ventricular
located tunnels, ligation should be done between between tunnel. Clinical features and surgical management. Br Heart J.
superior vena cava and aorta as close to the aorta as possible.72 1974;36:321-8.
External ligation of the tunnel close to the aorta should be 9. McKay R, Anderson RH, Cook AC. The aorto-ventricular
tunnels. Cardiol Young. 2002;12:563-80.
performed only after accurate evaluation of the external
10. Bharati S, Lev M, Cassels DE. Aortico-right ventricular tunnel.
anatomy and of the relationship between the coronary ostia
Chest. 1973;63:198-202.
and the orifice of the tunnel at the aortic end.74 If the coronary 11. Saylam A, Tuncali T, Ikizler C, et al. Aorto-right ventricular
artery arises from the tunnel, an alternative is to re-implant the tunnel. A new concept in congenital cardiac malformations.
artery as a button into the aortic sinus.71 Ann ThoracSurg. 1974;18:634-7.
Transcatheter treatment is an option in selected cases, 12. Jureidini SB, de Mello D, Nouri S, et al. Aortico-right
where the opening of the right atrial end is small or there is a ventricular tunnel with critical pulmonary stenosis: Diagnosis
constriction in the course of the fistula.72 The appropriate sizes by two dimensional and Doppler echocardiography and
of coils or device can be used. There are a few case reports of angiography. Pediatr Cardiol. 1989;10:99-103.
13. Kleinkamp G, Minami K, Thies WR, et al. Aorta right
transcatheter closure.75,76 However, persistence of the dilated
ventricular tunnel with a rudimentary valve and an anomalous
sinus of Valsalva with transcatheter device closure constitutes
origin of the left coronary artery. J Thorac Cardiovasc Surg.
a concern and demands further follow-up and evaluation for 1992;104:1759-60.
a determination of its evolution.75 Sometimes, if the tunnel is 14. Westaby S, Archer N. Aortico-right ventricular tunnel. Ann
very tortuous the device closure may not be possible. ThoracSurg. 1992;53:1107-9.
15. Rosengart TK, Redel DA, Stark JF. Surgical repair of aorto-
Conclusion right ventricular tunnel in an infant. Ann Thorac Surg. 1993;55:
520-2.
Aorticocameral tunnels are extremely rare congenital cardiac 16. Van Son JA, Hambsch J, Schneider P, et al. Repair of aortic right
ventricular tunnel. Eur J Cardiothorac Surg. 1998;14:214-7.
anomalies. Imaging by TTE and MRI are of great help in
17. Vargas FJ, Molina A, Martinez JC, et al. Aortico-right
diagnosis. Surgical closure of tunnel along with repair of the
ventricular tunnel. Ann Thorac Surg. 1998;66:1793-5.
associated cardiac defects has been achieved with satisfactory 18. Talwar S, Choudhary UK, Kothari SS, et al. Aortico-right
results in the past. Recently, transcatheter closure of tunnels ventricular tunnel. Int J Cardiol. 1999;70:201-5.
with Amplatzer duct occluder, Amplatzer duct occluder II 19. Hruda J, Hazekamp MG, Sobotka-Plojhar MA, et al. Repair of
and coil closures have become a better and more attractive aorto-right ventricular tunnel with pulmonary stenosis and an
alternative to surgery in selected cases without associated anomalous origin of left coronary artery. Eur J Cardiothorac
cardiac defects. Surg. 2002;21:1123-5.
20. Freund MW, Stoutenbeek P, Van der Laan M, et al. Aortico-
right ventricular tunnel. Prenatal diagnosis leading to neonatal
By medicine life may be prolonged, yet death will seize the
survival. Fetal DiagnTher. 2007;22:335-8.
doctor too.
21. Sheikh N. Repair of aorto-right ventricular tunnel: A case
—William Shakespeare report. Cardiovasc J. 2010;3:398-100.
22. Poptani VA, Thakkar BM, Patel NH. Transcatheter closure of a
rare case of aorto-right ventricular tunnel with single coronary
References artery. J Invasive Cardiol. 2010;22:611-4.
23. Lin BS, Zhang XH, Jiang YZ, et al. Diagnosis and surgical
1. Elwatidy AF, Galal AN, Rhydderch D, et al. Aorto-right atrial treatment of adult aortico-right ventricular tunnel. Ann Thorac
fistula. Ann Thorac Surg. 2003;76:929-31. Surg. 2010;89:2024-6.
2. Nihoyannopoulos P, Sapaford R, Oakley CM. Congenital fistula 24. Talwar S, Nair VV, Kothari SS, Gulati GS, Choudhary SK,
between aorta and left atrium. Br Heart J. 1987;57:387-90. Airan B. Aortico- right ventricular tunnel with anomalous right
3. QIU Xing-biao, SHI Hong-yu, LIU Lan, et al. Multiple aortico- coronary artery. J Card Surg. 2011;26:521-6.
cameral tunnels associated with bicuspid aortic valve in aged: a 25. Singh SK, Dwivedi SK, Kumar A, et al. Aneurysmal Aorto-
case report. Chin Med J. 2009;122:2184-5. Right Ventricular Tunnel . Ann ThoracSurg. 2012;93:e21–2.
344
4. Robert M. Freedom and Shi-JoonYoo. Aorto-cameral Commu 26. Vijayalakshmi IB, Chitra N, Ashish A. Closure of Aorto-right
nications in Robert M. Freedom, Shi-JoonYoo, Haverjmikai ventricular tunnel with Amplatzer Duct Occluder II. Accepted
for publication in Journal of Invasive Cardiology on September
21st, 2012.
47. Chen YF, Chiu CC, Wu JR. Correction of aortico-left
ventricular tunnel in a small Oriental infant: a brief clinical
23
27. Turley K, Silverman NH, Teitel D, et al. Repair of aortico- review. J CardiovascSurg (Torino). 1994;35:71-3.
left ventricular tunnel in the neonate: surgical, anatomic and 48. Grab D, Paulus WE, Terinde R, et al. Prenatal diagnosis of an
echocardiographic considerations. Circulation. 1982;65:1015-20. aortico-left ventricular tunnel. Ultrasound Obstet Gynecol.
28. Martins JD, Sherwood MC, Mayer JE Jr, et al. Aortico-left 2000;15:435-8.
ventricular tunnel: 35-year experience. J Am Coll Cardiol 49. Soulié P, Caramanian M, Pernot JM, et al. Communication
2004;44:446-50. ou tunnel aorto-ventriculaire gauche. [Left aorto-ventricular
29. Cook AC, Fagg NL, Ho SY, et al. Echocardiographic- communication or tunnel]. Arch Mal Coeur Vaiss. 1966;59:
anatomical correlations in aorto-left ventricular tunnel. Br 820-42.
Heart J. 1995;74:443-8. 50. Hucin B, Morvath P, Skovranek J, et al. Correction of aortic
30. Ho SY, Muriago M, Cook AC, et al. Surgical anatomy of aorto- left ventricular tunnel during the first day of life. Ann Thorac
left ventricular tunnel. Ann Thorac Surg. 1998;65:509-14. Surg. 1989;47:254-6.
31. Hovaguimian H, Cobanoglu A, Starr A. Aortico-left ventricular 51. Akalin H, Erd C, Oral D, et al. Aortic left ventricular
tunnel: a clinical review and new surgical classification. Ann tunnel: Successful diagnostic and surgical approach to the
Thorac Surg. 1988;45:106-12. oldest patient in the literature. J Thorac Cardiovasc Surg.
32. Bove KE, Schwartz DC. Aortico-left ventricular tunnel. A new 1989;97:804-5.
concept. Am J Cardiol. 1967;19:696-709. 52. Kafka H, Chan KL, Leach AJ. Asymptomatic aortico-left
33. Levy MJ, Schachner A, Blieden LC. Aortico-left ventricular ventricular tunnel in adulthood. Am J Cardiol. 1989;63:1021-22.
tunnel: collective review. J Thorac Cardiovasc Surg. 1982;84: 53. Perry JC, Nanda NC, Kicks DG, et al. Two-dimensional
102-9. echocardiographic identification of aortico-left ventricular
34. Serino W, Andrade JL, Ross D, et al. Aorto-left ventricular tunnel. Am J Cardiol. 1983;52:913-4.
communication after closure. Late postoperative problems. Br 54. Grant P, Abrams LD, De Giovanni JV, et al. Aortico-left
Heart J. 1983;49:501-6. ventricular tunnel arising from the left aortic sinus. Am J
35. Guyton RA, Michalik RE, McIntyre AB, et al. Aortic atresia Cardiol. 1985;55:1657-8.
and aortico-left ventricular tunnel: successful surgical 55. Humes RA, Hagler DJ, Julsrud PR, et al. Aortico-left ventricular
management by Konno aortoventriculoplasty in a neonate. J tunnel: diagnosis based on two-dimensional echocardiography,
Thorac Cardiovasc Surg. 1986;92:1099-101. color flow Doppler imaging, and magnetic resonance imaging.
36. Bitar FF, Smith FC, Kavey RE, et al. Aortico-left ventricular Mayo Clin Proc. 1986;61:901-7.
tunnel with aortic atresia in the newborn. Am Heart J. 56. Sreeram N, Franks R, Arnold R, et al. Aortico-left ventricular
1993;126:1480-2. tunnel: long-term outcome after surgical repair. J Am Coll
37. Jureidini SB, de Mello D, Norui S, et al. Aortico-right Cardiol. 1991;17:950-5.
ventricular tunnel and critical pulmonary stenosis: diagnosis 57. Biffanti R, Reffo E, Sanders SP, et al. Two-dimensional and
by two-dimensional and Doppler echocardiography and real-time three-dimensional echocardiographic fetal diagnosis
angiography. Pediatr Cardiol 1989;10:99-103. of aorto-ventricular tunnel. Circulation. 2005;111:e367-8.
38. Martin Jimenez J, Gonzales Diegues CC, Quero Jimenez C, et 58. Siepe M, Dittrich S, Beyersdorf F, et al. Aortic atresia with
al. Aortico-left ventricular tunnel associated with pulmonary aortico-left ventricular tunnel mimicking severe aortic incompe
valve stenosis. Rev Esp Cardiol. 1996;49:921-4. tence in utero. Eur J Cardiothorac Surg. 2006;29:845-7.
39. Knott-Craig CJ, van der Merwe PL, Kalis NN, et al. Repair 59. Webber S, Johnston B, LeBlanc J, et al. Aortic-left ventricular
of aortico-left ventricular tunnel associated with subpulmonary tunnel associated with critical aortic stenosis in the newborn.
obstruction. Ann Thorac Surg. 1992;54:557-9. PediatrCardiol. 1991;12:237-40.
40. Bash SE, Huhta JC, Nihill MR, et al. Aortico-left ventricular 60. Tuna IC, Edwards JE. Aortico-left ventricular tunnel and aortic
tunnel with ventricular septal defect: two-dimensional/ insufficiency. Ann Thorac Surg. 1988;45:5-6.
Doppler echocardiographic diagnosis. J Am Coll Cardiol. 61. Grünenfelder J, Zünd G, Prêtre R, et al. Right coronary artery
1985;5:757-60. from aorto-left ventricular tunnel: case report of a new surgical
41. Spooner EW, Dunn JM, Behrendt DM. Aortico-left ventricular approach. J Thorac Cardiovasc Surg. 1998;116:363-5.
tunnel and sinus of Valsalva aneurysm. Case report with 62. Norwicki ER, Abderdeen E, Friedman S, et al. Congenital left
operative repair. J ThoracCardiovasc Surg. 1978;75:232-6. aortic sinus-left ventricle fistula and review of aortocardiac
42. McKay R. Invited commentary. Ann Thorac Surg 1992;54:559. fistulas. Ann Thorac Surg. 1997;23:378-88.
43. Bonnet D, Bonhoeffer P, Sidi D, et al. Surgical angioplasty of 63. Chessa M, Chaudhari M, De Giovanni JV. Aorto-left ventricular
the main coronary arteries in children. J Thorac Cardiovasc tunnel: transcatheter closure using an amplatzer duct occluder
Surg. 1999;117:352-7. device. Am J Cardiol. 2000;86:253-4.
44. Horváth P, Balaji S, Škovránek S, et al. Surgical treatment 64. Vijayalakshmi IB, Chitra N, Prabhu Deva AN. Use of an
of aortico-left ventricular tunnel. Eur J Cardiothorac Surg. Amplatzer duct occluder for closing an aortico-left ventricular
1991;5:113-7. tunnel in a case of noncompaction of the left ventricle. Pediatr
45. Rauzier JM, Bonnet D, Zniber L, et al. Aortico-ventricular Cardiol. 2004;25:77-9.
tunnel with right coronary artery atresia. Arch Mal Coeur 65. Archer TP, Mabee SW, Baker PB, et al. Aorto-Left atrial
Vaiss. 1997;90:725-7. fistula. A reversible cause of acute refractory heart failure.
46. Sousa-Uva M, Touchot A, Fermont L, et al. Aortico-left Chest. 1997;111:828-31.
345
ventricular tunnel in fetuses and infants. Ann Thorac Surg. 66. Patsouras D, Argyri Q, Siminilakis S, et al. Aortic dissection
1996;61:1805-10. with aorto-left atrial fistula formation soon after aortic valve
4 replacement: A lethal complication diagnosed by transthoracic
and transesophageal echocardiography. J Am SocEchocardiogr.
72. Gajjar T, Voleti C, Matta R, et al. Aorta right atrial tunnel:
clinical presentation, diagnostic criteria, and surgical options. J
2002;15:1409-11. Thorac Cardiovasc Surg. 2005;130:1287-92.
Shunt Defects
67. Otero-Coto E, Caffarena JM, Such M, et al. Aorta-right atrial 73. Aggarwal SK, Sai V, Iyer VR. Imaging features of aorto-right
communication: report of an unusual case. J Thorac Cardiovasc atrial tunnel: a report of two cases. Congenit Heart Dis. 2007;2:
Surg. 1980;80:941-4. 429-32.
68. Rosenberg H, Williams WG, Trusler GA, et al. Congenital 74. Moraes F, Santos CL, Moraes CR. Aortic-right atrial tunnel.
aortico–right atrial communications. J Thorac Cardiovasc Cardiol Young. 2004;14:86-8.
Surg. 1986;91:841-7. 75. Chandra S, Vijay S, Kaur D, et al. Congenital aorta right atrial
69. Kalangos A, Beghetti M, Vala D. Aortico-right atrial tunnel. fistula: successful transcatheter closure with the Amplatzer
Ann Thorac Surg. 2000;69:635-7. occluder. Pediatr Cardiol. 2011;32:1057-9.
70. Ooman A, Mao R, Krishnan P, et al. Congenital aortocaval 76. Kappanayil Mahesh, Edwin Francis, and Raman Krishna
fistula to superior vena cava. Ann Thorac Surg. 2000;72:91-3. Kumar. Aorta to Right Atrial Tunnel: Prenatal Diagnosis and
71. Turkay C, Golbasi I, Belgi A, et al. Aorta–right atrial tunnel. J Transcatheter Management in a Neonate J. Am Coll Cardiol
ThoracCardiovasc Surg. 2003;125:1058-60. Intv. 2008;1:716-7.
346
C hapter
24 Aneurysm of Sinus of Valsalva
Biswajit Bandyopadhyay, Debasree Ganguly, Kumsi Sridhar
Introduction are often associated with prolapse of aortic cusps and aortic
incompetence. Coarctation of the aorta, atrial septal defect,
The sinuses of Valsalva are three small outpouchings in the tetralogy of Fallot and patent ductus arteriosus also may be
wall of the aorta immediately above the attachments of each associated with these aneurysms.5
aortic cusp. First report of ruptured sinus of Valsalva was Most aneurysms are single and most commonly affect
published in 1839 by Hope.1 Thurnam named the sinuses the right coronary aortic sinus. Two-thirds of the aneurysms
according to their relationship to the coronary arteries as are located in the right aortic sinus, one-fourth in the non-
the right coronary sinus, the left coronary sinus and the noncoronary sinus and the rest in the left aortic sinus.9
coronary sinus.2 Aneurysms of the right coronary aortic sinus usually
Aneurysm of sinus of Valsalva (ASV) accounts for 1 prolapse into the right ventricle or right atrium and those from
percent of congenital anomalies of the heart and circulation.3 the non-coronary sinus into the right atrium. Aneurysms of the
The aneurysms tend to be single although exceptionally more left coronary aortic sinus prolapse into the left ventricle.10,11
than one sinus is involved.4-7 Rupture can also occur through the septal leaflet of the
The incidence varies from 0.14 to 0.35 percent.4 The tricuspid valve, producing an acquired atrioventricular septal
prevalence is more in Asian population compared to Western defect.10 There is an increased incidence of rupture when
world.7 The developmental fault is at the junction of the aortic an aneurysm occurs in the presence of a doubly committed
media and the annulus fibrosis and sets the stage for avulsion subarterial ventricular septal defect. Rupture in these cases
and aneurysm formation.8 Rupture is rare in infancy and occur into the right ventricular outflow tract. Rarely, rupture is
childhood, being more commonly seen in adults. into the pulmonary artery,12-14 left ventricle,15-17 left atrium17
or pericardial cavity.18,19 Also rarely, a sinus aneurysm dissects
PATHOLOGY into the interventricular septum and either remains unruptured
or perforates into the left or right ventricle.15,20 Box 1 depicts
Mural weakness of aortic sinuses causes congenital aneurysm the working classification of ASV.17
of the sinuses, which produces downward prolapse of the A large unruptured aneurysm may compress the superior
leaflets. The dilated sinus may bulge into an atrium or ventricle vena cava, right atrium, right ventricle21,22 or a coronary
and may rupture. artery23,24 or may cause aortic regurgitation by interfering
Aneurysms can be congenital or acquired after bacterial with coaptation of aortic leaflets.25,26 A rare case of unruptured
endocarditis (BE). The BE can also occur on congenital aneurysm of both right and left sinuses causing right ventricular
aneurysms. Sometimes, it becomes difficult to identify ouflow tract (RVOT) and left ventricular outflow tract (LVOT)
whether BE is the effect or cause of the aneurysm rupture. obstruction and burrowing into interventricular septum, which
Rupture has been reported in Behçet disease and may also does not fit into any classification is reported (Figures 1
occur long time after repair of aortic dissection. and 2).27 The congenital etiology of an aortic sinus aneurysm is
In 30 to 50 percent cases, congenital aneurysms are debatable if it originates in the left coronary sinus and ruptures
associated with ventricular septal defect (VSD) especially into the left side of heart.17,28 At surgery most fistulas resemble
defects of the outlet septum. Proportion of VSD is higher windsocks projecting from the sinus into the chamber of entry,
with aneurysms of right aortic sinus. Subpulmonic VSDs with one or more openings near the end of the windsock.
4 Box 1: Sakakibara and Konno’s
classification of ASV17
Shunt Defects
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.
A B
Type IV: The aneurysm originates in the right portion of the
Figures 2A and B: A. The apical four-chamber view shows dilation of
non-coronary sinus and ruptures into the right atrium. The
the left ventricle and left atrium, with the aneurysm of the right sinus
presence of an associated VSD is uncommon. of Valsalva burrowing into the ventricular septum. Note the moderately
ASV = Aneurysm of the sinus of Valsalva; VSD = Ventricular septal severe mitral regurgitation. B. The apical five chamber view shows
defect. 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

Unruptured aneurysms are usually asymptomatic and are
A B
discovered during investigation for some other reasons such
Figures 1A and B: A. Transthoracic echocardiographic parasternal as a VSD. Occasionally, unruptured aneurysms can produce
long axis view shows aneurysms of both aortic coronary sinuses of
symptoms of intractable angina because of distortion of the
Valsalva obstructing the left ventricular outflow tract. B. Parasternal
short-axis view shows the aneurysm of the right sinus protruding origin of the coronary arteries.30
into the right ventricular outflow tract. Ao = Aorta; ASOV = Aneurysm Natural history of unruptured aneurysms is not known.
of sinus of Valsalva; LA = Left atrium; LV = Left ventricle; LVOT = Although rupture has been reported in the neonatal period,31
Left ventricular outflow tract; PA = Pulmonary artery; RVOT = Right
it occurs more frequently in the third or fourth decade of
ventricular outflow tract.
life. Rupture often, but not necessarily develop after physical
exertion.
PHYSIOLOGY Rupture may be accompanied by a tearing pain in the chest
or upper abdomen. The sudden onset of dyspnea rather than
About 75 percent of the patients are male. Ruptured aortic pain or mild chest pain may occur for weeks before the onset
sinus aneurysms typically express themselves in young men of dyspnea and tightness in the upper abdomen.32-34 If a huge
after puberty, but before the age of 30 years.29 Congenital sinus shunt develops rapidly, the symptoms of congestive heart
of Valsalva aneurysms come to attention because of the acute failure appear almost immediately, but with smaller fistulas
development of a large perforation, gradual development of a it may take several months for heart failure to develop.9
small perforation or because of an asymptomatic or symptomatic Pain is presumably related to the rupture itself. Occasionally,
348 unruptured aneurysm. The physiologic consequences of rupture the aneurysm compresses a coronary artery so symptoms of
depend on three factors: myocardial ischemia or infarction coexist.33
When chest pain, dyspnea and a continuous murmur suddenly Occasionally, there is only a diastolic murmur in fistulas 24
develops in a patient with a ventricular septal defect, the reason entering the left ventricle9 or the high-pressure right ventricle
is likely to be rupture of a coexisting aortic sinus aneurysm.34-36 in a neonate. Myocardial infarction may be the consequence
aneurysm of sinus of valsalva

The acute symptoms last for hours or days, sometimes of compression of the coronary arteries and may occasionally
subsiding gradually and leaving patient temporarily improved, be fatal.40 Other possible complications include transient
but congestive heart failure reappears and relentlessly ischemic attacks and cerebral embolism.25,32
progresses.37,38 About 20 percent of patients are asymptomatic. Death from congestive heart failure usually occurs within
Small insidious perforations progress gradually and initially a year after rupture.34,37 Sudden death follows perforation into
go unnoticed.39,40 Mild dyspnea without pain sometimes the pericardium and syncope or sudden death is an occasional
precedes congestive heart failure by months or years.41-43 sequel of complete heart block caused by a ruptured or
Patients who present during a relatively asymptomatic unruptured43 aneurysm that dissects into the base of the
interval have a continuous murmur, collapsing radial pulse, ventricular septum. Conversely, long survival sometimes
raised jugular venous pressure with tall ‘a’ wave, prominent follows small slow perforations.41
parasternal heave and thrill. Unlike the patent ductus arteriosus Unruptured aneurysms announce themselves by a to-and-
(PDA) murmur, in ruptured sinus of Valsalva (RSOV) the fro murmur due to flow in and out of the intact aneurysmal
continuous murmur does not peak around S2, infact the pouch, a murmur of tricuspid regurgitation or a midsystolic
intensity of murmur decreases at S2. The diastolic accentuation murmur caused by obstruction to right ventricular outflow,
of murmur at a atypical site is characteristic of RSOV. The myocardial ischemia due to coronary artery compression, aortic
diastolic murmur may be further accentuated if associated regurgitation caused by lack of apposition of aortic cusps,45
aortic regurgitation is present and that can be mistaken for a superior vena caval obstruction, a paracardiac mass in the chest
PDA.35 X-ray, systemic emboli, complete heart block or syncope or
Small perforations come to attention because of an sudden death.43,44
asymptomatic continuous murmur44 or a systolic murmur
caused by subpulmonary obstruction or a diastolic murmur INVESTIGATIONS
caused by aortic regurgitation or because of infective
endocarditis or because of diagnostic investigation or Small and slowly developing aortic sinus ruptures are
operation for VSD. accompanied by normal electrocardiograms. The rhythm is
There may be only a continuous murmur like that of a normal sinus even when a large rupture is into the right atrium.
PDA, but with its maximal intensity in the third or fourth The PR interval tends to be prolonged. Atrioventricular
intercostal space near the sternal edge; if the fistula enters the conduction defects including complete heart block and
right atrium, the murmur may be maximum to the right of right or left bundle branch block or bifascicular block5,43
the sternum (Figure 3).35 With larger fistulas, there will be a result when a ruptured or unruptured aneurysm penetrates
wide pulse pressure, a collapsing pulse and left ventricular the base of the ventricular septum. Varying degree of ST-T
hyperactivity. If the fistula enters the right side, there will be abnormalities are present depending on the presence of
right ventricular hyperactivity as well. A large fistula entering ischemia or infarction.
the left ventricle may give rise to a to-and-fro murmur. 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
Figure 3: Schematic diagram showing the location of the murmur cardiac border and a moderately dilated left ventricle occupies
depending on the site of rupture of the sinus of Valsalva. RA = Right the apex.39,48 Rupture into the left ventricle causes pulmonary 349
atrium; RV = Right ventricle
4 venous congestion without increased pulmonary arterial 1. Root of the aneurysm above the aortic annulus.
blood flow and with a selective increase in left ventricular 2. Saccular-shaped aneurysm.
size. Rarely, calcium is deposited in the aortic sinus aneurysm. 3. Normal size of aorta above the aneurysm.
Shunt Defects
Occasionally right or left aortic sinus aneurysm may project 4. Continuous systolic and diastolic turbulence detected by the
out as dense convex paracardiac shadow.49 pulsed wave Doppler just distal to the area of perforation at
Transthoracic echocardiography (TTE) can detect the ASV high velocities.
(Figure 4). 2D echocardiography with color flow imaging and 5. Color flow mapping with mosaic turbulence across the
Doppler identifies the ruptured or unruptured aneurysm, the perforated aneurysm in real time.
chamber receiving the shunted blood, volume overloading of Ischemic left ventricular regional wall motion abnormalities
the heart, associated defects and degree of aortic regurgitation caused by compression of the coronary artery origins by the
(Figures 5A and B). Unruptured defects are characterized aneurysm are evident on real time screening.
by phasic expansion and relaxation and to-and-fro pulsed Non-invasive imaging with computed tomography or
Doppler signals at the site of origin from the aorta, but no magnetic resonance scans have been shown to provide
color flow evidence of rupture. Echocardiographic diagnostic excellent definition of the aneurysm and the tissue planes
criteria50 include: involved.51
MANAGEMENT
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.
Figure 4: Transthoracic echocardiography (TTE) in parasternal Surgery is indicated for the extracardiac type of ASV (Type C).
short-axis shows aneurysm of the sinus of Valsalva
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
A B
volume overload greater than 1.5 cm/m2 and the margin of the
Figures 5A and B: A. Transthoracic echocardiogram (TTE) in defect at least 5 mm from the right coronary ostia are suitable
parasternal long-axis view shows non-compaction of of left ventricle for device closure.56 Device closure of the defect has been
with subaortic ventricular septal defect. B. TTE in parasternal long-axis
view with color Doppler shows rupture of aneurysm of sinus of Valsalva
shown to be a safe and effective alternative to surgery on short-
350 term follow-up of a small series of patients.57
into right ventricle and aortic regurgitation jet into left ventricle.
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
A B
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 After establishing femoral artery and venous access, intra
(ADO). The selected size of ADO should be 1 to 2 mm greater venous antibiotics and heparin is given at 100 mg/kg, right
than the measured defect size (Figures 7A and B). and left heart catheterization is done, and direct pulmonary
The procedure is performed under local anesthesia with artery pressure is measured. Coronary angiography is
fluoroscopic and transthoracic/transesophageal echocardio- performed to document coronary arteries anatomy and their
graphic guidance. Some centers prefer general anesthesia for distance from the defect before closure is attempted. Aortic 351
the procedure. root cine-angiogram is performed in at least two orthogonal
4 views to define the opening of the wind sock defect and its infusing antegrade cold cardioplegia through the coronary
size. ostia directly. The orifice of the RSOV is visualized and
The defect is then crossed with a multipurpose or a right the VSD if present is visualized by lifting the aortic cusp.
Shunt Defects
coronary catheter from the left ventricle to the right ventricular Redundancy or cusp prolapse is noted.
side. As the defect is crossed with the catheter, an exchange Repair of RSOV can be attempted through right atrium
length Terumo wire is advanced through the catheter across or right ventriculotomy. The thin windsock, which is the
the defect and is kept into the superior vena cava or the aneurysmal sac with a single opening or multiple perforations
pulmonary artery and snared from there and taken out from is excised, creating a large defect in the right sinus, which is
the femoral vein forming an arteriovenous circuit. down stream or cephalad to the VSD, separated by a hinge
Subsequently, an appropriate sized device is advanced line of the aortic cusp. Dacron or polytetrafluoroethylene
via a Mullins sheath from the femoral venous side and is (PTFE) patch is sewen to close the VSD and the defect in the
advanced into the ascending aorta. With the distal device end sinus of Valsalva, taking care to suture the aortic cusp hinge
open the whole assembly is then withdrawn to the opening to the patch at appropriate level. The ventriculotomy or atrial
of the defect on the aortic side. An aortography is then opening is closed with continuous polypropylene suture.
performed to check the position of the device and residual The aortic valve cusps are inspected and any cuspal
shunt. Simultaneously the device position is checked by redundancy or prolapse is addressed by performing a Trusler
transesophageal echocardiography and once satisfied with repair. If valve cusps are not suitable for repair, aortic valve
the position, the device is then deployed within the defect. may have to be replaced.
Selective coronary angiography may also be performed to rule The RSOV can be repaired through aorta or pulmonary
out any encroachment of the device.56 artery or right atrium. The approach could be through aorta or
Gianturco-Grifka vascular occlusion device is another right atrium alone if there is no associated VSD.
alternative from the venous route. Patients should receive anti
coagulant prophylaxis and infective endocarditis prophylaxis CONCLUSION
for 6 months after the procedure.
Device closure should not be attempted in patients with Aneurysm of the sinus of Valsalva is an uncommon disorder,
an aneurysm which has ruptured into the pulmonary artery most commonly presenting subsequent to rupture into a
and left ventricle, presence of associated lesions such as as cardiac chamber. The ruptured sinus of Valsalva is usually
VSD and aortic regurgitation, aneurysmal opening within 5 acquired later in life, usually with no history of heart disease.
mm of coronary ostia, right-to-left shunting across the defect It can occur spontaneously, following chest wall trauma or an
with systemic saturation less than 94 percent, patients with episode of bacterial endocarditis. The onset is usually sudden
pulmonary vascular resistance greater than 7 Wood units and or acute with a loud continuous murmur and often associated
significant right ventricle/left ventricle dysfunction with left with significant congestive heart failure. The timely surgical
ventricular ejection fraction less than 30 percent.58 closure or transcatheter device closure can reduce the
morbidity and mortality.
Surgical Management of Rupture of Sinus of Valsalva
People pay the doctor for his trouble; for his kindness they
A diagnosis of RSOV requires surgical intervention to still remain in his debt.
prevent progression of the disease resulting in death from —Seneca
right heart failure. There are many variants of RSOV,
which may require a specific technique to repair the defect. acknowledgment
However, the basic technique remains the same. Excision
of windsock, patch closure of RSOV, VSD closure if We express our thanks to Dr IB Vijayalakshmi, Professor of
present and an aortic valve repair or replacement for aortic Pediatric Cardiology, for providing all the illustrative images
regurgitation. for this chapter.
Initial preparation (CPB) is as for any open-heart
procedure. After midsternotomy, pericardium is opened and REFEReNCES
an external evaluation is done. There are no external evidence
of aneurysm. The sac of aneurysm may be palpated through 1. Hope J. A Treatise on the Diseases of the Heart and Great
the freewall of the right ventricle. Vessels, 3rd edition. J Churchill and Sons London, 1839.
Cardiopulmonary bypass is established after cannulation 2. Walmsley T. The heart. In Quain’s Elements of Anatomy, Volume
4. Part New York: Longmans, Green and Company, 1929.
of ascending aorta and direct caval cannulation.With mild-to-
3. Wells T, Byrd B, Neirste D, et al. Images in cardiovascular
moderate hypothermia, aorta is cross clamped, right atrium medicine. Sinus of valsalva aneurysm with rupture into the
opened and a vent suction introduced through foramen interventricular septum and left ventricular cavity. Circulation.
352 ovale.Aorta is opened transversly, cardiac arrest achieved by 1999;100:1843-84.
4. Chamsi-Pasha H, Musgrove C, Morton R. Echocardiographic
diagnosis of multiple congenital aneurysms of the sinus of
diagnosed by two-dimensional and Doppler echocardiography.
J Am Coll Cardiol. 1986;7:438-41.
24
Valsalva. Br Heart J. 1988;59:724-6. 25. Rubin DC, Carliner NH, Salter DR, et al. Unruptured sinus

5. Gibbs NM, Harris El. Aortic sinus aneurysms. Br Heart J. of Valsalva aneurysm diagnosed by transesophageal echo-
1961;23:131-9. cardiography. Am Heart J. 1992;124:225-7.
6. Micks RH. Congenital aneurysms of all three sinuses of 26. Haraphongse M, Ayudhya RK, Jugdutt B, et al. Isolated unrup-
Valsalva. Br Heart J. 1940;2:63-78. tured sinus of Valsalva aneurysm producing right ventricular
7. Pomerance A, Davis MJ. Congenital aneurysms of all three outflow obstruction. Cath Cardiovasc Diag. 1990;19:98-102.
sinuses of Valsalva. J Pathol Bacteriol. 1965;89:607-10. 27. Vijayalakshmi IB, Devananda NS, Chitra N. A patient
8. Edwards JE, Burchell HB. Specimen exhibiting the essential with aneurysms of both aortic coronary sinuses of Valsalva
lesion in aneurysm of the aortic sinus. Proc Staff Meet Mayo obstructing both ventricular outflow tracts. Cardiol Young.
Clin. 1956;31:407-12. 2009;19:537-9.
9. Norwicki ER, Aberdeen E, Friedman S, et al. Congenital left 28. Heiner DC, Hara M, White HJ. Cardioaortic fistulas and
aortic sinus-left ventricle fistula and review of aortocardiac aneurysms of sinus of Valsalva in infancy. A report of an aortic-
fistulas. Ann Thorac Surg. 1977;23:378-88. left atrial communication indistinguishable from a ruptured
10. Mayer JH 3rd, Holder TM, Canent RV. Isolated, unruptured aneurysm of the aortic sinus. Pediatrics. 1961;27:415-26.
sinus of Valsalva aneurysm: serendipitous detection and 29. Aletras H, Bjork VO, Cullhed I, et al. Ruptured congenital
correction. J Thorac Cardiovasc Surg. 1975;69:429-32. aneurysm of the sinus of Valsalva with ventricular septal
11. Hands ME, Lloyd BL, Hung J. Cross-sectional echocardio defect. Thorax. 1963;18:127-35.
graphic diagnosis of unruptured right sinus of Valsalva 30. Burakovsky VI, Podsolkov VP, Sabirow BN, et al. Ruptured
aneurysm dissecting into the interventricular septum. Int J congenital aneurysm of the sinus of Valsalva. Clinical manifes
Cardiol. 1985;9:380-3. tations, diagnosis and results of surgical corrections. J. Thorac
12. Brown JW, Health D, Whitaker W. Cardioaortic fistula; a case Cardiovasc Surg. 1988;95:836-41.
diagnosed in life and treated surgically. Circulation. 1955; 31. Breviere GM, Vaksmann G, Francart C. Rupture of a sinus of
12:819-26. Valsalva aneurysm in a neonate. Eur J Pediatr. 1990;149:603-4.
13. Heilman KJ 3rd, Groves BM, Campbell D, et al. Rupture of 32. Bulkley BH, Hutchins GM, Ross RS. Aortic sinus of Valsalva
left sinus of Valsalva aneurysm into the pulmonary artery. J Am aneurysms simulating primary right-sided valvular heart
ColI Cardiol. 1985;5:1005-7. disease. Circulation. 1975;52:696-9.
14. Scagliotti D, Fisher EA, Deal BJ, et al. Congenital aneurysm of 33. Chipps HD. Aneurysm of the sinus of Valsalva causing
the left sinus of Valsalva with an aortopulmonary tunnel. J Am coronary occlusion. Arch Pathol. 1941;31:627-30.
Coll Cardiol. 1986;7:443-5. 34. Besterman EM, Goldberg MJ, Sellors TH. Surgical repair of
15. Engel PJ, Held JS, Van der Bel-Kahn J, et al. Echocardiographic ruptured sinus of Valsalva. BMJ. 1963;2:410-6.
diagnosis of congenital sinus of Valsalva aneurysm with 35. Neill C, Mounsey P. Auscultation of patent ductus arteriosus;
dissection of the interventricular septum. Circulation. 1981; with a description of 2 fistulae simulating patent ductus. Br
63:705-11. Heart J. 1958;20:61-75.
16. Morgan RI, Mazur JH. Congenital aneurysm of aortic root 36. Peters P, Juziuk E, Gunther S. Doppler color flow mapping
with fistula to left ventricle. A case report and autopsy findings. detection of ruptured sinus of Valsalva aneurysm. J Am Soc
Circulation. 1963;28:589-94. Echocardiogr. 1989;2:195-7.
17. Sakakibara S, Konno S. Congenital aneurysm of the sinus of 37. Lukacs L, Bartek I, Haan A, et al. Ruptured aneurysms of the
Valsalva. Anatomy and classification. Am Heart J. 1962;63:405- sinus of Valsalva. Eur J Cardiothorac Surg. 1992;6:15-7.
24. 38. Jick H, Kasarjian P, Barsky M. Rupture of aneurysm of aortic
18. Lewis BS, Agathangelou NE. Echocardiographic diagnosis sinus of Valsalva associated with acute bacterial endocarditis.
of unruptured sinus of Valsalva aneurysm. Am Heart J. Circulation. 1959;19:745-9.
1984;107:1025-7. 39. Guo DW, Cheng TO, Lin ML, et al. Aneurysm of the sinus of
19. Eliot RS, Wollbrink A, Edwards JE. Congenital aneurysm of Valsalva: A roentgenologic study of 105 Chinese patients. Am
the left aortic sinus. A rare lesion and a rare cause of coronary Heart J. 1987;114:1169-77.
insufficiency. Circulation. 1963;28:951-6. 40. Hiyamuta K, Ohtsuki T, Shimamatsu M, et al. Aneurysm of
20. Chen WW, Tai YT. Dissection of interventricular septum by the left aortic sinus causing acute myocardial infarction.
aneurysm of sinus of Valsalva. A rare complication diagnosed Circulation. 1983;67:1151-4.
by echocardiography. Br Heart J. 1983;50:293-5. 41. Sakakibara S, Konno S. Congenital aneurysm of the sinus of
21. Gleason MM, Hardy C, Chin AJ, et al. Ruptured sinus of Valsalva Valsalva: A clinical study. Am Heart J. 1962;63:708-19.
aneurysm in childhood. Am Heart J. 1987;114:1235-8. 42. Adams JE, Sawyers JL, Scott HW Jr. Surgical treatment of
22. Okita Y, Miki S, Kusuhara K, et al. A giant aneurysm of the aneurysms of the aortic sinuses with aorticoatrial fistula;
non-coronary sinus of Valsalva. Thorac Cardiovasc Surg. experimental and clinical study. Surgery. 1957;41:26-42.
1987;35:316-7. 43. Krieger OJ, Lee EB, Lee NK. Congenital aneurysm of the
23. Gallet B, Combe E, Saudemont JP, et al. Aneurysm of the noncoronary sinus of Valsalva leading to complete heart block:
left aortic sinus causing coronary compression and unstable case report. Ann Intern Med. 1956;45:525-34.
angina: successful repair by isolated closure of the aneurysm. 44. Segab C, Davy JM, Scheuble C, et al. Atrioventricular block
Am Heart J. 1988;115:1308-10. disclosing an isolated congenital aneurysm of the sinus of
353
24. Kiefaber RW, Tabakin BS, Coffin LH, et al. Unruptured sinus Valsalva, extending into the septum and not ruptured. Arch Mal
of Valsalva aneurysm with right ventricular outflow obstruction Coeur Vaiss. 1981;74:1233-9.
4 45. Channer KS, Hutter JA, George M. Unruptured aneurysm of
the sinus of Valsalva presenting with ventricular tachycardia.
52. Vural K, Sener E, Taşdemir O, et al. Approach to sinus of
valsalva aneurysm:a review of 53 cases. Eur J Cardiothorac
Eur Heart J. 1988;9:186-90. Surg. 2001;20:71-6.
Shunt Defects
46. Kieffer SA,Winchell P. Congenital aneurysms of the aortic 53. Dong C, Wu QY, Tang Y. Ruptured sinus of valsalva
sinuses with cardioaortic fistula. Dis Chest. 1960;38:79-96. aneurysm: a Beijing experience. Ann Thorac Surg.
47. Ramsey TL, Mosquera VT. Ruptured congenital aneurysm of 2002;74:1621-4.
the sinus of Valsalva with superimposed endocarditis; rupture of 54. Hourihan M, Perry SB, Mandell VS, et al. Transcatheter
aortic cusp producing sudden death. Ohio Med. 1946;42:843-5. umbrella closure of valvular and paravalvular leaks. J Am Coll
48. Buzzi A. Evaluation of a precordial continuous murmur. Cardiol. 1992;6:1371-7.
Rupture of aneurysm of sinus of Valsalva into the right 55. Cullen S, Somerville J, Redington A. Transcatheter closure
ventricle. Am J Cardiol. 1959;4:551-3. of a ruptured aneurysm of the sinus of Valsalva. Br Heart J.
49. Reid PG, Goudevenos JA, Hilton CJ. Thrombosed saccular 1994;71:479-80.
aneurysm of a sinus of Valsalva: unusual cause of a mediastinal 56. Arora R. Catheter closure of perforated sinus of Valsalva.
mass. Br Heart J. 1990;63:183-5. In: Sievert H, Qureshi SA, Wilson N, Hijazi ZM (Eds).
50. Dev V, Shrivastava S. Echocardiographic diagnosis of Percutaneous Interventions for Congenital Heart Disease.
unruptured aneurysm of the sinus of Valsalva dissecting into Informa Healthcare, London; 2007. pp. 257-62.
the ventricular septum. Am J Cardiol. 1990;66:502-3. 57. Sen S, Chattopadhyay A, Ray M, et al. Transcatheter device
51. Noji Y, Hifumi S, Nagayoshi T, et al. Sixteen-slice computed closure of ruptured sinus of valsalva: Immediate results and
tomography, transthoracic real-time 3-dimensional echocardio short term follow up. Ann Pediatr Cardiol. 2009;2:79-82.
graphy and magnetic resonance imaging assessment of a long- 58. Arora R, Trehan V, Rangashetty UM, Mukhopadhyay S,
term survivor of rupture of sinus of valsalva aneurysm. Intern Thakur AK, Kalra GS. Transcatheter closure of ruptured sinus
Med. 2005;44:513-5 of valsalva. J Interv Cardiol. 2004;17:53-8.
354
Sec t i on
Right and Left Ventricular

Obstructive Lesions
C hapter
Right Ventricular Outflow

25 Tract Obstructions
Suresh Kumar R
The right ventricular outflow tract (RVOT) may be deemed to Clinical Features
commence at the infundibulum and to comprise the pulmonary
valve and the pulmonary arterial tree. The obstruction of this Valvar pulmonary stenosis has distinctive clinical features
region are discussed under the following headings: based on the age of presentation. Hence, clinical features may
1. Pulmonary valve stenosis. be described as for the neonate, child and adult.
2. Infundibular stenosis.
3. Double-chambered right ventricle. Valvar Pulmonary Stenosis in the Neonate
4. Peripheral pulmonary artery stenosis.
Critical valvar pulmonary stenosis in the neonate presents
VALVAR PULMONARY STENOSIS dramatically with profound hypoxia. The term critical
pulmonary stenosis with intact ventricular septum is applied
Isolated pulmonary valvar stenosis is an acyanotic malforma to severe pulmonary valvar stenosis resulting in systemic/
tion with normal or diminished pulmonary blood flow. The suprasystemic right ventricular pressures and right to left
ventricular septum is intact in 80 percent of cases. The first shunt across the atrial septum, often with significant tricuspid
description of this malformation was given by Morgagni in regurgitation. The pulmonary flow may be completely duct
1761.1 dependent—‘functional pulmonary atresia’. The affected
neonate has cyanosis, congestive heart failure, hypotension,
Incidence feeding difficulty and tachypnea. On clinical examination,
there is no impressive murmur quite often. The pulmonary
Stenosis of the pulmonary valve represents 8 to 12 percent component of the second sound is delayed, soft or absent.
of all congenital heart defects in children2,3 and 15 percent There may be a pansystolic murmur of tricuspid regurgitation.
of all congenital heart defects in adults.4-6 Isolated valvar Milder stenosis is asymptomatic and is characterized by the
pulmonary stenosis with an intact ventricular septum is the phasic ejection click and ejection systolic murmur, once the
second most common congenital cardiac defect in children of pulmonary vascular resistance has fallen. Two-dimensional
the United States. It occurs with equal incidence in both the (2D) echocardiography is diagnostic for this condition.
sexes.6
Valvar Pulmonary Stenosis in Children
Genetics
Valvar pulmonary stenosis is generally well tolerated and even
Non-syndromic pulmonary valve stenosis is an isolated severe stenosis is often asymptomatic. General examination is
lesion, even though autosomal dominant inheritance has unremarkable, though atypical moon-like facies and chubby
been reported in some families.7 Syndromes associated with cheeks have been described.6 Jugular venous pressure (JVP)
valvar pulmonary stenosis include Noonans’ syndrome, shows prominent ‘a’ waves in severe stenosis. Apex beat is
Williams’ syndrome, rubella syndrome, Leopard syndrome normal. A left parasternal heave represents severe stenosis.
and cardiofacial syndrome. Seven percent of children The second heart sound is often widely split with P2 well
with pulmonary stenosis have Noonans’ syndrome.8 The preserved in milder stenosis. The auscultatory hallmark of
critical region for Noonans’ syndrome type-1 is located on valvar pulmonary stenosis is the phasic ejection click. This
chromosome 12 q24. click is characteristically louder in expiration, representing
5 the greater range of mobility the valve has in this phase of Echocardiogram
respiration. The click moves closer to the first sound as the Two-dimensional echocardiography is the best diagnostic
stenosis progresses and eventually appears to merge with it. In modality for assessment of pulmonary valve anatomy,
Right and Left Ventricular Obstructive Lesions
severe pulmonary stenosis, the S1 appears to be accentuated localization of stenosis and evaluation of right ventricular size
in expiration in the pulmonary area, due to the fused click. A and function. Typical valvar stenosis is characterized by mildly
harsh ejection systolic murmur, often associated with a thrill thickened leaflets that dome in systole.15 Presystolic doming
in the left upper sternal border is characteristic of pulmonary of the valve may be seen during atrial contraction in patients
stenosis. A long murmur with delayed peak characterizes with severe stenosis and a non-compliant right ventricle.15
severe pulmonary stenosis. Truly dysplastic valves are characterized by markedly
thickened and seemingly immobile leaflets, small valve
Valvar Pulmonary Stenosis in Adults annulus and often supravalvular narrowing.16 It is important
to identify dysplastic valves, as balloon valvuloplasty in these
Survival into adulthood may occur in many uncorrected patients patients may achieve only suboptimal results. Continuous
with pulmonary stenosis. Fibrous thickening and occasionally wave Doppler measurement of peak systolic velocities
calcification of the valve occurs with age. Clinical features estimates the transpulmonic gradient, which is comparable
vary from mild exertional dyspnea to signs of right heart to values obtained at cardiac catheterization.17,18 The severity
failure. Moderate to severe obstruction leads to inability to is typically defined by the peak systolic gradient across the
augment pulmonary blood flow during exercise, resulting in pulmonic valve.19 Values less than or equal to 40 mm Hg
fatigue, syncope or chest pain. Adults with mild or moderate denote mild stenosis, while values more than equal to 80
pulmonary stenosis have findings similar to those described in mm Hg denote severe stenosis. However, in the outpatient
children. Severe pulmonary stenosis may present with features setting, values above 64 mm Hg may be considered to indicate
of right heart failure. JVP is elevated with prominent ‘a’ waves. moderate stenosis warranting intervention.
Cardiomegaly is common. Second heart sound is widely split, Color Doppler is particularly useful to identify the jet
the pulmonary component is often inaudible. Right ventricular width of severe pulmonary stenosis and to identify ductal
third and fourth heart sounds are heard. The murmur has flow. However, pulmonary regurgitation can also be detected
the characteristics already described. However, the tricuspid and quantitated.20
regurgitation murmur may overshadow the clinical presentation.
Management
Investigation
Children with mild pulmonary stenosis do not need intervention
in childhood.21 They should be clinically followed yearly.
Electrocardiogram
Limitations in exercise or activity levels are not needed.
Baseline electrocardiogram (ECG) is usually normal in mild Infective endocarditis prophylaxis is indicated during surgery
to moderate pulmonic stenosis.9 In more severe cases, right or any procedure likely to produce bacteremia.
atrial enlargement, right ventricular hypertrophy and right Patients with moderate to severe pulmonary stenosis
axis deviation are observed. Incomplete right bundle branch (Doppler gradient ≥ 64 mm Hg) should undergo intervention.
block (RBBB) may be seen. Left bundle branch block (LBBB) After the obstruction is relieved, routine care and endocarditis
and left axis deviation point to Noonans’ syndrome.10 The ‘T’ prophylaxis are recommended as in the case of mild
wave may be upright or inverted with occasional ST segment stenosis.
changes suggestive of ischemia.11 For patients between 2 Patients with signs of right ventricular failure should be
and 20 years, the resting right ventricular pressure can be treated with decongestive measures followed by intervention
calculated from the ECG using the following formula.12 to relieve the obstruction. The right ventricular function may
Right ventricular (RV) pressure in mm Hg = R wave length not recover completely in adults.
(mm) in V1 × 5.
Balloon Pulmonary Valvuloplasty
Chest Radiogram
Currently, balloon valvuloplasty is the treatment of choice for
In mild to moderate pulmonary stenosis, the heart size managing isolated pulmonary valve stenosis.22,23 Jean S Kan
and pulmonary vascular markings are normal. The most reported the first case of balloon pulmonary valvuloplasty in
distinctive feature is a prominent main pulmonary artery 1982.24
segment secondary to poststenotic dilatation of the pulmonary
trunk and the proximal part of the left pulmonary artery—seen Indications
in 90 percent of patients. Poststenotic dilatation may be absent
358 in infants, small children and in patients with dysplastic 1. Neonates with critical pulmonary stenosis (severe
pulmonary valve as in Noonan’s syndrome.13,14 pulmonary stenosis with systemic desaturation).
2. Infants or older children a peak-to-peak catheter gradient disturbing the wire position. Right ventricular pressure 25
or echocardiographic peak instantaneous gradient of > less than half-systemic levels denote good result. If the
40 mm Hg or clinically significant pulmonary valvar right ventricular pressure is more than the desired level, it
Right Ventricular Outflow Tract Obstructions

obstruction in the presence of RV dysfunction (Class I is important to look for infundibular spasm, a hypoplastic
indication).25 annulus or a supravalvar stenosis before upsizing the balloon
for a repeat attempt. When the residual infundibular gradient is
Technique more than 50 mm Hg, beta-blocker therapy is recommended.
This infundibular reaction greatly regresses at follow-up.30-32
The procedure is done under intravenous sedation. The
neonate/young infant with suprasystemic right ventricular Follow-up Evaluation
pressures may be electively ventilated. After appropriate
venous access, a right ventricular angiogram is done, usually Clinical evaluation, ECG and Doppler echo evaluation may be
in the lateral view (Figure 1). This helps in demonstrating done at 1-month, 6-month and 1-year after the procedure.33 ECG
the valve anatomy and in providing a measurement of the is a useful adjunct in the evaluation of follow-up results34 as it
valve annulus. Unsuspected infundibular or supravalvular shows regression of right ventricular hypertrophy. This change
pathology can be recognized. Further, the angiogram provides is usually seen 6 months after the procedure.34 Doppler gradient
the road map for crossing the valve. In the neonate, often a generally reflects residual obstruction and is a useful and reliable
hand injection is performed in the RVOT, while the older monitoring tool.35 Restenosis (gradient > 50 mm Hg on Doppler
infant/child could have a regular pressure injection. echo) is observed in nearly 10 percent of cases.36 Predictors
The key to crossing the valve in a severe stenosis is an of restenosis include a balloon-to-annulus ratio of less than
appropriate catheter. 4 Judkins right coronary catheter, 4F 1.2 and a gradient of more than 30 mm Hg immediately after
multipurpose catheter or a Swan-Ganz catheter serve the valvuloplasty. In addition, small valve annulus, postsurgical or
purpose. Using a hydrophilic wire, the valve is crossed. An complex pulmonary stenosis are also predictive of restenosis.37
appropriate size superstiff wire (e.g. Amplatz super-stiff wire) Data on long-term follow-up results is scarce. Some studies
is placed well buckled in the left pulmonary artery. A balloon have shown 1 to 2 percent recurrence of pulmonary stenosis.38
(e.g. Tyshak II) of appropriate length and diameter (balloon/ In one study, surgical intervention was needed in 5 percent of
annulus ratio = 1 : 1.25)26,27 is placed across the valve and the patients for subvalvar or supravalvar stenosis;38 freedom
inflated to recommended pressure. Disappearance of the waist from intervention was 88 percent and 84 percent at 5 and 10
is the radiological proof of abolition of stenosis. When the years respectively. Pulmonary insufficiency was noted in 80 to
pulmonary valve annulus is too large to be dilated with a 90 percent of the patients, but was usually mild.
single balloon, simultaneous inflation of two balloons across
the pulmonary valve may be performed.28,29 Right ventricular Other Catheter Interventions
pressure can be measured with a multitrack catheter without
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
1. Dysplastic pulmonary valve with valve ring hypoplasia.
Figure 1: Valvar pulmonary stenosis. Right ventricular angiogram in 2. Fixed infundibular and supravalvar stenosis with pulmonary
lateral view. Note the doming pulmonary valve valvar stenosis. 359
5 Isolated Infundibular Stenosis and lateral projections demonstrate the site of infundibular
obstruction well. The narrowing is more during systole, with
Infundibular stenosis commonly occurs in association with a normal pulmonary valve and no poststenotic dilatation of the
malaligned ventricular septal defect (VSD) in the setting of main pulmonary artery. The treatment of significant primary
tetralogy of Fallot (TOF). Isolated infundibular stenosis with infundibular stenosis is surgical resection of the fibrotic area
intact ventricular septum is a very uncommon defect, initially or hypertrophic muscle.
described by Elliotson in 1830. It accounts for 5 percent of all
cases of RVOT obstruction. It is of two types41 Double-Chambered Right Ventricle
1. A fibrous band at the junction of the infundibulum and cavity
of the right ventricle (Figure 2). This is the more common Double-chambered right ventricle (DCRV) is a distinctive
type resembling double-chambered right ventricle. anatomic entity, wherein there is a muscular obstruction
2. Fibromuscular obstruction directly below the pulmonary below the infundibulum dividing the right ventricle into a low
valve. pressure infundibulum and a high pressure apical portion.
The proposed embryologic abnormality is an arrest of Anderson has provided an elegant description of the
bulbus cordis involution during the development of the pathologic anatomy of this entity.42 The septal band of the
outflow tract. septomarginal trabeculation is a prominent muscular shelf on
The physical findings consist of a loud, systolic ejection the septal surface of the right ventricle, from where a series
murmur with a widely split second sound and soft pulmonary of muscle bundles extend to the free wall as septoparietal
component. Two findings that help to distinguish infundibular trabeculations—the most prominent one going to the anterior
from pulmonary valve stenosis are the relatively lower papillary muscle as the moderator band. The obstructive
location of the murmur at the lower sternal border and the muscle bundles of DCRV are abnormally hypertrophied septo-
absence of an ejection click. The ECG features are similar parietal trabeculations extending towards right ventricular
to those of pulmonary valve stenosis. The X-ray findings are apex. Two characteristic locations of obstruction include:
not distinctive. Echo-Doppler studies help in distinguishing a. Low oblique one close to the apex.
infundibular from valvar stenosis. Systolic fluttering of b. Higher horizontal one close to the infundibulum.
the pulmonary valve, as against doming, is the hallmark of The right ventricular inlet continuous with the apical
subvalvular obstruction. The severity of the obstruction can trabecular portion has a higher pressure and the infundibular
be estimated by continuous wave Doppler. Selective right chamber has a lower pressure.
ventriculogram in right anterior oblique (RAO) cranial
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
Associated Anomalies
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
Patients with isolated DCRV and mild to moderate
right ventricular outflow tract obstruction (RVOTO) are
Figure 2: Right ventricular (RV) angiogram in AP with 10° right anterior asymptomatic. When RVOTO is severe, exertional fatigue,
oblique view illustrates highly trabeculated RV with hypertrophied dyspnea, light headedness, or chest discomfort (right
bands causing isolated infundibular stenosis (arrows) in 8 years old girl.
INF = infundibulum; MPA = Main pulmonary artery; RV = Right ventricle
ventricular angina), may be experienced.45 The variability
360 of presentation is in part attributable to the multiplicity of
Image Courtesy: Dr IB Vijayalakshmi
associated lesions. If there is an interatrial communication severe forms, the obstruction is seen as a pyramidal filling 25
or if the VSD is proximal to the obstruction cyanosis may defect, with its base broadly attached to the anterior ventricular
occur. Severe RVOTO results in RV heave. The ejection wall and with the apex protruding superiorly47 (Figure 3A). In

systolic murmur, which is characteristically loud and long, is the lateral view, the filling defect is seen in the anterior wall
of maximal intensity in the third or even fourth left interspace. between the inflow and outflow portions of the right ventricle
The site of the thrill, if present, is also low. (Figure 3B).
A diminished right ventricular stroke output caused by the
small proximal chamber and the relatively low immediate Management
subvalvular pressure allows the pulmonary valve to close
earlier. Hence P2 is not too soft or too delayed. 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.
2D Echo
The best view for diagnosing DCRV is the subcostal short- A
axis 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 B
views is the ideal diagnostic technique in cases of DCRV.7 Figures 3A and B: A. Double-chambered right ventricle. Right
The anomalous muscle bundles in anteroposterior projection ventricle (RV) angiogram in anteroposterior view showing severe
sub-infundibular stenosis and the pyramidal filling defect with its base
take the form of one or more filling defects that cross the right
towards anterior RV wall; B. Double-chambered right ventricle. Same 361
ventricular cavity either diagonally or horizontally. In most findings in lateral view
5 Pulmonary Artery Stenosis – Reimplantation of pulmonary artery (truncus
arteriosus, aortopulmonary collaterals)
The word pulmonary artery stenosis refers to obstruction – Pulmonary arterioplasty
anywhere in the area from the main pulmonary artery and – Fibrosing mediastinitis
its branches to the distal intrapulmonary arteries. The term – Mediastinal tumor
peripheral pulmonary artery stenosis has generally been used – Takayasus’ arteritis.
synonymously. The word supravalvar pulmonary stenosis has
been used to describe main pulmonary artery (MPA) stenosis. Clinical Features
Gay and Smith have classified peripheral pulmonary artery
stenosis into four types (Figure 4): The diverse etiology of pulmonary artery stenosis makes
1. Proximal main pulmonary artery stenosis. difficult the prediction of an incidence figure. The disease
2. Bifurcation stenosis. may manifest itself at any age from neonatal period to late
3. Distal pulmonary artery stenosis. adulthood. Diffuse peripheral pulmonary artery stenosis
4. Combination of multiple levels of stenosis. can present with life threatening central pulmonary artery
hypertension in the neonatal period. Postoperative pulmonary
Causes artery stenosis may manifest at any age from immediate
post operative period to late adulthood. Discrete pulmonary
1. Congenital artery branch stenosis is usually asymptomatic, but may
• Ductal constriction worsen pulmonary regurgitation in a repaired TOF and cause
• tof congestive heart failure. Central pulmonary artery stenosis,
• Pulmonary atresia/VSD/major aortopulmonary collateral bilateral pulmonary artery stenosis or diffuse peripheral
arteries (MAPCAs) pulmonary artery stenosis may elevate central pulmonary
• Alagille syndrome artery and right ventricular pressure.
• William-Beuren syndrome Clinical examination reveals characteristic dysmorphic
• Noonan’s syndrome features in situations like Noonan’s syndrome or Williams
• Congenital rubella syndrome syndrome. Cyanosis may occur if right ventricular pressure
• Cutis laxa is high and a PFO is shunting right-to-left. JVP may
• Ehlers-Danlos syndrome show prominent ‘a’ waves. Left parasternal heave may be
• Silver syndrome. prominent. First heart sound is normal, while 2nd heart
2. Acquired sound may be variably split. Depending upon the degree of
• Postoperative: central pulmonary artery hypertension, RV S3 or S4 may
– TOF repair occur.
– Arterial switch operation for transposition of great
vessels Investigation
– Central or Blalock-Taussig shunt
– Pulmonary artery banding
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
These demonstrate the site and degree of stenosis best. Today,
these are the best guides for intervention.
Perfusion lung scan shows ventilation-perfusion mismatch
362 in affected areas.
Figure 4: Classification of peripheral pulmonary artery stenosis
Indications for Intervention48 across the RVOT and across the lesion. The sheath should be 25
across the lesion by a few mm. Now the stent balloon assembly
1. RV pressure more than 50 percent systemic pressure. is negotiated across the lesion. Once the stent-mounted balloon

2. Perfusion scan showing decreased perfusion by >20 percent. is across the lesion, repeat hand injection of contrast from
3. RV dysfunction/cyanosis. the side arm of the sheath confirms the placement. Initial
4. Symptomatic patient. gentle predilation with a small balloon at 4 to 6 atm, tests
the compliance and makes the passage of the larger balloon/
Management stent assembly easier. After suitable placement, balloon is
inflated to recommended pressure, deploying the stent. Further
angiograms from the sheath confirm accurate placement and
Transcatheter Intervention
stent expansion. The deflated balloon is withdrawn over the
The procedure has been applied to both central pulmonary wire into the PA proximal to the stent and then removed. Now
artery and its branches. While the basic technique is similar an end hole catheter is gently advanced over the wire and the
to pulmonary balloon valvotomy, the following guidelines are wire withdrawn into the catheter (Figures 5A to C). Catheter is
important: then gently withdrawn without displacing the stent.
1. Choose a balloon three to four times the waist, but not Complications include stent displacement, hemoptysis,
exceeding twice the diameter of normal segment. vessel rupture, hypotension. Long-term complications include
2. The waist in the inflated balloon should be more than or stent fracture and restenosis (2 to 15%).48
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.
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 A
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 B
sheath with dilator, size being chosen on +2F size principle. It 363
Figures 5A and B: Pulmonary artery stenting: A. Post-extracardiac
requires perseverance and skill to maneuver the sheath-dilator Fontan (LPA) stenosis; B. Post-Fontan LPA stenosis–stent positioning
5 Echocardiographic diagnosis of congenital heart disease.
Lippincott-Raven; 1999. p. 325.
2. Nadas A. Pulmonary stenosis. In: Flyer DC, Nadae AS (Eds).
Nadas pediatric cardiology, Hanley and Belfus; 1992. pp. 459-70.

3. Keith JD, Rowe RD, Viad P. Heart disease in infancy and
childhood, 3rd edition. New York; 1978. pp. 4-6,761-88.
4. Johnson LW, Grossman W, Dalen JE. Pulmonary stenosis
in the adult. Long-term follow-up results. N Engl J Med.
1972;287:1159-63.
5. Abrahams DG, Wood P. Pulmonary stenosis with normal aortic
root. Br Heart J. 1951;13:519-48.
6. Campbell M. Simple pulmonary stenosis; pulmonary valvular
stenosis with a closed ventricular septum. Br Heart J. 1954;
16:273-300.
7. Udwadia AD, Khambadkone S, Bharucha BA, et al. Familial
congenital valvar pulmonary stenosis: autosomal dominant
inheritance. Pediatr cardiol. 1996;17:407-9.
8. Helen V Firth, Jane A Hurst, Judith G Hall, Oxford Desk
Reference Clinical Genetic; Oxford University Press; 2005.
p. 85.
Figure 5C: Post-Fontan LPA stenosis: post stent angiogram 9. Levine OR, Blumenthal S. Pulmonary stenosis. Circulation.
1965;32:33-41.
10. Ellison RC, Restieaux NJ. Vectorcardiography in Congenital
Some of the currently available stents allow redilation at Heart Disease: A method for estimating severity. Philadelphia
WB Saunders, 1972.
a later date. Drug eluting stent may decrease restenosis rate
11. Gamboa R, Hugenholtz PG, Nadas. Accuracy of the
and self-dissolving stents may address the issue of future phonocardiogram in assessing severity of aortic and pulmonic
expansion limitation. stenosis. Circulation. 1964;30:35-46.
Cutting balloon angioplasty: In peripheral pulmonary 12. Cheatham PJ. Pulmonary stenosis. In: Arthur Garson, J
stenosis, involving very distal branches, especially in Timothy Bricker, Dan G Mcnamara (eds): The Science and
unifocalized systemic arteries, cutting balloon angioplasty has Practice Pediatric Cardiology, volume. 2 pp. 1382-406.
been found to be more useful. 13. Gasul BM, Arcilla RA, Lev M. Heart Disease in Children.
Philadelphia: JB Lippincott; 1966.
14. Jeffery RF, Moller JH, Amplatz K. The dysplastic pulmonary
Conclusion valve: a new; roentgenographic entity with a discussion
of the anatomy and radiology of other types of valvular
Right ventricular outflow tract may be obstructed anywhere pulmonary stenosis. Am J Roentgenol Radium Ther Nucl Med.
from the infundibulum to the distal pulmonary arteries. 1972;114:322-39.
Whereas valvar or arterial lesions are generally amenable 15. Weyman AE, Hurwitz RA, Girod DA, et al. Cross-sectional
to catheter interventions, infundibular/sub-infundibular echocardiographic visualization of the stenotic pulmonary
obstruction require surgical repair. Regular follow up of mild- valve. Circulation. 1977;56:769-74.
moderate lesions and a high index of suspicion can avoid silent 16. Musewe NN, Robertson MA, Benson LN, et al. The dysplastic
progression of obstruction to right heart failure. pulmonary valve: echocardiographic features and results of
balloon dilatation. Br Heart J. 1987;57:364-70.
17. Lima Co, Sahn DJ, Valdes-Cruz LM, et al. Non-invasive
Medicine heals doubts as well as diseases.
prediction of transvalvular pressure gradient in patients
—Karl Marx with pulmonary stenosis by quantitative two-dimensional
echoardiographic Doppler studies. Circulation 1983;67:
ACKNOWLEDGMENT 866-71.
18. Johnson GL, Kwan OL, Handshoe S, et al. Accuracy of
The work done by Dr Bhushan Chavan, Fellow in Pediatric combined two-dimensional echocardiography and continuous
Cardiology, Institute of Cardiovascular Diseases, The Madras wave Doppler recordings in the estimation of pressure gradient
Medical Mission, in the preparation of this manuscript is of right ventricular outflow obstruction. J Am Coll Cardiol.
sincerely acknowledged. 1984;3:1013-8.
19. Nugent EW, Freedom RM, Norra JJ, et al. Clinical course in
pulmonary stenosis. Circulation. 1977;56(supplement 1):38.
REFERENCES 20. Takao S, Miyatake K, Izumi S, et al. Clinical implications of
pulmonary regurgitation in healthy individuals: detection by
1. Lilliam M, Valdez-Cruz, Raul O Cayre. Anomalies of cross sectional pulse Doppler echocardiography: Br Heart J.
364 right ventricular outflow tract and pulmonary arteries. 1988;59:542-50.
21. Drossner DM, Mahle WT. A management strategy for mild 35. Rao PS. Value of echo-Doppler studies in the evaluation of 25
valvar pulmonary stenosis. Pediatr Cardiol. 2008;29:649-52. the results of balloon pulmonary valvuloplasty. J Cardiovasc
22. Rao PS. Balloon pulmonary valvuloplasty for isolated pulmonic Ultrasonography. 1986;309-12.

stenosis. Transcatheter Therapy in Pediatric Cardiology. Wiley- 36. Rao PS, Thapar MK, Kutayli F. Causes of restenosis after
Liss; 1993.pp.59-104. balloon valvuloplasty for valvular pulmonary stenosis. Am J
23. Rao PS. Transcatheter treatment of pulmonary outflow tract Cardiol. 1988;62:979-82.
obstruction: a review. Prog Cardiovasc Dis. 1992;35:119-58. 37. McCrindle BW. Independent predictors of long-term results
24. Kan JS, White RI, Mitchell SE, et al. Percutaneous balloon after balloon pulmonary valvuloplasty. Valvuloplasty and
valvuloplasty: a new method for treating congenital pulmonary- Angioplasty of Congenital Anomalies (VACA) Registry
valve stenosis. N Engl J Med. 1982;307:540-2. Investigators. Circulation. 1994;89:1751-9.
25. Feltes TF, Bacha E, Beekman RH 3rd, et al. Indications for 38. Rao PS, Galal O, Patnana M, et al. Results of three to
cardiac catheterization and intervention in pediatric cardiac 10 year follow-up of balloon dilatation of the pulmonary
disease: a scientific statement from the American Heart valve. Heart. 1998;80:591-5.
Association. American Heart Association Congenital Cardiac 39. Rao PS. Role of interventional cardiology in neonates:
Defects Committee of the Council on Cardiovascular Disease Part I. Non-surgical atrial septostomy. Congenital Cardiol
in the Young; Council on Clinical Cardiology; Council on Today. 2007;5:1-12.
Cardiovascular Radiology and Intervention; American Heart 40. Castaneda AR, Jonas RA, Mayer JE. Surgery for infants with
Association. Circulation. 2011;123:2607-52. congenital heart defects. Cardiac Surgery of the Neonate and
26. Berman W, Fripp RR, Raisher BD, et al. Significant pulmonary Infant, 1st edition. 1993. pp. 1013-35.
valve incompetence following oversize balloon pulmonary 41. Cheatham JP. Pulmonary stenosis. In: Arthur Garson, J Timothy
valveplasty in small infants: A long-term follow-up study. Catheter Bricker, Dan G Mcnamara (Eds). The Science and Practice in
Cardiovasc Interv. 1999;48:61-5; discussion 66. Pediatric Cardiology, vol. 2.pp.1406-7.
27. Rao PS. Late pulmonary insufficiency after balloon dila- 42. Restivo A, Cameron AH, Anderson RH, et al. Divided right
tation of the pulmonary valve. Catheter Cardiovasc Inter- ventricle: a review of its anatomical varieties. Pediatr Cardiol.
vent. 2000;49:118-9. 1984;5:197-204.
28. Rao PS. How big a balloon and how many balloons for 43. Hoffman P, Wojcik AW, Rozanski J, et al. The role of
pulmonary valvuloplasty? Am Heart J. 1988;116:577-80. echocardiography in diagnosing double-chambered right
29. Rao PS, Fawzy ME. Double balloon technique for percutaneous ventricle in adults. Heart. 2004;90:789-93.
balloon pulmonary valvuloplasty: comparison with single 44. Kobayashi S, Terumi Hayashi, Shiroh Nakahara, et al. A
balloon technique. J Interven Cardiol. 1988;1:257-62. case of double chambered right ventricle associated with an
30. Engle MA, Holswade GR, Goldberg HP, et al. Regression interventricular septal aneurysm in an elderly patient. J Med
after open valvotomy of infundibular stenosis accompanying Ultrasonics. 2002;29:55-61.
severe valvular pulmonic stenosis. Circulation. 1958;17: 45. Galal O, Al-Halees Z, Solymar L, et al. Double-chambered
862-73. right ventricle in 73 patients: spectrum of the disease
31. Johnson AM. Hypertonic infundibular stenosis complicating and surgical results of transatrial repair. Can J Cardiol.
simple pulmonary valve stenosis. Br Heart J. 1959;21: 2000;16:167-73.
429-39. 46. Matina D, van Doesburg NH, Fouron JC, et al. Subxiphoid
32. Gilbert JW, Morrow AG, Talbert JL. The surgical significance two-dimensional echocardiographic diagnosis of double-
of hypertrophic infundibular obstruction accompanying chambered right ventricle. Circulation. 1983;67:885-8.
valvular pulmonic stenosis. J Thorac Cardiovasc 47. Alva C, Ho SY, Lincoln CR, et al. The nature of the obstructive
Surg. 1963;46:457-67. muscular bundles in double-chambered right ventricle. J
33. Rao PS. Long-term follow-up results after balloon dilatation Thorac Cardiovasc Surg. 1999;117:1180-9.
of pulmonic stenosis, aortic stenosis, and coarctation of the 48. Kyong-Jin Lee. Transcatheter interventions on the central and
aorta: a review. Prog Cardiovasc Dis. 1999;42:59-74. pulmonary arteries—current techniques and outcomes. In:
34. Rao PS, Solymar L. Electrocardiographic changes following Andrew N Redington, Glen S Van Arsdell, Robert H Anderson
balloon dilatation of valvar pulmonic stenosis. J Intervent (Eds). Congenital Diseases in the Right Heart. Springer; 2009.
Cardiol. 1988;1:189-97. pp.73, 9.
365
C hapter
Left Ventricular
26 Outflow Tract Obstructions
Vijayalakshmi IB, Vimala J
INTROdUCTION is dealt in Chapter 33. Coarctation of the aorta and hypoplastic

left heart syndrome are discussed in Chapter 34 and 47
Left ventricular outflow tract obstructions (LVOTO) include a respectively.
series of stenotic lesions starting in the anatomic left ventricular
outflow tract (LVOT) and stretching to the descending portion SUBAORTIC STENOSIS
of the aortic arch.1 The obstruction can be at the subvalvar,
valvar or supravalvar region. These obstructions to the LVOT The SAS is the LVOT obstruction just below the aortic valve.
may be alone or frequently in association with other cardiac In 1842, Cheevers4 recorded the first description of subaortic/
defects. The patients with LVOTO comprise a diverse group subvalvular AS. It is classified by the nature of the obstructing
of neonates, infants, children and young adults. The patients lesion as either fixed or dynamic. The dynamic form, idiopathic
may be critically ill or asymptomatic.2 The LVOTO increases hypertrophic obstructive cardiomyopathy (HOCM), in which
the afterload on the left ventricle (LV) and if the obstruction is the obstruction is caused by a generalized hypertrophy of the
severe and untreated, it results in hypertrophy and eventually LVOT and interventricular septum, is discussed in Chapter 51.
dilatation and failure of the LV in some patients. In the vast The fixed SAS is the second most common form of
majority, the LVOTOs are congenital, with the exception of LVOTO. Rarely, abnormal accessory mitral valve tissue or
some variants of subaortic stenosis (SAS). All these patients chords may cause SAS. It has been found that the distance
with LVOTO are at high-risk for developing infective between the mitral and aortic valves in patients with SAS is
endocarditis. The incidence of LVOTO is 6/10,000 live births. consistently increased.5 The fixed SAS accounts for 15 to 20
The classification of LVOTO is given in Box 1.3 In percent of all types of LVOTO.6 The subaortic obstruction is
this chapter, the presentation, diagnosis, management and almost always progressive and is not static.
outcomes are discussed in patients with SAS, supraaortic
stenosis and Shone’s anomaly. The valvar aortic stenosis (AS) Anatomy and Embryology
There is some debate about whether this lesion is indeed
Box 1: Classification of left ventricular outflow obstruction congenital, since it is rarely observed in newborns. There is
Subvalvular clinical and experimental evidence that fixed SAS is an acquired
• Discrete membranous stenosis lesion with an underlying ill-defined congenital disorder. It
• Fibromuscular tunnel is therefore often regarded as an acquired lesion. It has been
• Hypertrophic obstructive cardiomyopathy (HOCM) hypothesized that the alteration in direction of blood flow near
Valvular the crest of the interventricular septum leads to differentiation
• Unicuspid
• Bicuspid
of embryonic cells into a fibrotic tissue variant.5 It is usually
• Dysplastic associated with other congenital anomalies in 50 to 65
Supravalvular percent of the cases, e.g. perimembranous type of ventricular
• Discrete (membranous or hourglass) septal defect (VSD) (Figure 1), bicuspid aortic valve (BAV),
• Aortic hypoplasia or atresia coarctation of aorta (COA), patent ductus arteriosus and left
• Interrupted aortic arch
superior vena cava.7 Subvalvar obstruction has also been
• Coarctation of aorta.
reported after surgical patch closure of malaligned VSDs and
26
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;
Figure 2: Parasternal long-axis view in a 12-year-old boy shows

is thought to be secondary to fibrous tissue proliferation at subaortic membrane (M with arrows) just below the aortic valve. AO =
the sites of turbulent ouflow.8 Persistent endocardial cushion Aorta; LV = Left ventricle;
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 These patients are more prone for infective endocarditis. The
obstructive lesions, as in Shone’s complex, which frequently SAS is almost always progressive and is not static. Subaortic
includes parachute mitral valve, mitral stenosis, BAV and obstruction may have a ‘diaphragm’ just beneath the AV, which
COA.10 may be crescentric or form a complete circle. Clinically it is
difficult to distinguish subaortic membrane from valvar AS.
Pathophysiology For example, a 12-year-old boy diagnosed as AS in fact had
subaortic membrane just below the aortic valve (Figure 2).
The physiology of isolated SAS is identical to that of valvar
AS. The left ventricular hypertrophy occurs in response to high Fibromuscular Subaortic Ridge
systolic pressure. Poststenotic dilatation is not a feature of SAS
and even if dilatation occurs it is mild. The aortic leaflets are It is associated with fibrous ring and muscular hypertrophy
frequently malformed, resulting in aortic regurgitation (AR) in and located just below the aortic valve to 1 cm or more
about 50 percent of cases. The aortic cusp abnormalities result into the body of the ventricle causing more diffuse area of
either from close proximity of the membrane or fibromuscular LVOTO.7 It also frequently encroaches on the anterior mitral
collar to the leaflets or from injury caused by the impact of leaflet (Figure 3).15
the eccentric jet when the obstruction is more distal to the
valve.11 The high-velocity systolic jet collides with the aortic Subvalvular Fibromuscular Collar or Tunnel
valve (AV) leaflets and results in damage, scarring, leaflet
redundancy and prolapse. This distortion of AV increases its It is a severe form of SAS and is seen in 10 to 15 percent of the
susceptibility to infective endocarditis.12,13 SAS patients.7 It produces a more extensive area of obstruction,
The subaortic obstruction is divided into three types: which is characterized by an inward bowing of the echoes
1. Discrete membranous ‘diaphragmatic’. from the anterior and posterior margins of the outflow tract
2. Fibromuscular ridge. immediately beneath the aortic valve. There is more diffuse
3. Tunnel-like obstruction. obstruction extending well into the ventricle associated with
left ventricular hypertrophy (LVH). In this type there is a
Discrete Subaortic Membrane dense fibroelastic endocardial tissue involving the entire LVOT
(Figure 4) with annular hypoplasia and fibrous cusps. These
The obstruction is caused by either a thin, fibrous membrane patients are a major surgical challenge.
(75 to 85 percent) or a thick, fibromuscular band and is found
more with left-sided obstructive lesions.7 The lesion is thought Clinical Features
to result from abnormal motion, growth or hypertrophy of the
left ventricle and is usually progressive in nature.14 The lesion The primary hemodynamic effect on the left ventricle is of
is often associated with aortic insufficiency, VSD and COA. increased afterload, resulting in increased intracavitary pressure 367
5 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
right and Left VentricuLar oBstructiVe Lesions
impulse is laterally displaced and sustained with a 3/6 late-

peaking 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

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
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 Transthoracic Echocardiography
of left ventricular outflow obstruction like a tunnel. The concentric
hypertrophy of left ventricle is seen. AML = Anterior mitral leaflet; Ao = Transthoracic echocardiography (TTE) is crucial in the
Aorta; LA = Left atrium; LVH = Left ventricular hypertrophy 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
Figure 4: Parasternal long-axis view in a 8-year-old boy shows
Tunnel (T) like subaortic stenosis caused by dense fibromuscular
membrane along with a limited myomectomy, it is important for
collar, attached to interventricular septum (IVS) and extends onto the an echocardiographer to evaluate the extent of the membrane or
anterior mitral leaflet (AML) with narrow orifice with severe obstruction the ridge. Color Doppler demonstrates associated AR and VSD
(gradient 114 mm Hg). Ao = Aorta; LA = Left atrium; LV = Left ventricle (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).
and wall stress. In accordance with Laplace’s law, the ventricle Often subaortic membrane may be attached to anterior mitral
hypertrophies in an attempt to reduce the wall stress. Patients leaflet (AML) and this crucial information should be reported
may present with one of the triad of symptoms associated with so that the surgeon can take precautions during excision of
severe valvar AS: angina, heart failure or syncope.1 Diminished the membrane and avoid damage to the AML. Because of the
and delayed arterial pulses is felt in severe SAS. In mild SAS likelihood of progressive damage to the aortic valve leading to
apical impulse is normal or non-sustained and non-displaced thickening, regurgitation and sometimes severe LV dysfunction,
with grade 2/6 midsystolic murmur (MSM) at left upper there is some consensus that the membrane should be removed
368 sternal border (LUSB) and right upper sternal border (RUSB). early to prevent progressive aortic valve damage. It has been
26

Figure 5: Electrocardiogram in half standardization shows severe left ventricular hypertrophy with strain pattern
in an 8-year-old boy with severe subaortic stenosis
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.
As SAS is usually associated with other cardiac anomalies both
Figure 6: M-mode shows fluttering of aortic valve and early systolic right and left heart catheterization is recommended. The LV
closure of the aortic valve
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
Figure 7: Subaortic membrane (M) seen just below the aortic valve
in parasternal long-axis view. Color Doppler shows turbulence in the
differential diagnosis 369
left ventricular outflow tract beyond the membrane and in the right
ventricle due to the ventricular septal defect. Ao = Aorta; LA = Left It is important to differentiate valvar, subvalvar and supralvar
atrium; LV = Left ventricle; RV = Right ventricle. stenosis (Table 1).
5 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 Normal to anacrotic Unequal-right radial, brachial better felt
tardus), depending on the severity 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 Subaortic membrane or Hourglass appearance or membrane in
gradient tunnel with gradient and AR aorta with gradient
Angiogram Prussian helmet appearance Gradient and AR Narrowing in ascending aorta
Membrane in LAO/RAO
view
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
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 catheter-
determined 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 inter-
vention. Asymptomatic patients planning to become pregnant
Figure 8: Left ventricular (LV) angio in a 8-year-old boy shows severe or wishing to participate in competitive sports should be
subaortic obstruction. LV pressure was 190 mm Hg and pressure considered for SAS resection if the gradient is greater than or
above and below the aortic valve was 114/84 mm Hg (Gradient is 76)
equal to 30 mm Hg.1
Surgical management consists of discrete membrane
excision and/or blunt dissection in focal SAS with focal
Management
septal myomectomy. Tunnel-type SAS is more surgically
Once the Doppler-derived LVOT gradient reaches 50 mm Hg, challenging and often necessitates concomitant myomectomy
there is an increased risk of moderate to severe AR.22 Some or application of the Konno-Rastan procedure to reconstruct
degree of AR occurs in 50 percent of patients with SAS and the LVOT.23,26,27 Concomitant repair of the AV is performed if
moderate or severe AR occurs in 12 percent of patients.23 AR severity is more than mild. SAS recurs in up to 37 percent
The degree of SAS may be underestimated by the pressure of cases after surgical resection.23 In this series, tunnel-type
gradient in the presence of depressed LV function or a non- SAS recurred in 71 percent of patients versus a 14.7 percent
restrictive VSD, that allows left-to-right shunting to the recurrence rate for discrete SAS over 6 years of follow-up.
370 pulmonary arterial circulation. Even discrete SAS was far more likely to recur, however,
if the resting preoperative gradient was greater than 40 mm to get the echocardiography done to detect the SAS in time 26
Hg. The presence of an immediate postoperative gradient of when it can be treated with simple surgical excision and
greater than 10 mm Hg led to progressive recurrent SAS in correction of associated lesions.

75 percent of patients; therefore, considerable attention must
be paid by a qualified surgeon to the excision of all abnormal SUPRAVALVAR AORTIC STENOSIS
tissue to include myomectomy of the base of the membrane
and removal of the membrane from the AML. Time to
definition
recurrence depends on SAS type; the tunnel-type lesions recur
earlier than the discrete lesions. Supravalvar aortic stenosis (SVAS) denotes obstructive
Progressive AR may develop despite relief of SAS. constriction of the ascending aorta above the AV. This anomaly
Persistently turbulent flow patterns in the LVOT after SAS is commonly associated with elfin facies like in Williams
resection may continue to cause valve damage. In the syndrome36 and other vascular lesions such as peripheral
surgical series by Brauner et al,23 a higher preoperative pulmonary stenosis and coarctation and coronary artery or renal
LVOT gradient predicted late progression of AR. Other artery stenosis. There are three additional features of SVAS:
investigators have reported less postoperative AR in patients 1. Anatomy of the extramural coronary arteries,
who underwent SAS resection at a younger age or had a low 2. Condition of the aortic leaflets and aortic sinuses,
LVOT gradient.28-30 It is reasonable to consider surgery at the 3. The association with Williams syndrome.
time of diagnosis even in patients with low gradients if late
outcome can be safely improved by this strategy. However, Historical Review
this early aggressive approach should be weighed against the
significant incidence of recurrent obstructive lesions even Supravalvar aortic stenosis was first described by Chevers
in patients with low LVOT gradients.31-33 One should not in 1842.4 Later Deniel et al in 1958 described SVAS during
allow it to progress to type II or III, as extensive myomectomy cardiac catheterization.37 In 1961, Williams, Barratt-Boyes
could lead to complete heart block in type II or extensive and Lowe described association of SVAS with characteristic
resection, aortic valve and/or root replacement is needed in type facies consisting of protruding lips, low-set ears, epicanthic
III. Therefore, although surgical resection is the treatment of folds and strabismus along with mental retardation. In 1964,
choice for this disease, the optimal timing for surgery can be Beuren et al described the full syndrome of SVAS, consisting
elusive. Percutaneous balloon dilation of a fixed focal stenosis of characteristic facies associated with peripheral pulmonary
causes short-term improvement in the gradient and may be arterial stenoses, a metallic timber of the voice, dental
considered for palliation of SAS.32,34 The long-term effects of hypoplasia and peripheral systemic arterial stenosis.36,38
percutaneous balloon intervention for SAS are uncertain.
Incidence
Natural History
The incidence of SVAS is found in about 7.7 percent of patients
The natural history of SAS is not clear, because until the with LVOTO.39 The peripheral pulmonary artery stenosis
widespread use of TTE for the precise diagnosis all the occurs frequently in patients with Williams syndrome. The
patients were grouped as AS. Many a times the natural history renal abnormalities occur in nearly half of afflicted patients
depends on associated lesions rather than SAS. In congestive and are represented by renal artery stenosis, segmental
heart failure sudden death can occur in some children, but scarring, cystic dysplasia, nephrocalcinosis, asymmetry of
this could be secondary to the associated lesions. SAS is a kidneys, single kidney or pelvic kidney.15 Williams-Beuren
progressive disease in which the gradient is said to increase syndrome (WBS) is generally sporadic with an incidence of
in more than 75 percent of patients by about 25 mm Hg in 1/13,700 to 1/25,000 live births with no sex preference.40 In
5 years.35 The progression of gradient is more rapid than in the familial form of the disease, children have normal facies
valvar AS especially in patients with fibromuscular tunnel. and mental development and there is a strong family history
The incidence of bacterial endocarditis is as high as 13 to of SVAS.41 The prevalence of associated cardiovascular
25 percent.24 The sudden deaths are reported but the exact anomalies is reported to be as high as 85 percent.42
incidence is not certain.17
Genetics
Summary—Subaortic Stenosis
Supravalvar aortic stenosis is an inherited obstructive vascular
The hypothesis that discrete SAS is a progressive disorder disease that affects the aorta, carotid, coronary and pulmonary
and may develop into tunnel-like SAS is documented by arteries. Previous molecular genetic data have led to the
serial hemodynamic and angiographic investigations. Early hypothesis that SVAS results from mutations in the elastin
detection is very important. Hence, the onus lies on clinicians gene (ELN). 371
5 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 Figure 9: Transthoracic echocardiography in parasternal long axis
shows diffuse narrowing of aorta (type II). Ao = Aorta; LA = Left atrium;
The origins of the coronary arteries may be involved. Other LV = Left ventricle.
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 are present in 7 percent.44 The origin of the coronary arteries
ostia. Occasionally, the coronary occlusion is complete, a is usually proximal to the obstruction and they are subjected
leaflet of the distorted AV adhering to the obstructing collar to high systolic pressure and limited diastolic flow. There
of tissue. When the aortic lumen is compromised, there is may be partial or complete ostial obstruction of the coronary
proportionate left ventricular hypertension and hypertrophy. arteries, ectasia or aneurysm of the coronary arteries. Proximal
The obstruction is commonly localized, but in about 20 coronary artery involvement may be caused either by coronary
percent, it extends diffusely into the ascending aorta (Figure artery medial hypertrophy or by adherence of aortic cusps to
9). The aortic cusps are often thickened and distorted, the ostial walls. Coronary artery involvement is a cause for
sometimes adherent to the aortic wall, but although AR is increased risk of sudden cardiac death in these children as
common, it is rarely severe. Williams-Beuren syndrome is a compared to the normal population.44
neurodevelopmental disorder with characteristic facies, SVAS
and mental retardation. Children with this condition have Clinical Features
distinctive elfin facial features, a hoarse voice associated with
growth retardation, mental retardation and an overfriendly Most children with SVAS are asymptomatic at the time of
personality; hyperacusis, infantile hypercalcemia and pre- diagnosis.44 Patients with significant LVOTO may present
maturely wrinkled skin are other associated features.40 with angina, dyspnea or syncope. On examination, children
may have dysmorphic features. The right radial, brachial
Classification pulses are better felt than the left as the jet of blood flow
from the SVAS has a preferential trajectory into the right
The SVAS is classified as three morphologic subtypes as brachiocephalic (innominate) artery. This is called the
shown in Figures 10A to C:7,45,46 ‘Coanda effect’ in which the blood pressure is more in the
1. Hourglass type/deformity (50–75%). right upper limb than in the left upper limb (the difference
2. Diffuse type (25%). being > 10 mm Hg). The rest of the clinical findings are that
3. Rarely there may be a third subtype, a discrete membrane of LVOTO similar to aortic valvar stenosis except for the
above the valve. This may be a localized variety of the absence of an aortic valve click.
hourglass deformity.
diagnosis
Associations
Electrocardiogram
The commonest associated anomaly is hypoplasia of the
372 right ventricular outflow tract and branch pulmonary arteries, Electrocardiogram may show LVH with or without ST
which is reported in 64 percent. Coronary artery abnormalities changes.
26

a B c
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 a
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
B
As there may be long-segment obstruction, assessment of
Figures 11A and B: A. Transthoracic echocardiography in apical five
the gradient may require cardiac catheterization for complete chamber view shows type III discrete membrane causing SVAS in a 6
assessment of hemodynamic severity of the stenosis. The year old boy; B. CW Doppler shows 107 gradient. AV = Aortic valve;
373
morphology of the stenotic lesion may be classified as either LV = Left ventricle; SVAS = Supravalvar aortic stenosis
5 loacalized (Figure 12) or diffuse. The localized phenotype is been seen to gradually improve with time. Therefore, most
limited to the sinotubular junction and proximal ascending of the children with SVAS are managed expectantly and a
aorta. This is described as the hourglass appearance large proportion of the children managed non-surgically,
angiographically. In the diffuse phenotype, changes are demonstrate stable peak LVOT gradients and gradual
not limited to the supravalvar region and luminal hypoplasia improvement in ascending aortic dimensions. The overall
may extend into the distal ascending aorta, arch or beyond. mortality in SVAS is low.44 Operation has been recommended
The transverse arch, coarctation shelf and descending thoracic for patients with SVAS of either the discrete or diffuse types
aorta may also display areas of narrowing. According to with symptoms such as angina, dyspnea or syncope and for
various studies about 18 to 30 percent are of the diffuse type. patients with mean gradient greater than 50 mm Hg or peak
A smaller indexed transverse aortic arch diameter has been instantaneous gradient by Doppler echocardiography greater
shown to be associated with Williams-Beuren syndrome.44 than 70 mm Hg. Surgical repair may also be recommended
for adults with lesser degrees of supravalvar LVOTO when
Computed Tomography/Magnetic Resonance Imaging associated with symptoms or LVH or LV systolic dysfunction
or if pregnancy is planned.54
The ECG-gated multidetector computed tomography (CT)
and magnetic resonance imaging (MRI) are also useful in the Summary—Supravalvar Aortic Stenosis
diagnosis of SVAS owing to their high sensitivity in diagnosing
anomalies of the mediastinal vessels.52,53 It is recommended The severity of SVAS is variable and it often requires surgical
that MRI or CT can be performed in adult patients to assess intervention. A lack of treatment may result in progressive
the anatomy of the LVOT, the ascending aorta, coronary artery heart failure and can be fatal.
anatomy and flow. Also one can assess the main and main and
branch pulmonary artery anatomy and flow.
SHONE’S ANOMALY
Management Multiple levels of left heart obstruction are found in patients
with Shone’s anomaly, which was first described in 1963 by
A large proportion of children with congenital SVAS may Shone et al.10 In their abstract they described this anomaly
not need surgical intervention because the lesion gradually as follows–“A developmental complex is described in which
regresses overtime. The indexed LVOT dimensions have four obstructive anomalies of the left side of the heart and
been observed to increase overtime in patients who did not aorta coexist.” These anomalies are:
undergo an operation. The natural history of pulmonary 1. Parachute mitral valve
arterial involvement in Williams-Beuren syndrome has also 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 Shone’s anomaly,
the lesions of valvar mitral, AS and SVAS have been included.
In patients with Shone’s 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
The clinical presentation of patients with Shone’s anomaly
depends on the dominant level of obstruction to flow within
the left heart. With obstruction at the level of the mitral
Figure 12: Aortic root angiogram shows type I hourglass supravalvar valve secondary to a supravalvar mitral ring (Figure 13)
374 stenosis (arrows) with both right and left coronaries arising from single
or a parachute mitral valve as the dominant lesion, these
left coronary ostia
Brauner et al56 described the presentation of 19 consecutive 26
patients with Shone’s 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.
Investigations
In the past, the complete diagnosis of Shone’s complex
diagnosis was done by autopsy but today the modern tool
like two-dimensional transthoracic echocardiography and
Figure 13: Transthoracic echocardiography in modified two chamber
view shows supramitral ring (SMR with arrow) with deformed parachute
Doppler evaluation is excellent for assessing the severity
mitral valve. LA = Left atrium; LV = Left ventricle. of various lesions. One of our patients, a 12 years old girl
of Shone’s complex had parachute mitral valve (Figures
14A and B), interruption of aorta diagnosed on TTE and
patients present with congestive heart failure (CHF), with confirmed on CT angio (Figures 15A and B). She also had
an enlarged left atrium and passive pulmonary congestion bicuspid aortic valve (Figure 16). Cardiac catheterization is
noted on chest X-ray. These patients are at risk for pulmonary performed to further evaluate the pressure gradients across
artery hypertension (PAH) and may have palpable pulmonary the LVOT (i.e. subvalvar, valvar, supravalvar and COA) and
component of the second heart sound (P2). When the dominant to obtain the pulmonary artery pressure, noting the presence
lesion is at the level of the aortic valve (i.e. subvalvar, or and severity of PAH. The angiogram is done to delineate the
supravalvar), these patients present with heaving apical various obstructions (Figures 17A to D). Serial evaluations
impulse due to LVH and a harsh ejection systolic murmur. are required because the obstructive nature of the lesions is
LVH with strain pattern is possibly seen on ECG. If the usually progressive.
dominant lesion is coarctation of the aorta, the patient may Of the patients in the study by Brauner et al,56 the anatomic
present with hypertension in upper limbs and decreased lesions found were as follows: mitral valve abnormalities
pressure in lower limbs with radiofemoral delay in pulse. Age in 100 percent (supravalvar mitral ring 47%, parachute
of presentation may vary from the newborn period in severely mitral valve 63%), SAS in 79 percent (discrete membrane
affected infants to early school age in less-affected children. 67%, long segment fibromuscular tunnel 33%), BAV in
a B
Figures 14A and B: A. Transthoracic echocardiography in a in 12-year-old girl shows parachute mitral valve (PMV) with single papillary muscle 375
(SPM) in apical 2 chamber view; B. Parasternal short axis view at papillary muscle level. LA = Left atrium; LV = Left ventricle.
5
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
79 percent, SVAS in 10 percent and coarctation of the aorta

in 68 percent.
Management
The management of patients with Shone’s 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
Figure 16: Parasternal short axis in the same patient with Shone's supravalvar mitral ring), the resultant CHF is treated medically
376 complex shows bicuspid aortic valve until surgical resection of the supravalvar mitral ring, mitral
26

a B
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.
c d AO = Aorta; LV = Left ventricle.
valvuloplasty or mitral replacement is performed. When the years. Of the 14 survivors, 10 had significant hemodynamic
dominant lesion is LVOTO then surgical resection of the SAS abnormalities, including AS, left ventricular dysfunction,
with or without ventricular septal myomectomy, aortic valve mitral stenosis or regurgitation, pulmonary hypertension, or
repair or left ventricle to ascending aorta homograft placement recoarctation of the aorta.
is performed.55 The median age at first operation in the 19
patients described by Brauner et al was 4.2 months (range, 2 Summary—Shone's Anomaly
day–4.5 year). Specifically, the median age at intervention for
coarctation of the aorta was 1.5 months (2 day–2 year); for LV Patients with Shone’s anomaly require lifelong follow-up
inflow obstruction, the median age was 2.1 years (1 month–7 even after transcatheter procedure or surgical correction,
year); and for LVOT obstruction, the median age was 2.5 ± because the obstruction at various levels may progress or
1.5 years. These 19 patients underwent 46 major operations, recur. Several procedures are usually required, either by
including 94 distinct surgical procedures.56 surgery or by interventional cardiac catheterization, to repair
or palliate the obstructive lesion. The treatment of these
Prognosis patients continues to evolve and, despite the complexity of
these patient's lesions, the morbidity and mortality rates have
The surgical outcomes of patients with Shone’s anomaly as decreased and are expected to decrease further in the future.
noted by Brauner et al56 seemed to vary with the age at initial
intracardiac repair, severity of PAH and severity of the mitral Formerly, when religion was strong and science weak, men
valve lesion. The operative mortality rate was as high as 16 mistook magic for medicine; now, when science is strong 377
percent, the total mortality rate was 26 percent. The actuarial and religion weak, men mistake medicine for magic.
survival rate was 79 percent at 1 year and 73 percent at 7 —Thomas Szasz, The Second Sin, 1973
5 REFERENCES 21. Suárez de Lezo J, Pan M, Sancho M, et al. Percutaneous
transluminal balloon dilatation for discrete subaortic stenosis.
1. Aboulhosn J, Child JS. Left ventricular outflow obstruction: Am J Cardiol. 1986;58:619-21.
subaortic stenosis, bicuspid aortic valve, supravalvar aortic 22. McMahon CJ, Gauvreau K, Edwards JC, et al. Risk factors for
stenosis, and coarctation of the aorta. Circulation. 2006;114: aortic valve dysfunction in children with discrete subvalvar
2412-22. aortic stenosis. Am J Cardiol. 2004;94:459-64.
2. Fedderly RT. Left ventricular outflow obstruction. Pediatr Clin 23. Brauner R, Laks H, Drinkwater D, et al. Benefits of early
North Am. 1999;46:369-84. surgical repair in fixed subaortic stenosis. J Am Coll Cardiol.
3. Armstrong WF, Ryan T (Eds). Feigenbaum’s Echocardiography. 1997;30:1835-42.
Lippincott Williams and Wilkins; Philadelphia. 2009. 24. Chaikhouni A, Crawford FA Jr, Sade RM, et al. Discrete
4. Cheevers N. Observations on the diseases of the orifice and subaortic stenosis. Clin Cardiol. 1984;7:289-93.
valves of the aorta. Guys Hosp Rep. 1842. pp. 387-442. 25. Gersony WM. Natural history of discrete subvalvar aortic
5. Rosenquist GC, Clark EB, McAllister HA, et al. Increased stenosis: management implications. J Am Coll Cardiol.
mitral aortic separation in discrete subaortic stenosis. 2001;38:843-5.
Circulation. 1979;60:70-4. 26. Konno S, Imai Y, Lida Y, et al. A new method for prosthetic
6. Campbell M. Natural history of congenital aortic stenosis. Br valve replacement in congenital aortic stenosis associated with
Heart J. 1968;30:514-26. hypoplasia of the aortic valve ring. J Thorac Cardiovasc Surg.
7. Latson LA. Aortic stenosis: Valvular supravalvular, and fibromus- 1975;70:909-17.
cular subvalvular. In: Garson A Jr, Bricker JT, Fisher DJ, Neish 27. Rastan H, Koncz J. Aortoventriculoplasty: a new technique
SR (Eds). The Science and Practice of Pediatric Cardiology. 2nd for the treatment of left ventricular outflow tract obstruction. J
edition. USA: Williams and Wilkins; 1998. pp. 1257-76. Thorac Cardiovasc Surg. 1976;71:920-7.
8. Cilliers AM, Gewillig M. Rheology of discrete subaortic 28. Coleman DM, Smallhorn JF, McGrindle BW, et al.
stenosis. Heart. 2002;88:335-6. Postoperative follow-up of fibromuscular subaortic stenosis. J
9. Urbach J, Glaser J, Balkin J, et al. Familial membranous Am Coll Cardiol. 1994;24:1558-64.
subaortic stenosis. Cardiology. 1985;72:214-7. 29. Rizzoli G, Tiso E, Mazzucco A, et al. Discrete subaortic stenosis:
10. Shone JD, Sellers RD, Anderson RC, et al. The developmental operative age and gradient as predictors of late aortic valve
complex of “parachute mitral valve,” supravalvular ring of incompetence. J Thorac Cardiovasc Surg. 1993;106:95-104.
left atrium, subaortic stenosis, and coarctation of aorta. Am J 30. Douville EC, Sade RM, Crawford FA Jr, et al. Subvalvar aortic
Cardiol. 1963;11:714-25. stenosis: timing of operation. Ann Thorac Surg. 1990;50:29-34.
11. Roberts WC. Valvular, subvalvular and supravalvular aortic 31. Firpo C, Maitre Azcarate MJ, Quero Jimenez M, et al. Discrete
stenosis: morphologic features. Cardiovasc Clin. 1973;5:97-126. subaortic stenosis in childhood: a congenital or acquired disease?
12. Wright GB, Keane JF, Nadas AS, et al. Fixed subaortic stenosis Follow up in 65 patients. Eur Heart J. 1990;11:1033-40.
in the young: medical and surgical course in 83 patients. Am J 32. de Vries AG, Hess J, Witsenburg M, et al. Management of fixed
Cardiol. 1983;52:830-5.
subaortic stenosis: a retrospective study of 57 cases. J Am Coll
13. Katz NM, Buckley MJ, Liberthson RR. Discrete membranous
Cardiol. 1992;19:1013-7.
subaortic stenosis: report of 31 patients, review of the literature,
33. Jacobs JP, Palatianos GM, Cintron JR, et al. Transaortic
and delineation of management. Circulation. 1977;56:1034-8.
resection of the subaortic membrane: treatment for subvalvular
14. Rayburn ST, Netherland DE, Heath BJ. Discrete membranous
aortic stenosis. Chest. 1994;106:46-51.
subaortic stenosis: Improved results after resection and
34. Rao PS, Wilson AD, Chopra PS. Balloon dilatation for discrete
myectomy. Ann Thorac Surg. 1997;64:105-9.
subaortic stenosis: immediate and intermediate-term results. J
15. Perloff JK, Marelli AJ. Congenital Aortic stenosis; Congenital
Invasive Cardiol. 1990;2:65-70.
Aortic regurgitation. In: Perloff JK, Marelli AJ (Eds). Perloff's
clinical Recognition of Congenital Heart Diseases, 6th edition. 35. Freedom RM, Pelech A, Brand A, et al. The progressive nature
Philadelphia: Saunders; 2010. pp. 74-100. of subaortic stenosis in congenital heart disease. Int J Cardiol.
16. Schneeweiss A, Motro M, Shem-Tov A, et al. Discrete subaortic 1985;8:137-48.
stenosis associated with congenital valvular aortic stenosis:a 36. Williams JCP, Barratt-Boyes BG, Lowe JB. Supravalvular
diagnostic challenge. Am Heart J. 1983;106:55-9. aortic stenosis. Circulation. 1961;24:1311-8.
17. Newfeld EA, Muster AJ, Paul MH, et al. Discrete subvalvular 37. Denie JJ, Verheugt AP. Supravalvular aortic stenosis.
aortic stenosis in childhood. Study of 51 patients. Am J Cardiol. Circulation. 1958;18:902-8.
1976;38:53-61. 38. Beuren AJ, Schulze C, Eberle P, et al. The syndrome of
18. Kelly DT, Wulfsberg E, Rowe RD. Discrete subaortic stenosis. supravalvular aortic stenosis, peripheral pulmonary stenosis,
Circulation. 1972;46:309-22. mental retardation and similar facial appearance. Am J Cardiol.
19. Reis RL, Peterson LM, Mason DT, et al. Congenital fixed 1964;13:471-83.
subvalvular aortic stenosis. An anatomical classification and 39. Kitchiner D, Jackson M, Malaiya N, et al. Incidence and prognosis
correlations with operative results. Circulation. 1971;43(5 of obstruction of the left ventricular outflow tract in Liverpool
suppl):111-8. (1960-91): a study of 313 patients. Br Heart J. 1994;71:588-95.
20. Kleinert S, Geva T. Echocardiographic morphometry and 40. Dutra RL, Pieri Pde C, Teixeira AC, et al. Detection of deletions
geometry of the left ventricular outflow tract in fixed subaortic at 7q11.23 in Williams-Beuren syndrome by polymorphic
stenosis. J Am Coll Cardiol. 1993;22:1501-8. markers. Clinics (Sao Paulo). 2011;66:959-64.
378
41. Martin EC, Moseley IF. Supravalvar aortic stenosis. Br Heart
J. 1973;35:758-65.
49. Weyman AE, Caldwell RL, Hurwitz RA, et al. Cross-sectional
echocardiographic characterization of aortic obstruction.
26
42. Keane JF, Fyler DC. Aortic outflow abnormalities. In: Keane 1. Supravalvular aortic stenosis and aortic hypoplasia.

JF, Lock JE, Fyler DC (Eds). Nada's Pediatric Cardiology. 2nd Circulation. 1978;57:491-7.
edition. Saunders: Pennsylvania; 2006. pp. 581-601. 50. Nasrallah AT, Nihill M. Supravalvular aortic stenosis. Echo-
43. Palmer SJ, Santucci N, Widagdo J, et al. Negative autoregulation cardiographic features. Br Heart J. 1975;37:662-7.
of GTF2IRD1 in Williams-Beuren syndrome via a novel DNA 51. Subahi SA, Nouh MS, Allam AR, et al. Diagnosis of Supra-
binding mechanism. J Biol Chem. 2010;285:4715-24. valvular Aortic Stenosis by Transesophageal Echocardio-
44. Edward JH. Congenital supravalvular aortic stenosis: graphy. Echocardiography. 1997;14:399-402.
defining surgical and nonsurgical outcomes; Ann Thorac 52. Liu PS, St John Sutton MG, Litt HI. Diffuse supravalvular
Surg. 2008;86:1919-27. aortic stenosis: comprehensive imaging with ECG-gated CT
45. Vaideeswar P, Shankar V, Deshpande JR, et al. Pathology of angiography. Int J Cardiovasc Imaging. 2007;23:269-72.
the diffuse variant of supravalvar aortic stenosis. Cardiovasc 53. Hernandez RJ. Magnetic resonance imaging of mediastinal
Pathol. 2001;10:33-7. vessels. Magn Reson Imaging Clin N Am. 2002;10:237-51.
46. Stamm C, Friehs I, Ho SY, et al. Congenital supravalvar 54. Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008
aortic stenosis: a simple lesion? Eur J Cardiothorac Surg. Guidelines for the Management of Adults with Congenital
2001;19:195-202. Heart Disease. Circulation. 2008;118:2395-2451.
47. Morrow AG, Waldhausen JA, Peters RL, et al. Supravalvular 55. Bolling SF, Ianettoni MD, Dick M II, et al. Shone’s anomaly:
aortic stenosis: clinical, hemodynamic and pathologic observa- Operative results and late outcome. Ann Thorac Surg. 1990;49:
tions. Circulation. 1959;20:1003-10. 887-93.
48. Vogt J, Rupprath G, Grimm T, et al. Qualitative and quantitative 56. Brauner RA, Laks H, Drinkwater DC Jr, et al. Multiple left heart
evaluation of supravalvular aortic stenosis by cross sectional obstructions (Shone’s anomaly) with mitral valve involvement:
echocardiography. Pediatr Cardiol. 1982;3:13-7. long-term surgical outcome. Ann Thorac Surg. 1997;64:721-9.
379
C hapter
27 Left Ventricular Inflow Obstructions
Left ventricular inflow obstructions are an extremely rare form a. Congenital mitral stenosis
of congenital heart disease (CHD). It includes a number of Parachute mitral valve
malformations, either single or in combination, that orginate Anomalous mitral arcade
proximal or at the mitral valve. These malformations are Double orifice mitral valve
acyanotic heart diseases with no shunt lesion, but they can Accessory mitral valve tissue/orifice
cause pulmonary venous and pulmonary arterial hypertension, b. Hypoplastic mitral valve.
with very similar clinical manifestations. Although their
existence in isolation is described, most of the left ventricular OBSTRUCTIONS ABOVE THE MITRAL VALVE
inflow anomalies exist in conjunction with anomalies of left
sided structures. The anomalies can be described as per the
Cor Triatriatum Sinister
anatomical site at the supramital , mitral valve annulus, mitral
leaflets and submitral apparatus levels. Cor triatriatum is a heart with three atria (triatrial heart). It is
They left ventricular inflow obstructions are broadly rare and has been reported in 0.1–0.5% of all congenital heart
divided into: diseases. In Cor triatriatum sinister (also known as divided
1. Obstruction above the mitral valve left atrium) a partition divides the left atrium into a proximal
a. Cor triatriatum portion (the pulmonary sinus), into which the pulmonary
b. Supravalvular stenosing ring veins drain and a distal portion (the left atrium) that empties
c. Pulmonary vein stenosis into the left ventricle through the mitral valve and to which
d. Hypoplastic pulmonary veins the appendage is attached (Figures 1A to C). Cor triatriatum
2. Obstruction at the level of the mitral valve dexter is the persistence of right valve of the sinus venosus.
A B C
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
27
(incidence of each lesion is mentioned in the brackets)
The partition in left atrium was first recognized by Andral in
Left Ventricular Inflow Obstructions

1829. Borst (1905) named the lesion as Cor triatrium and Church I. Accessory atrial chamber receives all pulmonary veins and
published the first detailed pathological description in 1971. communicates with left atrium
Cor triatriatum is an obliquely oriented fibro-muscular 1. No other connections—classic Cor triatriatum (67%)
partition between the two portions in the left atrium and has a
2. Other anomalous connections:
lenticular shape opening. This opening connects two portions.
It may be non-obstructive or small. Sometimes there may be a. To right atrium directly (17%)
multiple openings or it may be imperforate. b. With total anomalous pulmonary venous connection
(3.6%)
II. Accessory atrial chamber receives all pulmonary veins and
Embryology
does not communicate with left atrium
Embryologically the anomaly represents failure of the common 1. Anomalous connection to right atrium directly (3.6%)
pulmonary vein to fuse completely with the evaginating left 2. With total anomalous pulmonary venous connection
atrium. There are frequently associated abnormalities of (0.3%)
pulmonary venous connection, atrial septum. and sometimes III. Subtotal Cor triatriatum
systemic veins. Another theory states that abnormal growth of 1. Accessory atrial chamber receives part of pulmonary
the septum primum accounts for Cor triatriatum. The second veins and connects to left atrium
theory is difficult to reconcile with the observations of most i. Remaining pulmonary veins connect normally (2.6%)
workers in this field.
ii. Remaining pulmonary veins connect anomalously
(4.3%)
Classification 2. Accessory atrial chamber receives part of pulmonary
veins and connects to right atrium (1.3%)
Available classifications include Herlong and Lucas
i. Remaining pulmonary veins connect normally
classification. Herlong starts with letters, then numerical
followed by alphabetic subdivisions (e.g. A2a) and Lucas ii. Part of Lucas classification. Remaining pulmonary veins
connect abnormally.
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 hypertension (PAH). The pulmonary arterial pressure is
classification. It divides the Cor triatriatum into: (a) usually raised more than the increment in pulmonary venous
Diaphragmatic type: most common form with proximal pressure. This is because of increased pulmonary vascular
accessory chamber and distal true left atrial chamber separated resistance due to pulmonary vasoconstriction, pulmonary
by fibrous or fibromuscular ridge. (b) Tubular Cor triatriatum: edema or anatomic changes in the small pulmonary arteries.
it is a primitive form where the proximal chamber retains the Some pulmonary vascular disease is common, with increased
shape of the common pulmonary vein, the distal end joins the pulmonary arterial smooth muscle and even grade 3 intimal
left atrium directly without any membrane. (c) The hourglass lesions. Severe PAH has been associated with hemoptysis,
type: the constriction projects inward as an obstructing shelf wheezing and pulmonary hemosiderosis. Patients may
which is seen externally as an hourglass deformity at the have chest pain, almost always associated with pulmonary
junction of the accessory chamber and the true left atrium hypertension due to right ventricular ischemia. It is however
(Figures 2A to H). Herlong has another subtype not listed by possible to have a tiny communication between the upper
Lucas, namely C2b in which the remaining pulmonary veins and lower chambers without pulmonary hypertension, if
have a different anomalous connection (mixed connection). the upper chamber is decompressed by an atrial defect
or partial anomalous pulmonary venous connection or if
Pathophysiology and Clinical Presentation pulmonary venous return is very low, because of a cyanotic
congenital heart lesion. Under these circumstances, repair of
The hemodynamics of Cor triatriatum depends on the extent of the associated lesion without removing the membrane can
left ventricular inflow obstruction. If the holes in the membrane be disastrous. Occasionally, thrombi form proximal to the
are restrictive (some studies put it as observed value of less membrane and systemic embolism has been reported. Some
than 6 mm in diameter, roughly equivalent to 1 cm2), there is patients present with symptoms due to an atrial arrhythmia,
pulmonary venous hypertension. Frequently mean pulmonary usually atrial fibrillation.
arterial wedge pressures are over 20 mm Hg. Patients with The membrane moves towards the mitral valve during
an obstructive orifice usually have severe pulmonary arterial diastole, reflecting diastolic gradient and moves away from 381
5
right and left ventricular obstructive lesions
A B C D
E F G H
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).
the mitral valve during systole, reflecting the reversal of a persistent left superior vena cava, often associated with an
gradient as the left ventricular contraction exerts pressure on unroofed coronary sinus. Other abnormalities of the left atrium
the membrane through the closed mitral valve. or mitral valve can also occur, possibly more frequently than
Associations: As is evident with the hemodynamics of can be accounted for by coincidence. Mitral regurgitation often
the lesion, about two-thirds of the patients have associated occurs and can be severe and a supramitral stenosing ring has
congenital cardiac lesions. Atrial septal defect, either a patent been seen. Apart from these atrial and venous anomalies, there
foramen ovale or a true fossa ovalis defect, occurs in about are occasional associations with most other forms of congenital
half of the patients. If the defect connects the right atrium to heart disease: patent ductus arteriosus, ventricular septal defect
the true left atrium (lower chamber), then it is not a part of (VSD), coarctation of the aorta, pulmonary stenosis, valvar
the classification. A sinus venosus defect has been reported. aortic stenosis (including bicuspid aortic valve) or subvalvar
Atrioventricular septal defects are quite common, ranging aortic stenosis, tetralogy of Fallot, Ebstein anomaly, double-
from ostium primum defects (often intermediate) to a common outlet right ventricle, hypoplastic left heart syndrome and
atrium and less frequently, a complete atrioventricular canal. occasionally other anomalies. Abnormalities of situs and
Abnormalities of the pulmonary veins (partial or total heterotaxies are uncommon. The right-sided chambers are
382 anomalous pulmonary venous connection) are common, as is hypertrophied if there is significant pulmonary hypertension.
Coronary Sinus Obstruction leaflet and may or may not be obstructive (Figures 3A and 27
B). The tissue may form an obstructing fibrous ring or shelf
Persistent left superior vena cava may lead to coronary sinus involving the atrial wall and extending to the leaflet. The tissue

dilation and left ventricular inlet obstruction. The mitral may be several millimeters above the valve or may be closely
leaflets are normal; however, the thickened posterior atrial adherent to the valve, impairing diastolic annular and leaflet
wall produces a funnel-like obstruction within the left atrium mobility (annular type – Figures 3C and D). Isolated stenosing
requiring resection of the roof of the dilated coronary sinus. supramitral ring is a rare condition. Underlying mitral valve
apparatus is usually abnormal, as this condition is frequently
Supravalvular Stenosing Ring associated with other mitral and ventricular anomalies such
as commissural fusion or parachute mitral valve. Unlike Cor
Supravalvular stenosing ring is a fibrous ring just proximal to triatriatum, the foramen ovale and left atrial appendage
the mitral valve. The ring is often partly adherent to the mitral lie above the plane of the membrane. Obstruction is often
A B
C D
383
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.
5 severe. One should maintain a high index of suspicion for
this condition in patients with signs and symptoms of left-
sided 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 Figure 4: The various components of the mitral valve with chordae
been ascribed to the prolonged conduction in the proximal tendinae and two papillary muscles. AML = Anterior mitral leaflet;
PML = Posterior mitral leaflet
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.
OBSTRUCTIONS AT THE MITRAL VALVE
Anatomy
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 Figure 5: The mitral valve orientation within the heart and its resemb-
supported by attachment to the left atrium and by fibrous elance to the cardinal’s hat “mitre” and hence the name mitral valve
support to the aortic semilunar valve. The bicuspid mitral
valve has two leaflets—anterior (medial or aortic) and
posterior (inferior or mural, ‘wall’) resembling the cardinal’s
hat or mitre, hence the term mitral valve (Figure 5). The even when the atrium is contracting and the ventricle is filling.
anterior leaflet is trapezoidal shaped and its attachment on The junctions of the two leaflets are called anterolateral and
the annulus to its free edge is longer (twice that of posterior the posteromedial commissures. The line of apposition of
leaflet) than the length of attachment across the annulus. the leaflets during valvular closure is indicated by a fibrous
The posterior leaflet is relatively narrow, with a very long ridge. There are two papillary muscles that extend from the
attachment distance across the annulus with its free edge ventricular free wall. The anterior papillary muscle is slightly
subdivided into the anterior, central and posterior crescent larger than the posterior and each papillary muscle consists
shapes (Figures 6). of a major trunk that often has multiple chordae tendineae.
Papillary muscles in conjunction with chordae tendineae, The chordae tendineae of each papillary muscle extends to
attach to the leaflets in order to secure them in place to the two valvular commissures and to the multiple crescent
prevent the prolapse of the leaflets up into the atrium. There shapes of the posterior cusp. In addition, the posterior leaflet
is considerable overlap of the leaflets, when the valves are in occasionally has chordae that extend from the ventricular
384 the closed position and they remain relatively close together myocardium without a papillary muscle.
the free edges of the dysplastic valve leaflets are thickened 27
and rolled, the valve may be incompetent as well as stenotic.

Hypoplasia of the Mitral Valve and Mitral Valve Atresia
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
Figure 6: Apical four chamber view from an infant with congenital ventricular outflow tract obstruction is usually present. Such
mitral stenosis due to dysplastic mitral valve showing thickened and
domed mitral leaflets. This child also had single papillary muscle (not infants present with symptoms and signs of acute left heart
shown in this picture). LA = Left atrium; LV = Left ventricle; RA = Right obstruction during the 1st day of life.
atrium; RV = Right ventricle.
Anomalies of the Leaflets

Mitral Valvar Dysplasia
(Typical Congenital Mitral Stenosis) Imperforate Valve
Mitral valvar dysplasia (Figure 6) is the most common lesion Imperforate valve or mitral atresia (Figure 8) is an extreme
underscoring congenital mitral stenosis, found in 49 percent anomaly involving the leaflets, seen most frequently in
cases of congenital mitral stenosis. It can be isolated, but combination with aortic atresia, when they form an integral
most frequently is seen in the setting of hypoplasia of the part of the hypoplastic left ventricle syndrome. In this
left heart. All components of the complex are malformed, setting, from the stance of anatomy, the imperforate valve
when the valve is dysplastic and hypoplastic. The leaflets is distinguished from absence of the left atrioventricular
are thickened, the intercordal spaces often obliterated and connection, since both produce atrioventricular valvar atresia.
the papillary muscles are deformed, the last frequently Approximately, 12 percent of patients may have a relatively
extending as muscular strands directly into the leaflets. When normal left ventricle, although often associated with a large
A B
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 four- 385
chamber view showing dilated right ventricle and hypoplastic left ventricle. la = Left atrium; LV = Left ventricle; ra = Right atrium; RV = Right
ventricle
5 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 (45–50%), 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
Figure 8: Apical four chamber view from a child with atretic left 15 percent of cases (Figures 9A and B). More commonly,
atrioventricular valve. The left atrioventricular valve is also overriding they are unequal, with the smaller orifice directed toward
the interventricular septum with malalignment of interatrial and the anterolateral commissure (41%) or the posteromedial
interventricular septum (arrows). LA = Left atrium; RA = Right atrium; commissure (44%). In the latter, atrioventricular septal defects
Rud LV = rudimentary left ventricle; RV = Right ventricle.
are common (90%) and mitral regurgitation is often present.
The incidence of functional mitral stenosis is more common if
the atrioventricular septum is intact.
VSD or straddling tricuspid valve. In hypoplasia of the left Surgical intervention is not necessary except in those with
heart, when the left atrioventricular connection is absent, the severe stenosis. In the eccentric, small hole-type DOMV, the
right atrium is connected to a dominant right ventricle. The tissue between the orifices is usually normal valve tissue and
left atrioventricular connection can also be absent, when the should not be excised, as it may result in iatrogenic mitral
right atrium is connected to a dominant left ventricle. This valve insufficiency.
lesion is best considered in the setting of the functionally
univentricular heart. Hypoplasia of Mural Leaflets
Ebstein Malformation of the Mitral Valve A rarer abnormality that can result in congenital mitral valvar
regurgitation is hypoplasia of the mural leaflet, such that the
Ebstein malformation can rarely affect the morphological valve leaflets cannot coapt normally during systole.
mitral valve. When this is the case, the mural leaflet is plas-
tered down onto the ventricular wall, with its hinge below the Overriding of Valvar Leaflets
atrioventricular junction. In this setting, there is no thinning
of the atrialized inlet portion, as is usually seen when it is More frequent is straddling and overriding of the valvar leaflets.
the morphological tricuspid valve that is deformed in the set- These anomalies can affect either the tricuspid or the mitral
ting of concordant atrioventricular connections. Such lack of valve. Bridging of leaflets is also a common feature of the
morphologic atrialization is also a feature of Ebstein common atrioventricular valve, albeit that a common valve can
malformation of the left-sided atrioventricular valve in the set- be exclusively connected to one or other of the ventricles. It
ting of congenitally corrected transposition (Ebsteinoid valve). is the spectrum between the commitment of straddling valves
to one or other ventricle, underscoring the difference between
Funnel-Shaped Valve functionally univentricular and biventricular arrangements.
When the morphological mitral valve straddles and overrides,
Another isolated anomaly of the valvular leaflets is the so called the valve always straddles through an anterosuperior inter
funnel-shaped valve. This entity is characterized by thickening ventricular communication and is found with either discordant
and retraction of the leaflets, with fused tendinous cords, but in or double outlet ventriculoarterial connections.
the presence of normal papillary muscles. The funnel produces
mitral stenosis. It is rare in postmortem collections. Fibrous Ridge that Anchors Together the
Aortic and Mural Components
Dual Orifices of Mitral Valve
While discussing malformations of the leaflets, we should
Dual orifices of mitral valve (DOMV) are produced by a tongue also pay attention to a fibrous ridge that anchors together the
386 of valvular tissue that extends between the mural and aortic aortic and mural components, narrowing the valvular orifice.
27

A B
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 one can see either direct insertion of the leaflets into the
abnormal fibrous shelf is an integral part of the atrial surface papillary muscles or insertion through short, thick chordae.
of the leaflets and can readily be removed at surgery. Shelves Also seen is the bridge of fibrous tissue adherant to the
can exist within the left atrium and produce true supravalvular inferior aspect of anterior mitral leaflet (Figure 10). This
rings, but these are much rarer than the variant attached to the abnormality usually results in both mitral stenosis and mitral
atrial aspect of the leaflets. regurgitation. Abnormal mitral arcade may be association
with atrial septal defect, patent ductus arteriosus, valvular
Mitral Valve Prolapse and subvalvular aortic stenosis and coarctation of aorta.
The commonest lesion afflicting the leaflets of the mitral valve is Anomalies of the Papillary Muscles
prolapse. The problems concerning the pathology of prolapse of
the mitral valve, however, are as numerous as those concerning
Parachute Mitral Valve
its clinical features. There is no unanimity concerning
nomenclature or etiology and perhaps more important, no Parachute mitral valve is characterized by unbalanced chordal
standard definition of what precisely constitutes prolapse of the attachments to a single papillary muscle. Two variants include:
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).
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 Figure 10: Apical four chamber view in a case of Hammock mitral valve
subcostal four chamber view or apical two-chamber view, 387
showing the attachments of the papillary muscles to the mitral valve
5 1. Two papillary muscles, but focalized chordal attachments muscles and milder than those with supravalvular mitral
(commoner). ring.
2. A classic type with a single papillary muscle (Figures 11A Commonly associated conditions include isolated or
and B). combined supramitral ring, coarctation of the aorta, atrial

Generally, the chordae are shortened and thickened. Single septal defect and VSD, aortic subvalvular or valvular
papillary muscle has variable anatomy. The anterolateral or, stenosis or the complete Shone complex of anomalies.
rarely, both papillary muscles may be completely absent or In those with mild to moderate stenosis, a good long-
two identifiable, but partially fused papillary muscles may term prognosis has been described. The severity of mitral
be present and interpapillary muscle distance reduced. In stenosis remains relatively non-progressive and most will
those with single papillary muscle or true parachute mitral not require valvotomy. There is no progression in mean
valve, the commissures are variably fused or absent and the valvular pressure gradient over time. Higher pressure
valve tissue is funnel-like with its orifice centrally located gradients are associated with vsd and supravalvular stenotic
above the solitary papillary muscle. This classic form is ring. Survival without mitral valve surgery approaches 95
relatively rare. In most cases, a parachute-like mitral valve percent at 6 months and 80 percent at 10 years of age. Left
is present. Two papillary muscles are present; however, the ventricular endocardial sclerosis is often present, when
chordae are predominately committed to a single papillary associated with significant left ventricular outflow tract
muscle, generally the posteromedial, which is normal in obstruction, but left ventricular size is usually normal to
size and location. The anterolateral papillary muscle is mildly reduced (within 70% of normal) in most patients.
displaced superiorly toward the mitral leaflet and may be Long-term survival correlates best with left ventricular size
fused along its length to the posterior ventricular wall, and with risk factors including coarctation and subvalvular
appearing absent and simulating a true parachute mitral aortic stenosis, but not with mitral valve orifice size. When
valve with single papillary muscle. The free margin of the required, surgical valvotomy seems preferable to balloon
leaflet occasionally attaches directly to the lateral papillary valvuloplasty, particularly when the dominant obstructive
muscle. The remaining cords to the posteromedial muscle component is tethering of the leaflets by asymmetric chordal
are progressively shortened and fused, constraining the attachments.
leaflets. The annulus may be normal and the commissure
present, but the orifice is eccentrically directed between the Excessive Mitral Valvular or Chordal Tissue
leaflets over the dominant papillary muscle. This condition
has been termed a parachute-like asymmetric mitral valve. In the most severe form the interchordal spaces are obliterated
The degree of stenosis is progressive, according to the by excessive valvular tissue. Histopathology of such
tethering of the leaflets and reduction of the distal orifice. accessory valve leaflets shows fibrous tissue and myxoid
However, the degree of stenosis is generally milder than dysplasia. There may be the presence of left ventricular
that of cases of typical congenital mitral stenosis with outflow tract obstruction, because of redundant mitral leaflet
symmetric or balanced cord attachments to the papillary 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
388 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
variable degrees of subaortic obstruction and also because In children with mitral stenosis, isolated pulmonary venous 27
of anomalous mitral valve leaflet or chordal attachments to obstruction is associated with arterial and pulmonary venous
the left ventricular septum. Associated forms of congenital medial muscular hypertrophy, as early as 12 months of age.

heart disease include partial atrioventricular septal defects Subsequently, there may be arterial and venous intimal
particularly, when associated with Down syndrome. thickening. However, advanced and irreversible changes
such as intimal cellular proliferation and plexiform lesions,
Pathophysiology common in patients with left-to-right shunts such as VSD,
were not seen in children with pulmonary venous obstruction
Flow across a mitral orifice is between the leaflets (interleaflet) even when pulmonary pressures were similar in magnitude and
and between the chordae tendinae (interchordal). In mitral duration. Thus, the nature of pulmonary vascular pathology
inflow obstructive lesions either of the flow gets compromised, differs in patients with pulmonary venous obstruction. The
e.g. in parachute mitral valve the interchordal flow is origins of these differences are not entirely understood,
compromised because of reduced or obliterated interchordal but are likely related to the higher flow and greater intimal
spaces. In case the chordae are elongated the same will result shear forces and vessel wall stresses encountered with vsd.
in mitral regurgitation. The functional consequences and These differences account for the relatively good expectation
symptomatology of the congenital mitral stenosis is anologus for postintervention reversal of pulmonary hypertension
to acquired mitral stenosis as described below. during the first 2 to 3 years in patients with congenital mitral
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 Starling’s concept of A
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 B
pressures, which distend the vasculature and lead to a
compensatory lowering of pulmonary vascular resistance. Figures 12A and B: Hemodynamic changes in severe mitral stenosis.
A. Shows skiagram showing normal connections; B. Shows the effect
However, chronic mitral valve obstruction may lead to of mitral stenosis. Enlargement and hypertrophy of the left atrium
pulmonary venous and arterial hypertension and secondary (LA), pulmonary venous hypertension and possibly pulmonary edema
right ventricular dysfunction. The associated increase of result. Reflex vasoconstriction of the pulmonary arterioles leads to
pulmonary arterial pressure and resistance is complex and pulmonary arterial hypertension and right ventricular hypertrophy.
LV = Left ventricle; PAH = Pulmonary artery hypertension; RV = Right 389
has important clinical implications. ventricle; RVOT = Right ventricular outflow tract;
5 obstruction. The rise in pulmonary vascular resistance and presence and type of associated lesions and the growth rate
consequent fall in pulmonary blood flow, means that, on of the infant. Mitral inflow obstructive lesions are generally
sequential cardiac catheterizations in individuals with mitral symptomatic in fetal and early neonatal life. Infants with less
stenosis, the gradient is frequently found to fall. severe mitral valve obstruction or less significant associated
Although the natural history of pulmonary hypertension lesions, generally present beyond the neonatal period with
in children with acquired mitral valve stenosis suggests that a history of antecedent pulmonary infections and failure to
pulmonary hypertension, generally resolves postoperatively, gain weight appropriately. Other features include irritability,
this is not necessarily the case with longer-standing congenital exhaustion at feeding, diaphoresis, tachypnea and chronic
mitral valvular disease and severe or chronic pulmonary cough. Congenital mitral stenosis is associated with syncope,
hypertension. Consequently, the substrate for pulmonary but seldom with hemoptysis. Aphonia may occur because of
hypertension remains a significant acute postoperative risk compression of recurrent laryngeal nerve by hypertensive
factor and underscores the importance of pulmonary vasodilator pulmonary trunk. Clinical features associated with a
management in the initial postoperative period. In patients particularly poor outcome are presentation early in infancy,
with severe mitral stenosis, the reduction of left ventricular signs of low systemic cardiac output and right-sided heart
volume or mass, ischemia, fibrosis and left ventricular failure. On examination severe mitral valve obstruction is
dysfunction may also compromise cardiac output. Critical associated with diminished peripheral perfusion and pulses.
reduction of cardiac output and vital organ dysfunction leads Normal sinus rhythum is generally a rule in congenital
to metabolic insufficiency and cachexia. Chronic low cardiac mitral stenosis. Jugular venous pulse shows increased ‘a’
output is associated with peripheral circulatory maladaptation wave secondary to pulmonary hypertension. Palpation of the
including excessive stimulation of the sympathoadrenal axis heart will reveal either a normal impulse or right ventricular
and systemic vasoconstriction. hypertrophy and there may be an apical diastolic thrill.
Finally, renal insufficiency, fluid and electrolyte imbalance Pulmonary valvar closure will be palpable if pulmonary
are caused by abnormal intake, renal hypoperfusion and hypertension is severe. The first heart sound in contrast to
hormonal factors. While associated distal obstructive lesions acquired rheumatic mitral stenosis, is relatively soft and mitral
may exaggerate the mitral insufficieny, by contrast, severe valve opening sound (snap) is usually absent, because the
pulmonary stenosis in the setting of a VSD may mask entirely mitral valve leaflets are relatively inflexible and immobile. The
the effects of the valvar obstruction by reducing the flow of second heart sound varies from widely split to narrowly split
blood to the lungs. Left atrial pressure is bound to be lower than with an accentuated pulmonary component, when pulmonary
pulmonary arterial pressure, irrespective of the severity of the hypertension is present. Although, left ventricular inflow tract
mitral obstruction and hence the hemodynamic data observed. obstruction should preclude auscultation of ventricular filling
sounds, right ventricular third or fourth heart sounds may be
INCIDENCE AND ETIOLOGY present. A low-frequency, low-intensity mid-diastolic murmur,
often with presystolic accentuation, is heard at the apex.
Congenital deformities of the mitral valve are rare and constitute Because of the rapid heart rates and displacement of the apex
0.6 percent of postmortems and 0.21 to 0.42 percent of clinical by the dilated hypertensive right ventricle, apical mid-diastolic
series (those excluding associated AVSD). Development of one murmur with presystolic accentuation is rarely observed in
abnormality upstream, during morphogenesis, may result in a congenital mitral stenosis. In some cases, however, a loud,
series of more distal abnormalities owing to disturbance in the high-frequency diastolic murmur may be present and its timing
patterns of flow. Annular hypoplasia of the mitral valve is almost is confirmed only by palpation of the peripheral pulses. The
always associated with hypoplasia of the left ventricle and aortic murmur may diminish in intensity or may be completely absent
stenosis or atresia. VSD is quite common in this setting and when cardiac output is markedly reduced. The murmur of
double outlet right ventricle and tetralogy of Fallot occasionally mitral insufficiency, pulmonary valve insufficiency secondary
occur. When the mitral valve is imperforate, left ventricular to pulmonary hypertension (Graham Steell murmur) and
hypoplasia is inevitable unless there is an associated VSD. findings characteristic of associated cardiac malformations
There is male predilection (in contrast to aquired may be present.
rheumatic mitral stenosis) in congenital mitral stenosis.
Familial recurrence has not been reported in congeital mitral INVESTIGATIONS
stenosis.
Electrocardiography
CLINICAL PRESENTATION AND SYMPTOMATOLOGY
Sinus rhythm is the rule in children, in contrast to theumatic
where atrial fibrillation is observed though first-degree heart
History and Physical Examination
block is common, particularly when the left atrium is greatly
390 Manifestations of symptoms of mitral valve stenosis depend enlarged. Left atrial hypertrophy occurs in about nine-tenths
upon the degree of obstruction to left ventricular inflow, the of patients and right atrial hypertrophy is the rule in patients
with pulmonary hypertension. In mitral stenosis, the mean 27
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.
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 Figure 13: Chest X-ray in posterioranterior view view in a 12-year-
old girl of Shone’s complex with parachute mitral valve with stenosis
and diversion of blood to the upper lobes (cephalization). In and regurgitation, shows dilated left atrial appendage (LAA), double
infants, the pulmonary trunk and left atrial appendage do not shadow due to right atrial (RA) and grade 2 left atrial (LA) enlargement
form discrete bulges on the upper left cardiac border, which (courtesy: Dr I B Vijayalakshmi)
is consequently straighter than normal. In older children,
prominence of the left atrial appendage is the rule and, in Cross-sectional Echocardiography
patients with pulmonary hypertension, the pulmonary trunk
is prominent (Figure 13). Mitral valve is best visualized in parasternal long-axis,
Straigtening of the left heart border by an enlarged left apical four chamber and two chamber views. Also, it can be
atrial appendage is much less common than in rheumatic interrogated from the atrial aspect in parasternal short-axis
mitral stenosis. Calcification of the mitral valve is also view. Addition of color Doppler further helps to diagnose the
generally absent. These appearances may be profoundly abnormalities. Echocardiography and Doppler is also very
modified by associated abnormalities. If the ascending aorta helpful in providing assessment of the mitral valve apparatus.
is seen on the left upper cardiac border (l-malposed aorta) and Parasternal long-axis view shows the motion of mitral valve
the patient has clinical features of mitral incompetence, then leaftlets for any evidence of doming or prolapse. The chordal
congenitally corrected transposition with tricuspid rather than length, chordal thickening and chordal insertion, etc. are
mitral incompetence is the most likely diagnosis. also well seen in this view. Additional abnormalities of left
ventricular outflow tract like subaortic membrane, tubular
Echocardiography 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
M-mode Echocardiography
can be measured. The valve prolapse is also seen well in this
M-Mode echocardiography provides non-specific evidence view. Apical four chamber view is good for showing dilatation
as to enlargement of the left ventricle, left atrium and right of atria, which may occur secondary to atrioventricular valve
ventricle. Features suggestive of mitral stenosis, include stenosis and/or regurgitation. Parasternal short-axis view with
anterior movement of the mural leaflet in diastole, a sweep from base to apex, shows orientation of commissures,
prolonged time to reach one-fifth of the peak rate in change chordae and papillary muscles including the number of
of left ventricular dimensions and a reduced peak rate of these papillary muscles. Cleft mitral valve and double orifice mitral
changes in dimension. Flattening of the E-F slope is suggestive, valve (Figure 9A and B) are also best diagnosed in this view.
but difficult to recognize in infants with tachycardia. The Addition of color flow mapping is necessary for quantifying
time from closure of the aortic valve to opening of the mitral the regurgitation and in cases with stenosis, to see the level
valve and from left ventricular minimum dimension to mitral of stenosis (Figure 3). The effective orifice size cannot
opening, have proved unhelpful as indicators of congenital be determined by 2D echocardiography when the flow is
mitral stenosis, unlike their use in assessment of acquired interchordal and the valve closure is eccentric. Doppler is also
mitral valvar disease. useful in estimating gradients and valve area. Gradients by 391
5 Doppler may be underestimated due to associated interatrial Magnetic Resonance Imaging
defect or due to poor alignment secondary to multiple levels
of obstruction to left ventricular inflow. Pressure half time Use of Magnetic resonance imaging (MRI) for functional
method is often not reliable in this setting. Planimetry of assessment in congenital heart disease including assessment
the mitral valve orifice in parasternal short-axis view may of mitral regurgitation is an evolving concept. Using this
be the best method for assessment of mitral valve area. The technique, a very good correlation has been found between
normal mitral valve area is 2.4 to 3.6 cm2/m2. In mild mitral measured and calculated regurgitant volumes, with a
stenosis the valve area is reduced to 1.2 to 2.4 cm2/m2; in correlation coefficient of 0.99. MRI provides more reliable
moderate mitral stenosis, mitral valve area is 0.6 to 1.2 cm2/ data with regards to mitral annular diameter, when compared
m2 and in severe mitral stenosis, the valve area is < 0.6 cm2/ to cross-sectional echocardiography. Three-dimensional
m2. Echocardiography is useful for evaluation of associated echocardiography has shown good correlation to MRI
cardiac defects seen in 90 percent of cases with congenital assessment of mitral valve lesions.
mitral valve abnormality.
Pulsed and Continuous Wave Doppler Echocardiography
Two-dimensional and Doppler echocardiographic assessment
Doppler echocardiography is a useful modality for assessment of mitral valve stenosis, usually replaces the necessity for
of mitral stenosis. With mitral valvar stenosis, a turbulent cardiac catheterization, unless surgical or interventional
inflow jet is seen, on color Doppler. Both pulse and continuous catheterization management seems indicated. The important
wave Doppler (Figure 14) can be used to calculate the gradient characteristic of mitral obstruction is difference in diastolic
across the valve. In adults and older patients, the pressure half- pressures between the left atrium and ventricle. The high left
time provides an accurate assessment of area, independent atrial pressure seems to seal the valvar mechanism of the oval
of cardiac output. This same technique can be applied to foramen, thus may require transseptal puncture for the same. A
children, although absolute areas calculated in this way are satisfactory pulmonary capillary wedge pressure simultaneous
of little value, because of the wide variation in body surface with the left ventricular pressure may also be used for the same
area. Mean gradients across the valve, as assessed using color (Figure 15). The presence of a diastolic pressure gradient
flow images, have traditionally been used in assessment of between pulmonary artery pressure and mean pulmonary
congenitally malformed hearts, despite the limitation of their capillary wedge pressure suggests the presence of associated
dependency on cardiac output. Color flow Doppler of mitral pulmonary vasoconstriction or pulmonary vaso-occlusive
valve excludes or establishes associated regurgitation and, disease. Administration of oxygen or pulmonary vasodilators
pinpoints the site of obstruction and the pattern of flow across such as nitric oxide and occasional open lung biopsy, may
the valve. This technique also provides valuable clues about be necessary to define the underlying pulmonary vascular
the site of exit of the blood. In a parachute valve there appears pathology and prognosis. Finally, comparison of pulmonary
to be a conical jet of blood, whereas in those with two papillary capillary wedge and left atrial pressure is required if pulmonary
muscles, the jet is more dispersed. vein obstruction is suspected. Routine measurement of wedge
392 Figure 14: Continuous wave Doppler shows both mitral Figure 15: Showing simultaneous left atrial and left ventricular trace
stenosis and regurgitation 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 for as long as is possible. The exception to this conservative 27
towards detecting otherwise masked mitral stenosis. approach is that for the isolated cleft of the anterior mitral
leaflet, where the results of repair are so good as to justify

Angiocardiography surgery at any age if there is significant cardiomegaly.
Reconstructive surgery currently has acceptable results
Angiography is largely replaced nowadays with echo with regards to mortality and morbidity over the medium term.
cardiography. It should be performed with the greatest caution A younger age at presentation and association with additional
in patients with congestive failure or severe pulmonary intracardiac lesions are poor prognostic features. In general,
hypertension. Injections into the pulmonary artery or survival over the medium term is close to 90 percent, with
left ventricle in the right anterior oblique projection may a freedom from reoperation of approximately 76 percent
demonstrate thickening and restricted mitral valve leaflets in over the variously reported periods of follow-up. There are
patients with isolated mitral valve stenosis or an hourglass- multiple surgical techniques that are tailored to the specific
shaped diastolic left ventricular filling defect characteristic of pathology at the levels of the annulus, leaflets and supporting
parachute mitral valve malformation. Mitral insufficiency may tension apparatus. Frequently, due to the complex nature of
be present. Associated congenital cardiac malformations should the valvar pathology, one or more of these has to be applied
be actively considered. In rare instances of severe stenosis or to an individual patient. For regurgitant valves, it is possible
mitral atresia with VSD and normally developed left ventricle, to perform annuloplasty or insert mitral rings, with the latter
balloon or blade atrial septostomy or stenting of the foramen currently being designed, so as to fit the normal saddle-
ovale should be performed to decompress the obstructed shape of the mitral valvar annulus. For those with dysplastic
left atrium. However, this must be balanced with the need to leaflets, augmentation has been employed with some success.
maintain high pulmonary vascular resistance in neonates with Occasionally, it is necessary to place a stitch between the
ductus arteriosus dependent systemic blood flow. leaflets, so as to create double orifices within the valve. For
stenotic lesions, it is possible to resect supramitral ring, split
MANAGEMENT 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
Medical Management and Timing of Intervention
the tendinous cords, as well as insert synthetic cords.
Medical management is frequently dictated by the nature and
severity of the associated lesions. Treatment with diuretics Prosthetic Valve
may buy some time, while the definitive repair is awaited.
Although surgical repair is possible, the long-term results Mitral valve replacement is considered only after all other
are disappointing. Unfortunately, pulmonary hypertension is surgical options have been exhausted. The results of valvar
frequently encountered in these patients, thus forcing the hand replacement are somewhat disappointing, particularly in the
of the cardiologist and surgeon. There is little data for balloon very young child. The initial experience gained with insertion
angioplasty performed in the setting of congenital mitral valvar of homograft valves was disappointing, with reoperation
stenosis, albeit that encouraging results have now been reported. needed in two-fifths at 5 years and three fifths by 7 years.
Mechanical valves are the treatment of choice, with the valves
Surgical Management inserted usually being bileaflet and having a low profile. From
several series that followed patients for 10 to 15 years, overall
Patients with severe mitral valvar stenosis, who present in survival was in the mid-1960s, with freedom from the need
the neonatal period and frequently have some degree of left to insert a second valve varying between 54 percent and 66
ventricular hypoplasia and aortic valvar stenosis, now tend to percent.With improved management of anticoagulation, the
be managed by Norwood sequence of operations followed by incidences of thrombosis and infection are low, occurring in
univentricular pathway repair. less than one-tenth. It is the need for valvar replacement and
the size of the initial prosthesis, that stratifies the patients. In
Mitral Valve Repair many younger patients, where stenosis is the predominant
lesion, there is associated annular hypoplasia that limits the
Beyond the neonatal period mitral valve repair is the best size of the prosthesis, which can be inserted during the initial
option, as valvar replacement in children is still fraught with operation. Indeed, in some cases the annulus is deemed too
problems. The presence of intractable heart failure, severe small and the prosthesis has to be positioned in the supra-
pulmonary hypertension or pulmonary edema, means that annular position. To overcome this problem, some groups have
the need for operation in infancy or early childhood is forced used a pulmonary autograft in the so-called Ross-2 procedure.
upon the management team. In contrast, in congenital mitral The pulmonary valve removed from the patient is sewn into
incompetence, the generally good prognosis with medical a Dacron tube, which is then inserted into the mitral annulus. 393
management means that operation can usually be postponed Although experience is limited with this technique, the initial
5 results seem encouraging, with a low mortality, albeit that as 4. De Lange FJ, Moorman AFM, Anderson RH, et al. Lineage
yet there is no data over the long-term. and morphogenetic analysis of the cardiac valves. Circ Res.
2004;95:645-54.
5. Julien IE Hoffman. Cor Triatriatum Sinister in the Natural and

CONCLUSION Unnatural History of Congenital Heart Disease, 1st edition,
Wiley Blackwell. 2009. pp. 329-34.
Congenital obstruction to left ventricular inflow can originate
6. Kanani M, Moorman AFM, Cook AC, et al. Development of
at various levels. The anomalies may be associated with other the atrioventricular valves: Clinicomorphologic correlations.
left sided anomalies (e.g Shones Complex). The presentation Ann Thorac Surg. 2005;79: 1797-804.
of the patient depends on the degree of left ventricular 7. McElhinney DB, Sherwood MC, Keane JF, et al. Current
inflow obstruction and patients with severe obstruction management of severe congenital mitral stenosis, outcomes of
present in infancy. Echocardiography is helpful not only in transcatheter and surgical therapy in 108 infants and children.
understanding the pathophysiology, hemodynamics and Circulation. 2005;112:707-14.
anatomical basis to decide for the anatomical subtype of the 8. Nath RK, Saxena A.Congenital Atrioventricular valve aomalies
in Echocardiography in congenital heart diseases, A practical
obstruction. Echocardiography may also be helpful to look
approach. 1st edition. 2008. pp. 58-68.
for associated anomalies and also to guide the surgeon for
9. Rorie M, Xie GY, Miles H, et al. Diagnosis and surgical
appropriate surgical management. The outcome of the lesion correction of cor triatriatum in an adult: combined use of
depends on the underlying anatomical lesion and its severity transesophageal echocardiography and catheterization. Cath-
at the time of presentation. eter Cardiovasc Interv. 2000;51:83-6.
10. Shone JD, Sellers RD, Anderson RC, et al. The developmental
It is easy to get a thousand prescriptions but hard to get one complex of ‘parachute mitral valve’, supravalvular ring of left
single remedy. atrium, subaortic stenosis, and coarctation of aorta. Am J Car-
—Chinese Proverb diol. 1963;11:714-25.
11. Smallhorn J, Tommasini G, Deanfield J, et al. Congenital mitral
stenosis: Anatomical and functional assessment by echocardi-
Suggested Readings ography. Br Heart J. 1981;45:527-34.
12. Smallhorn JF, Anderson RH. Abnormalities of the morpho-
1. Asante-Korang A, O’Leary PO, Anderson RH. Anatomy and logically mitral valve In: Paediatric Cardiology. Anderson RH,
echo of the normal and abnormal mitral valve. Cardiol Young. Macartney RF, Shinebourne EA, Baker EJ, Rigby ML, Tynan
2006;16:27-34. M. 3rd edition. Churchill Livingstone, Harcourt Publishers lim-
2. Baylen BG,Atkinson DE. Mitral Inflow Obstruction. Iin ited; 2010. pp. 730-2.
Heart Disease in infants, children and Adolescents including 13. Van der Bel Kahn J, Duren DR, Becker AE. Isolated mitral
the fetus and young adult. Allen HD, Driscoll DJ, Shaddy valve prolapse: Chordal architecture as an anatomic basis in
RE, Feltes TF, 7th edition, Lippincort Williams and Wilkins older patients. J Am Coll Cardiol. 1985;5:1335-40.
Publishers;2008:922-37. 14. Wood AE, Healy DG, Nolke L, et al. Mitral valve reconstruction
3. Chauvaud SM, Milhaileanu SA, Gaer JAR, et al. Surgical in a pediatric population: Late clinical results and predictors
treatment of congenital mitral valvar stenosis: ‘The Hospital of long-term outcome.J Thorac Cardiovasc Surg. 2005;130:
Broussais’ experience. Cardiol Young. 1997;7:15-21. 66-73.
394
Sec t i on
Congenital Valvar Lesions
C hapter
28 Tricuspid Atresia
P Syamasundar Rao
INTRODUCTION on morphology of the atretic tricuspid valve, it is classified

into muscular, membranous, valvar, Ebstein, unguarded with
Tricuspid atresia is a cyanotic, congenital cardiac anomaly muscular shelf and atrioventricular canal types.10,15-17 The
and is defined as congenital absence or agenesis of the muscular type, constituting 89 percent of cases,15,17 is the most
morphologic tricuspid valve.1,2 It is the third most common common type, the remaining types account for 11 percent of
cyanotic congenital heart defect and is the most common cause cases. A classification based solely on the X-ray appearance
of cyanosis with left ventricular hypertrophy. Whereas, there of pulmonary vascular markings was put forward by Astley:11
is a controversy with regard to terminology (tricuspid atresia, Group A-Decreased pulmonary vascular markings and
univentricular heart or univentricular connection), the author Group B-Increased pulmonary vascular markings. Dick and
is of the opinion that the term ‘tricuspid atresia’ is the correct his associates9 added another group to Astley’s classification:
and logical term to describe this well-characterized pathologic Group C-Transition from increased to decreased pulmonary
and clinical entity; the reasons are detailed elsewhere.2-4 vascular markings in serial chest films. The above two
A methodical and thorough review by Rashkind5 suggests classifications have clinical value, but a classification based
that the first documented case of tricuspid atresia was that of on associated cardiac defects appears to be more useful
Kreyszig in 1817,6 although the 1812 report by the editors clinically.1,15 A classification based on great artery inter-
of London Medical Review7 appears to fit the description of relationship was first proposed by Kühne in 1906.12 This was
tricuspid atresia. later refined by Edwards and Burchell13 and by Keith, Rowe
The true prevalence of tricuspid atresia is not known. and Vlad.14,18,19 Because of some apparent inconsistencies in
Extensive review of the literature revealed an autopsy subgrouping and the need for inclusion of all variations in great
prevalence rate of 2.9 percent and a clinical prevalence rate artery anatomy, we proposed an unified classification,1,20 and
of 1.4 percent among subjects with congenital heart disease.8 this is listed in Box 1. First, the tricuspid atresia is classified
With the known prevalence of congenital heart defects of 0.8 into four major types based on the great artery relationship.
percent of live births, it is estimated that tricuspid atresia occurs Each type is identified with a Roman number:
approximately 1 in 10,000 live births.8 There is no gender • Type I: Normally related great arteries
preponderance for tricuspid atresia, but male preponderance • Type II: D-transposition of the great arteries
appears to be present in the subgroup of tricuspid atresia • Type III: Malpositions of the great arteries other than
patients with associated transposition of the great arteries— d-transposition
male to female ratio was 2 : 1.8,9 • Type IV: Truncus arteriosus.
In this chapter, classification, anatomic, physiologic and The type III is again subdivided into several subtypes (see
clinical features, non-invasive and invasive evaluation, Box 1) and is identified with an Arabic number (1 to 5).
management and prognosis of tricuspid atresia are discussed. Each type and subtype are further divided into subgroups
on the basis of pulmonary arteries; each subgroup is indicated
CLASSIFICATION by a lower case letter: Subgroup a – Pulmonary atresia, b –
Pulmonary stenosis or hypoplasia, and c – Normal pulmonary
Tricuspid atresia is classified on the basis of valve arteries (no pulmonary stenosis).1,15,17,20 Once a patient
morphology,10 roentgenographic appearance of pulmonary with tricuspid atresia is thus classified, the status of the
vascular markings11 and associated cardiac defects.1,12-15 Based interventricular septum, i.e. intact, small or large ventricular
6 Box 1: A unified classification of tricuspid atresia
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
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 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
septal defect (VSD), or multiple VSDs and other associated also shown. The impression that one gets from the literature is that this
dimple is present in most cases of tricuspid atresia. Careful inspection
malformations should be described. If one wants to follow of the heart specimen by several investigators suggests that this dimple
the terminology of congenital heart disease proposed and reis seen in only 29 to 83% of muscular type of tricuspid atresia cases.
emphasized by Van Praagh,21 one could include the remaining Courtesy: Rao PS, et al.23 Am Heart J 1991;122:829
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 the interatrial communication is obstructive and may form an
aneurysm of the fossa ovalis causing obstruction to the mitral
PATHOLOGIC ANATOMY flow. The left atrium is enlarged and may be more so if the
pulmonary blood flow is increased.
The most common type of tricuspid atresia, muscular variety, The mitral valve is morphologically a mitral valve, usually
is characterized by a dimple or a localized fibrous thickening bicuspid, but its orifice is large and rarely incompetent. The
in the floor of the right atrium (Figure 1) at the expected left ventricle is clearly a morphologic left ventricle with
site of the tricuspid valve14 and constitutes 89 percent of the only occasional abnormalities;25 however, it is enlarged and
cases.16,17 No valvar material can be identified either by gross hypertrophied.
or microscopic examination.14 The VSD may be large, small or non-existent (intact
Other anatomic types, namely, membranous type (6.6%) ventricular septum), or multiple VSDs may be present. When
with the atrioventricular portion of the membranous septum present, it may be:
forming the floor of the right atrium,24,25 valvar type (1%) a. Conoventricular or perimembranous (located inferior to
with minute valve cusps which are fused,15,26,27 Ebstein’s the septal band)
type (2.6%) with Ebstein deformity of the tricuspid valve b. Conal septal malalignment VSD (located in between the
leaflets with fusion of the valve leaflets,10,24,28 common anterosuperior and posteroinferior limbs of septal band)
atrioventricular canal type (0.2%) in which a leaflet of the c. Muscular (located inferiorly when compared to a and b)
common atrioventricular canal completely seals off the only d. Atrioventricular canal type.22
entry into the right ventricle,16,29 and unguarded (0.6%) with In the author’s experience, muscular VSDs are most
muscular shelf30 have been described. For further details the common.31-34 Also, most of these VSDs are restrictive and
reader is referred to our previous reviews.15,17 produce subpulmonary stenosis in the type I patients and
The right atrium is usually enlarged and its wall thickened subaortic stenosis in the type II patients.31-39
and hypertrophied. The interatrial communication, which is The right ventricle is small and hypoplastic; even the largest
necessary for survival, is usually a stretched patent foramen of the right ventricles that are present in patients with large
ovale, sometimes an ostium secundum atrial septal defect and VSDs and/or transposition of the great arteries are smaller
398 rarely an ostium primum atrial septal defect. Occasionally than those in normal. Its size, by and large, is determined
by anatomic type. It may be extremely small so that it may In type I (normally related great arteries) patients with 28
escape detection on gross examination of the specimen as in intact ventricular septum and/or pulmonary atresia (type Ia)
type Ia cases. It can be identified at the right upper aspect of and type II (transposition of the great arteries) patients with
Tricuspid Atresia
the ventricular mass. On occasion, it can be identified only pulmonary atresia (type IIa), the pulmonary blood flow must
on microscopic examination.13,14 However, in most cases the be derived entirely through the ductus. Since, the ductus is
ventricle is a true right ventricle24,40 consisting of: carrying only the pulmonary blood flow, representing 8 to 10
a. A sharply demarcated infundibulum with septal and percent of combined ventricular output in contradistinction
parietal bands to 66 percent in the normal fetus,43,44 the ductus arteriosus
b. A sinus with trabeculae, which communicates with the left is smaller than normal. This and the acute angulation of the
ventricle via a VSD. The inflow region of the right ventricle, ductus at its aortic origin because of reversal of direction of
by definition, is absent although papillary muscles may be ductal flow may render the ductus less responsive to the usual
present occasionally.19 postnatal stimuli.43
The relative position of the great vessels is quite variable In type I patients with moderate to large VSD, there is likely
and has been the basis for classification of this anomaly, to be anterograde blood flow from the left ventricle through
which has been described in the preceding section. The the VSD into the right ventricle, the pulmonary artery, and
ascending aorta may be normal in size or large. Pulmonary ductus arteriosus, whereas there may be retrograde blood flow
outflow obstruction may be either subvalvar or valvar in from the aorta to the ductus arteriosus in the fetus with small
patients with transposition of the great arteries, while in VSD. The larger the VSD, the greater is the probability of
patients with normally related great arteries the pulmonary normal anterograde ductal flow.
obstruction is often at the VSD level although, in a few cases, In type I patients with a small or no VSD, most of the left
subvalvar pulmonary stenosis, narrow tract of the hypoplastic ventricular blood is ejected into the aorta, which is then carried
right ventricle and rarely, valvar pulmonary stenosis may to the entire body including the placenta and lower part of
also be responsible for pulmonary outflow tract obstruction. the body. Thus, the aortic isthmus carries a larger proportion
With pulmonary atresia, either a patent ductus arteriosus or of ventricular output than normal; presumably this is the
aortopulmonary collateral vessels may be present. reason for the rarity of aortic coarctation in these subgroups
A large number of additional abnormalities may be present of tricuspid atresia patients. In type II (transposition) patients
in 30 percent of tricuspid atresia patients.41,42 Significant without significant pulmonary stenosis, because the VSD
among these are persistent left superior vena cava and is usually smaller than the pulmonary valve ring,45 a larger
coarctation of the aorta; the latter is much more common proportion of blood traverses the pulmonary artery and ductus
in type II (transposition) patients. The possible physiologic arteriosus and therefore the isthmic flow decreases, thus
reason for the latter is discussed in the next section. accounting for higher incidence of aortic coarctation and aortic
arch anomalies seen with these types of tricuspid atresia.
PATHOPHYSIOLOGY
Postnatal Circulation
Prenatal Circulation
An obligatory right-to-left shunt occurs at the atrial level in
Tricuspid atresia is not detrimental to normal fetal development. most types and subtypes of tricuspid atresia. Usually, this
In a normally formed fetus, the highly saturated inferior vena shunting is through a patent foramen ovale, but on occasion,
caval blood is preferentially shunted into the left atrium via the secundum or primum atrial septal defects may be present.
patent foramen ovale and from there into the left ventricle and Thus, the systemic and coronary venous blood mixes with
aorta. The superior vena caval blood containing desaturated pulmonary venous return in the left atrium. This mixed
blood is directed towards the tricuspid valve and right ventricle pulmonary, coronary and systemic venous blood enters the
and from there into the pulmonary arteries, ductus arteriosus left ventricle.
and descending aorta. Thus, in a normal fetus, the head, heart In type I (normally related great arteries) patients with a
and upper extremities are supplied with blood at higher PO2 VSD, left-to-right ventricular shunt occurs, thus perfusing the
and the lungs, the lower part of the body and placenta with lungs. In the absence of a VSD, the pulmonary circulation
lower PO2. In tricuspid atresia, both vena caval streams have is derived either via a patent ductus arteriosus or through
to be shunted across the foramen ovale into the left atrium and bronchopulmonary or persistent embryonic aortopulmonary
left ventricle. Therefore, the PO2 differential to various parts of collateral vessels. The presence of either a VSD or other
the body that is normally present does not exist. Whether this means of blood supply to the lungs is crucial for the patient’s
higher PO2 to lungs influences the pulmonary arteriolar smooth survival. The aortic blood flow is derived directly from the left
muscle development or not, is not known.43 Lower than normal ventricle.
PO2 to the brain and upper part of the body does not seem to In type II (d-transposition of the great arteries) patients,
impair their development, at least as observed clinically. the pulmonary blood flow is directly derived from the left 399
6 ventricle. The systemic blood flow is via the VSD and the Pulmonary Blood Flow
right ventricle. In type III, subtype 1 with l-transposition of the
great arteries, the atretic morphologic tricuspid valve is a left- The magnitude of pulmonary blood flow is the major
sided atrioventricular valve and therefore, in a physiological determinant of clinical features in tricuspid atresia. An infant
sense, it behaves as mitral (left or pulmonary venous atrial) with markedly decreased pulmonary blood flow will present
obstruction. In other type III and type IV patients, the systemic early in the neonatal period with severe cyanosis, hypoxemia
and pulmonary blood flows are determined by the size of the and acidosis. An infant with markedly increased pulmonary
VSD and other associated defects. flow does not have significant cyanosis, but usually presents
with signs of heart failure. Although there is some overlap,
Other Physiologic Principles patients with decreased pulmonary flow usually belong to type
I (normally related great arteries) and those with increased
Arterial Desaturation pulmonary blood flow are usually type II (transposition of the
great arteries) and occasionally type Ic.
Because of complete admixture of the systemic, coronary and The magnitude of pulmonary blood flow in an unoperated
pulmonary venous returns in the left atrium and left ventricle, patient is dependent upon the degree of obstruction of
systemic arterial desaturation is always present. The oxygen the pulmonary outflow tract and patency of the ductus
saturation is proportional to the magnitude of the pulmonary arteriosus. The pulmonary outflow obstruction is valvar or
blood flow.43,46 The data from our study patients are plotted in subvalvar in type II patients and valvar, subvalvar or at VSD
Figure 2; the pulmonary to systemic blood flow ratio (Qp : Qs) level in type I patients. In our own experience with several
which represents the pulmonary blood flow has a curvilinear series of tricuspid atresia, we found the obstruction to be
relationship with the arterial oxygen saturation. A Qp : Qs of located most commonly at the VSD level.31-34,37,38 When
1.5 to 2.5 appears to result in an adequate oxygen saturation.46 the VSD is large and non-restrictive and the pulmonary
Further increase in Qp : Qs does not result in better oxygen valve not stenotic, the pulmonary flow is proportional to
saturation, but may subject the left ventricle to larger volume the pulmonary to systemic vascular resistance ratio. When
overloading and, therefore is not advisable.46 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

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
Figure 2: The systemic arterial saturations, left ventricular (LV) or left atrial pressure. But, the entire systemic venous return must
aortic (Ao), are plotted against the pulmonary to systemic blood flow pass through the patent foramen ovale. Therefore, interatrial
ratio (Qp : Qs). Both type I and type II anatomy are included. Note obstruction is anticipated, but very few patients with tricuspid
curvilinear relationship between two parameters. At low Qp : Qs levels,
a slight increase in Qp : Qs produces large increases in systemic atresia have clinically significant obstruction.9 The right-to-
O2 saturation, whereas at higher Qp : Qs further increase does not left shunt occurs in late atrial diastole with augmentation
produce significant increase in O2 saturation. Ideal Qp : Qs appears during atrial systole (‘a’ wave).46,50 A mean interatrial
400 to be between 1.5 and 2.5, giving O2 saturations in low 80s. Aortic pressure difference greater than 5 mm Hg is usually indicative
saturations are marked as solid circles and LV saturations as open
circles. Courtesy: Rao PS: Tricuspid Atresia, p 196. Mount Kisco, NY, of interatrial obstruction. A tall ‘a’ wave in the right atrium is
Futura Publishing Co, 198246 also suggestive interatrial obstruction.
Changing Hemodynamics an occasional infant may present within the 1st week of life.9 28
They are only minimally cyanotic, but manifest symptoms of
With growth and development, several changes may take dyspnea, fatigue, difficulty to feed and marked perspiration.
Tricuspid Atresia
place in patients with tricuspid atresia. Closure of the ductus Recurrent respiratory tract infection and failure to thrive is
arteriosus occurring in early neonatal period may result in another mode of presentation. The majority of these patients
severe hypoxemia. The size of the interatrial communication belong to type IIc, although a small number of patients may
may diminish either in absolute terms or relative to the volume be of type Ic. The association of aortic coarctation with type
of the systemic venous return and cause systemic venous II patients has already been mentioned and coarctation, when
congestion and may require atrial septostomy. The ventricular present, makes them vulnerable to early cardiac failure.
septal defect may close spontaneously,31-39 causing pulmonary Examination reveals tachypnea, tachycardia, decreased
oligemia and hypoxemia in type I patients or subaortic femoral pulses (when associated with aortic coarctation, but
obstruction in type II patients. Such VSD closures occur over without significant-sized patent ductus arteriosus), minimal
a period of months and years. The reader is referred to other cyanosis, prominent neck vein pulsations and hepatomegaly.
publications17,38 for further discussion. Prominent ‘a’ waves in jugular veins and/or presystolic
hepatic pulsations may be observed with associated inter-
CLINICAL FEATURES atrial obstruction. The precordial impulses are increased and
hyperdynamic. The second heart sound may be single or split.
Approximately one-half of the patients with tricuspid atresia A holosystolic murmur of VSD is usually heard at the left
manifest symptoms on the 1st day of life and 80 percent would lower sternal border. An apical mid-diastolic murmur may be
be symptomatic by the end of the 1st month of life.9,51 As heard. Clear-cut signs of congestive cardiac failure are usually
previously mentioned, the magnitude of pulmonary blood flow present.
determines the clinical features. Two modes of presentation
are recognized—those with decreased pulmonary blood flow NON-INVASIVE EVALUATION
and those with increased pulmonary blood flow.
Chest Roentgenogram
Decreased Pulmonary Blood Flow
Roentgenographic picture is, by and large, dependent upon
Infants with pulmonary oligemia present with symptoms of the total pulmonary blood flow. In patients with diminished
cyanosis within the first few days of life; more severe the pulmonary flow (the majority of infants will fall into this
pulmonary oligemia, the earlier is the clinical presentation. category), the heart size is either normal or minimally
These hypoxemic infants may have hyperpnea and acidosis enlarged, whereas in those with increased pulmonary blood
if the pulmonary blood flow is markedly decreased. The flow, the heart size is moderately to severely enlarged. Several
majority of these infants belong to type Ib. Patients with patterns of cardiac configuration, namely ‘characteristic’
pulmonary atresia (Subgroup a) irrespective of the type will tricuspid atresia appearance,52 coeur en sabot configuration,53
also present with early cyanosis, especially when the ductus ‘egg-shaped’,19 ‘bell-shaped’,54 and square11 heart have been
begins to close. Hypoxic spells are not common in the neonate described, but in the author’s experience and that of others,19
although the spells can occur later in infancy. there is no consistent pattern that would be diagnostic of
Physical examination reveals central cyanosis, tachypnea tricuspid atresia. There may be concavity in the region
or hyperpnea, normal pulses, prominent ‘a’ wave in the jugular of pulmonary artery segment in patients with pulmonary
venous pulse (if there is significant interatrial obstruction), oligemia and small pulmonary artery. The right atrial shadow
and no hepatic enlargement (presystolic hepatic pulsations may be prominent.
may be felt if there is severe interatrial obstruction). Quiet Right aortic arch may be present in approximately 8
precordium and absence of thrills is usual. The second heart percent of patients with tricuspid atresia19 and is less common
sound is usually single. A holosystolic murmur, suggestive of than that observed in patients with tetralogy of Fallot (25%)
VSD may be heard at the left lower or left midsternal borders. and truncus arteriosus (40%). An unusual contour of the left
No diastolic murmurs are heard. In patients with associated border of the heart suggestive of 1-transposition may be
pulmonary atresia, no murmurs are usually heard, although in seen in association with type III, subtypes 1 and 5 tricuspid
an occasional patient, a continuous murmur of patent ductus atresia.55
arteriosus may be heard. Clinical signs of congestive heart The greatest use of the chest roentgenogram is its ability
failure are notably absent. to categorize babies into those with decreased pulmonary
vascular markings and into those with increased pulmonary
Increased Pulmonary Blood Flow vascular markings. Often, this is all that is necessary to make
a correct diagnosis once a history, physical examination
Infants with pulmonary plethora usually present with signs and electrocardiogram (see the next section) have been 401
of heart failure within the first few weeks of life, although obtained.55
6 Electrocardiogram pattern.58 Normal (0-+90°) or right axis deviation is present
in a minority of patients and most of these patients belong to
The electrocardiogram (ECG) can be virtually diagnostic type II or III anatomy. It has been suggested that the ASV may
of tricuspid atresia in a patient suspected to have a cyanotic be related to destructive lesions in the left anterior bundle,56
congenital heart defect. Right atrial hypertrophy, an abnormal, fibrosis of left bundle branch,59 abnormal distribution of the
superiorly oriented major QRS vector (so called left axis conduction system (unusually long right bundle branch and
deviation) in the frontal plane, left ventricular hypertrophy origin of left bundle branch very close to the nodal-His bundle
and diminished right ventricular forces (Figure 3) are junction),60-62 a small right ventricle or a large left ventricle.57
characteristic findings. Ventricular activation data from our group58,63 suggested that
The right atrial hypertrophy, manifested by tall, peaked this characteristic QRS pattern in tricuspid atresia is produced
P waves in excess of 2.5 mm, is present in the majority of by interaction of several factors, the most important being
the patients with tricuspid atresia.56 Although it has been the right-to-left ventricular disproportion and asymmetric
suggested that the amplitude of P wave in lead II is directly distribution of the left ventricular mass favoring the superior
proportional to the interatrial pressure difference and inversely wall.
proportional to the size of the interatrial communication, Regardless of the frontal plane mean QRS vector
detailed analysis of these parameters did not suggest a orientation, electrocardiographic criteria for left ventricular
consistent relationship.9,57 A double peak, spike and dome hypertrophy are present in the vast majority of patients. This
configuration of the P wave, referred to as ‘P-tricuspidale’56 may be manifested by increased (above 95th percentile) S
may be present. The first taller peak is contributed by the right waves in right chest leads and R waves in left chest leads or by
atrial depolarization and the second smaller peak is presumed ‘adult progression’ of the QRS in the chest leads in the neonates
to be due to left atrial depoloarization.56,58 and infants. ST-T wave changes suggestive of left ventricular
Abnormal, superiorly oriented major QRS vector (ASV), strain is present in 50 percent of patients.58 The reason for left
more popularly called left axis deviation, between 0 to –90° in ventricular hypertrophy is the anatomic nature of the lesion
the frontal plane is present in the majority of the patients with with the resultant hemodynamics as well as lack of opposition
tricuspid atresia. ASV is present in excess of 80 percent of of the forces of left ventricular activation by the hypoplastic
patients with type I anatomy (normally related great arteries) right ventricle. Occasionally, biventricular hypertrophy may
while only less than 50 percent of patients with type II and be present and majority of these patients belong to type II or
type III anatomy show such a typical electrocardiographic III anatomy with good-sized right ventricle.
402
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
Diminished R waves in right chest leads and S waves in be identified as pulmonary or aortic by following the great 28
left chest are related to right ventricular hypoplasia. vessel until the bifurcation of the pulmonary artery or arch
Vectorcardiographic features closely resemble the scalar of the aorta is seen; this will help to decide, whether there
Tricuspid Atresia
electrocardiogram, but vectorcardiography is no longer is associated transposition of the great arteries. Suprasternal
available for routine use. notch imaging will be of use in demonstrating coarctation of
the aorta, which is often seen in type II patients.
Echocardiogram Contrast echocardiography with two-dimensional imaging
will clearly demonstrate sequential opacification of the right
M-mode echocardiographic features include a large left atrium, left atrium, left ventricle and then the right ventricle.
atrium (usually proportional to the magnitude of pulmonary However, contrast study is neither necessary nor recommended
blood flow), dilated left ventricle with normal to decreased for making the diagnosis.
left ventricular shortening fraction, a large posterior Doppler examination is also useful in the evaluation of
atrioventricular valve in continuity with posterior semilunar tricuspid atresia patients. The obligatory right-to-left shunt
valve and a small right ventricle.55,64 The pulmonary valve may across the atrial septal defect can be demonstrated by placing
or may not be recorded. The tricuspid valve is conspicuously pulsed Doppler sample volume on either side of the atrial
absent.55 Tricuspid valve-like echoes of low amplitude may septum and by color flow Doppler. Left-to-right shunting
be recorded occasionally and this should not exclude the across the VSD may also be demonstrated by Doppler. In
diagnosis of tricuspid atresia.65 type I (normally related great arteries) patients, the VSD
Two-dimensional echocardiography, apart from showing peak Doppler velocity is helpful in estimating the size of the
enlarged right atrium, left atrium and left ventricle and a small VSD; the higher the velocity, the smaller is the VSD. Right
right ventricle demonstrates the atretic tricuspid valve directly. ventricular and pulmonary arterial pressure may also be
In the most common muscular type, a dense band of echoes estimated using modified Bernoulli equation:
is seen at the site, where tricuspid valve should be55,66 and RV/PA systolic pressure = systolic BP – 4V2
the anterior leaflet of the detectable atrioventricular valve is where, RV is right ventricle, PA is pulmonary artery, BP is arm
attached to the left side of interatrial septum (Figure 4). Apical systolic blood pressure and V is VSD peak Doppler velocity.
and subcostal four-chambered views are best to demonstrate In the presence of pulmonary hypertension or severe
the anatomy. infundibular or valvar pulmonary stenosis, the above VSD
Atrial and ventricular septal defects can also be Doppler velocities are not indicative of the size of the VSD. In
demonstrated by 2D echocardiography. Semilunar valves can 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.
Other Laboratory Studies

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
Figure 4: Apical four-chambered two-dimensional echocardiographic because the echo is good enough to define most of the issues
view of a baby with tricuspid atresia showing enlarged left ventricle related to tricuspid atresia. Occasionally, these studies may
(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; be indicated to define the pulmonary artery or aortic arch
MV = Mitral valve; RA = Right atrium anatomy, especially in older patients with poor echo windows. 403
6 Cardiac Catheterization 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
The diagnosis of tricuspid atresia based on clinical, saturations in 29 of 50 (58%) catheterizations in which the data
electrocardiographic and echocardiographic features is were adequate.50 However, in the shunt group, the left atrial ‘v’
relatively simple and cardiac catheterization and selective waves were equal to or higher than the right atrial ‘v’ waves
cineangiography, rarely, if ever, are essential for establishing accounting for the left-to-right atrial shunting. Simultaneous
the diagnosis.46 Even neonates with significant arterial pressure recordings from the left atrium and the right atrium
desaturation need not undergo cardiac catheterization and with isosensitized miniature pressure transducers mounted 5
selective cineangiography; the diagnosis of tricuspid atresia cm apart, revealed a higher pressure in the left atrium than
is usually made on the basis of clinical and non-invasive in the right atrium during atrial diastole (Figure 5). Based on
evaluation, particularly echo-Doppler studies. Catheterization findings of that study,50 it was concluded that:
may be indicated prior to bidirectional Glenn or Fontan 1. left-to-right shunt across the atrial septal defect occurs
operations. If catheterization is performed, the following frequently in tricuspid atresia
features may be found. 2. The left-to-right shunt is a result of instantaneous pressure
difference between atria and such shunts are ‘physiologic’.
Catheter Course The pulmonary venous saturations are usually in the normal
range. A significant decrease in left atrial saturation is expected
Because of atretic tricuspid valve, the right ventricle cannot because of obligatory right-to-left shunting across the patent
be directly catheterized from the right atrium. The catheter foramen ovale. Falsely high or falsely low saturations may
can easily be maneuvered into the left atrium across the patent be measured in the left atrium because of streaming. The left
foramen ovale. The catheter may follow a similar course in ventricular saturations are usually well mixed and are more
patients with pulmonary atresia (or severe stenosis) with reliable. The saturations in the left atrium and left ventricle as
intact ventricular septum and hypoplastic right ventricle or well as those in the right ventricle, the pulmonary artery and
severe tricuspid stenosis. Inability to enter the right ventricle the aorta are identical. Systemic arterial desaturation is always
from the right atrium is not necessarily diagnostic of tricuspid present and the extent of desaturation is proportional to the
atresia, but in experienced hands, it is highly suggestive of Qp : Qs (Figure 2).46
tricuspid atresia. The vena caval, left atrial, left ventricular and aortic
From the left atrium, the catheter can easily be manipulated oxygen saturations are usually lower in type I patients than
into the left ventricle. With the previous conventional those in type II patients.46 This is presumably related to greater
catheters, the left ventricle is the farthest structure that could preponderance of pulmonary oligemia in type I patients.
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.
Oxygen Saturations
Systemic venous oxygen saturations are usually diminished
Figure 5: Simultaneous pressures from the left atrium (LA) and right
and the extent of decrease is related to systemic arterial atrium (RA) are recorded by means of high fidelity miniature pressure
desaturation and the severity of congestive heart failure. transducers mounted on a catheter 5 cm apart. Note higher RA
Because of the obligatory right-to-left shunting across pressure during atrial systole and higher LA pressure during atrial
diastole; the later finding may help explain the “physiologic” left-to-
the patent foramen ovale, it is generally believed that the
right shunting at atrial level in tricuspid atresia patients. Courtesy: Rao
right atrial saturations are similar to vena caval saturations. PS: Br Heart J 1983;49:345.50 a = ‘a’ wave; ECG = Electrocardiogram;
404 However, we found left-to-right atrial shunting, represented v = ‘v’ wave
Pressures 28
The right atrial mean pressure is minimally elevated. In the
Tricuspid Atresia
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 Figure 6: Selected frame from a posteroanterior view of a right atrial
systemic level in type II patients. Systolic pressure gradient (RA) angiogram in a child with tricuspid atresia showing successive
across the VSD may be seen if it is restrictive. Pulmonary opacification of the left atrium (LA) and left ventricle (LV). There was no
direct and immediate opacification of the right ventricle; the negative
artery pressure may be normal or increased depending upon shadow, so called right ventricular window is shown with an arrow
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 ventricular window (Figure 6) seen in earlier frames of right
the coarctation may be present. atrial angiography is due to failure of direct right ventricular
filling, but the right ventricle is seen subsequent to left
Calculated Variables ventricular opacification. Although this area can be profiled
well in the elongated right anterior oblique and the four-
Systemic and pulmonary blood flows and resistances and chamber views,71 posteroanterior view is most commonly
shunts can be calculated by the Fick principle either by used to demonstrate these signs and is perhaps far superior.19
measuring oxygen consumption or by assuming it from tables The above described signs were initially thought to
of normal values.46 The principles and methods of calculation be pathagnomonic of tricuspid atresia, but it is now well-
have been detailed elsewhere46 and will not be discussed here. recognized that such appearance can be seen in patients with
Although most of the calculations can be performed, Qp : Qs is pulmonary atresia or severe stenosis with intact ventricular
the most useful calculated value. The Qp : Qs is diminished in septum and large right-to-left shunting at atrial level, tetralogy
type I hypoxemic infants with small or no VSD. It is markedly of Fallot with atrial septal defects (the so called pentology of
increased in type I patients with moderate to large VSDs and Fallot) and total anomalous pulmonary venous return to the
in most patients with type II anatomy. coronary sinus.19,71
Other calculated variables such as pulmonary vascular Although the right atrial angiography is helpful in the
resistance,46 preoperative catheterization index68 and trans- diagnosis, selective left ventricular angiography (Figure 7)
pulmonary gradient (pulmonary artery mean pressure—left should also be performed in order to delineate the anatomy
atrial mean pressure) are useful measures in the pre-Fontan and size of the left and right ventricles, size and type of
evaluation. ventricular septal defects(s), relationship of great arteries and
the source of pulmonary blood flow. Frontal and lateral views
Cineangiography of the ventriculogram are most commonly used although left
anterior oblique view, long axial oblique view or a four-
Since the initial description by Campbell and Hills69 and chambered view may help delineate desired anatomic detail.
Cooley et al,70 two signs, namely, ‘typical sequence of In most neonates, selective right atrial and left ventricular
tricuspid atresia’ and ‘right ventricular window’, on right angiograms are all that will be necessary. Selective
atrial angiography have been very helpful in the diagnosis of antegrade or retrograde aortography to demonstrate either
tricuspid atresia. Selective right atrial or superior vena caval the pulmonary arterial anatomy or aortic coarctation may
angiogram reveals successive opacification of the left atrium occasionally be needed. For additional discussion on
and left ventricle without immediate opacification of the right angiography in tricuspid atresia, the reader is referred to
ventricle (Figure 6). The negative shadow, so called right other publications.18,71 405
6 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 µg per kilogram of body weight per minute. I usually
begin with a dose of 0.05 µg/kg/min and reduce the rate of
infusion, provided the desired oxygen saturation levels are
Figure 7: Selective left ventricular (LV) cineangiogram in left anterior achieved; this has been most helpful in reducing the incidence
oblique view demonstrating the relative position of the aorta (Ao) and
pulmonary artery (PA). The ventricular septal defect (VSD) is also
and severity of some of the drug’s bothersome side effects,
clearly seen. RV = Right ventricle 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
MANAGEMENT heart failure (more common in type II patients) should be
treated with routine anticongestive measures.79 Patients with
Physiologically ‘corrective’ surgery for tricuspid atresia72,73 associated severe coarctation of the aorta may also be helped
and their modifications74-76 have improved the prognosis of with PGE1 infusion; this time the ductal dilation improves
patients with tricuspid atresia. Such physiologic correction systemic perfusion. This should be followed by surgical relief
is usually performed in patients older than 2 years. As stated of coarctation. Alternatively, balloon angioplasty may be
previously, most tricuspid atresia patients manifest symptoms utilized to relieve the aortic obstruction.80-82
in the neonatal period and should be effectively palliated to
enable them to reach the age at which surgical correction could Palliative Treatment of Specific Physiologic
be undertaken. The objective of any management plan, apart Abnormalities
from providing symptomatic relief and increased survival rate,
should be to preserve, protect and restore anatomy (good-sized The palliation of patients with tricuspid atresia would largely
and undistorted pulmonary arteries) and physiology (normal depend upon the hemodynamic abnormality produced by the
pulmonary artery pressure and preserved left ventricular basic lesion and associated cardiac defects. These may be
function) to normal such that a ‘corrective’ procedure could be broadly grouped42,79 into:
performed at an appropriate age. Keeping the above objective 1. Decreased pulmonary blood flow
in mind the management plan may be discussed under the 2. Increased pulmonary blood flow
following headings: 3. Intracardiac obstruction.
1. Medical management at the time of initial presentation
2. Palliative treatment of specific physiologic abnormalities Decreased Pulmonary Blood Flow
3. Medical management following palliative surgery
4. Historical aspects of physiologically ‘corrective’ surgery Since, the description of subclavian artery-to-ipsilateral
5. Physiologically ‘corrective’ surgery pulmonary artery anastomosis in 1945 by Blalock and
6. Follow-up after corrective operation. Taussig,83 several other types of operations have been devised
to improve the pulmonary aorta flow. These include other
Medical Management at the Time of Initial Presentation types of systemic-pulmonary artery shunts; namely, the
Potts anastomosis (descending aorta-to-left pulmonary artery
The need for prompt identification and rapid transfer of a shunt), Waterston-Cooley shunt (ascending aorta-to-right
cyanotic/distressed neonate with suspected serious heart disease pulmonary artery anastomosis) and aorta-to-pulmonary artery
406 to a regional pediatric cardiology center is well-recognized. Gore-Tex shunt; superior vena cava-to-right pulmonary artery
anastomosis (Glenn Procedure); formalin infiltration of the in pulmonary blood flow. Therefore, it is recommended that 28
ductal wall; stenting the ductus arteriosus and enlarging the pulmonary artery banding not be performed in this group of
VSD. Systemic-pulmonary artery shunts are most commonly patients. Among our 40 consecutive patients with tricuspid
Tricuspid Atresia
used in the palliation of pulmonary oligemia. Because of the atresia,38,42 only two with type I anatomy required pulmonary
problems associated with central shunts, Blalock-Taussig artery banding and there are only a few cases reported in the
type of shunt is preferred. At present, a modified Blalock- literature that required pulmonary artery banding. If optimal
Taussig shunt with a Gore-Tex graft interposed between anticongestive therapy with some time delay does not produce
the subclavian artery and the ipsilateral pulmonary artery, adequate relief of symptoms,42 pulmonary artery banding
described by deLeval84 appears to be the preferred choice in should be considered in type I patients; perhaps a serious
most institutions for palliation of the neonate and young infant consideration for using absorbable band material should be
with pulmonary oligemia. given.89-91 In those that did not have pulmonary artery banding
Enlargement of VSD and/or resection of right performed, careful follow-up studies with measurement
ventricular outflow tract obstruction has been performed, of pulmonary artery pressure and appropriate treatment are
and recommended by Annecchino and his colleagues85 as necessary to prevent pulmonary vascular obstructive disease.
a palliative procedure to augment the pulmonary blood In type II patients, banding of the pulmonary artery should
flow. This is an ingenious approach and attacks the site of be performed once the infant is stabilized with anticongestive
obstruction rather than bypassing it. However, it is an open therapy. If there is associated coarctation of the aorta or aortic
heart procedure and may not be feasible or necessary in the arch interruption or hypoplasia, adequate relief of the aortic
neonatal period.42 Placement of a stent in the ductus, to keep obstruction should be provided concurrent with pulmonary
it open to provide pulmonary flow is an attractive option,86,87 artery banding and the patent ductus arteriosus should be
but, because of limited experience and technically demanding ligated, if present. The importance of PGE1 administration
nature of the procedure, it currently is not a therapeutic in temporarily relieving aortic obstruction and thereby
procedure of choice. If the predominant obstruction is at the controling congestive heart failure has already been alluded.
pulmonary valve level, balloon pulmonary valvuloplasty88 The role of balloon dilation angioplasty of the coarctation80-82
may be considered. in these complicated lesions has not yet been completely
In conclusion, despite the availability of many types of delineated. Because of higher risk for poor outcome in patients
palliative procedures to increase pulmonary blood flow, most with transposition and those requiring pulmonary artery
of them are either not advisable or effective and if effective, banding and/or aortic arch repair, early, adequate appropriate
may produce serious complications to deter from performing a intervention is desirable.
successful Fontan-Kreutzer procedure subsequently. Modified
Blalock-Taussig anastomosis84 has the least number of long- Intracardiac Obstruction
term complications, but at the same time, preserves suitable
anatomy for subsequent corrective procedures. Therefore, it Intracardiac obstruction can occur at two different levels,
is recommended as the procedure of choice for palliation of namely, patent foramen ovale and VSD.
tricuspid atresia patients with decreased pulmonary blood flow. Interatrial obstruction: Since the entire systemic venous
return must egress through the patent foramen ovale, it should
Increased Pulmonary Blood Flow be of adequate size to accommodate it. A mean atrial pressure
difference of 5 mm Hg or more with very prominent ‘a’ waves
Infants with a modest increase in pulmonary blood flow do (15 to 20 mm Hg) in the right atrium is generally considered
not have any significant symptomatology and indeed are less to represent obstructed interatrial septum.9,46 Balloon atrial
cyanotic than the pulmonary oligemic patients. Markedly septostomy,92,93 if unsuccessful blade atrial septostomy,93-95
increased pulmonary blood flow, however, can produce and rarely surgical atrial septostomy may be necessary to
congestive heart failure. Only type Ic and Type IIc patients, relieve the obstruction. Significant interatrial obstruction
i.e. without associated pulmonary stenosis, will fall into the requiring atrial septostomy in the neonate is rare and unusual
category of pulmonary plethora. A majority of these patients although this can be a significant problem later in infancy.42,92
will have type II anatomy and will usually manifest during Interventricular obstruction: Spontaneous closure of the
early infancy. VSD causing severe pulmonary oligemia in type I patients
In type I patients, aggressive anticongestive measures and subaortic obstruction in type II patients can occur;31-39
should be promptly instituted. The natural history of the this usually takes months to years to develop. Management
VSD has been well documented in this group;31-38 the VSD of spontaneous closure of the VSD causing severe pulmonary
becomes smaller and patients with pulmonary plethora will, in oligemia in type I patients is as alluded to in the preceding
due course, develop pulmonary oligemia, requiring palliative section on pulmonary oligemia. Partial spontaneous closure of
surgical shunts. These patients can also develop right the VSD in type II patients causes subaortic obstruction,33,34,38
ventricular outflow tract obstruction with resultant decrease which should be relieved or bypassed lest the resultant left 407
6 ventricular hypertrophy pose increased risk at the time of cavopulmonary diversion,74 bidirectional Glenn,99 intra-atrial
the Fontan procedure.96 The obstruction must be tackled at tunnel74 and extracardiac conduit100 to divert the inferior vena
the time of either a bidirectional Glenn or a modified Fontan caval blood into the pulmonary artery, staged Fontan101,102
operation. Resection of the conal muscular septum,97,98 thus and fenestrated Fontan.103-105
enlarging the VSD, is a direct approach, although concern
for development of heart block and spontaneous closure of Physiologically Corrective Surgery
the surgically produced VSD remains.38 Alternatively, the
VSD, right ventricle and aortic valve may be bypassed by Operations that divide the pulmonary and systemic venous
anastomosis of the proximal stump of the divided pulmonary returns (Fontan-Kreutzer) are feasible for most patients
artery to the ascending aorta (Damus-Kaye-Stansel) at the with tricuspid atresia. Hydrodynamic studies by de Leval
time of bidirectional Glenn (or Fontan) operation. For further and colleagues74 concluded that the right atrium has no
discussion of this subject, the reader is referred elsewhere.33,34,38 efficient pump function; pulsations in non-valved circulation
generate turbulence with consequent decrease in net flow and
Medical Management Following Palliative Surgery energy losses occur in the non-pulsatile chambers, corners
and obstructions. To address this issue, they proposed total
Problems encountered with tricuspid atresia patients are similar cavopulmonary anastomosis. The advantages of this procedure
to those found in other types of cyanotic cardiac malformations. are technical simplicity, maintenance of low right atrial and
Appropriate monitoring for and treatment of relative anemia, coronary sinus pressure and reduction in risk of formation of
polycythemia, coagulopathy and hyperuricemia should be atrial thrombi and perhaps reduction in arrhythmias.
undertaken. The risks for development of a cerebrovascular In the bidirectional Glenn procedure, the upper end of the
accident or brain abscess are similar to those seen with divided superior vena cava is anastomosed end to side to the
other cyanotic anomalies. Antibiotic prophylaxis before any superior aspect of the undivided right pulmonary artery, thus
bacteremia producing procedures or surgery is indicated, as diverting the superior vena caval blood into both right and
is routine immunization plus consideration for Palivizumab left pulmonary arteries. Hemodynamic advantages associated
(for prevention of RSV infection in infancy), polyvalent with the bidirectional Glenn include, improved effective
pneumococcal vaccine or influenza vaccine. pulmonary flow, reduced total pulmonary flow and less left
ventricular volume overloading.
Historical Aspects of Corrective Surgery Staging the Fontan appears to decrease overall mortality,
for Tricuspid Atresia presumably related to improving the ventricular function
by correcting afterload mismatch associated with one stage
Fontan72 and Kreutzer73 concurrently described physiologi Fontan. At the present time, staged Fontan with bidirectional
cally corrective operations for tricuspid atresia in 1971. Glenn initially followed later by extracardiac conduit
Fontan operation, as described by Fontan consisted of diversion of the inferior vena caval blood into the pulmonary
superior vena cava—right pulmonary artery shunt (classical artery appears to be the preferred approach.
Glenn), anastomosis of the proximal end of the divided right As mentioned, currently preferred ‘corrective’ procedure
pulmonary artery to the right atrium directly or by means of is staged total cavopulmonary anastomosis. A bidirectional
an aortic homograft, closure of the atrial defect, insertion of a Glenn procedure (superior vena cava to pulmonary artery
pulmonary valve homograft into the inferior vena caval orifice anastomosis) may be performed around the age of 6 months.
and ligation of the main pulmonary artery, thus bypassing Preoperative catheter evaluation to define the pulmonary
the right ventricle completely;72 it would appear that Fontan artery pressure and anatomy and to exclude a persistent left
concept was to use the right atrium as a pump. Kreutzer’s superior vena cava (because it may divert blood away from
operation consisted of direct anastomosis of the right atrial the pulmonary arteries) prior to bidirectional Glenn surgery
appendage with the pulmonary artery or through a pulmonary should be undertaken. At the time of bidirectional Glenn
homograft and closure of the atrial septal defect.73 He did not procedure, stenoses, if any of the pulmonary artery should
perform a Glenn procedure nor insert a prosthetic valve into be repaired. Issues related to subaortic obstruction and mitral
the inferior vena cava. It appears that Kreutzer’s concept was valve regurgitation should also be addressed.
that the right atrium may not function as a pump and that the When the patient reaches the age and size (approximately
left ventricle is the only ‘suction’ pump in the system. Many 15 kg) suitable for Fontan-Kreutzer operation, diversion of
modifications of these procedures have been suggested, as inferior vena caval blood into the pulmonary artery either
reviewed elsewhere by us.75,76 Based on these reviews it by a lateral tunnel or extracardiac conduit is recommended.
would appear that direct atriopulmonary anastomosis (without At the present time extracardiac conduit diversion of inferior
a valved conduit) became the standard procedure for most vena caval blood into the pulmonary artery is preferred by
tricuspid atresia patients. Over a period of time, a number most surgeons. Immediately prior to Fontan conversion,
408 of other concepts/procedures evolved and these include total cardiac catheterization should be undertaken to ensure normal
anatomy and pressure of the pulmonary artery as well as be treated with appropriate pharmacologic therapy. In a 28
normal left ventricular end-diastolic pressure. At the same patient without adequate control, electrophysiologic study and
time, aortopulmonary collaterals should be evaluated by surgical or transcatheter ablation may be needed.108 Revision
Tricuspid Atresia
means of selective subclavian artery and descending thoracic of the Fontan pathway to a cavopulmonary connection with
aortic angiography. If collateral vessels are present, they elimination of the enlarged right atrium has been considered
should be occluded with coils or devices, as appropriate. an alternative solution. Sick sinus node syndrome and
The criteria outlined by Choussat and associates106 have atrioventricular block occur in some children and may require
been modified or exceeded by many groups of workers. pacemaker therapy. Ventricular arrhythmia is less frequent.
These factors, when present, would make the Fontan-Kreutzer Symptoms and signs indicative of obstruction to Fontan
operation a high-risk procedure and should be identified at pathways should be promptly investigated. Poor echo windows
the time of preoperative evaluation. They include elevated make non-invasive evaluation difficult and cineangiography
pulmonary artery pressure (mean pressure >18 mm Hg) or or imaging studies (CT or MRI) may become necessary.
resistance (> 4 Wood units/m2), distorted or small (McGoon Obstructive lesions should be treated with balloon angioplasty,
ratio of 1.8 or less) pulmonary arteries, poor left ventricular stenting or even surgery, as necessary.
function (end-diastolic pressure above 12 mm Hg), significant A persistent shunt may be due to intentional fenestration
mitral regurgitation, subaortic obstruction and severe left created at the time of Fontan or a residual atrial septal
ventricular hypertrophy. With one or more of these risk factors, defect. If significant hypoxemia is present, the residual shunt
physiologically corrective procedures of the Fontan type may should be closed, preferably by a transcatheter device.109,110
carry significant risk. In such high-risk Fontan-Kreutzer patients, Test occlusion109 of the defect to ensure that adequate
leaving open a small atrial septal defect to allow decompression cardiac output will be maintained after defect occlusion is
of the right atrium in the immediate postoperative period with a recommended. Closing the defect has beneficial effect in
plan to close the defect later has been proposed.103-105 The atrial preventing paradoxical embolism and stroke.
defect is closed by a preplaced suture103,104 or by transcatheter Recurrent pleural effusion, liver dysfunction and protein-
techniques.105 Significant improvement in postoperative pleural losing enteropathy have occurred in a small number of
effusions, systemic venous congestion and higher cardiac index patients. Protein-losing enteropathy carries a high (75%)
and possibly shorter hospitalization have been the beneficial mortality.110,111 The cause of protein-losing enteropathy is not
effects of the fenestration, but at the expense of systemic arterial well-understood, but appears to be related to loss of protein
hypoxemia. However, some surgeons prefer fenestration for all in the bowel by lymphatic distention secondary to increased
patients. Six to twelve months later, transcatheter closure of systemic venous pressure, although this can occur in patients
the fenestration may be undertaken if the fenestration did not with reasonably ‘normal’ pressures for the Fontan procedure.
spontaneously close. Symptoms usually appear 6 months following the Fontan-
In patients with transposition of the great arteries, early Kreutzer procedure or later. They manifest diarrhea, edema,
pulmonary artery banding, treatment of aortic coarctation, ascites and pleural effusion. Serum hypoalbuminemia and
and relieving or bypassing subaortic obstruction should also increased α1-antitrypsin in the stool are present. One should
be incorporated into the treatment plan. carefully scrutinize for evidence of obstruction in the Fontan-
Kreutzer pathway. If such is found it should be relieved.112
Follow-up after Corrective Operation Supportive therapy with medium-chain triglyceride diet
and parenteral albumin supplementation may be instituted.
Close follow-up after correction is indicated. Some patients A number of treatment regimens including prednisone,
may need inotropic and diuretic therapy. Afterload reduction regular high-molecular-weight heparin, low-molecular-weight
with an angiotensin-converting enzyme inhibitor is used by heparin, elementary diet, calcium replacement, somatostatin,
some cardiologists to improve left ventricular output. Because high-dose spironolactone, sildenafil and resection of localized
of the potential for development of thrombi in the right atrium, intestinal lymphangectasia (if demonstrated) have been
anticoagulants are routinely used by most cardiologists. attempted, all with variable success.112 Since protein-losing
I recommend platelet-inhibiting doses of Aspirin, others enteropathy appears to be a fatal complication of the Fontan
advocate Warfarin anticoagulation. procedure, aggressive management is suggested. Apart from
Most patients do well after operation.107 However, some excluding and addressing obstructions and residual shunts in
problems have been seen after corrective surgery namely, the Fontan circuit plus other conventional treatment options,
arrhythmia, obstructed pulmonary outflow pathways, consideration for:
persistent shunts and systemic venous congestion including 1. Reduction of right atrial pressure by creation of an atrial
protein-losing enteropathy. septal defect (Brockenbrough puncture plus static dilation
Supraventricular arrhythmias (atrial flutter or fibrillation, of the atrial septum)
paroxysmal supraventricular tachycardia) may be seen, 2. Right atrial and left ventricular (atrioventricular sequential)
particularly with older types of Fontan operation. They may pacing,113,114 409
6 3. Conversion of atrioventricular Fontan to total 4. Rao PS. Terminology: is tricuspid atresia the correct term to
cavopulmonary anastomosis,115,116 and/or use? In: Rao PS (Ed). Tricuspid Atresia, 2nd edition, Mount
4. Cardiac transplantation117,118 should be given. However, Kisco, NY, Futura Publishing Co. 1992.p.3.
most patients do well after the Fontan-Kreutzer procedure. 5. Rashkind WJ. Tricuspid atresia: A historical review. Pediat
Cardiol. 1982;2:85.
6. Kreyseg FL. Die Krankheiten des Herzens. Dritte Thies. 181.p.
PROGNOSIS 104.
7. Editors: London Medical Review 1812;5:262.
Untreated the prognosis of live born infants with tricuspid 8. Rao PS. Demographic features of tricuspid atresia. In: Rao PS
atresia is poor; only 10 to 20 percent may survive their first (Ed). Tricuspid Atresia, 2nd edition, Mount Kisco, NY, Futura
birthday.9,119 Palliative surgery to normalize the pulmonary Publishing Co. 1992.p.23.
blood flow has markedly improved the survival rate. But, as 9. Dick M, Fyler DC, Nadas AS. Tricuspid atresia: clinical course
one can see from survival data from several large studies,51,120 in 101 patients. Am J Cardiol. 1975;36:327.
there is still considerable early mortality. Because of recent 10. Van Praagh R, Ando M, Dungan WT. Anatomic types of
improvement in surgical mortality for the palliative surgery and tricuspid atresia: clinical and developmental implications
(abstract). Circulation. 1971;44:115.
advances in neonatal care, the initial mortality should decrease.
11. Astley R, Oldham JS, Parson C. Congenital tricuspid atresia. Br
Introduction of physiologically ‘corrective’ surgery in the Heart J. 1953;15:287.
early 1970s has, to some degree, improved the second bout of 12. Kühne M. Über zwei falle kongenitaler atreside des ostium
mortality seen in children beyond 15 years of age. Because of venosum dextrum. Jahrb Kinderh. 1906;63:235.
this improved prognosis, each neonate with tricuspid atresia 13. Edwards JE, Burchell HB. Congenital tricuspid atresia: a
should be offered aggressive medical and surgical therapy.121 classification. Med Clin North Am. 1949;33:1117.
14. Keith JD, Rowe RD, Vlad P. Tricuspid atresia. In: Heart Disease
in Infancy and Childhood, New York: Macmillian. 1958.p.434.
CONCLUSION
15. Rao PS. Classification of tricuspid atresia. In: Rao PS (Ed).
Tricuspid Atresia, 2nd edition, Mount Kisco, NY, Futura
Tricuspid atresia is the third most common cyanotic
Publishing Co. 1992.p.59.
congenital heart defect. There are significant variations in 16. Van Praagh R. Discussion after paper by Vlad P: Pulmonary
the morphology of the atretic tricuspid valve, the associated atresia with intact ventricular septum. In: Barrett-Boyes BG,
cardiac defects and physiology, resulting in different clinical Neutze JM, Harris EA (Eds). Heart Disease in Infancy: Diagnosis
presentations. The diagnosis is relatively simple and can often and Surgical Treatment, London: Churchill Livingstone,
be made on clinical features and simple laboratory studies 1973.p.236.
(chest roentgenogram and electrocardiogram), which can be 17. Rao PS. Tricuspid atresia: anatomy, imaging, and natural history.
confirmed by echocardiography and if necessary by cardiac In: Freedom RM (Ed). Congenital Heart Disease. In: Braunwald
catheterization and selective cineangiography. Aggressive E (Ed): Atlas of Heart Diseases: Philadelphia, Current Medicine.
1997;12:141.
management to normalize the pulmonary blood flow and
18. Keith JD, Rowe RD, Vlad P. Tricuspid atresia, In: Heart Disease
correct physiologically important associated defects (e.g. in Infancy and Childhood, 2nd edition, New York: Macmillian,
coarctation of the aorta) should be undertaken at the time of 1966.p.664.
presentation. Follow-up and treatment plans should strive 19. Vlad P. Tricuspid atresia. In: Keith JD, Rowe RD, Vlad P (Eds).
to maintain or normalize cardiac structures and function Heart Disease in Infancy and Childhood, 3rd edition, New York:
(pulmonary artery anatomy and pressure and left ventricular Macmillian. 1977.p.518.
function). Finally, performing staged Fontan-Kreutzer surgery 20. Rao PS. Classification of tricuspid atresia. In: Rao PS (Ed).
prior to deterioration of the left ventricular function should Tricuspid Atresia, Mount Kisco, NY, Futura Publishing Co.
markedly improve the prognosis for tricuspid atresia patients. 1982.p.41.
21. Van Praagh R. Terminology of congenital heart disease: glossary
and commentary. Circulation. 1977;56:139.
He is the best physician who is the most ingenious inspirer 22. Weinberg PM. Pathologic anatomy of tricuspid atresia. In: Rao
of hope. PS (Ed). Tricuspid Atresia, Mount Kisco, NY, Futura Publishing
—Samuel Taylor Coleridge Co. 1982.p.49.
23. Rao PS, Levy JM, Nikiciz E, et al. Tricuspid atresia: association
REFERENCES with persistent truncus arteriosus. Am Heart J. 1991;122:829.
24. Bharati S, McAllister HA Jr, et al. Anatomic variations in
1. Rao PS. A unified classification for tricuspid atresia. Am Heart J. underdeveloped right ventricle related to tricuspid atresia and
1980;99:799. stenosis. J Thorac Cardiovasc Surg. 1976;72:383.
2. Rao PS. Terminology: tricuspid atresia or univentricular heart? 25. Ando M, Santomi G, Takao A. Atresia of tricuspid and mitral
In: Rao PS (Ed). Tricuspid Atresia, Mount Kisco, NY, Futura orifice: anatomic spectrum and morphogenetic hypothesis. In:
Publishing Co, 1982.p.3. Van Praagh R, Takao A (Eds). Etiology and Morphogenesis of
3. Rao PS. Is the term “tricuspid atresia” appropriate? (Editorial). Congenital Heart Disease, Mount Kisco, NY, Futura Publishing
410
Am J Cardiol. 1990;6:1251. Co. 1980.p.421.
26. Anderson RH, Wilkinson JL, Gerlis LM, et al. Atresia of the 45. Marcano BA, Riemenschnieder TA, Ruttenburg HD, et al. 28
right atrioventricular orifice. Br Heart J. 1977;39:414. Tricuspid atresia with increased pulmonary blood flow: an
27. Weinberg PM. Anatomy of tricuspid atresia and its relevance to analysis of 13 cases. Circulation. 1965;40:399.
Tricuspid Atresia
current forms of surgical therapy. Ann Thorac Surg. 1980;29: 46. Rao PS. Cardiac catheterization in tricuspid atresia. In: Rao PS
306. (Ed). Tricuspid Atresia, Mount Kisco, NY, Futura Publishing
28. Rao PS, Jue KL, Isabel-Jones J, et al. Ebstein’s malformation Co. 1982.p.153.
of the tricuspid valve with atresia: differentiation from isolated 47. LaCorte MA, Dick M, Scheer G, et al. Left ventricular function
tricuspid atresia. Am J Cardiol. 1973;32:1004. in tricuspid atresia. Circulation. 1975;52:996.
29. Rao PS. Atrioventricular canal mimicking tricuspid atresia: 48. Graham TP, Erath HJG, Boucek RJ, et al. Left ventricular
echocardiographic and angiographic features. Br Heart J. function in cyanotic congenital heart disease. Am J Cardiol.
1987;58:409. 1980;45:1231.
30. Scalia D, Russo P, Anderson RH, et al. The surgical anatomy of 49. Rao PS, Alpert BS, Covitz W. Left ventricular function in
the heart with no direct communication between the right atrium tricuspid atresia. In: Rao PS (Ed). Tricuspid Atresia, 2nd edition.
and the ventricular mass so called tricuspid atresia. J Thorac Mount Kisco, NY, Futura Publishing Co. 1992.p.247.
Cardiovasc Surg. 1984;87:743. 50. Rao PS. Left-to-right shunting in tricuspid atresia. Br Heart J.
31. Rao PS, Sissman NJ. Spontaneous closure of physiologically 1983;49:345.
advantageous ventricular septal defects. Circulation. 1971;43:83. 51. Dick M, Rosenthal A. The clinical profile of tricuspid atresia.
32. Rao PS, Linde LM, Liebman J, et al. Functional closure of In: Rao PS (Ed). Tricuspid Atresia, Mount Kisco, NY, Futura
physiologically advantageous ventricular septal defects: Publishing Co. 1982.p.83.
observations in three cases with tricuspid atresia. Am J Dis 52. Taussig HB. The clinical and pathologic findings in congenital
Child. 1974;127:36. malformations of the heart due to defective development of the
33. Rao PS. Natural history of the ventricular septal defect in right ventricle associated with tricuspid atresia or hypoplasia.
tricuspid atresia and its surgical implications. Br Heart J. Bull Hopkins Hosp. 1936;59:435.
1977;39:276. 53. Wittenborg MH, Neuhauser EBD, Sprunt WH. Roentgenographic
34. Rao PS. Further observations on the spontaneous closure findings of congenital tricuspid atresia with hypoplasia of the
of physiologically advantageous ventricular septal defects right ventricle. Am J Roentgenol. 1951;64:712.
in tricuspid atresia: surgical implications. Ann Thorac Surg. 54. Elster SK. Congenital atresia of pulmonary and tricuspid valves.
1983;35:121. Am J Dis Child. 1950;79:692.
35. Gallaher ME, Fyler DC. Observations on the changing 55. Covitz W, Rao PS. Noninvasive evaluation of patients with
hemodynamics in tricuspid atresia without transposition of the tricuspid atresia (Roentgenography, echocardiography and
great vessels. Circulation. 1967;35:381. nuclear angiography). In: Rao PS (Ed). Tricuspid Atresia, 2nd
36. Sauer U, Hall D. Spontaneous closure or critical decrease in edition, Mount Kisco, NY, Futura Publishing Co. 1992.p.165.
size of the ventricular septal defect in tricuspid atresia with 56. Gamboa R, Gersony WM, Nadas AS. The electrocardiogram in
normally connected great arteries: surgical implications. Herz. tricuspid atresia and pulmonary atresia with intact ventricular
1980;5:369. septum. Circulation. 1986;34:24.
37. Rao PS. Physiologically advantageous ventricular septal defects 57. Patel R, Fox K, Taylor JFN, et al. Tricuspid atresia—clinical
(Letter). Pediat Cardiol. 1983;4:59. course in 62 cases (1967-1974). Br Heart J. 1978;40:1408.
38. Rao PS. Natural history of ventricular septal defects in tricuspid 58. Rao PS, Kulungara RJ, Boineau JP, et al. Electrovector
atresia. In: Rao PS (Ed). Tricuspid Atresia, 2nd edition, Mount cardiographic features of tricuspid atresia. In Rao PS (Ed).
Kisco, NY, Futura Publishing Co. 1992.p.261. Tricuspid Atresia, 2nd edition. Mount Kisco, NY, Futura
39. Rao PS. Subaortic obstruction after pulmonary artery banding Publishing Co. 1992.p.141.
in patients with tricuspid atresia and double-inlet left ventricle 59. Puri PS, Neill CA. Vectorcardiographic study in ten cases of
and ventriculoarterial discordance (Letter). J Am Coll Cardiol. tricuspid atresia. In: Cassels DE, Ziegler RF (Ed). Electrocardio
1991;66:406. graphy in Infants and Children, New York: Grune and Stratton.
40. Bharati S, Lev M. The concept of tricuspid atresia complex as 1966.p.269.
distinct from that of the single ventricle complex. Pediat Cardiol. 60. Bharati S, Lev M. Conduction system in tricuspid atresia with
1979;1:57. and without regular (d) transposition. Circulation. 1977;56:423-
41. Rosenthal A, Dick M II. Tricuspid atresia. In: Adams FH, 29.
Emmanouilides GC (Eds). Moss Heart Disease in Infants, 61. Dickenson DF, Wilkinson JL, Smith A, et al. Atrioventricular
Children and Adolescents. 3rd edition, Baltimore, Williams and conduction tissues in univentricular hearts of left ventricular
Wilkins. 1983.p.271. type with absent right atrioventricular connection (“tricuspid
42. Rao PS, Covitz W, Chopra PS. Principles of palliative atresia”). Br Heart J. 1979;42:1.
management of patients with tricuspid atresia. In: Rao PS 62. Guller B, Dushane JW, Titus JL. Atrioventricular conduction
(Ed). Tricuspid atresia, 2nd edition, Mount Kisco, NY, Futura system in two cases of tricuspid atresia. Circulation. 1969;40:217.
Publishing Co. 1992.p.297. 63. Kulungara RJ, Boineau JP, Moore HV, et al. Ventricular
43. Rudolph AM. Tricuspid atresia with hypoplastic right ventricle. activation and genesis of QRS in tricuspid atresia (abstract).
In: Congenital Disease of the Heart, Chicago Year Book Medical Circulation. 1981;64:IV-225.
Publishers. 1974.p.429. 64. Seward JB, Tajik AJ, Hagler DJ, et al. Echocardiographic
44. Rao PS. Perinatal Circulatory Physiology: It’s influence spectrum of tricuspid atresia. Mayo Clin Proc. 1978;53:100.
411
on clinical manifestations of neonatal heart disease – Part I. 65. Silverman NH, Payot M, Stanger P. Simulated tricuspid valve
Neonatology Today. 2008;3:6-12. echoes in tricuspid atresia. Am Heart J. 1978;95:761.
6 66. Beppu S, Nimura Y, Tamai M, et al. Two-dimensional echo
cardiography in the diagnosis of tricuspid atresia: differentiation
86. Gibbs JL, Rothman MT, Rees MR, et al. Stenting of arterial
duct: a new approach to palliation of pulmonary atresia. Br
from other hypoplastic right heart syndromes and common Heart J. 1992;67:240.
atrioventricular canal. Br Heart J. 1978;40:1174. 87. Siblini G, Rao PS, Singh GK, et al. Transcatheter management
67. Rao PS. Pathophysiologic consequences of cyanotic heart of neonates with pulmonary atresia and intact ventricular
disease. Indian J Pediat. 1983;50:479-87. septum. Cathet Cardiovasc Diagn. 1997;42:395.
68. Mair DD, Hagler DJ, Puga FJ, et al. Fontan operation in 176 88. McCredie RM, Lee CL, Swinburn MJ, et al. Balloon dilatation
patients with tricuspid atresia: results and a proposed new index pulmonary valvuloplasty in pulmonary stenosis Aust New
for patient selection. Circulation. 1990;82(Supp IV).164. Zealand J; Med. 1986;16:20.
69. Campbell M, Hills TH. Angiocardiography in cyanotic 89. Peck GJ, Arsiwala SS, Chan C, et al. Absorbable pulmonary
congenital heart disease. Br Heart J. 1950;12:65. artery band. Ann Thorac Surg. 1997;64:539.
70. Cooley RN, Sload RD, Hanlon CR, et al. Angiocardiography 90. Bonnet D, Sidi D, Vouhé PR. Absorbable pulmonary artery
of cyanotic type II. Observations as tricuspid stenosis or atresia banding in tricuspid atresia. Ann Thorac Surg. 2001;71:360.
with hypoplasia of the right ventricle. Radiol. 1950;54:848. 91. Rao PS. Absorbable pulmonary artery band in tricuspid atresia
71. Schwartz DC, Rao PS. Angiography in tricuspid atresia. In: (Editorial). Ann Thorac Surg. 2001;71:361.
Rao PS (Ed). Tricuspid Atresia, 2nd edition, Mount Kisco, NY, 92. Rashkind WJ, Waldhausen JA, Miller WW, et al. Palliative
Futura Publishing Co. 1992.p.223. treatment of tricuspid atresia: combined balloon atrial
72. Fontan F, Baudet E. Surgical repair of tricuspid atresia. Thorax. septostomy and surgical alteration of pulmonary blood flow. J
1971;26:240. Thorac Cardiovasc Surg. 1969;57:812.
73. Kreutzer G, Bono H, Galindez E, et al. Una operacion para la 93. Rao PS. Role of Interventional Cardiology. In: Neonates: Part
correccion de la atresia tricuspidea. Ninth Argentinean Congress I. Non-Surgical Atrial Septostomy. Congenital Cardiol Today.
of Cardiology, Buenos Aires, Argentina, Oct. 31-Nov. 6, 1971. 2007;5:1-12.
74. DeLaval MR, Kilner P, Gewilling M, et al. Total cavopulmonary 94. Park SC, Neches WH, Zuberbuhler JR, et al. Clinical use of
connection: a logical alternative to atriopulmonary connection blade atrial septostomy. Circulation. 1978;58:600.
for complex Fontan operation. J Thorac Cardiovasc Surg. 95. Rao PS. Transcatheter blade atrial septostomy. Cathet Cardiovasc
1988; 96:682. Diagn. 1984;10:335.
75. Chopra PS, Rao PS. Corrective surgery for tricuspid atresia: 96. Salim M, Muster AJ, Paul MH, et al. Relation between
which modifications of Fontan-Kreutzer procedure should be preoperative left ventricular muscle mass and outcome of the
used? A review. Am Heart J. 1992;123:758. Fontan procedure in patients with tricuspid atresia. J Am Coll
76. Rao PS, Chopra PS. Modification of Fontan-Kreutzer procedure Cardiol. 1989;14:750-55.
for tricuspid atresia: can a choice be made? In: Rao PS (Ed). 97. Ottenkamp J, Wenink ACG, Quaegebeur JM, et al. Tricuspid
Tricuspid Atresia, 2nd edition, Mount Kisco, NY, Futura atresia: Morphology of the outlet chamber with special
Publishing Co. 1992.p.361. emphasis on surgical implications. J Thorac Cardiovasc Surg.
77. Rao PS. Principles of management of the neonate with 1985;89:597-603.
congenital heart disease. Neonatology Today. 2007;2:1-10. 98. Smolinsky A, Castaneda AR, Van Praagh R. Infundibular
78. Freed MD, Heymann MA, Lewis AB, et al. Prostaglandin E1 septal resection: Surgical anatomy of the superior approach. J
in the infants with ductus arteriosus dependent congenital heart Thorac Cardiovasc Surg. 1988;95:486-94.
disease: The US experience. Circulation. 1981;64:899. 99. Hopkins RA, Armstrong SSE, Serwer GA, et al. Physiologic
79. Rao PS. Congenital Heart Disease. In: Rakel RE (Ed). Conn’s rationale for a bidirectional cavopulmonary shunt: a versatile
Current Therapy, Philadelphia, In: PA, WB Saunders, (Eds). complement to the Fontan principle. J Thorac Cardiovasc Surg.
1989.p.201. 1985;90:391.
80. Rao PS, Thapar MK, Galal O, et al. Follow-up results of balloon 100. Marcelletti C, Corno A, Giannico S, et al. Inferior vena cava-
angioplasty of native coarctation in neonates and infants. Am pulmonary artery extracardiac conduit. A new form of right
Heart J. 1990;120:1310. heart bypass. J Thorac Cardiovasc Surg. 1990;100:313-14.
81. Rao PS, Galal O, Smith PA, et al. Five to nine year follow-up 101. Pridjian AK, Mendelsohn AM, Lupinetti FM, et al. Usefulness
results of balloon angioplasty of native aortic coarctation in of the bidirectional Glenn procedure as staged reconstruction
infants and children. J Am Coll Cardiol. 1996;27:462-70. for the functional single ventricle. Am J Cardiol. 1993;71:959-
82. Rao PS. Current status of balloon angioplasty for neonatal and 62.
infant aortic coarctation. Progress Pediat Cardiol. 2001;14:35- 102. Tanoue Y, Sese A, Ueno Y, et al. Bidirectional Glenn procedure
44. improves the mechanical efficiency of a total cavopulmonary
83. Blalock A, Taussig HB. The surgical treatment of malformations connection in high-risk fontan candidates. Circulation.
of the heart in which there is pulmonary stenosis or pulmonary 2001;103:2176-80.
atresia. J Am Med Assoc. 1945;128:189. 103. Billingsley AM, Laks H, Boyce SM, et al. Definitive repair in
84. DeLeval M, McKay R, Jones M, et al. Modified Blalock-Taussig some patients with pulmonary atresia with intact ventricular
shunt: use of subclavian orifice as a flow regulator in prosthetic septum. J Thorac Cardiovasc Surg. 1989;97:746-54.
systemic-pulmonary artery shunts. J Thorac Cardovasc Surg. 104. Bridges ND, Lock JE, Castaneda AR. Baffle fenestration
1981;18:112. with subsequent transcatheter closure: modification of the
85. Annecchino FP, Fontan F, Chauve A, et al. An operation for the Fontan operation for patients with increased risk. Circulation.
correction of tricuspid atresia. Ann Thorac Surg. 1979;29:317. 1990;82:1681.
412
105. Laks H, Pearl JM, Haas GS, et al. Partial Fontan advantages trophysiologic benefit of early atrioventricular resynchroniza- 28
of an adjustable interatrial communication. Ann Thorac Surg. tion. Texas Heart Institut. 2007;34:96-101.
1991;52:1084. 114. Estner HL, Kolb C, Schmitt C, et al. Long-term transvenous
Tricuspid Atresia
106. Choussat A, Fontan F, Besse P, et al. Selection criteria for Fontan AV-sequential pacing in a failing atriopulmonary Fontan
procedure. In: Anderson RH, Shinebourne EA (Eds). Paediatric patient. Int J Cardiol. 2008;127:e93-95.
Cardiology, Edinburgh, Churchill Livingstone. 1978.p.559. 115. Marcelletti CF, Hanley FL, Mavroudis C, et al. Revision of
107. Freedom RM, Gow R, Caspi J, et al. The Fontan procedure for previous Fontan connections to total extracardiac cavopulmo-
patients with tricuspid atresia: Long-term follow-up. In: Rao nary anastomosis: A multicenter experience. J Thorac Cardio-
PS (Ed). Tricuspid Atresia, 2nd edition. Futura Publishing Co, vasc Surg. 2000;119:340-46.
Mount Kisco, NY. 1992. pp.377-86. 116. Sheikh AM, Tang AT, Roman K, et al. The failing Fontan circu-
108. Gandhi SK, Bromberg BI, Schuessler RB, et al. Characterization lation: successful conversion of atriopulmonary connections. J
and surgical ablation of atrial flutter after classic Fontan repair Thorac Cardiovasc Surg. 2004;128:60-66.
in acute canine model. Ann Thorac Surg. 1996;61:1666-78. 117. Gamba A, Merlo M, Fiocchi R, et al. Heart transplantation in
109. Rao PS, Chandar JS, Sideris EB. Role of inverted buttoned patients with previous Fontan operations. J Thorac Cardiovasc
device in transcatheter occlusion of atrial septal defect or Surg. 2004;127:555-62.
patent foramen ovale with right-to-left shunting associated 118. Jayakumar KA, Addonizio LJ, Kichuk-Chrisant MR, et al. Car-
with complex congenital cardiac anomalies. Am J Cardiol. diac transplantation after the Fontan or Glenn procedure. J Am
1997;80:914-21. Coll Cardiol. 2004;44:2065-72.
110. Goff DA, Blume ED, Gauvreau K, et al. Clinical outcome 119. Rowe RD, Freedom RM, Mehrizi A, et al. The Neonate
of fenestrated Fontan patients after closure: the first 10 with Congenital Heart Disease. Major Problems in Clinical
years. Circulation. 2000;102:2094-99. Pediatrics. 2nd edition, Vol 5, Philadelphia: WB Saunders Co.
111. Hill DJ, Feldt RH, Porter C, et al. Protein losing enteropathy 1981.p.456.
after Fontan operation: A preliminary report (Abstract). 120. Franklin RCG, Spregethalter DJ, Sullivan ID, et al. Tricuspid
Circulation. 1989;80:490. atresia presenting in infancy: survival and suitability for the
112. Rao PS. Protein-losing enteropathy following the Fontan Fontan operation. Circulation. 1993;87:427.
operation (Editorial). J Invasive Cardiol. 2007;19:447-48. 121. Rao PS. Tricuspid Atresia. In: Pediatric Cardiovascular Medi-
113. Lopez JA. Transvenous right atrial and left ventricular pacing cine. Moller JH, Hoffman JIE (Eds). Churchill Livingstone,
after the Fontan operation: long-term hemodynamic and elec- New York, NY. 2000.pp.421-41.
413
C hapter
29 Diseases of the Tricuspid Valve
INTRODUCTION No single gene defect has been consistently identified

with Ebstein anomaly. Ebstein anomaly appears to be
In this chapter, abnormalities of the morphologic tricuspid genetically heterogeneous and several candidate genes have
valve, namely Ebstein malformation of the tricuspid valve, been suggested including GATA4, NKX2.5 and hypothetical
Ebstein anomaly of the left-sided atrioventricular valve genes in 1p36.11 Mutations of sarcomere protein gene MYH7
in corrected transposition, tricuspid stenosis and tricuspid has been proposed in a small group of patients with Ebstein
regurgitation will be discussed; tricuspid atresia was discussed anomaly and left ventricular non-compaction.12 There is a
in Chapter 28. single case report suggesting association of Ebstein anomaly
with Williams syndrome.13
EbsTEIN MALFORMATION OF THE TRICUsPID VALVE There is a higher incidence for recurrence in the offspring
of women (6%) than that seen the offspring of men (0.6%).14
Ebstein anomaly of the tricuspid valve is a congenital
malformation, in which there is downward (apical) Pathology
displacement of insertion of septal and posterior leaflets.
Anterior leaflet is not usually affected. In addition, the There are several anatomic components of Ebstein anomaly,15
tricuspid valve leaflets are dysplastic. As a result of the namely:
displacement, there is poor coaptation of the valve leaflets 1. Displacement of the septal and posterior leaflets towards
leading to tricuspid regurgitation, which in turn causes right apex of the right ventricle (RV).
atrial enlargement of a variable degree depending upon the 2. Anterior leaflet is usually attached at the annular level
degree of tricuspid regurgitation. and is large and sail-like with multiple attachments to
ventricular wall.
Historical Aspects 3. The portion of RV that is proximal to the level of the
displaced septal and posterior leaflets is called the
This anomaly, now called Ebstein, was first described by ‘atrialized RV’ and is usually thin and dysplastic.
Wilhelm Ebstein in 1866 in an autopsy of a 19-year-old laborer 4. RV cavity beyond the attachment of the septal and posterior
who had cyanosis and dyspnea since early childhood.1 The very leaflets is the ‘functional RV’ and is smaller, lacks inlet
first reported case in a live patient was in 1949 by Tourniaire portion and has a small trabecular portion.
et al.2 Advent of two-dimensional echocardiography has led to 5. Infundibular portion of RV is sometimes obstructed by
increasing recognition of this anomaly, including milder cases. 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 Septal and posterior leaflets are adherent to RV and septal
heart defects.3,4 No gender predominance is noted. The majority myocardium and become free from myocardium at a lower
of cases are sporadic. Exposure to lithium during pregnancy level than the annulus of the tricuspid valve. Extent of this
has been reported as an etiologic factor.5-7 However, some displacement varies among patients leading to variation in the
recent studies have challenged Lithium as etiologic factor.8-10 severity of clinical manifestations.
There is redundancy and dysplasia of the leaflets as well. rare and include pulmonary stenosis (PS), pulmonary atresia, 29
Nodular appearance of the free edge of the leaflets is present. ventricular septal defect (VSD), patent ductus arteriosus
Anterior leaflet of the tricuspid valve is usually large and ‘sail- (PDA), tetralogy of Fallot (TOF), double out let right ventricle
Diseases of the tricuspiD ValVe

like’. This leaflet may have one or more holes in it leading to (DORV), right aortic arch, coarctation of aorta, transposition
additional tricuspid regurgitation. of the great arteries (TGA) and mitral valve prolapse or
Due to the displacement of the septal and posterior leaflets, stenosis, non-compaction of left ventricle (LV) or RV25 and
a portion of the right ventricular myocardium and ventricular absent pulmonary valve syndrome among others. A VSD may
septum are ‘atrialized’. This portion is between the ‘true’ be present either between LV and atrialized portion of RV
annulus and the false insertion point of septal and posterior (Gerbode defect) 26 or between LV and functional RV.
leaflets.
Tricuspid valve orifice is usually adequate. Rarely, there Classification
may be concomitant tricuspid stenosis16 or even atresia.17
There may also be multiple orifices in tricuspid valve. Some authors27 classify Ebstein’s anomaly as simple and
Redundancy of tricuspid valve tissue may encroach RV complex. Ebstein anomaly may be called simple when it is
outflow tract and cause sub pulmonary stenosis.18-20 not associated with other anomalies and complex when other
significant defects coexist.
Right Atrium However, surgical classification15 of Ebstein anomaly
categorizes it into four types (Carpentier types):
The right atrium (RA) is dilated and hypertrophied. Severity Type A: Mild displacement of proximal attachments of
of hypertrophy and enlargement of RA is proportional to the septal and posterior leaflets. The volume of functional RV is
degree of displacement of the tricuspid valve leaflets and adequate.
resultant tricuspid regurgitation. Massive enlargement of right Type B: Atrialized portion of RV is large, but anterior leaflet
atrium is common. is freely mobile
Type C: Anterior leaflet mobility is limited, right ventricular
Right Ventricle out-flow tract (RVOT) is severely obstructed.
Type D: Almost complete atrialization of RV except for a
In mild and moderate cases, the RV cavity size is normal small infundibular portion. A fenestration in the commissure
with some degree of RV hypertrophy. However, in more between anterior and septal leaflets is the only communication
severe cases, the right ventricular myocardium may be quite between atrialized RV and the infundibulum.
abnormal with variable thickness ranging from near-normal
thickness to very thin and dysplastic, similar to that seen with Pathophysiology
Uhl’s anomaly.21,22
Hemodynamic abnormalities are dictated by severity of the
Conduction System lesion;28 main determinants are the degree of displacement of
the tricuspid valve and the degree of tricuspid regurgitation.
Supraventricular tachycardia is seen in association with In patients with mild Ebstein tricuspid valve function is
Ebstein’s anomaly and may be related to accessory conduction close to normal. In moderate to severe forms, with each atrial
pathways simulating Wolf-Parkinson-White (WPW) syndrome. contraction, the blood is propelled into the atrialized RV.
Anomalies of the right bundle branch have been reported, With ventricular contraction that follows, the blood is forced
which may explain right bundle branch block pattern seen in back into the right atrium. This is even more pronounced in
the electrocardiogram (ECG). The area of triangle of Koch is children with significant tricuspid regurgitation. With the next
much smaller in Ebstein anomaly hearts than in normal hearts. atrial contraction, this blood is forced back into the atrialized
While AV node and its extensions are normal in size, they are RV. This back and forth blood flow, the so called ping-pong
displaced towards the base of Koch triangle and his bundle effect,29 causes right atrial dilatation and increases right atrial
penetrates well short of the apex of Koch triangle than normal. pressure; the latter results in right to left shunt across ASD/
Practical implication of this anatomy is that during treatment of PFO. This shunt results in arterial desaturation and pulmonary
supraventricular arrhythmias with ablation at the base of Koch oligemia.
triangle may result in higher incidence of AV block in patients Newborn babies with severe Ebstein anomaly are cyanotic
with Ebstein anomaly than in normal hearts.23,24 secondary to right to left shunt across the atrial septum as
detailed above. This is further accentuated by the usual high
Associated Lesions pulmonary vascular resistance that exists at this age.
Significant tricuspid regurgitation causes severe right atrial
In most cases, either a patent foramen ovale (PFO) or an atrial enlargement in utero as well as after birth. Since significant
septal defect (ASD) is present. Other associated anomalies are portion of RV may be atrialized in severe cases, there may be 415
6 inadequate RV myocardium to generate high enough pressure PFO. This leads to severe cyanosis and severe metabolic
to achieve forward flow via the pulmonary valve. This is acidosis in the newborn.
compounded by high pulmonary vascular resistance and PDA Cyanosis is noted in approximately 50 percent of the
congenital ValVular lesions
leading to inability of the pulmonary valve leaflets to open. newborn.3,31 In infants beyond the neonatal period, cyanosis is
This leads to ‘functional’ pulmonary atresia. In such patients, also a common presentation. Murmur and heart failure features
pulmonary valve may open after the pulmonary vascular are less common presenting features. Incidental finding of
resistance decreases either as natural course or by medical cardiomegaly in a chest X-ray performed for another purpose
treatment. is another mode of presentation. Supraventricular tachycardia
Right to left shunting at atrial septal level, leading to may also be a presenting feature.
cyanosis in the newborn, may resolve as the pulmonary
vascular resistance (PVR) decreases along with establishment Children, Adolescents and Adults
of forward flow via the pulmonary valve. Degree to which
such resolution occurs depends on the severity of the defect. They are largely asymptomatic and may be detected by a
Cyanosis may return in later childhood or adolescence when cardiac murmur or by echocardiogram performed for an
tricuspid valve function deteriorates (causing regurgitation). unrelated problem. Infants with moderate to severe forms,
This clinical course is described in the old literature as who improved after normalization of pulmonary pressures,
‘transient’ or ‘intermittent’ cyanosis. may become symptomatic as the tricuspid valve and right
ventricular function deteriorates. Easy fatigability, cyanosis
Clinical Presentation or arrhythmia may be presenting symptoms.
Celermajer et al32 reviewed 220 cases with Ebstein anomaly
Wide spectrum of pathophysiology, as noted above, allows for and found that most common presenting symptom varied with
differing presentations, which are dependent upon severity of age—prenatal scans for fetuses is 86 percent, cyanosis for
each component of lesion and associated lesions. Mild cases neonates is 74 percent, heart failure for infants is 43 percent,
may not be detected until adulthood. Mildest cases are detected incidental murmur for children is 63 percent and arrhythmia
serendipitously during an echocardiogram performed for an for adolescents and adults is 42 percent. Early presentations
unrelated reason. Most severe forms present during neonatal were associated with RV outflow tract obstruction.
period. Flores Arizmendi and associates33 followed 52 patients
from the time of diagnosis (ranging from fetal life to
Fetus adulthood) to a mean of 16.7 years. 24 patients presented
during newborn period and eleven (46%) of these patients
In fetus, Ebstein anomaly may present as cardiomegaly, died. Actuarial survival for the entire group at 30 years was
tricuspid regurgitation, with right atrial enlargement on fetal 65 percent. Twenty-seven (66%) of the 41 survivors had
echocardiography, arrhythmia or heart failure with hydrops. arrhythmias and 25 of the 27 were receiving medications for
Fetal presentation is associated with high incidence of fetal arrhythmia. Nine patients have had surgery. Celermajer index
loss.30 of three or four (See under Fetal and Neonatal Diagnosis
section) and CT ratio more than 65 percent were found to be
Neonates and Infants predictive of death.33
Infants with milder forms are largely asymptomatic. However, Arrhythmia

infants with severe forms become symptomatic and have
severe cardiomegaly and may have associated lung hypoplasia. Supraventricular tachycardia (SVT) is common; this may
There is no forward flow due to ineffective RV and inability to be secondary to accessory pathways or atrioventricular re-
overcome the high PVR that exists in the early neonatal period. entry. Atrial arrhythmias such as atrial flutter or fibrillation
There will be a functional/physiological pulmonary atresia. It may also be present. Accessory atrioventricular pathways are
may be difficult to differentiate it from anatomic pulmonary present in 20 percent of patients with Ebstein anomaly; nearly
atresia that may also coexist with Ebstein anomaly. Therefore, all of them are right-sided pathways. About half of these
pulmonary blood flow is dependent on ductal patency. patients have multiple accessory pathways.34 The accessory
Systemic venous return from the right atrium needs PFO pathways are usually located in the inferior portion of the
or ASD for egress. This causes significant cyanosis in the tricuspid valve annulus—most commonly posteroseptal and
newborn. If the PFO is restrictive, right atrial hypertension posterolateral pathways.35 Due to slow conduction properties
and systemic venous congestion occur. If ductus arteriosus is of the accessory pathways that are located in the atrialized
inadequate, there will be poor oxygenation from diminished portion of the RV, the conduction goes through AV node more
blood flow and inadequate cardiac output due to poor often and therefore, most of these accessory pathways do
416 pulmonary venous return coupled with small shunt via the manifest in sinus rhythm.
In a multicenter study of pediatric patients with Ebstein of multiple heart sounds. A holosystolic murmur of tricuspid 29
anomaly in Netherlands,36 there was 17 percent incidence regurgitation is present especially when pulmonary artery
of arrhythmias (16 of 93 patients). Nine of them developed pressures are high. Careful auscultation may reveal a low-

arrhythmias in the newborn period. One neonate died at 6 frequency mid-diastolic murmur signifying either increased
days of age from intractable SVT associated with heart failure forward flow through an adequate sized tricuspid orifice or
and cyanosis. Another neonate is suspected to have had through tricuspid stenosis.
arrhythmic death at 4 weeks of age. All 14 survivors exhibited In children with milder forms the only abnormality is
pre-excitation in the electrocardiogram (EKG), although four multiple cardiac sounds. Precyanotic rubra may be present. In
of them exhibited pre-excitation only intermittently. The moderate to severe Ebstein, cyanosis, multiple cardiac sounds
incidence of arrhythmia in pediatric patients with Ebstein and holosystolic murmur of tricuspid regurgitation at the left
anomaly is much lower than that in adults. In adults, additional lower sternal border may be present.
atrial arrhythmias due to long-standing tricuspid regurgitation
and right atrial dilatation adds atrial flutter or fibrillation to the Investigations
complement of arrhythmias.
Chest X-ray
Physical Examination
Severe cardiomegaly is the rule in Ebstein anomaly
In a newborn with mild form of Ebstein anomaly, there may (Figures 1A and B). Increase in cardio-thoracic ratio is mostly
be no cyanosis, but may have multiple cardiac sounds (third, due to right atrial enlargement. Lung fields are either normal
fourth and or both), described as triple or quadruple rhythm.29 or oligemic. Cardiomegaly in milder cases is commensurate
No significant murmur is heard. In moderate Ebstein anomaly, with the severity of tricuspid regurgitation.
there may be cyanosis with no significant respiratory distress.
The vital signs and peripheral pulses are normal. The Electrocardiogram
precordium is quiet and no other significant abnormality.
In severe cases, hyperdynamic precordium and a thrill at Right atrial enlargement, low QRS voltages and right bundle
the left lower sternal border may be present. Distension of branch block (RBBB) are typical findings in Ebstein anomaly
neck veins with a prominent ‘V’ wave may be seen. Liver (Figure 2). Right axis deviation is usual. Rarely, left axis
enlargement may be present. The first heart sound is usually deviation may be noted.31,37,38 Prolongation of PR interval
normal. The second heart sound may be widely split or normal. is noted in two-third of the nenonates.31,39 Features of WPW
Third, fourth and/or both are common leading to appreciation syndrome with short PR interval are reported with higher
a B
figures 1a and B: Panel A. Chest X-ray of a newborn with severe Ebstein anomaly of the tricuspid valve showing severe cardiomegaly, typical 417
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
6
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 are easy to detect. However, diagnosis of mild Ebstein
evidence of pre-excitation with normal PR interval.40 anomaly may be debatable since normal TV is displaced
slightly when compared with crux of the heart or mitral
Echocardiography valve annulus. In a study of 41 patients seen at Mayo clinic
(Minnesota) with mean age of 18 years, a displacement of
The diagnosis is established by echocardiographic studies greater than or equal to 8 mm/m2 of body surface area
and they provide necessary information for assessment of was established as a criterion to judge the displacement.41
severity and prognosis. Technological advances have made However, in the opinion of the authors of this chapter,
echocardiography the main modality of diagnosis for Ebstein this criterion alone will over-diagnose Ebstein anomaly
anomaly. Morphologic correlates of Ebstein anomaly have in the newborn whose usual body surface area is around
been well described in literature41-44 and well-reviewed in 0.20 m2. TV displacement of 1.5–2 mm below the mitral
textbooks.45 valve annulus or crux of the heart is not unusual in a
Objectives of echocardiography are to evaluate the degree normal newborn. Presence of other features should also
of dysplasia and displacement of tricuspid valve leaflets be taken into account in this diagnosis rather than isolated
from the true annulus (which in turn influence the degree of displacement of septal leaflets.
tricuspid valve regurgitation), RV size and RV function. 2. Dysplasia or absence of septal leaflet. Septal leaflet may
be dysplastic and/or fibrotic or absent. When the leaflet is
Evaluation of Tricuspid Valve and its Attachments absent, it may be represented by remnants of tissue seen at
the mid-portion of the ventricular septum.
1. Degree of inferior displacement of the tricuspid valve 3. Subvalvar apparatus. Short chordae may attach the septal
(TV) leaflets. The hinge points of the septal and posterior leaflet to the ventricular septum. Sometimes, the chordae
leaflets are usually displaced downward towards the may be absent with insertion of the leaflet directly to the
apex. Anterior leaflet usually is not displaced. Apical four ventricular septum in apical four chamber view.
chamber view (Figures 3A and B) is the best to estimate the 4. Anterior leaflet can be visualized in either apical four
displacement. Mitral valve annulus serves as a reference chamber view or parasternal long axis view aimed towards
to quantitate the degree of displacement. Severity of the right ventricular inflow. Anterior leaflet is usually
Ebstein anomaly varies with the degree of displacement very large with ‘sail-like’ mobility consisting of bulging
of the septal leaflet. Moderate to severe displacements into RVOT during diastole and folding during systole.46
418
29

a B
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 septum—to 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. figure 4: Subcostal coronal view of the chordal attachment of tricuspid
valve leaflets (unmarked arrow) in Ebstein anomaly. In this example
Tethering restricts mobility of the anterior leaflet and may
with Ebstein’s anomaly, chordal attachment is normal. Valve true
lead to obstruction of RV outflow. Degree of encroachment annulus is shown with an arrow. The right atrium (RA), atrialized right
of RVOT by anterior leaflet’s distal attachments can be ventricle (aRV) are also shown. RV = Right ventricle; RVOT = Right
seen in subcostal views. ventricular outflow tract
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 Evaluation of RA, RV and RVOT
situation, if the anterior leaflet has a linear distal attachment
along the junction of inlet and trabecular portions of the 1. Severe RA enlargement is usually seen in Ebstein
RV, the key hole become the only opening for forward flow anomaly, especially in the presence of significant tricuspid
through tricuspid valve. This may lead to ‘tricuspid stenosis’ regurgitation. However, this may be minor in patients with 419
or even an imperforate TV if this closes completely. mild Ebstein anomaly with mild tricuspid regurgitation.
6 RV volume overload with paradoxical septal movement 2. Certain degree of RV dysplasia may be present. This is
is also seen. Apical four chamber view helps to measure considered to exist if RV wall thickness is less than two
the sizes of the RA, atrialized RV and the functional distal standard deviation (SD), size of RV is more than two SD or
chamber of RV. Ratio of area of RA plus atrialized RV to there is dyskinesia of atrialized or the functional portion of
the combined area of functional, distal portion of RV, LV RV.43 Even though, the atrialized portion of RV bulges into
and LA (Figure 5) has been used as a prognostic factor to the LV outflow tract (Figures 6A and B), obstruction to LV
predict survival in newborn with Ebstein anomaly.47 (See outflow tract rarely occurs to a clinically significant degree.
under Fetal and Neonatal Diagnosis section below). 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
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
vascular resistance drops as the newborn transitions from
obtain the ratio (Celermajer index) for prediction of outcome in fetal and fetal circulation to postnatal circulation. There are reports
neonatal echocardiograms (see text for further details). Abbreviations of inhaled nitric oxide therapy helping to differentiate this
are same as those used in Figure 3 as well.48
a B
420
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 performed, right to left shunting at atrial level may be present 29
by oximetry. Left to right shunting is unusual unless there
Newer technology with three-dimensional imaging (transtho- is VSD or PDA. Pressure traces have some characteristic

racic and/or transesophageal echocardiography) now enables features—RA pressure (mean) is usually elevated; ‘a’ waves
reconstruction of tricuspid valve and ability to visualize all are more prominent than ‘v’ waves because of dissipation
three leaflets of the tricuspid valve at the same time. Such of tricuspid regurgitation in a large, compliant right atrium.
visualization helps with surgical planning.49,50 Right ventricular pressure is low or normal. Low RV systolic
Three-dimensional echocardiography also has enhanced pressure is a poor prognostic sign-indicative of inability of
the understanding and evaluation of tricuspid valve anatomy the RV to mount enough pressure to enable adequate forward
prior to surgery. Using multiplanar three-dimensional flow via pulmonary valve. High RV systolic pressure is
echocardiography, investigators in Southampton, United noted in the presence of VSD, PS or high PVR. RV end-
Kingdom (UK)51 have shown that the valve orifice faces RV diastolic pressure is usually elevated. Left sided pressures
outflow tract in Ebstein anomaly, while in tricuspid valve (left atrium, left ventricle and aorta) are normal and have no
dysplasia the valve orifice faces RV apex. Three-dimensional characteristic features in Ebstein anomaly.
echo also provides definition of degree of delamination of the Electrode catheter studies performed in the past29 for
leaflets, subvalvar apparatus and dynamic morphology and diagnosis are no longer routinely performed because the
functional characteristics of tricuspid valve.51 diagnosis can be made easily with echocardiography.
Selective right ventricular angiography (Figures 7A and
Cardiac CT or MRI B) demonstrates displaced TV leaflets, degree of tricuspid
insufficiency and size and function of the RV as well as
Computed tomography (CT) or magnetic resonance imaging pulmonary valve and pulmonary artery anatomy. Tricuspid
(MRI) are not usually necessary to define and evaluate insufficiency during selective right ventricular angiography
Ebsteins anomaly in newborn or children. In adults with poor and right atrial angiography (not necessary) produces a
acoustic windows, transesophageal echocardiography (TEE) trilobed heart representing, RA, atrialized portion of RV
and/or cardiac CT or MRI may be helpful in establishing and and RV (Figure 8). The notch separating right atrium and
completing the evaluation of Ebstein anomaly. RV function the atrialized portion of RV represents location of the true
and severity of Ebstein anomaly may also be evaluated.52,53 tricuspid valve annulus and the second notch represents origin
of displaced tricuspid valve leaflets.29
Fetal and Neonatal Diagnosis and Prediction of Outcome
Cardiac catheterization is not usually necessary, but is
indicated for therapeutic purposes, when there is associated, Features of Ebstein anomaly are likely to appear late in fetal life
significant pulmonary stenosis. When catheterization is (Figure 9), i.e. a fetus who had a normal fetal ultra sonogram
a B
figures 7a and B: A. Right ventricular angiogram in posteroanterior view from an adolescent with Ebstein anomaly. Contrast was injected via 421
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
6
figure 8: Right ventricular (RV) angiogram in postero-anterior view

figure 9: Fetal echocardiogram at 24 weeks gestation showing
from a newborn with Ebstein anomaly. Severe tricuspid valve regurgi-
four-chamber view of the heart with mild form of Ebstein anomaly.
tation lead to opacification of markedly enlarged right atrium (RA). In
Arrow denotes atrialized right ventricle (aRV). No hydrops was noted.
this example, pulmonary arteries are not opacified indicating presence
LA = Left atrium; LV = Left ventricle; RA = Right atrium
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 dis-
placed tricuspid valve leaflets (see text for details). RHC = Right heart
catheter; UVC = Umbilical venous catheter
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 four-
chamber views (Figure 5) are used for measurement. Ratio
of area of RA plus atrialized portion of RV to the combined
figure 10: Mortality rate based on the Celermajer index
area of functional, distal portion of RV, LV and LA is used for from their study47
grading; higher the grade greater is the mortality—Grade 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 Outcome based on SAS score—Scores of 0 to 10 are
percent mortality (Figure 10).44,47 possible. There were no survivors when the score was greater
Simpson-Andrews-Sharland (SAS) Score (Table 1)—SAS than or equal to 5. Conversely, when the scores were less
score is based on observations from 44 fetal studies at the first than or equal to 3, survival was 91 percent. In this study,
prenatal echocardiogram and includes: there was no one with score of 4. In addition, SAS score did
i. Cardiothoracic ratio—based on circumferences in not change in most fetuses during follow-up in the rest of
fetal echocardiogram. pregnancy. However, there was one non-survivor whose score
ii. Celermajer index. increased in successive fetal echocardiograms from zero at
iii. RV-LV ratio. approximately 22 weeks five at approximately 27 weeks and
iv. Reduced/absent pulmonary valve flow. reached 10 at approximately 32 weeks.
v. Retrograde ductus arteriosus flow. Prognostic factors—When fetal diagnosis of Ebstein
This score predicts survivors vs non-survivors and is useful anomaly or TV dysplasia is made, it is associated with
in counseling during pregnancy.55 high mortality. In a study from France, 37 cases of Ebstein
422

table 1 29
Simpson-Andrews-Sharland (SAS) Score used to predict fetal outcome from fetal echocardiogram during pregnancy

Variable 0 1 2
Cardiothoracic ratio (based on < 0.65 0.65 – 0.75 > 0.75
circumferences in the first fetal
echocardiogram)
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 1984–2010 LV compression by RV dilatation and Celermajer index
were reviewed.56 Twenty-six had Ebstein anomaly and eleven exceeding one.43, 57
had TV dysplasia. There were pregnancy terminations in
ten, intrauterine deaths in five and neonatal deaths in eight. Differential Diagnosis
Fourteen fetuses survived. Presence of retrograde flow across
the pulmonary valve in the first fetal echocardiogram was Severe cardiomegaly with pulmonary oligemia in a cyanotic
a strong predictor of fetal or neonatal death. Presence of newborn is highly suggestive of Ebstein anomaly; however,
antegrade flow through pulmonary valve was associated with the following conditions should also be considered in
good prognosis. Celermajer index did not predict outcome in such situations—Critical PS or pulmonary atresia with
this cohort adequately while the more extensive SAS predicted intact ventricular septum and ‘functional’ pulmonary
outcome adequately.56 atresia. Tricuspid atresia, TGA and TOF may rarely mimic
A recent single-center study from Boston Children’s Ebstein anomaly. But, their clinical features are distinctive.
Hospital reviewed 66 patients diagnosed between 1984 and Echocardiography will differentiate these conditions from
2004.57 Sixty-one of them were Ebstein anomaly and five were Ebstein anomaly.
TV dysplasia. Thirty-three were diagnosed prenatally, while It is of considerable concern when these patients are
33 were diagnosed after birth. Median follow-up duration referred for surgery in that there is a potential for error in
was 6.3 years. Of the 33 fetal diagnoses, 8 (24%) underwent the diagnosis of Ebstein anomaly when one is faced with a
medical termination, 9 (27%) died in utero and 16 were born tricuspid valve disease with significant tricuspid regurgitation.
alive. Nine of these 16 (56%) died in neonatal period. Overall, In a study of cases referred, diagnosed as Ebstein anomaly
7 of 33 fetal diagnosis patients survived beyond 1 month of for surgical repair between 1982 and 1995, 22 patients
age. Factors associated with poor outcome were moderate or were identified in whom the diagnosis was changed. All 22
severe tricuspid regurgitation, Celermajer index more than patients had prominent RA and RV enlargement. However,
1.0 and absence of forward flow through pulmonary valve. Of Ebstein anomaly was ruled out in these patients prior to
the 49 newborn babies, 29 percent died in the hospital and 35 surgery using two important echocardiographic parameters
were discharged home. Even though mortality was lower for namely:
the cohort diagnosed after 1997 (29% vs 54%), mortality still i. Significant apical displacement of septal leaflet of
remains high for the most severe group. Therefore, strategies tricuspid valve (≥ 8 mm/m2).
different from what are being used currently will be needed ii. Redundant, elongated anterior leaflet of the tricuspid
such as steroids in the third trimester to help lung maturity, valve.
delivery in middle of third trimester, early institution of Fifteen of these 22 patients underwent surgery and
ventilation and management of metabolic derangement after Ebstein anomaly was ruled out by surgical anatomy
birth to help avoid burden from poorly expanded/poorly as well. Alternative diagnoses established in these
formed lungs, etc.57 When the presentation is in the neonatal patients included TV dysplasia (n = 9), TV prolapse (n
period, severe RV outflow tract obstruction is also a risk factor = 4), trauma (n = 4), RV dysplasia (n = 3), endocarditis
for mortality.43,57 (n = 1) and annular dilatation secondary to free pulmonary
In summary, when the presentation is in fetal and regurgitation (n = 1). Absence of the two characteristic
newborn periods, the following are associated with death echocardiographic signs of Ebstein anomaly, mentioned
by 3 months of age—severe RV outflow tract obstruction, above should raise possibilities of other types of tricuspid
tethered distal attachment of anterior leaflet, RV dysplasia, valve diseases. 58 423
6 Natural History may relieve systemic venous congestion, one should be aware
Several studies38,59-62 examining natural history will be of the increase in cyanosis that may occur due to increased
reviewed in order to get a sense of how the patients do right to left shunting at the atrial level after septostomy.
over time. An early study from Boston Children’s Hospital Right ventricular outflow tract obstruction is commonly
reviewed the outcome of Ebstein anomaly;38 isolated Ebstein secondary to anterior leaflet attachments. Therefore, balloon
anomaly—70 percent survived up to 2 yrs and 50 percent pulmonary valvuloplasty is unlikely to help unless valvar
survived up to 13 yrs. Ebstein anomaly patients with associated stenosis is a significant part of RV outflow tract obstruction.
anomalies, however had a 15 percent survival at 2 years.59 In
another study of 505 patients,59 minimal disability was present Surgical Management
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. Multiple surgical approaches have been described for
Therefore, early diagnosis alone should not be an indication treatment of Ebstein anomaly and will be reviewed briefly.
for surgery.60 Carpentier type A and B14 babies are likely to Simple closure of ASD: Surgical closure of PFO/ASD
recover with medical management in the neonatal period.61 may provide symptomatic improvement by controlling a
A recent study from Belgium62 documents outcome in a significant left to right shunting and mild cyanosis (secondary
cohort of 49 patients who were more than 16 years old. Mean to right to left shunting) at baseline or with exercise. This may
follow-up period was 11.4 years (1–32 year). Half of them be useful in a small number of individuals. In such patients,
(51%) has undergone tricuspid valve surgery; surgical repair transcatheter closure of ASD63 may be considered after a test-
of the valve (valvuloplasty) in 16 and valve replacements in occlusion to prove that the cardiac output does not decrease
nine. Eight patients required reoperation to repeat tricuspid and right atrial pressure does not unduly increase. For most of
valve repair. Twenty-six (51%) patients had SVT. Typical the other patients, tricuspid valve (Ebstein anomaly) should
WPW syndrome was noted in 15 (31%) and ablation was be addressed surgically.
performed in 17 (34%). Pacemaker was implanted in 5 Repair or replacement of tricuspid valve: Danielson et
(10%).62 al64 performed repair of tricuspid valve and closed the ASD
(Figures 11A and B). Repair of TV consisted of plication
Management 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
Medical Management
tricuspid valve decreased the incidence of AV block following
The management depends on severity and age at presentation. surgery. In this method, the coronary sinus is left below the
Asymptomatic cyanotic newborn do not need any active prosthetic tricuspid valve.66,67
treatment unless cyanosis is severe. Treatment consists of Carpentier’s repair15 consists of placating the atrialized
temporarily keeping the PDA open using prostaglandin portion of RV and narrowing the tricuspid valve annulus
(PG) E1 infusion (0.05–0.1 mcg/kg/min) until PVR drops. but, in a direction at right angles from that performed by
Occasionally, use of inhaled nitric oxide to reduce PVR Danielson. This results in a more normal-sized and shaped RV
has helped to improve pulmonary blood flow and hence than in Danielson’s repair. Carpentier also used annuloplasty
the systemic oxygenation. Such therapy is usually needed ring.15 Quaegebeur et al68 performed repair similar to that of
for a few days only, after which they can be safely weaned. Carpentier repair, but without using annuloplasty ring.
Intubation and positive pressure ventilation may help to Some surgeons argue that a simple closure of ASD with
manage pulmonary hypertension more effectively. Deep replacement of TV without plication of atrialized portion of
sedation and muscle relaxant may be necessary for few days RV may be adequate. This argument is based on a consideration
to manage pulmonary hypertension. Correction of metabolic that plication of atrialized portion of RV does not seem to
acidosis with bicarbonate infusions and inotropic infusions add any functional advantage to the RV. But, the widely-held
for low cardiac output will be needed.28 Few neonates may view69,70 is that plication of the atrialized portion of the RV
require surgical systemic-pulmonary shunt to maintain should be performed especially when the displacement of the
adequate pulmonary blood flow and thus, maintain adequate tricuspid valve is moderate or severe.69,70
systemic oxygen saturation. Cone procedure: Da Silva et al71 described a repair that
Features of heart failure from tricuspid regurgitation may consisted of mobilizing the anterior and posterior leaflets from
be treated with anti-failure medications such as Furosemide their anomalous attachments, rotating the detached edges
and Digoxin. of these leaflets clockwise and suturing them to the septal
Supraventricular tachycardia from accessory pathway or edge of the anterior leaflet at the level of true tricuspid valve
atrial flutter from enlarged atrium should be controlled using annulus. This creates a cone with its apex at the RV apex and
appropriate anti-arrhythmic medications. the base at the true tricuspid annulus. Septal leaflets, when
424 Restrictive PFO/ASD may require balloon atrial septostomy present are incorporated into this cone. ASD is closed as in the
in order to stabilize the baby for further management. While this other techniques. This procedure was performed with minimal
29

a B
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 figure 12: Schematic showing the principle behind Starnes Procedure.
LV systolic function or a combination thereof. This surgery Patch – Patch closure of the tricuspid valve orifice. Fenestration is
consists of patch closure of ASD, repair of tricuspid valve created to allow for escape of blood that returns through thebesian
veins to the right ventricle. ASD – Atrial septal defect is enlarged.
with reduction of the atrialized portion of right ventricle and A systemic to pulmonary arterial shunt (central shunt) is shown in
a bidirectional Glenn operation (i.e. end to side anastomosis the figure. Alternatively Blalock-Taussig shunt may be performed.
of the superior vena cava to the right pulmonary artery). CS = Coronary sinus
This surgery accomplishes the following—unloads the right
atrial and right ventricular volume by approximately one-
third and still, right ventricle can contribute to the pulmonary the tricuspid valve without concern for tricuspid stenosis due
circulation maintaining pulsatile flow and allowing for to overcorrection.73-75
flexibility to cope with transient increases in pulmonary Fontan operation: This may be an optimal option for a rare
vascular resistance and allows for more aggressive repair of patient with tricuspid stenosis and hypoplastic right ventricle. 425
6 Fontan operation, of course, is usually preceded by either an 1. New York Heart Association (NYHA) III or IV.
aortopulmonary shunt in the newborn period and followed by 2. NYHA I and II, but with CT ratio of 0.65 or more.
a bidirectional Glenn operation, as a staged procedure.76 3. Significant cyanosis (80% or less; Hemoglobin 16 gm% or
Neonates and young children: Indications for surgery in more).

newborns and infants with cyanosis and congestive heart 4. Paradoxical embolism.
failure (CHF) are not clear and the decision to perform surgery 5. Intractable arrhythmia (even though arrhythmia may not be
should be individualized. General principle of management altered by surgery, but it is better tolerated after surgery).
of a newborn with symptomatic Ebstein anomaly is to allow A retrospective, single-center study from Munich,
sufficient time for medical management to work so that surgery Germany79 reviewed outcome from older age group of patients.
may be postponed or avoided early in life. In relatively milder One hundred and thirty patients with Ebstein anomaly who
cases, reduction in pulmonary vascular resistance may allow underwent valve repair or replacement between 1976 and 2007
discontinuation of PG infusion resulting in closure of PDA at a mean age of 24 years were studied; 90 percent patients
and weaning inhaled nitric oxide, if used in early treatment. underwent primary valve repair, while 10 percent underwent
The babies that do not stabilize following withdrawal of above valve replacement. Hospital mortality was 1.5 percent. Overall
management may need surgical repair as newborn. survival was 87, 85 and 81 percent at 10, 20 and 25 years
Neonates who require surgical repair present a great respectively. Risk factors for mortality were NYHA functional
challenge. Management objectives in a neonate, as emphasized class more than II and CT ratio more than 0.6. The investigators
above, are initially focused on avoiding surgical intervention. suggest that surgery should be performed, before functional
However, if the baby has significant cyanosis and heart failure, status deteriorates and significant cardiomegaly occurs.79
with or without RV outflow tract obstruction, anatomic or
functional, surgical treatment will become unavoidable. Adults with Ebstein Anomaly
One recent study from a single center reported 40
consecutive neonates seen over a 20 year period between Patients with mild Ebstein anomaly may be asymptomatic
1988 and 2008.77 No intervention was necessary in 16 babies. in adulthood. Patients with moderate Ebstein anomaly
Surgical intervention was performed in 24 babies at a mean become symptomatic during adolescence or early adulthood.
age of 6 days and a mean weight 3.2 kg. Surgery consisted of Commonest symptoms are exercise intolerance and palpitation
tricuspid valve closure (Starnes procedure) in 11 (3 of these from supraventricular tachycardia. When ASD is present,
babies died early), TV repair in four (3 of these died early) or cyanosis, stroke or transient ischemic attacks (TIA) may
only an aortopulmonary shunt in nine (all of them survived). occur. Sudden death from arrhythmias may also occur. Apart
Of the nine shunt patients, two needed closure of TV later. from transthoracic echocardiogram and ECG, diagnostic
Overall, six of 24 babies died early. Of the 18 early survivors, work-up may involve TEE, exercise testing with oximetry,
four died late during a 7 year follow-up period. Overall, Holter monitoring and/or electrophysiology (EP) study and
survival for surgical patients was 66 percent at 1 year, 62 MRI. Active management is indicated for NYHA class III
percent at five and 10 years and 52 percent at 15 years of age.77 or IV, Cardiothoracic ratio more than 65 percent, significant
Better survival in shunt—only group of 89 percent at 1 year cyanosis, severe tricuspid regurgitation with symptoms and
and 76 percent at five and 10 years was also observed. Worst stroke. As far as surgical repair is concerned, if the anterior
results were for the TV repair group in whom three of the four leaflet is mobile and there is adequate sized, functional RV,
babies had early mortality. This is a single center experience; valve repair or replacement should be attempted. Closure of
the results will inevitably vary from one institution to the ASD only may help some patients with exercise limitation.
other. These data would suggest aorto-pulmonary shunt or This can be performed using transcatheter technique if test
Starnes procedure are good options to consider in the newborn occlusion does not drop the cardiac output and RA pressure
babies. does not increase. Some patients are candidates for one and a
Postoperative management is largely dependent upon half ventricle repair described above or for Fontan operation.
the preoperative state of the child and quality of repair. In Atrial arrhythmias and supraventricular tachycardia are treated
a newborn, control PVR and initially support RV and LV either at surgery or by transcatheter techniques. Pregnancy is
function with intubation, ventilation, sedation and inotropic well tolerated if the patient does not have cyanosis, right heart
support. Low cardiac output state is the most common issue failure or arrhythmias. Slightly higher incidence of premature
that needs to be dealt with in this group of patients—probably delivery has been reported.76
secondary to large RA and atrialized RV and RV-LV interaction
leading to poor LV function. Postoperative arrhythmias may Arrhythmia Management
occur— specifically supraventricular tachycardia or atrial
arrhythmias and should be addressed aggressively. Supraventricular tachycardia (SVT) is common with Ebstein
Older children and adults: Indication for surgery in older as alluded to earlier. Types of arrhythmia noted in patients with
426 children and adults include the following:78 Ebstein’s anomaly are SVT secondary to accessory pathways
(manifest WPW syndrome or concealed pathway) or atrio- manage. Prognosis depends on severity of the lesion, age at 29
ventricular re-entry tachycardia (AVNRT), atrial flutter or presentation and type of surgical repair. Surgical outcomes
fibrillation. Rarely, junctional tachycardia and ventricular have improved over time but, early presentation as fetus and

tachycardia have been noted.36 If a patient with Ebstein newborn is associated with poor prognosis.
shows WPW syndrome in the ECG, management depends
on presence of arrhythmia, its severity and frequency. No EbsTEINOID MALFORMATION OF LEFT AV VALVE (WITH
consensus exists regarding the treatment of an asymptomatic L-TRANsPOsITION OF GREAT ARTERIEs)
patient with Ebstein anomaly and WPW syndrome.34 Some
investigators advise a risk-stratification EP study—either L-transposition of great arteries (L-TGA) was originally
transesophageal or intracardiac. If the refractory period of described by von Rokitansky in 1875.82 L-TGA is a congenital
the anomalous pathway is below a certain value (effective heart defect characterized by atrial situs solitus, atrio-
refractory period less than 280 ms), radiofrequency ablation ventricular discordance and ventriculo-arterial discordance,
is advised.80 Beta-blocker therapy remains the first-line of i.e. right atrium empties systemic venous blood into a right-
medical therapy for SVT in patients with Ebstein anomaly, sided, morphologic LV and then into the pulmonary artery
similar to children without Ebstein anomaly. (Figure 13A) and the left atrium empties pulmonary venous
Ablation is recommended if the arrhythmia is recurrent or blood into a left-sided, morphologic RV and then into the aorta
surgery is contemplated. Radiofrequency catheter ablation (Figure 13B).29,83 Since the pulmonary artery comes of the left
specifically may be technically challenging due to anatomic ventricle and the aorta from the right ventricle, transposition of
peculiarities of the tricuspid valve annulus, fragmented nature great arteries is deemed to exist. However, normal blood flow
of the ventricular electrograms from the atrialized portion pattern is preserved, hence, the term, congenitally corrected
of the right ventricle and relative instability of the ablation transposition of the great arteries or corrected transposition in
catheters. Use of appropriately pre-shaped catheters, use of short. In this condition the ventricles are essentially inverted
right coronary angiograms or use of 2-French catheter in right (Figure 13). Normally the aorta is located to the right of
coronary artery to mark the location of tricuspid valve annulus pulmonary artery; however, in this condition, the aorta is
and use of cryoablation have helped to ease the technical positioned to the left of pulmonary artery (Figure 13); hence
difficulties in Ebstein anomaly.34 Smaller area of triangle of the term L-TGA.
Koch in Ebstein anomaly hearts may result in higher incidence While patients without any associated cardiac defects are
of AV block with ablation in patients with Ebstein’s anomaly reported, the majority of the L-TGA patients have significant
than in otherwise normal hearts.23,24 associated defects, namely, VSD, PS, atrioventricular (AV)
Surgical therapy of arrhythmia is preferred by some block (spontaneous or after catheter or surgical intervention)
workers and is usually performed at the time of surgical repair and Ebstein like malformation of the left-sided, morphologic
of Ebstein anomaly. In a study of adult patients from Mayo atrio-ventricular valve.
clinic (median age of 25 years) with Ebstein anomaly and As discussed above, the morphologic RV is located on
arrhythmia, 83 of the 109 study patients underwent surgical the left side and morphologic LV is located on the right
therapy for arrhythmia at the time of surgery for Ebstein side. The AV valves correspond to morphologic ventricular
anomaly; these procedures consisted of at least one of: chambers.84-87 Consequently, the tricuspid valve is on the left
a. Surgical ablation of an accessory pathway for SVT. side of the heart, associated with the morphologic RV. Ebstein
b. Surgical perinodal cryoablation for AVNRT. malformation of such left-sided AV valve is sometimes called
c. Right-sided maze procedure and/or cryoablation of the Ebsteinoid or Ebstein a like malformation to differentiate it
atrial isthmus for atrial flutter-fibrillation.81 from classic Ebstein anomaly discussed in the preceding
Freedom from arrhythmia recurrence was 100 percent for section. L-TGA is more extensively discussed elsewhere
SVT at a mean follow-up of 48 months, 100 percent for atrio- in this book. A brief description relevant to tricuspid valve
ventricular nodal reentry tachycardia at a mean follow up of abnormalities is provided here.
57 months and 75 percent for atrial flutter or fibrillation at
a mean follow up of 34 months.81 Whether recent advances Clinical Presentation
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
CONCLUsION shunting or VSD and pulmonary outflow tract obstruction
together causing pulmonary oligemia rather than from
Ebstein anomaly is a rare congenital heart disease. Clinical Ebsteinoid malformation. Sometimes, the regurgitation of
manifestations vary depending upon the severity of the the Ebsteinoid valve may be the sole reason for symptoms
lesion. Mild forms may be asymptomatic and may not of heart failure in early life.87 The symptoms (dyspnea on
need any treatment. Moderate forms may be managed with exertion) occur more often latter in life as seen in the patient 427
relative ease. Severe forms of the disease are a challenge to shown in Figures 13A and B.
6
a B
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
Physical Examination Echocardiogram

Loud single second heart sound may be heard because
of antero-posterior orientation of great arteries leading to Echocardiogram is diagnostic, but may be challenging to
muffling of the posteriorly placed pulmonary valve sound. perform and interpret to a novice. Absence of continuity
Left sided AV valve regurgitation produces a holosystolic between left AV valve and aortic valve due to presence of
murmur at apex and left lower sternal border. This may be conus on the left-side is one of the echocardiographic features.
similar to VSD murmur but may be differentiated based on Degree of downward displacement of the left-sided tricuspid
radiation to anterior and mid-axillary lines. valve may be assessed in a four chamber view. Left AV valve
regurgitation may be semi-quantified. Associated lesions may
also be defined.
Investigations
Other Studies
Chest X-ray
Simultaneous recording of pressures and intracavitary ECG
Chest X-ray findings include left atrial enlargement and peculiar may help firm up the diagnosis,87 a manner similar to normally
contour (straightening) of the left superior mediastinum due to located Ebstein anomaly of the tricuspid valve.29 But, such
superior extension of left border of the cardiac silhouette. This studies may not be necessary given the diagnostic accuracy
appearance is created by the ascending aorta arising from the of echocardiographic studies. Similarly, angiography is no
anterior and leftward aortic valve. longer needed to confirm this diagnosis.
Electrocardiogram Management
Electrocardiogram is characteristic with absence of Q wave in Patients with mild AV valve insufficiency may need
left precordial leads and presence of Q wave in V1 indicating periodic follow-up. Treatment of congestive heart failure
reversal of septal depolarization.86 Left atrial enlargement including afterload reducing agents may be needed in
and right ventricular dominance are other features. Atrio- moderate to severe AV valve insufficiency. Some of these
ventricular conduction block (prolonged PR interval through infants may require surgical repair or replacement of
428 3rd degree heart block) may be present. left AV valve later in life. Discussion of considerations
for double switch operation is beyond the scope of this Echocardiogram 29
chapter.
Echocardiogram will help to distinguish this lesion from

TRICUsPID VALVE sTENOsIs tricuspid atresia and elucidate associated lesions. By cardiac
catheterization, diastolic gradient may vary depending upon
Congenital tricuspid valve stenosis is very rare as an isolated right atrial dilatation, severity of stenosis and chronicity of the
lesion. Tricuspid valve stenosis may occur in association with stenosis at the time of evaluation.
other defects such as pulmonary atresia or stenosis, double
outlet right ventricle, single ventricle, tetralogy of Fallot, Management
transposition of great arteries, ventricular septal defect or
Uhl’s anomaly.29 Isolated lesions are more common in female. Management is similar to tricuspid atresia. Associated lesions
Familial cases have also been reported.29 Tricuspid valve will dictate management. Restrictive atrial level shunt may
stenosis may also be acquired secondary to rheumatic fever, warrant an emergency atrial septostomy in neonates. However,
though rare. in some marginal patients with adequate size right ventricle
and adequate tricuspid valve annulus, commissurotomy or
Pathology valve excision or replacement have been attempted. Rare
descriptions of balloon valvuloplasty of isolated tricuspid
Pathology of tricuspid valve stenosis includes either hypoplasia valve stenosis have been reported, mostly in adult patients.91-93
of the valve including valve annulus, leaflets and chordae,
two-leaflet (mitralized) tricuspid valve with abnormal chordal TRICUsPID REGURGITATION
attachments or conversion of a sheet of valve structure attached
to short chordae and small or markedly abbreviated papillary Tricuspid regurgitation occurs in various clinical settings,
muscles.88 Parachute tricuspid valve has been reported in frequently in association with other pathologies. In these
association with tetralogy of Fallot and double-outlet right clinical settings, tricuspid regurgitation may be considered
ventricle. There is usually corresponding hypoplasia of the secondary, with largely a normal valve anatomy. However,
right ventricle.89 isolated tricuspid regurgitation, while rarely encountered, is
well-documented in association with anatomic abnormality
Clinical Manifestation of the tricuspid valve94-98 such as tricuspid valve dysplasia
characterized by thickened, elongated or partially absent
Chief clinical manifestation is cyanosis from right to left leaflets, shortened and abnormally-inserted chordae tendinae
shunting across the patent foramen ovale or atrial septal defect. and underdeveloped papillary muscle.97
Associated lesions will dictate rest of the clinical features. Transient tricuspid regurgitation in newborn is very
Features of elevated right atrial pressure may be evident if the common in association with persistent pulmonary hyper-
atrial level shunt has restriction to flow. As right atrial pressure tension of newborn or transient myocardial ischemia
increases, venous congestion with distension of jugular veins, secondary asphyxia.99-102
noticeable in older children and adults, liver enlargement, Tricuspid regurgitation associated with other congenital
ascites, pleural effusion and peripheral edema may become heart lesions such as pulmonary atresia or critical pulmonary
evident. Chronic fatigue and exercise intolerance will be the stenosis are secondary to extremely high right ventricular
presentation in chronic patients who have mildly low cardiac pressure and lack of egress from right ventricle. Generally,
output or low reserve. Atrial arrhythmias may occur due to right tricuspid valve is likely to be normally formed, though the
atrial enlargement. Since the atrium may hypertrophy and dilate annulus may be hypoplastic to a variable extent depending
to accommodate the venous congestion, right atrial pressure upon the right ventricular size.
may remain low when measured by cardiac catheterization. Tricuspid regurgitation associated with Ebstein anomaly,
Uhl’s anomaly and atrioventricular septal defect (endocardial
Chest X-ray cushion defects) are associated with abnormal valve
development and have been discussed elsewhere in this book.
Chest X-ray demonstrates significant right atrial enlargement Straddling and/or overriding tricuspid valve may also be
and diminished pulmonary vascular markings. regurgitant.
Finally, a category of patients who constitute a large group
Electrocardiogram in pediatric cardiology practice include tricuspid regurgitation
that occurs after surgical repair of atrioventricular septal
Electrocardiogram demonstrates right atrial enlargement, left defects. Rarely such tricuspid regurgitation may occur also
axis deviation of the QRS in the frontal plane, because it, along after repair of cardiac defects such as tetralogy of Fallot,
with tricuspid atresia belong to a spectrum of morphologic double outlet right ventricle and many other conditions 429
abnormalities of the tricuspid valve.90 associated with placement of RV-PA conduit. Tricuspid valve
6 is usually normal in these lesions. Tricuspid regurgitation Cardiac Catheterization
may also occur secondary to chronic volume overload of
the right ventricle from free pulmonary regurgitation—with Cardiac catheterization may be indicated for a variety of
or without associated pressure overload secondary to right reasons depending upon the etiology in a given patient. Right
ventricular outflow obstruction. These patients become atrial mean pressure may be elevated. However, in chronic
symptomatic over several years during long-term follow-up tricuspid regurgitation, right atrial enlargement and venous
after surgical repair. compliance may accommodate the regurgitant volume
leading to relatively lower right atrial mean pressure than
Clinical Presentation expected. Prominent ‘v’ wave in right atrial trace is indicative
of tricuspid insufficiency. Systemic desaturation occurs
Neonates present with cyanosis at birth. If the cause if there is right to left shunting at atrial level. RV systolic
of tricuspid regurgitation is transient such as persistent pressure may be elevated depending upon associated cardiac
pulmonary hypertension of newborn or myocardial depression lesions. Right ventricular end-diastolic pressure is elevated as
from birth asphyxia, this will resolve as the primary cause well. Right ventriculogram demonstrates the enlarged right
resolves and patent foramen ovale starts to close. Transient ventricle, reveals the severity of tricuspid regurgitation and
heart failure features may occur, but uncommon. In older outlines the right atrium that is usually enlarged.
children, presentation usually is chronic fatigue and exercise
intolerance. Clinical examination may include features of Management
heart failure, single S2, holosystolic murmur with thrill at
the left lower sternal border and sometimes a mid-diastolic In newborn with tricuspid regurgitation secondary to persistent
murmur may be heard at the left lower sternal border.29 pulmonary hypertension or myocardial depression, treatment
should be directed at the primary cause such as nitric oxide for
Investigations pulmonary hypertension. In newborn with isolated tricuspid
regurgitation, prostaglandin infusion may help decrease
systemic hypoxia until pulmonary vascular resistance decreases
Chest X-ray
enough to decrease right ventricular pressure. Heart failure
Chest X-ray shows severe cardiomegaly usually secondary may need diuretics and Digoxin. Other supportive therapy
to right atrial enlargement and right ventricular enlargement. depending upon the severity of the clinical manifestations will
Decreased pulmonary vascular markings are usually expected be required such as monitoring arterial blood gases, correction
in a newborn. In older children, this may not be present. of any acidosis, electrolyte abnormalities, providing assisted
ventilation, etc. Every attempt is made to avoid neonatal surgery
Electrocardiogram for tricuspid regurgitation which may include annuloplasty
alone, valve repair or valve replacement. DeVega tricuspid
Electrocardiogram shows right axis deviation, right atrial annuloplasty procedure was originally described in 1973 and is
enlargement and sometimes, right bundle branch block. This performed either by itself or along with another cardiac repair
may vary depending upon associated cardiac lesions and prior and provides excellent relief from tricuspid regurgitation.105,106
heart surgery. In older children, results of tricuspid valve surgery are better.
Although echocardiographic tricuspid regurgitation may
Echocardiography increase with time following repair, reintervention is rarely
necessary.107
Echocardiography is diagnostic and provides good
evaluation of severity and may help elucidate the mechanism sUMMARY AND CONCLUsION
of regurgitation. Objectives of echocardiography include
assessing the severity of tricuspid regurgitation using a In this chapter, Ebstein’s malformation of the tricuspid valve,
combination of chamber size and pulse, continuous wave Ebstein’s anomaly of the left-sided atrioventricular valve
Doppler and color Doppler imaging. Reversal of flow in vena in corrected transposition, tricuspid stenosis and tricuspid
cavae and hepatic veins are helpful in assessing severity. regurgitation were discussed.
Mechanism of tricuspid regurgitation including assessment In Ebstein’s anomaly of the tricuspid valve, there is
valve anatomy, subvalvar apparatus and coaptation of downward (apical) displacement of insertion of septal
leaflets should be assessed. In older children and adults, TEE and posterior leaflets along with valve dysplasia leading to
may help when transthoracic acoustic windows are poor and tricuspid regurgitation, right atrial enlargement and varying
the image quality is inadequate. Assessment of severity of degrees of atrialization of the right ventricle. It is a rare
other co-existing cardiac lesions should be performed as anomaly accounting for 0.3 – 0.6% of all congenital heart
430 well.103,104 defects. Differing presentations are seen which depend upon
severity of each component of lesion and associated lesions. 8. Yacobi S, Ornoy A. Is lithium a real teratogen? What can we
conclude from prospective versus retrospective studies. A
29
Mild cases may not be detected until adulthood. More
severe forms present during neonatal period or even in the review. Isr J Psychiatry Relat Sci. 2008;45:95.

fetus. Clinical features, chest X-ray and electrocardiogram 9. Gentile S. Lithium in pregnancy: the need to treat, the duty to
ensure safety. Expert Opinion in Drug Safety. 2012;11:425.
are suggestive of the diagnosis and echocardiogram is
10. Restrepo CG, Pedraza RS, Camacho A. Use of lithium during
confirmatory. Celermajer index (RA + atrialized portion of
pregnancy: A case report using clinical decision analysis. Rev
RV ÷ the combined area of functional, distal portion of RV + Bras Psiquiatr. 2010;32:95.
LV + LA) is useful in grading the disease and is of prognostic 11. Digilio MC, Bernardini L, Lepri F, et al. Ebstein’s anomaly:
value. Management depends upon the severity of the lesion Genetic heterogeneity and association with microdeletion 1p36
and may include simple observation to surgery in the neonatal and 8p23.1. Am J Genetics. 2011;155:2196.
period. Supraventricular tachycardia may need treatment with 12. van Engelen K, Postma AV, van de Meerakker JB, et al. Ebstein’s
medications, some require ablation of the WPW tract. Surgical anomaly may be caused by mutations in the sarcomere protein
outcomes have improved over time but, early presentation as gene MYH7. Neth Heart J 2011 May 21. E-Published ahead of
print. http://www.springerlink.com/content/4t3k67tw5264814
fetus and newborn is associated with poor prognosis.
7/?MUD=MP.
Ebstenoid malformation of left atrioventricular valve,
13. Changela V, Maheshwari S, Bhat M. Williams syndrome and
associated with L-transposition of great arteries is extremely Ebstein’s anomaly: A rare association. Ann Pediatr Cardiol.
rare. Severe atrioventricular valve insufficiency may need 2009;2:165.
surgical repair or replacement of left AV valve. Isolated 14. Connolly HM, Warnes CA. Ebstein’s anomaly: Outcome of
congenital tricuspid valve stenosis is very rare, but may be pregnancy. J Am Coll Cardiol. 1994;5:1194.
seen along with a variety of other congenital heart defects. It 15. Carpentier A, Chauvaud S, Mace L, et al. A new reconstructive
may also be acquired secondary to rheumatic fever. Tricuspid operation for Ebstein’s anomaly of the tricuspid valve. J Thorac
regurgitation is frequently seen in association with other cardiac Cardiovasc Surg. 1988;96:92.
16. Takayasu S, Obunai Y, Konno S. Clinical classification of
pathologies. However, isolated tricuspid regurgitation, while
Ebstein’s anomaly. Am Heart J. 1978;95:154.
rarely seen, is well documented in association with anatomic
17. Rao PS, Jue KL, Isabel-Jones J, et al. Ebstein’s malformation
abnormality of the tricuspid valve. Conservative management of the tricuspid valve with atresia. Am J Cardiol. 1973;32:1004.
is usually effective in the neonatal period and severe forms 18. Newfeld EA, Cole RB, Paul MH. Ebstein’s malformation of
may require surgical (De Vega tricuspid annuloplasty alone, the tricuspid valve in the neonate. Functional and anatomic
valve repair or valve replacement) intervention. outflow tract obstruction. Am J Cardiol. 1967;19:927.
19. Lev M, Liberthson RR, Joseph RH, et al. The pathologic
Despite all our toil and progress, the art of medicine still anatomy of Ebstein’s disease. Arch Pathol. 1970;90:334.
falls somewhere between trout casting and spook writing. 20. Zuberbuhler JR, Allwork SP, Anderson RH. The spectrum of
Ebstein’s anomaly of the tricuspid valve. J Thorac Cardiovasc
—Ben Hecht, Miracle of the Fifteen Murderers
Surg. 1979;77:202.
21. Anderson KR, Lie JT. The right ventricular myocardium in
REFERENCEs Ebstein‘s anomaly. A morphometric histopathologic study.
Mayo Clin Proc. 1979;54:181.
1. Ebstein W. Uber einen sehr seltenen Fall von insufficienz 22. Uhl HS. Uhl’s anomaly revisited. Circulation. 1996;93:1483.
der valvula tricuspidalis, bedingt dwich eine tangeborene 23. Sanchez-Quintana D, Picazo-Angelin B, Cabrera A, et al. Koch’s
hochgradige Missbildung derselben. Arch Anat Physiol triangle and the atrioventricular node in Ebstein’s anomaly:
Wissensch Med 1866;238:254. English translation in Am J Implications for catheter ablation. Rev Esp Cardiol. 2010;63:660.
Cardiol. 1968;22:867. 24. Anderson RH. The triangle of Koch in the setting of Ebstein’s
2. Tourniaire A, Dreyrieuz F, Tartulier M. Maladie d’Ebstein: malformation. Rev Esp Cardiol. 2010;63:633.
Eassai de diagnostic Clinique. Arch Mal Coeur. 1949;42:1211. 25. Song ZZ. A combination of right ventricular hypertrabeculation/
3. Keith JD, Rowe RD, Vlad P. Heart disease in infancy and non-compaction and Ebstein’s anomaly. Int J Cardiol.
childhood. 3rd ed. Macmillan, New York. 1978;1-13;847-55. 2010;143:e30.
4. Rowe RD, Freedom RM, Mehrizi A, Bloom KR. The 26. Bayar N, Canbay A, Ucar O, et al. Association of Gerbode-type
neonate with congenital heart disease. Major Problems in defect and Wolff-Parkinson-White syndrome with Ebstein’s
clinical pediatrics. 2nd edition. W.B. Saunders, Philadelphia. anomaly. Anadolu Kardiyol Derg. 2010;10:88.
1981;5:101-9, 515-28. 27. Bharati S, Lev M. Ebstein’s anomaly. In: Armork (Ed). The
5. Nora JJ, Nora AH, Toews AH. Lithium, Ebstein’s anomaly, and pathology of congenital heart disease. New York: Futura
other congenital heart defects (Letter). Lancet. 1974; 2(7880):594. Publication Company. 1996.pp.815-39.
6. Park JM, Sridaromont S, Ledbetter EO, et al. Ebstein’s anomaly 28. Castaneda AR, Jonas RA, Mayer JE, et al. Ebstein’s anomaly.
of the tricuspid valve associated with prenatal exposure to In: Cardiac Surgery of the Neonate and infant. Philadelphia:
Lithium carbonate. Am J Dis Child. 1980;34:703. WB Saunders Company. 1994.pp.273-80.
7. Weinstein MR, Goldfield MD. Cardiovascular malformation 29. Rao PS. Other tricuspid valve anomalies. In: Long WA (Ed).
with lithium use during pregnancy. Am J Psychol. 1975;132: Fetal and Neonatal Cardiology. Philadelphia: WB Saunders
431
529. Company. 1959;19:165.
6 30. Hornberger LK, Sahn DJ, Kleinman CS, et al. Tricuspid valve
disease with significant tricuspid insufficiency in the fetus:
51. Bharucha T, Anderson RH, Lim ZS, et al. Multiplanar review
of three-dimensional echocardiography gives new insights into
Diagnosis and treatment. J Am Coll Cardiol. 1991;17:167. the morphology of Ebstein’s malformation. Cardiol Young.
31. Schiebler GL, Adams P Jr, Anderson RC, et al. Clinical 2010;20:40.
study of 23 cases of Ebstein’s anomaly of the tricuspid valve. 52. Yalonetsky S, Tobler D, Greutman M, et al. Cardiac magnetic
Circulation. 1959;19:165. resonance imaging and the assessment of Ebstein’s anomaly in
32. Celermajer DS, Bull C, Till JA, et al. Ebstein’s anomaly: adults. Am J Cardiol. 2011;107:767.
presentation and outcome from fetus to adult. J Am Coll 53. Tobler D, Yalonetsky S, Crean AM, et al. Right heart
Cardiol. 1994;23:170. characteristics and exercise parameters in adults with Ebstein’s
33. Flores Arizmendi A, Fernandez Pineda L, Quero Jiminez C, et anomaly: New Perspectives from cardiac magnetic resonance
al. The clinical profile of Ebstein’s malformation as seen from imaging studies. Int J Cardiol 2011 Aug 26 Epub ahead
fetus to the adult in 52 patients. Cardiol Young. 2004;14:55. of print. http://www.sciencedirect.com/science/article/pii/
34. Kanter RJ. Pearls for ablation in congenital heart disease. J S0167527311008291.
Cardiovasc Electrophysiol. 2010;21:223. 54. Zimmer EZ, Balzer S, Lorber A, et al. Fetal Ebstein’s anomaly:
35. Cappato R, Schluter M, Weiss C, et al. Radiofrequency current early and late appearance. Prenat Diagn. 2012;32:228.
catheter ablation of accessory atrioventricular pathways in 55. Andrews RE, Tibby SM, Sharland GK, et al. Predictors of
Ebstein’s anomaly. Circulation. 1996;94:376. outcome of tricuspid valve malformations diagnosed during
36. Delhaas T, Sarvaas GJ, Rijlaarsdam ME, et al. A multicenter, fetal life. Am J Cardiol. 2008;101:1046.
long-term study on arrhythmias in children wth Ebstein’s 56. Barre E, Durand I, Hazelset T, et al. Ebstein’s anomaly and
anomaly. Pediatr Cardiol. 2010;31:229. tricuspid valve dysplasia: prognosis after diagnosis in utero.
37. Bialostozsky D, Medrano GA, Munoz L, et al. Vectorcardio- Pediatr Cardiol. 2012;33:1391-6.
graphic study and anatomic observations in 21 cases of Ebstein’s 57. McElhinney DB, Salvin JW, Colan SD, et al. Improving
malformation of the tricuspid valve. Am J Cardiol. 1972;30:354. outcomes of fetuses and neonates with congenital displacement
38. Kumar AE, Fyler DC, Miettinen OS, et al. Ebstein’s anomaly: (Ebstein’s anomaly) or dysplasia of tricuspid valve. Am J
Clinical profile and natural history. Am J Cardiol. 1971;28:84. Cardiol. 2005;96:582.
39. Rowe RD, F Jreedom RM, Mehriz A, et al. The neonate 58. Ammash NM, Warnes CA, Connolly HM, et al. Mimics of
with congenital heart disease. In: Major prodems in clinical Ebstein’s anomaly. Am Heart J. 1997;134:508.
pediatrics. 2nd edition. Philadelphia: WB Saunders Company. 59. Watson H. Natural history of Ebstein’s anomaly of tricuspid
1981;5:101-9,515-28. valve in childhood and adolescence. Br Heart J. 1974;36:417.
40. Follah F, Hallidie-Smith KA. Unusual electrocardiographic 60. Radford DJ, Graff RF, Neilson GH. Diagnosis and natural
changes in Ebstein’s anomaly. Br heart J. 1972;34:513. history of Ebstein’s anomaly. Br Heart J. 1985;54:517.
41. Shiina A, Seward JB, Edwards WD, et al. Two-dimensional 61. Radford DJ, Graff RF, Neilson GH. Diagnosis and natural
echocardiographic spectrum of Ebstein’s anomaly: Detailed history of Ebstein’s anomaly. Br Heart J. 1985;54:517.
anatomic assessment. J Am Coll Cardiol. 1984;3:356. 62. Legius B, Van De Brugeng A, Van Deyk K, et al. Behavior
42. Rusconi PG, Anderson RH, Rigby ML, et al. Morphologic and of Ebstein’s anomaly: Single-center experience and mid-term
echocardiographic correlates of Ebstein’s malformation. Eur follow-up. Cardiology. 2010;117:90.
Heart J. 1991;12:784. 63. Rao PS, Chandar JS, Sideris EB. Role of inverted buttoned
43. Roberson DA, Silverman NH. Ebstein’s anomaly: Echocar- device in transcatheter occlusion of atrial septal defect or patent
diographic and clinical features in the fetus and neonate. J Am foramen ovale with right-to-left shunting associated with
Coll Cardiol. 1989;14:1300. previously operated complex congenital cardiac anomalies.
44. Celermajer DS, Dodd SM, Greenwald SE, et al. Morbid Am J Cardiol. 1997;80:914.
anatomy in neonates with Ebstein’s anomaly of the tricuspid 64. Danielson GK, Maloney JD, Devloo RAE. Surgical repair of
valve: Pathophyisologic and clinical implications. J Am Coll Ebstein’s anomaly. Mayo Clin Proc. 1979;54:185.
Cardiol. 1992;19:1049. 65. Danielson GK, Driscoll DJ, Mair DD, et al. Operative
45. Snider AR, Serwer GA, Ritter AB. Abnormalities of ventricular treatment of Ebstein’s anomaly. J Thorac Cardiovasc Surg.
inflow. In: Echocardiography in Pediatric Heart Disease. 2nd 1992;104:1195.
edition. St Louis: Mosby. 1996.pp.385-407. 66. Barnard CN, Schrire V. Surgical correction of Ebstein’s
46. Rusconi PG, Zuberbuhler JR, Anderson RH, Rigby ML. anomaly with prosthetic tricuspid valve. Surgery. 1963;54:302.
Morphologic and echocardiographic correlates of Ebstein’s 67. Kirklin JK. Christian Barnard’s contribution to the surgical
malformation. Eur Heart J. 1991;12:784. treatment of Ebstein’s malformation. Ann Thorac Surg.
47. Celermajer DS, Cullen S, Sullivan ID, et al. Outcome in neonates 1991;51:147.
with Ebstein’s anomaly J Am Coll Cardiol. 1992;19:1041. 68. Quaegebeur JM, Sreeram N, Fraser AG, et al. Surgery for
48. Andelfinger G, Shirali GS, Raunikar RA, et al. Functional Ebstein’s anomaly: The clinical and echocardiographic
pulmonary atresia in neonatal Marfan’s syndrome: Successful evaluation of a new technique. J Am Coll Cardiol.
treatment with inhaled nitric oxide. Pediatr Cardiol. 2001;22:525. 1991;14:1300.
49. Mararu D, Badano LP, Sarais C, et al. Evaluation of tricuspid 69. Timmis HH, Hardy JD, Watson DG. The surgical management
valve morphology and function by transthoracic three- of Ebstein’s anomaly. The combined use of tricuspid valve
dimensional echocardiography. Curr Cardiol Rep. 2011;13:242. replacement, atrioventricular plication and atrioplasty. J Thorac
50. Van Noord PT, Scohy TV, McGhie J, et al. Three-dimensional Cardiovasc Surg. 1967;53:385.
432
transesophageal echocardiography in Ebstein’s anomaly. 70. Hardy KL, Roe BB. Ebstein’s anomaly: Further experiences
Interact Cardiovasc Thorac Surg. 2010;10:836. with definitive repair. J Thorac Cardiovasc Surg. 1969;58:553.
71. Da Silva JP, Baumgratz JF, da Fonseca L, et al. The cone
reconstruction of the tricuspid valve in Ebstein’s anomaly. The
tricuspid atresia and stenosis. J Thorac Cardiovasc Surg.
1976;72:383.
29
operation: Early and mid-term results. J Thorac Cardiovasc 89. Marwah A, Suresh PV, Shah S, et al. Parachute tricuspid valve.

Surg. 2007;133:215. European Journal of Echocardiography. 2006;7:226.
72. Starnes VA, Pitlick PT, Bernstein D, et al. Ebstein’s anomaly 90. Rao PS. Is the Term ‘Tricuspid Atresia’ appropriate? (Editorial).
appearing in neonate. J Thorac Cardiovasc Surg. 1991;53:385. Am J Cardiol. 1990;66:1251.
73. Corno AF, Chassot PG, Payot M, et al. Ebstein’s anomaly: One 91. Bourdillon PDV, Hookman LD, Morris SN, et al. Percutaneous
and a half ventricle repair. Swiss Med Wkly. 2002;132:485. balloon valvuloplasty for tricuspid stenosis: Hemodynamic
74. Chauvaud S, Fuzelier JF, Berrebi A, et al. Bidirectional and pathologic findings. Am Heart J. 1989;117:492.
cavopulmonary shunt associated with ventriculo and 92. Rabalino BB, Whitlow PL, Marwick T, et al. Percutaneous
valvuloplasty in Ebstein’s anomaly: Benefits in high risk balloon valvotomy for the treatment of isolated tricuspid
patients. Eur J Cardiothorac Surg. 1998;13:514. stenosis. Chest. 1991;100:867.
75. Chowdury UK, Airan B, Sharma R, et al. One and a half ventricle 93. Shaw TRD. The Inoue balloon for dilatation of the tricuspid
repair with pulsatile bi-directional Glenn: Results and guidelines valve: A modified over-the-wire approach. Br Heart J.
for patient selection. Ann Thorac Surg. 2001;71:1995. 1992;67:263.
76. Silversides CK, Kiess M, Beauchesne L, et al. Canadian Cardio- 94. Barritt DW, Urich H. Congenital tricuspid incompetence. Br
vascular Society 2009 Consensus conference on the manage- Heart J. 1956;18:133.
ment of adults with congenital heart disease: Outflow tract 95. Kincaid OW, Swan HJC, Ongley PA, et al. Congenital tricuspid
obstruction, coarctation of the aorta, tetralogy of Fallot, Ebstein’s insufficiency: Report of two cases. Mayo Clin Proc. 1962;37:640.
anomaly and Marfan’s syndrome. Can J Cardiol. 2010;26:e80. 96. Antia AU, Osunkeya BO. Congenital tricuspid insufficiency.
77. Bove EL, Hirsch JC, Ohye RG, et al. How I Manage Neonatal Br Heart J. 1969;31:664.
Ebstein’s Anomaly. Semin Thorac Cardiovasc Surg Pediatr 97. Becker AE, Becker MJ, Edwards JE. Pathologic spectrum of
Card Surg Ann. 2009.p.63. dysplasia of the tricuspid valve: Features in common with
78. Mair DD, Seward JB, Driscoll DJ, et al. Surgical repair Ebstein’s malformation. Arch Path. 1971;91:167.
of Ebstein’s anomaly: Selection of patients, early and late 98. Barr PA, Celermajer JM, Bowdler JD, et al. Severe congenital
operative results. Circulation. 1985;72:II70. tricuspid incompetence in the neonate. Circulation. 1974;49:962.
79. Badiu CC, Schreiber C, Horer J, et al. Early timing of surgical 99. Boucek RJ Jr, Graham TP Jr, Morgan JP, et al. Spontaneous
intervention in patients with Ebstein’s anomaly predicts superior resolution of massive congenital tricuspid insufficiency.
long-term outcome. Eur J Cardiothorac Surg. 2010;37:186. Circulation. 1976;54:795.
80. Pappone C, Manguso F, Santinelli R, et al. Radiofrequency 100. Bucciarelli R, Nelson RM, Egan EA II, et al. Transient
ablation in children wth asymptomatic Wolff-Parkinson-White tricuspid insufficiency in the newborn: A form of myocardial
syndrome. N Engl J Med. 2004;351:1197. dysfunction in stressed newborn. Pediatrics. 1977;59:330.
81. Khositseth A, Danielson GK, Dearani JA, et al. Supraventricular 101. Riemenschneider TA, Nielsen HC, Ruttenberg HS, et al.
tachyarrhythmias in Ebstein’s anomaly: Management and Disturbances of the transitional circulation. Spectrum of
outcome. J Thorac Cardiovasc Surg. 2004;128:826. pulmonary hypertension and myocardial dysfunction. J
82. Von Rokintansky K. Die defekte der Scheidewande de Herzenz. Pediatr. 1978;89:622.
Vienna, Wilhelm Braumuller. 1875.pp.83-85. 102. Rowe RS, Hoffman T. Transient myocardial ischemia of the
83. Reddy SCB, Chopra PS, Rao PS. Aneurysm of the membranous newborn infant: A form of severe cardiorespiratory distress in
ventricular septum resulting in pulmonary outflow tract full term infants. J Pediatr. 1972;81:243.
obstruction in congenitally corrected transposition of the great 103. Snider AR, Serwer GA, Ritter SE. Methods for obtaining
arteries: A review. Am Heart J. 1997;133:112. quantitative information from echocardiographic examination.
84. Paul MH, van Praagh S, van Praagh R. Corrected transposition In: Echocardiography in pediatric heart disease. 2nd edition. St
of the great arteries. In: Watson H. (Ed). Pediatric Cardiology, Louis: Mosby. 1997.pp.223-24.
St Louis: C.V. Mosby Co. MI. 1968.p.611. 104. Snider AR, Serwer GA, Ritter SE. Abnormalities of ventricular
85. Schiebler GL, Edwards JE, Burchell HB, et al. Congenital inflow. In Echocardiography in pediatric heart disease. 2nd
corrected transposition of the great vessels: A study of 33 edition. St Louis: Mosby. 1997.pp.385-88.
cases. Pediatrics 1961;27:851. 105. De Vega NG, De Rabago G, Castillon L, et al. A new tricuspid
86. Rao PS. Dextrocardia: Systematic approach to differential repair: Short term clinical results in 23 cases. J Cardiovasc
diagnosis. Am Heart J. 1981;102:389. Surg (Torino). 1973;Spec No:384.
87. Rogers JH Jr, Rao PS. Ebstein’s anomaly of the left atrioven- 106. Rabago G, De Vega ND, Castillon L, et al. The new De Vega
tricular valve with congenitally corrected transposition of the technique in tricuspid annuloplasty (results in 150 patients). J
great arteries: Diagnosis by intracavitary echocardiography. Cardiovasc Surg (Torino). 1980;21:231.
Chest. 1977;72:253. 107. Kanter KR, Doelling NE, Fyfe DA, et al. DeVega tricuspid
88. Bharati S, McAllister HA, Tatooles CJ, et al. Anatomic annuloplasty for tricuspid regurgitation in children. Ann
variations in underdeveloped right ventricle related to Thorac Surg. 2001;72:1344.
433
C hapter
30 Pulmonary Valve Diseases
Asha Moorthy, Jain T Kallarakkal
Introduction blood flow. The atrial septum is usually intact; if not the defect
is usually a patent foramen ovale, although a secundum atrial
Congenital pulmonary valve disorders could be stenotic or septal defect may coexist.
regurgitant. Rarely the pulmonary valve could be absent or
atretic. The pulmonary valve disorder may be isolated or History
associated with other congenital heart diseases (CHD).
Pulmonary valvar or valvular stenosis is one of the more
Pulmonary valve anatomy common forms of congenital heart malformations and it has
been extensively studied since the original description of
The pulmonary valve separates the right ventricular outflow pulmonary valve stenosis by John Baptist Morgagni in 1761.3
tract from the pulmonary artery. In normal conditions this The anatomical details of the anomaly was described in his
valve prevents regurgitation of the deoxygenated blood classic monograph.
from the pulmonary artery back to the right ventricle. It is a
semilunar valve and is located anterior, superior and slightly Incidence
to the left of the aortic valve. Pulmonary valve is formed by
three cusps, each with a fibrous node at the midpoint of the Isolated pulmonary valve stenosis is found in 80 to 90 percent
free edges as well as lunulae, which are the thin, crescent- of all patients with right ventricular outflow obstruction and 8
shaped portions of the cusps that serve as the coaptive surfaces to 10 percent of patients with CHD.
of the valve. The cusps of the pulmonary valve are supported Familial occurrence of pulmonary stenosis has been
by free-standing musculature with no direct relationship with reported. Campbell4 found a 2.1 percent incidence of cardiac
the muscular septum; its cusps are thinner and lack a fibrous disease, usually pulmonary stenosis or tetralogy of Fallot
continuity with the anterior leaflet of the right atrioventricular (TOF), in siblings of patients with pulmonary stenosis. In the
valve.1 The cusps of the pulmonary valve are defined by their Second Natural History Study of Congenital Heart Defects, the
relationship to the aortic valve and are thus termed anterior or occurrence of definite and possible congenital heart defects in
non-septal, right and left cusps. They can also be defined by 1,356 siblings of 449 patients with valvar pulmonary stenosis
their relationship to a commissure found in the pulmonary and was 1.1 and 2.1 percent respectively.5
aortic valves and hence termed right adjacent (right facing),
left adjacent (left facing) and opposite (non-facing). The Embryology and Pathology
pulmonary valve, like the other three cardiac valves, is formed
by the endocardial folds that are supported by the internal The exact embryologic process resulting in pulmonary valve
plates of dense collagenous and elastic connective tissue and stenosis is not well understood. Maldevelopment of the distal
are continuous with the cardiac skeleton.2 part of the bulbus cordis,6 fetal endocarditis7 and genetic factors
with multiple somatic abnormalities8 have been proposed.
Pulmonary Stenosis In the classic form of pulmonary valve stenosis, the valve is
conical or dome shaped and two to four raphes may be visible,
Isolated pulmonary valve stenosis is a form of acyanotic con- but there is no separation into the valve leaflets.9 As primarily
genital malformation with normal or diminished pulmonary there is an inherent medial abnormality, the pulmonary trunk
is usually dilated. Less commonly, the valve may be diffusely Clinical Features 30
thickened with one, two or three leaflets and commissural fu-
sion. The unicuspid or bicuspid pulmonary valve is generally Symptoms
Pulmonary Valve diseases

a feature of tetralogy of Fallot, and the stenosis is variable. Patients with moderate-to-severe pulmonary stenosis may
A distinct pathology, pulmonary valve dysplasia, where the experience chest pain, syncope and even sudden death
valves are trileaflet with markedly thickened cusps, composed with strenuous exercise. Decreased myocardial perfusion
of disorganized myxomatous tissue, has been described in 10 caused by inadequate cardiac output during exercise,
to 20 percent of patients10 and found in most patients with leading to ischemia and ventricular arrhythmias, is thought
Noonan syndrome. to be the mechanism for these events. Children with valvar
Secondary changes of pulmonary valve obstruction include pulmonary stenosis usually exhibit normal growth and
infundibular hypertrophy with or without dynamic subvalvar development regardless of the severity of obstruction.
obstruction, thickening of the tricuspid valve and chordal Infants with critical pulmonary stenosis are cyanotic at
attachments, tricuspid regurgitation, thickening and dilatation birth.11 Neonates with critical PS present with cyanosis,
of the right atrium. In many cases, a patent foramen ovale or, CHF, hypotension, feeding difficulty, tachypnea, without
less often an atrial septal defect is seen. Most patients develop appreciable murmur.
poststenotic dilation of the pulmonary artery trunk, sometimes
extending to the proximal left pulmonary artery. One notable Physical Appearance
exception to this finding is patients with dysplastic pulmonary
valves. The degree of dilation is not necessarily proportional Five physical appearances are relevant in patients with
to the severity of obstruction, often being more pronounced pulmonary stenosis. Mobile dome-shaped pulmonary valve
in mild cases. Poststenotic dilation may result from the high stenosis is characterized by chubby, round, bloated face,
velocity jet of flow ejected through the small valve orifice. well developed fat deposits and erythematous digits. Noonan
syndrome is characterized by short stature, webbed neck,
Etiology pterygium colli, ptosis, hypertelorism, lymphedema, low-set
ears, low anterior and posterior hair lines, flat or shield chest,
The most common etiology of pulmonary stenosis is pectus excavatum or carinatum, hyperelastic skin, inguinal
congenital. Rarely, pulmonary stenosis can be acquired due hernia, nevi, dystrophic nails, micrognathia, hypospadias and
to rheumatic heart disease, infective endocarditis, carcinoid small undescended or cryptorchid testes. Rubella syndrome is
syndrome etc. characterized by cataracts, retinopathy, deafness, hypotonia,
dermatoglyphic abnormalities and mental retardation.
Physiology Williams syndrome is characterized by mental retardation,
small chin, large mouth, patulous lips, blunt upturned nose,
The main physiologic effect of valvar pulmonary stenosis is wide-set eyes, broad forehead, baggy cheeks and malformed
a rise in right ventricular pressure, which is proportional to teeth. Alagille syndrome is characterized by prominent
the severity of the obstruction. This is accompanied by an overhanging forehead, deep set eyes and a small pointed
increase in muscle mass. Increased muscle mass may enable chin.
the hypertensive right ventricle to maintain a normal stroke
volume. If the size of the stenotic orifice remains fixed, the Pulse
degree of obstruction becomes relatively more severe as the
individual grows. The right ventricle eventually may dilate Arterial pulse is reduced when, severe pulmonary stenosis is
and fail. This process is exacerbated by the development of accompanied by right ventricular failure and left ventricular
tricuspid insufficiency in many patients. As right ventricular dysfunction.
output decreases with a failing ventricle, adequate tissue
oxygenation can be maintained only by increasing tissue Jugular Venous Pulse
oxygen extraction. Any increase in oxygen demand, such as
exercise, may result in frank peripheral cyanosis. In patients Jugular venous ʻaʼ wave gets progressively larger as the
with a patent foramen ovale or atrial septal defect, central severity of pulmonary stenosis increases. Powerful right atrial
cyanosis is observed as a result of right-to-left atrial shunting, contraction generates a giant jugular venous ʻaʼ wave and a
when the right atrial pressure exceeds the left atrial pressure. presystolic liver pulse. With the advent of right ventricular
Progressive hypertrophy and decreased compliance of the failure and tricuspid regurgitation, the ʻvʼ wave increases, the
right ventricle or myocardial failure with subsequent dilation Y descent becomes brisk and the liver manifests presystolic
may lead to central cyanosis in some patients. and systolic pulsations.
435
6 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 Figure 1: Schematic illustration of valvar pulmonic stenosis. In mild
to the degree of stenosis. The split may become fixed stenosis, the ejection click (EC) is clearly separated from the first heart
in severe stenosis as a result of fixed stroke volume. The sound (S1). The murmur starts with the click, peaks in early systole,
and ends way before the aortic component of the second heart sound
intensity of pulmonary component decreases with increasing (A2). The pulmonary component of the second heart sound (P2) is
obstruction. A fourth heart sound is heard at the left sternal normal or decreased in intensity. In moderate pulmonic stenosis,
border with severe stenosis. The systolic murmur of valvular the click is closer to the first heart sound, the ejection murmur peaks
pulmonary stenosis increases with severity, radiates over later in the systole and the murmur reaches A2 and the second heart
sound is widely split with soft pulmonary component. In severe valvar
the entire precordium and neck, characteristically heard in obstruction, the click is either absent or occurs so close to S1 that it
the back and is ejection in quality with maximal intensity at cannot be heard separately, and the murmur peaks late in systole and
the upper left sternal border (Figure 1). Patients with severe extends beyond the A2. The second heart sound is widely split with an
stenosis and right heart failure may have an unusually soft extremely soft or inaudible P2
murmur because of low cardiac output.
In patients between 2 and 20 years of age, a pure R wave is
Diagnosis present in lead V112 (Figure 2).
In pulmonary stenosis, the electrocardiogram findings of left
Electrocardiogram axis deviation with right ventricular hypertrophy is suggestive
of Noonan syndrome (dysplastic pulmonary valve).
In mild pulmonary stenosis, slight rightward deviation of QRS
frontal axis and right ventricular conduction delay is usually Chest X-ray
seen on the electrocardiogram (ECG).
In moderate pulmonary stenosis only 10 percent of patients The most distinctive feature in valvular pulmonary stenosis
have a normal tracing. Right-axis deviation is usually present. is a prominent main pulmonary artery resulting from post-
The R:S ratio in V1 is usually more than 4:1 and the R wave is stenotic dilatation, which is present in 80 to 90 percent of the
typically less than 20 mm. The T waves in the right precordial cases. The apex of the heart is usually rounded and pointing
leads are upright in approximately 50 percent of patients. downwards (Figure 3). A left aortic arch is virtually always
In severe pulmonary stenosis, the mean frontal QRS axis is present. When heart failure develops, marked cardiomegaly
usually more than 110 degrees. A pure R, Rs or qR is usually results owing to right atrial and right ventricular enlargement
seen in right precordial leads and the R wave is usually more and pulmonary vascularity is decreased as a result of reduced
than 20 mm. The R:S ratio in V6 may be less than 1. The pulmonary flow.
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 Echocardiography
in right precordial leads.
In lead V1, the height of R wave in millimeters, multiplied The two-dimensional echocardiogram clearly demonstrates
436 by 5 approximates the right ventricular pressure in mm Hg. 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).
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
Figure 3: Fluroscopic image in anterioposterior view in a 3 month old a pressure gradient across the pulmonary valve of more than
infant with severe valvar pulmonic stenosis showing cardiomegaly with 10 are considered abnormal. An end-hole catheter is used to
right ventricle, right atrium and main pulmonary artery dilatation with
oligemia
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
standard and high parasternal short-axis and long-axis views end-diastolic pressure may be normal, but usually is elevated
as well as the subcostal sagittal views. The leaflets are usually with severe obstruction or right ventricular failure. The right
thickened, doming with restricted systolic motion. Post- atrial pressure is normal in mild-to-moderate obstruction, but
stenotic dilation of the main and branch pulmonary arteries, tall right atrial ʻaʼ waves are seen with severe obstruction.
right ventricular hypertrophy and anatomy of the tricuspid Pulmonary artery pressure is normal in mild cases, but is
valve can be assessed. Features of dysplastic pulmonary valve decreased and dampened in severe cases. This depression 437
6
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 meas-
urements 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
A B
right ventricular pressure more than or equal to 75 percent of
the left ventricular pressure or a gradient more than 60 to 70 Figures 5A and B: A. Fluoroscopy in lateral view shows Tyshak
Balloon across the stenotic pulmonary valve with a waist; B. Fully
mm Hg. inflated balloon with no waist
Treatment
Balloon Valvuloplasty 20 mm, the double-balloon technique may be necessary, with

simultaneous inflation of two angioplasty balloons. A method
First described by Kan and associates in 1982.13 The technique to calculate the effective diameter of two balloons was
of balloon valvuloplasty is relatively easy. After obtaining described by Radke et al. Following balloon dilation, a careful
appropriate hemodynamic and angiographic information pullback with an end-hole catheter is performed to evaluate
about the severity and location of obstruction, an exchange the degree and site of any residual obstruction.14
guidewire is introduced through an end-hole catheter and Shortly after the introduction of pulmonary valvuloplasty
positioned in the distal left pulmonary artery. A balloon is in children, the procedure was performed successfully in
chosen that is 20 to 40 percent larger than the angiographically neonates with critical pulmonary valve stenosis. Pulmonary
measured pulmonary valve annulus and it is positioned over balloon valvuloplasty (PBV) is most risky and demanding
a guidewire with the valve at its midpoint. As the balloon in in newborns, but life saving as in this 15-day-old neonate,
inflated, a waist from the stenotic valve should be observed 2.5 kg, with a pulmonary valvar peak systolic gradient of 155
438 initially and should disappear at full inflation (Figures 5A mm Hg (Figures 6A to C). Several technical advances, such as
and B). In patients with an annulus diameter of more than the introduction of low profile balloons, upper limb approach
30

A B C
Figures 6A to C: Pulmonary balloon valvuloplasty (PBV) in a 15-day-old neonate
A B
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 Surgical Valvotomy
balloon dilation in this group of patients, such that it is now
considered the treatment of choice. The use of angled-tip Since the advent of pulmonary valvuloplasty, surgical valvotomy
catheters and high-torque wires has facilitated crossing the tiny is reserved for patients with dysplastic pulmonary valve resistant
pulmonary valve orifice. to dilation or patients with multiple levels of fixed obstruction.
The short and intermediate-term results of pulmonary Valvotomy can be achieved using either a closed or open
valvuloplasty in children and adults with typical pulmonary technique through the main pulmonary artery. Simple valvotomy
valve stenosis have been excellent.15 Long-term outcome has is ineffective, when the pulmonary valve is dysplastic. Partial
been reported in smaller series of patients.16 The significantly or more often total removal of the pulmonary valve may be
lower success rate for patients with dysplastic pulmonary necessary. In addition, insertion of a trans-annular patch may be
valves is not surprising given the anatomic features of these necessary to enlarge the hypoplastic annulus and main pulmonary
valves. The mechanism of obstruction relief in patients with artery. These patients are usually left with at least moderate
typical doming pulmonary valves has been shown to be pulmonary insufficiency, which is well tolerated on follow-up.
commissural splitting, in most cases. Long-term relief of obstruction after pulmonary valvotomy is
Most patients who have been treated with pulmonary excellent, and restenosis is uncommon.
valvuloplasty have some degree of pulmonary insufficiency.
The incidence of moderate pulmonary insufficiency early Indications for the Procedure
after valvuloplasty has been variably reported from less than
5 percent to as much as 24 percent at intermediate-term Currently pulmonary balloon valvuloplasty is the first line
follow-up. of treatment for pulmonary valve stenosis at any age.
439
6 Valvuloplasty should be performed in any symptomatic patient pulmonary regurgitation. Ventricular stiffness is thought to
as soon as the diagnosis is made including infants with critical increase with hypertrophy or increased fibrosis.
pulmonary valve stenosis, but if this is unsuccessful, surgery
should be performed without delay. Even asymptomatic Clinical features

patients with severe obstruction should be treated with
valvuloplasty shortly after diagnosis. Patients with moderate Symptoms
obstruction should undergo elective valvuloplasty, if the right
ventricular pressure is ≥ 50 percent of systemic or higher. No Symptoms of right-sided heart failure can occur when the
intervention is necessary for patients with mild obstruction. severity and duration of the regurgitation result in right
ventricular enlargement and decompensation. Dyspnea on
Conclusion exertion is the most common complaint. Easy fatigability,
light-headedness, peripheral edema, chest pain, palpitations,
Isolated pulmonary valve stenosis is characterized by normal and frank syncope may occur in patients with any cause of
or diminished pulmonary blood flow. Beyond infancy, mild right-sided heart failure and do little to elucidate the etiology
congenital pulmonary stenosis tends not to progress in of the right-sided failure.
severity. Clinical findings in concert with Doppler studies
permit excellent non-invasive assessment of the severity. Jugular Venous Pressure
Intervention for pulmonary stenosis has evolved from surgery
to catheter-based intervention. Balloon valvuloplasty for Jugular venous pressure is usually increased. Often, an
patients more than 2 years provides excellent outcomes. increased ʻaʼ wave is present, but this may be less apparent,
A systolic pressure gradient more than 40 to 50 mm Hg is when significant tricuspid regurgitation with ʻvʼ dominant v
an indication for intervention. Balloon valvuloplasty with wave is also present.
oversized balloons especially in neonates tends to induce
pulmonary insufficiency. Pulmonary stenosis secondary Palpation
to dysplastic valve may require surgery with valvectomy ±
a transannular patch in those with a small annulus. Balloon When right ventricular enlargement is present, a palpable
valvuloplasty is the procedure of choice for critical pulmonary impulse (lift or heave) is usually present at the left lower
stenosis in neonates. sternal border. Palpable pulmonary artery pulsation at the left
upper sternal border may be present in the setting of significant
Pulmonary regurgitation pulmonary artery dilatation. With significant pulmonary
hypertension, pulmonic valve closure can be palpated.
William Osler described pulmonary regurgitation in The
Principles and Practice of Medicine in 1892. The distinctive Auscultation
diastolic murmur of low-pressure pulmonary regurgitation
was characterized in 191017 and in 1936, isolated congenital The pulmonic component of the second heart sound (P2) is
pulmonary valve regurgitation was reported with a review inaudible in the absence of a pulmonic valve. In pulmonic
of the literature.18 The morphology of the congenitally regurgitation due to pulmonary hypertension, P2 is accentuated;
malformed valve is variable. The basis of the valvular with increased right ventricular end-diastolic volume, the
insufficiency may reflect complete absence of the pulmonary ejection time is increased, P2 is delayed and the S2 split is
valve leaflets, rudimentary vestigial leaflets that do not widened. A low-pressure regurgitant flow across the pulmonic
coapt or isolated deficiency of one of the pulmonary valve valve, as occurs when the pulmonary arterial pressure is
leaflets. normal, is heard as a brief, decrescendo early diastolic
murmur at the upper left sternal border. It is made louder by
Pathophysiology squatting or inspiration and softer by Valsalva maneuvers or
expiration. An S3 or S4 may be noted at the left mid-to-lower
Right heart hemodynamics is explained in Figure 8. Pulmonary sternal border because of the presence of right ventricular
regurgitation is driven by the diastolic pressure difference hypertrophy or failure and is augmented by inspiration. The
between the pulmonary artery and the right ventricle. These Graham Steell murmur of pulmonary hypertension is a high-
pressure differences are often small. Hence small increments pitched, early diastolic decrescendo murmur noted over the left
in airway or intrathoracic pressure can increase pulmonary upper-to-left midsternal area and is a result of high-velocity
regurgitation markedly. However, the most important regurgitant flow across an incompetent pulmonic valve. The
determinants are the right ventricular stiffness and right regurgitant flow murmur may be present during the whole
ventricular afterload. A stiff right ventricle will raise the right of diastole because there is a pulmonary-to-right ventricular
440 ventricular diastolic pressure and decrease the gradient for pressure gradient throughout this time period. Typically, the
murmur occurs in severe pulmonary hypertension, when the arterial mean pressure can be estimated by converting the 30
pulmonary artery systolic pressure is more than 60 mm Hg. early diastolic regurgitation velocity to a pressure gradient
The quality of this high-pitched early decrescendo diastolic and then adding it to the estimated right atrial pressure.

murmur is identical to that of aortic insufficiency. However,
the peripheral manifestations of aortic insufficiency are Treatment
absent. The associated findings of tricuspid regurgitation are
frequently present, prominent jugular venous pressure with Pulmonic regurgitation is seldom severe enough to warrant
surging ʻvʼ waves, holosystolic murmur at the lower left special treatment because the right ventricle normally adapts
sternal border (louder with inspiration) and enlarged, pulsatile to low-pressure volume overload without difficulty. High-
liver. pressure volume overload leads to right-sided heart strain
and ultimately, heart failure. Underlying etiologies causing
Diagnosis severe pulmonic regurgitation, must be treated to prevent or
reverse right-sided heart strain and failure that may further
Electrocardiogram complicate the clinical picture. When right-sided heart
failure due to pulmonary regurgitation cannot be ameliorated
Volume overload of the right ventricle represented by terminal by medical management, appropriate options include
r waves in lead V1 and aVR and S waves in lead I and V5-6 surgical reconstruction or replacement of the pulmonic
is the most common change. Atrial fibrillation is exceptional. valve, preferably with a bioprosthetic valve. More recently,
percutaneous intervention for dysfunctional right ventricular
Chest X-ray outflow tract conduits has become available. The intermediate
term results have shown that percutaneous bioprosthetic
Plain radiographs change little with pulmonic regurgitation valve implantation is a reasonable option for patients with
unless tricuspid regurgitation also occurs, in which case dysfunctional right ventricular outflow tract conduits,
cardiomegaly and enlargement of the right-sided heart especially those with high surgical risk.
contour are observed. Prominent central pulmonary arteries
with enlarged hilar vessels and loss of vascularity in the Transcatheter Pulmonary Valve Replacement
peripheral lung fields (‘pruning’) suggests severe pulmonary
hypertension. A variety of implantable pulmonary valves are being
developed,21 but the Bonhoeffer valve is the most mature
Echocardiography technology. This consists of a bovine jugular venous
valve sewn into a stent mounted on a balloon (18 mm,
Two-dimensional echocardiography and M-mode echocardio 20 mm or 22 mm) and delivered via a custom designed
graphy reveal right ventricular hypertrophy and dilatation 20F sheath. Techniques are being developed to allow
and abnormal septal wall motion. In some cases, pulmonic percutaneous insertion of pulmonary valves into the dilated
ring dilatation with poor valve leaflet coaptation may be native right ventricular outflow tract by first reducing the
observed. Color flow Doppler echocardiography is the diameter of the right ventricular outflow tract by a cuff and
mainstay for recognizing pulmonic regurgitation. In trivial- then delivering the valve into the cuff.22 The hemodynamic
to-mild pulmonic regurgitation, the jet is central and narrow. and clinical benefits of this approach have yet to be
In moderate-to-severe pulmonic regurgitation, the width of demonstrated.
the jet increases, as does the penetration of the jet into the
right ventricular outflow tract. In free or open pulmonic Conclusion
regurgitation, color Doppler can miss the jet altogether due
to the brisk and laminar regurgitant flow. Using pulsed wave The deleterious effects of chronic pulmonary regurgitation
and continuous wave Doppler, pulmonary artery systolic and are clearly seen as the syndrome of exercise intolerance
diastolic pressures can be calculated. Pulmonary artery systolic or arrhythmias associated with low pressure dilated right
pressure can be estimated (using continuous wave Doppler) in ventricles. Along with pulmonary regurgitation right ventricular
the presence of tricuspid regurgitation by measuring the peak dilatation is often seen. Percutaneous pulmonary valve insertion
regurgitant flow velocity across the tricuspid valve, converting is a significant advance, but the long-term fate is yet to be
it to a pressure gradient (by use of the modified Bernoulli determined.
equation) and then adding the gradient to an estimate of the
right atrial pressure. Pulmonary artery diastolic pressure can Absent pulmonary valve syndrome
be estimated by measuring the end-diastolic regurgitant flow
velocity across the pulmonic valve (at the QRS complex on Total or subtotal absence of pulmonary artery leaflets is
the ECG), converting it to a pressure gradient and then adding defined as absent pulmonary valve (APV) syndrome. This was 441
the gradient to the estimated right atrial pressure. Pulmonary first described by Chevers in 1847.19 APV may be the result of
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

The main clinical findings include pulmonary insufficiency,
Figure 8: Right heart hemodynamics in severe pulmonary regurgitation. ostial stenosis and bronchial obstruction secondary to
Premature tricuspid valve closure (PTC) occurs in mid-diastole, when
right ventricular diastolic pressure (RV; black line) exceeds right atrial aneurysmally dilated pulmonary arteries. Clinical presentation
pressure (RA; purple line). Premature pulmonic valve opening (PPO) of infants, with either Fallot-type or non-Fallot-type APV,
occurs when right ventricular end-diastolic pressure rises above is essentially the same and include air-trapping and CO2
pulmonary artery (PA) diastolic pressure 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
error or complete failure in valve development. Mild stenosis of the mediastinum on chest X-ray (Figure 9) and right
of the pulmonary artery orifice and aneurysmal dilatation of ventricular hypertrophy on ECG. Diagnosis is confirmed by
the main pulmonary artery as well as of the right or left or echocardiography in the subxiphoid long-axis and short-axis
both pulmonary artery branches coexist. Compression of the views of aneurysmally dilated pulmonary arteries (Figure 10).
major bronchi at the hilum is a secondary phenomenon and is Pulmonary stenosis and insufficiency are shown by Doppler
assumed to develop in fetal life. color-flow (Figure 11). The clinical picture varies according
to onset and severity of symptoms, especially those of
Anatomical Variations respiratory insufficiency.
Thus, patients with APV are divided into two groups:
The spectrum of malformations to which APV may be 1. Adults and children without respiratory complications who
associated can be categorized into two types: APV with or had corrective operation electively between 5 and 20 years.
without ventricular septal defect (VSD).
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

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
442 Figure 9: Chest X-ray in a patient of tetralogy of Fallot with absent
of pulmonary insufficiency and bronchial obstruction by pulmonary valve shows aneurysmally dilated pulmonary artery instead
aneurysmal pulmonary arteries is unique. It is both prenatally of empty pulmonary bay
In the fetus with non-Fallot type and large ductus, there is an 30
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
Figure 10: TTE in parasternal short axis view shows rudimentary
pulmonary valve (absent PV), color Doppler shows both pulmonary
studies and postnatal evaluation and treatment in specialized
stenosis (due to annular narrowing) and regurgitation. Ao = Aorta; LPA centers. Immediate respiratory support and earlier corrective
= Left pulmonary artery; MPA = Main pulmonary artery; RPA = Right operation will improve outcome.
pulmonary artery; RVOT = Right ventricular outflow tract. 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 postop-
erative complications and persistent respiratory symptoms
due to reoccurrence of pulmonary artery dilation and bron-
chial compression or underlying tracheobronchial malacia.
Management
The life-threatening symptom is respiratory distress in the
newborn. It occurs predominantly in the Fallot-type APV. Air-
way management as a primary procedure involves intubation,
mechanical ventilation and extracorporeal membrane oxy-
genation in some infants. It is usually performed under emer-
gency circumstances. Urgent complete surgical repair should
relieve the compression of the tracheobronchial tree. This
is achieved by combined anterior and posterior plication
Figure 11: Transthoracic parasternal short-axis view at the basal level of the pulmonary arteries or by translocation of the pulmo-
with color Doppler demonstrates severe, hardly turbulent pulmonary nary artery anterior to the aorta and away from the airways,
insufficiency (PI) in early diastole in a patient with absent pulmonary ‘maneuver de Lecompte’ procedure.
valve 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
2. Infantile group presenting commonly as critically ill- includes additional closure of the VSD with a patch. In infants
newborns with severe respiratory distress requiring with non-Fallot APV, the ductus arterious must be closed.
mechanical ventilation. Asymptomatic infants can undergo repair within the first 6 to
Recently, the fetus with APV became another important 12 months. Repair should however not be delayed for too long
group. During the first half of pregnancy, the diagnosis in order to avoid the harmful effect of the dilated pulmonary
seems to be incomplete. In the fetus with Fallot-type APV, arteries on the tracheobronchial tree. Apart from conduit
a distinct echocardiographic feature is the right-to-left shunt replacement in children as they grow, other reinterventions
during systole and diastole across the unrestricted VSD may be required, mainly for persistent respiratory symptoms.
secondary to the pressure-volume overload of the right Midterm outcome for patients with Fallot-type APV who
ventricle. Furthermore, the risk of survival of the fetus with survive the initial repair is favorable. Repeat plication of
this condition in later pregnancy may be related to cessation pulmonary arteries and/or utilization of intrabronchial
of the physiological flow from the pulmonary artery into the expandable stents may improve the outcome in patients with
descending aorta through the ductus arteriosus prior to its persistent airway compression who cannot be weaned from 443
premature closure. the respirator because of severe tracheobronchial malacia.
6 Conclusion 8. Noonan JA. Hypertension with Turner phenotype: A new
syndrome with associated congenital heart disease. Am J Dis
Total or subtotal absence of pulmonary artery leaflets is defined Child. 1968;116:373-80.
9. Edwards JE. Congenital malformations of the heart and great

as absent pulmonary valve syndrome. It can be categorized
vessels. In: Gould SE (Ed). Pathology of the Heart. Springfield
into APV with or without VSD. Major clinical findings IL: Charles C, Thomas Publisher; 1953.
include pulmonary insufficiency, ostial stenosis and bronchial 10. Koretzsky ED, Moller JH, Korns ME, et al. Congenital
obstruction. Surgical correction includes placement of a valved pulmonary stenosis resulting from dysplasia of the valve.
conduit in the right ventricular outflow tract and surgical repair Circulation. 1969;40:43-53.
to relieve the compression of the tracheobronchial tree. 11. Freed MD, Rosenthal AR, Bernhard WF, et al. Critical
pulmonary stenosis with a diminutive right ventricle in
To me the ideal doctor would be a man endowed with neonates. Circulation. 1973;48:875-81.
profound knowledge of life and of the soul, intuitively 12. Rudolph AM. Congenital diseases of the heart. Chicago:
Yearbook Medical; 1974.
divining any suffering or disorder of whatever kind, and
13. Kan JS, White RI, Mitchell SE, et al. Percutaneous balloon
restoring peace by his mere presence. valvuloplasty: a new method for treating congenital pulmonary
—Henri Amiel valve stenosis. N Engl J Med. 1982;307:540-2.
14. Radtke W, Keane JF, Fellows KE, et al. Percutaneous balloon
Acknowledgement valvotomy of congenital pulmonary stenosis using oversized
balloons. J Am Coll Cardiol. 1986;8:909-15.
We express our thanks to Dr IB Vijayalakshmi, Professor of 15. Stanger P, Cassidy SC, Girod DA, et al. Balloon pulmonary
Pediatric Cardiology, for providing some of the illustrative valvuloplasty: results of the valvuloplasty and angioplasty
images for this chapter. of congenital anomalies registry. Am J Cardiol. 1990;65:
775-83.
16. Garty Y, Veldtman G, Lee K, et al. Late outcomes after
References pulmonary valve dilatation in neonates, infants and children. J
Invasive Cardiol. 2005;17:318-22.
1. Goss CM, Gray H. Valves of the heart. In: Gray’s Anatomy 17. Hirschfelder A. Diseases of the heart and aorta. Philadelphia
of the Human Body. 29th edition. Philadelphia, Pa: Lea and JB Lippincott Company; 1910.
Febiger; 1973. p. 543. 18. Kissin M. Pulmonary insufficiency with supernumerary
2. Kerr A Jr, Goss CM. Retention of embryonic relationship cusp in pulmonary valve; report of a case and review of the
of aortic and pulmonary valve cusps and suggested literature. Am Heart J. 1936;12:206-27.
nomenclature. Anat Rec. 1956;125:777-82. 19. Chevers N. Recherches maladies arteres pulmonaires. Arch
3. Morgagni JB. De Sedibus et Causis Morboprum [The seats and Gen Med. 1847;15:488-508.
causes of diseases] Vol 1 Venice: Remondini; 1761. p. 154. 20. Cabrera Duro A, Gilbert Valencia J, Idoate Carvajal M, et al.
4. Campbell M. Factors in the aetiology of pulmonary stenosis. Magnetic resonance in a case of a newborn with pulmonary
Br Heart J. 1962;24:625-32. valve agenesis and deletion of chromosomal region 22q 11,2.
5. Driscoll DJ, Michels VV, Gersony WM, et al. Occurrence risk An Esp Pediatr. 2000;52:485-7.
for congenital heart defects in relatives of patients with aortic 21. Hijazi ZM. Transcatheter valve replacement: a new era of
stenosis, pulmonary stenosis, or ventricular septal defect. percutaneous cardiac intervention begins. J Am Coll Cardiol.
Circulation. 1993;87:I114-20. 2004;43:1088-9.
6. Keith A. The Hunterian lectures on malformation of the heart. 22. Boudjemline Y, Agnoletti G, Bonnet D, et al. Percutaneous
Lancet. 1909;2:359. pulmonary valve replacement in a large right ventricular
7. Moore GW, Hutchins GM, Brito JC, et al. Congenital malfor- outflow tract: an experimental study. J Am Coll Cardiol.
mations of the semilunar valves. Hum Pathol. 1980;11:367-72. 2004;43:1082-7.
444
C hapter
31 Congenital Mitral Valve Diseases
Neeraj Awasthy, Radhakrishna S
Congenital mitral valve diseases are a heterogeneous group, Embryology and Anatomy
often complex and are commonly associated with other
congenital heart diseases (CHD) (Table 1). They are rare Embryology
as isolated lesions, occurring in approximately 4 of 1,000 Formation of the atrioventricular (AV) valve is completed
children with CHD. The spectrum of mitral valve disease are early in embryologic development (by approximately 14
shown in Table 1. Mitral valve diseases have been subdivided to 19 weeks of gestation). The mitral valve is formed from
into stenotic, regurgitant or mixed lesions. This chapter will endocardial cushions that originate both at the AV orifice and
focus on the regurgitant lesions and congenital mitral valve from muscular tissue of the ventricular wall. This process
prolapse. The mitral stenotic lesions have been dealt in is driven by regulatory protiens that are expressed in genes
Chapter 27. 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
Table 1
 atrioventricular valves. The papillary muscles are derived
Spectrum of congenital anomalies of mitral valve from the horseshoe-shaped myocardial ridge, which forms
along the left ventricular wall. Delamination and selective
1.
Supramitral ring (SMR) or membrane apoptosis leads to the formation of deep trabeculae leading to
2.
Hypoplasia of the mitral apparatus
the formation of papillary muscles. Chordae tendineae form
3.
Dysplasia of the mitral valve
4.
Parachute mitral valve from the process of selective apoptosis of the endocardial
Cleft mitral leaflet
5. cushions. These processes create the four major components
6.
Abnormal mitral arcade of the mitral valve appartus, which are the annulus, leaflets,
7.
Double orifice mitral valve chordae tendineae and the papillary muscles.
8.
Accessory mitral valve tissue/orifice
9.
Ebstein’s anomaly of the mitral valve
10.
Mitral valve prolapse Anatomy
11.
Mitral regurgitation due to other congenital causes:
i. Papillary muscle dysfunction due to ischemia The normal mitral valve consists of two leaflets and is
caused by: suspended from the fibrous mitral valve annulus at the
– Anomalous origin of the left coronary artery from level of the atrioventricular junction (Figure 1). The mitral
the pulmonary artery (ALCAPA)
annulus is derived from the fibrous skeleton of the heart. This
ii. Cardiomyopathy
– Dilated cardiomyopathy fibrous ring surrounding the mitral valve is part of a larger
– Hypertrophic cardiomyopathy fibrous structure, which attaches to the right and left fibrous
– Non-compaction of left ventricle trigones, the membranous septum and the aortic root. As this
iii. Storage disease/infiltration is discontinuous in the posterior aspect, there is an increasing
– Hurler disease risk for posterior annular dilatation. There is fibromuscular
– Amyloidosis
continuity between the mitral valve annulus and the aortic
iv. Connective tissue disorders
valve. The anterior mitral leaflet is in continuity with the
6
Figure 1: Schematic diagram showing the mitral valve, well enclosed

in annulus fibrosus and the various components of the mitral valve Figure 2: The mitral valve with anterior and posterior components and
viz. Leaflets, chordae, papillary muscles and its insertion into the its relationship with the cusps of the aortic valve
ventricles. AML = Anterior mitral leaflet; PML = Posterior mitral
leaflet
noncoronary cusp and the left coronary cusp of the aortic are attached to the anterior and posterior mitral valve leaflets
valve. Active contraction of the annulus fibrosus begins at via the chordae tendineae. Hence, ventricular geometry can
the onset of atrial contraction and continues through the affect the function of the papillary muscles.
ventricular systole leading to a substantial reduction in the The four anatomic components of the mitral valve function
annular orifice area. On further contraction of the muscle fibers to allow unobstructed blood flow from the LA to the left
the mitral leaflets assume a concave shape, which contributes ventricle (LV) during diastole and to maintain competent
to an effective seal. The mitral valve leaflets (anterior closure during systole. The leaflets open fully during the early
and posterior) consist of collagen fibrosa and spongiosa rapid-filling phase of diastole. They begin to close passively
peripherally and mucoid myxomatous tissue centrally. as LV pressure and volume increase. Then, the leaflets reopen
The anterior mitral leaflet is larger, sail-like and guards briefly as atrial contraction occurs, adding additional volume
approximately two-thirds of the left atrioventricular orifice, to the LV. During atrial contraction, annular contraction
but occupies only one-third of its annular circumference. The effectively decreases the circumference of the mitral valve
height of the anterior mitral leaflet often is used clinically by 20 to 30 percent throughout systole. Contraction of the
to size the mitral valve prostheses. The posterior leaflet is papillary muscles serves to maintain the length of the chordae
smaller, more rectangular and guards approximately one- under the pressure that develops during systole.
third of the left atrioventricular orifice, but occupies about
two-thirds of its annular circumference. The posterior Classification
leaflet is typically subdivided into three scallops, denoted
P1, P2, and P3. These scallops oppose the A1, A2, and A3 The congenital mitral valve diseases can be classified according
regions of the anterior mitral leaflet (Figure 2). The leaflets to three criteria: hemodynamic, anatomic and functional. The
free edge is termed the bare or membranous zone and the valves can be hemodynamically predominantly regurgitant or
remainder part of the leaflet is called the rough zone. The two stenotic. Anatomically, the congenital mitral valve anomalies
leaflets are separated by the anterolateral and posteromedial can be those with nondysplastic leaflets and those with
commissures. The valve leaflets are normally prevented from dysplastic leaflets. The annular dilatation can occur with
prolapsing into the left atrium (LA) by the tendinous cords, nondysplastic leaflet anatomy, with or without elongation
the chordae tendineae. The chordae tendineae are a complex of the chordae or the papillary muscle. They can be seen in
network of collagenous cord-like structures that extend from anomalies with significant volume loading of the left ventricle
the free edges of the mitral valve leaflets and insert into the like in large ventricular septal defect or large patent ductus
papillary muscles. The two papillary muscles, the anterolateral arteriosus. The dysplastic leaflets usually have a lack of
and posteromedial, arise from the ventricular free wall. They valvular tissue.
446
The anatomic classification by the STS-Congenital Heart hypoplasia. Group B is further subdivided into 31
Surgery Nomenclature and Database Committee has classified parachute mitral valve, hammock mitral valve and
congenital mitral valve disease into four types. The type 1 papillary muscle hypoplasia.
Congenital Mitral Valve Diseases

lesions are supravalvar, type 2 lesions are valvar, with the
category divided into group A or annular defects and group B Congenital Mitral Regurgitation
or leaflet defects. Type 3 are subvalvar lesions with group A
involving abnormalities of the chordae tendineae and group B Congenital mitral regurgitation (MR) is an uncommon condition
involving defects of the papillary muscles. Type 4 are mixed and is very rarely seen. Anything that disrupts any one or more
lesions. of the mitral valve apparatus is liable to cause regurgitation in
The 1976 functional Carpentier classification of congenital systole.
mitral valve disease is the most commonly utilized nomen- Congenital MR may result from an abnormality or disease
clature. Carpentier and colleagues classified the lesions based process that affects any one or more of the functional components
upon their work in 145 patients into three main types. of the mitral valve apparatus (leaflets, annulus, chordae
Type 1: Normal leaflet motion with valvar insufficiency tendineae, papillary muscles and the subjacent myocardium).
from a dilated or deformed annulus or by a defect MR is associated with other congenital cardiac anomalies like
or cleft in the leaflet. These lesions are subdivided dysplasia of the valve, double orifice, deficient leaflet tissue,
into annular dilatation, cleft leaflet and partial leaflet isolated cleft of the mitral leaflet, atrioventricular septal defects,
agenesis. displacement of the mitral valve like Ebstein type, an unguarded
Type 2: Leaflet prolapse which is due to the absence or mitral orifice and abnormal mitral arcade. The MR can occur
elongation of the chordae or papillary muscles and in the newborn due to papillary muscle infarction due to
produces valvar insufficiency. These defects are myocardial ischemia. Papillary muscle ischemia and infarction
subdivided into chordal elongation, papillary muscle in children with critical aortic stenosis is well reported. It is
elongation, and chordal agenesis. also seen in ALCAPA, coarctation of aorta and endomyocardial
Type 3: Restricted leaflet motion and hence mitral stenosis, diseases. MR can also occur in Marfan syndrome (Figures 3A
although valvar insufficiency can also be seen with and B).
certain lesions. The stenosis is due to commissural
fusion, imperforation, thickening or shortening of Abnormalities of Valve Leaflets
the subvalvar apparatus. These lesions are divided
into group A – normal papillary muscles and group Mitral regurgitation caused by involvement of the valve
B – abnormal papillary muscles. Group A is further leaflets occurs in many situations. Mitral valve prolapse
subdivided into papillary muscle commissural fusion (MVP) involves both leaflets and chordae and may also
and shortened chordae. This group also includes affect the annulus. Infective endocarditis can cause MR by
excessive leaflet tissue, valvar ring and annular perforating valve leaflets; vegetations can prevent leaflet
A B
Figures 3A and B: Echocardiography from a child with Marfan syndrome: A. Parasternal modified view showing myxomatous thickened 447
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.
6 coaptation and valvular retraction during the healing phase vulnerable to ischemia and any disturbance in coronary
of endocarditis. Destruction of the mitral valve leaflets can perfusion may result in papillary muscle dysfunction. When
also occur in patients with penetrating and non-penetrating ischemia is transient, it results in temporary papillary muscle
trauma. The MR associated with drug exposure also results dysfunction and may cause transient episodes of MR that
from anatomical changes in the valve leaflets. are sometimes associated with attacks of angina pectoris or
pulmonary edema. When ischemia of papillary muscles is
Abnormalities of the Mitral Annulus severe and prolonged, it causes papillary muscle dysfunction
and scarring, as well as chronic MR. The posterior papillary
The mitral annulus is saddle shaped and measures muscle, which is supplied by the posterior descending branch
approximately 10 cm in circumference in adults. It is soft of the right coronary artery, becomes ischemic and infarcted
and flexible and contraction of the surrounding LV muscle more frequently than does the anterolateral papillary muscle;
during systole causes the annular constriction that contributes the latter is supplied by diagonal branches of the left anterior
importantly to valve closure. The MR secondary to dilation descending coronary artery and often by marginal branches
of the mitral annulus can occur in any form of heart disease from the left circumflex artery as well. Ischemia of the
characterized by dilation of the LV, especially dilated papillary muscles is due to hypoxia, severe anemia, shock,
cardiomyopathy and also in post-tricuspid shunt lesions coronary arteritis of any cause or an anomalous left coronary
causing LV volume overloading. LV submitral aneurysm artery. Infact this is to be carefully looked for especially in
is a cause of annular MR commonly seen in sub-Saharan children. Infarcted and hyperechoic papillary muscle is
Africa due to a congenital defect in the posterior portion of an important echocardiographic criteria and corroborative
the annulus. Diagnosis by transesophageal echocardiography evidence of ALCAPA.
(TEE) and surgical repair have been reported. Various other disorders of the papillary muscles may also
Annular calcification may also be accelerated by an be responsible for the development of MR. These include
intrinsic defect in the fibrous skeleton of the heart, as occurs congenital malposition of the muscles; absence of one
in the Marfan and Hurler syndromes. In these two latter papillary muscle, resulting in the so-called parachute mitral
syndromes, the mitral annulus is not only calcified, but also valve syndrome and involvement or infiltration of the papillary
dilated, further contributing to MR. muscles by a variety of processes including abscesses,
granulomas, neoplasms, amyloidosis and sarcoidosis.
Abnormalities of the Chordae Tendineae
Left ventricular dysfunction: LV dilatation of any cause
The abnormalities of the chordae tendinae are important including ischemia due to ALCAPA can alter the spatial
causes of MR. Lengthening and rupture of the chordae relationships between the papillary muscles and the chordae
tendineae are cardinal features of the MVP syndrome. The tendineae and thereby result in functional MR. There may
chordae may be congenitally abnormal; rupture may be be additional ischemic damage to the papillary muscles,
spontaneous (primary) or may occur as a consequence of dilation of the mitral valve ring and/or loss of systolic annular
infective endocarditis, trauma, rheumatic fever or, rarely, contraction contributing further to MR. The incidence and
osteogenesis imperfecta or relapsing polychondritis. In most severity of regurgitation vary inversely with the LV ejection
patients, no cause for chordal rupture is apparent other than fraction and directly with the LV end-diastolic pressure.
increased mechanical strain. Chordae to the posterior leaflet Other causes of MR include obstructive hypertrophic
rupture more frequently than those to the anterior leaflet. cardiomyopathy (HCM), the hypereosinophilic syndrome,
Patients with idiopathic rupture of mitral chordae tendineae endomyocardial fibrosis, left atrial myxoma and various
frequently exhibit pathological fibrosis of the papillary congenital anomalies including cleft anterior leaflet.
muscles. It is possible that the dysfunction of the papillary Irrespective of cause, severe MR is often progressive, since
muscles may cause stretching and ultimately rupture of the enlargement of the LA places tension on the posterior mitral
chordae tendineae. Chordal rupture may also result from acute leaflet, pulling it away from the mitral orifice and thereby
LV dilation, regardless of the cause. Depending on the number aggravating the valvular dysfunction. Similarly, LV dilatation
of chordae involved in rupture and the rate at which rupture increases the regurgitation, which in turn enlarges the LA and
occurs, the resultant MR may be mild, moderate or severe and LV further, causing chordal rupture and resulting in a vicious
acute, subacute or chronic. circle; hence the aphorism MR ‘begets’ MR.
Cleft mitral valve: This rare anomaly (Figures 4A and
Involvement of the Papillary Muscles B) was found by echocardiography in 10/13,400 children
(0.75/1,000). A cleft in the anterior mitral cusp (less often,
Diseases of the LV papillary muscles are a frequent cause the posterior leaflet) is occasionally noted without an AV
of MR. Because these muscles are perfused by the terminal septal defect. There is no ‘gooseneck’ deformity and the
448 portion of the coronary vascular bed, they are particularly mitral annulus and leaflets are otherwise normal. The cleft
31

A B
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 orifice can vary and the border of the accessory orifice is
atrioventricular septal defect in which the cleft (commissure) usually devoid of chordae tendineae. In some cases, chordae
in the left atrioventricular valve points posteriorly towards may insert into an independent papillary muscle.
the inlet interventricular septum. Cleft leaflet could be termed Accessory mitral orifice is best visualized in parasternal
partial or complete depending upon its extension to mitral short axis and subcostal four-chamber view with color Doppler
valve annulus. One of the important reasons to make this interrogation. An abnormal position and orientation of MR
differentiation of isolated clefts from AV clefts is also that the jet may help to suspect this condition and warrants further
specialized conduction tissue differs so importantly between evaluation in different views. This condition is sometimes
these two lesions. About half of these clefts are isolated and associated with transposition of great arteries, partial
the rest associated with other congenital cardiac anomalies, atrioventricular septal defect and interrupted inferior vena cava.
including secundum atrial septal defects. There is a variable Mitral arcade: The tips of the two papillary muscles of the
degree of MR that depends on the degree of separation of the left ventricle are connected by a fibrous cord to which the
tissue on each side of the cleft and the chordal support, but free edge of the anterior leaflet is attached, either directly or
often clefts are not accompanied by significant regurgitation. by short chordae tendineae. The entity was first described in
Double-orifice mitral valve: An accessory bridge or limbus 1967 by Layman and Edwards. The entity has also been called
of tissue may partially or completely divide the mitral inlet Hammock mitral valve. In most patients, there is severe MR
into two orifices, termed as DOMV. It can cause both mitral from tethering of leaflet. In a few cases, MS has also been
stenosis (MS) and MR, with regurgitation in 45 to 50 percent described and involvement of tricuspid valve has rarely been
of the cases. These orifices are usually unequal, with the reported with AV valve regurgitation of both AV valves. The
smaller orifice directed towards the anterolateral commissure age at presentation or death varies widely. Most patients
(41%) or the posteromedial commissure (44%). In the latter, present in infancy, a few in early childhood and very rarely
atrioventricular septal defects are common (90%), and mitral in adults.
regurgitation is often present. This is described under LV Ebstein's Anomaly of Mitral Valve: This is a rare anomaly
inflow obstructions obstructions (Chapter 27). with very few published case reports. Here, the LA is dilated
Accessory mitral orifice: This abnormality results from and the posterior leaflet of mitral valve, which is dysplastic,
a circular deficiency of mitral leaflet tissue. The size of the is displaced downward with normal insertion of anterior 449
6 mitral leaflet into the ventricular septum (above the septal Clinical Features
tricuspid leaflet). Few case reports have shown associated
thin left ventricular wall. This abnormality is best visualized Symptoms
in apical, subcostal four-chamber views and in parasternal

long-axis view. The severity of MR can be assessed by color The nature and severity of symptoms in patients with
and spectral Doppler interrogation. MR relates to etiology, rate of onset and progression, LV
Ebstein anomaly of mitral valve should not be confused function, pulmonary artery pressure and the presence of
with Ebstein anomaly of left AV valve in association with pre-existing valvular or myocardial diseases. Children with
corrected transposition, where septal leaflet of morphologic minor degrees of MR are usually asymptomatic. Infants and
tricuspid valve is apically displaced. children exhibit signs and symptoms of congestive heart
The reported associations include Ebstein anomaly of failure relatively early, generally within 3 years of diagnosis.
tricuspid valve, Marfan syndrome, double-outlet right ventri- These include failure to thrive, diaphoresis, pallor, tachypnea
cle, atrial septal defect, patent ductus arteriosus, coarctation and a predisposition to lower respiratory tract infections
of aorta, hypoplasia of ascending aorta and valvular aortic or wheezing. Children may remain asymptomatic with no
stenosis. complications of MR until the second or third decade of life.
Once pulmonary hypertension develops, complaints such as
Pathophysiology dyspnea become more prominent with light activity. With
severe MR, children may experience limited growth and
In mitral regurgitation, the normal blood flow from the LA to failure to thrive. Hemoptysis can develop during the later
the LV and subsequently to the systemic circulation is altered. stages. An indolent course of MR may be deceptive because
In the presence of MR, blood flows antegrade from the LV of the ability of the heart to compensate for the altered
into the aorta, and the regurgitant volume flows retrograde hemodynamics. This occurs because of changes in cardiac
from the LV into the LA. This causes a proportionate increase pump loading such that increased diastolic filling increases
in LV ejection volume. The regurgitant fraction re-enters preload, whereas LV ejection, in part into the left atrium,
the LV, producing left ventricular volume overload. The LV reduces afterload.
compensates via the Frank-Starling mechanism, resulting
in a greater ventricular stroke volume. The volume of the Physical Findings
regurgitant fraction depends on several factors, including
size of the orifice allowing regurgitation and the pressure There is increased precordial activity and a diffuse apical
gradient between the LV and LA. This volume also depends impulse. The first heart sound is diminished and the
on the ventricular systolic pressure; therefore, the regurgitant pulmonary component of the second heart sound is loud
volume increases in situations that increase afterload, such and narrowly split when pulmonary hypertension is present.
as aortic stenosis or hypertension. The regurgitant volume In patients with severe MR, the aortic valve may close
varies directly with the LV systolic pressure and the size of the prematurely, resulting in wide but physiologic splitting of
regurgitant orifice is influenced profoundly by the extent of LV S2. A low-pitched S3 occurring 0.12 to 0.17 seconds after
and mitral annular dilatation. Since ejection fraction (EF) rises the aortic valve closure sound, i.e. at the completion of the
in severe MR in the presence of normal LV function, even a rapid-filling phase of the LV, is believed to be caused by the
modest reduction in this parameter (< 60%) reflects significant sudden tensing of the papillary muscles, chordae tendineae
dysfunction. and valve leaflets. The murmur may assume various
During early diastole as the distended LA empties, there is configurations dependent on the anatomy and severity. A
a particularly rapid descent in the absence of accompanying high-frequency, plateau-type blowing or harsh holosystolic
MS. A brief, early diastolic LA-LV pressure gradient (often murmur is typically heard at the apex with radiation to the
generating a rapid filling sound [S3] and mid-diastolic murmur axilla and back, but occasionally it is maximal anteriorly
masquerading as MS) may occur in patients with pure MR as at the left sternal border when the anterior leaflet is cleft
a result of the very rapid flow of blood across a normal-sized In patients with ruptured chordae tendineae, the systolic
mitral orifice. murmur may have a cooing or ‘sea gull’ quality, while a
As described previously, ventricular systole contributes flail leaflet may cause a murmur with a musical quality.
substantially to mitral valve function. Active contraction The systolic murmur of chronic MR not due to MVP is
at the level of the annulus both reduces the surface area intensified by isometric exercise (handgrip), but is reduced
of the valve annulus and changes the shape of the valve during the strain phase of the Valsalva maneuver. A low-
leaflets in order to optimize valve function and contraction frequency, apical diastolic murmur and third heart sound
of the papillary muscles further supports leaflet position and may be present with more severe degree of valvular
prohibits mitral insufficiency. Therefore, systolic dysfunction insufficiency. Tachycardia is usually present with adequate
450 can independently cause or exacerbate mitral insufficiency. systolic blood pressure.
Differential Diagnosis severity (Figures 5A and B). The LV function can be assessed 31
from LV end-diastolic and end-systolic volumes and EF. The
The holosystolic murmur of MR resembles that produced evaluation of leaflet structure, function, chordal integrity,

by a ventricular septal defect. However, the latter is usually the size of LA , LV, annulus, the regional and global LV
loudest at the sternal border rather than the apex and is often systolic function can be done by TTE. The mitral valve
accompanied by a parasternal rather than an apical thrill. The apparatus, annulus, leaflets, chordae, and papillary muscles,
murmur of MR may also be confused with that of TR, but should be systematically assessed by echocardiography.
the latter is usually heard best along the left sternal border, Doppler imaging should demonstrate the width or area of
is augmented during inspiration and is accompanied by a the color flow MR jet within the LA, the intensity of the
prominent ʻvʼ wave and ʻyʼ descent in the jugular venous pulse. continuous wave Doppler signal, the pulmonary venous
When the chordae tendineae to the posterior leaflet of the flow contour, the early peak mitral inflow velocity and the
mitral valve rupture, the regurgitant jet is eccentric, often quantitative measures of regurgitant volume, regurgitant
directed anteriorly, so that it impinges on the atrial septum fraction and effective regurgitant orifice area. In addition,
adjacent to the aortic root and causes a systolic murmur that the pulmonary artery pressures can be estimated from the
is most prominent at the base of the heart. This murmur can tricuspid regurgitation jet velocity. The echocardiogram in
be confused with that of AS. On the other hand, when the patients with MVP is described in the next section. Studies
chordae tendineae to the anterior leaflet rupture, the jet is have demonstrated that a high level of accuracy can be
usually directed to the posterior wall of the left atrium and the achieved when analyzing mitral valve pathology using
murmur may be transmitted to the back. 2D echocardiography and an incremental benefit can be
attained when combined with 3D imaging. Transesophageal
Investigations echocardiography provides greater detail than TTE.
Electrocardiogram Chest X-ray

Electrocardiography demonstrates left atrial and left ventricular The LA and LV are the dominant chambers enlarged in chronic
enlargement when significant mitral insufficiency is present. MR. The LA may be massively enlarged and forms the right
border of the cardiac silhouette. Pulmonary venous congestion,
Echocardiogram interstitial edema and Kerley B lines are sometimes noted.
Echocardiography is the most important imaging modality to Radionuclide Angiography

access congenital mitral valve insufficiency. Transthoracic
echocardiography (TTE) with Doppler imaging is indicated Although echocardiography is the imaging method most
to assess the mechanism of the MR and its hemodynamic suited for routine evaluation of structure, function and MR
A 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
6 severity, radionuclide gated or first pass blood-pool imaging percent have died or undergone surgical correction. This latter
may be helpful in instances in which the echocardiographic series included many patients who were initially symptomatic
images are suboptimal or there is a discrepancy between the or had LV dysfunction or AF and thus might be considered to
clinical and the echocardiography information or there is a be at higher risk.

need for more precise measurement of LV ejection fraction. Double-orifice mitral valve has the best prognosis because
37 to 50 percent of these lesions have normal mitral valve
Cardiac Magnetic Resonance function. Even with mitral valve abnormal function surgery
was needed in only few cases. Patients with double-orifice
Cardiac magnetic resonance (CMR) provides accurate mitral valves have been described till older age, even upto
measurements of regurgitant flow that correlate well with 75 years. They had severe MR which was most often due to
quantitative Doppler imaging. It is also the most accurate late chordal rupture. Probably these adults had double-orifice
non-invasive technique for measuring LV end-diastolic mitral valves had no or only minor symptoms.
volume end-systolic volume and mass. Although detailed Many older patients would be expected with cleft valves
visualization of mitral valve structure and function is obtained if they have no significant regurgitation. In small series of
more reliably with echocardiography, CMR offers a promising studies, children with cleft mitral valve with significant
approach for more accurate assessment of severity of the regurgitation had a low survival.
mitral regurgitation. For the rare Ebstein-like malformation, most patients
The cause of the regurgitation (e.g. prolapse of the mitral presented in early infancy with severe congestive heart
valve) and a flail leaflet can often be distinguished by angio failure and the oldest and least severely affected patient had a
graphy, but this assessment has been superseded by echocar- mitral valve replacement at the age of 2 years and 9 months.
diography in most institutions. There are no available studies of the age at death of untreated
patients with pure congenital MR of all types and even the
Natural History series reporting the age at clinical presentation give mean ages
and range, but not individual ages.
The natural history of MR is highly variable and depends Even though there are probably many older patients with
on a combination of the volume of regurgitation, the state milder congenital MR with no surgery, the outlook for MR
of the myocardium and the cause of the underlying disorder. is better than for congenital MS. They are less likely to have
Asymptomatic patients with mild primary MR usually remain severe pulmonary venous and arterial hypertension and more
in a stable state for many years. Severe regurgitation develops of them are suitable for repair rather than replacement. This
in only a small percentage of these patients, most commonly tendency was noted specifically in one series reported by
because of intervening infective endocarditis or rupture of the Daliento et al who found the mean age at presentation to be
chordae tendineae. In patients with mild MR related to MVP, 1.4 years for mitral stenosis and 6.55 years for MR.
the rate of progression in severity of MR is highly variable; in
most patients progression is gradual unless a ruptured chordae Treatment
or flail leaflet supervenes. Regurgitation tends to progress more
rapidly in patients with connective tissue diseases, such as the
Medical
Marfan syndrome, than in those with chronic MR of rheumatic
origin. The role of pharmacological therapy for MR remains another
Atrial fibrillation (AF) is a common arrhythmia in patients subject of uncertainty and some debate. The medical therapy
with chronic MR, associated with age and left atrial dilation is mainly aimed at increasing systemic cardiac output and
and its onset a marker for disease progression. Patients with decreasing regurgitant flow. There are no clear guidelines
AF have an adverse outcome compared to patients who regarding when to initiate medical management. The
remain in sinus rhythm and development of AF is considered treatment is probably indicated when the LV begins to dilate.
an indication for operative intervention, especially in patients In patients with moderate to severe regurgitation, afterload-
who are candidates for mitral valve repair. Because the natural reducing agents such as angiotensin converting enzyme
history of severe MR has been altered greatly by surgical (ACE) inhibitors can improve cardiac output. Afterload
intervention, it is difficult now to predict the course of patients reduction may be the most beneficial therapy because it
who receive medical therapy alone. However, Horstkotte reduces work on the heart by decreasing systemic arteriolar
and associates reported a 5-year survival of only 30 percent resistance, thereby decreasing the regurgitant volume.
in patients who were candidates for operation (presumably However, no studies have demonstrated that afterload
because of symptoms), but who declined. Among patients reduction actually delays (or eliminates) the need for surgery.
with severe MR resulting from flail leaflets, the annual If the LA is markedly dilated or if pulmonary congestion
mortality rate is as high as 6.3 percent and at 10 years, 90 develops, diuretics are indicated.
452
Surgery echocardiography rising above 40 mm. These aggressive 31
recommendations for surgery are predicated on the outstanding
In infants and children, surgery for congenital mitral valve results achieved with mitral valve repair, particularly when

disease is a major therapeutic challenge. There are many applied to patients with myxomatous disease. Repair is feasible
technical difficulties due to the wide spectrum of morphologic in up to 95 percent of patients with myxomatous disease.
abnormalities and a high prevalence of associated cardiac Long-term durability is excellent; the incidence of reoperative
anomalies. Hence, the outcomes of surgical management of surgery for failed primary repair is approximately one percent
mitral insufficiency are highly variable. As the anomalies are per year for 10 years after surgery. For patients with AF, a LA
usually complex, intervention is ideally postponed to allow Maze procedure or radiofrequency ablation of the pulmonary
time for annular growth and tissue maturity. Children are also vein ostia is often performed to reduce the risk of recurrent
more sensitive to insufficiency than adults. Surgery is needed AF. In patients with significantly impaired LV function (EF
in patients with severe congestive cardiac failure and/or LV <30%), the risk of surgery rises, the recovery of LV
dysfunction refractory to maximal medical therapy. It maybe performance is incomplete and the long-term survival is
needed in the first months of life in some cases. Surgery should reduced.
be undertaken before the onset of left ventricular deterioration.
Mitral Valve Replacement
Mitral Valve Repair
Historically, mitral valve replacement in children has been
The initial surgical approach to patients with congenital associated with high morbidity and mortality rates. As a
mitral valve lesions is reconstructive surgery, as mitral valve result, it is generally reserved for patients who have mitral
replacement in infants and small children is associated with valve disease, which has failed at least one attempt at surgical
high mortality and reoperation rates. Repair spares the patient repair. Single center and multi-institutional long-term studies
the long term adverse consequences of valve replacement, have found 10-year survival rates ranging from 56 to 74
i.e. thromboembolic and hemorrhagic complications in the percent. More recent experience has found improved long-
case of mechanical prostheses and accelerated and premature term survival rates, ranging from 83 to 91 percent, although
degeneration necessitating repeat valve replacement in the the need for repeat mitral valve replacement remains common.
case of bioprostheses. In addition, by preserving the integrity Morbidities associated with mitral valve replacement include
of the papillary muscles, subvalvular apparatus and chordae arrhythmia, heart block, thromboembolic phenomena and
tendineae, mitral repair and valvuloplasty maintain LV hemorrhagic complications of anticoagulation.
function to a relatively greater degree. The repair of mitral The late problems after mitral valve repair or replacement
insufficiency also depends on the cause. The congenital cleft are similar to those occurring after operating on stenotic
in the septal leaflet of the mitral valve can be closed with a mitral valves. Some valves after repair still have or develop
few sutures and the long-term result will be good. If the valve so much regurgitation that the valve has to be replaced and
annulus is dilated but LV is well preserved, an annuloplasty can some prosthetic valves develop thrombus or other functional
be done and the results are generally good. Techniques used to difficulties and have to be replaced. The prognosis after
treat annular dilation include reconstructing the annulus with valve repair is much better than after valve replacement.
a prosthetic ring (Carpentier ring) and a rectangular resection Valve repair by itself does not require anticoagulation for the
of a portion of the annulus with annulus plication. If there is patient. The reasons for reoperation include severe residual
a flail mitral valve leaflet, artificial chordae can be inserted or recurrent MR or MS and for those with valve replacement
and a plastic procedure can be performed on the leaflet. either deterioration of a bioprosthesis or thromboembolism
However, prosthetic rings and artificial chordae have no associated with a prosthetic valve.
growth potential, and hence there are concerns about the use
of such prosthetic materials. In patients with a rigid prosthetic Mitral Valve Prolapse
ring, somatic growth of the heart may result in progressive MS
and proportional changes in the repaired valve may lead to Mitral valve prolapse (Figures 6A and B), also called as
recurrence of regurgitation in patients with artificial chordae. systolic click-murmur syndrome, myxomatous mitral valve
Surgery for chronic severe MR is indicated once symptoms disease, floppy-valve syndrome, billowing mitral leaflet
occur, especially if valve repair is feasible. Other indications for syndrome and Barlow’s syndrome. It is a relatively common
early consideration of mitral valve repair include recent-onset but highly variable clinical syndrome resulting from diverse
AF and pulmonary hypertension, defined as a PA pressure 50 pathogenic mechanisms of the mitral valve apparatus. It is one
mm Hg at rest or 60 mm Hg with exercise. Surgical treatment of the most common valvar anomalies. Prevalence of MVP
of chronic severe MR is indicated for asymptomatic patients increases with age and is about 1 to 2 percent in pediatric
when LV dysfunction is progressive, with LVEF declining population. The prevalence of MVP is about 5 to 15 percent
below 60 percent and/or end-systolic cavity dimension on in older age group. 453
6
A B
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 ectasia, ischemic heart disease, hypertrophic cardiomyopathy,

Macroscopic changes in MVP include excessive or redundant pectus excavatum, and in those whose body habitus is asthenic.
mitral leaflet tissue with myxomatous degeneration and A disproportion between left ventricular cavity and the mitral
greatly increased concentrations of acid mucopolysaccharide. valve when LV cavity is small as compared to mitral valve is
MVP is characterized by leaflet thickening, redundancy causative for the functional prolapse as seen in patients with
with interchordal hooding, chordal elongation, and annular hypertrophic cardiomyopathy or ostium secundum atrial septal
dilatation. Both the anterior and posterior leaflets may be defect. MVP is seen in about 20 percent of patients with OS-
involved, although the middle scallop of the posterior leaflet ASD due to decreased LV volume and altered LV geometry,
is most frequently affected. Tricuspid and aortic valves which usually resolves on repair. Some studies describe MVP
may be involved in 43 percent and 10 percent patients as a condition in which heart appears trapped in chest cavity that
respectively. is small for its size leading to alteration in cardiac architecture
In most patients with MVP, the cause is unknown, but and distortion in mitral annulus.
in some it appears to be a genetically determined collagen
disorder. A reduction in the production of type III collagen Genetics
has been incriminated and electron microscopy has revealed
fragmentation of collagen fibrils. The disruption of collagen MVP is usually sporadic but some patients show familial
bundles coupled with valve leaflets that are more distensible aggregation with autosomal dominant transmission with
and less rigid, predisposes to rupture of chordae. In many variable penetrance and X-linked inheritance. Three different
patients, elongated, redundant or ruptured chordae tendineae loci on chromosomes 16, 11 and 13 have been linked to MVP,
cause or contribute to the regurgitation. MVP may lead to but no specific gene identified. Mitral valve prolapse is not
excessive stress on the papillary muscles, which in turn leads seen in echocardiography of newborn babies.
to dysfunction and ischemia of the papillary muscles and
the subjacent ventricular myocardium. Rupture of chordae Clinical Features
tendineae and progressive annular dilatation and calcification
also contribute to valvular regurgitation, which then places Mitral valve prolapse is more common in females and although
more stress on the diseased mitral valve apparatus, thereby congenital is usually diagnosed in adolescent children and
creating a vicious circle where in MR begets MR. young adults. The clinical course in MVP is often benign and
Apart from the primary myxomatous degeneration, MVP encompasses a broad spectrum of severities, ranging from only
is also associated with other connective tissue disorders like a systolic click and murmur and mild prolapse of the posterior
Marfan syndrome, Ehlers-Danlos syndrome, adult polycystic leaflet of the mitral valve to severe MR due to chordal rupture
kidney disease, osteogenesis imperfecta, pseudoxanthoma and massive prolapse of both leaflets. In many patients, this
elasticum, straight back syndrome and Stickler syndrome. Other condition progresses over years or decades. In others it worsens
454 common conditions associated with MVP include, annuloaortic rapidly as a result of chordal rupture or endocarditis.
Most patients are asymptomatic and remain so for their appreciated by continuous auscultation occurs on sudden 31
entire lives. However, in North America MVP is now the standing from the squatting position, when the systolic click
most common cause of isolated severe MR requiring surgical and murmur move to early systole, on a beat-to-beat basis as

treatment. Many patients have chest pain that is difficult to the heart rate increases.
evaluate. It is often substernal, prolonged and poorly related
to exertion and it rarely resembles angina pectoris. Chest pain Investigations
may be caused due to excessive stretch on chordae tendineae
leading to papillary muscle ischemia, coronary microvascular
Electrocardiography
perfusion anomalies, hyperadrenergic state with increased
myocardial oxygen demand and coronary vasospasm. Patients with MVP usually have normal ECG, but may show
Arrhythmias, most commonly ventricular premature inverted or biphasic T waves in inferior leads II, III and AVF
contractions and paroxysmal supraventricular and ventricular and or V5 and V6. There may be occasional evidence of
tachycardia, as well as AF, have been reported and may cause supraventricular or ventricular premature beats. Patients with
palpitations, light-headedness and syncope. Sudden death is a MVP show higher than normal incidence of left accessory
very rare complication and occurs most often in patients with pathways and prolonged QTc. The clinical implications of
severe MR and depressed LV systolic function. There may these findings and their prevalence in asymptomatic patients
be an excess risk of sudden death among patients with a flail with MVP is not clear.
leaflet. A constellation of features including atypical chest pain,
exertional dyspnea, palpitations, dizziness, syncope, panic Echocardiography
attacks and anxiety along with findings of low blood pressure,
thin build, and ECG changes have been termed “mitral valve Transthoracic echocardiography is particularly effective in
prolapse syndrome”. identifying the abnormal position and prolapse of the mitral
Transient cerebral ischemic attacks secondary to emboli valve leaflets. Echocardiographic criteria of MVP is systolic
from the mitral valve due to endothelial disruption have been displacement of the mitral valve leaflets by at least 2 mm
reported, though a causal relationship has not been established. into the LA superior to the plane of the mitral annulus in the
Infective endocarditis may occur in patients with MR and/or parasternal long-axis view. As mitral annulus is saddle shaped
leaflet thickening. and not planar, any prolapse in four chamber view should not
be used to diagnose MVP and the same should be confirmed
Auscultation in parasternal long axis or two chamber view. Most cases
of prolapse involve the posterior middle scallop according
Classic auscultatory findings are the most important feature to Carpentier’s nomenclature. M-mode echocardiography is
on which diagonosis is suspected and patient is refered for useful in measuring the thickness of the valve leaflets at the
echocardiogram. The most important finding is the mid- or late midpoint of the EF slope and demonstrating the late systolic
(non-ejection) systolic click, which occurs 0.14 s or more after posterior displacement of mitral leaflets. The long-axis view
the S1 and is thought to be generated by the sudden tensing can also be used to measure leaflet thickening during diastole
of slack, elongated chordae tendineae or by the prolapsing when the leaflets are slack. Patients with greater than 2
mitral leaflet when it reaches its maximum excursion. Systolic mm leaflet displacement and maximum leaflet thickness of
clicks may be multiple as different parts of leaflets prolapse at greater than 5 mm are considered to have “classic” MVP,
different times. The click is associated with a high-pitched, late while those with leaflet thickness less than 5 mm have
systolic crescendo-decrescendo murmur, which occasionally is “nonclassic” MVP.
‘whooping’ or ‘honking’ and is heard best at the apex. The click Redundancy of the mitral valve leaflets is diagnosed on
and murmur occur earlier with standing, during the strain of the the parasternal short axis view when the circumference of
Valsalva maneuver and with any intervention that decreases LV the leaflets appears to be disproportionate to the chamber
volume, exaggerating the propensity of mitral leaflet prolapse. size. Other features associated with MVP include dilated
In other conditions with decreased venous return or increased annular dilation and chordal elongation. Color flow and
heart rate or increased contractility, the click and murmur also continuous wave Doppler imaging is helpful in revealing
occurs earlier. Conversely, squatting and isometric exercises, and evaluating associated MR. TEE is indicated when more
which increase LV volume, diminish the prolapse and the click- accurate information is required regarding vegetations or
murmur complex is delayed, moves away from S1 and may flail leaflets and routinely for intraoperative repair.
even disappear. In conditions with increased venous return or
decreased heart rate, the click and murmur occurs later. Some Management
patients have a mid-systolic click without the murmur; others
have the murmur without a click. Still others have both sounds All patients with suspected features should have a thorough
at different times. The most dramatic changes which can be initial evaluation for correct diagnosis, risk stratification and 455
6 for associated other cardiac and non-cardiac conditions. Their with many physicians who continue to stick to contemporary
first degree relatives should be evaluated for MVP and other guidelines.
connective tissue disorders.
Principles of management of pediatric patients of mitral Sudden Cardiac Death

valve prolapse include:
• To assure regarding benign nature of disease in majority of Sudden cardiac death (SCD) is a rare complication of MVP,
patients and ensure that no undue restrictions are imposed. with an estimated incidence of 0.1 to 0.4 percent per year,
• Identification of patients who are at higher risk for similar to the risk in the general adult population of the United
complications and preventing them. States.
• To optimize the timing for mitral valve surgery, if necessary. Risk factors for SCD include history of recurrent syncope or
Most patients with mitral valve prolapse remain sustained supraventricular or complex ventricular arrhythmias
asymptomatic throughout their lives and should be encouraged or family history of cardiac sudden death. Therapy with
to exercise regularly and may have clinical assessment every b blockers may be useful in these patients.
3 to 5 years or earlier if any symptoms appear.
Mitral Regurgitation
Symptomatic Patients
Severe mitral regurgitation resulting either from progressive
Patients with MVP and symptoms like palpitations or non- myxomatous degeneration or chordal rupture with flail leaflet
anginal chest pain, anxiety, or fatigue often respond to therapy is the most common complication of MVP.
with β-blockers. However, in many cases, the cessation of On echocardiography, the presence of thickened
stimulants like caffeine, alcohol, smoking and reassurance leaflets, posterior leaflet prolapse, increased left ventricular
may be sufficient. These patients may be sensitive to volume dimensions, higher systolic blood pressure, higher body
depletion and chronic diuretic therapy should be avoided. weight, older male predict a greater risk for development of
In patients with recurrent palpitations or history of syncope, severe mitral regurgitation. By contrast, individuals with thin
continuous or event-activated ambulatory ECG recordings leaflets have a very low-risk of developing significant mitral
may establish the cause and guide management. regurgitation. The indications for repair/surgery are same as
Upright tilt test may be useful in patients with dizziness or for other forms of congenital MR.
syncope when vasodepressor/vasovagal cause is suspected .
Indications for electrophysiology study are similar to those Physical Activity
in general clinical practice and are necessary in patients with
supraventricular tachycardia as accessory atrioventricular There is no evidence to demonstrate that strenuous exercise in
pathways may be common. Exercise testing is useful in patients with MVP predisposes to sudden cardiac death that
patients with palpitations and exercise-related symptoms. otherwise would not have occurred. The Bethesda conference
report on eligibility recommendations for competitive
Complications athletes with cardiovascular abnormalities dealt with a broad
spectrum of matters dealing with athletics. Several consensus
recommendations are appropriate to this discussion.
Infective Endocarditis
MVP patients with the following conditions are restricted to
MVP is the most common lesion associated with infective low-intensity competitive sports only (class 1A): Arrhythmia
endocarditis (IE). Patients with MVP have a three to eightfold mediated syncope; Repetitive nonsustained or sustained
higher risk of developing IE, with an estimated incidence of supraventricular tachycardia or frequent/complex ventricular
about 0.02 percent per year. Predictors of increased risk for tachyarrhythmias on ambulatory Holter monitoring; Color
development of IE include male sex, age older than 45 years, Doppler evidence of severe mitral regurgitation; Left
the presence of a systolic murmur, and leaflet thickening ventricular ejection fraction <50%.
and redundancy. In the absence of mitral regurgitation, the Otherwise, MVP patients are permitted participation in
incidence of IE is similar to that of the general population, but all competitive sports. Patients with syncope or presyncope
in patients with mitral valve prolapse and a systolic murmur, should not participate in competitive sports until the cause
the risk increases to about 0.05 percent per year. The 2007 of syncope has been defined and appropriately treated.
AHA Infective Endocarditis Guidelines specifically no longer Patients with cardiac arrhythmia should have periodic
recommend that patients with MVP be given antibiotic for exercise tests performed and ambulatory ECG recordings
IE, whether or not they have regurgitation or thickened valve obtained while doing the type of exercise they are likely to
leaflets. But these guidelines have still not gained acceptance undertake.
456
Conclusion 5. Parr GV, Fripp RR, Whitman V, et al. Anomalous mitral arcade:
echocardiographic and angiographic recognition. Pediatr
31
The mitral valve is the most complex of the heart’s four Cardiol. 1983;4:163-65.

6. Grenadier E, Sahn DJ, Valdes-Cruz LM, et al. Two-dimensional
valves and is the one most commonly associated with disease.
echo Doppler study of congenital disorders of the mitral valve.
Mitral valve prolapse is the most common but is not usually
Am Heart J. 1984;107:319-25.
a harmful condition, although it can lead to significant mitral 7. Feindel CM, Tufail Z, David TE, et al. Mitral valve surgery
regurgitation in a small minority. Medical therapy may in patients with extensive calcification of the mitral annulus. J
provide symptomatic improvement in the cases with severe Thorac Cardiovasc Surg. 2003;126:777.
regurgitation. Mitral valve repair is preferable to replacement 8. Barber JE, Ratliff NB, Cosgrove DM, et al. Myxomatous
whenever possible. mitral valve chordae. I: Mechanical properties. J Heart Valve
Dis. 2001;10:320.
Body and soul cannot be separated for purposes of treatment, 9. Kumanohoso T, Otsuji Y, Yoshifuku S, et al. Mechanism of
higher incidence of ischemic mitral regurgitation in patients
for they are one and indivisible. Sick minds must be healed
with inferior myocardial infarction: quantitative analysis of left
as well as sick bodies.
ventricular and mitral valve geometry in 103 patients with prior
—C Jeff Miller myocardial infarction. J Thorac Cardiovasc Surg. 2003;125:135.
10. Levine RA. Dynamic mitral regurgitation—more than meets
Acknowledgement the eye. N Engl J Med. 2004;351:1681.
11. Thourani VH, Weintraub WS, Guyton RA, et al. Outcomes and
We wish to thank Dr Milan for his assistance in preparing the long-term survival for patients undergoing mitral valve repair
manuscript. 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
Suggested Reading regurgitation. In: Alpert JS, Dalen JE, Rahimtoola SH (Eds.).
Valvular Heart Disease 3rd. Philadelphia: Lippincott Williams
1. Carpentier A, Branchini B, Cour JC, et al. Congenital
and Wilkins; 2000. pp. 113-142.
malformations of the mitral valve in children. Pathology and
13. Braunberger E, Deloche A, Berregi A, et al. Very long-term
surgical treatment. J Thorac Cardiovasc Surg. 1976;72:854-66.
results (more than 20 years) of valve repair with Carpentier’s
2. Creech O Jr, Ledbetter MK, Reemtsma K. Congenital
techniques in nonrheumatic mitral valve insufficiency.
mitral insufficiency with cleft posterior leaflet. Circulation.
Circulation. 2001;104:I-I8.
1962;25:390-94.
14. Bishay ES, McCarthy PM, Cosgrove DM, et al. Mitral valve
3. Sigfússon G, Ettedgui JA, Silverman NH, et al. Is a cleft
surgery in patients with severe left ventricular dysfunction. Eur
inthe anterior leaflet of an otherwise normal mitral valve an
J Cardiothorac Surg. 2000;17:213.
atrioventricular canal malformation? J Am Coll Cardiol.
15. Remadi JP, Baron O, Roussel C, et al. Isolated mitral valve
1995;26:508-15.
replacement with St. Jude medical prosthesis. Long-term
4. Zalzstein E, Hamilton R, Zucker N, et al. Presentation, natural
results: A follow-up of 19 years. Circulation. 2001;103:1542.
history, and outcome in children and adolescents with double
16. Maskatia SA. Fellows forum. Congenital anomalies of the
orifice mitral valve. Am J Cardiol. 2004;93:1067-69.
mitral valve. Congenital Heart Dis. 2011;6:77-82.
457
C hapter
32 Mitral Atresia
INTRODUCTION atresia with normal aortic root was reviewed early on by

Watson et al3 in 1960 and later in 1981 by Thiene et al.1
Mitral or left atrioventricular (AV) valve atresia patients
may have aortic atresia or a patent aortic root.1 Mitral atresia Atrioventricular Valves
coexisting with aortic atresia may be considered as a variant
of hypoplastic left heart syndrome (HLHS) and will not be Mitral atresia may be an absent atrioventricular connection or
discussed in this chapter; this defect will be reviewed in an imper forate valve membrane; this distinction was
the chapter on HLHS (Chapter 47). This division, though emphasized by Anderson and Thiene6 although the
arbitrary, is also justified on the basis of different therapeutic difference may simply be secondary to the timing of onset
approaches for these two conditions; in HLHS patients almost of embryological insult, just has been postulated for tricuspid
uniformly require Norwood procedure2 in the neonatal period atresia hearts7 and may not be clinically significant.6 In hearts
in contradistinction to mitral atresia with normal aortic root associated with ventricular inversion, the atretic valve may
patients, who require different types of therapeutic intervention be a morphologic tricuspid valve such as that seen in type
at varying ages depending upon the pathophysiology, largely III, subtypes 1 and 5 of tricuspid atresia hearts,8 although
determined by the associated cardiac defects. Mitral atresia the physiology is that of mitral atresia. These considerations
with normal aortic root is a rare complex heart defect justify the use of the term ‘left atrioventricular valve atresia’.
characterized by atresia of the mitral or left AV valve and is With absent atrioventricular connection, the atrioventricular
usually associated with several other abnormalities and is the sulcus separates the muscular floor of the left atrium from the
subject of this chapter. The term 'isolated mitral atresia' to ventricular myocardium beneath it;6 there may be a dimple
differentiate from mitral atresia/aortic atresia and aortic root in the floor of the left atrium,9 representing the valve. In
hypoplasia or HLHS has been used by some investigators, but imperforate valve membrane, the membrane separates the
such use is discouraged.1 left atrial and ventricular cavities. These hearts may have
primitive elements of mitral valve apparatus.9 Mitral atresia
EPIDEMIOLOGY may also be seen in patients with atrioventricular septal
defects (endocardial cushion defects) in that the common
Even though there have been earlier reports of mitral atresia atrioventricular valve occludes the entrance into the left
with normal aortic root, largest number of cases (n = 52) ventricle,9 in a manner similar to that seen with tricuspid
were reported first in 1960 by Watson et al, consisting of 11 atresia.10 In the pathologic specimens (N = 30) studied by
cases of their own and 41 from the literature.3 This is a rare Thiene and associates,1 24 had absent left atrioventricular
condition; Maude Abbott4 had only five cases in her 1,000 connection and six had imperforate left atrioventricular valve.
cases of congenital heart defects and Edwards5 had five cases The tricuspid valve is patent, large or normal in size and
in a collection of 212 specimens of major cardiovascular connects the right atrium to a right ventricle or a 'single'
malformations. ventricle.
PATHOLOGY Atria
The description of pathologic features will be confined to The left atrium may be small and hypoplastic in most cases,
mitral atresia with normal aortic root. The pathology of mitral but the left atrial wall is thick and hypertrophied. Endocardial
32
fibroelastosis of LA may be present.3,11-13 The right atrium is subvalvar and 1 combined) out of a total of 52 cases. In another
always enlarged and hypertrophied. clinical study of 40 patients, 11 (27%) had pulmonary stenosis
Mitral Atresia
or atresia and 29 (73%) had no pulmonary stenosis.18 Of note,
Atrial Septum coarctation of aorta has not been reported in association
with this lesion when pulmonary stenosis or atresia was
Patent foramen ovale or an atrial septal defect is usually present;1,3,18 this is presumably because of fetal flow patterns
present; patent foramen ovale is seen in approximately two- as reviewed elsewhere19 and in the chapter on tricuspid atresia
thirds and atrial septal defect in one-third.9 The atrial defect in this book (Chapter 28).
may be restrictive and rarely, intact atrial septum may be
present; in such cases levoatriocardinal vein14,15 may partially Other Associated Defects
decompress the completely obstructed left atrium. Other
communications between left atrium and coronary sinus may Ductus arteriosus is patent in nearly 80 percent patients.9
be seen. Communications between left atrium and coronary sinus are
commonly seen. Persistent left superior vena cava may be
Ventricles seen in some patients. Abnormalities of both systemic and
pulmonary venous return may be present especially when
Univentricular hearts are most common with mitral atresia associated with heterotaxy syndrome.
with normal aortic root; most of these are right ventricular
type and a few have two ventricles with atrioventricular Extracardiac Anomalies
concordance. Double outlet right ventricle and double inlet
left ventricle with imperforate left atrioventricular valve, Major extracardiac anomalies are present in nearly half of the
though rare, have been reported. In the pathologic specimens patients. Heterotaxy (asplenia or polysplenia) may be seen in
examined by Thiene et al,1 15 of the 30 specimens were right nearly 25 percent of patients.3
ventricular type of univentricular heart, nine left ventricular
type, five were biventricular and one double inlet left ventricle. PATHOPHYSIOLOGY
When there are two ventricles, the majority of patients
have small left ventricles communicating with right ventricle Pulmonary venous blood from the left atrium exits via the atrial
via a small ventricular septal defect (VSD). Approximately 10 septal defect into the right atrium and mixes with systemic
percent of cases had normal sized left ventricles.3 The right venous return. If the interatrial communication is restrictive,
ventricle is always large and hypertrophied. pulmonary venous congestion and edema develop. If the atrial
septum is intact, the neonate is unlikely to survive unless there
Ventricular Septum is an alternative drainage such as levoatriocardinal vein.14,15
Once in the right atrium, the blood is passed on to the right
In the presence of two ventricles, the majority have a small or single ventricle via the tricuspid valve. The blood is then
VSD, although large VSDs have been reported. distributed into the aorta and pulmonary artery; the relative
flows into the two circuits are dependent upon the resistances
Great Vessels offered by the respective circulations. This results in systemic
arterial desaturation in all patients with mitral atresia. The
Transposition of the great arteries was stated to be degree of desaturation is proportional to the degree of right
frequent,9,16,17 but was present only in 30 percent of cases ventricular outflow obstruction, which is either at valvar
reported by Watson.3 By definition, the aortic valve and aortic and/or subvalvar level. In cases of pulmonary atresia, the
root are near normal in size. Right aortic arch, coarctation of pulmonary blood flow is derived from either via the patent
the aorta and interrupted aortic arch have been reported. In ductus arteriosus or through aortopulmonary collateral
the Watson series, right aortic arch was present in 8 percent vessels.
hearts, coarctation of the aorta was seen in 22 percent cases
and interrupted aortic arch was found in 4 percent specimens.3 CLINICAL FEATURES
Coarctation of the aorta and interrupted aortic arch were seen
only in subjects with normal pulmonary valve. Clinical presentation is largely dependent upon the patho
In the majority of patients, the pulmonary valve is normal physiology related to the amalgamation of associated lesions
and not stenotic; however, valvar and/or subvalvar stenosis seen in these patients. The scenarios include pulmonary
or atresia may be present in 25 to 30 percent of cases. In venous congestion secondary to interatrial obstruction,
series analyzed by Watson and colleagues,3 pulmonary atresia decreased pulmonary blood flow secondary to severe
was seen in four and pulmonary stenosis in 11 (8 valvar, 2 pulmonary stenosis or atresia and increased pulmonary blood 459
6
flow causing volume overload and heart failure in the absence Electrocardiogram
of pulmonary stenosis.
These patients usually present as neonates (usually in Tall, peaked P waves consistent with right atrial enlargement
the 1st week of life) with cyanosis or difficulty in breathing. are present in many patients. Right-axis deviation is seen
Cyanosis in the newborn, in the presence of pulmonary in most patients and a few cases (12%) may show left-axis
stenosis or atresia is due to diminished pulmonary blood flow deviation. Right ventricular hypertrophy is seen in almost all
and complete-mixing of the pulmonary and systemic venous patients. Q wave in right precordial leads is commonly seen;
returns in the right atrium and the right ventricle. Cyanosis a qR pattern in right precordial leads is a fairly consistent
due to diminished pulmonary blood flow is manifested as the feature in one study.3
patent ductus arteriosus begins to constrict. Cyanotic spells
are occasionally noted in infants. Features suggestive of Echocardiography
increased pulmonary blood flow and congestive heart failure
are presenting symptoms in nearly half of the patients; these Echocardiogram is useful in the diagnosis and provides nece
are the patients without any pulmonary stenosis. The clinical ssary information for planning effective clinical management.
features of congestive heart failure appear as the pulmonary Evaluation of cardiac anatomy in subcostal, apical, parasternal
vascular resistance drops with the increasing age of the and suprasternal notch views provides complete assessment.
baby. In babies with interatrial obstruction, tachypnea and/or Key structure to define is the crux cordis, the spatial relationship
dyspnea along with cyanosis may be the presenting features; between atrial and ventricular septae and the atrioventricular
these may be occur shortly after birth or weeks and months (AV) junction.22 It is possible to visualize the atretic atrial floor
following birth as and when the interatrial communication in cases with absent connection vs imperforate valve in cases
becomes restrictive. In babies with intact atrial septum (rare) with imperforate valve membrane in the majority of patients,22
the presentation will be immediately after birth. although this distinction may not be important in terms of
Later during infancy, failure to thrive, irritability, lethargy diagnosis or management. Another important distinction to
and dyspnea may be present. Exercise intolerance is present make is whether the patent right-sided AV valve represents one
in children who live beyond infancy. Clubbing may be present AV valve, as in complete AV septal defect or it represents one AV
later in infancy and childhood.3,18,20 valve and the other AV valve is atretic (Figures 1A to D). This
Diminished femoral pulses may be seen in patients with determination is important with regard to clinical management.
aortic coarctation and as mentioned above, coarctation of the In the former with complete AV septal defect, there is usually
aorta is present in only patients who do not have pulmonary no left atrial hypertension. In the latter, with mitral atresia, there
stenosis. The precordial impulses show either hyperdynamic is a potential for a hypoplastic left atrium and the interatrial
right ventricle or right ventricular heave. Second sound is communication should be evaluated for restrictive flow from
often loud or may be single. Subjects with pulmonary stenosis the left atrium to right atrium.
have long ejection systolic murmurs along the left sternal Another determination to make is the looping of the
border. Continuous murmur, related to high-velocity flow ventricular mass. While d-looping is noted in majority of
across the restrictive atrial septal defect, may be heard in some hearts with this defect, l-looping of the ventricles have
patients.9,21 Otherwise, there is no characteristic murmur been reported in approximately 20 percent of cases.18 In
noted. Signs of congestive heart failure are evident in most the presence of l-loop, the left AV valve atresia, of course,
patients without associated PS. However, if there is severe represents a tricuspid valve atresia with morphologic RV
restriction of atrial septal communication, signs of pulmonary underneath the left AV valve; however, the physiology is that
edema may be seen instead. of mitral atresia.
Adequacy of atrial septal communication is assessed using
INVESTIGATIONS three criteria:
1. Diameter of the atrial level communication in 2-dimensional
image (Figures 1C and 2B).
Chest X-ray
2. Mean Doppler gradient using pulse and or continuous
Chest X-ray findings are nonspecific and reflect the combined wave signal.
effect of associated heart defects and status of pulmonary 3. Color Doppler signal (Figure 2A).
blood flow. Cardiomegaly, with globular enlargement of the Mean Doppler gradient will depend on size of the
heart is usually seen. Increased pulmonary vascular markings communication and the amount of pulmonary blood
are seen in subjects with increased pulmonary blood flow, flow at the time of evaluation. Apart from evaluating the
while the pulmonary vascular markings are diminished in adequacy of atrial level shunt initially, this should be
patients with pulmonary oligemia. In the presence obstruction performed at every follow-up study as well as after balloon
460 at the level of interatrial septum signs of pulmonary edema/ atrial septostomy or surgical septectomy since the atrial
venous congestion may be noted. communication may become inadequate over time.23
32
Mitral Atresia
A B
C D
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 these babies is to relieve left atrial hypertension in cases of
ventricle(s), size of the VSD, great artery origins and relation- restrictive patent foramen ovale or atrial septal defect by
ship and presence of stenosis or atresia of the pulmonary valve balloon atrial septostomy, blade septostomy, static balloon
may be determined in multiple views in a conventional man- dilatation of the atrial septum or stent placement. These
ner; apical four-chamber and subcostal views are most helpful interventions will be discussed below under management
in this regard. Suprasternal notch views should be scrutinized section. Also, cardiac catheterization is indicated prior to
along with Doppler interrogation to confirm or exclude aortic bidirectional Glenn and Fontan surgeries that these patients
coarctation. will eventually require.
When cardiac catheterization is performed, left-to-right
Cardiac Catheterization and Selective Cineangiography shunt at right atrial level is demonstrated and the oxygen
saturations in the RV, aorta and pulmonary artery are similar.
The diagnosis and assessment of associated defects can often Systemic arterial desaturation is always present and is
be made by good quality echocardiographic studies and cardiac proportional to the degree of RV outflow tract obstruction.
catheterization and angiography are rarely needed solely for Pressure pullbacks across the atrial septum should be 461
diagnostic purposes. The main reason for catheterization in performed to ensure adequacy of the atrial septal defect.
6
A B
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 study from Brazil which was published in 1991,24 reporting
significant, requiring intervention. The ventricular pressures outcome of a cohort of 23 patients, five babies died at ages
are at systemic level without any gradient across the aortic ranging from 11 days to 12 months, before any surgical
valve. Pressure gradient across the pulmonary outflow tract therapy could be undertaken. Remaining 18 patients (11 had
is present in patients with significant valvar or subvalvar congestive heart failure and 7 had cyanosis due to pulmonary
pulmonary stenosis. The pulmonary artery pressures are high stenosis) underwent palliative surgical procedures involving
and are at systemic level in patients with no pulmonary outflow surgical atrial septectomy, pulmonary artery banding or
tract obstruction, but are normal or decreased in subjects with Blalock-Taussig shunt. Twelve (66%) of the 18 patients
pulmonary stenosis. Pressure pullback recording across the were alive at follow-up that ranged from 1 to 57 months.
aortic arch may show pressure gradient in the descending Causes of death included heart failure (n = 1), cyanosis
aorta in cases with aortic coarctation. (n = 3) and septicemia (n = 1). One patient has had Fontan
Injection of contrast material into the left atrium may operation at the age of 10 years. Eleven of the 12 patients
provide some clarity in the mitral atresia diagnosis (Figures were in New York Heart Association functional class I and
3 and 4). Selective cineangiography in the ventricle(s), aorta are awaiting further surgical procedures. Given the recent
and pulmonary artery are likely to define the associated developments in diagnosis and treatment of the neonate with
cardiac defects. congenital heart defects, the current prognosis is likely to be
lot better than reported in the above two studies.
NATURAL HISTORY
MANAGEMENT
In the clinical/pathologic review of 52 cases by Watson et al
in 1960,3 two were stillborn and 23 babies died during the Management is dictated by the clinical presentation. The
462 neonatal period. Average survival was 6 months. Only five severity of cyanosis and level of oxygen saturation in
babies (10%) lived up to 1 year or more.3 In a more recent the newborn are largely dependent upon the severity of
32
Management at the Time of Initial Presentation
Mitral Atresia
Initial management of these babies is similar that used in
other cyanotic neonates.25 The infant’s 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
0.05–0.1 µg 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 1–2 mEq/kg diluted half
and half with 5 or 10% dextrose solution) immediately. In
the presence of respiratory acidosis, appropriate suctioning,
Figure 3: Selected cine frames from a left atrial (LA) angiogram in intubation and assisted ventilation should be undertaken.
a left axial oblique (30° LAO and 30° cranial) view demonstrating Since hypoglycemia can be a significant problem, the infant’s
atretic mitral valve (AMV). Note the opacification of the coronary sinus
(CS) via a connecting (C) vein. Such communications have been
serum glucose should be monitored. The neonates should
documented in the literature 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.
Interatrial Obstruction
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
Figure 4: Selected cine frames from a left atrial (LA) angiogram in the atrial septum30,31 with a balloon angioplasty catheter
a left axial oblique (30° LAO and 30° cranial) demonstrating atretic (Figures 5A and B) may be used which may not only relieve
mitral valve (AMV) in a patient who had previously undergone surgical the obstruction, but also keep some restriction such that there
atrial septectomy. Note the restrictive opening (two small arrows) and is no rapid fall in the pulmonary vascular resistance. Static
dilated pulmonary veins (PV). RA = Right atrium
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
pulmonary stenosis or atresia, adequacy of pulmonary blood passage of a catheter. In such situations, puncture of the atrial
flow determined by pulmonary outflow tract obstruction, size septum by Ross technique32 or radiofrequency perforation of
of patent ductus arteriosus, pulmonary vascular resistance and the atrial septum33-35 followed by static balloon atrial septal
degree of restriction at the atrial level shunt. dilatation30,31 or stent (Figures 6 and 7) implantation29,36-38 463
6
A B
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
may become necessary. These transcatheter methods may not of these patients will go into congestive cardiac failure and
be feasible or successful in some infants and surgical atrial this should be treated with adequate anticongestive measures.
septectomy is needed. Open atrial septectomy is considered As soon as a reasonable control of congestive heart failure is
more appropriate than the closed, Blalock-Hanlon atrial achieved, pulmonary artery banding should be performed to
septectomy.18,20,39 attain better control of heart failure, to prevent development
There is evidence that atrial level opening that is adequate of pulmonary vascular obstructive disease and to reduce
early in the neonatal period may become restrictive with time. It pulmonary artery pressures to near normal level.
is suggested that all babies with this condition undergo balloon
atrial septostomy performed, if they have cardiac catheterization Decreased Pulmonary Blood Flow
prior to 1 month of age. In babies who did not require early
atrial septostomy or septectomy, serial echocardiograms should In the subgroup of patients with decreased pulmonary blood
be performed to assess adequacy of atrial septal defect. Atrial flow, placement of systemic-pulmonary artery shunt40,41
septostomy or septectomy may be required later–especially along with ligation of patent ductus arteriosus may become
in the group with unrestricted pulmonary blood flow or after necessary. This is required in all babies with pulmonary
systemic-pulmonary artery shunt.18 atresia and in some babies with pulmonary stenosis.
Increased Pulmonary Blood Flow with Increased Pulmonary Blood Flow along
or without Heart Failure with Interatrial Obstruction
As the transition occurs from fetal circulation in patients This combination can occur frequently.20 We have demon-
464 without pulmonary stenosis or atresia, pulmonary blood flow strated that rapid and predictable fall in pulmonary vascular
increases as the pulmonary vascular resistance drops. Some resistance occurs in patients who undergo relief of restrictive
32
Mitral Atresia
A B
C D
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 followed by Fontan operation.44-46 Details of these surgical
Pulmonary artery band for such patients will prevent heart palliative procedures for single ventricle repair are discussed
failure and development of pulmonary vascular obstructive in chapters on Tricuspid Atresia (Chapter 28) and Hypoplastic
disease and should be performed at the time of relieving atrial Left Heart Syndrome (Chapter 47) and will not be reviewed
septal obstruction. here.
'Corrective' Surgery CONCLUSION

At the present time, no definitive intracardiac repair is Mitral atresia with normal aortic valve is a rare cardiac
feasible for these conditions. All mitral atresia patients are anomaly associated with left atrial hypoplasia and has a
likely candidates for single ventricle palliation and will need tendency to have restrictive atrial level communication. Early 465
staged palliation42,43 with bidirectional Glenn operation,42,43 balloon atrial septostomy and placement of pulmonary artery
6
A B
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 4. Abbott ME. Atlas of congenital cardiac disease. American
main components of early palliative management. Systemic Heart Association, New York, NY; 1936. p. 50.
to pulmonary arterial shunt may be necessary for patients with 5. Edwards JE. Congenital mitral atresia: In Gould S (Ed).
Pathology of the heart. Thomas, Springfield, MO. 1953. p. 386.
pulmonary atresia or severe pulmonary stenosis. As the babies
6. Anderson RH, Thiene G. The clinical morphology of mitral
grow, close attention should be paid to evaluate adequacy atresia. Atresia of the left atrioventricular valve. G Ital Cardio.
of atrial septal defect by serial echocardiograms. Atrial 1981;11:1860.
septostomy or septectomy may be necessary later in infancy, 7. Rao PS. Is the term “tricuspid atresia” appropriate? (Editorial).
if it were not required or not performed in the neonatal period. Am J Cardio. 1990;66:1251.
Therefore, recognizing this constellation of cardiac defects 8. Rao PS. A unified classification of tricuspid atresia. Am Heart
helps to guide early management decisions. Later 'corrective' J. 1980;99:799.
surgical therapy consists of bidirectional Glenn and Fontan 9. Keith JD. Congenital mitral atresia. In: Keith JD, Rowe
operations, similar to other single ventricle lesions. RD, Lad P (Eds). Heart Disease in Infancy and Childhood
Macmillan: 3rd edition. New York; 1977. pp. 549.
10. Rao PS. Atrioventricular canal mimicking tricuspid atresia:
When health is absent, wisdom cannot reveal itself, art echocardiographic and angiographic features. Br Heart J.
cannot manifest, strength cannot fight, wealth becomes 1987;58:409.
useless, and intelligence cannot be applied. 11. Edwards JT, Rodgers HM. Atresia of the orifice of the mitral
—Herophilus valve. J Tech Methods. 1947;27:62.
12. Edwards JE, Dushanbe JW. Thoracic venous anomalies: 1
REFERENCES Vascular connection of the left atrium and left innominate
vein (levo atrio-cardinal vein) associated with mitral atresia
1. Thiene G, Daliento L, Frescura C, et al. Atresia of left atrio in premature closure of the patent foramen ovale. Arch Path.
ventricular valve. Anatomic investigation in 62 cases. Br Heart 1950;49:517.
J. 1981;45:393. 13. Hollman A. Electrocardiographic diagnosis of right ventricular
2. Norwood WI, Kirklin JK, Sanders SP. Hypoplastic left heart hypertrophy in infancy and childhood. Br Heart J. 1958;20:129.
syndrome: experience with palliative surgery. Am J Cardio. 14. Lucas RV Jr, Lester RG, Lillehei CW, et al. Mitral atresia with
1980;45:87. levoatriocardinal vein. A form of congenital pulmonary venous
3. Watson DG, Rowe RD, Conen PE, Duckworth JW. Mitral obstruction. Am J Cardiol. 1962;9:607.
atresia with normal aortic valve. Report of 11 cases and review 15. Lee ML, Wang JK, Lue HC. Levoatriocardinal vein in mitral
of literature. Pediatrics. 1960;25:450. atresia mimicking obstructive total anomalous pulmonary
466 venous connection. Int J Cardiol. 1994;47:1.
32
16. Eliot RS, Shone JD, Kanjuh VI, et al. Mitral atresia. A study of 33. Justino H, Benson LN, Nykanen DG. Transcatheter creation
32 cases. Am Heart J. 1965;70:6. of an atrial septal defect using radiofrequency perforation.
Mitral Atresia
17. Moreno F, Quero M, Diaz LP. Mitral atresia with normal aortic Catheter Cardiovasc Intervent. 2001;54:83.
valve: A study of eighteen cases and a review of the literature. 34. Sakata Y, Feldman T. Transcatheter creation of atrial septal
Circulation. 1976;53:1004. perforation using a radiofrequency transseptal system: novel
18. Mickell JJ, Mathews RA, Park SC, et al. Left atrioventricular approach as an alternative to transseptal needle puncture.
valve atresia: Clinical management. Circulation. 1980;61:123. Catheter Cardiovasc Intervent. 2005;64:327.
19. Rao PS. Tricuspid Atresia. eMedicine from WebMD. Updated 35. Hill SL, Mizelle KM, Vellucci SM, et al. Radiofrequency
February 09, 2009. Available at: http://www.emedicine.com/ perforation and cutting balloon septoplasty of intact atrial
ped/topic2550.htm. septum in a newborn with hypoplastic left heart syndrome
20. Rao PS, Kulangara RJ, Moore HV, et al. Syndrome of using transesophageal ICE probe guidance. Cath Cardiovasc
single ventricle without pulmonary stenosis but with left Interv. 2005;64:214.
atrioventricular vale atresia and interatrial obstruction. J 36. Gewillig D, Boshoff L, Mertens L. Creation with a stent of
Thorac Cardiovasc Surg. 1981;81:127. an unrestrictive lasting atrial communication, Cardiol Young.
21. Ross J Jr, Braunwald E, Mason DT, et al. Interatrial communica 2002;12:404.
tion and left atrial hypertension: a cause of continuous murmur. 37. Eicken H, Gildein C, Schreiber C, et al. Stenting of a restrictive
Circulation. 1963;28:853. foramen ovale in a patient with hypoplastic left heart syndrome.
22. Magherini A, Azzolina G, Careri J. Anatomy of the echocardio Internat J Cardiol. 2006;113:254A.
graphic crux cordis in the evaluation of the spectrum of 38. Holzer RJ, Wood A, Chisolm JL, et al. Atrial septal inter
atrioventricular valve atresia. Int J Cardiol. 1984;5:163. ventions in patients with hypoplastic left heart syndrome. Cath
23. Perry SB, Lang P, Keane JF, et al. Creation and maintenance of Cardiovasc Interv. 2008;72:696.
an adequate interatrial communication in left atrioventricular 39. Weldon CS. Classics in thoracic surgery: The Blalock-Hanlon
valve atresia or stenosis. Am J Cardiol. 1986;58:622. operation. Ann Thorac Surg. 1987;43:448.
24. Atik E, Ikari NM, Aiello VD, et al. Atresia of the left 40. Blalock A, Taussig HB. The surgical treatment of malformations
atrioventricular valve with patency of the aorta: anatomico- of the heart in which there is pulmonary stenosis or atresia. J
functional analysis of 23 patients. Int J Cardiol. 1991;32:281. Am Med Assoc. 1945;128:189.
25. Rao PS. Principles of management of the neonate with 41. de Leval MR, McKay R, Jones M, et al. Modified Blalock-
congenital heart disease. Neonatology Today. 2007;2(8):1. Taussig shunt. Use of subclavian artery orifice as flow regulator
26. Rashkind WJ, Miller WW. Creation of an atrial septal defect in prosthetic systemic-pulmonary artery shunts. J Thorac
without thoracotomy: Palliative approach to complete transpo- Cardiovasc Surg. 1981;81:112.
sition of the great arteries. J Am Med Assoc. 1966;196:991. 42. Pridjian AK, Mendelsohn AM, Lupinetti FM, et al. Usefulness
27. Park SC, Zubebuhler JR, Neches WH, et al. A new atrial of the bidirectional Glenn procedure as staged reconstruction
septostomy technique. Cath Cardiovasc Diagn. 1975;1:195. for the functional single ventricle. Am J Cardiol. 1993;71:959.
28. Park SC, Neches WH, Zuberbuhler JR, et al. Clinical use of 43. Tanoue Y, Sese A, Ueno Y, et al. Bidirectional Glenn procedure
blade atrial septostomy. Circulation. 1978;58:600. improves the mechanical efficiency of a total cavopulmonary
29. Rao PS. Role of Interventional Cardiology In Neonates: connection in high-risk Fontan candidates. Circulation.
Part I. Non-Surgical Atrial Septostomy. Neonatology Today. 2001;103:2176.
2007;2:9. 44. Fontan F, Baudet E. Surgical repair of tricuspid atresia. Thorax.
30. Shrivastava S, Radhakrishnan S, Dev V, et al. Balloon dilatation 1971;26:240.
of atrial septum in complete transposition of great arteries—a 45. Kreutzer G, Bono H, Galindez E, et al. Una operacion para
new technique. Indian Heart J. 1987;39:298. la correccion de la atresia tricuspidea. Ninth Argentinean
31. Rao PS. Static balloon dilation of atrial septum (Editorial). Am Congress of Cardiology, Buenos Aires, Argentina, Oct. 31-
Heart J. 1993;125:1826. Nov. 6, 1971.
32. Atz AM, Feinstein JA, Jonas RA, et al. Preoperative mana 46. de Laval MR, Kilner P, Gewilling M, et al. Total cavopulmonary
gement of pulmonary venous hypertension in hypoplastic connection: a logical alternative to atriopulmonary connection
left heart syndrome with restrictive atrial septal defect. Am J for complex Fontan operation. J Thorac Cardiovasc Surg.
Cardiol. 1999;83:1224. 1988;96:682.
467
c hapter
33 aortic valve diseases
Smita Mishra, Neeraj Awasthy
IntroductIon and the left ventricular outflow tract (LVOT). The theory
of hemodynamic moulding postulates that the failure of
The aortic valve (AV) is one of the semilunar valves of the development of cardiac structures is caused by diminished
heart, normally located at the left ventriculoarterial junction. blood flow through them. In fact, restrictive foramen ovale,
It has a critical role in maintaining the fine coordination of left ventricle, hypoplastic left ventricle (LV) and abnormal
fluid mechanics between the systemic ventricle and systemic mitral valve are often seen in association with aortic stenosis/
arterial system during the entire cardiac cycle. Inherently, it is atresia and coarctation or interruption of arch.1,9-15
tricuspid, i.e. guarded by three leaflets. However, occasionally We will see later in the chapter that the AV forms an
the number of leaflets differs, leading to a restrictive or important boundary of the LVOT and has a complex
regurgitant valve.1,2 These numerical variations were known relationship with membranous and muscular interventricular
in ancient era. In fact, Major Leonardo da Vinci was one of septum and with both the mitral leaflets. Any embryological
the first to call attention to the aortic valve with two leaflets.3 malformation of these structures carry a composite anatomical
and therapeutic implications.16
Prevalence
genetIcs and FamIlIal InherItance1-4,14,17,18
The bicuspid aortic valve (BAV) is the most common abnor-
mality of the aortic valve. It has an incidence of 0.03 to 0.34 There are compelling evidences of the familial occurrence of
per 1,000 live births and constitutes about 7 percent of all con- aortic stenosis. It is known to occur with Turner syndrome
genital cardiac malformations. The prevalence of congenital and Jacobsen syndrome. Non-syndromic occurrence occurs
BAV is 1.3 percent. Of that 2 percent patients will experience sporadically following the pattern of multifactorial inheri-
significant aortic stenosis or regurgitation by adolescence.1,4-9 tance. However, the male predominance (male-to-female
ratio ≥ 3:1) as well as association of BAV with Turner’s
embryology10–16 syndrome (45X chromosomal pattern) suggests an X-linked
etiology. A heritability study found no X-linkage but did find
The embryonic truncus arteriosus is divided by the spiral linkage to chromosomal regions 5q, 13q, and 18q. Mutations
conotruncal septum. The normal right and left aortic leaflets in the NOTCH1 gene (chromosome 9q) leads to signaling
form at the junction of the ventricular and arterial ends of the abnormalities that may be responsible for the development
conotruncal channel. The non-septal leaflet (posterior) cusp of a bileaflet aortic valve. Ellison et al studied an extended
normally forms from additional conotruncal channel tissue. family with BAV and found no evidence of linkage of BAV
The conotruncal channel tissue is subendocardial and needs in their pedigree to either the NOTCH1 gene or to the
to undergo the process of cavitation and hollowing to form chromosome 15 locus. They concluded that the disorder in
the leaflets. In the 5th week of embryological development, this family might be caused by a gene at a novel locus.13
excess mesenchymatous tissue is absorbed to form an outline Although aorta in patients with BAV have histopathological
of the aortic valve at the apex of the aortic vestibule. The findings similar to aorta in Marfan syndrome the underlying
aortic valve cusps and sinuses are well formed by the 8th genetic abnormality of Marfan syndrome, mutation in the
week. The failure of any of the developmental steps leads FBN1 gene that encodes fibrillin-1 and is not found with
to isolated or combined malformation of the aortic valve BAV disease.
aortIc root: anatomIcal and FunctIonal asPects 33
definition of the aortic root
Aortic VAlVe DiseAses

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 A
Aortic root extends from the basal attachments of the leaflets

within the LV to the sinotubular junction (STJ) (Figures 1–2
A and B).
components of the aortic root14-15

1. Ventriculoarterial junction
2. Aortic annulus
3. Sinotubular junction
4. Interleaflet fibrous triangles
5. Sinuses of Valsalva
6. Aortic valve (AV leaflets)
7. Ostium of right and left coronary artery.
Ventriculoarterial Junction—Attachment of the

Aortic Root to the Heart
Attachment of the aortic root to the LVOT is such that B
approximately two-third of the circumference of the lower
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 root—attachment of the leaflets and interleaflet Aortic Annulus 469
fibrous triangles. LC = Left coronary ostium; LCC = Left coronary
cusp; NCC = Non-coronary cusp; RC = Right coronary ostium; RCC The aortic annulus is a 3-pronged crown-like ring and has a
= Right coronary cusp. base formed by aortic annulus, a top formed by sinotubular
6 Sinotubular Junction—The Outlet of the Aortic Root
The STJ is the junction between the aortic root and ascending
congenitAl VAlVAr lesions
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

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
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 communication with extracardiac space (Figures 1 and 2). The
attachment points of the leaflets within the left ventricle. Ring 1 is the triangles are thinner and less collagenous; and hence, are a
true ring formed at sinotubular junction (STJ). The ring 2 represents vulnerable site for aneurysm formation. The triangle between
aortic attachment of leaflet at an imaginary plane and demonstrates the right and the noncoronary leaflets adjoins the interventricular
the pocket like attachment buttressed by the nodule of Arantius
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
junction, and in between a ring formed by pocket-like attach- the area of the left-posterior aortic commissure. The left trigone
ment of leaflets. is a part of extensive curtain of the aortic-to-mitral valve fibrous
continuity. The third triangle present in between the right and
Echocardiographically, the annulus is well defined. To left coronary cusp, is least extensive.
understand this complex morphology of the aortic annulus,
we need to review the Figures 1 to 3. The ring joining the Sinus of Valsalva—Structure and Function
hinge points of the valve in parasternal long-axis view is
designated as annulus, but factually an “annulus” is one of Sinus of Valsalva are the three bulgings at the root of the aorta.
the several such rings incorporated within the aortic root. The aortic root has three bulgings in its circumferential wall
Evidently, aortic annulus is no discrete anatomic structure. to accommodate the extra size of the valvar leaflet, known as
Surgically, the annulus is described as a semilunar crown- sinus of Valsalva. Normally, the right sinus of Valsalva projects
like structure demarcated by the hinges of the leaflets. towards the right side of the intact interventricular septum.
Furthermore, the aortic root contains at least 3 circular rings Therefore, any ventricular septal defect (VSD) in the area may
and the leaflets are attached throughout the length of the create the impression that the aorta is overriding. In congenital
root in the three dimensional imaginary plane. Therefore, heart defects (CHDs) like tetralogy of Fallot, true override is seen
the leaflets take the form of a three-pronged crown-like and the degree of override may vary from 15 to 95 percent. In the
ring, hinging on the supporting ventricular structures. en face view, the aortic valve in closed position shows triradiating
Therefore, the annulus has a base of the crown, the virtual lines of apposition between the adjacent leaflets reaching to the
ring joining the basal attachment points of the leaflets peripheral commissures, and encircled by the aortic wall.
within the LV. This plane represents the outlet of the LVOT As mentioned below, the opening and closing of the aortic
(Figure 3, ring 3) or the inlet of the aortic root. The true valve is related to the principles of fluid hemodynamics, i.e.
ring is formed at the STJ and forms at the top of crown. In acceleration, vortex formation and subsequent deceleration of
between these two rings, a third ring exists at a plane which the blood column. Along with that, there are changes in pressures
(Figure 3, ring 1) passes through the attachment of the leaflet on both sides of the AV. The sinuses of Valsalva play a definitive
against the wall of the sinus of Valsalva. The scalloped role in the dynamic interactions of the aortic root with the LV on
configuration of the hingelines of the leaflets (Figure 3, the one side and systemic vascular pressure on the other side.14-20
ring 2) crosses the ventriculoarterial junction, leaving
interleaflet fibrous triangles between the sinuses that are Aortic Valve
anatomically aortic, but hemodynamically ventricular. The
semilunar hinges also cross the anatomic ventriculoarterial Structure of the aortic valve: As we know AV contains three
470 junction14-17 (Figures 2 and 3). cusps or leaflets. In the normal AV, the cusps are symmetrical,
mobile, free upto the commissures so to achieve equal overlap 33
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 Figure 4: Origin of coronary arteries from the facing sinuses.
LAD = Left anterior descending artery; LCC = Left coronary sinus;
diastolic pressure exceeds the LV pressure. This allows the PA = Pulmonary artery; RAA = Right atrial appendage; RCA = Right
pocket of leaflets to expand with the diastolic aortic pressure coronary artery; RCC = Right coronary sinus.
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 It is exceedingly rare to encounter origin of a coronary artery
the aorta. It can be postulated that a fluid dynamic control from the ‘non-facing’ aortic sinus.14,15,25
mechanism exists which positions the cusps away from the
wall of the aorta without the need of subvalvar apparatus, and hIstologIcal asPect oF aortIc valve
the slightest reversed flow leads to efficient valve closure.14-23
Robicsek et al studied the functioning of congenital Each AV leaflet has a fibrous core, which has two
BAVs and reported that, the anatomical length of the leaflet components—1. Fibrosa made up of mainly collagens, 2.
edges is constant, but their ‘functional’ length must change, Spongiosa, which has elastin. The two aspects of the covering
to match the geometry of full closure and opening. The of the leaflets are known as arterialis and ventricularis
gradual folding and unfolding of the cusps is a necessity in on the respective sides. The collagen bundles are aligned
the process. As opposed to the normal tricuspid aortic valve, circumferentially, parallel to the free margin, adding to the
the folding is not only excessive, but some folds and creases undulations on the arterial aspect. Radially aligned collagen
persist throughout the cardiac cycle. They are also sharper fibers are found near to the hinge line. In the middle of the
and shaped in more acute angles. The authors noticed that free edge of each cusp on the ventricular surface, is a fibrous
to compensate for the leaflet length discrepancy in the mound made up of mass of elastic tissue that is called nodule
congenital BAVs between the full opening and full closure, of Arantius. Coaptation of the three nodules ensures complete
there is the extension of the area of approximation of the central closure of the valve during diastole. It has been
cusps. This is achieved by an increased bulge (doming) of demonstrated in the pig valve that the ventricularis contains
the ‘leaflet bellies,’ which allows the leaflet edges to either a considerable amount of sheet elastin, whereas the elastin
fold or travel in an upward convex arch or both. They also fibres in the fibrosa are arranged like tubular meshwork,
observed the geometrical alteration by which the line of extended circumferentially across the leaflet.14,26,27
apposition deviates from the centre.24
InterPlay oF Pressure dynamIcs
Origin of Coronary Arteries—Concept of Facing Sinuses between lv and aorta
Two of the aortic sinuses give rise to the main coronary During the systole, when the LV pressure exceeds the aortic
arteries and the sinuses are termed as right (or anterior) and root pressure, AV opens to eject the blood. Precisely, the LV
left coronary (left posterior) sinuses (Figure 4). The third sinus in systole is the upstream chamber of the high pressure arterial
is conveniently termed as the non-coronary (right posterior) system. The diastole starts with isovolumic relaxation of the
aortic sinus. Universally, irrespective of the aortic and ventricles. When the LV pressure decreases to less than the
pulmonary valve relationship, aortic sinuses adjacent to the aortic pressure, blood column moves backwards, leading
pulmonary valve (PV) gives origin to the coronary arteries. to closure of the AV. Interestingly, with closure of AV and
Accordingly, they are described as the ‘facing’ aortic sinuses. opening of the mitral valve, LV becomes the downstream 471
6 chamber for the low pressure pulmonary venous system. needs a constant diastolic pressure to maintain the mean
To achieve this lowest pressure, the ventricle needs active systemic blood pressures, so as to maintain the physiological
relaxation, a process, which requires energy. This active requirement of the peripheral tissues as well as to maintain the
relaxation creates a suction effect, which helps in the early coronary blood flow during the diastole. The incompetent AV
rapid filling phase of diastole. The atrial systole provides hinders these physiological necessities.
atrial kick and the remaining left atrial blood is pushed
forward into the LV. To understand the mechanics of the relatIonshIPs oF the aortIc root and Its
ventricle one must understand the concept of ‘preload’ and clInIcal ImPortance
‘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
aortic root and left ventricular outflow tract
diastole, and the term afterload can be defined as all of the The left ventricular outflow is a small area. This subaortic
factors that contribute to the total myocardial wall stress (or area, also known as aortic vestibule, is smaller and less
tension) during systolic ejection. The preload refers to the well defined than right ventricular outflow tract (RVOT).
stretch of the LV just before the onset of contraction. The Anteriorly, it is formed by the muscular and membranous
inflow of the atrial blood contributes to the preload of the ventricular septum. The posterior boundary is drawn mostly
ventricle. During ejection phase, the aortic pressure almost by the free inferior margin of the anterior mitral leaflet that
equalizes to LV and little gradient exists. The blood flows forms a curtain between the inflow and the outflow of the LV.
unobstructed to the peripheral tissues.14,15,28-30 Also, a small part of the posterior boundary is contributed by
Physiologically, during each cardiac cycle, the aortic root the intervalvar septum and the posterior mitral leaflet where
varies in symmetry and dimensions. Geometrically, aortic it fuses with the AML.14-17
root dimensions differed approximately by 12 percent during
the cardiac cycle in animal experiments. Recently, Heer et al relationship of the right and left ventricular outflow
demonstrated the significant individual dynamic changes in tracts to the aortic root
the dimensions of the aortic root in a study utilizing ECG-
gated multidetector computed tomography.30 Despite the fact that RVOT and LVOT have significant difference
The model of the aortic root was studied for its inherent in length, at the base of the heart, aortic and pulmonary valve
capacity to effectively withstand prolonged sheering forces can be seen almost at the same plane (Figures 5 and 6). This
generated during the extreme change in pressures on either is possible because the RVOT wraps circumferentially around
side of the AV. Now it is known, that various anatomical the LVOT. Therefore, the anterior wall of the LVOT shares
asymmetries customary at the level of the cusps give part of the posterior wall of the RVOT. This sharing of the
mechanical advantage to the aortic root during the cardiac common wall exists beyond the semilunar valves. The main
cycle. Dagum et al published their experimental work in a pulmonary artery (MPA) and the proximal right pulmonary
three-dimentional model of the bovine aortic root on how artery, share their walls with the proximal ascending aorta.
it undergoes complex, asymmetric deformations during Echocardiographically, this arrangement is described as ‘cup
the various phases of the cardiac cycle. The description and saucer’ appearance seen in parasternal short-axis or basal
included strain happening at the aorto-ventricular and STJ, view, where the AV can be seen as a circle or cup. The right
as well as the elongation, compression, sheer and torsional and left atrium forms the posterior part of the saucer and the
deformation of the aortic root.30 These deformations were not tricuspid valve, RVOT, PV and MPA, all opening up in the
homogeneous among the left, right, and non-coronary regions. long-axis in this view, form the anterior and the lateral part. The
Furthermore, changes in the left ventricular volume, pressure, PV lies to the left and anterior to the AV. As described above,
and contractility affected the degree of deformation in a non- the AV is in fibrous continuity with the AML.13,14,16,30
uniform manner in the three regions studied and these effects
varied during isovolumic contraction, ejection, isovolumic aortic root and membranous septum
relaxation and diastole.13,14,28-30
They concluded that the aortic valve repair techniques or The membranous interventricular septum is morphologically
methods of replacement using unstented autograft, allograft, an important area. Posteroinferiorly, it is related with the
or xenograft tissue valves that best preserve this normal tricuspid valve. The anterosuperior boundary is formed by the
pattern of aortic root dynamics should translate into a lower AV (Figure 7). On the left side due to the higher attachment of
risk of long-term cusp deterioration.30A the mitral leaflet, the membranous septum is atrioventricular
Obstructive lesions of the aortic valve manifest as systolic and a defect in this area presents with a obligatory LV to RA
gradient between LV and aorta which in turn, increases the shunt. Due to this important relationship, the anatomy of this
left ventricular afterload. On the contrary, ineffective closure area has enormous therapeutic importance. A septal defect in
472 of the AV exposes the aorta to the ventricular diastolic low this area may be complicated by aortic valve prolapse and
pressure and promotes reverse flow across the AV. The aorta may cause an incompetent valve.
33

A B
Figures 5A to c: A. Cartoon showing the base of the heart—the

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 Echo—parasternal short-axis
view showing the AV opening axis. AV = Aortic valve; LA = Left atrium;
PV = Pulmonary valve; RA = Right atrium; RVOT = Right ventricular
c outflow tract; TV = Tricuspid valve.
A B
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
6
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

table 1
lower part of the right atrium and upper part of the right ventricle and Terminologies related to the aortic valve
is thin and fibrous
Aortic sclerosis It is defined as a irregular area of focal
thickening of the aortic valve without causing
obstruction.
Literally, the aortic root is allied to all four cardiac Aortic override When aorta straddles the ventricular septal
chambers, both interatrial as well as interventricular septum defect (VSD) and seems to arise from both
and the conduction system. Therefore, both surgeons and the ventricles.
the interventional cardiologists must have a clear anatomical Prolapse of the Aortic valve can prolapse into the adjacent
understanding about it.3,14,15,17 aortic valve VSD. The outpouching of the aortic valve
is seen below the hinge point of the valve
attachment.
aortic root and the conduction system Aneurysm Aneurysm of sinus of Valsalva is dilatation
of sinus of and outpouching of the sinus of Valsalva
The most important surgical relationship of the aortic root, Valsalva (aortic wall). It is located above the hinge
nonetheless, is probably to the atrioventricular node and point of aortic valve.
the penetrating atrioventricular bundle (Figure 8). The Aortico-left ALVT is a extracardiac channel usually
node, located in the wall of the right atrium at the apex of ventricular connecting the aortic root above the right
the triangle of Koch, is relatively distant from the root. As tunnel (ALVT) coronary artery origin (tubular aorta) to the
the conduction axis penetrates through the central fibrous left ventricle (90% cases), in relation to the
body, however, it is positioned at the base of the interleaflet infundibular septum and the right sinus.
Sometimes its position may be unusual.
triangle between the non- and right coronary aortic sinuses.
The fibrous triangle between the right and the non-coronary Normal Aortic valve is positioned to the right and
leaflets is the guide to the location of the atrioventricular great vessel posterior, in relation to the pulmonary valve.
relationship
conduction bundle. After penetrating through the insulated
fibrous plane at the atrioventricular junction, the bundle then D-malposed Aortic valve is positioned to the right and
branches on the crest of the muscular ventricular septum. The aorta side by side or anterior, in relation to the
pulmonary valve.
left bundle branch fans out on the smooth LV side, whilst
the cord-like right bundle branch penetrates back through L-malposed Aortic valve is postioned anterior and to the
aorta left, in relation to the pulmonary valve.
the muscular septum, emerging out on the septal surface in
the environs of the medial papillary muscle. In this position, Inversely Aortic valve is positioned left and posterior,
therefore, the muscular axis responsible for atrioventricular placed great in relation to the pulmonary valve (in situs
vessels inversus).
conduction should be relatively distant from most surgical
maneuvers carried out to replace or repair the aortic valve Anterior aorta Aortic valve is positioned directly anterior in
relation to the pulmonary valve.
and its supporting structures.31-33 Although, the lesions of the
aortic root like aneurysm and abscess can lead to compression Posterior aorta Aortic valve is positioned directly posterior in
relation to the pulmonary valve.
of the node or bundle (Figures 8 and 9).
474
33

A A
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 can interfere with the competency of the valve and can
ImPlIcatIons In InterventIons culminate into the valve replacement procedure, in the long
run. The understanding of the aortic root and its dimensional
The aortic root and its adjacent cardiac structures are subject of variation at different levels are significant. The sizing of the
immense clinical interest because many surgical and catheter aortic annulus at hinge points in 2D echocardiogram has to
interventions are performed, in this vicinity, to restore the be precise for the optimum choice of balloon.9,36
normal and natural functioning of the diseased heart. There
can be two kinds of cardiac interventions: when manipulation is in the adjacent structures:
1. When the aortic root and aortic valve are directly cardiac catheter and surgical Interventions37
manipulated.
2. When interventional manipulation is in the adjacent Many catheter interventions, like device closure of atrial septal
structures where the aortic root is used as a passage or to defect (ASD), VSD, aortopulmonary window, ruptured sinus
anchor the artificial material. of Valsalva or paravalvular leaks take place in or around the
aortic root. For example, in the device closure of ASD, wrong
when the aortic root and aortic valve are choice or placement of device may lead to aortic perforation.37
directly manipulated A wrongly placed device for perimembranous VSD can lead to
deformation of the aortic cusp. Surgical complications can also
The aortic root and its components are continuously working happen in the form of perforation or valvar dysfunction.38 Both
under high pressures and the resulting shear forces. There may types of interventions may cause conduction abnormalities.
be inherent problems like numerical cuspal abnormalities or
abnormalities of the aortic root wall. Moreover, the functional dIseases oF the aortIc valve
abilities of the aortic root may also decline due to the neonatal
or infantile surgical procedures like arterial switch, Ross As mentioned above there are two typical processes that can
procedures or adult aortic root reconstruction.14,15,17,34,35 affect the aortic valve. One is aortic stenosis in which the
As we have learned that the aortic root has a mechanism valve fails to open fully, thereby obstructing blood flow from
to make it physiologically effective in the presence of shear the heart and the second is aortic valve insufficiency, causing
forces, it is clear that all interventional methods are yet to be increased LV preload due to regurgitation of blood from
differential to this innate ability. This may be the explanation aorta to LV during diastole. These two conditions frequently
for the relatively rapid deterioration of the artificial material coexist. Besides, pathological aortic root dilatation is also
in the aortic position. These facts must be considered, while seen frequently, in bicuspid valve disease.22-24,39-48
choosing the interventional steps and prosthesis. Common causes of aortic stenosis include rheumatic fever,
The ballooning procedures are less interfering with degenerative calcification and congenital diseases such as
the natural functional abilities of the aortic root. But they BAV (Table 2).22-24,39-46,48 The spectrum of congenital aortic 475
6 
table 2 morphology of stenotic aortic valve
Causes of aortic stenosis
Routinely, morphology of the AV is evaluated on echo-
Congenital Abnormal number of cusps—unicuspid, cardiography. The parasternal views (short-axis view at the
bicuspid, tricuspid, quadricuspid, six-cuspid
base of the heart and long-axis view) are used to determine
Calcific or degenerative the morphology and number of cusps. Subcostal coronal view
Rheumatic valve disease with anterior tilt, apical four-chamber with anterior tilt and
Other conditions: Homogenous type II hyperlipoproteinemia parasternal long-axis views are particularly useful to define
Metabolic (Fabry’s disease) the valve motion.17,22,23,41
Systemic lupus erythematosus Normal AV is tricuspid and has three leaflets of nearly
Alkaptonuria 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
stenosis (AS) ranges from mild AS to a severe form of the (Figures 10A). The congenital anomalies of AV comprise
disease, which may manifest in fetal life and terminates into a spectrum of deformities, which includes abnormal form,
hypoplastic left heart. size and the number of leaflets (Table 3).22-24,39-46,48 Normal
The aortic root and aortic valve may have morphological AV leaflets are thin and have unrestricted mobility. In
and positional abnormalities, as is shown in Table1. stenotic valves, leaflets are thickened and domed in systole.
Common causes of aortic regurgitation (AR) include Doming of valve leaflets during systole occur due to limited
dilation of the aorta, infective endocarditis, myxomatous cusps separation leading to restricted mobility of valve
degeneration of the AV and Marfan syndrome.22,23,38-43 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, A unicuspid valve can be of two pathological varieties—
accounting for 70 to 91 percent of aortic obstructions. It is acommissural and unicommissural and can be seen in SAX
caused by cusp deformities with or without narrowing of view. The acommissural valve is a rare anomaly and has a
the ‘annulus’. It may manifest early, in a neonate or later in single membrane-like leaflet with a central circular orifice.
infants and children due to the progressive obstruction of the Unicommissural unicuspid valves occur more frequently and
inherently abnormal valve.22,23,38-43 are the most common cause of symptomatic AS in neonates.
The evaluation of valvar aortic stenosis should include: The orifice is typically eccentric and circular in systole
a. Morphology of the stenotic valve (Figures 11 and 12). In diastole, an eccentrically located
b. Dimensions of the aortic root valve closure is seen with no raphae. The unicuspid valve is
c. Severity of valvar obstruction generally stenotic in neonatal period though occasionally it
d. Left ventricular function has sufficient redundancy and may be the cause of obstruction
e. Associated anomalies. in adult life.22,23,46
A B
476 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 parasternal short-axis view. Additional short axis features that 33
Morphology of the valve support the diagnosis, include leaflet redundancy, infolding
and eccentric valve closure. In parasternal long-axis view,

• Unicuspid aortic valve an abnormal eccentric coaptation line with systolic leaflet
– Acommissural doming and an abnormal pattern of systolic opening is seen.
– Unicommissural Though there is no fixed pattern of coronary artery origin
• Bicuspid aortic valve with BAV, usually the coronary arteries emerge from the anterior
sinus in case of anterior and posterior cusps with normally related
– Fused right and left coronary cusps
great vessels, and from posterior sinus in case of transposition of
– Fused right and non-coronary cusps
great vessels. In presence of right and left cusps, left coronary
– Fused left and non-coronary cusps artery arises from the anterior part of the left sinus and the right
• Tricuspid aortic valve coronary from anterior part of the right sinus.
– Symmetrical cusps The majority of the BAV will cause no problems. This
– Asymmetrical condition is often undiagnosed until later in life when the
person develops symptomatic aortic stenosis. Aortic stenosis
• Quadricuspid aortic valve (rare)
occurs in this condition usually in patients in their 40s or 50s,
– 3 cusps equal size, one smaller an average of 10 years earlier than it occurs in patients with
– 4 cusps of equal size congenitally normal aortic valves.14,15,17,22-24,38-43,47-49
• Pentacuspid aortic valve (very rare) 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
A B c of aortic valve stenosis is variable and may be related to the
valvar characteristics. The patients with anteroposteriorly
Figures 11A to c: A. Unicuspid valve—unicommissural valve (toilet
seat shape); B. Unicuspid valve—unicommissural valve (tear drop (as opposed to right-left) and eccentric (vs symmetric) valve
shape); C. Unicuspid valve—acommissural valve (only raphae seen, leaflets have faster rate of progression of aortic obstruction.43
no commissures seen reaching the wall of aorta and centrally stenotic Also, the patients with fusion of the right coronary and non-
opening)
coronary leaflets are more likely to have AR. There are various
classifications of BAV based on the type of fusion of the cusps,
Congenital Bicuspid Aortic Valve position of the raphae, orientation of the commisures as well as
other criteria like leaflets size and interleaflet triangles.47-49 Two
As we know that the BAV is one of the commonest congenital simple classifications are shown in the Figures 14A and B.47-49
malformation involving AV (Figures 10B and 13A to E). Cheitlin et al,demostrated that in few cases of BAV
It includes certain spectrum of different phenotypes that can obstruction is secondary to the dysplastic cusps, and dysplastic
be comprehensively classified into three types (Type 0, 1 changes rather than the commissural fusion were responsible
and 2) according to the number of raphes.47 for the observed aortic stenosis.42 These valves do not appear
Echocardiographic diagnosis of a BAV is based on amenable to valvotomy because obstruction is due to the
demonstration of two cusps and two commissures on direct abnormal valve tissue.
A B c
477
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
6
A B
c D e
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
A B
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
Congenitally Stenotic Tricuspid Aortic Valve LV mass associated with an increased relative wall thickness. 33
This is usually calculated as 2 × posterior wall thickness/LV
Congenitally stenotic tricuspid AV has three aortic cusps. The diastolic diameter and a value > 0.45 is abnormal.52

edges of the cusps are rolled or gnarled with varying degrees The stroke volume, cardiac output, baseline heart rate and
of commissural fusion. This abnormality is often associated ejection fraction are normally maintained because of this
with a narrowed aortic annulus. The annular hypoplasia or adaptation. However, after sometime, the ventricle starts failing
myxoid dysplasia of tricuspid valve leaflets may also lead to and stroke volume decreases and ventricle dilates. So, left-
aortic stenosis.17,22,23,46 sided obstructive lesions must be ruled out before labelling a
patient with low ejection fraction as a case of cardiomyopathy.
Quadricuspid Aortic Valve These patients have an imbalance between the coronary blood
flow to the hypertrophied LV and the increased myocardial
The quadricuspid AV is a very rare (0.013%) congenital anomaly. oxygen demand owing to the pressure overload. The principal
Hurwitz and Robert classified the quadricuspid semilunar determinants of subendocardial blood flow are the length of
valve based on the relative sizes of the four cusps. However, diastole and the coronary artery driving pressure.51
no correlation has been found between anatomic variation and Moderate hypertrophy allows for a lower heart rate,
functional status. Though aortic stenosis is rare, approximately increased diastolic volume and thus higher stroke volume. The
50 percent cases have aortic insufficiency. Aortic regurgitation increased thickening of the ventricular muscle associated with
is more common with small accessory cusp.17,22,23,40,49 pathological conditions like AS results in decreased chamber
In parasternal short-axis view, four diastolic closure lines compliance. As a result, LV pressures are elevated, the end
are present forming a characteristic ‘X’ pattern, and in systole, systolic volume (ESV) is increased and the end diastolic
four cusps open and form a rectangular configuration (Figures volume (EDV) is decreased, causing an overall reduction in
15A and B). Color flow mapping shows presence of AR. cardiac output.
Pentacuspid Aortic Valve left ventricle in aortic stenosis: some Facts

Pentacuspid aortic valves also have been described rarely in a. The left ventricle response to AS includes LV remodeling
case reports.55 and myofibrillar hypertrophy with fibrosis.
b. The LV mass is not directly in proportional to the degree of
eFFect oF aortIc stenosIs on leFt ventrIcle valvar obstruction.
c. The LV responds to AS by concentric hypertrophy (wall
The LV in AS undergoes the adaptive changes, which can be thickness is increased disproportionately more than cavity
defined as concentric remodeling, which results in normal size) (Figures 16A to D).
A B
Figures 15A and B: Quadricuspid aortic valve. Parasternal short axis view shows the valve. A. Closed position; B. Open position. 479
CA = Coronary artery ; LA = Left atrium; RA = Right atrium; RVOT = Right ventricular outflow tract
6
A B
c D
Figures 16A to D: A. PLAX—maladaptive 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. PLAX—turbulent flow at LVOT (systolic anterior motion of MV); D. M-mode
echo—systolic 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 incidental finding on echocardiographic examination or at
adaptive change is actually maladaptive and leads to autopsy. Only 2 percent of the patients with congenitally
diastolic dysfunction and abnormal coronary flow and malformed AV may experience clinically significant AS or
can add up adversely, to the overall outcome. The animal regurgitation by the adolescence.14,15,17,22,23,58,60
experiments have showed an advantage if this maladaptive Children who develop early progressive, pathologic chang-
LVH can be prevented.52 es in the BAV are more likely to develop valve regurgitation
e. In the older patient population, women have more wall than stenosis.46,48
thickness than cavity size, while men have relatively less Many patients with abnormal AV may develop endocarditis
thickening and more cavity space.52 and may present with fever or systemic embolization at early
f. The favorable role of drug therapy with statins, angiotensin or late age.56,57
converting enzyme (ACE) inhibitors and certain other drugs
on the progression of AS in adults has been studied and aortic stenosis in older children
published but there is no such study in pediatric age group.52-54
Symptoms14,17,18,58,59,60
clinical Presentation
Grown up children are generally asymptomatic during
Unicuspid valves generally present early in the neonatal age childhood. They have normal growth and development. The
group with severe AS. Usually, the results of the interventional most commonly reported symptoms are fatigability, exertional
procedures are suboptimal. BAV may be diagnosed in patients dyspnea, angina pectoris and syncope. Easy fatigability is
480 of any age. BAV may remain silent and be discovered as an the frequent symptom and has been reported in 15 percent of
patients with mild AS and 31 percent of patients with severe the rapid distention of the proximal aorta at the onset of 33
AS. Interpretation of the clinical significance of this symptom ejection. Aortic ejection clicks are usually best heard with
is difficult. In severe AS, angina or syncope are reported in less the diaphragm in the second right intercostal space or at the

than 10 percent of patients even when peak-to-peak pressure apex. The aortic ejection click, usually, occurs immediately
gradients are more than 80 mm Hg. However, when present, before or coincident with the initial carotid upstroke. Unlike a
angina or syncope suggests severe stenosis and mandates prompt PV ejection click, timing and intensity of an aortic click does
evaluation and treatment.14,17,18,59,60 not vary with respiration (constant ejection click). The aortic
ejection click must be distinguished from tricuspid component
Physical Examination14,17,18,59,60 (T1) of S1 and S4. The aortic click tends to disappear in the
presence of a calcific valve and severe stenosis. Nonetheless,
Vital signs are normal except in children with severe AS and the presence of an ejection click and suprasternal notch thrill,
congestive heart failure. However, the pulse in significant AS strongly suggests that the AS is valvar rather than subvalvar or
is usually of different types. The pulse with anacrotic character, supravalvar.
(anacrotic pulse) gives the impression of interruption of the The systolic crescendo-decrescendo systolic ejection
upstroke of the carotid pulse. Aortic stenosis is likely to be murmur of AS usually follows an early systolic ejection
hemodynamically significant when the anacrotic notch is felt click (Figure 17). The ejection murmur is generally loudest
immediately after the onset of upstroke. When an anacrotic at the upper right sternal border or in younger children at
notch occurs very early on the ascending limb of the arterial the upper left sternal border, and it radiates into the neck
pulse, it can be appreciated in the radial pulse and suggests over the carotid arteries bilaterally. Increasing severity of
moderate to severe AS. The pulse with delayed upstroke of the the stenosis is accompanied by a louder, harsher, and a late
ascending limb is called as pulsus tardus. A delayed peak of peaking ejection murmur. In patients with AR, a diastolic
pulse correlates with severity of AS. The pulsus parvus is a low decrescendo murmur can be heard in the aortic area. The
amplitude pulse. Also a thrill can be palpated in the ascending presence of the systolic and diastolic murmur may be
phase of the carotid pulse which is known as carotid shudder. misdiagnosed as a continuous murmur.17,18,53,59,60 There
In patients with mixed AS and AR, bisferiens pulse, pulse are clinical findings with good sensitivity and specificity to
with two systolic peaks, occurs when the regurgitation is the assess the severity of AS. They are—low volume of carotid
predominant lesion. A carotid thrill is present in the presence pulse, slow upstroke of carotid pulse, >3/6 delayed peaking
of AS. It correlates with severity of AS. The thrill may also be ejection systolic murmur, single second heart sound.
present in cases presenting with a hyperdynamic circulation The valvar AS must be differentiated from supra and
and AR. However, pulses are brisk and good volume in the subvalvar aortic stenosis, HOCM, valvar PS. The valvar
absence of AS. The apical impulse is usually normal in mild pulmonary stenosis is associated with variable ejection
AS, but with increasing severity of the stenosis, the apical click, soft delayed P2 and the area of murmur and radiation
cardiac impulse becomes more forceful. The presence of is different. The character of pulse varies in three types of
a presystolic tap indicates forceful atrial contraction and AS. For example, supravalvar AS has differential pulses in
suggests elevated LV end-diastolic pressure. A suprasternal upper limbs (Coanda effect) and pulse in HOCM is double
notch thrill is palpable in as many as 85 percent of patients peaked and brisk (spike and dome). In valvar AS, the type of
with valvar AS. A precordial thrill is also usually present in pulse is pulsus tardus. Dynamic auscultation is another way
patients with moderate or severe obstruction. to differentiate the three. Unlike in HOCM, the murmur of
The first heart sound is usually normal. Splitting of the valvar AS decreases on standing but increases in intensity
second heart sound may be narrow or absent owing to the on squatting or on giving amyl nitrite. Valvar AS is usually
prolonged ejection time of LV and the resultant delayed A2. associated with constant ejection click which is suggestive of
However, sometimes this change may not be appreciable BAV.
clinically. In exceptionally severe cases, there may be
paradoxical splitting of the second heart sound. A paradoxical InvestIgatIons
split S2 occurs in any setting that delays the closure of the
aortic valve. Furthermore, fourth heart sound may be present,
electrocardiography
indicating severe stenosis with LV diastolic dysfunction and
high end-diastolic pressures. Although the presence of a third In older infants and children, the resting electrocardiogram
heart sound is common in children and adolescents with (ECG) must be evaluated for voltage criteria of LVH. However,
normal hearts, it is more frequent in AS. the reflection of the presence or severity of AS may not be
The constant ejection systolic click is a hallmark of the well represented on ECG and it may be normal in one-third of
bicuspid valve even if the valve is functionally normal. the patients, even if the peak-to-peak gradient is greater than
Systolic ejection clicks occur in early systole and may result 80 mm Hg. Similarly, ECG criteria for LVH, often fails to
from either the abrupt opening of the semilunar valves or correlate well with left ventricular mass calculated by other 481
6
Figure 17: Phonocardiogram: (A) Normal heart sounds; (B) Aortic stenosis; (C) Aortic regurgitation
modalities. The presence of LVH with ST segment depression so called wide QRS-T angle. Various criteria for LVH in
and T wave inversion in the left precordial leads (strain respect to reference charts can be applied.60-62
pattern), though, less sensitive (< 25%) are fairly specific for In neonates and infants, there may be significant right
severe stenosis (Figure 18). The Holter monitoring of these ventricular hypertrophy (RVH) and normal left ventricular forces.
patients may help in recognizing the dysrhythmias. This is In infants having hypoplastic LV, R wave in the left precordial
important to know as there is evidence of a strong relationship leads will be smaller. Increased left ventricular forces are not seen
between ventricular arrhythmias and sudden death in patients in neonatal period. The P wave may be normal or bifid and T
with AS. waves may be inverted or flattened in lead I, aVL, V5, V6.60-62
The P wave is normal or bifid suggesting the presence of
mitral regurgitation (MR). The QRS axis may be normal. The radiology17,58,60
depolarization loop is clockwise with Q waves seen in the
inferior leads—aVF, III. LVH is represented by tall R wave Heart size is usually normal or minimally enlarged on chest
in lead II, aVF, deep S in V1, tall R waves in V5-6, deeply radiograph in children with AS. The cardiac apex may be
inverted T waves also seen pointing against the QRS complex, 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
displacement of the cardiac silhouette in the lateral projection heart borders and often with left atrium (LA) enlargement 33
in patients with LVH (Figure 19A). Left atrial enlargement, if (Figure 19B).17,60
present, strongly suggests a severe degree of stenosis or presence

of associated lesions like MR or patent ductus arteriosus (PDA). Echocardiographic Evaluation for Aortic Valve2,17,22,23,41
Pulmonary venous congestion and other signs of congestive
heart failure may be present in patients with severe stenosis As discussed above, a detailed echocardiographic evaluation
and left ventricular dysfunction. Ascending aortic enlargement is warranted to evaluate the aortic valve and root, the
is a common finding in older children and in adolescents with hemodynamic effect of AS, as well as the presence and absence
valvar AS (Figure 19A). Computed tomography (CT) scanning of associated lesions. Aortic root dimensions are assessed at
or magnetic resonance imaging (MRI) accurately delineates 4 levels: the annulus, the sinuses of Valsalva, STJ, and the
ascending aortic anatomy. Adults with congenital AV stenosis proximal ascending aorta (Figure 20B). The parasternal
frequently have radiographic evidence of valve calcification. long-axis view is the best view to measure the AV annulus
The latter two investigations are generally not warranted for the and aortic root. Ascending aorta and arch can be measured in
diagnosis or management of AS. suprasternal long-axis view.
Neonates with severe AS present with varying degree of In literature, it is now well established that the BAV is a
cardiomegaly, pulmonary venous hypertension, less sharp 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.
A B To assess the severity of the AS, continuous wave Doppler
Figures 19A and B: A. Plane X-ray in a case of bicuspid aortic valve
is the best modality (Figure 22A and Tables 4A and B). The
with severe AS in a 19-year-old male patient shows the post-stenotic cursor must be aligned with the jet, to pick up maximum
dilatation of ascending aorta (arrow), prominent aortic knuckle and velocity. Therefore, it must be placed beyond the narrow
bulging, convex left ventricular (LV) contour; B. 15-day-old newborn orifice of valve, which is accountable for creation of the high
with severe AS, severe LV dysfunction (EF:15%) and PDA showing
cardiomegaly, LA enlargement and pulmonary venous hypertension.
velocity jet. As mentioned earlier, by using color Doppler the
AS = Aorti stenosis; LA = Left atrium; LV = Left ventricle; PDA = Patent best alignment must be obtained. This endeavor may need
ductus arteriosus; RA = Right atrium. multiple echo views. The best view, in our experience, is
A B 483
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
6
A B c
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 BAV—coarctation of aorta. Image courtesy: Dr Apoorva Goyal
right upper parasternal view and to keep the probe along the mean gradient (Figure 22A). The peak gradient is determined
long axis of the ascending aorta and marker pointing towards from the peak velocity using the modified Bernoulli equation
the neck. Angle correction should be avoided while taking (p = 4V2) and mean gradient by squaring the instantaneous
the gradients. In addition, the cursor must be kept away from velocities during the systolic ejection period.17,22,23,41
the mitral valve. A difference in timing of the systolic signals, The catheter derived peak-to-peak gradient is the accepted
may distinguish between AS and MR (Figure 22A). The MR standard used for prognosis and to plan interventions. In
signals starts during the isovolumic contraction and continue general, the Doppler measured peak gradient corresponds
throughout isovolumic relaxation. Figure 22B demonstrates to the catheter measured peak instantaneous pressure
the overshooting LV pressure tracing in the catheterization gradient, which is fundamentally different from the peak-
laboratory, suggestive of AS in a patient diagnosed on the to-peak catheter gradient. This correlation between the two
basis of high velocity signals on TTE. measurements is not nearly as close as with PV stenosis. In
some children, especially with moderate degree of stenosis,
Overestimation of the Gradient Across the AV two measurements can differ by 30 mm Hg. Mean gradients,
measured by averaging the instantaneous catheter or Doppler
The velocity determination across the AV is flow related. gradients over the systolic ejection period, correspond more
Hence, the conditions causing increased flow such as AR, closely to each other. The Doppler mean gradient has several
elevated cardiac output and heart rate, as seen in anemia, advantages over the Doppler peak instantaneous gradient:17,41
anxiety, pregnancy and exercise, will increase the flow 1. Doppler mean gradient is comparable to the mean pressure
velocity across the AV.17,18,23,41 gradient measured at the cardiac catheterization.
2. Doppler mean gradient is the average of all the peak
Underestimation of the Gradient Across the AV instantaneous gradients throughout the systole and is not
based on single peak velocity. Therefore, it can be obtained
The AV velocities recorded when cardiac output is low such with greater accuracy and reproducibility.
as in left ventricular failure associated with neonatal or elderly 3. Mean gradient is less affected by transvalvular flow.
aortic stenosis, does not represent the severity of the AS. 4. Mean gradient is the basis of calculation of valve area by
Also, underestimation of true severity can occur due to a using Gorlin equation.
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 aortIc valve area
gradient.17,18,23,41
Aortic valve area can be measured by the following
calculatIon oF the Pressure gradIent methods: 17,22,23,41
1. Planimetery: The AV area can be measured by direct
484 Transvalvar pressure gradients are usually calculated from tracing from the parasternal short-axis view at the level of
the Doppler aortic velocity profiles, the peak gradient and the the great vessels on two-dimensional echocardiography.
33

A
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
B 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 To assess the severity of AS, the following echocardiographic
criteria are used:
Peak velocity < 3.0 3.0–4.0 > 4.0
(meter/second) 1. Measurement of doppler pressure gradients17,18,23,41:
a. Peak instantaneous gradient
Mean gradient (mm Hg) < 25 25–40 > 40 b. Mean pressure gradient
2. Measurement of valve area:
Ao valve area (cm2/m2) 1.5–0.8 0.8–0.5 < 0.5
a. Direct planimetery in 2D echocardiography
AV area (cm2) 1.5 1.0–1.5 < 1.0 b. Continuity equation
c. Proximal isovelocity surface area method from color
Ao = Aorta; AV = Aortic valve Doppler
3. indirect evidence of stenosis:
a. Left ventricular mass from 2D echocardiography
b. LV mass/volume ratio 485
c. LV acceleration time and acceleration time/ejection time
ratio
6 There are some limitations in pediatric patients. Those are: procedure rather than valvotomy, even if left ventricular
a. Fast heart rate leading to limitation of frame rates volume is not critically small.65
b. Error in measurement of small orifice The critical AS presenting in neonatal period is a lethal
c. Irregular valve opening that are difficult to trace. disease. Kim et al have highlighted the morphological
2. Aortic valve area by continuity equation: abnormalities found in critical AS.63 They examined the
postmortem specimen of two cases with critical AS and
CSA LVOT × VTI LVOT reported an extreme pattern of myocardial abnormalities of two
(CSA AV) =
VTI AV types, one consisted of numerous clefts of intertrabeculated
CSA = Cross sectional area of aortic valve spaces and endocardial fibroelastosis and other was
VTI = Velocity time integral suggestive of myocardial ischemic changes. These findings
AV = Aortic valve suggest that only functional and anatomical assessment is not
LVOT = Left ventricular outflow tract adequate to predict the outcome and there are more complex
morphological issues modifying the outcome.
echocardiographic evaluation of diastolic Usually, critical AS does not manifest as fetal congestive
Function of left ventricle heart failure, but has many severe hemodynamic effects leading
to additional structural malformations. In view of the fact,
Diastolic ventricular function is assessed by the filling that these fetuses have a potential for developing hypoplastic
abnormalities of the LV. From the MV inflow Doppler left heart syndrome, many centers are offering them fetal
recordings, peak flow velocities, filling-rates, proportion valvotomy, a procedure to avoid the underdevelopment of the
of flow in various phases of diastole may be assessed. left side of heart. Seemingly, these procedures are attractive
Comparative studies of these subjects with normal controls solutions to the CHDs with otherwise grave prognosis, yet
have revealed higher E velocity, a much higher A velocity, they have high procedural risk and limitations. The fetal
therefore an inverse E/A ratio. The percentage of total Doppler cardiac interventions are not allowed in India as of now.
area in the first-third of diastole was significantly lower and The routine clinical examination and tests of the neonates
the percentage of the total Doppler area under the A wave was with critical AS, usually differ from older infants and children
higher.41 and show involvement of the right heart instead of the left. This
is possible, as the two sides of the heart is directly connected
tissue doppler Imaging in aortic stenosis63 by the atrial communication as well as patent ductus. The
hepatomegaly, epigastric pulsation, right heart pulsation,
Tissue Doppler has some role in assessing the ventricular right ventricular dominance can be seen. Due to the presence
function. Bruch et al assessed 23 cases of moderate to severe of pulmonary venous hypertension and relatively small
aortic stenosis by tissue Doppler and found that in patients hypertrophied LV, radiological picture may mimic obstructed
with AS, systolic (S′) and early diastolic mitral annular total anomalous pulmonary venous connection or pneumonia.
velocities (E′) were significantly reduced in comparison to The baby may have small failing LV, obstructive mitral valve,
control subjects (systolic, 5.5 +/– 1.2 vs 8.3 +/– 1.3 cm/s; early MR, coarctation of aorta and PDA. Echocardiography will
diastolic, 5.6 +/– 1.6 vs 10.2 +/– 3.0 cm/s, P < .001 for both provide the anatomical diagnosis, but then again, Doppler based
comparisons), but ejection fraction, fractional shortening, and assessment of severity may be underestimated. The outcome of
cardiac index were normal. In patients with AS, LV pre-A aortic balloon valvuloplasty (ABV) may be suboptimal, but it
pressures (14 +/– 4 mm Hg)64 and end-diastolic pressures provides, a life saving palliation. Figures 23A and B show the
were high (19 +/– 7 mm Hg). In such patients, the mitral E/E′ changes in myocardium and papillary muscles. Figures 23A
ratio was significantly related to LV pre-A pressure (r = 0.75, to D are TTE images of a 14-hour-old neonate with hydrops
P < .001) and to LV end-diastolic pressure (r = 0.78, P < .001). fetalis on ventilator, who underwent successful balloon
In patients with AS, an E/E′ ratio more or equal to 13 identified valvuloplasty. The X-ray before ABV shows cardiomegaly
the LV end-diastolic pressure greater than 15 mm Hg, with a and after ABV shows reduction in cardiomegaly (Figures 23E
sensitivity of 93 percent and a specificity of 88 percent. and F). The neonate was weaned off ventilator within 24 hours.
The ejection fraction (EF) improved from 35 to 55 percent. The
Infantile aortic stenosis17,64,65 surgical intervention, in absence of proper artificial valve, has
poor prospects of success. The extensive procedures like Ross
The adverse effects of small inflow, outflow, and/or cavity size operation provide alternative solutions. Left ventricular size
of the LV are cumulative. The accuracy of prediction of the and its maladaptive concentric hypertrophy remains the biggest
outcome based only on preoperative anatomy indicates that concern for outcome of any intervention done for restoration of
adequacy of valvotomy is not generally a limiting factor for biventricular morphology of the heart. Hence, with exceedingly
survival in this group of patients. It is possible to identify better results of Norwood and associated procedures, critical
486 subjects whose chance of survival is better after a Norwood analysis is desirable for selection of the procedure.
33

A B c
D e F
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 2. An indexed aortic root diameter of 3.5 cm/m2 or less
in diagnosis like the hypoplastic LV is usually globular and 3. An indexed mitral valve area of 4.75 cm2/m2 or less
does not extend to the cardiac apex. Additionally, LV inflow 4. An LV mass index of 35 g/m2 or less.
dimension (hinge point of posterior mitral leaflet to cardiac They selected 65 babies up to 33 days of age out of which
apex of less than 25 mm, mitral valve annulus diameter of 46 underwent valvuloplasty as a first procedure. Outcome
less than 9 mm, ventriculoaortic junction of less than 5 mm, all was predicted with 95 percent accuracy when they used the
measured from apical four chamber or long-axis view at end following equation:65
diastole will indicate hypoplastic LV. Left ventricular cross- Score = 14.0 (BSA) + 0.943 (AoR/m2) + 4.78 (LAR)
sectional area measured in the parasternal long-axis view that + 0.157(MVA/m2) – 12.03
included the mitral valve, AV and left ventricular apex at end A score less than – 0.35 is considered to be not compatible
diastole, of less than 2 cm2. with survival after two ventricle repair.
Rhodes et al analyzed the cases of critical AS applying one (BSA = Body surface area; AoR = aortic root dimencion
risk scoring system with good predictive value. in cm indexed to BSA; LAR = ratio of long axis of LV to
Risk scoring system for biventricular palliation or repair in long axis dimension of heart; MVA = mitral valve area [cm2]
critical AS: indexed to BSA).
For the four risk factors identified, the critical levels were: This scoring system has potential for errors and also pres-
1. A left ventricular long axis to heart long-axis ratio of 0.8 or ence of additional problems like MR may lead to fallacious
less calculation. 487
6 rheumatic heart disease and aortic stenosis22,23,66,67 
table 5
Criteria of an abnormal exercise test in patients with
In developing countries rheumatic heart disease is not asymptomatic aortic stenosis
uncommon. It is the most serious complication of rheumatic Symptoms during exercise: dyspnea, angina, syncope or
fever. Acute rheumatic fever follows 0.3 percent of cases near syncope
of group A beta-hemolytic streptococcal pharyngitis in • Fall in blood pressure or < 20 mm Hg rise in systolic blood
children. Rheumatic AV characterized by three leaflets, pressure during exercise
rolled up, thickened margins fusion of commissures between • < 80% of normal level of exercise tolerance
the aortic leaflets. AV is the second most favored site for • > 2 mm ST segment depression during exercise
(horizontal or downsloping, in comparison to baseline, not
rheumatic activity. It usually presents as combined lesions
attributable to other causes)
and rarely as an isolated involvement. Rarely, it manifests • Ventricular arrhythmias
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 
table 6
isolated AV disease as 4.5 percent in patients below 18 years. Causes of aortic regurgitation
1. Primary congenital cardiac abnormality.

echocardiographic evaluation of additional a. Aortic valve abnormality
abnormalities41 - Quadricuspid aortic valve
- Bicuspid aortic valve
A PDA is seen in 20 to 65 percent cases of valvar AS. Coarctation - Absence of aortic valve cusps (unguarded aortic orifice)
of aorta is found in 11 to 53 percent cases and stenosis of the b. Aortico–left ventricular tunnel
mitral valve in 25 percent cases. Other anomalies like VSD; 2. Connective tissue disorder with aortic root dilatation
mitral valve abnormalities are also common. - Marfan’s syndrome, Ehlers-Danlos syndrome
- Turner syndrome with aortic ectasia
3. Association with other forms of congenital heart defects
role of exercise testing in the diagnosis - Aortic valve prolapse with ventricular septal defect (doubly
of aortic stenosis17,68 committed, perimembranous)
- Dilatation of the aortic root as in tetralogy of Fallot
Exercise testing can identify a limited exercise capacity and - Truncus arteriosus
reveal symptoms in many (usually one-third) apparently 4. Infectious processes of the aortic valve
asymptomatic patients. The one year prognosis of patients - Bacterial endocarditis
with a normal exercise test is excellent. In contrast, a positive - Rheumatic fever
exercise test predicts the onset of a cardiac event in a sizeable
proportion of patients (Table 5).17,68
cusps are redundant and prolapsing) should be defined.
aortIc regurgItatIon14,15,17,18,22,23,59 Determination of the severity of regurgitation, ventricular
dimensions and ventricular function is very important before
Congenital AR is rare entity as an isolated lesion. It frequently taking the decision about management, regarding whether
occurs in association with other congenital heart defects, aortic patient will requires medical follow-up, valve repair or will
root dilatation and infectious processes involving the aorta. need aortic valve replacement. Aortic valve annulus and
The causes of AR are listed in Table 6. aortic root size should be measured in the patient undergoing
While evaluating the patient with AR, the following things AV replacement in parasternal long-axis view. If patient is
should be assessed on echocardiography: undergoing the Ross procedure then pulmonary root should
1. Left ventricular outflow abnormality-cause of AR be measured in addition to aortic root measurement.
2. Severity of regurgitation Etiology of AR in other heart defects for example, VSD
3. Left ventricular dimensions—end systolic and end diastolic with AV prolapse (common association with doubly committed
4. Left ventricular systolic and diastolic function. 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 Acute AR is a serious disease, which manifests with stormy
the level of great vessels are the best views to define the LVOT onset of acute left ventricular failure. However, chronic AR
abnormalities as described in Chapter 26. Aortic valve cusps is more common. The LV undergoes compensatory eccentric
488 number and anatomy (rolled, gnarled and adequate or whether hypertrophy, i.e. there is increase in both, cavity and wall
 table 7 33
Differential diagnosis of aortic regurgitation

Aortic regurgitation Aortico-left ventricular Pulmonary regurgitation Pulmonary hypertension/PR
tunnel with organic valve disease Graham Steell murmur
Heart sound
S1 Normal Normal Normal Normal
S2 Normal split Normal split May be delayed P2 or Narrow or imperceptible split
soft P2 P2 accentuated
S3 Usually not present in _ _ _
isolated AR unless there
is myocardial dysfunction
Diastolic murmur
Site Right and left lower Right and left lower 2nd and 3rd intercostal at 2nd and 3rd intercostal at left
sternal border/apex sternal border/apex left sternal border sternal border
Onset Early diastolic Has systolic and Delayed diastolic Early diastolic
diastolic component
Best heard Diaphragm Diaphragm Bell Diaphragm
Start with A2 A2 After a clear interval from With loud P2
P2
Intensity High pitch High pitch Low pitch High pitch
Posture Better heard in leaning
forward
Shape Decrescendo Loud to-fro murmur Crescendo-decrescendo Uniform throughout diastole
widely heard on chest stop well before S1
thickness. The chronic AR may occur due to variety of lesions. related normograms. They should be followed up serially. Any
However, AR is better tolerated in long term follow-up. undue dilatation or rapid increase in these parameters will
Clinically it presents with high systemic pulse pressure and very identify the patient at risk of development of aortic dissection
low diastolic blood pressure. Sometimes, diastolic pressures needing elective aortic root replacement procedure.45-48,50
can approximate to zero in chronic severe AR. It represents Beppu et al reviewed current concepts of anatomic
the inability of aortic root to maintain pressure in diastole due classification, pathophysiology, natural history, and clinical
to the incompetent AV which leads to increased LVEDP. The management of BAV disease with associated ascending aortic
significant AR is associated with central diastolic runoff of the aneurysms and suggested that optimal management of patients
blood into the LV cavity, which in turn may be reflected in the with BAV disease and associated ascending aortic aneurysms
classical physical findings (Tables 7 and 8). 17,18,22,23,41,59,60 often requires a thoughtful approach, careful assessment of
risk factors.43
aortic root dilatation
aortic regurgitation in aortic valve Prolapse in
Aortic root dilatation occurs in connective tissue disorders ventricular septal defect
such as Marfan syndrome, Ehlers-Danlos syndrome, Turner
syndrome and polyvalvular heart diseases. In connective In the presence of perimembranous or doubly committed
tissue disorders, aortic root dilatation is progressive. VSD, AV may prolapse progressively, prohibiting coaptation
Initially it involes sinus of Valsalva, ascending aorta, then of the cusps and leading to incremental AR.
dilatation progresses to involve aortic annulus leading to Saleeb et al reported that aortic cuspal prolapse and clinical
distortion of the AV and AR. While evaluating the patient AR are not uncommon in patients with subaortic VSDs. They
with connective tissue disorders such as Marfan syndrome, studied hundred patients, with a mean age at VSD diagnosis of
aortic root measurements should be taken at four levels: 0.1 +/– 0.5 years, with follow-up period of 7.1 +/– 10.1 years.
aortic annulus, sinus of Valsalva, STJ and ascending aorta Aortic cuspal prolapse developed in 14 patients (14%) at a
1 cm above the sinotubular junction and compared with age- mean age of 7.1 +/– 6 years (range 0.4–18.4). AR murmurs 489
6  table 8
Peripheral signs of aortic regurgitation
Signs What they mean

Becker sign Arterial pulsations in the retina
Müller 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.
Hill’s 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 Post-aortic valvuloplasty aortic regurgitation
years, all of whom had aortic cuspal prolapse and underwent Aortic regurgitation of varying degree is the usual finding
VSD closure and aortic valvuloplasty. Mori et al published after balloon aortic valvuloplasty and sometimes may
the data of 99 consecutive patients with supracristal VSD and lead to surgical intervention. Brown et al concluded in
found that the thirty patients (30%) had AV prolapse (VSD their retrospective study that although, transcatheter aortic
+ AoVP group), and 31 patients (31%) had AoVP with AR valvuloplasty is effective for relief of congenital AS, there are
(VSD + AoVP + AR group). In the VSD + AoVP group, AoVP steady long-term hazards for surgical AV reintervention and
was detected first by echocardiography at the age of 6.8 +/– replacement that are independent of factors like age of initial
4.2 years (mean +/– SD). In the VSD + AoVP + AR group, the intervention or severity of AS. They followed up 563 patients
interval from detection of AoVP to the appearance of AR was for a median follow-up period of 9.3 years. Survival free from
3.4 +/– 2.0 years.17,18,70,71 any aortic valve reintervention, was 89 ± 1% at 1 year, 72 ±
Why does prolapse occur in the adjoining VSD? The most 2% at 5 years, 54 ± 3% at 10 years, and 27 ± 3% at 20 years.
acceptable explanation is that this is the result of the interaction Freedom from AV replacement was 90 ± 2% at 5 years, 79
between the anatomical defects and hemodynamic factors like ± 3% at 10 years, and 53 ± 4% at 20 years.73 In multivariate
Venturi effect caused by a rapid blood flow through the VSD analyses, lower post-dilatation AS gradient and lower grade
in accordance to the Bernoulli’s theorem. With progress of of post-dilation AR were associated with longer freedom from
the disease, this syndrome is clinically subdivided into three AV replacement, but age, era, and pre-dilation AS severity
stages: were not.17,73
1. The prolapsing stage, which is characterized by the Venturi
effect Infective endocarditis and aortic regurgitation
2. The reversible AR stage, which has AR and the Venturi effect
3. The irreversible AR stage in which the corrosion of the AV Infective endocarditis can lead to acute or chronic AR,
is complete.72 depending upon the virulence of the bacteria. Aranki et al
Moreover, sometimes, the sinus of Valsalva may prolapse published a retrospective study of 2,000 patients of whom
without distorting the hinge point and and AV coaptation may 66 percent patients were those who underwent AV surgery
490 not be affected (Figures 24A and B). due to endocarditis of native valve.69 The operative mortality
33

A B
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. PLAX—showing 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 a mechanical adaptation to both pressure and volume overload.
eats away the valve in few of the cases. It may cause aortic In AR, compensatory hypertrophy decreases wall stress;
root abscess, embolization of vegetations and may leads to however ultimately hypertrophic changes are detrimental as
complications involving various organs. they induce contraction and relaxation abnormalities. These
abnormalities lead to progressive inadequacy of coronary
severIty oF regurgItatIon vascular supply. Studies have shown that with same mass/
volume ratio, chances of arrhythmias are more in patients with
With the use of two-dimensional echocardiography (left combined AR and AS than AS alone.17,23,41
ventricular dilatation, ventricular function), M-mode echo-
cardiography (ventricular dimensions), color flow mapping,
and pulsed Doppler interrogation, severity of regurgitation natural hIstory oF aortIc valve lesIons17,18,75-77
should be assessed (Figures 25A to D). Echocardiographic
criteria with the assessment of specific, supportive, and Progression of gradient across the aortic valve
quantitative parameters are given in Table 9. Table 10
describes the angiographic criteria for AR. Despite the lack of very long-term intervention-free data,
Calculation of effective regurgitant orifice (ERO) by natural history studies have provided important information.
proximal isovelocity surface area (PISA) method was Patients who present in infancy with AV stenosis generally
originally used for MR. Now it is a valid method for have more severe stenosis and higher mortality with or
regurgitatant AVs also. Though, the procedure is cumbersome without treatment. Twenty-five of the patients in the original
and needs more time than other methods. NHS-1 cohort were younger than 2-years-old; the 1-year
survival rate was 64 percent, and most had undergone surgical
ventricular dimensions and ventricular Function interventions. In contrast, the 25-year survival in-patients who
were 2 years of age or older at the time of original enrollment,
Left ventricular dimensions should be measured by traditional was 85 percent. An earlier study by Campbell, published in
M-mode done in parasternal long axis (PLAX) view. With 1968, found that the mean age of death in patients with AS was
significant AR, left ventricular end-diastolic dimension will be 35 years, with 40 percent mortality by age 30 and 60 percent
high because of the increased filling. Left ventricle end-systolic mortality by age. More than half of the patients who died had
dimension remains normal. Therefore, left ventricular fractional sudden unexpected death, whereas most of the remaining
shortening is increased. It shows capacity of LV to eject more deaths were due to progressive congestive heart failure. The
volume (normal stoke volume plus regurgitant volume). With notion that sudden death is extremely rare in the absence of
onset of LV failure, left ventricular end-systolic dimension starts preceeding symptoms has been challenged by several recent
increasing. Intervention should be done before left ventricular studies including NHS-2. About half of sudden death cases
end-systolic dimension reaches 55 mm (in adults). The LVH is from AS occurred during or immediately after exercise. 491
6
A B
c D
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 Doppler—mild AR; D. CW Doppler—severe AR. Image courtesy:
Dr Nagendra Chauhan
 table 9
Grading of severity of aortic regurgitation
Echocardiographic parameters Mild Moderate Severe

I. Specific signs a. Jet width/LVOT < 25% 25–64% > 65%
b. Vena contracta < 3 mm 3–6 mm > 6 mm
c. Diastolic flow reversal in descending aorta Early diastolic flow Intermediate prominent
reversal holodiastolic
reversal
II. Supportive signs a. Pressure half-time > 500 ms 200–500 ms < 200 ms
b. LV size Normal – Enlarged
c. Deceleration slope < 200 cm/sec2 200–350 cm/sec2 >350 cm/sec2
III. Quantitative a. RV (mL/beat) < 30 30–59 ≥ 60
b. RF (%) < 30 30–49 ≥ 50
c. EROA (cm2) < 0.10 0.1–0.29 ≥ 0.30
492 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 There is definite phenotypic variance noticed in these 33
Severity of aortic regurgitation on angiogram74 patients, mid ascending aortic dilatation is the commonest
pattern in BAV disease and is usually seen in older age,

1+ Mild Contrast is visible in the left ventricle, but whereas younger patients, particularly male gender, usually
it clears out during the emptying phase
of cardiac cycle
present with aortic root dilatation. Serial echocardiographic
evaluation of aortic annulus, aortic root and ascending aorta
2+ Moderate Contrast is visible within the entire left must be done. Once the ascending aorta reaches 4.0 cm,
ventricle and does not clear out during
the emptying phase of cardiac cycle
annual imaging with echocardiography, MRI, or CT scan
is indicated. The question regarding the optimum timing of
3+ Moderately Regurgitant contrast opacifies the left prophylactic intervention is still unanswered. It is suggested
severe ventricle and the opacification becomes that elective surgical repair of BAV with associated aortic
denser with each cardiac cycle
dilatation should be done at a diameter of > 5.0 cm, with
4+ Severe The left ventricle is completely opacified even earlier intervention at > 4.5 cm in the subset of BAV
during the first cardiac cycle patients with factors of higher risk and at > 4.0 cm in those
with concomitant indication for AV replacement.
Although mild AS may remain stable for many years, bacterial endocarditis78,79
ultimate progression is the rule.9 It may be greater in children
than in adolescents and adults because of the inability of the Bacterial endocarditis risk has been reported to be as high as
valve orifice to increase in proportion to somatic growth. 1 percent per year, but is probably lower, based on the data
The outcome is highly correlated with the initial gradient, from NHS-2 where the incidence rate was 27.1 cases per
with those having higher gradients developing symptoms, 10,000 person years (0.27% per year). Although bacterial
dying, or having valve replacement sooner than those with endocarditis risk is present even in very mild aortic valve
lower gradients. In addition to the progression of AS, many stenosis, the incidence of endocarditis is higher in patients
patients may develop significant and progressive aortic valve with more severe stenosis. BAV endocarditis predominantly
regurgitation, particularly if they have had surgical valvotomy occurs in young adults and there is a strong male dominance
or percutaneous balloon valvuloplasty. (73–100%). Staphylococci and viridans streptococci have
accounted for nearly three-quarters of the cases, as in native
changes in aortic root17,18,75-77 valve endocarditis. Complications, especially heart failure and
valvular or myocardial abscesses are common. Most patients
Isolated BAV seems to have a relatively benign course in require surgery, often on an emergency basis. Recent surgical
childhood. However, compared with those with a normal series show that 25 to 54 percent of all infected AVs are bicuspid.
AV, those with BAV disease have a higher prevalence and
faster rate of ascending aortic dilatation which may culminate management oF aortIc valve dIsease
into dissection or rupture at a younger age. The fact that
pulmonary trunk shares this potential for abnormal dilatation,
medical management
suggests an embryological basis. The vascular smooth muscle
cells (VSMCs) that undergo apoptosis in the media of the In AS, medical management does not carry much role except
ascending aorta are of neural crest origin. There are 3 main for decongestive therapy in failing heart and supportive
histopathological features described in literature to define therapy like blood transfusion for very low hemoglobin or
the formerly called cystic medial necrosis: noninflammatory ventilation for very sick children. The neonates presenting
loss of VSMCs, fragmentation of elastic fibers, and increased early may get benefit from prostaglandin by keeping the PDA
basophilic ground substance within cell-depleted areas of the open (see chapter 5 on duct dependent circulation). With the
ascending aortic media. The pulmonary trunk demonstrates use of prostaglandin infusion, transport can be easy.
same histological feature in patients with BAV disease. The There is a definite role for medical management in
strong association between BAV and coarctation of aorta, both regurgitant lesions of the AV. Unless systolic function
with and without Turner syndrome, may indicate that BAV is abnormal, intervention is not recommended. Usually
disease involves the ascending aorta and aortic arch extending vasodilator therapy is most effective as it decreases the
to the ligamentum arteriosum, where most coarctations occur. afterload and improves the end systolic contraction indices
The convexity of the aorta is particularly affected by the and dimensions. Nowadays, ACE inhibitors are the drugs
medial degeneration, demonstrating less collagen, greater of choice. In presence of moderate severe LV dysfunction
elastic fragmentation, and fewer VSMCs. diuretic therapy is recommended.
493
6 Intervention in aortic stenosis78-87 D. In patients with left ventricular dysfunction normalization
of ventricular function following successful aortic valvotomy
Aortic Stenosis: Timing of Intervention82 may be associated with increase in gradients compared to
immediate post dilatation values. The procedural success

For infants and older children has been reported to be in between 88 to 96 percent. New or
1. Left ventricular dysfunction: Immediate intervention by increase in AR occurred in 10 percent of cases. Jindal et al
balloon dilatation, irrespective of gradients (Class I). reported a series of 74 patients (age 1–20 years) with the follow
2. Normal left ventricular function: Balloon dilatation if any up of 2–12 years. The procedure was successful in 71 patients
of these present: (96%). The mean (+/– SD) reduction in peak-to-peak systolic
i. Gradient greater than 80 mm Hg peak and 50 mm Hg gradient (PSG) was 68.7 +/– 13.5%. No patient required
mean by echo-Doppler (Class I). immediate surgical intervention. Survival after dilatation was
ii. ST-T changes in ECG with peak gradient of greater 100 percent at 12 years. At follow up (mean 5.5 +/– 2.9 years;
than 50 mm Hg (Class I). range: 2–12 years), 20 percent of patients had restenosis and
iii. Symptoms due to AS with peak gradient of greater 21 percent had significant AR (grade > or = 3). Reintervention
than 50 mm Hg (Class IIa). In case of doubt about was performed in 14 percent of patients. Severity of AR and
severity/symptoms, an exercise test may be done for high residual stenosis immediately after balloon dilatation
older children (Class IIb). were associated with the late event rates. The actuarial
For neonates: Balloon dilatation if symptomatic or if there is intervention-free rates at 5, 7 and 12 years were 92.9 percent,
evidence of left ventricular dysfunction/mild left ventricular 84.4 percent and 60 percent, respectively.83 According to
hypoplasia (Class I), or if Doppler gradient (peak) greater than O Reich et al, independent predictors of unfavorable outcome
75 mm Hg (Class IIa). are the small aortic annulus, BAV, poor function of the LV or
mitral valve, and limited operator experience.86 Daehner et
balloon dIlatatIon oF the al reported better success rate if the balloon is stabilized with
aortIc valve2,17,18,23,80-87 rapid right ventricular pacing or use of adenosine.87 Table 11
shows the differences between aortic vs pulmonary balloon
The balloon dilatation of aortic valve was first reported by valvuloplasty.17,18,23,28
Lababdi et al in 1983 in children. Subsequent studies have
confirmed the efficacy and safety of this palliative technique surgical Intervention2,17,18,23,84,88,89-95
in neonates, infants and children. It has been accepted as
preferred mode of intervention in very small babies with In children valve replacement is always difficult as adequate
critical AS and borderline LV. McElhinney et al reported size of prosthesis may not be available. Ross procedure
good results in 113 babies who were <60 days of age and remains the choice for small infants but there might be gross
were diagnosed to have critical AS.79 Echocardiography is aortic and pulmonary annulus mismatch and hence it may
the mainstay for the evaluation of the aortic valve in valvar not be very successful. Hence, the necessity to intervene in
AS. The technique besides giving accurate information on a child with AR must be evaluated with utmost care. Ross
gradients, left ventricular function, AR also accurately assesses et al published their recommendations in 1985 and no major
the valvar morphology. Measurement of the size of the aortic change happened for small children since then. Criterias are:
annulus is most accurately done by echocardiography. ejection fraction < 40%; LV fractional shortening < 25%; LV
Procedure: The aortic valve is usually crossed through the end-diastolic diameter 7 mm or 3.8 cm/m2 : LV endsystolic
femoral approach although the carotid and rarely antegrade diameter > 5 cm or 2.6 cm/m2, radius/wall thickness ratio at
transvenous approach through the PFO/ASD via mitral valve, end-diastole multiplies by systolic pressure > 600.88
have also been attempted in neonates and infants. The valve Aortic valve repair is still not a very preferred mode of
is most commonly crossed by a guide wire supported by a treatment due to the poor outcome in long run, though short-
catheter. The right Judkins, pigtail or the multipurpose catheter term results in good surgical hands are comparable to any
are the most common catheters used as a support to the guide- type of valve replacement. Patients with rheumatic valvular
wire. After crossing the valve with the catheter the guide-wire disease appear to have an increased incidence of recurrence
is changed to an extra-stiff J tipped wire. The balloon size and repair failure. There are various techniques of repair and
used should not exceed the aortic annular size. The balloon often a combined technique is used (Figures 27A to D).89-92
valvuloplasty is accomplished by balloon inflation up-to 90- A good review was published by Carr et all comparing all the
100% of annulus size (Figure 26A and B). Following the methods in an online search and meta-analysis.89
balloon valvotomy an accurate assessment of the gradient is
mandatory. The echocardiography is usually used to see the aortic valve repair in aortic valve Prolapse
valve area, gradient and presence of any newly developed
494 AR. A successful valvotomy is defined as fall in gradients of Boodhwani et al described their techniques of repair in
more that 50 percent of predilatation values Figure 26 C and AV prolapse based on classification of type of the AVP
33

A B
c D
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 Muscular annulus
(incomplete)
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 Regurgitation is better tolerated. In severe case it may
to increase create problem later
Postprocedure dynamic Normally there is no subaortic muscular After successful balloon pulmonary valvuloplasty
obstruction infundibulum hence unlike the pulmonary hypertrophied sub pulmonary infundibulum goes into
stenosis no sudden increase in LV pressure spasm in absence of high systolic pressure produced
by stenotic pulmonary valve condition known as suicidal
right ventricle.. It is treated with volume and beta-
blockers 495
Outcome Success rate: 88–96% 95–100% (depending on case selection)
Chances of reintervention Repeated procedures may be required and Mostly one time procedure in most of the cases.
future valve replacement may be needed Reintervention may be needed in dysplastic valves and
neonatal pulmonary stenosis
6
B
A
c D
Figures 27A to D: Aortic valve repairtechniques.89-91 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 Type of Artificial Valves
echocardiographically.92 The artificial valve are designed to imitate the purpose of the
Normal AV cusp coaptation occurs approximately, at a native valves. There are two basic types of artificial heart
level, corresponding to the middle of the sinuses of Valsalva, valve:
i.e. halfway between the ventriculoaortic junction and STJ. Cusp 1. Mechanical valves
prolapse, therefore, is strictly defined as the motion of the cusp 2. Tissue valves.
free margin below this level. The AV prolapse may involve a
single cusp or all the three cusps. The prolapse of cusp can be Mechanical Valve
appreciated ‘relative’ to other cusps or “absolute’ in relation to
physiological coaptation level. Mechanical heart valves are more durable in comparison to
their bioprosthetic counterparts. Newer mechanical devices
aortic valve replacement 2,14,17,18,23,93-95 are bileaflet structure and the struts and occluders are made
out of either with pyrolytic carbon. Usually, the sewing
Aortic valve replacement is usually management of choice ring cuff is Teflon, polyester or dacron. Replacement with a
in absence of a successful repair technique. The mechanical mechanical prosthesis currently provides the most durable
valves have shown acceptable long-term results. Eventual result. Disadvantages associated with mechanical prosthesis
outcome of ballooning procedures or surgical repair is the are the constant need for anticoagulation and lack of growth
496 valvar replacement. potential. Evidently, these are the significant problems in small
children. These valves tend to produce noise. Postsurgical, 33
paravalvar leak and valve dysfunction may lead to re-
intervention (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 Figure 29: Ross procedure—main pulmonary artery with pulmonary
growth potential is still a major issue and longevity of these valve with sleeve of wall dissected out (pulmonary autograft) to be
valves is frequently poor, particularly in small children. 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.
autograft: ross Procedure17,18,94,95 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 about the series of 32 patients with mean age of 13 +/– 5.7 years
involves replacement of diseased aortic valve by putting the and a follow-up period of of 3 to 7 years. Actuarial survival
pulmonary autograft along with sleeve of main pulmonary at 7 years was 94 ± 2.5% and there was 100 percent freedom
artery and placing a homograft or heterograft in place of the from reoperation for autograft valve dysfunction or any
patient’s original pulmonary valve (Figure 29). The pulmonary other cause. Balloon dilatation was required in 2 patients for
autograft is advantageous as it is the patient’s own tissue, hence, pulmonary homograft stenosis.94
has growth potential and is not subjected to immunologic The pulmonary homograft in the RVOT is regarded as the
degenerative changes. It is free from risks associated with limiting factor in the long term success of the Ross procedure.
anticoagulation and has excellent hemodynamic characteristics. However, modifications of the Ross operation have reduced
Therefore, it is an excellent choice for children and young the incidence of pulmonary autograft dysfunction, and in
adults needing AV replacement. Raja et al published their paper some cases the function of this valve remains excellent for
A B
497
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
6 many years. The patients with rheumatic aortic valve are not  table 12
Various aortic valves for percutaneous implantation
good candidate for Ross procedure.95
Valve Manufacturer Mechanism

Percutaneous aortIc valve ImPlantatIon Cribier-Edwards Edwards Balloon-
Lifesciences expandable
Percutaneous AV implantation (TAVI) is a promising new
CoreValve ReValving CoreValve Self-expanding
technique that is currently being developed as an alternative to
System
surgical valve replacement in adult patients who have severe
Edwards SAPIEN Edwards Balloon-
AS and are deemed inoperable. The TAVI was first reported in
Lifesciences expandable
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 and PVE should be classified as either being acquired
high-risk surgical groups. Recently, in our institute, few cases perioperatively, and thus nosocomial (early PVE), or as
were done successfully. Although this technology is rapidly community acquired (late PVE). The proposed interval between
developing, this procedure is not an option for children and early and late PVE is one year.
adolescents with congenital AS.96 Table 12 shows the various Chances of having endocarditis is more when surgery is
types of aortic valves used for percutaneous implantation done in patients with infective endocarditis (IE). The incidence
(Figures 30A to D). is relatively less in mechanical valve than bioprostheses. The
PVE is more frequent for prosthesis in aortic position than
endocarditis in Prosthetic aortic valve97-99 mitral and for multiple implant.
Mechanical prosthetic infections originate from the
Prosthetic valve endocarditis (PVE) is an endovascular, sewing cuff or from nearby located thrombi and culminate
microbial infection occurring on parts of a valve prosthesis into periprosthetic leaks, ring abscesses, invasion of adjacent
or on reconstructed native heart valves. It is recommended to tissue. Bioprosthesis infections mostly are restricted to the
determine the involved valve:: cusps leading to secondary bioprosthetic failure.
a. A mechanical prosthesis Staphylococci (especially novobiocin susceptible, coagulase
b. A bioprosthetic xenograft, stented or unstented negative staphylococci), bacteria of the HACEK group, and
c. An allograft fungi occur more frequently in PVE. Streptococci and entero-
d. A homograft, or cocci are found more frequently in native valve endocarditis.
e. A repaired native valve with or without implantation of an As the risk for infection is much higher in patients with
annular ring. prosthetic heart valves than in patients with valvar heart
It has been suggested that, infections of the devices or lines disease, more intensive prophylaxis with prolonged duration
placed inside the heart, but not connected to the endocardial is needed in these patients. Patients may need surgical
structures should be classified as ‘polymer associated infections’ intervention to avoid complications.
A B c D
498
Figures 30A to D: Transcutaneous aortic valve implantation (TAVI)
aortic stenosis in Fetus100-104 demanding. Fetal position and left ventricular size remain 33
the critical factors for technical success and good long-term
Aortic stenosis in fetus may eventually present as hypoplastic outcome of the procedure.102,103

left heart syndrome and a careful evaluation is recommended.
In mid-gestation fetuses with AS and normal LV length, conclusIon
reversed flow in the transverse aortic arch and foramen
ovale, monophasic mitral inflow, and LV dysfunction have The alteration in number of cusps, leads to abnormal flow
high probability of worst outcome. Nonetheless, these pattern across the valve. Quadricuspid valves are usually
physiological features may help in prognostication. With regurgitant. The bicuspid valves are common and may
growing experience worldwide, fetal interventions are done be incompetent or stenotic. Unicuspid valves are often
to avoid this hemodynamic fate. stenotic and present early. Aortic valve and aortic root are
integrated structurally. The aortic root and its components are
Fetal aortic valvotomy specialized to withstand the high pressure sheering forces.
Hemodynamically, the aortic root has unique capability to
The first known fetal aortic valvuloplasty was performed in tolerate the deforming forces acting on two sides of aortic
1989. Since then experience is growing and many centers valve. The LVOT and AV may have congenital and acquired
worldwide, are performing it routinely. In India it is not been lesions, leading to dysfunction in sizable population of patients.
done till date.100,101 Aortic stenosis and regurgitation, infective endocarditis and
The goal of intervention for fetal AS is to alter left heart aortic dissection are the most common complications. The
physiology and growth, sufficiently to allow postnatal recognition of the BAV as the culprit for isolated AV disease,
survival with a healthy biventricular circulation. In a recently remains an important challenge to the clinicians, whereas
published experience, just over 30 percent of patients who preoperative knowledge of valve morphology would be
underwent technically successful fetal cardiac intervention for helpful in planning the surgery. This lesion can manifest from
this indication had a biventricular circulation from birth, and fetal to elderly age group. The rheumatic fever is anytime,
another 8 percent were converted to a biventricular circulation important etiological factor for combined aortic and mitral
after initial univentricular palliation.102 valve disease. Recent technical advancements have fetched
tremendous refinement in diagnostic and interventional
Fetal aortic balloon valvuloplasty 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
procedure is the alternative surgical procedure for this group
The procedure is performed at 21 to 32 weeks of gestation. It is as it may ensure the growth of pulmonary autograph at the
done under maternal local anesthesia and sedation. A needle is aortic position. The percutaneous valve implantations are
inserted through the mother’s abdominal wall, into the uterine now routinely done for adults in many countries. Also, for
cavity under ultrasound guidance. Fetal analgesic is then elderly patients with AS , there is scope for medical therapy to
injected before advancing the needle through the fetal chest modify the natural history of moderate AS. For pediatric age
wall into the LV of the fetus. A guide-wire is inserted through group no modifying effect of drugs has been demonstrated
the needle and across the aortic valve. A balloon catheter is then as yet. The fetal interventions are another attractive modality
inserted and inflated to dilate the stenotic valve. The catheter and are being refined to improve success rate. The genetic
and needle are withdrawn after the completion of procedure. interventions and evolution of prosthetic materials, which
Fetal positioning is critical for success of the procedure.103 are more in concordance with aortic root physiology are the
Goldstein et al reported the novel use of a pressure guidewire future goals.105
during aortic valvuloplasty in a fetus at 21 weeks’ gestation
with critical AS and evolving hypoplastic left heart syndrome. Medicine heals doubts as well as diseases.
They demonstrated that this technique augments fetal safety —Karl Marx
as it relates to operator awareness of catheter and wire
position (with continuous monitoring of pressure waveforms), acknowledgments
improves the intraprocedural fetal hemodynamic monitoring
and responsiveness to resuscitation. Also, it provides a rich I am grateful to Dr KS Iyer Director, Pediatric cardiac
new data set of invasive fetal hemodynamics.104 surgery, Dr YK Mishra, Director, Cardiac surgery for their
inputs regarding aortic valve surgery, Dr Apoorva Goyal,
safety of the Procedure senior consultant radiologist FEHI, for CT angio images
Dr Nagendra Chauhan, Sr Consultant, Medanta Medicity, for
Though the various centre have claimed the good success rate 3D images, Dr IB Vijayalakshmi and Dr Pradeep Vaideeshwar 499
in fetal AS, the procedure is technically, ethically and morally for providing some of the images.
6 reFerences 19. Davies MJ. Pathology of cardiac valve. London: Butterworth,
1980.
1. Smallhorn JF, Redington AN Anderson RH. Congenital
20. Bellhouse BJ, Talbot L. The fluid mechanism of Aortic valve J.
anomalies of the aortic valve and left ventricular outflow tract.
Fluid Mech. 1969;35:721-35.

In: Anderson RH, Backer EJ, Penny DJ, Redington AN, Rigby
21. Anderson RM, Bloomer WE, Kay JH. Suspension of Aortic
ML, Wernovsky G (Eds). Paediatric cardiology, 3rd edition,
Cusps for Correction of Aortic Insufficiency Annals of Surgery.
Churchil Livingstone, 2010.
1961.pp.523-26.
2. Nguyen KH. Congenital Heart Surgery Database and
22. Otto CM. Valvar heart disease:pathology and prevalence and
Nomenclature Project: aortic valve disease. Ann Thorac Surg.
clinical outcome, In Otto (Eds). Valvular Heart disease, 2nd
2000;69:S118-31.
edition. Saunders, 1904.
3. Leonardo (da Vinci) Leonardo on the human body. Newyork:
23. Otto CM. Aortic Stenosis: In Valvular Heart disease, second
Henry Schumam, 1952.
ed, Otto, Publishers: Saunders, 1904.
4. Kirklin WJ, Barratt-Boyes BG. Congenital aortic stenosis. In:
24. Robicsek F, Thubrikar MJ, Cook JW, et al. The congenitally
Kirklin JW, Barratt Boyes BG (Eds). Cardiac surgery, 2nd
bicuspid aortic valve: how does it function? Why does it fail?
editor. New York: Churchill Livingstone 1993.pp.1195-237.
Ann Thorac Surg. 2004;77:177-85.
5. Lupinetti FM, Bove EL. Left ventricular obstruction. In:
25. Trivellato M, Angellini P, Leachman RD. Variations in coronary
Mavroudis C, Backer CL (Eds). Pediatric cardiac surgery, 2nd
artery anatomy: Normal Vs Abnormal. Cardiovascular
editor St. Louis: Mosby. 1994.pp.425-39.
disease.1980;7:357-70.
6. Hoffman JI. Aortic stenosis. In: Moller JH, Neal WA, (Eds).
26. Scott M, Vesely I. Aortic valve cusp microstructure: the role of
Fetal, neonatal and infant cardiac disease. Norwalk, Conn:
elastin. Ann Thorac Surg. 1995;60:S391-4.
Appleton and Lange. 1990.pp.451-73.
27. Vesely I. The role of elastic in aortic valve mechanics. J
7. Clark DR, Bishop DA. Congenital malformations of the aortic
Biomech. 1998;31:115-23.
valve and left ventricular outflow tract. In: Baue EA, Geha AS,
28. Opie L. Mechanism of cardiac contraction and relaxation
Hammond GL, Laks H, Nauheim KS (Eds). Glenn’s thoracic
Brounwald E, Douglas P, Peter L, Heart disease, a textbook
and cardiovascular surgery. Stamford, CT: Appleton and
of cardiovascular medicine (Eds), 6th edition: WB Saunders.
Lange. 1996.pp.1221-42.
2001.pp.479-503.
8. Fyler DC. Aortic outflow abnormalities. In: Fuler DC, (Ed.)
29. Brewer RJ, Deck JD, Capati B, Nolan SP. The dynamic aortic
Nadas’ pediatric cardiology. Philadelphia: Hanley and Belfus,
root. Its role in aortic valve function. J Thorac Cardiovasc
Inc. 1992.pp.493-512.
Surg. 1976;72:413-7.
9. Bonow RO, Carabello B, de Leon AC, et al. CC/AHA guidelines
30. de Heer LM, Budde RP, Mali WP, de Vos AM, van Herwerden
for the management of patients with valvular heart disease. J
LA, Kluin J. Aortic root dimension changes during systole
Am Coll Cardiol. 1998;32:1486-1582.
and diastole: evaluation with ECG-gated multidetector
10. Duckworth JW. Embryology of congenital heart disease. In:
row computed tomography. Int J Cardiovasc Imaging.
Keith JD, Rowe RD, Vlad P (Eds). Heart disease in infancy and
2011;27:1195-204.
childhood. New York: Macmillan Publishing Co. Inc. 1978.
30A. Dagum P, Green GR, Nistal FJ, et al. Deformational Dynamics
pp.129-52.
of the Aortic Root Modes and Physiologic Determinants.
11. Weldon CS. Congenital obstruction of the left ventricular
1999;100:II-54-II-62 doi: 10.1161/01.CIR.100.suppl_2.II-54.
outflow. In: Aberdeen E, Benson CD, Randolph J, et al. (Eds).
31. Davies MJ, Anderson RH, Becker AE. The conduction system
Pediatric surgery, 3rd edition. Chicago: Year Book, 1978.
of the heart. Butterworth and Co. London. 1983.pp.1-336.
pp.633-49.
32. Waller BF. Clinicopathological correlations of the human
12. Keith A. Schorstein lecture on the fate of the bulbus cordis in
cardiac conduction system. In: Zipes DP, Jalife J Cardiac
the human heart. Lancet. 1924;2:1267-70.
Electmphysiology. Fmm Cell to Bedside (Eds). WB Saunders,
13. Ellison JW, Yagubyan M, Majumdar R, et al. Evidence of
Philadelphia. 1990.pp.249-69.
genetic locus heterogeneity for familial bicuspid aortic valve. J
33. Waller BF, Gering LE, Branyas NA, et al. Anatomy, Histology
Surg Res. Sep 2007;142:28-31.
and Pathology of the Cardiac Conduction System-Part VI:
14. Anderson RH. Multimedia Manual of Cardiothoracic Surgery/
Clin. Cardiol. 1993;16:623-8.
doi:10.1510/mmcts.2006.002527.
34. Delmo Walter EM, Huebler M, Alexi-Meshkishvili V, Fate of
15. Ho SY. Structure and anatomy of the aortic root. Eur J
the aortic valve following the arterial switch operation. J Card
Echocardiogr. 2009;10:i3-10.
Surg. 2010;25:730-6.
16. Walmsley R. Anatomy of left ventricular outflow tract. Br
35. Underwood MJ, Khoury G El, Deronck D, et al. The aortic
Heart J. 1979;41:263-7.
root: structure, function and surgical reconstruction; Heart.
17. Schneider DJ, Moore JW. Aortic Stenosis. In: Allen HD,
2000;83:376-80.
Driscoll DJ, Shaddy RE, Feltes TF (Eds). Moss’ Heart Disease
36. Jánosi RA, Kahlert P, Plicht B, et al. Measurement of the aortic
in Infants, Children, and Adolescents 4th edition. Baltimore:
annulus size by real-time three-dimensional transesophageal
Williams and Wilkins, 1985.
echocardiography. Minim Invasive Ther Allied Technol.
18. Tadros TM, Klein MD, Shapira OM. Ascending Aortic Dilatation
2011;20:85-94.
Associated With Bicuspid Aortic Valve. Pathophysiology,
37. Divekar A, Gaamangwe T, Shaikh PN. Cardiac perforation
Molecular Biology, and Clinical Implications; (Contemporary
after device closure of atrial septal defects with the
Reviews in Cardiovascular Medicine). Circulation. 2009;119:
Amplatzer septal occluder; J Am Coll Cardiol. 2005;45:
500 880-90.
1213-8.
38. Hill AC, Bansal RC, Razzouk AJ, Liu M, Bailey LL, Gundry
SR.Echocardiographic recognition of iatrogenic aortic valve
57. Janatuinen MJ, Vanttinen EA, Nikoskelainen J, et al. Surgical
treatment of active native endocarditis. Scand J Thorac
33
leaflet perforation. Ann Thorac Surg. 1997;64:684-9. Cardiovasc Surg. 1990;24:181-5.

39. Valvular, Subvalvular and supravalvular aortic stenosis: 58. Rudolf AM. Congenital diseases of the heart. In: Clinical
morphologic features, Cardio vase Clin. 1973;5:98-126. Physiological considerations. 2nd edition. Rudolf AM (Ed),
40. Angelini A, Ho SY, Anderson RH, et al. The morphology of the Futura Publishing Co. Inc, 2001.
normal aortic valve as compared with aortic valve having two 59. Brounwald E, Perloff JK. Physical examination of heart and
leaflets. J Thorac Cardiovas Surg. 1989;98:362-7. circulation. Brounwald E, Douglas P, Peter L. Heart disease,
41. Abnormalities of ventricular outflow, In: Echocardiography a textbook of cardiovascular medicine, 6th edition, Publisher:
in pediatric heart disease. Snider AR, Serwer GA, Ritter SB WB Saunders, 2001.
(Eds). 2nd edition. Mosby year book. 1997.pp.408-51. 60. Perloff JK. Congenital aortic stenosis/Congenital aortc
42. Cheitlin MD, Fenoglio JJ, McAllister HA, Davia JE, DeCastro regurgitation. In: Perloff JK (Ed), The clinical recognition
CM. Congenital aortic stenosis secondary to dysplasia of of congenital heart diseas, 5th edition. Publishers: Saunders,
congenital bicuspid aortic valves without commissural fusion, 2003.
Am J Cardiol. 1978;42:102-7. 61. Beyerbacht HP, Bax JJ, Lamb HJ et al. Evaluation of ECG
43. Beppu S, Suzuki S, Matsuda H, et al. Rapidity of progression criteria for LVH before and after the aortic valve replacement
of aortic stenosis in patients with congenital bicuspid aortic using magnetic resonant imaging. J cardvasc Mag Res.
valves. Am J Cardiol. 1993;71:322-7. 2003;5:465-74.
44. Pachulski RT, Weinberg AL, Chan KL. Aortic aneurysm 62. Rijnbeek PR, van Herpen G, Kapusta L, et al. Electrocardio-
in patients with functionally normal or minimally stenotic graphic criteria for left ventricular hypertrophy in Children.
bicuspid aortic valve. Am. J. Cardiol. 1991;67:781-2. Pediatr Cardiol. 2008;29:923-28.
45. Hahn RT, Roman MJ, Mogtader AH et al. Association of aortic 63. Kim SH, Woo HO, Kim YM, et al. Abnormal morphological
dilation with regurgitant, stenotic and functionally normal pattern of LV myocardium in critical aortic stenosis of the aortic
bicuspid aortic valves. J Am Coll Cardiol. 1992;19:283-8. valve and intact ventricular septum. JKMS. 1997;12:49-54.
46. Roberts WC, Ko JM. Frequency by decades of unicuspid, 64. Bruch C, Stypmann J, Grude M, et al. Tissue Doppler imaging
bicuspid, and tricuspid aortic valves in adults having isolated in patients with moderate to severe aortic valve stenosis:
aortic valve replacement for aortic stenosis, with or without clinical usefulness and diagnostic accuracy. Am Heart J.
associated aortic regurgitation. Circulation. 2005;111:920. 2004;148:696-702.
47. Sabet HY, Edwards WD, Tazelaar HD, et al. Congenitally 65. Rhodes LA, Colan SD, Perry SB, et al. Predictors of
bicuspid aortic valves: a surgical pathology study of 542 cases survival in neonates with critical aortic stenosis; circulation.
(1991 through 1996) and a literature review of 2715 additional 1991;84:2325-35.
cases. Mayo Clin Proc. 1999;74:14-26. 66. Chockalingam A, Gnanavelu G, Elangovan S, et al. Clinical
48. Roberts WC. The congenital bicuspid aortic valve. Am J spectrum of chronic rheumatic heart disease in India. J Heart
Cardiol. 1970;26:72-83. Valve Dis. 2003;12:577-81.
49. Sievers HH, Schmidtke C. A classification system for the 67. Rheumatic fever and rheumatic heart disease: report of a WHO
bicuspid aortic valve from 304 surgical specimens. J Thorac Expert Consultation, Geneva, 29 October-1 November, 2001;
Cardiovasc Surg. 2007;133:1226-33. http://books.google.com/books/about/Rheumatic_fever_and_
50. Fazel SS, Mallidi HR, Lee RS, et al. The aortopathy of bicuspid rheumatic_heart_dise.html?id=mFzYS-NyuCYC.
aortic valve disease has distinctive patterns and usually 68. Piérard LA, Lancellotti P. Stress testing in valve disease. Heart.
involves the transverse aortic arch. J Thorac Cardiovasc Surg. 2007;93:766-72.
2008;135:901-7. 69. Aranki SF, Santini F, Adams DH, et al. Aortic valve
51. Hongo M, Goto T, Watanabe N, et al. Relation of phasic endocarditis. Determinants of early survival and late morbidity.
coronary flow velocity profile to clinical and hemodynamic Circulation. 1994;90:II175-82.
characteristics of patients with aortic valve disease. Circulation. 70. Saleeb SF, Solowiejczyk DE, Glickstein JS, et al. Frequency of
1993;88:953-60. development of aortic cuspal prolapse and aortic regurgitation
52. Chambers J. The left ventricle in aortic stenosis: evidence for in patients with subaortic ventricular septal defect diagnosed at
the use of ACE inhibitors. Heart. 2006;92:420-3. < 1 year of age. Am J Cardiol. 2007;99:1588-92.
53. Weinberg EO, Schoen FJ, George D, et al. Angiotensin converting 71. Mori K, Matsuoka S, Tatara K, et al. Echocardiographic
enzyme inhibition prolongs survival and modifies the transition evaluation of the development of aortic valve prolapse
to heart failure in rats with pressure overload hypertrophy due to in supracristal ventricular septal defect. Eur J Pediatr.
ascending aortic stenosis. Circulation. 1994;90:1410-22. 1995;154:176-81.
54. Seth LR, Arora R. Statin Therapy and Aortic Stenosis: A 72. Ando M, Takao A. Pathological anatomy of ventricular septal
Systematic Review of the Effects of Statin Therapy on Aortic defect associated with aortic valve prolapse and regurgitation
Stenosis; American Journal of Therapeutics: July/August 2010 Heart vessels. 1986;2:117-126.
- Volume 17 - Issue 4 - pp e110-e114. 73. Brown DW, Dipilato AE, Chong EC, et al. Aortic valve
55. Kamata S, Sakagoshi N, Ohata T, et al. Successful surgical reinterventions after balloon aortic valvuloplasty for congenital
treatment of pentacuspid aortic valve with severe aortic aortic stenosis-intermediate and late follow-up; J Am Coll
regurgitation. Jpn J Cardiovasc Surg. 2008;37:53-5. cardiol, 2010;56:1740-49.
56. Lamas CC, Eykyn SJ. Bicuspid aortic valve–A silent danger: 74. Michel PL, Vahanian A, Besnainou F, et al. Value of qualitative
501
analysis of 50 cases of infective endocarditis. Clin Infect Dis. angiographic grading in aortic regurgitation. Eur Heart J.
2000;30:336-41. 1987;8:11-14.
6 75. Valdes-Cruz LM, Cayre RO. Miscellaneous anomalies of left
ventricular outflow tract. In: Valdes-Cruz LM, Cayre RO (Eds).
91. Pettersson GB, Ramankutty RM. Repair of bicuspid aortic
valve with severe regurgitation. MMCTS, 2010.
Echocardiographic diagnosis of congenital heart disease–An 92. Boodhwani M, Kerchove LD, Glineur, et al. Repair of Aortic
embryologic and anatomic approach. Philadelphia New York valve prolapse, Multimedia manual of cardio-thoracic surgery
Lippincott-Raven publishers. 1999.pp.371-7. mmcts. 2008.003806 doi: 10.1510/mmcts.2008.2008.003806.
76. Mills P, Leech G, Davies M, et al. The natural history of a non- 93. Arnold R, Ley-Zaporozhan J, Ley S, et al. Outcome after
stenotic bicuspid aortic valve. Br Heart J. 1978;40:951-7. mechanical aortic valve replacement in children and young
77. Mahle WT, et al. Outcome of isolated bicuspid aortic valve in adults. Ann Thorac Surg. 2008;85:604-10.
childhood. J Pediatr. 2010;157:445. 94. Raja SG, Pozzi M. Growth of pulmonary autograft after ross
78. Yener N, Oktar GL, Erer D, et al. Review: Bicuspid aortic operation in pediatric patients. Asian Cardiovasc Thorac Ann.
valve, Ann Thorac Cardiovasc Surg. 2002;8:264-167. 2004;12:285-90.
79. McElhinney DB, Lock JE Keane JF, Moran AJ, Colan SD,Left 95. Raja SG, Atal manyuk I, Kostolny M, et al. In young patients
Heart Growth, Function, and Reintervention After Balloon with rheumatic aortic regurgitation compared to non-
Aortic Valvuloplasty for Neonatal Aortic Stenosis;Circulation. rheumatics is a Ross operation associated with increased
2005; 111: 451-458 incidence of autograft failure? Interact CardioVasc Thorac
80. Magee AG, Nykanen D, McCrindle BW, Wax D, Freedom RM, Surg. 2010;10:600-4.
Benson LN. Balloon dilation of severe aortic stenosis in the 96. Al-Lamee R, Godino C, Colombo A. Transcatheter aortic
neonate: comparison of anterograde and retrograde catheter valve implantation: current principles of patient and technique
approaches. J Am Coll Cardiol. 1997; 30: 1061–1066. selection and future perspective: Circulation Cardiovascular
81. Zeevi B, Keane JF, Castaneda AR, Perry SB, Lock JE. Neonatal interactions. 2011;4:387-95.
critical valvar aortic stenosis: a comparison of surgical and 97. Piper C, Kopfer C, Horstkotte D. Valve Disease Prosthetic
balloon dilation therapy. Circulation. 1989; 80: 831–839. valve endocarditis. Heart. 2001;85:590-3.
82. Consensus on Timing of Intervention for Common Congenital 98. Karchmer AW, Gibbons GW. Infections of prosthetic heart
Heart Diseases; working group on management of congenital valves and vascular grafts. In: Bisno AL, Waldvogel FA
heart diseases in India. Indian pediatrics: volume 45, february (Eds). Infections associated with indwelling medical devices.
17, 2008.p.121. Washington: ASM Press. 1994.pp.213-49.
83. Jindal RC, Saxena A, Juneja R, et al. Long-term results of 99. Baddour LM, Wilsom LM. Infection of prosthetic valve
balloon aortic valvulotomy for congenital aortic stenosis in and other cardiovascular devices: intravascular devices. In:
children and adolescents. J Heart Valve Dis. 2000;9:623-8. Mandell GL, Bennete JE, Dolin R, (Eds). Mandel Douglas,
84. Levine MJ, Berman AD, Safian RD, et al. Palliation of valvular and Bennette’s principle and practices of infectious diseases.
aortic stenosis by balloon valvuloplasty as preoperative 5th ed. Philadelphia, Pa: Elssevier: 1022-44.
preparation for noncardiac surgery. The American Journal of 100. McCaffrey FM, Sherman FS. Prenatal diagnosis of severe
Cardiology. 1988;62:1309-10. aortic stenosis. Pediatr Cardiol. 1997;18:276-81.
85. Thomson JD. Management of valvar aortic stenosis in children. 101. Maxwell D, Allan L, Tynan MJ. Balloon dilatation of aortic valve
Heart. 2004;90:5-6. in the fetus: a report of two cases: Br Hear J. 1991;65: 256-8.
86. Reich O, Marek J, Gilík J, et al. Long-term results of 102. McElhinney DB, Marshal AC, Wilkins-Haug LE, et al.
percutaneous balloon valvoplasty of congenital aortic stenosis: Predictors of technical success of postnatal biventricular repair
independent predictors of outcome. Heart. 2004;90:70-6. outcome after in utero aortic valvoplasty for aortic stenosis
87. Daehnert Rotzsch C, Wiener M et al. Rapid right ventricular with evolving hypoplastic left heart syndrome. Circulation.
pacing is an alternative to adenosine in catheter interventional 2009;120:1482-90.
procedures for congenital heart disease. Heart. 2004;90:1047-50. 103. Percutaneous fetal balloon valvuloplasty for aortic stenosis;
88. Ross J Jr. Afterload mismatch in aortic and mitral valve disease: NHS national institute of health and clinical excellence;
implications for surgical therapy J. Am Coll Cardiol. 1985;5:811. Issue date May 2006; http://www.nice.org.uk/nicemedia/
89. Carr JA, Savage EB. Aortic valve repair for aortic insufficiency live/11266/31597/31597.pdf.
in adults: a contemporary review and comparison with 104. Goldstein BH, Fifer CG, Armstrong AK, et al. Use of a Pressure
replacement techniques Eur J Cardiothorac Surg. 2004;25: Guidewire in Fetal Cardiac Intervention for Critical Aortic
6-15. Stenosis. Pediatrics. 2011;128:e716-9. Epub 2011 Aug 15.
90. Izumoto H, Kawazoe K, Oka T, et al. Leaflet Suspension 105. Apte SS, Paul A, Prakash S, Shum-Tim D. Current developments
and subvalvular annuloplasty in aortic valve prolapse Asian in the tissue engineering of autologous heart valves: moving
Cardiovasc Thorac Ann. 2009;17:278-81. towards clinical use.Future Cardiol. 2011;7:77-97.
502
Sec t i on
Diseases of the Aorta
C hapter
34 Coarctation of the Aorta
Bentham J, Wilson N
IntroDuCtIon extreme end of severity is interrupted aortic arch, which will

be dealt with in chapter 35.
Coarctation of the aorta can be defined as an obstruction
in the descending aorta located most commonly at the site PrevAlenCe AnD etIology
of insertion of the ductus arteriosus. In practice, this is too
simplistic definition to be of clinical use and coarctation is Aortic arch obstruction is relatively common in newborn
more appropriately viewed as a complex cardiovascular infants1,2 with a higher incidence in the stillborn.3,4 Aortic arch
disorder where aortic obstruction is only one part of a obstruction is most commonly secondary to coarctation of aorta
generalized arteriopathy with life-long implications persis- with an incidence approaching 1:2,000 live births. It also results
ting after initial correction of the aortic obstruction. It is from hypoplastic aortic arch and aortic arch interruption.1,5
without apology that the emphasis of this chapter falls Although pathogenesis is likely to be multifactorial, the
heavily on clinical management. The intention is to leave genetic factors are clearly important with significantly higher
the reader with sufficient knowledge to be able to devise a recurrence risks noted in family members and with notable
management strategy for each of the diverse morphology of syndromic associations (Turner, Noonan and Williams-Beuren
arch obstructions encountered at any age as well as a long- syndromes in particular).6-8 Useful in prenatal counselling,
term view of the need for surveillance and management of published recurrence rates of any congenital cardiac defect
complications often some years following initial treatment. given a first degree relative with coarctation of aorta are
The illustrations also focus on these aspects using a case- increased by several orders of magnitude at between 6.5 to 10
based approach. Although, this allows the chapter to be more percent.6,9-11 There is some suggestion of concordance for the
focused even this is a formidable challenge. Many surgical same or other left-sided phenotypes.9-11
and interventional options exist with differing indications
dependent on whether presentation is in the neonatal period MorPhology
or in later life; the location of obstruction (discrete, longer
segment or multiple level); the type of obstruction (native, The morphological spectrum of aortic arch obstruction is quite
recoarctation or residual), the prevailing center experience varied. In neonates and infants accompanying a coarctation
and availability of technology. It will quickly become shelf of ductal tissue there is usually aortic arch isthmus
evident that no single approach is universally applicable and and transverse arch tubular hypoplasia in contrast to a more
interventional cardiologists and surgeons employ different discrete stenosis distal to the left subclavian artery which is the
strategies to combat arch obstruction and the complications typical lesion in older patients (Figures 1 to 3).1,5 Like most
that ensue. A thorough understanding of the nature and clinical congenital heart defects, aortic arch obstruction occurs either
relevance of the arch obstruction informs these decisions and in isolation or in association with other cardiac anomalies
time will be spent reviewing these factors in turn. Discrete where the term complex rather than simple or uncomplicated
coarctation of aorta along with associated tubular hypoplasia coarctation of aorta is employed.12,13 The main associations of
will be the main consideration with brief comments made coarctation of aorta include bicuspid aortic valve, ventricular
about associated lesions in so far as how the management septal defect (VSD) and aortic and mitral valve anomalies
strategy adopted may need to be altered accordingly. At the (Figures 4 and 5). Coarctation of aorta may also complicate
7
Diseases of the aorta
a B
figures 1a and B: Echocardiographic assessment of the arch anatomy of a newborn infant in preparation for surgical repair. A. A 2.5 kg one-
day-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
figure 2: A neonate with coarctation and transverse and isthmus figure 3: A neonate with coarctation and isthmus arch hypoplasia.
arch hypoplasia. The aortic arch between the brachiocephalic artery Here, there is transverse arch hypoplasia at 3 mm in a 3.5 kg neonate
and left common carotid artery is hypoplastic. The arch after the (distance 2) with further tapering of the arch at the aortic isthmus to
left common carotid artery is also small. An extended end-to-end 2.4 mm (distance 4). As in Figure 2 an extended end-to-end
anastomosis was performed through a median sternotomy to achieve anastomosis was performed through a median sternotomy to achieve
a more satisfactory repair a more satisfactory repair
complex congenital heart disease, notably transposition of discrete coarctation through tubular hypoplasia to interruption
506 the great arteries, double outlet right ventricle, double inlet is open to debate. Recognizing such a spectrum of disease as
left ventricle, tricuspid atresia and hypoplastic left heart well as the typical patterns of associated anomalies where
syndrome. Whether there is a sequence of anomalies from coarctation of aorta is a frequent accompanying feature led
Rudolph to speculate that a reduction in the volume of blood instituted as part of resuscitation. Not infrequently inotropes 34
passing through the ascending aorta in fetal life is causative in are an important part of resuscitation in these circumstances
the development of coarctation.14 Although other etiological and occasionally emergency interventional or surgical relief
CoarCtation of the aorta

theories exist Rudolph’s hypothesis is the most useful to of obstruction is necessary (see below). Evidence for efficacy
remember in clinical practice as coarctation of aorta and/or from high dose PgE (doses greater than 20 ng/kg/minute) in
transverse arch hypoplasia should be suspected until proven improving ductal patency and relieving aortic obstruction
otherwise, when there is potential for preferential ductal arch is controversial with no convincing evidence for increased
over aortic arch flow during fetal life. efficacy at higher dose.17,18 Not all infants with coarctation of
aorta will be duct dependent and some will present in heart
PreSentAtIon failure as left ventricular function becomes impaired over the
early weeks to months of life. A smaller number of infants will
neonate remain asymptomatic and present with a cardiac murmur.
Increasingly, coarctation of aorta is diagnosed antenatally with older Child and Adult
suspicion raised by marked ventricular or great vessel dispro-
portion15 (Figures 1A and B). There is evidence for improved Older children and adults may present with systemic hyper-
outcome for these infants as prostaglandin E2 or E1 (PgE) can tension or a cardiac murmur. Less commonly they exhibit
be commenced in the hours following birth to maintain ductal complications of aortic obstruction including left ventricular
patency and systemic blood flow thus avoiding cardiovascular failure, infective endarteritis, intracranial hemorrhage, regur-
collapse.16 These infants do however, continue to present di- gitation of an associated bicuspid aortic valve, premature
agnostic difficulty postnatally as ductal patency is maintained coronary artery disease or aortic dissection or rupture.
such that aortic arch obstruction may not be immediately
evident on echocardiography. Often one can be confident to IMAgIng
proceed to treatment on the basis of echocardiographic morpho-
logical appearances of coarctation whilst if there is uncertainty Chest radiography
discontinuing PgE under close observation allowing ductal
constriction and aortic arch obstruction to develop before con- The asymptomatic older child may demonstrate a prominent
sidering treatment is prudent (Figures 1 to 3). aortic knuckle and rib notching. Rib notching is rare in early
Given the subtlety of the antenatal features of possible childhood and most likely seen beyond 10 years of age. Chest
coarctation postnatal presentation will remain frequent. Whe- radiography is neither diagnostic nor prognostic, but may
ther screening methods such as lower limb pulse oximetry contribute if there is complex disease.
prior to neonatal discharge will increase detection of this
lesion remains to be proven.16 Clinical suspicion should be echocardiography
raised by lower limb saturations less than 95 percent, an
upper-lower limb blood pressure difference of more than The characteristic features of coarctation of aorta on
20 mm Hg and weaker femoral pulses than the upper limb echocardiography is indentation of the posterior aorta by
pulses. When both upper and lower limb pulses are weak this a wedge or ‘shelf’ of tissue (Figures 1 to 3). This can on
may result in diagnostic confusion and may reflect reduced occasion be difficult to demonstrate in the presence of a large
cardiac output from many causes, most commonly an infant patent ductus in an infant maintained on a PgE infusion.
with pulmonary hypertension of the newborn, septicemia or Serial echocardiography may be required in this circumstance
left heart obstructive lesions (aortic stenosis and hypoplastic with PgE discontinued. The transverse and isthmus arch
left heart syndrome). An aberrant right subclavian artery dimensions can be clearly defined by suprasternal views
(ARSA) could theoretically fail to detect both a difference in with echocardiography. Doppler interrogation may not be
upper limb and lower limb blood pressure or pulse oximetry informative if ductal flow is large, but if the ductus is closed or
readings as the right subclavian artery may arise below the constricted classical features of acceleration with flow into and
site of coarctation. In practice, this is a rare association (less through diastole are easily demonstrated. Considerable clinical
than 3%). A bruit may be heard between the scapulae, but is judgement may be required in borderline cases particularly in
not typical of neonatal coarctation. the setting of complex hearts with multiple malformations.
Any neonate presenting with cardiovascular collapse should Aortic arch obstruction will most likely progress over time
undergo cardiac evaluation as part of a diagnostic workup and and the classical features of aortic arch obstruction are not
echocardiography forms the mainstay of diagnostic evaluation immediately apparent. Associated features need to be defined
of the aortic arch (Figures 4A to E). Such duct dependent by a full echocardiographic study as they will impact greatly
infants rarely present diagnostic difficulties and PgE can be on the management strategy (Figures 4 and 5).
507
7
a B C
D e
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 aortic arch anatomy. Modern multislice scanners are able
to achieve sufficient resolution to be superior to MRI in
In the older child and adult, magnetic resonance imaging small infants and would be complimentary to detailed echo-
(MRI) is more informative than echocardiography and is the cardiography albeit at the expense of radiation exposure.
imaging modality of choice for planning intervention. MRI General anesthesia is rarely required.
is able to define accurately whether one or multiple sites of
obstruction exist, the proximity to the head and neck vessels Angiography
as well as the length of hypoplastic segments. MRI is also a
useful surveillance tool for complications following treatment With the advent of noninvasive imaging, angiography is
of coarctation and many units routinely perform MRI as part of generally not required as a diagnostic tool in the evaluation
transition from pediatric to adult practice particularly if there of native coarctation of aorta. Angiography is performed as
is a degree of systemic hypertension.19 Standard protocols part of interventional treatment of coarctation of aorta in the
have been extensively published. older child and adult but rarely in isolation. Occasionally,
diagnostic angiography is necessary to assess the adequacy
Computed tomography of repair and would form an important part of the interstage
assessment of aortic arch reconstructive surgery following the
508 Occasionally, computed tomography (CT) can be useful in Norwood procedure for example. The difficulty here however
infants where there is diagnostic uncertainty about complex is that, gradients obtained under general anesthesia bear little
indications for intervention in each case. Debate exists over 34
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.
Surgical treatments
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.
figure 5: Associated findings in children with coarctation can There will be circumstances where options are limited and one
impact greatly on the treatment strategy adopted and careful for full
echocardiographic evaluation is essential. A two-year-old girl presents
technique is preferred in view of the arch anatomy even if
with a cardiac murmur to her local pediatrician. Coarctation of aorta associated with higher risk of complications. The capability to
and a volume loaded left heart was evident on echocardiography. offer more than one technique occasionally in the same patient
There was pulmonary hypertension and a large aortopulmonary will be an important prerequisite of success in managing the
window was found (arrow). Repair of aortic coarctation by end-to-end
anastomosis and repair of aortopulmonary window was performed with
diversity of aortic arch obstructions encountered.
resolution of pulmonary hypertension in the days following surgery.
The aortopulmonary window had been missed by an incomplete End-to-End Anastomosis Including Extended Repair
echocardiographic study at another institution
End-to-end anastomosis has become the procedure of choice
for many centers managing infant and neonatal coarc-
resemblance to gradients likely to be experienced by the tation.27,28 The mortality rate in uncomplicated patients is very
patient under stress. Consequently, an infusion of an inotrope low,23,29 but rises with more complex disease and associated
such as adrenaline may be required to reveal suspected residual lesions.29,30 Residual obstruction in up to 34 percent of patients
obstruction. In the setting of patients with univentricular is noted at early follow-up. Residual obstruction is strongly
circulation, such diagnostic studies may be important when associated with weight at the time of surgery.26,28-32,37 Whether
considering higher risk interventions once other therapeutic obstruction at follow-up can be defined as recoarctation
strategies have been exhausted. resulting from scar tissue formation or failure to adequately
treat the primary lesion is open to debate (Figures 6 to 9).
InDICAtIonS for treAtMent Managing tubular arch hypoplasia with an extended or end-to-
side repair may be preferable and highlights the importance of
In infants with hemodynamic compromise the indication careful pre-operative assessment.33
for treatment is unequivocal. In older patients a consistent
systolic blood pressure gradient between the arms and legs Subclavian Flap Repair
of more than 20 mm Hg may be considered as an indication
for treatment although this is not universally accepted.20,21 Concerns about inadequate relief of obstruction with subclavian
The gradient across the site of aortic obstruction will be flap repair and the long-term risk of aneurysm formation has
influenced by the degree of collateral vessel formation such rendered this technique less popular. Occasionally, subclavian
that gradient alone is not a good indication for treatment in flap repair may be combined with end-to-end anastomosis to
some patients. Systemic hypertension at rest or following more adequately treat long segment obstruction.33
provocation with exercise greater than the 97th percentile for
age along with evidence of important luminal stenosis would Interposition Grafts, Bypass Tube, Extra-anatomic
form indications for treatment in this group of patients.22 The Bypass Grafts
complexity of arch obstruction, the procedure related risk and
the likelihood of procedural success form important parts of In older patients and adults, there is significant concern about 509
the joint cardiac and surgical discussion as to the timing and the ability to sufficiently mobilize tissue in a timely fashion to
7
a B C
D e f
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 child’s 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 Influence of Associated Lesions

significant risk of spinal cord ischemia from prolonged aortic
cross-clamp. For these reasons, interposition grafts and bypass The commonest associated findings with discrete coarctation
grafts are occasionally necessary to satisfactorily relieve of aorta are bicuspid aortic valve and ventricular septal defect.
obstruction. With the advent of interventional options these Bicuspid valves are rarely sufficiently stenotic to require sur-
circumstances are becoming increasingly uncommon. gical or interventional treatment in the neonatal period. In the
context of severe aortic stenosis, surgical valvotomy along-
Patch Aortoplasty side coarctation repair might be preferred over interventional
balloon valvuloplasty and surgical arch repair as two sepa-
Prosthetic patch aortoplasty is now seldom used as a primary rate procedures. VSDs are sufficiently common to frequently
treatment because of the unacceptable risk of aneurysm influence surgical decisions. Large VSDs may be closed as
formation associated particularly with the use of Dacron a primary procedure alongside aortic arch repair if the sur-
patches.34 Patch aortoplasty is however sometimes necessary geon feels able to close the defect in a small heart without
with complex arch obstruction in young patients particularly significant morbidity. This will be consequent on the number
in the context of early recoarctation (Figure 8). and morphology of the VSDs. Apical or large VSDs, which
510
34

a B
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 figure 9: Residual or recoarctation is not uncommon following surgery.
with the underlying arch anatomy being a critical factor in the likelihood This hypertensive teenager was initially palliated as a low-birth-weight
of recurrence. A three-month-old infant presents for follow-up following infant with a turn down procedure of the left subclavian artery. The
end-to-end anastomosis repair of neonatal coarctation. There is coarcted segment is still evident. An 18 mm surgical interposition graft
generalized hypoplasia of the aortic arch as well as the head and was placed across the coarctated segment and the left subclavian
neck vessels. No discrete obstruction is identified to guide therapeutic artery turn down left producing effectively a double aortic arch with a
intervention. The arch is augmented after the left subclavian artery satisfactory result
with a patch aortoplasty though the descending aorta is similarly small.
This infant most likely has a vasculopathy (no elastin mutation was
identified)
511
7
a B
C D
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
may be more difficult to repair in a small heart whilst preserv- recent technological advance have become the preferred
ing satisfactory left ventricular function may be alternatively treatment option in older patients weighing more than 25 kg.
treated by placement of a pulmonary artery band with the in-
tention of further surgery at a later stage (Figures 10A to D). Balloon Angioplasty
Interventional treatments Balloon angioplasty is a controversial treatment for native

coarctation of aorta because of the damage to the aortic intima
There is appreciable morbidity associated with surgical repair and media that is necessary for satisfactory relief of stenosis
of coarctation of aorta including spinal cord damage, pleural but which results in recurrent stenosis and appreciable risk of
effusions, paradoxical hypertension and infection. Although dissection, rupture and long-term aneurysm formation.24,35,36 In
mortality is low, residual or recurrent aortic arch obstruction infancy, although efficacious in relieving stenosis there is good
is sufficiently common to remain an important concern.29 evidence to support there being a higher risk of recurrence than
These surgical risks may increase for recoarctation. Lateral that found with surgical techniques.37-39 Balloon angioplasty
thoracotomy is a painful surgical incision and recovery can does have a place in managing the sick hemodynamically
be prolonged. It is against this background that interventional compromised infant in allowing successful resuscitation and
512 treatments for aortic arch obstruction have emerged and with to act as a bridge to definitive surgical repair at lower risk.40
Some centers also perform balloon angioplasty in lower-birth- for complications differ markedly between series. A single 34
weight infants (less than 2.5 to 3 kg) in order to delay surgery randomized study included only 36 patients at an age range
until an infant has grown and achieve a more satisfactory of 3 to 10 years.42 There was a comparable reduction in

surgical result (Figures 11A to D).33 Balloon angioplasty systolic gradients across aortic arch obstruction between the
should also be considered in children weighing less than two groups. As expected restenosis occurred more commonly
25 kg when faced with significant residual or early recurrence in the angioplasty group although this failed to reach
of gradient.24,41 Some centers might consider balloon angio- statistical significance. Neurological complications occurred
plasty in smaller children beyond infancy as a bridge to stent more frequently in the surgical group and aneurysms in the
placement when heavier than 25 kg thus avoiding the need angioplasty group. Late follow-up showed equivalence for need
for surgery. The risks of complications in this setting may for reintervention but an appreciable number of aneurysms
be appreciable with the need for repeat procedures. In older developed late in the angioplasty group.43
children and adults, primary stent placement is generally
preferred by most operators for management of recurrent Stent Placement
aortic arch obstruction following previous surgery.
It is difficult to make meaningful comparisons between Endovascular bare metal stents have been used to treat re-
balloon angioplasty beyond infancy and surgery for treatment coarctation, native coarctation and aortic arch obstruction
of coarctation of aorta based on individual centers published for over a decade and were viewed as a potential solution to
experience. Furthermore, follow-up protocols for surveillance the problems of aneurysm formation associated with balloon
a B
C D
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 513
in childhood (stent placement)
7 angioplasty.44 Furthermore, bare metal open cell designed The most frequent complication following interventional
stents potentially offer an effective solution for complex stent placement relates to vascular access with need for large
arch obstruction in adults and older children where balloon sheaths. This has undoubtedly improved with technological
angioplasty is often ineffective because of elastic recoil and advances allowing delivery of stents through smaller and
surgery may require extra-anatomic bypass grafts. There smaller sheaths as well as vascular closure techniques. Whether
remains concern, however that bare metal stents are still interventional treatments will become a panacea for managing
associated with aortic aneurysm formation with a long-term aortic arch obstruction from infancy to adult life remains to
risk of aortic rupture albeit less than the risk with balloon be realised, but the adaptability of these techniques to varying
angioplasty alone.45 Covered stents may thus be preferred situations makes aortic arch intervention an important part of
where possible (Figures 12 and 13).46-48 Covered stents a comprehensive cardiac program (Figures 13A to D).
are, however, relatively contraindicated if placed in such a
position as to occlude head and neck vessels. Head and neck PrognoSIS
vessels may be covered with a stent only after evaluation
of the circle of Willis and with the availability of vascular The natural history of coarctation of aorta is extremely poor.
surgical grafting. Complications relating to exclusion of the Campbell reported mortality in excess of 75 percent of patients
left subclavian artery, even in adults, are rare.49,50 by 46 years of age.62 In the largest follow-up series of 646
Placement of endovascular stents in infants and small patients who underwent treatment for simple coarctation of aorta
children (< 25 kg) remains a controversial therapy despite at the Mayo clinic between 1946 and 1981 the postoperative
improvements in methods of access, balloon and stent size 10-year survival rate was 91 percent, falling to 84 percent at 20
and the use of smaller and smaller sheaths.24,51 The fact that years and 72 percent at 30 years. Earlier age at operation was
children will by necessity, be committed to several future associated with improved survival.63 Causes of death included
cardiac catheter procedures because of need for stent re- premature coronary artery disease, left ventricular failure,
dilation causes concern for most; thus preferring surgical stroke, sudden cardiac death and ruptured aortic aneurysm.
alternatives, balloon angioplasty or stent therapy only as a Given such poor outcomes conservative management of
bridge to definitive surgery later in childhood52,53 or potentially important residual gradients is not an attractive option. However,
as a bridge to adult size stent placement.54 whether these risks may be reduced by adequately treating
Short-term published results for stent implantation to residual obstructions remains to be proven.64 Such a guarded
successfully manage native and recurrent coarctation in prognosis may in-part relate to a coexisting vasculopathy that
older children and adults suggest that stenting gives more poses a significantly increased risk of systemic hypertension
predictable and lasting results than balloon angioplasty. Death throughout a patient's life.65-67 Life-long follow-up, treatment
has been reported between 0 to 1.4 percent and neurological of systemic hypertension and intermittent surveillance imaging
damage between 0 to 3.7 percent.45-48,55-61 to detect occult obstruction and/or aneurysm are essential.
a B C
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

a B
C D
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 The healing process demands more than science; it requires

mobilizing patient's positive expectations and stimulating faith in
Coarctation of aorta can present in early infancy to adult life. physician's ministration. I know of few remedies more powerful
The lesion is highly variable and although surgical treatments than a carefully chosen word. Patients crave caring, which is
have proved and remain superior in infancy, interventional dispensed largely with words. Talk, which can be therapeutic
treatments are emerging as the preferred strategy in older is one of the underrated tools in a physician's armamentarium.
children and adults. Early mortality for these treatments is —Bernard Lown, MD
low, but morbidity over long-term follow-up is extremely
high with need for careful follow-up and surveillance for referenCeS
complications. Whether the natural history can be modified
by a more aggressive interventional approach remains to 1. Hoffman JI, Kaplan S. The incidence of congenital heart
be proven, but given the poor long-term prognosis for this disease. J Am Coll Cardiol 2002;39:1890-900.
condition, significant residual obstructions are best managed 2. Hoffman JI, Kaplan S, Liberthson RR. Prevalence of congenital
heart disease. Am Heart J 2004;147:425-39.
by interventional techniques. There is an increasing reluctance
3. Hoffman JI. Incidence of congenital heart disease: II. Prenatal
to accept even small gradients in the setting of systemic incidence. Pediatric cardiology 1995;16:155-65. 515
hypertension with the hope of better survival for these patients 4. Hoffman JI. Incidence of congenital heart disease: I. Postnatal
in the years to come. incidence. Pediatric cardiology 1995;16:103-13.
7 5. Ferencz C, Rubin JD, McCarter RJ, et al. Congenital heart
disease: prevalence at livebirth. The Baltimore-Washington
23. Sakopoulos AG, Hahn TL, Turrentine M, et al. Recurrent aortic
coarctation: is surgical repair still the gold standard? J Thorac
Infant Study. Am J Epidemiol 1985;121:31-6. Cardiovasc Surg 1998;116:560-65.
6. Burn J, Brennan P, Little J, et al. Recurrence risks in offspring 24. Kothari SS, Juneja R, Saxena A, Reddy SC, Sharma S. Balloon
of adults with major heart defects: results from first cohort of dilatation of simple aortic coarctation in neonates and infants.
British collaborative study. Lancet 1998;351:311-16. Indian Heart J 1998;50:187-92.
7. Siggers DC, Polani PE. Congenital heart disease in male and 25. Ebeid MR, Prieto LR, Latson LA. Use of balloon-expandable
female subjects with somatic features of Turner’s syndrome and stents for coarctation of the aorta: initial results and intermediate-
normal sex chromosomes (Ullrich’s and related syndromes). term follow-up. J Am Coll Cardiol 1997;30:1847-852.
British heart journal 1972;34:41-6. 26. Tyagi S, Singh S, Mukhopadhyay S, et al. Self- and balloon-
8. Miettinen OS, Reiner ML, Nadas AS. Seasonal incidence of expandable stent implantation for severe native coarctation of
coarctation of the aorta. British heart journal 1970;32:103-07. aorta in adults. Am Heart J 2003;146:920-28.
9. Loffredo CA, Chokkalingam A, Sill AM, et al. Prevalence of 27. Barreiro CJ, Ellison TA, Williams JA, et al. Subclavian flap
congenital cardiovascular malformations among relatives of aortoplasty: still a safe, reproducible, and effective treatment
infants with hypoplastic left heart, coarctation of the aorta, for infant coarctation. Eur J Cardiothorac Surg 2007;31:649-
and d-transposition of the great arteries. American journal of 53.
medical genetics Part A 2004;124A:225-30. 28. Kaushal S, Backer CL, Patel JN, et al. Coarctation of the aorta:
10. Rose V, Gold RJ, Lindsay G, et al. A possible increase in the midterm outcomes of resection with extended end-to-end
incidence of congenital heart defects among the offspring of anastomosis. Ann Thorac Surg 2009;88:1932-938.
affected parents. Journal of the American College of Cardiology 29. Kobayashi M, Ando M, Wada N, et al. Outcomes following
1985;6:376-82. surgical repair of aortic arch obstructions with associated
11. Lewin MB, McBride KL, Pignatelli R, et al. Echocardiographic cardiac anomalies. Eur J Cardiothorac Surg 2009;35: 565-68.
evaluation of asymptomatic parental and sibling cardiovascular 30. Merrill WH, Hoff SJ, Stewart JR, et al. Operative risk factors
anomalies associated with congenital left ventricular outflow and durability of repair of coarctation of the aorta in the
tract lesions. Pediatrics 2004;114:691-96. neonate. Ann Thorac Surg 1994;58:399-402; discussion -3.
12. Gutgesell HP, Barton DM, Elgin KM. Coarctation of the aorta 31. Cobanoglu A, Thyagarajan GK, Dobbs JL. Surgery for
in the neonate: associated conditions, management, and early coarctation of the aorta in infants younger than 3 months:
outcome. Am J Cardiol 2001;88:457-59. end-to-end repair versus subclavian flap angioplasty: is either
13. Tani LY, Minich LL, Hawkins JA, et al. Spectrum and influence operation better? Eur J Cardiothorac Surg 1998;14:19-25;
of hypoplasia of the left heart in neonatal aortic coarctation. discussion-6.
Cardiol Young 2000;10:90-7. 32. Karamlou T, Bernasconi A, Jaeggi E, et al. Factors associated
14. Rudolph AM, Heymann MA, Spitznas U. Hemodynamic with arch reintervention and growth of the aortic arch after
considerations in the development of narrowing of the aorta. coarctation repair in neonates weighing less than 2.5 kg. J
The American journal of cardiology 1972;30:514-25. Thorac Cardiovasc Surg 2009;137:1163-167.
15. Franklin O, Burch M, Manning N, et al. Prenatal diagnosis 33. Thomson JD, Mulpur A, Guerrero R, et al. Outcome after
of coarctation of the aorta improves survival and reduces extended arch repair for aortic coarctation. Heart 2006;92:90-
morbidity. Heart 2002;87:67-9. 4.
16. de-Wahl Granelli A, Wennergren M, Sandberg K, et al. Impact 34. Botta L, Russo V, Oppido G, et al. Role of endovascular
of pulse oximetry screening on the detection of duct dependent repair in the management of late pseudo-aneurysms following
congenital heart disease: a Swedish prospective screening open surgery for aortic coarctation. Eur J Cardiothorac Surg
study in 39,821 newborns. BMJ 2009;338:a3037. 2009;36:670-74.
17. Lewis AB, Freed MD, Heymann MA, et al. Side effects of 35. Park Y, Lucas VW, Sklansky MS, et al. Balloon angioplasty
therapy with prostaglandin E1 in infants with critical congenital of native aortic coarctation in infants 3 months of age and
heart disease. Circulation 1981;64:893-98. younger. Am Heart J 1997;134:917-23.
18. Silove ED. Pharmacological manipulation of the ductus 36. Isner JM, Donaldson RF, Fulton D, et al. Cystic medial necrosis
arteriosus. Archives of disease in childhood 1986;61:827-29. in coarctation of the aorta: a potential factor contributing to
19. Puranik R, Tsang VT, Puranik S, et al. Late magnetic resonance adverse consequences observed after percutaneous balloon
surveillance of repaired coarctation of the aorta. European angioplasty of coarctation sites. Circulation 1987;75:689-95.
journal of cardio-thoracic surgery: official journal of the 37. Fletcher SE, Nihill MR, Grifka RG, et al. Balloon angioplasty
European Association for Cardio-thoracic Surgery 2009;36: of native coarctation of the aorta: midterm follow-up and
91-5; discussion 5. prognostic factors. Journal of the American College of
20. Beekman RH, Rocchini AP, Dick M 2nd, et al. Percutaneous Cardiology 1995;25:730-34.
balloon angioplasty for native coarctation of the aorta. Journal 38. Redington AN, Booth P, Shore DF, et al. Primary balloon
of the American College of Cardiology 1987;10:1078-084. dilatation of coarctation of the aorta in neonates. British heart
21. Mendelsohn AM, Lloyd TR, Crowley DC, et al. Late follow- journal 1990;64:277-81.
up of balloon angioplasty in children with a native coarctation 39. Lock JE, Bass JL, Amplatz K, et al. Balloon dilation angioplasty
of the aorta. The American journal of cardiology 1994;74:696- of aortic coarctations in infants and children. Circulation
700. 1983;68:109-16.
22. Rao PS, Solymar L. Transductal balloon angioplasty for 40. Al-Ata J, Arfi AM, Hussain A, et al. Stent angioplasty: an
516
coarctation of the aorta in the neonate: preliminary observations. effective alternative in selected infants with critical native
American heart journal 1988;116:1558-562. aortic coarctation. Pediatric cardiology 2007;28:183-92.
41. Holzer CE, Jr. Gunshot wounds involving the abdominal aorta;
a report of two cases. Surgery 1948;23:645-52.
obstruction. Catheterization and cardiovascular interventions:
official journal of the Society for Cardiac Angiography and
34
42. Shaddy RE, Boucek MM, Sturtevant JE, et al. Comparison of Interventions 2010;76:852-59.

angioplasty and surgery for unoperated coarctation of the aorta. 55. O’Laughlin MP, Perry SB, Lock JE, et al. Use of endovascular
Circulation 1993;87:793-99. stents in congenital heart disease. Circulation 1991;83:1923-
43. Cowley CG, Orsmond GS, Feola P, et al. Long-term, 939.
randomized comparison of balloon angioplasty and surgery 56. Magee AG, Brzezinska-Rajszys G, Qureshi SA, et al. Stent
for native coarctation of the aorta in childhood. Circulation implantation for aortic coarctation and recoarctation. Heart
2005;111:3453-456. 1999;82:600-06.
44. Forbes TJ, Moore P, Pedra CA, et al. Intermediate follow-up 57. Thanopoulos BD, Hadjinikolaou L, Konstadopoulou GN, et al.
following intravascular stenting for treatment of coarctation Stent treatment for coarctation of the aorta: intermediate term
of the aorta. Catheterization and cardiovascular interventions: follow up and technical considerations. Heart 2000;84:65-70.
official journal of the Society for Cardiac Angiography and 58. Forbes TJ, Garekar S, Amin Z, et al. Procedural results and
Interventions 2007;70:569-77. acute complications in stenting native and recurrent coarctation
45. Chessa M, Carrozza M, Butera G, et al. Results and mid-long- of the aorta in patients over 4 years of age: a multi-institutional
term follow-up of stent implantation for native and recurrent study. Catheterization and cardiovascular interventions :
coarctation of the aorta. European heart journal 2005;26:2728- official journal of the Society for Cardiac Angiography and
732. Interventions 2007;70:276-85.
46. Kenny D, Margey R, Turner MS, et al. Self-expanding and 59. Qureshi AM, McElhinney DB, Lock JE, et al. Acute and
balloon expandable covered stents in the treatment of aortic intermediate outcomes, and evaluation of injury to the aortic
coarctation with or without aneurysm formation. Catheterization wall, as based on 15 years experience of implanting stents
and cardiovascular interventions: official journal of the Society to treat aortic coarctation. Cardiology in the young 2007;17:
for Cardiac Angiography and Interventions 2008;72:65-71. 307-18.
47. Butera G, Piazza L, Chessa M, et al. Covered stents in patients 60. Mahadevan VS, Vondermuhll IF, Mullen MJ. Endovascular
with complex aortic coarctations. American heart journal aortic coarctation stenting in adolescents and adults: angio-
2007;154:795-800. graphic and hemodynamic outcomes. Catheterization and
48. Tanous D, Collins N, Dehghani P, et al. Covered stents in the cardiovascular interventions: official journal of the Society for
management of coarctation of the aorta in the adult: initial Cardiac Angiography and Interventions 2006;67:268-75.
results and 1-year angiographic and hemodynamic follow-up. 61. Harrison DA, McLaughlin PR, Lazzam C, et al. Endovascular
International journal of cardiology 2010;140:287-95. stents in the management of coarctation of the aorta in the
49. Caronno R, Piffaretti G, Tozzi M, et al. Intentional coverage adolescent and adult: one year follow up. Heart 2001;85:
of the left subclavian artery during endovascular stent graft 561-66.
repair for thoracic aortic disease. Surgical endoscopy 2006;20: 62. Campbell M. Natural history of coarctation of the aorta. British
915-18. heart journal 1970;32:633-40.
50. Rehders TC, Petzsch M, Ince H, et al. Intentional occlusion 63. Cohen M, Fuster V, Steele PM, et al. Coarctation of the aorta.
of the left subclavian artery during stent-graft implantation in Long-term follow-up and prediction of outcome after surgical
the thoracic aorta: risk and relevance. Journal of endovascular correction. Circulation 1989;80:840-5.
therapy: an official journal of the International Society of 64. English KM. Stenting the mildly obstructive aortic arch: useful
Endovascular Specialists 2004;11:659-66. treatment or oculo-inflatory reflex? Heart 2006;92:1541-543.
51. Patel HT, Madani A, Paris YM, et al. Balloon angioplasty of 65. McElhinney DB, Bergersen L, Marshall AC. In situ fracture
native coarctation of the aorta in infants and neonates: is it of stents implanted for relief of pulmonary arterial stenosis in
worth the hassle? Pediatr Cardiol 2001;22:53-7. patients with congenitally malformed hearts. Cardiol Young
52. Mohan UR, Danon S, Levi D, Connolly D, Moore JW. Stent 2008;18:405-14.
implantation for coarctation of the aorta in children <30 kg. 66. Chessa M, Dua JS, Carminati M. Long-term outcome after
JACC Cardiovasc Interv 2009;2:877-83. balloon angioplasty of coarctation of the aorta in adolescents
53. Holzer RJ, Chisolm JL, Hill SL, et al. Stenting complex aortic and adults: is aneurysm formation an issue? Catheter
arch obstructions. Catheter Cardiovasc Interv 2008;71:375-82. Cardiovasc Interv 2009;74:529.
54. Bentham J, Shettihalli N, Orchard E, et al. Endovascular 67. Horlick EM, McLaughlin PR, Benson LN. The adult
stent placement is an acceptable alternative to reoperation with repaired coarctation of the aorta. Curr Cardiol Rep
in selected infants with residual or recurrent aortic arch 2007;9:323-30.
517
C hapter
35 Interruption of Aortic Arch
Vijayalakshmi IB, Prasanna Simha Mohan Rao
introduction the isthmus. This in conjunction with right-to-left flow via

the ductus to the descending aorta leads to absence of the
Interruption of the aortic arch (IAA) is defined as the isthmus.14 In patients with IAA, the right subclavian artery
congenital absence of the anatomical and luminal continuity (RSCA) is often malposed as it is also derived in part from
between the ascending and descending portions of the aorta.1,2 the fourth aortic arch. This anomaly is especially common in
It is the ultimate expression of obstructive thoracic aortic patients with IAA type B, but it can also be associated with
anomalies that begin with isthmic coarctation.3 The condition COA or can be an independent anomaly.15
is extremely rare and occurs in less than 1.5 percent of all the
congenital heart diseases (CHD).4 Prognosis of this anomaly Pathogenesis
is very poor, unless it is diagnosed and repaired during the
neonatal period. IAA is extremely rare in adults.5 The exact cause of IAA is uncertain and several theories have
been proposed. Altered hemodynamics through the fourth
Historical review aortic arch and teratogenic exposure (bis-dichloroacetyl
diamine, isotretinoin) during the intrauterine period have been
The anomaly was first described by the Viennese surgeon, proposed as its potential causes. Several mechanisms have
Raphael Steidele in 1778.6 The classification of IAA by been suggested.
Celoria and Patton7 refers to one of the three sites, two of 1. Abnormal involution of the third and fourth aortic arches.16
which were described in 1927 by Maude Abbott.8 Steidele 2. Decreased antegrade blood flow in the ascending aorta
complex is occasionally applied as an eponym to this rare due to the almost constant presence of ventricular septal
malformation, which is characterized by complete anatomic defect (VSD) and left ventricular outflow tract obstructions
discontinuity or by an atretic fibrous strand between the (LVOTO).17
aortic arch and the descending aorta.9,10 In 1955, Merrill and The malalignment of the conal septum with the resulting
his associates performed the first known surgical correction subaortic stenosis is thought to be responsible for the in utero
of type A IAA.11 The first successful one-stage correction of involution of the ascending aorta and aortic arch (fourth aortic
type A IAA was performed by Barratt-Boyes et al in 1970.12 arch) and there is reciprocal development of the pulmonary
In 1975, Trusler and Izukawa reported correction of a type B artery and ductus arteriosus (sixth aortic arch).18 The degree
IAA in a 13 day baby.13 of the subaortic stenosis is therefore inversely proportional to
the size of the ascending aorta and directly proportional to the
Embryology size of the pulmonary trunk.18,19
The IAA develops as a result of abnormal formation of Associations

the aortic arch system during the 5th to 7th week of fetal
development. The left fourth arch in the embryo forms the The IAA seldom occurs as an isolated anomaly. In 98
transverse aortic arch from the left carotid to the ductal site. percent of the cases, it is usually associated with additional
The type B and type C IAA and rarely type A is due to the cardiovascular anatomic defects. The most common
abnormalities in the formation of this area. Type A IAA can associations are patent ductus arteriosus (PDA) and VSD,
be due to the decreased flow across the arch and hence across which can be present in 97 and 90 percent of the patients
35
Interruption of Aortic Arch

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 Pathology

decrease the blood flow to the aortic arch as seen in LVOTO
including subaortic stenosis, bicuspid aortic valve and in At autopsy, the great vessels are usually related in a normal
truncus arteriosus and aortopulmonary window.20,21 The fashion. The pulmonary trunk is larger than the ascending
transposition of great arteries (TGA), double outlet right aorta, which is often hypoplastic. The ductus continues as
ventricle, functional single ventricle, can also be associated the descending thoracic aorta (DTA) and a slender cord of
with IAA. Genetic abnormalities, such as DiGeorge tissue without a lumen is the connecting interrupted segment
syndrome (chromosome 22q11.2 deletion syndrome), have (Figure 2). On the contrary, in coarctation of aorta (COA),
been found in 50 to 80 percent of patients with IAA.2,23 This the narrow segment between the left subclavian artery and
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
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
Figure 2: Autopsy specimen of aortic arch Interruption: The arch is
c. Subtype 3: Isolated subclavian artery that arises from the connected to the descending thoracic aorta (DTA) by a slender cord
ductus arteriosus. of tissue (arrow) in interrupted segment—Type A. The ductus (D)
These three types of IAA are distinct anatomical entities. continues as DTA. AA = Ascending aorta; LAA = Left atrial appendage;
Shone’s complex having multiple obstructive lesions of the LCCA = Left common carotid artery; LSA = Left subclavian artery; PT
left side of heart is implicated with this anomaly. = Pulmonary trunk; RBCA = Right brachiocephalic artery; RV = Right 519
ventricle. Image courtesy: Dr Pradeep Vaideeswar
7 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
Figure 3: Autopsy specimen of coarctation of aorta: Arrow points to condition known as reversed differential cyanosis. In neonates
the narrow coarcted segment between left subclavian artery (LSA) with significant lung disease and pulmonary hypertension due
and insertion of the ductus arteriosus*, which appears to continue as
to the pulmonary venous desaturation, reversed differential
descending thoracic aorta (DTA). There is tubular hypoplasia. AA =
Ascending aorta; LAA = Left atrial appendage; LCCA = Left common cyanosis may not be apparent. In the presence of an aberrant
carotid artery; PT = Pulmonary trunk; RAA = Right atrial appendage; right subclavian artery arising after the interruption, the
RBCA = Right brachiocephalic artery; Image courtesy: Dr Pradeep oxygen saturation measured on the right arm may not be
Vaideeswar
different from those measured in the lower extremities.15
Clinical Presentation
the insertion of the ductus arteriosus has a lumen and appears
to continue as the DTA (Figure 3). The right ventricle is The clinical presentation of IAA is similar to that in patients
hypertrophied and somewhat dilated. The parietal band of the with COA and they are usually clinically stable as long as the
crista supraventricularis is often absent. The aortic valve is PDA remains open. These neonates present on the first day
bicuspid in nearly half of the autopsied specimens.25 Other of life and become desperately ill whether they have other
multiple cardiac anomalies are usually present. major cardiac defects or not. They are in cardiogenic shock,
tachypneic, with increased work of breathing and may appear
Pathophysiology terminally ill with multiorgan dysfunction. The neonates with
PDA may survive longer than a few weeks. They may or may
The IAA is a duct-dependent anomaly. The PDA is necessary not be cyanotic, as this is dependent on the associated cardiac
for the adequate blood supply to the descending aorta. The defects.14
neonate appears ill in the first few days of life and develops
cardiogenic shock, metabolic acidosis and multiorgan Pulse
dysfunction as the spontaneous closure of the PDA occurs.
The neonates with COA present with congestive heart failure Proper examination of the peripheral pulses gives a definite
in the 2nd week of life, probably due to the presence of some clue to the diagnosis of IAA. However, the accurate
antegrade flow through the obstructed isthmus. In the setting examination of all the pulses in a very sick neonate is often
of an intact atrial and ventricular septum, the lower half of the difficult. All the pulses are well felt if the ductus is patent.
body will be supplied by the PDA with desaturated blood and If lower limb pulses are feeble with a radio femoral delay, it
differential cyanosis will be present.26 indicates the ductus is closed and patient has collaterals. If the
The pathophysiology of IAA with VSD and/or atrial septal upper limb pulses are weak then severe LVOTO, ventricular
defect (ASD) is different. A left-to-right shunt across ASD or dysfunction and/or severe aortic stenosis must be suspected.28
VSD level is present and the blood that is ejected from the If the left brachial pulse is diminished or absent, it indicates
right ventricle and shunted through the PDA to the descending that the left subclavian artery is arising from the descending
520 aorta is less desaturated than the blood in patients without aorta distal to the interruption. The weak right brachial pulses
may be present in patients with an aberrant right subclavian Aortic knob is absent. Depending on the site of interruption, 35
artery arising below the interruption. If carotid pulses are either unilateral or bilateral rib notching may be seen in
well felt, but both upper (brachial) and lower limb (femoral) older patients. Origin of one subclavian artery distal to the

pulses are feeble or absent, it indicates that the interruption is interruption produces rib notching on the contralateral side.
proximal to the left subclavian artery and the right subclavian
artery, which is anomalous in origin distal to the interruption. Imaging
If both upper limb vessels are well felt and both lower limb
vessels are poorly felt, it indicates both the subclavian arteries The echocardiography is the primary imaging technique for
are proximal to the interruption like in COA. Weak left upper characterizing cardiac abnormalities (Figures 4A and B), but it
limb and femoral pulses with normal right arm and carotid is not the optimal method by which to evaluate the aortic arch
pulses indicates type B interruption and if carotids are weak, and descending aorta, as it might not allow differentiation of
it indicates type C interruption. IAA from severe aortic coarctation with a hypoplastic arch.4
Usually there is a right ventricular type of apical impulse, The combination of echocardiography and magnetic resonance
shifted laterally. Both the heart sounds are normal. Ejection imaging (MRI) or computed tomography (CT) (Figures 5A
click is heard if the patient has a bicuspid aortic valve. to C) can enable definitive diagnosis of the interrupted aortic
Significant murmurs are not heard in infants. Usual machinery arch and associated cardiac abnormalities.1,2,23
murmur of PDA is not heard as the pulmonary trunk, ductus The diagnosis should be suspected on echocardiography
and the descending aorta are like one continuous vessel with when there is a marked difference in size between the ascending
no pressure difference or runoff. Sometimes, a loud systolic aorta and the main pulmonary artery, with a malaligned type of
murmur due to either a VSD or LVOTO is audible along with VSD with a posterior deviation of the infundibular septum. The
the features of poor systemic perfusion. morphology of the aortic arch and its branches can be visualized
from the suprasternal view.29 Simultaneous injection of contrast
Diagnosis 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
Electrocardiogram
of the thoracic aorta and great vessels and coexisting cardiac
The electrocardiogram (ECG) changes are different in the two anomalies. In addition, MRI can also provide useful information
groups of patients, the highly symptomatic neonate and the regarding cardiac chamber and valve function. Multiple MRI
asymptomatic older children. The ECG shows right axis devi- techniques can be used to evaluate the thoracic aorta and heart in
ation, right atrial enlargement, right ventricular hypertrophy. cases of suspected IAA. MRI sequences can be performed both
Rarely biventricular hypertrophy is seen if there is an associ- with and without intravenous gadolinium-containing contrast
ated large VSD. Rarely QT interval may be prolonged, if there material. Unenhanced evaluation may include double, inversion
is a associated DiGeorge syndrome with hypocalcemia. recovery fast spin-echo ‘black-blood,’ gradient-recalled echo
‘white blood’ and balanced [e.g. 2D and 3D balanced-steady
Chest Radiography state free precession (SSFP)] imaging sequences.1
The chest X-ray demonstrates cardiomegaly, with right Preoperative Management

ventricular and right atrial enlargement. The pulmonary artery
is prominent. Pulmonary vascularity is increased or normal The preoperative management of IAA is similar to that of
depending on the presence or absence of intracardiac shunt. critical COA. The neonate has to be treated promptly with
A B
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 521
artery.
7
A B C
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 tissue is removed and the left common carotid artery can
and acidosis should be treated. The goal of therapy is to also be turned down after division. The distal left common
maintain optimal descending aorta perfusion with right-to-left carotid artery is anastomosed to the right carotid artery.
shunting across the PDA. This can be monitored by physical Associated defects should be addressed. Care should be
examination (peripheral pulses, perfusion and urine output). taken to use irradiated blood in patients with associated
A preductal saturation above 90 percent and a postductal DiGeorge syndrome. Patients with an associate single
saturation of approximately 70 percent signifies good gas ventricle physiology will require arch reconstruction and a
exchange and appropriate distribution of the cardiac output.28 pulmonary artery band to limit pulmonary blood flow, to
Once the neonate has been stabilized, surgical correction allow the patient to go through a staged Fontan pathway.
should be contemplated as soon as possible. Type A interruption can be treated like a coarctation and
after mobilization, anastomosis can be done after excising
Surgery the ductal tissue. A reverse left subclavian flap can be used to
reconstitute the arch (Figure 6).
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
Figure 6: Interruption (Type A) repaired with a subclavian artery turn
the cerebral vessels. The ductus is divided and all ductal down and augmentation with a Gore-Tex patch via a left thoracotomy
522
Prognosis Congenital Heart Disease, 6th edition. Philadelphia. Saunders, 35
The IAA is invariably a fatal illness, with death occurring an imprint of Elsevier Inc. 2012. pp. 101-128.
within days of birth. If the condition is left untreated, 90 4. Collins-Nakai RL, Dick M, Parisi-Buckley L, et al. Interrupted

percent of the affected neonates die at a median age of 4 days.4 aortic arch in infancy. J Pediatr. 1976;88:959-62.
Type B IAA, major associated cardiac anomalies, low-birth 5. Messner G, Reul GJ, Flamm SD, et al. Interrupted aortic arch
in an adult single-stage extra-anatomic repair. Tex Heart Inst J.
weight and young age at presentation are the chief risk factors
2002;29:118-21.
for death and the associated cardiac anomalies are the main
6. Steidele RJ. Sammlung Verschiedener in der chirurgisch
predictor of the outcome. Praktik: Lehrschule Germachten Beobb. 1777;2:114-16.
Early mortality is related to the patient’s condition, as well 7. Celoria GC, Patton RB: Congenital absence of the aortic arch.
as the associated anomalies and early mortality with a one Am Heart J. 1959;58:407-13.
stage repair is between 10 to 20 percent. The overall survival 8. Abbott ME. Congenital cardiac disease. Osler’s modern
at 16-years has been found to be 59 percent in patients medicine. Philadelphia: Lea and Febiger; 1927.
with interrupted aortic arch; the survival rate increased to 9. Lie JT. The malformation complex of the absence of the arch
approximately 70 percent in patients who had undergone of the aorta—Steidele’s complex. Am Heart J. 1967;73:
preoperative therapy and appropriate surgical techniques.28 615-25.
10. Takashina T, Ishikura Y, Yamane K, et al. The congenital
Patients with associated truncus arteriosus can have an early
cardiovascular anomalies of the interruption of the aorta—
mortality of upto 67 percent in multicentric reports.
Steidele’s complex. Am Heart J. 1972;83:93-99.
11. Merrill DL, Webster CA, Samson PC. Congenital absence of
Conclusion the aortic isthmus; report of a case with successful surgical
repair. J Thorac Surg. 1957;33:311-20.
The IAA is a very rare CHD, which commonly appears in the 12. Barratt-Boyes BG, Nicholls TT, Brandt PW, et al. Aortic
newborns as a critical disease and leads to death very early arch interruption associated with patent ductus arteriosus,
in life without surgical palliation or total repair. IAA is rarely ventricular septal defect and total anomalous pulmonary
encountered in an adult. Echocardiography with multislice venous connection. Total correction in an 8-day-old infant by
CT angiography appears to be a useful combined diagnostic means of profound hypothermia and limited cardiopulmonary
by pass. J Thorac Cardiovasc Surg. 1972;63:367-73.
imaging method in patients with this congenital anomaly. The
13. Trusler GA, Izukawa T. Interrupted aortic arch and ventricular
accurate and early diagnosis of interrupted aortic arch and its septal defect. Direct repair through a median sternotomy incision
associated cardiovascular anomalies is profoundly important in a 13-day-old infant. J Thorac Cardiovasc Surg. 1975;69:126-31.
for the patient’s survival. 14. Keane JF, Fyler. Coarctation of aorta. In: Keane JF, Lock
JE, Fyler DC (Eds) Nadas’ Pediatric Cardiology. Saunders,
Nature, time and patience are the three great physicians. Philadelphia, PA; 2006. pp. 627-44.
—HG Bohn 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.
Acknowledgments pp. 641-48.
16. Conley ME, Beckwith JB, Mancer J, et al. The spectrum of the
The authors thank Dr Pradeep Vaideeswar, Professor DiGeorge syndrome. J Pediatr. 1979;94:883-90.
(Additional), Department of Pathology (Cardiovascular and 17. Rudolph A, Hoffman J. Rudolph”s Pediatrics. 18th edition.
Thoracic Division), Seth GS Medical College, Mumbai, Appleton and Lange; Norwalk, CT: 1987. pp. 1382-63.
India for the nice pictures of the pathological specimens of 18. Luciani GB, Ackerman RJ, Chang AC, et al. One-stage
IAA and COA and to Dr Hala ElMarsafawy, Professor of repair of interrupted aortic arch, ventricular septal defect,
Pediatrics and Pediatric Cardiology, Director of Cardiac and subaortic obstruction in the neonate: a novel approach. J
Catheterization Laboratory, Children Hospital, Mansoura Thorac Cardiovasc Surg. 1996;111:348-58.
19. Konstantinov IE, Karamlou T, Blackstone EH, et al. Truncus
University, Mansoura, Egypt for the CT images. Also to Mr P
arteriosus associated with interrupted aortic arch in 50
Madhusudan for the good schematic diagram. neonates: a Congenital Heart Surgeons Society study. Ann
Thorac Surg. 2006;81:214-22.
References 20. Reardon MJ, Hallman GL, Cooley DA. Interrupted aortic arch:
brief review and summary of an eighteen-year experience. Tex
1. Dillman JR, Yarram SG, D’Amico AR, et al. Interrupted Heart Inst J. 1984;11:250-59.
aortic arch: spectrum of MRI findings. AJR Am J Roentgenol. 21. Ho SY, Wilcox BR, Anderson RH, et al. Interrupted aortic arch:
2008;190:1467-74. anatomical features of surgical significance. Thorac Cardiovasc
2. Mishra PK. Management strategies for interrupted aortic Surg. 1983;31:199-205.
arch with associated anomalies. Eur J Cardiothorac Surg. 22. Everts-Suarez EA, Carson CP. The triad of congenital absence
2009;35:569-76. of aortic arch (isthmus aortae), patent ductus arteriosus and
3. Perloff JK, Marelli AJ. Coarctation of the aorta and interrupted interventricular septal defect; a trilogy. Ann Surg. 1959; 523
aortic arch. Perloff JK, Marelli AJ. Clinical Recognition of 150:153-9.
7 23. Yang DH, Goo HW, Seo DM, et al. Multislice CT angiography
of interrupted aortic arch. Pediatr Radiol. 2008;38:89-100.
27. Muñoz R, Tsifansky M, Morell VO. Interrupted Aortic Arch.
In: Muñoz R, Morell VO, Cruz EM, VetterlyVO (Eds). Critical
24. Goo HW, Park IS, Ko JK, et al. CT of congenital heart Care of the Children with Heart Disease. Springer-Verlag
disease: normal anatomy and typical pathologic conditions. London Limited; 2010. pp. 267-72.
Radiographics. 2003;23:S147-65. 28. McCrindle BW, Tchervenkov CI, Konstantinov IE, et al.
25. Arey JC. Cardiovascular Pathology. Philadelphia: WB Risk factors associated with mortality and interventions
Saunders 1981. in 472 neonates with interrupted aortic arch: a Congenital
26. Matsui H, Adachi I, Uemura H, et al. Anatomy of coarcta- Heart Surgeons Society study. J Thorac Cardiovasc Surg.
tion, hypoplastic and interrupted aortic arch: relevance to 2005;129:343-50.
interventional/surgical treatment. Expert Rev Cardiovasc Ther. 29. Pongiglione G. Aortic arch interruption. Orphanet Encyclope-
2007;5:871-80. dia. Februrary 2004.
524
c hapter
Vascular rings, slings

36 and other Anomalies
Maitri Chaudhuri
IntroductIon artery. They form an additional location of vascular ring

(Figure 1).
Vascular rings are developmental abnormalities of the aortic During normal development, the left arch and left ductus
arch system, where vascular structures encircle and compress persist whereas the right aortic arch, distal to the origin of right
the tracheobronchial tree and esophagus. Anatomically, this subclavian artery (RSA) and the right ductus regress (Figures
encirclement may be complete or incomplete. By convention, 2A and B). As a result, the proximal part of the embryological
we call it as ‘vascular ring’ when the encirclement is complete right arch forms the brachiocephalic (innominate) artery,
and ‘vascular sling’ when it is incomplete.1,2 which bifurcates into the right common carotid artery (RCCA)
and RSA. The embryological left aortic arch gives rise, in
HIstory 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 Figure 1: This schematic diagram shows the hypothetical model for
by symmetrical arches on each side, thus forming a complete double aortic arch as proposed by Jesse Edwards. LAA = Left aortic
vascular ring around trachea and esophagus. Each arch gives arch; LCCA = Left common carotid artery; LPA = Left pulmonary
artery; LSA = Left subclavian artery; PT = Pulmonary trunk; RAA =
origin to ipsilateral common carotid and subclavian arteries.
Right aortic arch; RCCA = Right common carotid artery; RPA = Right
Also on each side, corresponding ductus arteriosus is located pulmonary artery; RSA = Right subclavian artery. Courtesy: Reprinted
connecting the ipsilateral pulmonary artery and subclavian with permission from reference 1
7 Abnormal development
By following this model, the abnormalities can be either
Diseases oF the aorta
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 1. Left aortic arch with aberrant right subclavian or brachio-
the segments that regress. Courtesy: Reprinted with permission from cephalic artery and left sided ductus.
reference 1 2. Right aortic arch with aberrant left subclavian or brachio-
cephalic 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
Here the ascending aorta arises normally, but as it leaves the
pericardium, it bifurcates into left and right arches, on either
Figure 2B: This schematic diagram illustrates that in continuation of
Figure 2A, the disappearance of right aortic arch distal to the origin of side of trachea and then they join posteriorly to form the
the right subclavian artery (RSA), along with right sided ductus. LAA descending aorta. The left arch passes anteriorly and to the left
= Left aortic arch; LCCA = Left common carotid artery; LPA = Left of trachea and is joined by left ductus, where it becomes the
pulmonary artery; LSA = Left subclavian artery; PT = Pulmonary trunk;
descending aorta. The right arch passes to the right and then
RAA = Right aortic arch; RBA = Right brachiocephalic artery; RCCA =
Right common carotid artery; RPA = Right pulmonary artery. Courtesy: posterior to esophagus to join the left sided descending aorta,
Reprinted with permission from reference 1 thereby completing the vascular ring6 (Figures 3A and B).
526
are equal (balanced) and in remaining 25 percent, the left arch 36
is dominant (left dominant). The apex of the larger arch is
located at a higher level. In the usual right dominant arch, the
Vascular rings, slings anD other anomalies

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
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

Embryology: Mirror image branching arises due to abnormal
regression of embryonic left arch distal to the origin of LSA
Figure 3a: This computed tomography angiogram shows the balanced
type of double aortic arch with ascending aorta bifurcating into right
(Figures 4A and B). The usual branching pattern is as follows—
and left aortic arches. Each arch is giving rise to ipsilateral common first branch—left brachiocephalic artery bifurcating into LSA
carotid and subclavian arteries. AAo = Ascending aorta; LAA = Left and LCCA, second branch—RCCA, third branch—RSA
aortic arch; LCCA = Left common carotid artery; LSA = Left subclavian (Figures 4C and D). This is particularly common with TOF
artery; RAA = Right aortic arch; RCCA = Right common carotid artery;
RSA = Right subclavian artery.
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
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
Figure 4a: The schematic diagram shows the hypothetical double 527
percent of cases, the right arch is larger than the left and is arch model with the two red bars showing the segments that regress.
called right dominant. In 25 percent of cases, the two arches Courtesy: Reprinted with permission from reference 1
7
Figure 4B: In majority of cases, the left sided ductus persists and the Figure 4D: This computed tomography (CT) angiogram depicts a right
left aortic arch regresses distal to the origins of left subclavian artery aortic arch with mirror image branching pattern in a 20-year-old lady
(LSA) and the left ductus, along with the right sided arterial ductus. After with tetralogy of Fallot with aortopulmonary collaterals from left internal
birth, the left sided ductus connects the base of left brachiocephalic mammary artery. LCA = Left carotid artery; LIA = Left innominate
or subclavian artery to the left pulmonary artery. Persistence of right artery; LSA = Left subclavian artery; MAPCA = Major aortopulmonary
sided arterial ductus is uncommon. LBA = Left brachiocephalic artery; collaterals; RCA = Right carotid artery; RSA = Right subclavian artery;
LCCA = Left common carotid artery; LPA = Left pulmonary artery; PT Courtesy: Reprinted with permission from Dr Aysel Turkvatan, Ihtisas
= Pulmonary trunk; RAA = Right aortic arch; RCCA = Right common Hospital, Turkey, Korean J Radiol. 2009;10:176-84
carotid artery; RPA = Right pulmonary artery; RSA = Right subclavian
artery; Courtesy: Reprinted with permission from reference 1
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
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
Figure 4c: This schematic diagram shows the usual branching (ALSA) as the fourth branch. The persistent arterial ductus is
pattern in right aortic arch with mirror image branching. 1st branch: usually left sided (Figure 5C).
left brachiocephalic artery bifurcating into left subclavian (LSA) and left
common carotid artery (LCCA), 2nd branch: right common carotid artery
This is the second most common type of vascular ring;
(RCCA), 3rd branch: right subclavian artery (RSA). AAo = Ascending however, they are usually loose when compared to the double
aorta; LIA = Left innominate artery; LPA = Left pulmonary artery arch. Associated cardiac anomalies are rare.12
528
36

Figure 5a: This schematic diagram shows the morphogenesis of Figure 5B: In the postnatal circulation, consequent to the closure of
a right aortic arch with aberrant origin of left subclavian artery and a the arterial ductus, the proximal part of the aberrant LSA, representing
left sided arterial ductus. The hypothetical model of the double arch the distal remnant of the left aortic arch usually persists, as the so-
is shown with the red bars indicating the segments that will regress. called diverticulum of Kommerell. LAA = Left aortic arch; LCCA =
LAA = Left aortic arch; LCCA = Left common carotid artery; LPA = Left Left common carotid artery; LPA = Left pulmonary artery; LSA = Left
pulmonary artery; LSA = Left subclavian artery; PT = Pulmonary trunk; subclavian artery; PT = Pulmonary trunk; RAA = Right aortic arch ;
RAA = Right aortic arch; RCCA = Right common carotid artery; RPA RCCA = Right common carotid artery; RPA = Right pulmonary artery;
= Right pulmonary artery; RSA = Right subclavian artery. Courtesy: RSA = Right subclavian artery. Courtesy: Reprinted with permission
Reprinted with permission from reference 1 from reference 1
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
7
a B
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 between origins of RCCA and RSA and disappearance of right
Persistent Right Ductus 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 with aberrant left subclavian artery with right aortic arch take a retroesophageal course. Previously this
persistent right ductus is a rare anomaly embryologically anomaly was called ‘arteria lusoria’. Usually the left ductus
explained by abnormal regression of left arch segment persists in this case and therefore an incomplete vascular ring
between LSA and LCCA and disappearance of left ductus and arises.
persistence of right ductus (Figures 6A and B).
This produces an incomplete encirclement or vascular Morphology
sling around right side of trachea and esophagus.
The right subclavian artery originates as the last vessel of
Right Aortic Arch with Aberrant Origin of Left Brachio- the aortic arch, from the junction of the aortic arch with the
cephalic Artery descending aorta. If the right ductus persists and the left one
disappears, then a complete vascular ring will be produced. The
This is rare and arises from abnormal regression of left arch ARSA courses behind the esophagus in 80 percent of cases,
segment proximal to LCCA with persistent left ductus. Again between esophagus and trachea in 15 percent, and anterior
this produces a complete vascular ring. to trachea in remaining 5 percent (Figure 7C). The aberrant
subclavian artery is usually an isolated malformation, although
left Aortic Arch with Aberrant right subclavian Artery it is associated with cardiac malformations in 12 percent of
with Persistent left ductus cases. The most frequent associated anomalies are TOF, aortic
coarctation, and interruption of the aortic arch.12
Left aortic arch with aberrant right subclavian artery with
persistent left ductus (PLD) is the most common anomaly of circumflex Aortic Arch
the aortic arch; however, it is usually asymptomatic.
Circumflex aortic arch is a rare anomaly, where the aortic arch
Embryology and the proximal part of descending aorta are on contralateral
sides of the spine. Here, the aortic arch makes an additional
530 Aberrant right subclavian artery (ARSA) with PLD occurs arch posterior to trachea and esophagus to reach the descending
when the embryological right arch has an abnormal regression aorta13 (Figures 8A and B).
36

a B
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. cervical Arch
The pattern of branching is as follows: 1st branch—LCCA,
2nd and 3rd branches—RCCA and RSA respectively and the The arch is called cervical when its apex reaches into the neck
terminal branch is the LSA arising at the point of transition above the clavicles. This produces a pulsatile swelling in the
of the retroesophageal arch to the left sided descending aorta. neck. This can be associated with a retroesophageal arch or even 531
Hypoplasia of the retroesophageal segment of the arch is double aortic arch. This produces overcrowding of structures
common. within the narrow neck and causes respiratory compression.14
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
natural History
are on opposite sides of the spine. The aortic arch passes posterior
to trachea and esophagus to reach the descending aorta. LCCA = Untreated severe respiratory obstruction, especially starting
Left common carotid artery; LSA = Left subclavian artery; LVA = Left soon after birth, is fatal before the child reaches his first
vertebral artery; PT = Pulmonary trunk; RCCA = Right common carotid birthday. Symptoms first presenting after 6 months of age are
artery; RSA = Right subclavian artery; RVA = Right vertebral artery.
Courtesy: Reprinted with permission from reference 1
less severe and rarely progressive, except when active chest
infection or aspiration occurs. Borderline symptoms may
disappear with growth of the child.16
Symptoms
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.
Figure 8B: This 3D reconstructed computed tomography (CT) • Hoarse cry.
angiogram shows a circumflex aortic arch. AAo = Ascending aorta;
DAo = Descending aorta; * = Retroesophageal circumflex arch • Persistent barking cough—‘seal bark’ cough17
• Apnea especially in children with brachiocephalic artery
compression and in those with complete tracheal rings.
B. Manifestations due to esophageal obstruction:
clInIcAl PrEsEntAtIon oF VAsculAr rIngs • Dysphagia usually to solids. This may be caused by
aneurysmal dilatation of diverticulum of Kommerell or
Epidemiology elongation of aorta.
• Frequent aspiration pneumonitis
Vascular rings of aortic origin represent 1 to 3 percent of • ‘Dysphagia lusoria’—difficulty in swallowing due to trick
all congenital heart diseases, although exact incidence may of nature. In 1761, David Bayford performed autopsy on
be underestimated.15 ARSA is the most common anomaly a 63-year-old woman with lifelong swallowing problems
532 (0.5% of autopsy series). The incidence is especially high and noted an ARSA coursing posterior to esophagus and
(38%) among Trisomy 21 children with heart disease. thereby indenting it. He opined that this abnormal course
of the artery caused deglutition problems and coined the dIAgnostIc WorKuP 36
term ‘dysphagia lusoria’.
The ARSA is usually asymptomatic and occurs in 1 in chest X-ray

200 individuals. It usually does not cause stridor in infants.
However, if complications like aneurysmal transformation The points to look for in suspected vascular rings are:18,19
or ectasia develop, deglutition problems are more likely a. Laterality of arch in posterioanterior view: The tracheal
(Figures 9A and B). 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.
barium Esophagogram
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
Figure 9a: This schematic diagram shows the mechanism of oblique, left anterior oblique views are fundamental (Figures
dysphagia lusoria, where an aberrant right subclavian artery courses 11A to C).
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.
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. 533
radiologyassistant.nl/en/
7
a B c
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
a B c
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 Echocardiogram

vascular rings and sling20
Echocardiogram is an important noninvasive, nonionizing,
Anterior tracheal Posterior Vascular ring,
indentation esophageal likely double arch widely available modality for definitive diagnosis of aortic
indentation or RAA with ALSA arch anomalies.21-23
and persistent left a. Which view? The ‘suprasternal short axis view,’ where
ductus transducer is placed horizontally in the suprasternal notch
Normal trachea Posterior ARSA with left arch with an extended neck. Start with a downward angulation
esophageal (dysphagia lusoria) and then gently sweep upwards to acquire the best view for
indentation diagnosing aortic arch anomalies.
Posterior tracheal Anterior Pulmonary arterial The ascending aorta, transverse and descending
indentation esophageal sling thoracic aorta are best visualized in the ‘suprasternal
534 indentation
long axis view’. To obtain this view, the transducer
Anterior tracheal Normal esophagus Abnormal is placed in the suprasternal notch with the plane of
indentation brachiocephalic
ultrasound beams oriented between the right nipple and
artery
the left scapular tip.
b. What to look for? The position of the aortic arch in relation magnetic resonance Imaging24,25 36
to tracheal rings and the origin and branching pattern of the
arch vessels. Magnetic resonance (MR) angiography is an alternative

c. The different echocardiographic patterns (Box 2) (Figures non-invasive tool without the need for contrast material or
12A to E): radiation exposure. However, this is time-consuming and
requires prolonged sedation in pediatric patients. Although
Box 2: Various echocardiographic patterns in aortic arch anomalies MR delineates the vascular anatomy excellently, the
technique gives limited information about airways and
First branch of Then first branch Normal left aortic
esophagus.
aortic arch to bifurcates into two: right arch
right subclavian and right
common carotid artery bronchoscopy
First branch of Then 1st branch Right aortic arch
aortic arch to bifurcates into two: with mirror image Bronchoscopy is rarely done to identify the sites of vascular
left left subclavian and left branching compression. For example, rigid bronchoscopy in brachio-
common carotid artery cephalic artery syndrome shows compression from an ante-
Left or Right But first branch does not Aberrant rior pulsating mass and the compression progresses from most
arch bifurcate subclavian artery severe on the right to less severe on the left, following the
four arch vessels (suspect vascular course of brachiocephalic artery as it passes from the right to
demonstrated ring)
left. Pressing the bronchoscope anteriorly against the tracheal
Double circle Tracheal ring in center Double aortic wall will typically suppress the right radial or right carotid
arch (suspect arterial pulses.16,18
vascular ring)
Pulsatile mass Transducer positioned Cervical arch
in neck over mass and long mAnAgEmEnt
axis view shows long
ascending aorta medical
Medical care is supportive and limited to treatment of
cardiac catheterization and Angiography hypoxemia, recurrent pulmonary infections and supervised
Although once considered a gold standard, it role has been feeding. Surgery is indicated in all symptomatic patients, as
largely limited now-a-days by the advent of newer diagnostic mortality rates of 90 percent has been reported with isolated
modalities. The arch anatomy, branch vessels, aberrant medical management.26
courses and hemodynamic data can be very clearly inferred,
but it gives limited information regarding type and level of surgical
tracheobronchial and esophageal compression.
Precise diagnosis is very important for appropriate life Indications
saving management strategy. In this direction echocardio-
graphy may not be adequate. Hence, angiogram and computed The simple existence of vascular ring per se is not an
tomographic angiogram could be more informative (13 A to C). indication for surgery as the child may outgrow the symptoms
with increasing age and consequent increase in chest and neck
computed tomogram23,24 dimensions. However, presence of recurrent apneic spells,
pulmonary infections and persistent respiratory distress are
Multislice CT angiograms gives us excellent information definite indications for surgery. Other potential complications
regarding both vascular structures and airways. One added of unrepaired lesions include aortic aneurysm and dissection.27
advantage is the need for minimal sedation. The real challenge The various surgical procedures in vascular rings is given in
is to take images of diagnostic quality with lowest possible Box 3.28
doses of radiation. Use of 3D reconstruction allows more
elaborate spatial orientation and provides a definite road timing of surgery
map for surgery. However, a significant discrepancy in the
assessment of severity of airway narrowing between routine The decision regarding when to operate depends on the
CT and bronchoscopy is often found. This is because routine severity of symptoms and can be done in infancy for the most
CT fails to assess the dynamic changes in airway lumen severe cases. However, infants with minimal symptoms and
between inspiration and expiration and children often fail to without significant respiratory obstruction can be managed
follow the instructions to hold breath or exhale! medically.
535
7
a B c
D e
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.
a B
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 pulmonary artery (MPA), arises extrapericardially from the 36
posterior aspect of right pulmonary artery (RPA) and then
Double aortic arch Division of the smaller of the two
takes a hairpin bend towards the left lung in the space between

arches or the atretic arch by left
thoracotomy. trachea and esophagus. As a consequence, a vascular sling is
formed around the right side of trachea (Figure 14). This is
Right aortic arch and left Ligation and division of
ligamentum arteriosum Ligamentum by left thoracotomy. almost always associated with congenital tracheal stenosis
Kommerell diverticulum, if found, and complete cartilaginous tracheal rings with absence of pars
is ligated and left subclavian artery membranaceae posteriorly.30
is transferred to left carotid artery
by left thoracotomy
History
Left aortic arch and right Similar concept as above by right
ligamentum arteriosum thoracotomy. Pulmonary arterial sling was first described in 1897 by
Anomalous Suturing of innominate artery to Glaevecke and Doehle during an autopsy of a 7-month-
brachiocephalic artery posterior sternum through right old baby, who died due to asphyxia.31 In 1958, Contro and
anterolateral thoracotomy
colleagues coined the term vascular sling to distinguish the
Circumflex Through midline sternotomy, the condition from vascular ring.32 Much later, Berdon et al
retroesophageal aortic retroesophageal part of arch is introduced the phrase ring-sling complex to emphasize the
arch divided and the mobilized aortic
arch is translocated to the other
often coexisting tracheal anomaly.33
side of trachea and anastomosed
to the descending aorta. Pathophysiology
Aberrant right subclavian Usually no treatment is required
artery 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
Box 4: Surgical Results (Excluding Associated Complete
Tracheal Rings)28
hypoplasia of right lung and compensatory emphysema of
left lung. Sixty-five percent of patients have diffuse tracheal
Number of patients Mortality (%)
stenosis, complete rings and tracheomalacia.33 Conversely,
Van Son (1994) 39 2.6 one-third of patients with complete tracheal rings have
Backer (1993) 249 3.6 associated pulmonary arterial slings. In addition, patients
Chun (1992) 39 5.1 often have right and less frequently, left bronchomalacia.
Azarow (1992) 21 4.8
An interesting feature seen in fourth-fifth of patients is
abnormal branching of tracheobronchial tree.33 Typically
Marmon (1984) 54 1.9
the trachea bifurcates into right and left bronchus at a
Roesler (1983) 51 3.9 lower level and with a wide angle between them producing
Arcinegas (1979) 53 3.8 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
special Postoperative care28,29 low inverted T bifurcation of airways, with or without a
Aggressive respiratory care is the key to success in post- separate origin of right upper lobe bronchus are associated
operative period in small infants. Use of continuous positive with narrowing of a long segment of lower airways above
airway pressure (CPAP) with infant breathing spontaneously the bifurcation. Rarely, the sling is associated with agenesis
is advantageous. Post extubation, continued use of warm of right lung.
and humidified oxygen administered by nasal prongs, chest
physiotherapy and gentle meticulous suctioning help to keep Associations
the airway patent and mucosa undamaged The surgical results
of procedures done in vascular rings from various series, is Fifty percent of these children have cardiac abnormalities
given in Box 4.28 mainly atrial septal efect, ventricular septal defect, patent
ductus arteriosus (PDA), TOF and left superior vena cava.
PulmonAry ArtErIAl slIng The PDA when present connects MPA to descending aorta
on left side of trachea and completes a vascular ring. The
definition anomalous LPA is often relatively hypoplastic than the
RPA. The extracardiac anomalies seen are imperforate anus,
Pulmonary arterial sling is a congenital anomaly, where the congenital megacolon, biliary atresia and genitourinary
left pulmonary artery (LPA), instead of arising from the main abnormalities.1 537
7 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 Echocardiogram36,37
arterial (PA) sling where the left pulmonary artery arises from the right
pulmonary artery instead of the pulmonary trunk. It also shows a left a. Continuation of MPA as RPA without normal origin of
sided ligamentum arteriosum connecting the left pulmonary artery to
the descending aorta. LPA = Left pulmonary artery; PT = Pulmonary LPA in parasternal short axis view. The other differential
trunk; RPA = Right pulmonary artery. Courtesy: Reprinted with diagnosis of this are absent LPA and aberrant origin of LPA
permission from reference 1 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.
clinical manifestations
Pulmonary arterial sling often presents within infancy, more Cardiac Catheterization and Angiography
among males with obstructive respiratory symptoms like
stridor, wheezing and cough. Symptoms due to esophageal Although sparingly used now-a-days, this was a gold standard
compression are less common. in past. Angiography with injection of radiocontrast in
a B
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
538
36

Figure 16: This echocardiogram in high left parasternal short axis view Figure 17: This angiogram shows the classical appearance of
reveals that the main pulmonary artery (MPA) continues as the right pulmonary arterial sling in angiography, where the left pulmonary
pulmonary artery (RPA), without giving rise to a normal left pulmonary artery (LPA) arises from the right pulmonary artery (RPA) and
artery (LPA). The LPA arises from the RPA behind the ascending then takes a tortuous circuit towards the hilum of the left lung.
aorta. The LPA then makes a hairpin turn to the left side, encircling the PT = Pulmonary trunk
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.
MPA in a steep oblique view with cranial angulation of 60º of tracheobronchial involvement and efficacy of the surgery
to 70º elucidates the origin and course of anomalous LPA done. Postoperatively, it is used to assess the tracheal surgery,
(Figure 17).38 cause of endotracheal tube bleeding, cause of prolonged
ventilation etc.33
Computed Tomography with Three-Dimensional
Reconstruction management of Pulmonary Arterial sling
Computed tomography with three-dimensional reconstruction Medical
is especially important for all suspected cases of ring-sling
complex as it beautifully demonstrates both the vascular a. General supportive care and treatment of chest infections.
and airway abnormalities. It guides the surgeon to plan b. Symptomatic children should undergo surgical correction
the appropriate surgical therapy (Figure 18). Furthermore, without delay.29,39
complications of the pulmonary parenchyma like collapse-
consolidation, hyperinflation etc. can also be assessed. Surgical
Magnetic Resonance Imaging In 1954, Willis Potts reported the first surgical repair for
pulmonary arterial sling from children’s hospital, Chicago.
Magnetic resonance imaging (MRI) is probably less useful a. The surgical repair involves division and mobilization of
than CT in this respect as it is time-consuming, requires LPA from its origin in RPA and reimplantation of the LPA
sedation and anatomical details of airways and lungs are not into MPA and resection of all ductal tissue (Figure 19A).
elucidated as good as CT here. The usual approach is through median sternotomy and
after establishment of cardiopulmonary bypass.40,41
Bronchoscopy b. The tracheal stenosis also needs to be corrected if more
than mild in severity. The various approaches are:
In many centers, a preoperative bronchoscopy is part of the i. Short segment tracheal stenosis: Simple resection and
investigational protocol. Often external imaging of the trachea end-to-end anastomosis.
may not show internal abnormalities like complete rings. ii. Long segment stenosis: Tracheoplasty using a part of
Bronchoscopy informs us about the level, length and degree rib cartilage or pericardial patch (Figure 19B). In a
of luminal narrowing and allows precise surgical planning. long trachea, a piece of narrow segment from trachea
Also intraoperatively, it allows the surgeon to gauge the extent is resected and then the same segment can be used to 539
7
Figure 19a: This schematic diagram shows the principle of surgical

Figure 18: This computed tomography angiogram shows the pulmo-
management of pulmonary arterial sling. The origin of left pulmonary
nary arterial sling with anomalous origin of left pulmonary artery (LPA)
artery (LPA) from the right pulmonary artery (RPA) is transected
with abnormal tracheobronchial branching and stenosis. MPA = Main
and the RPA opening is repaired with interrupted prolene sutures.
pulmonary artery.
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
augment the tracheal lumen. This procedure is called from reference 29
tracheal autograft41 and considered superior to other
autologous patch materials (Figure 19C).
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 Figure 19B: This schematic diagram shows the pericardial tracheo-
of reimplanted LPA. Marmon et al studied 17 asymptomatic plasty technique. The trachea is opened anteriorly through the area
of complete tracheal rings. On cardiopulmonary bypass support,
patients at a mean 6.1 years after surgery.25 No correlation was the trachea is patched with autologous fresh pericardium anchored
found between age of diagnosis and surgery, type of vascular with interrupted sutures. Courtesy: Reprinted with permission from
lesion, or severity of presenting symptoms and abnormal reference 29
pulmonary function test. More long-term data is desirable,
using objective quantification of respiratory function, before
confirming the eventual curative nature of surgery.
arch far on the left side of midline and then courses to the
otHEr cAusEs oF VAsculAr comPrEssIon right and thus compresses the anterior wall of trachea. This
oF AIrWAys42,43 produces respiratory symptoms from stridor, cyanosis and
bradycardia. However, the symptoms are noted only if there is
a coexisting crowded superior mediastinum, either secondary
brachiocephalic Artery compression of Airways
to cardiomegaly or dilated vessels, etc. The treatment in severe
540 Brachiocephalic artery compression of airways is a condition, cases involves surgical suturing of brachiocephalic artery to
where the brachiocephalic artery arises from the aortic sternum (Figures 20A and B) .
36

Figure 19c: This schematic diagram shows the principle of using
tracheal autograft. The trachea is opened anteriorly through the area Figure 20a: This schematic diagram shows the brachiocephalic
of complete tracheal rings. The mid-portion of the stenotic trachea or innominate artery arising from the left side of midline and then it
(usually 6–8 rings, 1.5–2.0 cm) is resected to be used later as the courses in front of trachea and compresses the trachea. The arrow
autograft. Courtesy: Reprinted with permission from reference 29 shows the level of compression of the trachea
Absent Pulmonary Valve syndrome compresses the right pulmonary artery, which in turn presses
This entity, most commonly associated with TOF, is associated on the left and right main bronchus (Figure 21).
with aneurysmally dilated pulmonary arteries, which exert
direct mechanical compression of tracheobronchial tree. In Elongated Aortic Arch
addition, the tracheobronchial tree is often inherently abnormal
including abnormal branching pattern, abnormal alveolar The classic example is right aortic arch in congenitally
architecture, etc. Surgical correction includes not only an corrected transposition. Here, the ascending aorta is
intracardiac repair but also plication and anterior translocation L-posed and ascends to the left and then takes a long
of pulmonary arteries. transverse course in front of trachea to connect to the
descending aorta in the right posterior mediastinum. Once
Posteriorly displaced Ascending Aorta the lungs are hyperinflated, they extend to the midline
behind sternum, pushing the mediastinal structures and
In this situation, the displaced ascending aorta may directly heart backward, further compromising the tracheal and
compress on the right side of trachea.The posterior aorta also 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 541
subclavian artery. The white arrow shows the brachiocephalic artery, the black arrow shows the trachea and the white overhead shows the es-
ophagus. 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
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) diagnostic Algorithm for Vascular tracheoesophageal
towards spine, the left bronchus gets squashed between the ascending compressive syndrome
and descending aorta (DA). The arrow depicts the left bronchus. RV =
Right ventricle. Courtesy: Reprinted with permission from reference 1
The diagnositc algorithm for vascular tracheoesophageal
compressive syndrome is shown in Figure 24.
miscellaneous Key messages

1. Vascular etiology of tracheoesophageal compressive syn-
Double-barreled Aorta dromes account for 1 to 3 percent of all congenital heart
diseases.
Double-barreled aorta is a rare anomaly in which the ascending 2. Persistent respiratory and feeding difficulties may prove life
threatening for small infants.
and descending components of the aorta are connected by two 3. Diagnosis may be difficult as not all cases are symptomatic.
aortic arches on the same side of trachea (Figures 22A and B). 4. Multimodality evaluation of aortic arch and its branches
This is not to be confused with double aortic arch, where the including CT and MRI adds to the diagnosis and surgical
two arches are on the opposite sides of trachea.44 planning.
Previously, this was explained as persistence of fifth 5. Surgical treatment of anomalous vascular structures and
aortic arch. However, modern embryologists disregard tracheal reconstruction gives excellent results in most of the
cases.
this view as existence of fifth aortic arch during normal
a B
Figures 22a and B: The echocardiogram of the aortic arch in suprasternal view. A. Shows the double-barreled aorta in which an aortic arch
542 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

a B c
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
1. Vascular rings, pulmonary arterial sling, and related condi-

tions, chapter 47. In: Robert H Anderson, Edward J Baker,
Daniel Penny, Andrew N Pedington, Michael L Rigby, Gil
Wernovsky (Eds). Paediatric Cardiology, 3rd edition, Churchill
Livingstone; 2010. pp.967-89.
2. Backer CL, Mavroudis C. Congenital Heart Surgery Nomen-
clature and Database Project: vascular rings, tracheal stenosis,
Figure 24: The diagnostic algoithm for vascular pectus excavatum. Ann Thorac Surg. 2000;69:308-18.
tracheoesophageal compressive syndrome 3. Gross RE. Surgical relief for tracheal obstruction from a
vascular ring. N Engl J Med. 1945;233:586-90.
4. Edwards JE. Anomalies of the derivatives of the aortic arch
system. Med Clin N Am. 1948;32:925-48.
Let the young know they will never find a more interesting, 5. Alsenaidi K, Gurofsky R, Karamlou T, et al. Management
more instructive book than the patient himself. and outcomes of double aortic arch in 81 patients. Pediatrics.
—Giorgio Baglivi 2006;118:e1336-e1341.
6. Ekstrom G, Sandblom P. Double aortic arch. Acta Chir Scand.
1951;102:183-202.
AcKnoWlEdgmEnts 7. Lincoln JC, Deverall PB, Stark J, et al. Vascular anomalies
compressing the esophagus and trachea. Thorax 1969;24:295-306.
I express my heartfelt gratitude to Dr Robert Anderson for his 8. Higashino SM, Ruttenberg HD. Double aortic arch associated
kind permission to reprint the embryological cartoons depicting with complete transposition of the great vessels. Br Heart J.
development of aortic arch and their postnatal imaging. 1968;30:579.
543
7 9. Stewart JR, Kincaid OW, Edwards JE. An atlas of vascular
rings and related malformations of the aortic arch system.
27. Midulla PS, Dapunt OE, Sadeghi AM, et al. Aortic dissection
involving a double aortic arch with a right descending aorta.
Springfield, IL: Charles C Thomas; 1964. Ann Thorac Surg. 1994;58:874-5.
10. Kommerell B. Verlagerung des osophagus durch eine abnorm 28. Dodge-Khatami A, Tulevski II, Hitchcock JF, et al.Vascular
verlaufende arteria subclavia dextra (arteria lusoria). Fortschr rings and pulmonary arterial sling: from respiratory collapse
Geb Roentgenstr. 1936;54:59. to surgical cure, with emphasis on judicious imaging in the hi-
11. Hastreiter AR, D’Cruz IA, Cantez T, et al. Right-sided aorta. I. tech era. Cardiol Young. 2002;12:96-104.
Occurrence of right aortic arch in various types of congenital 29. Backer CL, Mavroudis C, Rigsby CK, et al. Trends in vascular
heart disease. II. Right aortic arch, right descending aorta, and ring surgery. J Thorac Cardiovasc Surg. 2005;129:1339-47.
associated anomalies. Br Heart J. 1966;28:722-5. 30. Potts WJ, Holinger PH, Rosenblum AH. Anomalous left
12. Mustard WT, Trimble AW, Triusler GA. Mediastinal vascular pulmonary artery causing obstruction to right main bronchus:
anomalies causing tracheal and esophageal compression and report of a case. JAMA. 1954;155:1409-11.
obstruction in childhood. Can Med Assoc J. 1962;87:1301-5. 31. Glaevecke H, Doehle W. Ueber eine seltene angeborene.
13. Berman W Jr, Yabek SM, Dillon T, et al. Vascular ring due Anomalie der Pulmonarterie. Munch Med Wochenschr.
to left aortic arch and right descending aorta. Circulation. 1897;44:950.
1981;63:458. 32. Contro S, Miller RA, White H, et al. Bronchial obstruction due
14. van Son JA, Bossert T, Mohr FW. Surgical treatment of to pulmonary artery anomalies. I. Vascular sling. Circulation
vascular ring including right cervical aortic arch. J Card Surg. 1958;17:418.
1999;14:98. 33. Berdon WE, Baker DH, Wung JT, et al. Complete cartilage-ring
15. Nadas AS, Fyler DC. Pediatric cardiology. Philadelphia: WB tracheal stenosis associated with anomalous left pulmonary
Saunders; 1972. p.749. artery: the ring-sling complex. Radiology. 1984;152:57.
16. Godtfredsen J, Wennevold A, Efsen F, et al. Natural history of 34. Dodge-Khatami A, Tsang VT, Roebuck DJ, et al. Management
vascular ring with clinical manifestations. A follow-up study of congenital tracheal stenosis: a multidisciplinary approach.
of eleven unoperated cases. Scand J Thorac Cardiovasc Surg. Images Paediatr Cardiol. 2000;2:30-40.
1977;11:75. 35. Idriss FS, DeLeon SY, Ilbawi MN, et al. Tracheoplasty with
17. Backer CL, Mavroudis C. Surgical approach to vascular rings. pericardial patch for extensive tracheal stenosis in infants and
In: Karp RB, Laks H, Wechsler AS (Eds). Advances in Cardiac children. J Thorac Cardiovasc Surg. 1984;88:527-36.
Surgery. Chicago Mosby Year Book; 1997. pp.9:29-64. 36. Mitchell JH, Austin EH III. Vascular rings, slings, and other
18. Arciniegas E, Hakimi M, Hertzler JH, et al. Surgical arch anomalies. In: Kaiser, Kron, Spray (Eds). Mastery of
management of congenital vascular rings. J Thorac Cardiovasc Cardiothoracic Surgery. Philadelphia; Lippincott-Raven, 1998,
Surg. 1979;77:721-7. pp. 663-76.
19. Woods RK, Sharp RJ, Holcomb GW III, et al. Vascular anomalies 37. Newman B, Cho YA. Left pulmonary artery sling—anatomy
and tracheoesophageal compression: a single institution’s 25- and imaging. Semin Ultrasound CT MR. 2010;31(2):158-70.
year experience. Ann Thorac Surg. 2001;72:434-9. 38. Freedom R, Culham J. The Angiography of Congenital Heart
20. Berdon WE. Rings, slings, and other things: vascular compres- Disease. 1998.
sion of the infant trachea updated from the midcentury to the 39. Grover FL, Norton JB Jr, Webb GE, et al. Pulmonary sling.
millennium—the legacy of Robert E Gross, MD and Edward Case report and collective review. J Thorac Cardiovasc Surg.
BD Neuhauser, MD. Radiology. 2000; 216:624-32. 1975;69(2):295-300.
21. Allen HD, Goldberg ST, Sahn DJ, et al. Suprasternal notch 40. Fiore AC, Brown JW, Weber TR, et al. Surgical treatment of
echocardiography: assessment of its clinical utility in pediatric pulmonary artery sling and tracheal stenosis. Ann Thorac Surg.
cardiology. Circulation. 1977;55:605. 2005;79:38-46.
22. Abnormal vascular connections and structures. In: Snider AR, 41. Backer CL, Mavroudis C, Dunham ME, et al. Pulmonary artery
Serwer GA, Ritter SB (Eds). Echocardiography in Pediatric sling: results with median sternotomy, cardiopulmonary bypass,
Heart Disease. 2nd edition. 1999 Mosby year book, 452-96. and reimplantation. Ann Thorac Surg. 1999;67:1738-44.
23. Murdison KA, Andrews BA, Chin AJ. Ultrasonographic dis- 42. Kim YM, Yoo SJ, Kim TH, et al. Tracheal compression by
play of complex vascular rings. J Am Coll Cardiol. 1990;5: elongated aortic arch in patients with congenitally corrected
1645-53. transposition of the great arteries. Pediatr Cardiol. 2001;22:471-7.
24. Oddone M, Granata C, Vercellino N, et al. Multi-modality 43. Kim YM, Yoo SJ, Kim WH, et al. Bronchial compression
evaluation of the abnormalities of the aortic arches in children: by posteriorly displaced ascending aorta in patients with
techniques and imaging spectrum with emphasis on MRI. congenital heart disease. Ann Thorac Surg. 2002;73:881-8.
Pediatr Radiol. 2005;35:947-60. 44. Bernasconi A, Goo HW, Ypp SJ. Double-barrelled aorta with
25. Hernanz-Shulman M. Vascular rings: a practical approach to tetralogy of Fallot and pulmonary atresia. Cardiol Young.
imaging diagnosis. Pediatr Radiol. 2005;35:961-79. 2007;17:98-101.
26. Marmon LM, Bye MR, Haas JM, et al. Vascular rings and 45. Sun A, Alhabshan F, Branson H, et al. MRI diagnosis of isolated
slings: long-term follow-up of pulmonary function. J Pediatr origin of the left subclavian artery from the left pulmonary
Surg. 1984;19:683-92. artery. Pediatr Radiol. 2005;35:1259-62.
544
Sec t i on
Cyanotic Heart Diseases
C hapter
37 Tetralogy of Fallot
R Suresh Kumar, IB Vijayalakshmi, Bhushan Chavan
Introduction the underdevelopment of the subpulmonary infundibulum,

Van Praagh called TOF, the monology of Stensen. The more
Tetralogy of Fallot (TOF) is a congenital heart defect, which marked the anterior displacement of the conal septum, the
has four anatomical components—non-restrictive large more pronounced is the aortic override. Often even the spi-
subaortic ventricular septal defect (VSD), infundibular ral septum is displaced anteriorly. This may explain anoma-
stenosis, overriding aorta and right ventricular hypertrophy. lies of the pulmonary valve like bicuspid valve or stenosis/
TOF is the most common cyanotic heart defect seen in children atresia. It may also explain the unusually large aortic root
beyond infancy, accounting for a third of all congenital heart and ascending aorta in TOF.3
disease (CHD) in this age group. Even though Stenson in
1671 and Sandifort in 1777 had made references to what Pathology
would eventually be called TOF, it was Etienne–Louis Arthur
Fallot who first designated the four morphologic hallmarks The central abnormality in TOF is the hypoplasia of the
and outlined a clinical diagnosis. The term tetralogy of Fallot infundibular septum, which causes the septum to move
was to take birth much later, in 1924, in the works of Maude anteriorly and create an anterior malalignment type VSD. The
Abbot. The first surgical palliative aortopulmonary shunt crista supraventricularis is displaced anteriorly relative to the
was done by Alfred Blalock and Helen Taussig in 1945. parietal and septal bands, narrowing the right ventricle outflow
In 1946, Potts described a descending aorta to pulmonary tract (RVOT). The medial papillary muscle is not present. A
artery (Potts-Smith) shunt. Ten years later, Lillehei in 1954 VSD, almost always large, is present just behind the anteriorly
did the first intracardiac repair (ICR) with controlled cross- displaced crista supraventricularis.The right sinus of Valsalva
circulation. In 1962, Waterston described an ascending aorta is located at a higher position as compared to normal hearts
to pulmonary artery shunt. Kirklin in 1966 performed the first and the aorta can be easily entered from the right ventricle
ICR using transannular patch and valved conduits and he also (RV). When the infundibular stenosis is marked or severe the
proposed the 50% rule. This rule is a standard practice now. overriding of aorta is to a very marked degree. The pulmonary
The Washington-Baltimore infant study found a prevalence valve is commonly, stenotic. Very often it is bicuspid; in one-
of 0.262 per 1,000 live births. The disorder may be associated fourth of cases, the pulmonary valve is atretic.3 Absence of
with extracardiac anomalies such as cleft lip and palate, the pulmonary valve creates a unique syndrome, which is
hypospadias and skeletal and craniofacial abnormalities.1 discussed in chapter 30. Coronary abnormalities occur in 5
percent, anomalous origin of left anterior descending (LAD)
Embryology artery from the right coronary artery (RCA) being the most
common. The pattern of involvement of RVOT, pulmonary
Tetralogy of Fallot is characterized by underdevelopment of valve and other anomalies assosciated with TOF are discussed in
the subpulmonary infundibulum. Failure of normal growth Boxes 1A-E.4,5
of the subpulmonary infundibulum results in an obstructive
pulmonary outflow tract.2 Because the subpulmonary conus Genetics
is too small, it fails to fill with the help of the membra-
nous septum—the interventricular foramen. Persistent pa- In most cases, TOF is sporadic and non-familial. The inci
tency of the interventricular foramen results in the typical dence in siblings of affected parents is 1 to 5 percent. TOF
malaligned VSD of TOF. Paying tribute to the primacy of could be a syndromic defect, often associated with chromosomal
8 Box 1A: Pulmonary valve configuration Box 1E: Associated anomalies
in patients with tetralogy of Fallot in tetralogy of Fallot5
Cyanotic Heart diseases
Bicuspid 66% ASD 9%

Tricuspid 15% Persistent LSVC 8%
Vestigial 10% Anomalous origin of LAD from RCA 4%
Not Recorded 09% Aberrant origin of right subclavian artery 0.3%
Based on the analysis 365 patients who underwent tetralogy of Fallot Vascular ring 0.2%
surgery at Green Lane Hospital (GLH Series) between 1960-1978. Congenital heart block 0.2%
Absent RSVC 0.2%
Juxtaposition of atrial appendages 0.2%
Box 1B: Prevalence of the pulmonary ASD = Atrial septal defect; LAD = Left anterior descending; LSVC =
valve lesion Left superior vena cava; RCA = Right coronary artery; RSVC = Right
superior vena cava
Tethering alone 63%
Commissural fusion 14%
Tethering + fusion 06%
Vestigial valve 10% techniques have led to the identification of syndromes due
Atretic valve 01% to submicroscopic defects, such as the microdeletion of
Unrecorded 06% chromosome 22q11.2 (DiGeorge/Velocardiofacial syndrome).
Some series have reported 15 percent incidence of 22q11
Based on the analysis 365 patients who underwent tetralogy of Fallot
surgery at Green Lane Hospital (GLH Series) between 1960-1978. 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
Box 1C: Patterns of right ventricular outflow tract
conditions with multiple malformations have TOF as their
obstruction in tetralogy of Fallot cardiac component. These include CHARGE (coloboma, heart
defect, atresia choanae, retarded growth and development, genital
Isolated infundibular stenosis 26
abnormality, ear abnormality) syndrome, VACTERL (vertebral
Infundibular + valvular stenosis 26
defects, anal atresia, cardiac defects, tracheo-esophageal fistula,
Infundibular + valvular stenosis + annular stenosis 16 renal anomalies, limb abnormalities) association and Goldenhar
Diffuse right ventricular outflow tract hypoplasia 27 syndrome (oculoauriculovertebral spectrum). Specific anatomic
Dominant valvular stenosis 05 characteristics can be detected in congenital heart defects
Based on the analysis 365 patients who underwent tetralogy of Fallot associated with specific syndromes. Patients with TOF and
surgery at Green Lane Hospital (GLH Series) between 1960-1978. 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
Box 1D: Patterns of coronary artery anomalies discontinuity and diffuse hypoplasia of the pulmonary arteries
in tetralogy of Fallot4 (PAs). Patients with TOF and Down syndrome frequently have
Single coronary ostium 4.2% a particularly large VSD in the inlet septum. Non-syndromic
LAD arising from RCA or right sinus of Valsalva 4.2% TOF occurs sporadically in families, but multiple affected
LCX arising from RCA 0.8%
family members may also be found. In the majority of the cases,
inheritance is multifactorial, several genetic loci interacting
Large conus artery 9.3%
in association with environmental factors. Some of the genes
Fistulas between coronary artery and PA or RA 1.7%
known to be involved in non-syndromic TOF are low-mutations
Anastomosis between coronary artery and the in NKX2.5 (4% of TOF cases), JAGGED1 and FOG2 (4% of
bronchial arteries 6.0% the cases). In practical genetic counselling, the recurrence risk
Hypoplastic coronary artery 0.8% for congenital heart defect among siblings of patients affected
LAD = Left anterior descending ; LCX = Left circumflex; PA = Pulmonary by TOF is about 3 percent.6
artery; RA = Right atrium; RCA = Right coronary artery
Clinical features
anomalies and monogenic syndromes. Chromosomal anomalies
History
are involved in about 12 percent of the cases, e.g. trisomy 21
548 (Down syndrome), trisomy 13 (Patau syndrome) and trisomy 18 Tetralogy of Fallot is slightly more common in males than
(Edwards syndrome). Advances in cytogenetic and molecular in females.7 Patients with TOF most often present in infancy
with cyanosis due to right to left shunting of blood at the
Box 2A: Mechanism of cyanotic spells
37
level of the VSD.8 The degree of right ventricular outflow
tract obstruction (RVOTO) often correlates with the degree
Tetralogy of Fallot
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, Box 2B: Theories for explanation of mechanisms
deepening cyanosis, limpness or syncope. Convulsions, of cyanotic spells10-13
cerebrovasclur accident and death are potential complications. A. Wood's theory: Postulated that hypoxemic spells are
Spells are less common after 2 years. Initiated usually by caused by spasm of the infundibulum of the right ventricle
crying, feeding or bowel movement, spells are particularly which precipitates a cycle of progressively increasing right to
common after getting up from sleep. It is postulated that a left shunting and metabolic acidosis.
vulnerable respiratory center, which is particularly sensitive B. Catecholamine release: Leads to increased myocardial
after prolonged sleep, reacts to sudden increase in cardiac contractility and infundibular stenosis (both these theories
output provoked by feeding, crying or straining to initiate do not explain the cause of cyanotic spells in patients with
tetralogy of Fallot with pulmonary atresia).
the vicious cycle of spell. Such actions lead to increased
venous return to the right heart. In presence of obstruction C. Guntheroth's theory: Episodes of paroxysmal hyperpnoea
are the cause rather than the effect of cyanotic spells.
to pulmonary flow, right to left shunt increases. This right Hyperpnoea increases the systemic venous return leading
to left shunt leads to acidosis, which in turn stimulates the to right to left shunt as well as oxygen consumption through
respiratory center, provoking hyperpnea, further worsening increase work of breathing.
systemic oxygen saturation. A vicious cycle of progressive D. Kothari's theory: Argued against the other hypotheses
hypoxia, acidosis and hyperpnea ensues. Infundibular spasm and suggested the role of stimulation of mechanoreceptors in
secondary to increased sympathetic tone aggravates the the right ventricle to be the cause of spells.
problem by increasing right to left shunt. The drop in SVR E. Morgan’s theory: Vulnerable respiratory centre which
with muscular activity is a major contributor to right to left over-reacts to hypoxic stimuli like crying, feeding causes
shunt. an increase in cardiac output and heart rate which in turn
increases venous return causing an increase in right to left
Exertional dyspnea is common in the older child. A shunt across the ventricular septal defect which leads to a fall
characteristic posture older children with TOF assume to in PaO2 and increase in PCO2. The respiratory centre over-
increase pulmonary blood flow and to alleviate dyspnea is reacts to this stimulus and causes hyperpnea which again
squatting. Squatting is of diagnostic significance in TOF. increases the venous return, thereby causing a vicious cycle.
Squatting increases peripheral vascular resistance and thus F. Young’s theory: It was proposed that the spell was
decreases the magnitude of the right to left shunt across the precipitated by an atrial tachycardia.
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 Clinical Examination
of squatting. Exertional dyspnea usually worsens with age.
Occasionally, hemoptysis may occur in the older child due Most infants are smaller than expected for age. Cyanosis of
to rupture of bronchial collaterals. RV failure is uncommon the lips and nail bed may be noticed at birth or may appear
in TOF patients but the various circumstances in which the later. Cyanosis in TOF is determined by the severity of
patient can present with RV failure are given in Box 3 pulmonary stenosis and also to a lesser extent by systemic
549
8 Box 3: Causes of right ventricular failure
in 6.7 percent. A reticular pattern in the lung fields due to
in tetralogy of Fallot bronchial collaterals was seen in 23.1 percent. The incidence of
right aortic arch (19.9%), absent left pulmonary artery (2.8%),
1. Pulmonary atresia with large systemic arterial collaterals absent right pulmonary artery (0.7%) and dextrocardia (1.4%)
2. Accessory tricuspid leaflet tissue partially occluding the is brought out. The right atrial mean pressure was increased
ventricular septal defect making it restrictive and causing in 4.8 percent and a prominent “a” wave greater than 10
supra systemic right ventricular pressure.
mm Hg was present in 10.9 per cent. The right ventricular
3. Absence of pulmonary valve causing combination of
end-diastolic pressure was increased in 23.8 percent and the
stenosis (annular narrowing) and free pulmonary
regurgitation. left ventricular end-diastolic pressure in 25.9 percent of the
4. Systemic hypertension
patients.This study clearly shows that a lot of clinical features
which are usually considered uncharacteristic in TOF patients
5. Acquired calcific aortic stenosis or regurgitation of the
biventricular aortic valve can be present in adult uncorrected TOF patients.14
6. Infective endocarditis affecting the aortic valve
7. Hyperdynamic circulatory status like due to anaemia, Chest X-Ray
thyrotoxicosis
Plain films may classically show a "boot shaped" heart with
8. Adult tetralogy of Fallot with aortic regurgitation
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
to pulmonary collaterals. Infundibular stenosis worsens as in 25 percent.15
the infant grows so that a previously pink baby turns blue.
In the case of pulmonary atresia, cyanosis sometimes may be Electrocardiogram
absent due to systemic pulmonary collaterals. Clubbing may
be present after 3 months of life. General examination may Right ventricular hypertrophy and right axis deviation are the
reveal subtle features of 22q11 microdeletion. Precordium salient features of TOF. Older children and adults may show
is quiet. S1 is normal, while S2 is single due to a faint right atrial enlargement. Whereas the R wave in V1 is tall and
P2. Delayed and hesitant closure of the pulmonary valve usually monophasic, R wave in V2 is much shorter – the so
due to the slow pressure drop in the stenotic infundibular called “sudden transition” is characteristic (Figure 2). In patients
chamber, associated valvar stenosis and the overrding aorta with pulmonary stenosis and restrictive VSD, right precordial
all contribute to the single S2. A prominent ejection systolic leads show deeply inverted T waves in right precordial leads.16
murmur, is heard at the mid and upper left sternal border. Left axis deviation denotes an inlet VSD.
The intensity of this murmur is inversely proportional to the
severity of stenosis. With more severe stenosis RV pumps Echocardiography
more into the aorta and less across the RVOT, decreasing the
murmur. The murmur disappears during a spell. An aortic Echocardiography allows examination of all essential features
ejection click due to the dilated ascending aorta may be heard of tetralogy of Fallot and has a crucial role in diagnosis
over the apex. A continuous murmur below the left clavicle and preoperative evaluation (Figures 3A and B). Complete
denotes a patent ductus arteriosus (PDA). A more widely echocardiographic evaluation usually obviates the need for
heard continuous murmur, especially over the back, is due to further imaging. Most of the information can be achieved
systemic-pulmonary collaterals. with transthoracic echocardiography, but occasionally trans
esophageal echocardiography may be helpful for specific
Adult TOF questions raised by transthoracic echocardiography. A
complete study must address:
A large group of TOF patients are seen to survive to adulthood 1. The location and number of VSDs
without surgical correction and with the vast prevalence of 2. The anatomy and severity of RVOTO (Figures 4A and B).
TOF the number of such patients presenting to a clinician The size and anatomy of the main pulmonary artery, the
is increasing. Some of the studies have addressed the basic pulmonary arterial confluence, and the proximal branch
difference in the pathophysiology and the presentation of these pulmonary arteries, as far distally as possible, must be
patients. The largest study on adult TOF patients was done by demonstrated.
Abraham et al in which he evaluated the presentation of 147 3. The coronary arteries must be imaged, specifically looking
patients, above the age of 18 with TOF. Cardiac catheterization for any major branch crossing the RVOT. The LAD arises
and selective cine angiography were performed in all. Cardiac from the RCA and crosses the RVOT in 5 percent.
enlargement was seen in 25.8 percent of the patients, and 15.6 4. Aortic arch laterality must be shown. The presence of
550 percent were in congestive cardiac failure; 9.5 percent had any associated anomalies like atrial septal defect PDA,
systemic hypertension, and aortic regurgitation was present additional VSDs must also be looked for.
37
Tetralogy of Fallot
A B
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
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
A B shunting is best shown by the degree of systemic desaturation.
Angiographic assessment should be geared towards the
Figures 3A and B: Echocardiography in tetralogy of Fallot. A. Five-
information that is needed; biplane angiography is ideal. 551
chamber view shows large ventricular septal defect (VSD), overriding
of the aorta; B. Bidirectional shunt across the VSD. RV angiogram (anteroposterior [AP] cranial, shallow
8 Box 4: Salient features of oximetry run
in tetralogy of Fallot
• RA, RV and PA saturations are similar to that of vena cava

• MVO2 is markedly reduced to about 20–40% 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 40–60%)
• PA saturation higher than that of RV if PDA and/or multiple
collaterals are present
A
• 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.
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,
Figure 5: Right ventricular angiogram in frontal view shows
although selective injections may occasionally be needed. trabeculated right ventricle (RV) with simultaneous opacification of
The arch and descending aorta may also be seen in this view aorta (Ao) and pulmonary artery (PA) with severe infundibular stenosis
and show a PDA or collateral vessels. If collateral vessels are and pulmonary valvar and supravalvar stenosis
identified, selective injections are helpful to assess the areas
of the pulmonary bed that they supply and whether they are
Medical Management
the sole supply to these areas. The VSD is best seen from a
left ventricular injection in a long axial oblique projection. Medical mangement in TOF patients is directed towards
Multidetector computed tomography (MDCT) angiography preventing cyanotic spells, avoiding problems associated
is a safe and effective non-invasive technique to answer with anemia or polycythemia, preventing complications
questions remaining after echocardiography in patients with from infection like brain abcess or infective endocarditis.
TOF. Major aortopulmonary collateral arteries (MAPCA) The general measures include correction of anemia by iron
from all sources are best shown by this technique.17 supplementation and nutritional supervision. The child is
The various indices for prediction of successful intracardiac started on oral propranolol (1–4 mg/kg/day in three or four
552 repair are given in Box 5. divided doses) to prevent cyanotic spells until surgical
Box 5: Indices for prediction of
5. Sodium bicarbonate in a dose of 1–2 meq/kg IV is given 37
success of intracardiac repair slowly to correct metabolic acidosis.This may reduce
the respiratory centre stimulating effect of acidosis
Tetralogy of Fallot
Nakata index: Sum of the cross sectional areas of the left and may diminish the increase in pulmonary vascular
and right pulmonary arteries at their prebranching points
as related to body surface area. The normal Nakata index
resistance caused by hypoxia and acidosis. It can be
is + 330 mm2 /m2. An index of more than 150 mm2 /m2 is repeated in 10-15 minutes.
acceptable for complete repair without prior palliative shunt. 6. Beta blockers like injection propanolol is given in
Tetralogy of Fallot with pulmonary stenosis should have an a dose of 0.1-0.2 mg/kg IV over 5 minutes and can
index of more than 100 for surgery. be repeated once after 15 minutes. It decreases the
McGoon ratio: Ratio of the sum of the pre branching heart rate, infundibular spasm and increases SVR. If
diameters of the left and right pulmonary arteries to the propanolol is not available then injection metoprolol
diameter of the descending aorta just above the level of the
can be given in a dose of 0.1 mg/kg over 5 minutes.
diaphragm. Ratio above 1.2 is associated with acceptable
postoperative right ventricular systolic pressure in tetralogy of Another short acting beta blocker which can be given is
Fallot. injection esmolol in a dose is 0.5 mg (500 mcg)/kg over
Z-Score: The branch pulmonary artery diameter Z-score is the 1 minute and then as an infusion of 50 to 200 mcg/kg/
most important determinant of surgical strategy, with the worst min up to 48 hours.
figures being associated with no surgical options or palliative 7. In refractory cases vasopressors can be given to
surgery and the best figures leading to corrective surgery increase the SVR and promote the redirection of blood
Z = Observed dimension - Mean normal dimension/standard deviation flow through the pulmonary circulation. Phenylephrine
around mean normal dimension 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.
correction is done. A cyanotic spell is usually self limiting and 8. Avoid any actions that agitate the baby like vigorous
lasts less than 15-30 minutes. examination, repeated attempts to venipuncture etc.
But sometimes they can be prolonged and require The drugs to be avoided are inotropes (e.g. digoxin,
emergency measures like: dopamine, or dobutamine) and diuretics.
1. Hold the child in knee chest position.This increases the 9. If the spell is persistent or refractory, then intubation
SVR and decreases the desaturated systemic venous and mechanical ventilation maybe required.
return. 10. A emergency Blalock-Taussig (BT) shunt / pulmonary
2. Calm the child. The ideal sedative is morphine. It causes balloon valvuloplasty (PBV) may be required in
respiratory centre suppression and sedation thereby refractory cases.
reducing hyperpnea. It reduces the ventilatory drive and The stepwise approach for management of TOF patient
decreases systemic venous return (venodilator). This who present in a cyanotic spell is given in Box 6.
will decrease the release of catecholamines, increase
the period of right ventricular filling by decreasing CATHETER INTERVENTIONS IN TOF
the heart rate and relax the infundibulum. The dose of
morphine is 0.1 mg/kg and it can be given intravenous Catheter based interventions can identify and apply the
(IV), intramuscular (IM) or subcutaneous. It may be most effective but least invasive solutions to most difficult
repeated after 5 minutes. The ventilation facilities pathologies of TOF. Interdisciplinary approach can decide
should be at hand. The other alternative sedatives on the best approach and combine interventional and surgical
are: midazolam 0.05–0.1 mg/kg (IV, intranasal or alternatives for the best possible outcome resulting in fast
intrarectal) or dexmedetomidine 0.5 -1 mcg/kg IV or recovery, significantly reduce morbidity and mortality over
infusion of 0.2 mcg/kg/hr or fentanyl 1–2 mcg/kg IV. traditional surgery.
Ketamine has dual benefit of causing sedation and The various transcatheter interventions in TOF are:
increasing SVR. The dose is 0.25- 1.0 mg/kg IV or IM. 1. Balloon dilatation of pulmonary stenosis.
3. 100% Oxygen supplementation. This causes pulmonary 2. Balloon dilatation and/or ductal stenting.
vasodilation and hence decreases the pulmonary 3. The coil closure of MAPCAs (Figures 6A and B).
vascular resistance (PVR). The least aggravating 4. Balloon dilatation of peripheral pulmonary artery stenosis
method of delivery should be used. with or without stenting.
4. Establish immediate IV access to allow prompt 5. Balloon dilatation of blocked BT shunt.
administration of fluids, which will improve right 6. Stenting of RVOT for infundibular stenosis by
ventricular preload. Initially, fluid is given as a bolus of balloon expandable stainless steel stents (Johnson &
10-20 cc/kg, which may be increased to 60cc/kg. Bolus Johnson).
fluid should be isotonic saline or colloid. 7. Transcatheter pulmonary valve replacement. 553
554
8
Box 6: Infant with central cyanosis

37
Tetralogy of Fallot
A B
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

with very low SO2 the very attempt to cross the infundibulum
In patients with TOF, balloon dilatation of pulmonary can precipitate the cyanotic spell.The mortality can occur due
stenosis may be an effective palliative procedure in a subset to either cyanotic spell or tamponade in very sick infants.
of patients, obviating the need for a palliative shunt. The
PBV is recommended if the patient’s size or cardiac anatomy INTERVENTIONS IN Blalock-Taussig SHUNT
makes that patient an unsuitable candidate for total surgical
correction. The valvar obstruction should be a significant In patients with a narrowed BT shunt, balloon angioplasty
part of the RVOTO obstruction. Also due to the multiple with or without stent may improve pulmonary oligemia.
obstructions in the RVOT, the subvalvar obstruction still Improve systemic arterial hypoxemia and may obviate the
remains thus preventing flooding of the lungs after PBV.18 need for a second systemic-to-pulmonary artery shunt. The
The supravalvar pulmonic stenosis, if discrete, can be BT stenosed anastomosis can be opened up with thrombolytic
relieved by balloon dilatation. With the balloon dilatation, therapy or balloon dilatation (Figures 8A to C). Balloon
immediate surgical intervention with high risk is avoided. dilatation was performed in 60 patients with various cyanotic
The result of surgery in TOF with branch pulmonary artery CHDs in a study.19 The results were good in 39 (65%)
stenosis varied from poor to catastrophy. Integrated approach patients, satisfactory in 19 (31.7%), and unsatisfactory in
between cardiologists and cardiac surgeons with balloon only 2 (3%) cases. Complicated cases like pulmonary atresia
dilatation with or without stent have excellent results or hypoplastic pulmonary valve and pulmonary artery and
(Figures 7A and B). collaterals can benefit from a series of interventions prior to
surgery. Interdisciplinary approach avoids need for extensive
Advantages of Pulmonary Balloon Valvuloplasty and prolonged open heart surgery and repeat surgery for
residual defect. It also improves the chances of full recovery
The various studies have shown favourable results with: in complicated cases of TOF.
a. Substantial increase in saturation (SO2).
b. Growth of pulmonary valve annulus and pulmonary Surgery
arteries.
c. The need for transannular patch is reduced by 40 percent. The ideal age for TOF repair remains controversial. Most
d. The high risk intracardiac repair (ICR) is postponed in centers prefer to operate by 1 year of age. Cases with
infants. good anatomy could be operated much earlier, even in the
e. PBV in TOF acts as a safe bridge to surgery. neonatal period. Transannular-transpulmonary approach is
usually followed.20 The various techniques of performing
Disadvantages of Pulmonary Balloon Valvuloplasty intracardiac repair surgery in patients with TOF are given
in Box 7. Neonates and young infants with an unacceptable
Pulmonary balloon valvuloplasty may not be successful in level of oxygen saturation and/or hypercyanotic spells may 555
all patients. Very rarely in severely hypoxic and sick patients be palliated with a modified BT shunt. Although there is
8
A 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
A B C
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 Long-Term Follow-up
reported excellent outcome with this approach.21-23 The Patients with repaired TOF have the potential to lead normal
various contraindications to performing an intracardiac repair lives with excellent cardiac function. Most survivors are in
are given in Box 8. The various palliative procedures which New York Heart Association (NYHA) Class I or II. Some
can be performed in TOF patients to augment the pulmonary patients have more symptoms on exertion. 90 percent of
blood flow are given in Box 9. The difference between classic patients with total repair develop progressive pulmonary
and modified BT shunt has been discussed in Box 10. regurgitation (PR). Patients also may have some degree
of residual RVOTO and damage to the conduction system
Natural History of the heart. The incidence of bradyarrhythmias after
TOF repair has been drastically reduced in recent years.
If left untreated, TOF results in progressive right ventricular The incidence of late atrial arrhythmias after TOF repair
hypertrophy and right ventricular dilatation and threatens is relatively high, about 30 percent, including atrial
survival. If pulmonary atresia is present as well, survival is fibrillation, flutter, focal or reentrant atrial tachycardia.25
even poorer with only 50 percent of patients surviving to 1 Therefore, lifetime surveilance is recommended to assess
year and only 8 percent of patients surviving to 10 years. and monitor these risks and to recommend treatment. TOF
556 Survival without treatment is given in Box 11. patients are at risk for sudden cardiac death with 1 to 5
Box 7: Surgical techniques Box 9: Palliative procedures augmenting 37
for intracardiac repair pulmonary blood flow
Tetralogy of Fallot
1. Transventricular approach: This was the earliest • Blalock-Taussing shunt (classical): Subclavian artery to
approach which was used for RVOT resection but fell into pulmonary artery anastomosis (end-to-side). Infrequently, this
disrepute due to the high incidence of ventricular arrhythmias, may lead to pulmonary hypertension.
conduction system defects and right ventricular dysfunction. • Blalock-Taussing shunt (modified): Interposition graft
This difference from other surgical approaches has been between subclavian artery and ipsilateral pulmonary artery.
proven in various follow up studies. Controlled augmentation of pulmonary blood flow. Usually
2. Transatrial approach: The transatrial approach for a 4mm Gore-Tex shunt is required early in infancy. Larger
tetralogy of Fallot repair was proposed by Hudspeth et al24 shunts would be required for older patients, although the
in 1963. This method has significant advantages as over the possibility of repair should always be explored first.
transventricular approach for intracardiac repair. The salient • Waterston shunt: Ascending aorta-to-main or right
features of this method are: pulmonary artery (side-by-side). No artificial material
• Preservation of ventricular function used; shunt grows with the patient. May lead to pulmonary
• Decreased severity of PR hypertension. Infrequently, problems have been encountered
with pulmonary artery disruption, requiring extensive
• No risk of injuring branches of RCA arterioplasty.
• No scar on ventricle • Potts shunt: Descending aorta-to-left pulmonary artery
• Decreased arrhythmias (side-by-side). Frequent complication with narrowing
• Adequate annulus is a must and kinking of the left pulmonary artery at the site of the
anastomosis. The latter necessitates reconstructive surgery
3. Combined transatrial and transpulmonary approach:
during repair, occasionally through an additional thoracotomy,
The salient features of this approach are:
which made this shunt unpopular.
• Small ventriculotomy
• Central interposition tube graft: A Gore-Tex graft is often
• Minimizes RV dysfunction used for patients not suitable for early repair.
• Excellent exposure • Infundibular resection (Brock procedure) or closed
• Lower RVEDP, higher RVEF during isoprenaline infusion pulmonary valvotomy: Often effective palliative procedure
• Lower incidence of ventricular arrhythmias from an earlier surgical era.
• Suitable for all patients • Relief of RVOT obstruction without VSD closure or with
fenestrated VSD closure: In patients with multiple pulmonary
PR = Pulmonary regurgitation; RCA = Right coronary artery; RV = Right artery stenoses or hypoplasia.
ventricle; RVEDP = Right ventricle end diastolic pressure; RVEF = Right
ventricle ejection function; RVOT = Right ventricular outflow tract RVOT = Right ventricular outflow tract; VSD = Ventricular septal defect
Box 8: Contraindications to primary repair Reoperation may be required in 7 to 10 percent of

• Weight less than 3 kg (arbitrary and relative)
patients after TOF repair.26-28 Freedom from reoperation is
88 percent at 30 years. Reoperation is indicated for residual
• Severe hypoplasia of pulmonary annulus (Z value < 4)
RVOTO, residual VSD or PR. The most common reason
• Associated anomalies
for reoperation is progressive pulmonary regurgitation for
• Multiple ventricular septal defects which pulmonary valve replacement is done. PR results from
• Anomalous coronaries especially if the left coronary transannular patching or pulmonary valvotomy. Pulmonary
artery crosses the right ventricular outflow tract
valve replacement is indicated for severe PR when there is
• Small pulmonary arteries are a relative contraindication 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
percent lifetime incidence. Risk factors for sudden cardiac size and QRS duration and improves symptoms of congestive
death include older age at repair, male sex, advanced NYHA heart failure; data are conflicting as to whether right ventricular
class, repair via atriotomy, complete heart block beyond the function improves postoperatively.31,32 Several long-term
third postoperative day and QRS duration greater than 180 follow-up series have reported gross measures of functional
milliseconds. A large follow up series which had assessed status and quality of life (QOL) at late follow-up: 90 to 95
the long term follow up of TOF patients post ICR is given in percent of patients report being in NYHA class I or II, 71 to 85
Box 12. The indications for repeat surgery in these patients percent are employed, 17 to 25 percent take routine medications
is given in Box 13 and 50 percent participate in recreational sports.26-28
557
8 Box 10: Classic v/s modified Blalock-Taussig shunt Box 11: Survival without treatment in patients
with tetralogy of Fallot
CLASSIC BLALOCK-TAUSSIG SHUNT (CBTS) • 1 year 66%

Anastomosis is done between the subclavian artery • 3 years 50%
or the subclavian branch of the innominate artery and • 10 yrs 25%
the pulmonary artery, usually on the side opposite the
descending aorta. • 20 yrs 11%
Advantages • 30 yrs 6%
• It requires no prosthetic material • 40 yrs 3%
• Predictability of blood flow
• Subclavian artery diameter prevents the excessive flow
to pulmonary arteries and prevents congestive heart Box 12: Postsurgical follow up26
failure
In a group of 490 children who survived past the first year of
• Ease of closure during corrective surgery
surgery in Germany, actuarial survival rates were:
• Potential adaptive growth of anastomosis
10 years: 97%
Disadvantages
20 years: 94%
• Requires careful, lengthy dissection
30 years: 89%
• Can cause distortion of the peripheral pulmonary artery
36 years: 85%
• Blood supply to the ipsilateral arm is compromised which
The most common cause of death was sudden death (n = 13),
may result in a discrepancy in growth and strength.
followed by congestive heart failure (n = 6).
• Thrombosis of shunt (small size)
• Neurologic (rare): recurrent laryngeal nerve injury, phrenic
nerve injury, Horner syndrome
• Subclavian Steal syndrome Box 13: Indications for re-intervention
in tetralogy of Fallot
MODIFIED BT SHUNT
1. Symptoms of right heart failure
Prosthetic graft material is interposed between the subclavian
artery and the pulmonary artery. 2. RV enlargement or evidence for RV dysfunction, especially
if pulmonary regurgitation is present
Advantages
3. Clinically significant arrhythmias (atrial or ventricular)
• Can be performed on either side
4. Progressive aneurysmal dilation of an RV outflow tract
• Subclavian blood supply to the arm is preserved patch
• Kinking of the subclavian artery is not a problem 5. Onset or progression of tricuspid regurgitation
• Excellent patency rates: 90% at 2 years 6. Residual VSD with shunt > 1.5 : 1
• Prevent mutilating effects of CBTS 7. Residual patent arterial-pulmonary shunts leading to LV
• Pulmonary artery distortion less likely volume overload
• Can be performed < 3 months age 8. Residual RV outflow tract obstruction or pulmonary
Disadvantages stenosis with systolic RV/LV 0.67
• May be more difficult than classic BT shunts to take down 9. Significant aortic insufficiency with evidence of LV
dysfunction
• Leakage of serous fluid through PTFE in chest
10. Dilated aortic root > 5.5 cm
• Pseudoaneurysm formation which can lead to fatal
hemoptysis LV = Left ventricle; RV = Right ventricle; VSD = Ventricular septal defect
Conclusion Symptoms are the body's mother tongue; signs are in a

The timing of surgery in TOF needs to be decided based on foreign language.
the clinical status of the baby and the institutional experience. —John Brown
The word total intracardiac repair is misleading as the child
could have residuae, sequelae and complications that may Acknowledgment
appear at any time during subsequent life. Hence, life-long
follow-up is mandatory, even though the majority of patients We express our thanks to Dr Navin Agrawal, Sri Jayadeva
can expect near normal life span with good quality of life. Institute of Cardiovascular Sciences and Research,
558 MR angiography may assume an important role in follow-up. Bengaluru, for providing the various charts for this chapter.
References 18. Rao PS. Pulmonary valve in cyanotic heart defects with
pulmonary oligaemia. In Percutaneous Interventions for
37
1. Behrman RE, Kliegman RM. Nelson Essentials of Pediatrics. Congenital Heart Disease. Sievert H, Qureshi SA, Wilson N,
Tetralogy of Fallot
5th edition. Philadelphia, Pa.: Saunders; 2006. Hijazi Z (eds). Informa UK Ltd. 2007. 197-200.
2. Van Praagh R, Van Praagh S, Nebesar RA, et al. Tetralogy of 19. Alekian BG, Petrosian IuS, Podzolkov VP et al. Catheter
Fallot: Underdevelopment of the pulmonary infundibulum and therapy of congenital cardiovascular defects. Vestn Rentgenol
its sequelae, report of a case with cor triatriatum and pulmonary Radiol. 1995;2:16-26.
sequestration. Am J Cardiol. 1970;26:25-33. 20. Karl TR, Sano S, Pornviliwan S, et al. Tetralogy of Fallot:
3. Van Mierop LHS. Developmental aspects of tetralogy of Fallot. Favorable outcome of nonneonatal transatrial, transpulmonary
Singapore Med J. 1973;14:166-68. repair. Ann Thorac Surg. 1992;54:903-7.
4. Dabizzi RP, Caprioli G, Aiazzi L, et al. Distribution and 21. Gladman G, McCrindle BW, Williams WG, et al. The modified
anomalies of coronary arteries in tetralogy of Fallot. Blalock-Taussig shunt: Clinical impact and morbidity in
Circulation. 1980 ;61:95-102. Fallot's tetralogy in the current era. J Thorac Cardiovasc
5. Kirklin JW, Blackstone EH, Kirklin JK, et al. Surgical results Surg.1997;114:25-30.
and protocols in the spectrum of tetralogy of Fallot. Ann Surg 22. Stewart RD, Backer CL, Young L, et al. Tetralogy of Fallot:
1983;198:251-65. Results of a pulmonary valve-sparing strategy. Ann Thorac
6. MC Digilio. Genetic basis of tetralogy of Fallot - 2008. Surg. 2005;80:1431-38.
EUROGENE portal. Jan 2009. 23. Makaryus AN, Aronov I, Diamond J, et al. Survival to the
7. Starr JP. Tetralogy of Fallot: Yesterday and today. World J age of 52 years in a man with unrepaired tetralogy of Fallot.
Surg. 2010;34:658-68. Echocardiography. 2004;21:631-37.
8. Gatzoulis MA, Webb GD, Daubeney PEF, (Ed). Diagnosis and 24. Hudspeth AS, Cordell AR, Meredith JH, et al. An improved
management of adult congenital heart disease. 2nd edition. transatrial approach to the closure of ventricular septal defects.J
London: Churchill Livingstone; 2011. Thorac Cardiovasc Surg. 1962 Feb;43:157-65.
9. Wyszynski DF, Graham TP, Correa-Villasenor A (Eds). 25. Murphy JG, Gersh BJ, Mair DD, et al. Long-term outcome in
Congenital Heart Defects: From Origin to Treatment. Oxford patients undergoing surgical repair of tetralogy of Fallot. N
University Press, New York, 2010. Engl J Med. 1993;329:593-99.
10. Wood P. Attack Of Deeper Cyanosis And Loss Of Consciousness 26. Nollert G, Fischlein T, Bouterwek S, et al. Long-term survival
(Syncope) In Fallot’s Tetralogy. Br Heart Journal 1958;20:282- in patients with repair of tetralogy of Fallot: 36-year follow-up
6. of 490 survivors of the first year after surgical repair. J Am Coll
11. Guntheroth WG, Morgan BC, Mullins GL, Physiologic Studies Cardiol. 1997;30:1374-83.
Of Paroxysmal Hyperpnea In Cyanotic Congenital Heart 27. Norgaard MA, Lauridsen P, Helvind M, et al. Twenty-to-thirty-
Disease. Circulation 1965;31: 70-6. seven year follow-up after repair for tetralogy of Fallot. Eur J
12. Kothari S.S., Mechanism Of Cyanotic Spells In Cardiothorac Surg. 1999;16:125-30.
Tetralogy Of Fallot--The Missing Link?, Intl. Journal Of 28. Harrison DA, Harris L, Siu SC, et al. Sustained ventricular
Cardiology,1992;37:1-5. tachycardia in adult patients late after repair of tetralogy of
13. Young D, Elbl F. Supraventricular tachycardia as cause of Fallot. J Am Coll Cardiol. 1997:30;1368-73.
cyanotic syncopal attacks in tetralogy of Fallot. N Engl J Med. 29. Gatzoulis MA, Clark AL, Cullen S, et al. Right ventricular
1971;284:1359-60. diastolic function 15 to 35 years after repair of tetralogy
14. Abraham KA. Tetralogy of Fallot in adults. A report on 147 of Fallot: Restrictive physiology predicts superior exercise
patients. Am J Med. 1979;66:811-6. performance. Circulation. 1995;91:1775-81.
15. Siwik ES, Erenberg F, Zahka KG, Goldmuntz E. Tetralogy of 30. Cesnjevar R, Harig F, Raber A, et al. Late pulmonary valve
Fallot. In Allen HD, Driscoll DJ, Shaddy RE (Eds). Moss and replacement after correction of Fallot’s tetralogy. Thorac
Adams’ Heart Disease in Infants, Children, and Adolescents: Cardiovasc Surg. 2004;52:23-28.
Including the Fetus and Young Adults. Lippincott. Williams 31. Yemets IM, Williams WG, Webb GD, et al. Pulmonary valve
and Wilkins, Baltimore, MD 2008.pp 888-910. replacement late after repair of tetralogy of Fallot. Ann Thorac
16. Kasar PA, Ravikumar R, Varghese R, et al. Computed Surg 1997;64:526-30.
tomographic angiography in tetralogy of Fallot. Asian 32. Therrien J, Siu SC, McLaughlin PR, et al. Pulmonary valve
Cardiovasc Thorac Ann. 2011;19:324-32. replacement in adults late after repair of tetralogy of Fallot: Are
17. Karl TR. Tetralogy of Fallot: Current surgical perspective. Ann we operating too late? J Am Coll Cardiol. 2000;36: 1670-75.
Pediatr Cardiol. 2008;1:93-100.
559
C hapter
Pulmonary Stenosis
38 with Interatrial Communication
Vijayalakshmi IB
DefInItIon The stenosed pulmonary valve places a tremendous load

on the right side of the heart due to difficulty in expulsion
Pulmonary stenosis (PS) with reversed interatrial shunt is of blood into the pulmonary artery. This leads to right
called Trilogy of Fallot or Trilogie de Fallot.1 This eponym ventricular hypertrophy (RVH) and progressive increase
has been applied to a triad of pulmonary stenosis, intra-atrial in the systolic pressure. This gradually leads to increase in
septal defect and a closed interventricular septum (IVS). the diastolic pressure within the right ventricle (RV) as it is
This combination results in right-to-left shunt at the atrial unable to empty itself completely. The force of the right atrial
level causing cyanosis. This syndrome of pulmonary valve contraction increases and this causes a presystolic right to
stenosis with patency of the foramen ovale is a distinct left shunt at the atrial level. This stretches the margins of the
entity though readily confused clinically with the tetralogy PFO or increases its patency.16 The volume of unoxygenated
of Fallot (TOF). blood shunting from right to left is large enough for visible
cyanosis to be seen. The cyanosis is at first transitory, then
HIStorICal revIew becomes persistent and deepens as the patient grows older.
As the volume of shunt increases, polycythemia appears.10
Pulmonary valve stenosis with a patent foramen ovale (PFO) Subsequently, as the RV fails, tricuspid regurgitation (TR)
was described in 1769 by Giovanni Battista Morgagni2 and in occurs and this further decreases the pulmonary blood flow.
1848, Thomas Peacock3 published “Contraction of the Orifice Retarded growth and development are consequences of RV
of the Pulmonary Artery and Communication Between the failure that begins in infancy or early childhood.16 The child
Cavities of the Auricles by a Foramen Ovale.” In 1950 Joly is cyanotic, but in congestive heart failure.
et al termed this condition as “Fallot’s Trilogies”.1
ClInICal featureS
anatomy
The primary symptom is dyspnea on exertion which is mainly
Pulmonary stenosis is usually valvar in nature. Occasionally, due to the decreased pulmonary blood flow and is usually
the stenosis can be subvalvar (infundibulum) or supravalvar present from early life. As the shunting of blood through
(pulmonary artery and its branches).4-7 The right to left shunt the foramen ovale from the right atrium to the left becomes
through the interatrial communication is either a PFO or an established, the pulmonary blood flow further diminishes and
ostium secundum atrial septal defect (ASD).4,8-11 It is less hence exertional dyspnea becomes more pronounced. The
commonly through the ostium primum12 or sinus venosus exertional dyspnea generally precedes the onset of cyanosis
ASD.13 Rarely there is anomalous pulmonary venous and is out of proportion to the cyanosis. Cyanosis of varying
connection.14 degree can present from birth to later in life. Patients with
critical PS present with cyanosis at birth. Sometimes, the
PatHoPHySIology cyanosis can be obvious only during exercise. Patients can
present with easy fatigability or due to a murmur. In the TOF
The physiological consequences of this pathology of PS with patients, the cyanosis and dyspnea are directly proportionate
right-to-left shunt through a ASD or PFO depends on the to each other and usually appear in early infancy.10 In the
degree of stenosis and size of interatrial communication.8,15 degree of cyanosis, trilogy of Fallot patients occupy an
The severely cyanosed patients invariably have severe PS intermediate place between TOF and Eisenmenger syndrome.4
with PFO or small restrictive ASD. The symptoms of giddiness, light-headedness and syncope are
typically related to effort. In these patients, death is usually restrictive ASD, except for the conspicuous thrill and systolic 38
from RV failure and less commonly from hypoxia, cerebral murmur of PS. In patients with RV failure, the murmur is short
abscess or infective endocarditis.4 Physical under development and soft and a murmur of TR is audible. Liver enlargement
pulmonary stenosis with interatrial communication

coincides with the catabolic effects of right ventricular failure. and pulsations are manifestations of the RVH. Table 1 shows
The clinical features are cyanosis and clubbing and there the differences between Tetralogy and Trilogy of Fallot.
is precordial bulge due to RVH during early childhood.
There is parasternal heave and prominent ‘a’ waves in the eleCtroCarDIogram
jugular venous pulse. In patients with RV failure, ‘v’ wave
may become prominent especially if TR is present. The long Electrocardiogram is similar to that of severe PS. The right
ejection systolic murmur is heard maximal in the pulmonic atrial (RA) enlargement is seen as tall, peaked P waves in
area of grade 4-5/6. The pulmonary component (P2) of the lead 2 and in V1, V2. The right axis deviation and RVH are
second sound is soft in intensity due to the severe stenosis of the usual findings. In patients with suprasystemic RV systolic
the pulmonary valve. Mild to moderate pulmonary stenosis pressure, there is a qR pattern in V1 with tall R waves in the
with non-restrictive ASD clinically resembles an isolated non- 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 Pulmonary valvar stenosis with PFO/
with anterocephalad deviation of outlet restrictive ASD with right to left shunt with
outlet septum with infundibular stenosis intact IVS
2. Cyanosis Occurs 2–3 month after birth, all cyanotic by Usually in late childhood, puberty or
5–8 years, even on rest adulthood, mild cyanosis appears on
exertion initially
3. Spell or squatting Usual Unusual
4. Erythema of tips of fingers Absent Present

and toes
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 Grade > 3/6 loud, long ESM beyond
of murmur decreases with increase in A2 in second left ICS, TR murmur in RVF
infundibular stenosis
12. Ejection sound Eddy sounds may be heard Pulmonary EC may be heard
13. ECG P waves normal, RAD, Tall peaked P waves, RAD

QRS—no notching or slurring (20%—extreme RAD)
RVH—monophasic R in V1 with sudden QRS—occasionally terminal slurring,
transition in V2, T waves normal Gross RVH with strain pattern with T wave
inversion
14. Chest X-ray Boot-shaped heart with RVH, no RAE, Oligemic lung fields with cardiomegaly,
oligemic lung fields, pulmonary bay empty, RAE, RVH, MPA prominent
right-sided aortic arch in 25%
561
Contd...
8 Contd...
Tetralogy Trilogy
cyanotic heart diseases
15. Cath and RV angiogram Shows simultaneous opacification of dilated Dilated RV with dysfunction, valvar
aorta and small pulmonary arteries, mainly stenosis, poststenotic MPA dilatation
infundibular stenosis
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 of R wave in V1 multiplied by 5 gives the transvalvar
in left precordial leads.16 In patients with true ASD, there is an gradient.
rsR′ or Rsr′ pattern17 (Figure 1).
eCHoCarDIograPHy
CHeSt raDIograPHy
The transthoracic 2D echocardiography (TTE) with continuous
The chest X-ray is similar to that of severe isolated PS. There wave Doppler and color flow is adequate for both the anatomic
is cardiomegaly due to RA and RV enlargement. The main and physiologic diagnosis. The TEE is similar to that in severe
pulmonary artery is dilated due to poststenotic dilatation. The PS. M-mode shows RVH with thick interventricular septum
chest X-ray in these patients are in an intermediate position (Figure 2). The systolic doming of the thickened pulmonary
between the small shadows of the pulmonary vessels in TOF valve can be visualized in the parasternal short-axis view.
and the very prominently dilated and congested pulmonary The continuous Doppler is used to assess the pulmonary
vessels of the Eisenmenger syndrome.4 The lung fields are valve gradient (Figure 3A). The subcostal four chamber view
oligemic and is more pronounced with RV failure. The RV shows interatrial septum bulging towards left atrium with a
apex is not boot-shaped as in TOF as the size of the left PFO or ASD (Figure 3B). The color flow imaging shows the
ventricle is not reduced16 and the pulmonary bay is not right-to-left shunt. Also one can assess RVH, RV function
empty. On fluoroscopy, “rocking boat” effect is seen in and the severity of TR. The pulmonary annulus, the size of
the anteroposterior view as first the RA, forming the right the ASD and its rims can be measured by TTE. This helps in
heart border, contracts forcefully and then the hypertrophied selecting the size of the balloon and device for non-surgical
RV, forming the left heart border, contracts. The height transcatheter management.
562
Figure 1: Electrocardiogram shows right axis deviation with right atrial and ventricular hypertrophy with rsR′ pattern in right precordial leads.
38
pulmonary stenosis with interatrial communication

Figure 3a: 12 year-old cyanotic boy with anasarca with Hb–22.8
gms%, PCV–71.5% and SaO2–48%. 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 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 Figure 3B: Transthoracic echocardiographic apical four-chamber view
shows giant right atrium (RA) with bulging of interatrial septum towards
appropriate size, the valve can be dilated. The reduction in left atrium (LA), severe tricuspid regurgitation (TR) with hypertrophied
the gradient across the pulmonary valve can be measured by right ventricle (RV), small atrial septal defect (ASD) with right to left
multitrack catheter passed on the guide wire. If the patient shunt. LV = Left ventricle
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 In one Chinese series, in which the surgical results of 42 adults
Fallot were treated with the percutaneous balloon pulmonary with this condition were described with one mortality. Surgical
valvuloplasty and device closure of ASD. All of the 16 repair involves ASD closure, right ventricle outflow tract
patients were treated successfully, without any complication. resection, pulmonary valvotomy and transannular patching.19
After therapy, right ventricular systolic pressure decreased Chinese surgeons have also described an on-pump beating
from (81 ± 26) mm Hg to (38 ± 12) mm Hg and systolic heart technique for this operation.20
pressure gradient across the pulmonary valve decreased
from (68 ± 24) mm Hg to (15 ± 13) mm Hg immediately. ConCluSIon
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) Pulmonary valve stenosis with a right-to-left shunt through
mm.18 Interventional therapy for trilogy of Fallot is safe, a PFO is accompanied by a conspicuous systolic murmur,
easy and effective. except for the disarmingly soft murmur of pinpoint pulmonary
valve stenosis and RV failure. Mild or intermittent cyanosis
Surgery or digital erythema precedes persistent cyanosis. Symptoms
can be appreciable even when cyanosis is mild. Giddiness, 563
Although surgery is the traditional management, it carries higher light-headedness and syncope are typically related to effort.
morbidity and mortality than catheter-based interventions. In severe PS with PFO, early balloon valvotomy is indicated.
8 If PS is progressive, valve is dysplastic, and annulus is very with intact ventricular septum. A distinct hemodynamic-
morphologic syndrome. Chest. 1980; 78:759-62.
narrow, then the surgical valvotomy with transannular patch
with surgical closure of ASD is indicated. 10. Engle MA, Taussig HB. Valvular pulmonic stenosis with
cyanotic heart diseases
intact ventricular septum and patent foramen ovale; report of

illustrative cases and analysis of clinical syndrome. Circulation.
The two best physicians of them all — Dr. Laughter and 1950;2:481-93.
Dr. Sleep. 11. Ordway NK, Levy 2nd L, Hyman AL, et al. Pulmonary stenosis
—Gregory Dean Jr. with patent foramen ovale. Am Heart J. 1950;40:271-84.
12. Rudolph AM, Nadas AS, Goodale WT. Intracardiac left-to-
referenCeS right shunt with pulmonic stenosis. Am Heart J. 1954;48:808-
16.
1. Joly F, Carlotti J, Sicot JR, et al. Congenital heart disease. II. 13. Hardy WE, Gnoj J, Ayres SM, et al. Pulmonic stenosis and
Fallot’s trilogies. Arch Mal Coeur Vaiss. 1950;43:687-704. associated atrial septal defects in older patients. Report of three
2. Morgagni J. Seats and causes of diseases. London, Millar & cases, including one with calcific pulmonic stenosis. Am J
Cadell in the Strand and Johnson and Payne in Pater-Noster Cardiol. 1969;24:130-4.
Row, 1769. 14. Neptune WB, Bailey CP, Goldberg H. The surgical correction
3. Peacock T. Contraction of the orifice of the pulmonary artery of atrial septal defects associated with transposition of the
and communication between the cavities of the auricles by the pulmonary veins. J Thorac Surg. 1953;25:623-34.
foramen ovale. Transactions of the Pathological Society of 15. De Castro CM, Nelson WP, Jones RC, et al. Pulmonary
London. 1848;1:200. stenosis: cyanosis, interatrial communication and inadequate
4. Selzer A, Carnes WH, Noble CA Jr, et al. The syndrome of right ventricular distensibility following pulmonary valvotomy.
pulmonary stenosis with patent foramen ovale. Am J Med. Am J Cardiol. 1970;26:540-3.
1949;6:3-23. 16. Perloff JK, Marelli AJ. Pulmonary stenosis with interatrial
5. Shafter HA, Bliss HA. Pulmonary artery stenosis. Am J Med. communication. In: Perloff JK, Marelli AJ (Eds). In: Clinical
1959;26:517-26. Recognition of Congenital Heart Disease, 6th edition.
6. Campbell M. Simple pulmonary stenosis; pulmonary valvular Philadelphia PA: Saunders; 2012. pp. 273-82.
stenosis with a closed ventricular septum. Br Heart J. 1954;16: 17. Sathpathy M. Pulmonary stenosis with interatrial septal defect.
273-300. In: Sathpathy M (Ed). Clinical Diagnosis of Congenital
7. White PD, Hurst JW, Fennell RH. Survival to the age of Heart Disease, Jaypee Brothers Medical Publishers; 2008.
seventy-five years with congenital pulmonary stenosis and pp. 270-2.
patent foramen ovale. Circulation. 1950;2:558-64. 18. XIE Q,GAO L,WANG Z et. al. Interventional Therapy and
8. Roberts WC, Shemin RJ, Kent KM. Frequency and direction Therapeutic Evaluation for Trilogy of Fallot. Journal of
of interatrial shunting in valvular pulmonic stenosis with Applied Clinical Pediatrics. 2006;23: http://en.cnki.com.cn/
intact ventricular septum and without left ventricular inflow Article_en/CJFDTOTAL-SYQK200623009.htm.
or outflow obstruction. An analysis of 127 patients treated by 19. Li NF. Surgical treatment of trilogy of Fallot in 42 adults.
valvulotomy. Am Heart J. 1980;99:142-8. Zhonghua Wai Ke Za Zhi. 1993;31:118-9.
9. Arnett EN, Aisner SC, Lewis KB, et al. Pulmonic valve 20. Mo A, Lin H, Wen Z, et al. Efficacy and safety of on-pump
stenosis, atrial septal defect and left-to-right interatrial shunting beating heart surgery. Ann Thorac Surg. 2008;86:1914-8.
564
C hapter
Pulmonary Atresia with

39 Ventricular Septal Defect
Anurakti Srivastava, Anil Sivadasan Radha, Girish Warrier
INTRODUCTION as the cause of the velo-cardiofacial syndrome, which typically

consists of TOF along with facial and aural anomalies, cleft
Pulmonary atresia with ventricular septal defect (PA-VSD) palate, and developmental delay. About 10 percent of patients
constitutes a group of diverse malformations but lacks a uni- with 22q11 deletion have PA-VSD.2 Factors such as maternal
form definition and is used interchangeably, albeit wrongly insulin dependent diabetes mellitus, phenylketonuria, ingestion
with Tetralogy of Fallot- pulmonary atresia (TOF-PA). of retinoic acids or trimethadione have been implicated in
It is best defined as a group of congenital cardiac increased risk of PA-VSD in the fetus.3
malformations in whom there is lack of luminal continuity
and absence of blood flow from either ventricle and the EMBRYOLOGICAL BASIS
pulmonary artery, in a biventricular heart that has an opening
in the interventricular septum. In its severe form, there is either The etiology and pathogenesis of the pulmonary circulation
partial or complete absence of the native pulmonary arteries.1 was studied by Kutsche and Van Mierop, who concluded
that in PA-VSD the pulmonary ostium becomes atretic
NOMENCLATURE—THE HISTORY much earlier in development, shortly after the truncoconal
partitioning but before the closure of the ventricular septum.
This malformation was initially considered a truncus arteriosus On the other hand, in pulmonary atresia—intact ventricular
type IV in the classification by Collett and Edwards. In the septum (PA-IVS), pulmonary atresia occurs much later after
same year, 1949, Manhoff and Howe used the term absence of the cardiac septation has been completed. This explains why
the pulmonary artery for the condition, where the pulmonary in PA-IVS blood flow is provided by the ductus arteriosus into
blood supply was entirely derived from the systemic arteries. the well developed, main and confluent branch pulmonary
Based on the embryological considerations, the term absent arteries and there are no MAPCA(s), whereas in PA-VSD the
sixth aortic arch was used by Stuckey and associates. The term pulmonary circulation is so heterogeneous and highly variable
pseudotruncus was used by Bharati and associates in 1975, with the high incidence of MAPCA(s).4,5
to describe patients with PA-VSD. The term pseudotruncus
was subsequently felt to be inappropriate by Van Praagh and MORPHOLOGY
associates because of its vagueness. The term major aorto-
pulmonary collateral arteries (MAPCA) was first used by Pulmonary atresia exists when there is either complete
Macartney, Deverall and Scott to differentiate them from the obstruction or absence of the communication normally present
bronchial arteries.1 between the cavities of the ventricular mass and the pulmonary
arteries.6
PREVALENCE
Ventricular Outflow Tract
The lack of uniformity in classifying these patients makes
it difficult to provide precise prevalence and incidence data. The ventricle terminates blindly against an atretic pulmonary
Tetralogy of Fallot (TOF) with pulmonary atresia constitutes valve or against imperforate muscle. The obstructive form can
15 to 20 percent of TOF and is known to be associated with sometimes be produced by an imperforate pulmonary valve.
deletions of chromosome 22q11. Such deletions are established More usually, the blockage of the pathway is muscular, either
8 • Stenosis of the systemic arterial channels – pulmonary
arteries may be hypoplastic.
Interventricular Communication
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
A B C can extend to be doubly committed or juxta-arterial. It can
Figures 1A to C: Anatomy of ventricular outflow tract in pulmonary have entirely muscular borders, when the posteroinferior
atresia-ventricular septal defect (PA-VSD). A. Imperforate pulmonary limb of the septomarginal trabeculation fuses with the
valve or valvular atresia; B. Muscular atresia; C. Extreme form—
absence of pulmonary trunk
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
at the entrance to or at the distal end of the subpulmonary
infundibulum. The extreme form is represented by the Aorta
absence of all the intrapericardial pulmonary arteries. In
the most common pattern, the muscular outlet septum fuses The biventricular aorta is dilated and often continues as a
directly with the parietal musculature of the right ventricle, right aortic arch. It is related to the aorta receiving the entire
thus obliterating the ventriculo-pulmonary junction. In a cardiac output as well as to the inherent medial abnormality.
small number of cases, the atresia is found at the mouth of the The incidence of right aortic arch is as high as 50 percent in
muscular infundibulum and the pulmonary valve itself may cases of TOF-PA.3,13
then be patent (Figures 1A to C).3,7-9
Collaterals
Pulmonary Artery
In PA-VSD, the lungs are perfused by systemic to arterial
The pulmonary trunk is either a vestigial cord or a hypoplastic collaterals, which are essential for survival. The term collateral
funnel-shaped channel that widens as it approaches the artery refers only to the vessel connecting the aorta with a
bifurcation. The proximal pulmonary arteries are hypoplastic pulmonary arterial segment.14 The pulmonary circulation
and may be discontinuous.7 in PA-VSD is characterized by extreme heterogeneity and
When the pulmonary valve is imperforate, the pulmonary variability in terms of origin of the blood flow, the presence
trunk is present and patent to the level of the ventriculopulmonary or absence of the native pulmonary arteries (NPA), the
junction. In many other cases, the pulmonary trunk itself is presence or absence of MAPCA(s) and the distal distribution
atretic. In extreme cases, it is recognisable only as a fibrous of the pulmonary blood flow with frequent arborization
strand. When the right and left pulmonary arteries are present, abnormalities. The type of intracardiac malformation is not
usually they are confluent. The right and left pulmonary predictive of the pulmonary circulation.15,16
arteries can be nonconfluent, but one of them usually retains its A MAPCA is a large tortuous collateral artery, which almost
connection to the remnant of the pulmonary trunk.10,11 always arises from the anterior surface of the descending
aorta just beneath the carina or subclavian arteries, loops
CALIBER OF CENTRAL Pulmonary artery independent of the course of the bronchus to the lung and
connects with intrapulmonary arteries at the posterior aspect
The caliber of the central pulmonary artery12 is directly related of the hilum.12,15
to: The NPA may be severely hypoplastic, either confluent or
• Amount of blood flow nonconfluent or may be completely absent. They may derive their
• Connection of ductus or collaterals blood flow from either the ductus arteriosus, communicating
– Ductus/collaterals connect proximal to the central MAPCA(s) or both.17-20 Rabinovitch and associates21 have
pulmonary artery or lobar branches – pulmonary artery categorized systemic pulmonary collateral arteries into three
is mildly hypoplastic or normal. types (Figure 2), based on their site of origin as well as the way
– Multiple collaterals anastomose more distally at the they connect to the pulmonary circulation. These are direct
segmental or subsegmental levels – pulmonary arteries aortopulmonary collaterals, indirect aortopulmonary collaterals
are more likely to be hypoplastic. and true bronchial arteries (Table 1).21
566
Table 1
 39
Characteristics of systemic collateral arteries21
Pulmonary Atresia with Ventricular Septal Defect

Characteristic Bronchial Direct aortic branch Indirect aortic branch
Origin Aorta, Thoracic branches Descending aorta Descending thoracic aorta, Subclavian
of aorta, systemic collateral artery, abdominal aorta or its branches,
arteries coronary arteries
Anastomosis Intrapulmonary Hilar, additional intrapulmonary Extrapulmonary; additional
anastomoses to subpleural intra-acinar
arteries
Course Follow bronchi or spread Continue as a single vessel followed Variable distribution
over pleural surfaces by distribution similar to segmental
pulmonary arteries
Embryological Bronchial arteries develop Originate from the intersegmental Become prominent later in life
considerations in the 9th gestational branches of the dorsal aorta, which are
week, after the paired normally present during the 3rd and
intersegmental arteries have 4th week of gestation, when looping
been resorbed. The bronchial and conoseptal alignment occur.
artery branches become Development of atresia at this time
the dominant collateral results in persistence of the connections
blood supply when atresia between the intrapulmonary arteries
develops later in gestation and the local intersegmental arteries
Reasons for Large bronchial artery 1. The site of anastomosis is at the Aortic branches are found coexistent
embryological branches are not coexistent hilum with bronchial artery branches but not
basis with direct aortic branches 2. The stenosis at the anastomotic with direct aortic collaterals
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  Table 2

Comparison of ductus and systemic collateral arteries as sources
Types of the collateral-pulmonary artery anastomosis:22 of pulmonary blood flow in PA-VSD14
1. END TO END with intrapulmonary arteries. Ductus Systemic collateral arteries
• Peripheral histologic appearance like pulmonary artery
Widely patent in fetus, Stable source of pulmonary
• Changes position in relation to bronchi
so pulmonary artery size blood flow
2. END TO SIDE in hilum of lung (50% patients). normal at birth
• Into a complex manifold including hilar portion of
Sole precarious source Multiple
the pulmonary artery from which inter and intralobar
Postnatal ductal narrowing/ Progressive stenosis may make
pulmonary arteries distribute distally; central pulmonary
closure them inadequate for patient as
arteries are filled retrogradely he grows
• Sometimes central pulmonary arteries do not
Normal intrapulmonary Hyperperfusion of some areas
communicate with collaterals distribution and flow and hypoperfusion of some-
3. END TO SIDE to central pulmonary artery. pulmonary vascular bed exhibits
4. END TO END with hilar portion of ipsilateral pulmonary pulmonary arterial disease as
artery. well as stasis/thrombosis
Ductus
similar to a systemic arterial collateral with few differences
The pulmonary arteries are supplied primarily, if not (Table 2).14 This ductal structure is appropriate for 567
exclusively by a long, narrow, sigmoid shaped ductus intrauterine flow, which is directed from the aorta into the
arteriosus i.e. structurally a muscular systemic artery pulmonary artery. It is also termed ‘vertical ductus’ as it
8 i. Type A—NPAs are present. Pulmonary blood flow is
supplied by the patent ductus arteriosus (PDA). There are
no MAPCA(s).
ii. Type B—both NPAs and MAPCA(s) are present.

iii. Type C—there 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 i. Group I: The pulmonary circulation is through the ductus
arteriosus into the native, confluent pulmonary arteries,
arises from undersurface of arch and descends vertically

down to supply the pulmonary artery.
• To confluent central pulmonary artery (80%). Intrapulmo-
nary 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)
A B C
• Nonconfluent pulmonary arteries with B/L ductus (rare).3
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;
VARIATIONS 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
A B
Classification can be based on either pulmonary circulation or
on intracardiac anatomy.
Based on Pulmonary Circulation
Congenital Heart Surgery and Database Project C D

568 Pulmonary atresia-ventricular septal defect (based on pulmo- Figures 4A to D: Classification of PA-VSD based on development of
nary blood supply)1 the central pulmonary artery. A. Type 1; B. Type 2; C. Type 3; D. Type 4
with the main pulmonary artery being present. No high flow and pressure and prevents changes of excessive 39
MAPCA(s). muscularity and intimal hyperplasia. An anastomosis without
ii. Group II: The pulmonary circulation is through the a stenosis in a large collateral can lead to severe pulmonary

ductus arteriosus into the native, confluent pulmonary vascular changes. In most patients, the intra-acinar arteries are
arteries, with the main pulmonary artery being absent. No smaller than normal. In patients who have large, surgically
MAPCA(s). created shunts of long duration, the intra-acinar arteries may
iii. Group III: The NPAs are very hypoplastic and do not supply be fewer in number, of greater muscularity and with severe
all the bronchopulmonary segments. There are MAPCA(s) occlusive changes of intimal hyperplasia. The number of
supplying a variable degree of pulmonary parenchyma. alveoli is reduced in almost all patients.22-24
The NPAs receive their blood flow either through a ductus Pulmonary arterial disease tends to develop in segments
arteriosus or from communicating MAPCA(s). which are centrally connected and progresses at accelerated
iv. Group IV: There are no NPAs, with the entire pulmonary rate. It is termed as pulmonary arterial disease as it can not
blood supply provided by MAPCA(s). be judged how much of the pulmonary vascular resistance
is due to hypertensive vascular disease and how much due
Based on Intracardiac Anatomy1 to hypoplasia and stenosis of the distal pulmonary arteries
and collaterals. The quantum of effective pulmonary blood
This level of definition defines intracardiac anatomy, the atrio- flow depends on progressive intimal fibroplasia and the long
ventricular (AV) connection, and the ventriculo-arterial (VA) tortuous course of vessels.22
connection.
CLINICAL PRESENTATION
PA-VSD, AV Concordance
The spectrum of presentation ranges from cyanosis evident
• PA-VSD, AV concordance, VA concordance: TOF, PA after ductal narrowing/closure in a neonate to congestive
• PA-VSD, AV concordance, VA discordance: transpositon cardiac failure in a pink child with increased pulmonary
of great arteries (TGA), VSD, PA blood flow through large ductus or MAPCAs. Some children
• PA-VSD, AV concordance, double outlet right ventricle have balanced circulation and present late with cyanosis and
(DORV), PA exertional dyspnea. Digital clubbing and failure to thrive
• PA-VSD, AV concordance, double outlet left ventricle may be evident. Few children can present due to facial
(DOLV), PA dysmorphism or features of 22q11 deletion.3,9,11
Most of the children have a quiet precordium unless there
PA-VSD, AV Discordance is excessive pulmonary blood flow. As biventricular pressures
are equal, generally there is no right ventricular lift. The first
• PA-VSD, AV discordance, VA concordance: Isolated heart sound is normal, the second heart sound being single
ventricular inversion, PA-VSD (A2) loud and may be palpable. S3 can be heard if there is
• PA-VSD, AV discordance, VA discordance: Corrected excessive pulmonary blood flow. Sometimes, a vascular
TGA, PA-VSD ejection click can be appreciated due to the dilated aortic
• PA-VSD, AV discordance, DORV, PA root. Loud, localized continuous murmur often is predictive
• PA-VSD, AV discordance, DOLV, PA of a ductus, while widespread continuous murmurs suggest
MAPCAs. Continuous murmurs may not be heard in the
HEMODYNAMICS setting of reduced flow through collaterals as well as in the
presence of pulmonary arterial disease.9,13
Presence of a large non-restrictive VSD ensures equal
biventricular pressures and allows complete mixing of the INVESTIGATIONS
systemic and pulmonary venous blood in the aorta. Thus,
relative flow in the systemic or pulmonary circuits depends Electrocardiogram
on the relative resistances offered by these circuits. The
pulmonary vascular resistance is a complex interplay of the Electrocardiogram (ECG) shows a right atrial abnormality
number of collaterals, their course and blood flow through and a right ventricular hypertrophy with mean frontal QRS
them, the extent of intrapulmonary anastomosis and the axis +100 to +180 degrees, in contrast to PA-IVS where there
presence of areas of narrowing in the collaterals. is left axis deviation.13
Pulmonary Arterial Disease Chest X-ray

Narrowing at the site of anastomosis with a pulmonary artery A posteroanterior chest radiograph shows an empty pulmonary 569
apparently protects the peripheral intra-acinar arteries from bay due to hypoplastic pulmonary trunk. The heart size and
8 pulmonary vascularity depend on the pulmonary blood flow. Abrupt change in the caliber of aorta or its branches gives
Children with balanced circulation show a normal sized an insight into the origin of the collateral arteries.
cardia with apparent normal pulmonary vascularity. Children Transthoracic echocardiography can serve as a sensi
with excessive pulmonary blood flow have cardiomegaly tive and specific diagnostic test for the detection of aorto
and excessive pulmonary vascularity. Cyanosed children pulmonary collaterals in infants with TOF/PA. The extent
usually have a normal sized cardiac silhouette with patchy of aortopulmonary collaterals is inversely related to the
lung markings depending on collateral supply. Some areas diameters of the central pulmonary arteries. The presence
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
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 Figure 6: Subcostal view showing a blindly ending muscular
subcostal views to see a blindly ending muscular infundibulum infundibulum. IVS = Interventricular septum; LV = Left ventricle; RV
= Right ventricle.
(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 Figure 7: Suprasternal long-axis view showing large vertical ductus
aorta. IVS = Interventricular septum; LV = Left ventricle; RV = Right with distal constriction arising from undersurface of aortic arch and
ventricle; VSD = Ventricular septal defect. supplying pulmonary arteries arteries (PA).
Computerized Tomography 39
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
Diagnostic Cardiac Catheterization and Angiography

Analysis of the pulmonary artery anatomy is the single most
Figure 8: Modified suprasternal view for simultaneous imaging of important aspect of diagnostic imaging of patients with PA-
ductus and the pulmonary artery confluence. LPA = Left pulmonary VSD. Right ventricular (RV) angiogram in frontal view
artery; RPA = Right pulmonary artery.
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:
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 571
Figure 10: Axial CT section showing confluent pulmonary arteries supplied
procedure without further invasive study.28 by ductus. LPA = Left pulmonary artery; RPA = Right pulmonary artery.
8
Figure 13: 3D CT reconstruction delineating ductal anatomy
Figure 11: Sagittal CT section showing large ductus supplying ANATOMICAL DELINEATION
pulmonary arteries (PA)
• 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
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).
Figure 12: VR CT angiogram in a 15 months old child with PA/VSD 3. Photographic subtraction of appropriately chosen large film
showing nonconfluent pulmonary arteries arising from the aorta. angiograms can serve to delineate sources of pulmonary
Image Courtsey: Dr Madhav Hegde
blood flow.35,36
• Determine source (s) of pulmonary blood flow Cardiac Magnetic Resonance Imaging
• Delineate size and distribution of true pulmonary arteries
(Figure 15) Gadolinium enhanced three-dimensional magnetic resonance
• Ascertain extent of collateral blood supply to lungs (Figures angiography (Gd-MRA) has been shown to noninvasively
16 and 17) and accurately evaluate various lesions of the vascular
• True pulmonary artery pressure and resistance. system. Magnetic resonance angiography can delineate all
572
39

A B
C D
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 estimate the pulmonary to systemic blood flow ratio (QP/QS
heart disease with pulmonary stenosis and/or atresia as well = QPV/(QAO-QPV)) and the amount of blood flow to each
as provide accurate assessment of pulmonary artery size for lung. The contribution of a PDA or large aortopulmonary
planning corrective surgery.37 Magnetic resonance imaging collateral to the pulmonary blood supply may be assessed, but
in pulmonary atresia provides an alternative non-invasive investigation of all aortopulmonary collaterals would be tedious
method of obtaining much of the anatomical information and imprecise if they are small. With optimisation of current
required to plan surgical treatment and should reduce the need CMR techniques for imaging neonates, it should be possible to
for invasive angiography in these patients, besides depiction measure flow volumes with sufficient accuracy in vessels larger
of the pulmonary arterial anatomy.38 than 2 mm diameter. Contrast-enhanced magnetic resonance
Cardiovascular magnetic resonance (CMR) may also angiography (CE-MRA) is a useful diagnostic tool in clinical
provide hemodynamic information by obtaining additional routine for the preoperative evaluation of the morphology of
velocity-encoded phase-contrast cine sequences. In patients the pulmonary arteries and pulmonary circulation in neonates
with pulmonary atresia, flow volume measurements in the with pulmonary atresia. In most cases additional diagnostic
ascending aorta and in each pulmonary vein can be used to cardiac catheterization can be avoided.39 573
8
Figure 15: Pulmonary artery angiography of native pulmonary arteries Figure 16: Angiography through injection in left subclavian artery
supplied by a vertical ductus. LPA = Left pulmonary artery; RPA = showing an indirect aortic collateral
Right pulmonary artery.
Figure 17: Aortic root angiogram in left anterior oblique projection Figure 18: Balloon occlusion to facilitate delineation of coronary to
showing pulmonary artery originating from coronary artery. LMCA = pulmonary artery supply. LMCA = Left main coronary artery. MPA =
Left main coronary artery; MPA = Main pulmonary artery. Main pulmonary artery.
PRENATAL DIAGNOSIS MANAGEMENT
Pulmonary atresia-ventricular septal defect can be diagnosed Pulmonary atresia-ventricular septal defect remains one of
by fetal echocardiography with a high degree of accuracy. the most challenging groups to manage. The quest for optimal
574 However, it can be difficult to determine the morphology management of this complex anomaly is, as yet, an ongoing
of the central pulmonary arteries and to locate the source of process. The treatment of PA-VSD has been largely determined
pulmonary blood supply.40 by the morphology of the pulmonary circulation (Figure 20).
Systemic-pulmonary Shunts 39
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
Patent Ductus Arteriosus Stenting

Patent ductus arteriosus stenting is an attractive alternative
Figure 19: Pulmonary venous wedge angiography showing opacification to surgical palliative shunt operations. With the use of the
of native pulmonary arteries in levophase. LPA = Left pulmonary artery
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
Unifocalization
The unifocalization procedures are designed to improve
the arborization pattern of the central pulmonary arteries.
Figure 20: Plan for management of PA-VSD. Type A- Restoration of Systemic collateral arteries are essentially arterial conduits
neonatal pulmonary blood flow by systemic to pulmonary (S-P) shunt connecting the systemic circulation to the true pulmonary
or patent ductus arteriosus (PDA) stenting followed by intracardiac
repair (ICR). They can go for neonatal ICR, if feasible. Type B and arterial segments. This allows their use for the purposes
C- Treatment strategy is individualized and involves unifocalization of increasing pulmonary arterial runoff from the central
procedures, establishing ventricle-pulmonary artery continuity and pulmonary arteries. Systemic collateral arteries that connect
closure of ventricular septal defect. Cases where biventricular repair freely with the central pulmonary arteries (communicating)
is not feasible, one can follow the usual strategy for a single ventricle
pathway in suitable patients can be interrupted, whereas those that do not have
unrestricted connections with the central pulmonary arteries
(non-communicating) must be detached from their origin,
Pulmonary Artery Rehabilitation mobilized and connected surgically to the central pulmonary
arteries or their branches.
A strategy aiming at the development of native pulmonary arteries Pulmonary reperfusion injury is common after the
and a biventricular repair is feasible in most cases and should unifocalization procedure. Severity of MAPCA stenosis and
be done early in life, since long term future of true pulmonary bilateral unifocalization are associated with the development 575
arteries may possibly be better than flow through the collaterals.41 of reperfusion injury.42
8 via anastomosis of collaterals to other collaterals and to the
native pulmonary arteries.61
Complete Repair
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
Figure 21: Aortic injection showing coronary stent in position repair.
across the vertical ductus into pulmonary artery
Ventricular Septal Defect Closure

Multistaged Postoperative right ventricular systolic pressure (RVSP) is
A staged surgical approach yields low overall mortality and a marker for whether VSD closure can be physiologically
acceptable hemodynamics after complete repair.50 tolerated. If the VSD is closed and there is subsequent
A different type of strategy using two stage procedure suprasystemic RV pressure, morbidity and mortality are high.
with stage one including left major aortopulmonary collateral Preoperative anatomic evaluation has been used to determine,
unifocalization and modified Blalock-Taussig shunt from which patients will have a successful complete repair.
left posterolateral thoracotomy; stage two comprising right Data utilized are the total number of incorporated pulmonary
unifocalization, ligation of the shunt, followed by VSD segments or a pulmonary segment artery ratio (PSAR) after
closure and RVOT reconstruction can be effective with good unifocalization. More recently, a combined area index for
outcome, thus offering an alternative surgical approach in the all MAPCA’s and the central pulmonary artery, i.e. total
treatment of PA-VSD and MAPCAs.51 neopulmonary artery index (TNPAI) has been suggested and
The Clamshell approach in complex TOF/PA provides seems to be promising.62
simultaneous exposure of bilateral central and peripheral But preoperative anatomic findings have not always
pulmonary artery lesions and intracardiac pathologic predicted postoperative functionality.
conditions. This procedure appears safe and may decrease the A functional measurement of pulmonary vascular perform
number of operations required to complete repair of TOF/PA ance may be more predictive of post reconstruction pressures.
in selected patients.52 Reddy et al described an intraoperative pulmonary blood
flow study that measured mean pulmonary artery pressure
Single Stage simultaneous to pumping blood flow through the unifocalized
pulmonary arteries at a cardiac index of 2.5 L/min per m2. A
In the earlier period, patients with PA-VSD were treated with mean pulmonary artery pressure less than 30 mm Hg was
conventional multistage procedure. Previously published thought to allow successful VSD closure at a reasonable
data showed that multistage procedure required a median of RV pressure. An intraoperative pulmonary blood flow study
three procedures (range 2 ± 6) before complete repair. A one- is an opportunity to obtain data on the functionality of the
stage that completes unifocalization and repair from a midline entire pulmonary vasculature once it has been unifocalized
sternotomy approach reduces the number of operations but before closing the VSD. It offers the possibility for more
and hospitalization and hence may be more cost effective refined decision-making, regarding the appropriateness
than multistaged procedures.53-58 Final correction can be of VSD closure.63 The integrated approach to total repair
accomplished in early infancy with acceptable morbidity and of pulmonary atresia, VSD and major aortopulmonary
mortality. The initiation of normothermic cardiopulmonary collaterals by preoperative calculation of total neopulmonary
bypass greatly facilitates dissection of collaterals and prevents arterial index, RVOT reconstruction (when required) and
hypoxemia.59 Single stage complex unifocalization early in intraoperative flow study may lead to optimal results.64
life, preferably by 6 months of age, with maximal use of The VSD can be closed with fenestration if RVSP is high.
native tissue in the reconstruction yield excellent functional The fenestration can be tackled later by transcatheter
576 results,60 with emphasis on native tissue-to-tissue connections means.
TECHNICAL CONSIDERATIONS SUMMARY OF TRANSCATHETER PROCEDURES 39
IN Pulmonary atresia with ventricular
1. Conduits: The integrity of the pulmonary vascular bed is a septal defect

major issue in the management of pulmonary atresia with
MAPCAs. Most staged approaches use circumferential 1. PDA stenting.
nonviable conduits in the central and peripheral 2. Coil embolization of MAPCAs in lung segments with dual
pulmonary circulation, which limits growth potential and supply.
the ability to perform complete repair in early infancy. 3. Balloon dilatation/ stenting of stenosed pulmonary arteries/
Aggressive and creative reconstructive techniques to MAPCAs.
maximize native tissue-to-tissue connections and avoid 4. VSD closure of fenestration.
nonviable conduits has shown better results.65 Although 5. Stenting of stenosed conduits.
homografts are seen to be the ‘gold standard’ for conduits
in the right ventricle to pulmonary artery (RV-PA) Conclusion
position, they too are affected by structural degeneration.
Lately, there have been reports of tissue engineering to Pulmonary atresia with ventricular septal defect and
grow sheets of pluripotent cells, which can then convert MAPCAs is a complex and rare lesion in which considerable
to pulmonary arterial tissue. However these are still in morphologic variability exists regarding the sources of
the experimental stage. There has also been interest in pulmonary blood flow. The therapeutic approaches have
providing viable scaffolding for new overgrowth of native included unifocalization, shunting, coiling of collateral
tissue. Once again, these are still to be evaluated for their vessels, and heart/lung transplantation. The results have
use in patients. been variable and frustrating. An individualized approach
2. Right ventricular decompression: Important questions must based on the morphology of the pulmonary arterial supply
be asked regarding the long-term behavior of conduits and has a low rate of reoperation and mortality. As there is further
anastomoses to the pulmonary arteries and regarding the advances in genetic understanding and technology, there is
fate of the pulmonary arterioles. Although the limitations considerable promise for development of future therapies.
of prosthetic conduits of all types are well understood, of
greater concern is the adequacy of the right ventricular But science is the collection of nature's answers.
decompression after complete intracardiac repair. — Sir Gavin de Beer
Persistent stenosis at numerous sites of the reconstructed
pulmonary vasculature often results in less than ideal peak REFERENCES
right to left ventricular systolic ratios. In addition, there
is a distinct possibility of pulmonary vascular obstructive 1. Tchervenkov CI, Roy N. Congenital Heart Surgery
disease affecting in variable degree the different pulmonary Nomenclature and Database Project: Pulmonary Atresia—
arterial segments.66-70 ventricular septal defect. Ann Thorac Surg. 2000;69:
S97-105.
2. van Engelen K, Topt A, Keavney BD, et al. 22q11.2 Deletion
FUNCTIONAL SINGLE VENTRICLE Syndrome is under-recognised in adult patients with tetralogy
of Fallot and pulmonary atresia. Heart. 2010;96:621-24.
In selected patients with functional single ventricles and 3. O' Leary PW, Edwards WD, Julsrud PR, et al. Pulmonary
MAPCAs, the pulmonary vascular bed can be reconstructed atresia and ventricular septal defect. In: Allen HD, Driscoll DJ,
sufficiently to allow for cavopulmonary connections. Venous Shaddy RE, Feltes TF (Eds). Moss and Adams' Heart Disease
flow to the pulmonary vasculature decreases cardiac volume in Intants, Children, and Adolescents Including the Fetus and
load and is likely to increase life expectancy and quality of life young Adult 7th edition. Philadelphia: Lippincott Williams and
for these patients.71 Wallcins; 2008.pp.879-87.
4. Kutsche LM, van Microp LH. Pulmonary atresia with and
without ventricular septal defect: a different etiology and
OUTCOME pathogenesis for the atresia in the 2 types? Am J cardiol.
1983;51:932-35.
The outcomes are negatively affected by neonatal age and 5. Sadler TW, Langman J. In: Sadler TW (Ed). Langman's
low body weight and positively affected by simultaneous or Medical Embryology. 9th edition. Lippincott Williams and
staged ventricular septal defect closure. Finally, chromosome Wallcins; 2003.pp.223-74.
22q11 deletion remains an independent variable affecting 6. Anderson RH, Razavi R, Taylor AM. Cardiac anatomy
survival.72 revisited. J Anat. 2004;205:159-77.
577
8 7. Edwards JE Mchoon DC. McGoon. Absence of anatomic
origin from heart of pulmonary arterial supply. Circulation.
25. Markowitz RI, Fahey JY, Hallen brand We Am J Roentoenol,
et al. Bronchial compression by a patent ductus arteriosus
1973;47:393-98. associated with pulmonary atresia. AJR. 1985;144:535-40.
8. Freedom RM, Yoo S, Makailian H, William W (Eds). The 26. Snider AR, Serwer GA, Ritter SB. Echocardiography in
natural and modified history of Congenital heart disease. Ist pediatric Heart Disease. 2nd edition. Mosby.
edition. Wiley-Blackwell. 27. Mackie AS, Gauvreau K, Perry SB, et al. Echocardiographic
9. Anderson RH, Baker EJ. In: Anderson RH, Baker EJ, Penny predictors of aortopulmonary collaterals in infants with
DJ, Redington AN, Rigby ML, Wernovsky G (Eds). Pediatric tetralogy of Fallot and pulmonary atresia. J Am Coll Cardiol.
Cardiology, 3rd edition. Churchill Livingstone Elsevier. pp. 2003;41:852-7.
775-793. 28. Marino, Pasquini L, Guccione P, et al. Pulmonary atresia with
10. Thiene G, Bartolotti U, Gallucci V, et al. Pulmonary atresia ventricular septal defect. Selection of patients for systemic-
with ventricular septal defect. Further anatomical observations. to-pulmonary artery shunt based on echocardiography. Chest.
Br Heart J. 1977;39:1223-33. 1991;99:158-61.
11. Freedom RM, Benson LN, Smallhorn JF (Eds). Neonatal Heart 29. Rajeshkannan R, Moorthy S, Srukumar KP, et al. Role of 64-
Disease, 1st edition. Springer Verlag. MDCT in evaluation of pulmonary atresia with ventricular
12. Haworth SG, Macartney FJ. Growth and development of septal defect. AJR 2010;194:110-18.
pulmonary circulation in pulmonary atresia with ventricular 30. Yu CH, Chen MR. Clinical investigation of systemic-
septal defect and major aortopulmonary collateral arteries. Br pulmonary collateral arteries. Pediatr Cordiol. 2008;29:334-38.
Heart J. 1980;44;14-24. 31. Prieto Lr. Management of tetralogy of Fallot with pulmonary
13. Perloff JK. Ventricular septal defect with pulmonary stenosis. atresia. Images Paediatr Cardiol. 2005;24:24-42.
Clinical Recognition of Congenital Heart disease. 5th edition. 32. Moll JN, Santos MA, Drumond C, et al. Improved visualization
WB Saunders. pp. 348-82. of aortopulmonary collateral arteries by abdominal aortic
14. Haworth SG. Collateral arteries in pulmonary atresia with compression during angiography. Circulation. 1982;65:
ventricular septal defect. A precarious blood supply. Br Heart J 953-55.
1980;44:5-13. 33. Feltes TF, Bacha E, Beckman RH, et al. Indications for cardiac
15. Jefferson K, Rees S, Somerville J. Systemic arterial supply to catheterization and intervention in pediatric cardiac disease:
the lungs in pulmonary atresia and its relation to pulmonary a scienfic statement from the American heart Association.
artery development. Br Heart J. 1972;34:418-27. Circulation. 2011;123:2607-52.
16. Macartney FJ, Scott O. Deverall PB. Haemodynamic and 34. Lim JSL, Desai T, Stumper O. Dual-catheter balloon occlusion
anatomical characteristics of pulmonary blood supply in aortography in pulmonary atresia with ventricular septal
pulmonary atresia with ventricular septal defect - including a defect and major aorto-pulmonary collaterals. Pediatr Cardiol.
case of persistent fifth aortic arch. Br Heart J. 1974;36:1049- 2004;25:500-02.
60. 35. Fsulton RE, Davis GD. Congenital pulmonary atresia:
17. Amin Z, McElhinney DB, Reddy VM, et al. Coronary to photographic subtraction as an aid in recognizing hypoplastic
pulmonary artery collaterals in patients with pulmonary atresia pulmonary arteries. Am J Roentgenol. 1978;131:1003-07.
and ventricular septal defect. Ann Thorac Surg. 2000;70:119- 36. Elliott LP, Bargeron LM Jr, Brean PR, et al. Axial
23. cineangiography in congenital heart disease. Section II. Special
18. Nørgaard MA, Alphonso N, Cochrane AD, et al. Major aorto- lesions. Circulation. 1977;56(6):1048-93.
pulmonary collateral arteries of patients with pulmonary atresia 37. Srinivas B, Patnaik AN, Rao DS. Gadolinium-enhanced three-
and ventricular septal defect are dilated bronchial arteries. Eur dimensional magnetic resonance angiographic assessment of
J Cardiothorac Surg. 2006;29:653-58. the pulmonary artery anatomy in cyanotic congenital heart
19. Faller K, Haworth SG, Taylor JF, et al. Duplicate sources of disease with pulmonary stenosis or atresia: comparison with
pulmonary blood supply in pulmonary atresia with ventricular cineangiography. Pediatr Cardiol. 2011;32(6):737-42.
septal defect. Heart. 1981;46:263-68. 38. Rees RSO, Somerville J, Underwood SR, et al. Magnetic
20. Ramsay JM, Macartney FJ, Haworth SG. Tetralogy of resonance imaging of the pulmonary arteries and their
Fallot with major aortopulmonary collateral arteries. Heart. systemic connections in pulmonary atresia: comparison with
1985;53:167-72. angiographic and surgical findings. Br Heart J. 1987;58:621-26.
21. Rabinovitch M, Herrera-deLeon V, Costaneda AR, et al. 39. Kawel N, Valsangiocomo-Buechel E, Hoop R, et al.
Growth and Development of the Pulmonary Vascular Bed in Preoperative evaluation of pulmonary artery morphology and
Patients with Tetralogy of Fallot with or Without Pulmonary pulmonary circulation in neonates with pulmonary atresia-
Atresia. Circulation. 1981;64:1234-49. usefulness of MR angiography in clinical routine. J cardiovase
22. Kirklin JW, Barrat-Boyes BG, Ventricular Septal Defect magn reson. 2010;12:52.
and Pulmonary stenosis and Atresia. 2nd edition. Churchill 40. Vessel S, Roltings S, Jones A, et al. Prenatally diagnosed
Livingstone: pp.816-1012. pulmonary atresia with ventricular septal defect: echocardio
23. Jonas RA. Comprehensive Surgical Management of Congenital graphy, genetics, associated anomalies and outcome. Heart.
Heart Disease. 1st edition. Hodder Arnold. 2006;92:1501-05.
24. Haworth SG, Rees PG, Taylor JFN, Macartney FJ, et al. 41. Metrasa D, Chetailleb P, Kreitmanna B, et al. Pulmonary
Pulmonary atresia with ventricular septal defect and major atresia with ventricular septal defect, extremely hypoplastic
aortopulmonary collateral arteries Effect of systemic pulmonary arteries, major aortopulmonary collaterals. Eur J
578 pulmonary anastomosis. Br Heart J. 1981;45:133-41. cardiothorac Surg. 2001;20:590-96.
42. Liava'a M, Thomson LD, et al. Pulmonary atresia, ventricular ventricular septal defect be closed? J Thorac Cardiovasc Surg. 39
septal defect, and major aortopulmonary collaterals: neonatal 1997;113:858-68.
pulmonary artery rehabilitation without unifocalization. Ann 58. Murthy K, Reddy KP, Nagarajan R, et al. Management of

Thorac Surg. 2012;93:185-191. ventricular septal defect with pulmonary atresia and major aorto
43. Rodefeld MD, Reddy VM, Thompson LD, et al. Surgical pulmonary collateral arteries: Challenges and controversies.
creation of aortopulmonary window in selected patients with Ann Pediatr Cardiol. 2010;3(2):127-35.
pulmonary atresia with poorly developed aortopulmonary 59. Lofland GK. The management of pulmonary atresia, ventricular
collaterals and hypoplastic pulmonary arteries. J Thorac septal defect, and multiple aorta pulmonary collateral arteries
Cardiovasc Surg. 2002;123:1147-54. by definitive single stage repair in early infancy. Eur J Cardio-
44. Dragulescu A, Kammache I, Fauilloux V, et al. Long-term thorac Surg. 2000;18:480-86.
results of pulmonary artery rehabilitation in patients with 60. McElhinney DB, Reddy VM, Hanley FL. Tetralogy of Fallot
pulmonary atresia, ventricular septal defect, pulmonary artery with major aortopulmonary collaterals: early total repair.
hypoplasia, and major aortopulmonary collaterals. J Thorac Pediatr Cardiol. 1998;19:289-96.
Cardiovasc Surg. 2011;142:1374-80. 61. Reddy VM, Liddicoat JR, Hanley FL. Midline one-stage
45. Davenport JJ, Lam L, Whalen-Gless R, et al. The successful complete unifocalization and repair of pulmonary atresia with
use of alternative routes of vascular access for performing ventricular septal defect and major aortopulmonary collaterals.
pediatric interventional cardiac catheterization and cardiovasc J Thorac Cardiovasc Surg. 1995;109:832-44.
interv. 2008;72:392-98. 62. Carottia A, Albanesea SB, Minnitia G, et al. Increasing
46. Stumper O, Bhole V, Andeuon B, et al. A novel technique for experience with integrated approach to pulmonary atresia with
stenting pulmonary artery and conduit bifurcation stenosis. ventricular septal defect and major aortopulmonary collateral
Catheter Cardiovasc Interv. 2011;78:419-24. arteries. Eur J Cardio-thoracic Surg. 2003;23:719-27.
47. Gibbs JL, Rothman MT, Rees MR, et al. Stenting of the arterial 63. Honjo O, et al. The functional intraoperative pulmonary blood
duct: a new approach to palliation for pulmonary atresia. Br flow study is a more sensitive predictor than preoperative
Heart J. 1992;67:240-45. anatomy for right ventricular pressure and physiologic
48. Kannan BRJ, Anil SR, Kumar RK. Cannulation of patent arterial tolerance of ventricular septal defect closure after complete
duct in patients with pulmonary atresia and ventricular septal unifocalization in patients with pulmonary atresia, ventricular
defect. Catheter Cardiovasc Interv. 2005;65:455-58. septal defect, and major aortopulmonary collaterals.
49. Gewillig M, Boshott DE, Dem J, et al. Stenting the neonatal Circulation. 2009;120:S46-S52.
arterial duct in duct-dependent pulmonary circulation: new 64. Carotti A, Di Donato RM, Squitieri C, et al. Total repair of
techniques, better results. J Am Coll Cardiol. 2004;43:107-12. pulmonary atresia with ventricular septal defect and major
50. Duncan BW, Mee RB, Prieto LR, et al. Staged repair of tetralogy aortopulmonary collaterals: an integrated approach. J Thorac
of Fallot with pulmonary atresia and major aortopulmonary Cardiovasc Surg. 1998;116:914-23.
collateral arteries. J Thorac Cardiovasc Surg. 2003;126:694-702. 65. Reddy VM, McElhinney DB, Amin Z, et al. Early and intermediate
51. Mei J, Ding FB, Zhu JQ, et al. A novel two-stage complete outcomes after repair of pulmonary atresia with ventricular septal
repair method for pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries: experience
defect and major aortopulmonary collateral arteries. Chine with 85 patients. Circulation. 2000;101:1826-32.
Medi J. 2010;123(3):259-64. 66. FJ Puga. Unifocalization for pulmonary atresia with ventricular
52. Luciani GB, Wells WJ, KhongA, et al. The clamshell incision septal defect. Ann Thorac Surg. 1991;51:8-9.
for bilateral pulmonary artery reconstruction in tetralogy 67. Cho JM, et al. Early and long-term results of the surgical
of Fallot with pulmonary atresia. J Thorac Cardiovasc Surg. treatment of tetralogy of Fallot with pulmonary atresia, with
1997;113:443-52. or without major aortopulmonary collateral arteries. J Thorac
53. Murthy KS, Krishnanaik S, Coelho R, et al. Median sternotomy Cardiovasc Surg. 2002;124:70-81.
single stage complete unifocalization for pulmonary atresia, 68. Ishibashi N, Shin’oka T, Ishiyama M, et al. Clinical results
major aorto-pulmonary collateral arteries and VSD-early of staged repair with complete unifocalization for pulmonary
experience. Eur J Cardio-thorac Surg. 1999;16:21-25. atresia with ventricular septal defect and major aortopulmonary
54. Murthy KS, Rao SG, Naik SK, et al. Evolving surgical collateral arteries. Europ J Cardio-thoracic Surg. 2007;32:202-08.
management for ventricular septal defect, pulmonary atresia, 69. Belli E, Mace iL, Ly M, et al. Surgical management of pulmonary
and major aortopulmonary collateral arteries. Ann Thorac atresia with ventricular septal defect in late adolescence and
Surg. 1999;67:760-4. adulthood. Europ J Cardio-thoracic Surg. 2007;31:236-241.
55. Maskatia SA, Feinstein JA, Newmon B, et al. Pulmonary 70. Griselli, et al. The influence of pulmonary artery morphology
reperfusion injury after the unifocalization procedure for on the results of operations for major aortopulmonary collateral
tetralogy of Fallot, pulmonary atresia, and major aortopulmonary arteries and complex congenital heart defects. J Thorac
collateral arteries. J Thorac Cardiovasc Surg. 2012;144:184-89. Cardiovasc Surg. 2004;127:251-58.
56. Tchervenkov CI, Salasidis G, Cecere R, et al, One-stage 71. Reinhartz O, et al. Unifocalization of Major Aortopulmonary
midline unifocalization and compute repair in infancy versus Collaterals in Single-Ventricle Patients. Ann Thorac Surg.
multiple-stage unifocalization followed by repair for complex 2006;82:934-9.
heart disease with major aortopulmonary collaterals. J Thorac 72. Carotti A, et al. Determinants of outcome after surgical
Cardiovesc Surg. 1997;144:727-37. treatment of pulmonary atresia with ventricular septal defect
57. Reddy VM, Petrussion E, McElthime DB, et al. One- and major aortopulmonary collateral arteries. J Thorac
579
stage complete unifocalization in infants: when should the Cardiovasc Surg. 2010;140:1092-03.
C hapter
Pulmonary Atresia with Intact

40 Ventricular Septum
Marhisham Che Mood, Mazeni Alwi
INTRODUCTION The incidence of this malformation over a 5 year study period

was 4.5 per 100,000 live births.
In a congenital cardiac malformation where there is a combi- From our own hospital data, right heart hypoplasia—a
nation of major lesions, pulmonary atresia features common- great part of which falls under the spectrum of PAIVS—
ly. This may be hearts with two-ventricle physiology such as is more common than hypoplasia of the left heart, which
tetralogy of Fallot with pulmonary atresia, transposition of encompasses the variants of hypoplastic left heart syndrome
great artery with ventricular septal defect and pulmonary atre- and some neonates with critical aortic stenosis in the setting of
sia, or those with single ventricle physiology such as tricuspid a small left ventricle. This appears to be the shared experience
atresia, and those in association with atrial isomerism. of other large centers in Asia. Whether this is a reflection of
Pulmonary atresia with intact ventricular septum (PAIVS) the true incidence in the population remains to be validated in
denotes an isolated abnormality of the right ventricular outflow a well-conducted population-based study.
tract, i.e. complete obstruction of forward flow from the right However, the incidence of PAIVS in modern population
ventricle into the pulmonary arteries. However, the range of based studies must be interpreted in light of the impact that
pathology embraced by this diagnosis, its management and fetal echocardiography service has made. This is a diagnosis
long-term outcome are far from simple that the designation that can be made readily in fetal life and it is one of the
tends to suggest. While echocardiography allows accurate commoner causes for termination.4 From the same UK and
diagnosis of this congenital lesion even in fetal life, Ireland population-based study, 86 fetal diagnosis were made
angiography remains an important imaging technique to fully at a mean of 22 weeks gestation, leading to 53 terminations
describe the anatomic details. Even with advances in cardiac (61%).
surgery, interventional techniques and intensive care unit
(ICU) care today, PAIVS remains a management challenge to MORPHOLOGY
the team that dedicates itself to the care of infants and children
with congenital heart disease (CHD). Right Ventricle
Incidence Although the designation of the disease suggests an anomaly
primarily of the right heart outflow, PAIVS generally
From the various hospital data, PAIVS makes up from 0.71 to involves other structures of the right heart and in a small,
2.5 percent of children with CHD.1 At the National Heart Insti- but significant subgroup of patients, the coronary arterial
tute, Kuala Lumpur, from 2000 to 2010 PAIVS makes up 1.1 circulation as well. There is a remarkable morphologic
percent of all new cases seen annually. Accurate data on the inci heterogeneity in PAIVS particularly with regard to the right
dence of this malformation in the population is scant. The Balti- ventricle (RV) and right ventricular outflow tract (RVOT).
more Washington Infant study reported an incidence of 8.1 per This morphologic variation represents a continuum from a
100,000 live births for the period 1981 to 1989.2 In the modern near-normal RV to one where there is very severe hypoplasia
era, the United Kingdom (UK) and Ireland Collaborative Study of the RV,5-10 and somewhat outside of this continuum are
on PAIVS was a comprehensive population based study on this those with very severe tricuspid regurgitation (TR) due to
disease that provides valuable data on the incidence, morpho- associated severe Ebstein’s anomaly, with thinned out and
logic details, the various management strategies and outcome.3 markedly dilated right ventricle.11
Qualitative and Quantitative Evaluation, Classification the extreme end of the critically stenotic pulmonary valve. 40
Nevertheless the RV size is seldom 'normal' as hypertrophy
Because of the diversity of RV morphology and size, some of the RV myocardium causes mild hypoplasia and reduction
Pulmonary Atresia with Intact Ventricular Septum

sort of classification and quantitative assessment would be of the RV cavity.1,17-19 In this group of patients the TV is
useful in understanding the nature of the disease, planning often normal in appearance although mild dysplasia with
its management and counseling parents in regard to long- regurgitation is not uncommon. Its dimension as measured by
term prognosis. Beyond the earlier, simplistic classification annulus size is smaller than normal and the TV/mitral valve
of the RV size as small or large, De Leval’s morphologic annulus ratio is > 0.75. In this group of patients the TV Z-score
classification into tripartite, bipartite and unipartite RV is > –2.0 as calculated by the normogram by Rowlatt.13 In
according to the number of parts of the RV not obliterated some patients the trabeculations in the RV infundibulum are
by muscular overgrowth remains a useful guide in describing prominent and may cause dynamic obstruction once the valvar
the RV and subsequent management.9 For a more quantitative atresia is abolished.20 Occasionally, there is fixed subvalvar
assessment of the RV size, the diameter of the tricuspid valve muscular obstruction caused by abnormal muscle bundles that
(TV) normalized to body surface area—the Z score—has been will require additional intervention in the form of surgery
advocated by the Congenital Heart Surgeons Society (CHSS).12 (Figure 1C).
However the normogram used is based on Rowlatt’s 'normal' Usually, in hearts with mild RV hypoplasia and membranous
data obtained from postmortem measurement of formalin fixed atresia the coronary circulation is normal, i.e. there is no
specimens.13 The UK and Ireland collaborative study used the persistence of RV-coronary sinusoidal communication or
normograms based on echocardiographic data of 125 normal RV-coronary arterial connections. However, there are few
children by Daubeney.14 For a given TV diameter, there is a instances where these connections exist in hearts with this
wide discrepancy between the Z score values derived from very favourable anatomy. From the UK and Eire collaborative
the 2 normograms, the former understandably giving less study, this subgroup make up 58.7 percent of the entire cohort
marked departure from the normal values due to shrinkage of and our own observation is very much in accordance with
formalin-fixed specimens. The tricuspid/mitral annulus ratio this.3
and RV inlet length Z scores are also helpful in giving an idea
of the RV size.15,16 Muscular Atresia, Very Severe RV Hypoplasia (Unipartite)
Membranous Atresia, Tripartite RV, Mild RV Hypoplasia At the other end of this continuum is the RV which is severely
hypoplastic on account of complete or near obliteration of the
At one end of this spectrum are hearts where the RV is infundibulum by muscle, i.e. 'muscular' atresia.9,17,21,22 Often,
near normal in size and morphology. The inlet, trabecular what appears to be complete obliteration of the infundibulum,
and infundibular components are well developed and the upon probing with a catheter at angiography may reveal a tiny
pathologic abnormality is a thin membranous imperforate slit reaching up to the valve annulus (Figure 2). However it is
valve (Figures 1A and B). This can perhaps be considered doubtful if this can be refashioned into a functioning RVOT.
A B C
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 581
'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
8
A B A B
Figures 2A and B: Muscular atresia with generally hypoplastic right Figures 3A and B: Membranous atresia with moderate right ventricle
ventricle (RV): A. RV angiogram in anteroposterior (AP) projection (RV) hypoplasia (intermediate): A. RV angiogram in anteroposterior
showing mainly an inlet component of the RV. The outlet component projection showing an overall small RV, but three components of the RV
is merely a slit that extends towards where the valve annulus should are present. The apical trabecular component is the least developed.
normally be (thin arrow). An RV-coronary connection with stenosis is Numerous minor RV-coronaries connections are present; B. Bipartite
seen (broken arrow); B. RV angiogram in AP projection of another RV- the inlet and outlet components are well-developed, but the apical
patient with muscular atresia with severely hypoplastic RV. 2 large trabecular component is virtually obliterated by muscles except for
RV-coronary connections are seen (arrows) some intertrabecular recesses. There is mild tricuspid regurgitation
The trabecular component, except for slits of inter-trabecular Minor connections < 2 mm are not uncommon, but ectatic
spaces is also virtually obliterated by muscle, leaving a severely connections may also be present. In our series of 143 patients,
attenuated inlet part of the RV guarded by a TV, which has a 25.9 percent were categorized as those with 'intermediate'
hypoplastic annulus. These are hearts whose RV is unlikely subgroup or having bipartite RV.27 With adequate opening
to be able to support the pulmonary circulation independently, of the atretic valve, the well-developed infundibulum allows
hence destined for single ventricle management pathway. This unobstructed flow into the pulmonary arteries.
subgroup made up 7.7 percent of the UK and Eire collaborative
study3 whereas it appeared to make up a far higher proportion Thinned and Dilated RV, Ebstein’s Anomaly or
in one hospital based study.23 Dysplastic Tricuspid Valve
There is a strong correlation between muscular atresia of
the infundibulum and severe RV hypoplasia with the presence Somewhat outside this continuum of RV morphology from
of major RV—coronary arterial connections. Some of these near normal RV to the severely hypoplastic, unipartite RV
are associated with major obstructions and interruptions of the are the rare patients with PAIVS in association with severe
proximal coronary arteries, making the coronary circulation Ebstein’s anomaly or dysplasia of the TV. The RA and
‘RV dependent’ (Figures 2A and B).24-26 atrialized RV are markedly dilated giving rise to a 'wall to
wall' heart. The remaining part of RV and infundibulum
Moderate RV Hypoplasia, Bipartite RV, Membranous are also markedly thinned and dilated, ending blindly in
Atresia (Intermediate) an atretic pulmonary valve with a small annulus. This may
account for up to one-sixth of patients with PAIVS.11 In the
Between the two ends of the continuum are gradations of UK and Eire collaborative study this made up 5.4 percent.3
RV cavitary hypoplasia. In some of these patients, the three RV-coronary arterial connections are virtually unknown in
components of the RV are moderately hypoplastic due this subgroup.
to muscular overgrowth significantly reducing the apical
trabecular component and the infundibulum. However, we also Right Atrium, Right Ventricle and Tricuspid Valve
observe that in others only the apical trabecular component is
virtually obliterated save for slits of inter-trabecular spaces The tricuspid valve too often exhibits a range of abnormalities
whereas the inlet and the infundibulum are reasonably well from the severely stenotic valve with very small annulus
developed, i.e. a ‘bipartite’ RV. The infundibulum ends blindly to the severely dysplastic valve or frank Ebstein’s anomaly
with membranous atresia (Figures 3A and B). We term this causing severe regurgitation.5 Even when the valve apparatus
group of patients as ‘intermediate’ RV. The TV Z score may appears normal, a mild degree of TR is often seen due to the
not be as satisfactory as those with favourable anatomy, giving high RV pressure.
values between –2.0 to –5.0 and, so are the other values of RV The RA is often mildly dilated in the presence of a
dimensions such as inlet length and TV/mitral valve annulus competent TV due to poor RV compliance. When there is
ratio. The occurrence of RV-coronary arterial connections severe TR due to dysplastic valve or Ebstein’s anomaly, the
582 in this subgroup also lies somewhat in between the two. RA will be markedly dilated.
Patent Ductus Arteriosus, Pulmonary Arteries Coronaries Arteries 40
and Pulmonary Valve
A peculiar feature of PAIVS is its association with

The patent ductus arteriosus (PDA) is almost always present ventriculo- coronary connections between the RV and
providing the sole source of pulmonary blood flow. Hence, subepidcardial coronary arteries.24-26 These may be major
PAIVS is generally a duct-dependent cyanotic heart disease. fistulous communications with ectatic coronary arteries
However in rare cases the pulmonary blood supply is by major or minor communications. Reports on the incidence of
aortopulmonary collaterals. The PDA morphology is often ventriculo- coronary connection vary greatly. Giglia in 1992
nearly similar to isolated PDA where it is short and arises from reported an incidence of about one third,30 whereas Calder
the proximal descending aorta, inserting onto the dome of the reported 60 percent incidence in a postmortem series.31 The
main pulmonary artery (MPA). However, not uncommonly the UK and Ireland collaborative study reported major fistulae
PDA resembles that of other cyanotic CHD where it arises more in 33 patients and minor in 28 from a cohort of 183 patients,
proximally from underneath the aortic arch, often long and may giving total incidence of 45.8 percent.3 Minor connections
be tortuous in this configuration and inserts onto the proximal were defined as slight filling of non-dilated coronary
part of the left pulmonary artery (LPA) with the potential of arteries with RV angiogram whereas 'major' describes
causing LPA stenosis following ductal constriction.28,29 prominent filling of one or more, usually dilated, coronary
In hearts with mild RV hypoplasia, the main and branch arteries with retrograde filling of the aorta. A phenomenon
pulmonary arteries are often mildly hypoplastic or near- normal associated with major ventriculo-coronary connections is
in dimensions, with well-developed sinuses 'cupping' over the the RV-dependent coronary circulation (RVDCC). This is
membranous valve with near-normal annulus size (Figure1B). due to coronary arterial interruption, absent aortocoronary
In those with more severe RV hypoplasia especially of the connection or unequivocal stenosis of one or more of the
RVOT, the annulus is small and the valve plate is thick and coronary arteries.12,17,25,32-34 Markedly ectatic coronary
non-doming. The pulmonary root and sinuses are not as well arteries are also considered in this category by many as
developed (Figure 4). RV decompression would result in major coronary steal
In hearts with 'muscular' atresia of the infundibulum, the through the ectatic vessels to the RV. Modern angiography
pulmonary root and annulus may be severely hypoplastic, and catheter interventions afford some insight into this.
but nevertheless the branch pulmonary arteries tend to be In our limited experience, given that major RV-coronary
confluent and fairly well developed. 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
CLINICAL PRESENTATION AND FINDINGS

Figure 4: Simultaneous angiogram of right ventricular outflow tract The pulmonary circulation in PAIVS is ductus dependent,
and descending aorta opposite the patent ductus arteriosus in lateral
projection showing well-developed infundibulum, but thick valve plate
except in the rare cases where systemic-to-pulmonary
collateral arteries supply the pulmonary blood flow. Hence, 583
(arrow) and poorly developed main pulmonary artery sinuses
8
A B C
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 Chest X-ray
constriction and closure of the ductus arteriosus, which
generally takes place in the neonatal period. Cyanosis is Features that may suggest the diagnosis of PAIVS are right
the most common presentation. Occasionally, especially in atrial enlargement in cases where there is significant TR,
communities with limited access to medical care, these infants and an oligaemic lung fields. This however may be difficult
may present in a critical state with low output and acidosis to distinguish from normal in the neonate. The appearance
consequent to severe hypoxemia. of wall-to-wall heart, a feature of severe Ebstein’s anomaly,
As fetal cardiac service is increasingly becoming a should also raise the possibility of coexisting true, anatomic
norm, fetal diagnosis of PAIVS allows early transfer to pulmonary atresia (Figure 6).
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 Ebstein’s 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.
INVESTIGATIONS
Electrocardiogram
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
Figure 6: Postero-anterior chest radiograph showing a 'wall to wall'
than the usual right ventricular hypertrophy.5 The tall peaked heart in a neonate with PAIVS in association with severe Ebstein’s
584 P-waves of right atrial enlargement may be present. malformation of the tricuspid valve
Imaging and Hemodynamics—Echocardiography, hypoplastic, with only a very small inlet guarded by a small 40
Cardiac Catheterization and Angiography TV. The apical trabecular component is obliterated as is the
outlet, i.e. muscular atresia.

The wide anatomic spectrum of PAIVS, embracing hearts In hearts where the atresia is membranous with all three
whose RV is near-normal to those with severe RV hypoplasia, parts fairly well-developed, this is termed a tripartite RV. In
which is unlikely to be functional as an independent pump between is the bipartite RV where there are well-developed
for the right heart circulation means that the management inlet and infundibulum with membranous atresia, but the
strategy will be radically different from one subgroup to the apical trabecular part is virtually obliterated by muscle.
other, i.e. two-ventricle pathway with excellent medium term For quantitative evaluation of RV size, the TV diameter in
outcome for patients with favourable morphology and the diastole is measured and its Z value derived from available
single ventricle pathway with its attendant late morbidities normograms.13,14 The RV inlet length Z-score (TV annulus
and attrition for patients at the other end of the anatomic to apex at ventricular end-diastole) and area Z-score at end-
spectrum. Hence, merely confirming the diagnosis, whilst not diastole with maximal area bordered by RV endocardium are
difficult, is insufficient. Detailed evaluation particularly of additional measurements that may be useful in defining the
the RV morphology and size is essential for the appropriate degree of RV hypoplasia.15 The ratio of tricuspid to mitral
management strategy of each individual patient. valve diameters in diastole is also useful as it provides an
Echocardiography provides excellent information for immediate comparison between the RV and LV sizes.16 While
this initial decision making. However, angiography, a very assessing the RV, large ventriculo-coronary connection may
invasive technique in a fragile newborn, remains an essential be readily identified by color Doppler, but its entire course and
imaging technique that confirms the echocardiography obstruction, if present, can only be ascertained by angiography.
findings and complements what the latter is unable to provide Apart from measuring the TV diameter, the valve apparatus
with certainty. In the modern era, as interventional catheter- should also be examined as stenosis, dysplasia and Ebstein’s
based therapies play a major role in the first line management malformation are common associations. The degree of TR and
of PAIVS in at least half of the patients, i.e. those with RA dilatation should be described and an estimate of the RV
membranous atresia, the place of cardiac catheterization in systolic pressure can be obtained by Doppler CW (Figures 7A
diagnosis and therapy becomes all the more central. and B).
The pulmonary valve annulus and pulmonary artery
Echocardiography dimensions should also be measured. The PDA morphology
and dimensions as described earlier should be noted
The diagnosis of PAIVS can be readily made by especially if PDA stenting is to be offered as part of the initial
echocardiography.38-40 Except for hearts where the RV is treatment. However PDAs that are long and tortuous may not
nearly normal in size and appearance, the features of a be adequately visualized by echocardiography.
hypertrophied RV with reduced cavity guarded by a small Finally, in patients with severe Ebstein’s malformation,
tricuspid valve on the 4-chamber view are immediately it should be determined whether the atresia is functional or
striking and Doppler evaluation of the pulmonary flow pathologic in nature. Color Doppler by means of documenting
confirms the diagnosis of absence of forward flow from the pulmonary regurgitation often allows this distinction to be
RV occasioned by complete obstruction. However, much made.11
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. A B
The RV morphology should also be described and Figures 7A and B: Echocardiography—A. Apical four-chamber view
categorized whether the parts—inlet, apical-trabecular and of a patient with PAIVS. The tricuspid valve annulus is small (8 mm)
compared to the mitral valve (14 mm). The apical trabecular component
outlet—are present, well developed or otherwise obliterated is attenuated. The right atrium is dilated with the atrial septum bowing
with muscle. Unipartite RV is where the RV cavity is severely to the left. B. Color Doppler showing severe tricuspid regurgitation
585
8 Cardiac Catheterization and Angiography infants or those small for gestational age, prolonged PGE1
infusion may be necessary before it is considered safe or
Although echocardiography can readily confirm the diagnosis feasible for surgical or catheter intervention. In our own
and provide anatomic details that would be important for experience, it is best for the infant to achieve a weight of
management strategy, PAIVS is one condition where cardiac 3.0 kg before any form of intervention is considered.
catheterization and angiography remains an essential part Today, better understanding of the wide morphologic
of the initial evaluation.1 This is particularly so for centers variation of the disease, as well as advances in surgical and
where catheter based therapy plays a prominent role in the interventional techniques have led to better early survival and
management of this disease. at least medium term outcome of this disease.8,9,12,17,23,43-48
Firstly, even if the size and morphology of the RV can be In patients with the most favorable anatomy with
obtained by echocardiography, detailed characterization of the membranous atresia and all three parts of the RV being well
RV such as the degree of obliteration of the apical trabecular developed, RV decompression in the neonatal period with
zone and the RVOT may be difficult. Intertrabecular spaces either surgical valvotomy or transcatheter method would often
in this region may not be obvious. In the RVOT, presence of be the only procedure required, and thereafter it is reasonable
muscle bundles that reduce the infundibular cavity or cause to expect normal two-ventricle circulation with no further
fixed subvalvar obstruction, the size of the pulmonary valve procedures required at least until early adult life. However this
annulus, thickness of the atretic valve plate and the dimension may apply to only about half of PAIVS patients.
of pulmonary artery root can only be detailed accurately by In the remainder, multiple interventions, either surgical or
angiography. In hearts with diminutive unipartite RV, a tiny transcatheter, will be required at least in the first few years
slit-like infundibulum is not uncommonly present when RV of life. Hence, a good teamwork between the interventional
angiography is performed (see Figure 2A). This impacts on cardiologist, cardiac surgeons and the rest of the care givers
one’s decision whether transcatheter perforation of the atretic involved is essential in the management of these patients.
valve and RV decompression by balloon dilatation would be From the outset the parents should be counselled regarding
the appropriate management. the nature of their infant’s specific morphologic details, the
Another reason for angiography remaining an essential likely clinical course and the long-term treatment plan and
imaging technique is for the detailed evaluation of ventriculo- goals, which may require significant revisions along the way
coronary connections (see Figure 5).17,35 Whilst large ectatic according to the outcome of preceeding treatments.
connections can be seen by echocardiography without The desired goal is to achieve eventual two-ventricle
difficulty, the dimensions, course and more importantly the circulation with all intracardiac and extracardiac shunts
presence or otherwise of stenoses, interruptions and absent (PFO/ASD and Blalock Taussig shunt/PDA stent) closed,
aortic-coronary connection of this abnormality is beyond the obstruction to RV outflow virtually abolished and significant
capability of this otherwise excellent non-invasive imaging tricuspid valve regurgitation corrected. However this goal is
technique. Minor connections may not be detected by perhaps realistically achievable in only 50 to 60 percent of
echocardiography. Similarly echocardiography is limited in patients. Some patients from the outset appear destined for
its capability for full characterization of the PDA morphology, the single ventricle track and in between are those in whom it
an important consideration when PDA stenting is planned as is reasonable to set the objective of two ventricle-circulation
alternative to conventional systemic-pulmonary shunt.41,42 at the first assessment but eventually this may need to be
Additionally, cardiac catheterization provides important downgraded to what is termed '1½ ventricle circulation'
hemodynamic data such as RV systolic pressure, central when the RV does not grow sufficiently after successful RV
venous pressure (CVP), aortic pressure, LV end-diastolic decompression. Cardiac transplantation may be advocated in
pressure and systemic oxygen saturation. the rare cases of severe RV hypoplasia with major ectatic RV-
coronary connections and RVDCC and in those with extreme
MANAGEMENT Ebstein’s anomaly with wall-to-wall heart, it may be wise to
offer compassionate care.
Pulmonary artesia with intact ventricular septum (PAIVS) Our management algorithm is based on morphologic
being a duct-dependent lesion, survival beyond the neonatal evaluation by echocardiography and RV angiography. As
period or early infancy is not possible without intervention described in the foregoing sections there is a spectrum of
except in the rare cases where aortopulmonary collaterals RV size and morphology. For making clinical decisions and
provide a stable source of pulmonary blood flow. Intravenous long term plan and counseling, it is practical to categorize
PGE1 infusion to maintain ductal patency is an important first patients as having good RV size and morphology, severe RV
line treatment. Acidosis, hypothermia and poor peripheral hypoplasia with muscular atresia and in between these two
perfusion should be corrected when present. For preterm extremes, those with 'intermediate' RV.10
586
Good Right Ventricular Size and Morphology 40
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
A B
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, C D
open transpulmonary valvotomy or RV outflow patch/ Figures 8A to D: PAIVS with membranous atresia-valvotomy with
reconstruction especially when the RVOT and valve annulus balloon dilatation. A. Simultaneous right ventricular angiogram
and aortogram opposite the patent ductus arteriosus showing thin
is small or fixed subvalvar stenosis is also present.46,49-53 There
membranous with well-developed infundibulum, valve annulus and
is considerable morbidity and mortality to these procedures main pulmonary artery (MPA) sinuses. The tip of a Judkins right
especially with the more extensive RVOT reconstruction. Not catheter is placed underneath the valve plate; B. The tip of the
uncommonly, Blalock Taussig shunt (BT shunt) is performed 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
concomitantly with RV decompression as a significant
number of patients remained hypoxic after unobstructed flow
into the pulmonary arteries has been established, even in wall due to inaccurate positioning of RF wire are potential
patients whose RV appear only mildly hypoplastic.50,54 This major complications.18
may be explained by reduced RV compliance in patients with Uncommonly, despite seemingly good RV size and adequate
PAIVS where the RV is generally hypertrophied. Routine RV decompression, the patient remains deeply cyanosed due
'prophylactic' BT shunt avoids the need for unplanned to poor RV compliance. A BT shunt or PDA stenting can be
reintervention early following the initial surgery. Otherwise performed to augment pulmonary blood flow. Otherwise the
the patient may need to be on PGE1 infusion for a few weeks patient may remain hospital bound for weeks on PGE1.60
until RV compliance improves significantly. The medium-term outlook is excellent with adequate RV
In the early 1990s transcatheter valvotomy and balloon decompression. Normal or near normal RV growth can be
dilatation provided alternative to conventional surgery. expected and further interventions often not required at least
Perforation of the atretic valve with laser wire and the sharp until early adult life, where progressive pulmonary or TR
stiff end of the coronary guidewire were reported at nearly may require to be addressed surgically. However, restenosis
the same time.55-57 The former is bulky, the initial capital of the pulmonary valve may occur requiring repeat balloon
outlay is expensive and poses risk of retinal injury to catheter dilatation. It is well known that concomitant fixed subvalvar
laboratory staff, requiring them to wear protective goggles. stenosis may coexist and requires RVOT reconstruction.20 In
The latter, due to its stiffness affords little control for accurate general, if the patient is stable, it is reasonable to delay surgical
perforation of the valve and may instead cause perforation of reintervention until the infant is at least 4 to 6 months of age
the RVOT, sometimes with major consequences. Perforation when the risk of mortality and morbidity is lower. Additional
with radiofrequency (RF) wire has rendered the above two problems that may also require surgical reintervention is
methods largely obsolete as better control and accurate significant TR.
perforation can be achieved, and the RF generator is
inexpensive, small and portable.20,58,59 Severe Right Ventricular Hypoplasia
Once valvotomy is successful, the valve is progressively with Muscular Atresia
dilated with a coronary balloon followed by the appropriate
sized balloon for annulus size (Figures 8A to D). This For patients at the other end of the spectrum—those with
technique has gained acceptance in many institutions today. severe RV hypoplasia where there is muscular atresia of the
Perforation of the RVOT or dissection of the pulmonary artery infundibulum, the apical trabecular part obliterated by muscles 587
8 and only a diminutive inlet is present guarded by a very small problems with transplantation, this is hardly considered
tricuspid valve, RV decompression is not likely to be feasible today.23,64,65
at the outset. Repair towards single-ventricle circulation is the
appropriate management plan.10 Added to the problem of a “Intermediate” Right Ventricular

non-functional diminutive RV is the presence of RV-coronary
connections in a significant number of patients in this group, There is a significant proportion of patients whose RV size and
some with RVDCC. After a successful Fontan completion, morphology fall between the two extremes, what we would
long-term exposure of the coronary arteries to very high term 'intermediate' RV.10 These patients have reasonably well
RV pressures may lead to early, progressive coronary artery developed infundibulum and the atresia is at valvar level,
disease, ischaemia and infarction. which is often thin and membranous, but may be thicker than
The first procedure is creation of a systemic pulmonary the usual. The inlet part is also well developed, albeit with
shunt, which invariably in today’s surgical practice is the the tricuspid valve diameter smaller than those with the most
modified BT shunt. Neonatal BT shunt is a commonly favourable morphology, but not diminutive as those with
performed procedure for lesions with duct-dependent unipartite RV and muscular atresia. The TV Z score generally
pulmonary blood flow. However, the diagnosis of PAIVS is falls between –2.0 to –5.0 and the TV/MV diameter ratio of
an independent risk factor for mortality and morbidity. In 0.50 to 0.75. However, the apical trabecular part is virtually
a recent publication from the STS database, the discharge obliterated by muscles except for slits of inter-trabecular
mortality for PAIVS patients was 15.6 percent, compared spaces. Minor RV-coronary connections are not uncommon
to 7.2 percent for the overall group of neonatal BT shunts.61 but major connections may also be present. Because of
However this risk was not further stratified according to the fairly well developed infundibulum and atresia limited to
presence or otherwise of major RV-coronary connections the valve, even though valve annulus and infundibulum
and RV dependent coronary circulation. Because of this high may be smaller than those with favourable anatomy above,
mortality risk for neonatal BT shunt, our preference in patients RV decompression is feasible and it is reasonable to have
with this morphology is to stent the PDA, a far less invasive the objective of biventricular circulation pathway at the first
procedure.10 In general, the PDA in PAIVS is not as complex evaluation. This means RV decompression by conventional
as those in other cyanotic heart disease. They may be more surgery or transcatheter valvotomy and balloon dilatation as
elongated than isolated PDA and arise further proximally from the first procedure. Surgically, RVOT reconstruction is more
the aortic arch, but exceeding tortuosity is not common. PDA often required because of a tendency for smaller valve annulus
stenting can generally be performed without great technical and subvalvar muscle bundle to be present. However because
difficulty.62,63 Unlike other cyanotic heart disease, the PDA in of the smaller RV cavity due largely to near-obliterated apical
PAIVS intends to insert onto the dome of main pulmonary trabecular part, the patient may remain severely hypoxic even
artery rather than proximal left pulmonary artery, making late after an adequate RV decompression. A BT shunt should also
LPA stenosis a less common problem. In our opinion, a PDA be created at the time of RVOT reconstruction.
that inserts onto the proximal LPA is a contraindication for Our preference is to perform RF valvotomy and balloon
PDA stenting because of the above problem, in which case dilatation to decompress the RV and concomitantly stent
surgical systemic-pulmonary shunt is the preferred initial the PDA to tide the patient over in the expectation that in a
palliation. LPA stenosis often eventually occurs in this setting significant proportion of patients the RV will grow sufficiently
but ductal stenting accelerates the process. Another advantage and complete biventricular circulation will be achieved
of PDA stenting is that balloon atrial septostomy can be (Figures 9A to E).27 With pulmonary blood flow from RV and
performed at the same time if the inter-atrial communication the stented PDA, if the patient remains clinically stable we
appears restrictive. Durability of palliation afforded by PDA would closely monitor until 3 to 4 years of age. If the RV
stenting generally is shorter compared to surgical shunt has grown adequately as assessed by echocardiography and
because of neointimal proliferation.41 angiography and the patient is clinically pink, we would close
As the first stage of single ventricle repair, the bidirectional all shunts (PFO and stented PDA) by transcatheter method
Glenn shunt needs to be performed at 12 months. Occasionally and consider that biventricular circulation has been achieved.
this has to be performed even earlier, at 4 to 6 months due Often, flow through the stented PDA would be very restrictive
to very restrictive flow through the stented PDA. Fontan by this time and if the PFO is also restrictive, this procedure is
completion is generally performed at 4 to 6 years of age. not required.
Because of the risk of premature coronary artery disease In patients in whom there has been sufficient RV growth,
and high risk of BT shunt, transplantation is another option it is often the apical trabecular part that manifests this most
for patients with muscular atresia, diminutive unipartite RV, remarkably. However other patients may not exhibit as good
major RV-coronary connections and RVDCC. However, RV growth and cyanosis persists. They should be considered
with improved survival with Fontan surgery and the inherent for one and half ventricle circulation, where a bidirectional
588
40

A B C
D E
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 Instead of conventional surgery with the construction of BT
closed.12,66-68 shunt and repair of the TV, RVOT reconstruction + reduction
Additional problems such as subvalvar stenosis and TR are of the grossly dilated right chambers, the technique advocated
tackled preferably at the same time. Only short and medium by Starnes has shown some commendable, if mixed results.70
term data is available, but this approach appears a reasonable This involves converting the TR to atresia and the construction
strategy for this group of patients with 'intermediate' RV.27 of BT shunt, followed later by single-ventricle palliation.
Starnes’ original patients were those with severe Ebstein’s
Thinned and Dilated Right Ventricular, Ebstein’s with functional pulmonary atresia, but fundamentally the
Anomaly, Severe Tricuspid Regurgitation technique can be equally applied to those with anatomic
atresia of the pulmonary valve. Nevertheless this subgroup of
The final subgroup of PAIVS patients are those associated patients, whose grossly dilated and thinned out RV falls outside
with severe Ebstein’s malformation or dysplasia of the TV, the continuum of mild to very severe hypoplasia, continues
leading to very severe TR, thinned out RV and grossly dilated to have the poorest prognosis when major improvement in
right heart chambers, i.e. the 'wall-to-wall heart'. While early medium term survival has been achieved for the others.
and medium term survival of those with diminutive RV and One of the attractive, potential merits of fetal intervention
major RV-coronary connections have improved significantly is alteration of natural course of disease. If fetuses who can
with single ventricle palliation, the prognosis for those be predicted to develop grossly dilated right heart and severe 589
severely dilated thinned out RV remains very poor.11,43,69 tricuspid regurgitation can be identified, perhaps this is one
8 indication for such a procedure.71,72 However, apart from essentially a near normal RV with membranous atresia of
accurate diagnosis and 'patient' (fetus) selection, there are the pulmonary valve to a complex malformation where the
major issues of competence and training of the fetal cardiology RV is almost obliterated by muscles except for a diminutive
team, service organization and of ethics that make this still an inlet cavity and frequently associated with major RV-coronary
experimental procedure. connections. Between the extremes are hearts with varying
degrees of RV cavitary hypoplasia particularly involving the
PROGNOSIS AND LONG-TERM SURVIVORS apical and infundibular parts, abnormalities of the tricuspid
OF pulmonary atresia with INTACT valve and less severe forms RV-coronary connections.
ventricular septum Echocardiography has played a major role in the
understanding PAIVS morphology and morphometry of
Pulmonary atresia with intact ventricular septum remains the right heart structures such as the size of the TV and RV
among lesions that have higher risks for morbidity and lower 1 inlet length allows a semi-quantitative assessment of the
and 5 year survival. Low birth weight, unipartite RV, significant severity RV underdevelopment. However PAIVS is one
RV dilatation/Ebstein’s anomaly and greater severity of condition where the invasive cardiac catheterization remains
coronary arterial abnormalities and earlier era of surgery an essential imaging tool especially in the evaluation of RV-
are the commonly cited independent risk factors.12,43,69,73 coronary connections. This is particularly so in the current
However, with better understanding of the remarkably varied era of interventional cardiology where pulmonary valvotomy
anatomy of PAIVS and management strategies based on RV with balloon dilation, and to certain extent PDA stenting are
morphology, the outlook for these patients has continued to the preferred initial management in many centers.
improve. Advances in surgical techniques, ICU care and the A better understanding of the RV morphology allows
less invasive transcatheter techniques have also in a large formulation of management strategies that will result in
measure contributed to the current medium term results. It the best outcome for the patients. Although the 2-ventricle
remains to be seen, however, what happens to these patients circulation is desirable, this is only achievable in only about
in the long term. 60% of patients. For patients with the most severe form of
Present adult survivors of PAIVS belong to an earlier the disease, clearly the single-ventricle track is the only
surgical era and data is understandably scant. In a 12 year viable option, with the attendant late problems following the
study of 20 adult survivors of PAIVS, John et al reported five Fontan operation. Premature atherosclerosis due to coronary
deaths and all patients required reinterventions. 74 12 patients arteries perfused by hypertensive RV in those with RV-
had single ventricle anatomy and received Fontan operation or coronary connections is an added facet of late survival. The
palliative shunts and the remainder had 2 ventricle repair. The 1½ ventricle is an attractive option for those with moderate
highest number of reinterventions were in the biventricle repair RV hypoplasia where the bidirectional Glenn shunt partially
group, consisting of multiple pulmonary and TV replacements off loads the RV while maintaining pulsatile flow into the
and repairs, RV-PA conduit replacement, RVOT reconstruction, pulmonary circulation.
treatment of shunt-related RPA stenosis and mitral valve repair The outlook for many patients with PAIVS is better today
or replacement. In the single ventricle patients reoperation than it was 2 to 3 decades ago. However, for many who
were Fontan revision and conversion, fenestration and shunt survive into adult life with 2-ventricle circulation, progressive
revision or creation of an additional systemic-pulmonary shunt. tricuspid regurgitation and pulmonary regurgitation are likely
Although these patients were operated in an earlier era, to lead to re-interventions after many years of reasonably
the study highlights the multiple reinterventions that many normal survival. Transcatheter valve therapies are likely to
patients from the current era will likely need to undergo in change how this will be managed in the near future.
adult life due to the associated pathologies involving the The coming decades would be interesting to watch as
TV and pulmonary regurgitation that commonly results the cohort of patients from the current era reach adulthood,
following transcatheter or surgical valvotomy. However, especially those with 1½ and single ventricle circulation.
in the setting of two ventricle circulation, it is gratifying
to learn that late pulmonary valve replacement for severe It is not always in a physician's power to cure the sick; at
pulmonary regurgitation can be performed in PAIVS patients times the disease is stronger than trained art.
with excellent results, although results of TV repair suggest —Ovid
a need for further refinement of current surgical technique.75
REFERENCEs
Conclusion
1. Freedom RM, Nykanen DG. Pulmonary atresia and intact
In the last 2 decades there has been a tremendous improvement ventricular septum. In: Allen HD, Clark EB, Gutgesell HP,
in the understanding of the morphology of PAIVS, one that Driscoll DJ (Eds). Moss and Adams heart disease in infant,
590 is characterized by a remarkable diversity ranging from children and adolescents: including the fetus and young adult,
New York: Lippincott Williams and Wilkins; 2000. p. 845.
2. Perry LW, Neill CA, Ferencz C, Infants with congenital heart
disease: the cases. In: Ferencz C, Rubin JD, Loffredo CA,
20. Alwi M, Geetha K, Bilkis AA, et al. Pulmonary atresia with
intact ventricular septum percutaneous radiofrequency-assisted
40
Magee CA (Eds). Epidemiology of congenital heart disease. valvotomy and balloon dilation versus surgical valvotomy and

The Baltimore-Washington Infant Study 1981-1989. Mount Blalock Taussig shunt. J Am Coll Cardiol. 2000;35:468-76.
Kisco, New York: Futura; 1993.p.38. 21. Anderson RH, Anderson C, Zuberbuhler JR. Further
3. Daubeney PEF, Delany DJ, Anderson RH, et al. Pulmonary morphologic studies on hearts with pulmonary atresia and
atresia with intact ventricular septum. Range of morphology in intact ventricular septum. Cardiol Young. 1991;1:105-13.
population based study. J Am Coll Cardiol. 2002;39:1670-79. 22. Freedom RM, Moes CAF. The hypoplastic right heart complex.
4. Daubeney PEF, Sharland GK, Cook AC, et al. Pulmonary Semin Roentgenol. 1985;20:169-83.
atresia with intact ventricular septum: Impact of fetal 23. Jahangiri M, Zurakowski D, Bichell D, et al. Improved
echocardiography on incidence at birth and postnatal outcome. results with selective management in pulmonary atresia
Circulation. 1998;98:562-66. with intact ventricular septum. J Thorac Cardiovasc Surg.
5. Fricker FJ, Zuberbuhler JR. Pulmonary atresia with intact 1999;118:1046-55.
septum in Paediatric Cardiology, 2nd Edition. Eds: Anderson 24. Freedom RM, Harrington DP. Contribution of intramyocardial
RH, Baker EJ, Macartney RFJ, Rigby ML, Shinebourne EA, sinusoids in pulmonary atresia and intact ventricular septum to
Tynan M. Churchill Livingstone, 2002. a right-sided circular shunt. Br Heart J. 1974;36:1061-65.
6. Bowman FO, Malm JR, Hayes CJ, et al. Pulmonary atresia 25. Gittenberger-De Groot AC, Sauer U, et al. Competition of
with intact ventricular septum. J Thorac Cardiovasc Surg. coronary arteries and ventriculo-coronary arterial communica-
1971;61:85-93. tions in pulmonary atresia with intact ventricular septum. Int J
7. Murphy DA, Murphy DR, Gibbons JE, et al. Surgical treatment Cardiol. 1988;18:243-58.
of pulmonary atresia with intact ventricular septum. J Thorac 26. Kasznica J, Ursell PC, Blanc WA, et al. Abnormalities of the
Cardiovasc Surg. 1971;62:212-19. coronary circulation in pulmonary atresia and intact ventricular
8. Bull C, De Leval M, Mercanti C, et al. Pulmonary atresia and septum. Am Heart J. 1987;114:1415-20.
intact ventricular septum: a revised classification. Circulation. 27. Alwi M, Choo KK, Radzi NAM, et al. Concomitant stenting
1982;66:266-72. of the patent ductus arteriosus and radiofrequency valvotomy
9. De Leval M, Bull C, Hopkins R, et al. Decision-making in in pulmonary atresia with intact ventricular septum and
the definitive repair of the heart with a small right ventricle. intermediate right ventricle: early in- hospital and medium-
Circulation. 1985;72:52-60. term outcomes. J Thorac Cardiovasc Surg. 2011;141:1355-61.
10. Alwi M. Management algorithm in pulmonary atresia with 28. Elzenga NJ, Gittenberger-de Groot AC. The ductus arteriosus
intact ventricular septum. Catheterization and Cardiovascular and stenoses of the pulmonary arteries in pulmonary atresia. Int
Interventions. 2006;67:679-86. J Cardiol. 1986;11:195-208.
11. Freedom RM, Jaeggi E, Perrin D, et al. The “wall-to-wall” heart 29. Moon-Grady AJ, Teitel DF, Hanley FL, et al. Ductus- associated
in the patient with pulmonary atresia and intact ventricular proximal pulmonary artery stenosis in patients with right heart
septum. Cardiol Young. 2006;16:18-29. obstruction. Int J Cardiol. 2007;114:41-5.
12. Hanley FL, Sade RM, Blackstone EH, et al. Outcomes in 30. Giglia TM, Mandell VS, Connor AR, et al. Diagnosis and
neonatal pulmonary atresia with intact ventricular septum. J management of right ventricle-dependent coronary circulation
Thorac Cardiovasc Surg. 1993;105:406-27. in pulmonary atresia with intact ventricular septum. Circulation.
13. Rowlatt JF, Rimoldi MJA, Lev M. The quantitative anatomy of 1992;86(5):1516-28.
the normal child’s heart. Pediatr Clin North Am. 1963;10:499-88. 31. Calder AL, Co EE, Sage MD. Coronary arterial abnormalities
14. Daubeney PEF, Blackstone EH, Weintraub RG, et al. in pulmonary atresia with intact ventricular septum. J Thorac
Relationship of the dimension of cardiac structures to body Cardiovasc Surg. 1986;59:436-42.
size: an echocardiographic study in normal infants and 32. Burrows PE, Freedom RM, Benson LN, et al. Coronary
children. Cardiol Young. 1999;9:402-10. angiography of pulmonary atresia, hypoplastic right ventricle
15. Hanseus K, Bjorkhem G, Lundstrom NR. Dimensions of cardiac and ventriculocoronary communications. Am J Roentgenol.
chambers and great vessels by cross-sectional echocardiography 1990;154:789-95.
33. O’Connor WN, Cottrill CM, Johnson GL, et al. Pulmonary
in infants and children. Pediatr Cardiol. 1988;9:7-15.
atresia with intact ventricular septum and ventriculocoronary
16. Minich LL, Tani LY, Ritter S, et al. Usefulness of the
communications: surgical significance. Circulation. 1982;65:
preoperative tricuspid/mitral valve ratio for predicting outcome
805-9.
in pulmonary atresia with intact ventricular septum. Am J
34. O’Connor WN, Stahr BJ, Cottrill CM, et al. Ventriculocoronary
Cardiol. 2000;85:1325-28.
connections in hypoplastic right heart syndrome: autopsy serial
17. Freedom RM, Perrin D. The right ventricle: Morphological
section study of six cases. J Am Coll Cardiol. 1988;11:1061-72.
considerations. In: Freedom RM (Ed), Pulmonary atresia with
35. Haworth SG, Shinebourne EA, Miller GAH. Right-to-left
intact ventricular septum. Mount Kisco: Futura Publishing Co.
interatrial shunting with normal right ventricular pressure. A
Inc.; 1989. pp. 53-75.
puzzling haemodynamic picture associated with some rare
18. Cheatham JP. The transcatheter management of the neonate and
congenital malformations of the right ventricle and tricuspid
infant with pulmonary atresia and intact ventricular septum. J
valve. Br Heart J. 1975;37:386-91.
Interven Cardiol. 1998;11:363-87.
36. Tanaka T, Yamaki S, Ohno T, et al. The histology of the lung in
19. Zuberbuhler JR, Anderson RH. Morphological variations in
neonates with tricuspid valve disease and gross cardiomegaly
pulmonary atresia with intact ventricular septum. Br Heart J. 591
due to severe regurgitation. Pediatr Cardiol. 1998;19:133-38.
1979;41:281-88.
8 37. Lang D, Oberhoffer R, Cook A, et al. Pathologic spectrum of
malformations of the tricuspid valve in prenatal and neonatal
54. Kouchoukos NT, Blackstone EH, Doty DB, Hanley FL, Karp
RB (Eds). Cardiac surgery: morphology, diagnostic criteria,
life. J Am Coll Cardiol. 1991;17:1161-67. natural history, techniques, results and indication. 3rd Edition.
38. Leung M, Mok CK, Hui PW. Echocardiographic assessment of Philadelphia: Elsevier; 2003. pp. 1095-112.
neonates with pulmonary atresia and intact ventricular septum. 55. Qureshi SA, Rosenthal W, Tynan M, et al. Transcatheter laser-
J Am Coll Cardiol. 1988;12:719-25. assisted balloon pulmonary valve dilation in pulmonary valve
39. Silove E, de Giovanni J, Shiu M, et al. Diagnosis of right atresia. Am J Cardiol. 1991;67:428-31.
ventricular outflow obstruction in infants by cross-sectional 56. Parsons JM, Rees MR, Gibbs JL. Percutaneous laser valvoto-
echocardiography. Br Heart J. 1983;50:516-20. my with balloon dilatation of the pulmonary valve as primary
40. Trowitzsch E, Colan S, Sanders S. Two-dimensional treatment for pulmonary atresia. Br Heart J. 1991;66:36-38.
echocardiographic evaluation of right ventricular size and 57. Latson LA. Nonsurgical treatment of a neonate with pulmonary
function in newborns with severe right ventricular outflow atresia and intact ventricular septum by transcatheter puncture
obstruction. J Am Coll Cardiol. 1985;6:388-93. and balloon dilation of the atretic valve. Am J Cardiol.
41. Alwi M, Choo KK, Latiff HA, et al. Initial results and medium- 1991;68:277-9.
term follow up of stent implantation of patent ductus arteriosus 58. Agnoletti G, Piechaud JF, Bonhoeffer P, et al. Perforation
in duct-dependent pulmonary circulation. J Am Coll Cardiol. of the atretric pulmonary valve. J Am Coll Cardiol.
2004;44(2):438-45. 2003;41:1399-403.
42. Michel-Behnke I, Akintuerk H, THul J, et al. Stent 59. Humpl T, Sőderberg B, McCrindle BW, et al. Percutaneous
implantation in the ductus arteriosus for pulmonary blood balloon valvotomy in pulmonary atresia with intact
supply in congenital heart disease. Catheter Cardiovasc Interv. ventricular septum–impact on patient care. Circulation.
2004;61:242-52. 2003;108:826-32.
43. Ashburn DA, Blackstone EH, Wells WJ, et al. Determinants of 60. Gibbs JL, Blackburn ME, Uzun D, et al. Laser valvotomy
mortality and type of repair in neonates with pulmonary atresia with balloon valvuloplasty for pulmonary atresia with
and intact ventricular septum. J Thorac Cardiovasc Surg. intact ventricular septum: five years experience. Heart.
2004;127:1000-08. 1997;77:225-28.
44. Odim J, Laks H, Plunkett MD, et al. Successful management 61. Petrucci O, O’Brien SM, Jacobs ML, et al. Risk factors for
of patients with pulmonary atresia with intact ventricular mortality and morbidity after the neonatal Blalock Taussig
septum using a three tier grading system for right ventricular shunt procedure. Ann Thorac Surg. 2011;92:642-52.
hypoplasia. Ann Thorac Surg. 2006;81:678-84. 62. Schneider M, Zartner P, Sidiropoulos A, et al. Stent implantation
45. Yoshimura N, Yamaguchi M, Ohashi H, et al. Pulmonary of the arterial duct in newborns with duct-dependent circulation.
atresia with intact ventricular septum: strategy based on right Eur Heart J. 1998;19:1401-09.
ventricular morphology. J Thorac Cardiovasc Surg. 2003;126: 63. Gewillig M, Boshoff DE, Dens J, Mertens L, benson LN.
1417-26. Stenting the neonatal arterial duct in duct-dependent pulmonary
46. De Leval M, Bull C, Stark J, et al. Pulmonary atresia and intact circulation: new techniques, better results. J Am Coll Cardiol.
ventricular septum: surgical management based on revised 2004;43:107-12.
classification. Circulation. 1982;66:272-80. 64. Mair DD, Julsrud PR, Puga FJ, et al. The Fontan procedure
47. Rosenthal E, Qureshi SA, Chan KC, et al. Radiofrequency- for pulmonary atresia with intact ventricular septum: operative
assisted balloon dilation in patients with pulmonary and late results. J Am Coll Cardiol. 1997;29:1359-64.
valve atresia and on intact ventricular septum. Br Heart J. 65. Najm H, Williams WG, Coles JG, et al. Pulmonary atresia
1993;69:347-51. with intact ventricular septum: results of the Fontan procedure
48. Justo RN, Nykanen DG, Williams WG, et al. Transcatheter [abstract]. Circulation. 1995;92(Suppl I):I-55A.
perforation of the right ventricular outflow tract as initial therapy 66. Reddy VM, Mc Elhinney DB, Silverman NH, et al. Partial
for pulmonary valve atresia and intact ventricular septum in the biventricular repair for complex congenital heart defects: an
newborn. Cathet Cardiovasc Diagn. 1997;40:408-13. intermediate option for complicated anatomy or functionally
49. Hawkins JA, Thorne JK, Boucek MM, et al. Early and late borderline right complex heart. J Thorac Cardiovasc Surg.
results in pulmonary atresia and intact ventricular septum. J 1998;116:21-27.
Thorac Cardiovasc Surg. 1990;100:492-97. 67. Van Arsdell GS. One and one half ventricle repairs. Pediatric
50. Shaddy RE, Sturtevat JE, Judd VE, et al. Right ventricular Cardiac Surgery Annual of the Seminars in Thoracic and
growth after transventricular pulmonary valvotomy and Cardiovascular Surgery. 2000;3:173-78.
central aortopulmonary shunt for pulmonary atresia and intact 68. Maluf MA, Carvalho AC, Carvalho WB. One and a half
ventricular septum. Circulation. 1990;82(Suppl IV):157-63. ventricular repair as an alternative for hypoplastic right
51. Cole RV, Muster AJ, Lev M, Paul MH. Pulmonary atresia with ventricle. Rev Bras Cir Cardiovasc. 2010;25(4):466-73.
intact ventricular septum. Am J Cardiol. 1968;21:23-31. 69. Daubeney PEF, Wang D, Delany DJ, et al. Pulmonary atresia
52. Trusler GA, Yamamoto N, Williams WG, et al. Surgical with intact ventricular septum: predictors of early and medium-
treatment of pulmonary atresia with intact ventricular septum. term outcome in a population-based study. J Thorac Cardiovasc
Br Heart J. 1976;38:957-60. Surg. 2005;130:1071-78.
53. Steinberger J, Berry JM, Bass JL, et al. Results of right 70. Starnes VA, Pitlick PT, Bernstein D, et al. Ebstein’s anomaly
ventricular outflow patch for pulmonary atresia with intact appearing in the neonate: a new surgical approach. J Thorac
ventricular septum. Circulation. 1992;86(Suppl II):167-75. Cardiovasc Surg. 1991;101:1082-7.
592
71. Salvin JW, McElhinney DB, Colan SD, et al, Fetal tricus-
pid valve size and growth as predictors of outcome in pul-
of, and outcomes for, a cohort of 210 consecutive patients.
Cardiol Young. 2004;14:299-308.
40
monary atresia with intact ventricular septum. Pediatrics. 74. John AS, Warnes CA. Clinical outcomes of adult survivors of

2006;118;e415-e420. pulmonary atresia with intact ventricular septum. Article in
72. Tworetzky W, McElhinney DB, Marx GR, et al. In utero press–published on line, Int J Cardiol, 2011.
valvuloplasty for pulmonary atresia with hypoplastic right 75. Bautista-Hernandez V, Hasan BS, Harrild DM, et al. Late
ventricle: techniques and outcomes. Pediatrics. 2009;124; pulmonary valve replacement in patients with pulmonary
e510-e518. atresia and intact ventricular septum: a case-matched study.
73. Dyamenahalli U, McCrindle BW, McDonald C, et al. Ann Thorac Surg. 2011;91:555-60.
Pulmonary atresia with intact ventricular septum: management
593
C hapter
41 Double Outlet Right Ventricle
Vimala J, Vijayalakshmi IB, Prasanna Simha Mohan Rao
Introduction the aorta and pulmonary trunk malaligned with respect to

the ventricles resulting in DORV, dextroposed aorta and/or
Double outlet right ventricle (DORV) is a term that tetralogy of Fallot (TOF).5
encompasses a wide range of cardiac malformations with
varied clinical presentation. DORV comprises 1 to 3 percent Genetics
of all congenital heart defects.1 The congenital heart surgery
nomenclature and database project has defined DORV as In most cases, the defect is sporadic in nature and there is no
a spectrum of congenital heart diseases, in which both the identifiable genetic cause. A small number of familial cases
great arteries arise entirely or predominantly from the RV.2 have been reported and the defect has been produced in animal
This spectrum ranges from ventricular septal defect (VSD) models by the deletion of particular genes, especially those
with overriding aorta at one end to DORV with subpulmonic associated with neural crest migration. 22q11 micro deletion
VSD (Taussig-Bing anomaly), which resembles transposition has been associated with some cases of DORV.6 In a literature
of great arteries (TGA) at the other end. The clinical survey of 140 case reports of DORV; various chromosomal
manifestations vary depending on the relationship of the great anomalies were reported in 40 percent of the patients.1
vessels to each other and location of the VSD and the presence
or absence of stenosis of the semilunar valves. Though an Morphology
attempt to classify DORV was attempted by Neufield, the
widely accepted classification was described in 1972 by Lev
Ventricular Septal Defect
and Bharati.2
Double outlet right ventricle can be diagnosed: Ventricular septal defect is the only outlet of the left ventricle
1. If the aorta and the pulmonary artery are related to the and is an integral part of DORV. It is usually unrestrictive. In
morphologic RV either by both arising from the conus/ 10 percent of cases, the VSD is restrictive and in 13 percent
infundibulum of cases, VSDs are multiple. Rarely, it may be absent when
2. One great artery arising from the conus and the other the DORV is part of a complex anomaly associated with
great artery having fibrous continuity with only the right hypoplasia of the mitral valve and left ventricle.2 DORV as
ventricular portion of the atrioventricular (AV) valve. part of a univentricular heart shall not be discussed in this
chapter.
Embryology
Position of the Ventricular Septal Defect
In the developing heart persistence of a primitive relationship
of the truncoconal structures with the ventricles without The location of the VSD is described in relation to the great
leftward shifting results in DORV with the primitive VSD arteries. It is described as subaortic, subpulmonary, doubly-
(bulboventricular defect) persisting as the only outlet of the committed or non-committed (remote). These terms do not
left ventricle.3,4 Neural crest cells have been implicated in the strictly mean that one of the borders of the VSD is formed
formation of the aorticopulmonary septum of the developing by any of these great arteries. This relationship of the VSD
outflow tract. Partial ablation of the cardiac neural crest has to the great arteries has a special implication in the clinical
been shown to lead to normal aorticopulmonary septum with manifestation and also surgical management.
41
Double Outlet Right Ventricle

Figure 1: Double outlet right ventricle with subaortic ventricular Figure 2: Double outlet right ventricle with subpulmonic ventricular
septal defect. A = Anterior ; Ao = Aorta; IS = infundibular septum; septal defect. A = Anterior ; Ao = Aorta; IS = infundibular septum;
P = Posterior; PA = Pulmonary artery; RA = Right atrium; RV = Right P = Posterior; PA = Pulmonary artery; RA = Right atrium; RV = Right
ventricle; SMT= Septomarginal trabeculation. 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 hyper-
tension. 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 subpulmo-
nary conus the pulmonary valve will override the VSD (also
called as juxta-pulmonary VSD). If subpulmonary conus is Figure 3: Double outlet right ventricle with remote ventricular
present, the infundibular septum (conus) is so oriented that it septal defect. A = Anterior ; Ao = Aorta; IS = infundibular septum;
does not form a part of the interventricular septum, but serves P = Posterior; PA = Pulmonary artery; RA = Right atrium; RV = Right
ventricle; SMT= Septomarginal trabeculation.
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 vessels arising 200 percent from the RV and a double conus9; the
obstruction, which is commonly associated with the Taussig- term noncommited/remote or uncommitted is not anatomical,
Bing anomaly. but only descriptive that the VSD is at a considerable distance
Non-committed (remote) ventricular septal defect: The away from the outflow tracts. These are either inlet VSDs
term non-committed was introduced by Lev et al in 1972.8 without perimembranous extension, muscular VSDs or even
These VSDs are far from either the aorta or the pulmonary any of the other VSDs, where the conus is long and separates
artery. They are separated from the great arteries by muscular the VSD from the great arteries. The inlet VSDs may occur as
tissue (Figure 3). Though some have described DORV with part of the DORV with atrioventricular canal defect. Remote
remote VSD as VSD separated from both the great arteries by VSDs are present in 10 to 20 percent of patients who undergo
a distance more than the aortic diameter or as both the great 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
Associated Anomalies
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 Taussig-
Bing 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 Subaortic Stenosis
septum; P = Posterior; PA = Pulmonary artery; RA = Right atrium;
RV = Right ventricle; SMT= Septomarginal trabeculation. 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
Doubly-committed ventricular septal defect: It is reported outflow tract (LVOT), AV valve tissue or accessory valve tissue.
in 10 percent of patients with DORV, who have been surgically Aortic arch obstruction may be present in such patients.2
treated.2 The VSD lies beneath the aortic and the pulmonary
valves (Figure 4). The pulmonary and aortic valves are conti Coronary Artery Anomalies
guous as the infundibular septum is absent. The conus may be
deficient bilaterally or a single conus may be present beneath In DORV, the left coronary artery arises more posteriorly
both the great arteries. and the right coronary artery arises more anteriorly. When
the aorta is right and anterior, the coronary artery anatomy
Great Artery Relationship appears similar to that of TGA with RCA arising from the
posteriorly facing sinus and the LCA arising from the anterior
The great artery relationships fall into two basic categories, facing sinus.2 The origin and proximal course of the coronary
spiraling normally related great arteries or parallel great arteries vary depending on the proximity of the facing sinuses
arteries. This classification is important to determine the to the atrioventricular or the interventricular grooves.11 Single
appropriate type of corrective surgery. coronary artery has been reported in upto 11 percent of the
patients with DORV.12 In all cases of DORV with L-malposition
Normally Related Great Arteries of the great vessels, the right coronary artery passes anterior to
the pulmonary outflow tract, which is of surgical significance.7
The great arteries are normally related and spiral around each
other. The aorta is right and posterior to the pulmonary artery. Conduction System
The VSD in these cases is usually subaortic.2
In DORV, the AV node lies in the usual position of the AV
Parallel Great Artery Relationships septum. The bundle of His lies along the posteroinferior
margin of the VSD in DORV with juxtatricuspid defects like
i. Rightward and side-by-side aorta: The VSD is usually the subaortic, subpulmonary and doubly-committed VSDs.
subpulmonary. When the defect is separated by muscular tissue from the
ii. Right and anterior aorta: In a study by Guo et al, in 50 tricuspid valve, the bundle runs within the muscular tissue and
percent of angiographically studied patients, the aorta is not present at the posteroinferior part of the VSD.2
was either directly to the right or right and anterior to
the pulmonary artery.10 Clinical Presentation
iii. Aorta directly anterior to the pulmonary artery.
596 iv. Left and anterior aorta (L–malposition): This is the least The clinical manifestations of DORV vary depending on the site
common great artery position. The aorta arises from of the VSD, relationship of the great arteries to each other and to
41
the VSD and the presence or absence of stenosis of the semilu-
nar 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
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
Figure 5: Parasternal long-axis shows double outlet right ventricle with
cyanosis at all. These children are likely to develop early large nonrestrictive ventricular septal defect with pulmonary stenosis.
pulmonary arterial hypertension. Ao = Aorta; LA = Left atrium; LV = Left ventricle; PA = Pulmonary
artery; RA = Right atrium; RV = Right ventricle.
TOF Type
TOF type (DORV with subaortic VSD and pulmonary stenosis, border of the cardiac silhouette shows a bulging vascular
DORV with doubly-commited VSD and pulmonary stenosis). shadow with no discrete pulmonary segment observed.7,10
The clinical picture is similar to that of TOF. Cyanosis is Two-dimentional echocardiography shows both great
present from early months of life; a systolic murmur is audible arteries arising from the anterior RV. The features in parasternal
in the new born period. These children may have progressively long-axis view (Figure 5) are inability to identify a great
worsening cyanosis with cyanotic spells. artery arising from the left ventricle and the lack of continuity
between the anterior mitral leaflet and any semilunar valve
TGA Type caused by the conus. The conus is seen either as a dense echo
(fibromuscular) or as a muscular conus separating the two
TGA type (DORV with subpulmonary VSD without pulmonary valves and producing a separation and a more superior postion
stenosis). The clinical presentation is similar to that of TGA of the semilunar valve.13 There is no other outflow to the left
with VSD. The children are cyanosed in the newborn period ventricle other than the VSD. The left ventricular outflow tract
and develop worsening breathlessness, poor feeding and poor may have a tunnel-like configuration. There is hypertrophy of
weight gain. Associated coarctation may be present and such the RV.
children may present with heart failure in the early newborn Identifying the location of the VSD is essential in
period. planning the type of surgical intervention. Subaortic or
subpulmonary defects can be seen in parasternal or subcostal
Remote VSD Type long and short-axis views. Doubly-committed VSD is seen
as a defect that is nearly equally committed to both the
Remote VSD type: They present like patients with single great arteries. Non-committed VSDs are usually complete
ventricle. Children have mild cyanosis and the pulmonary AV septal defects and isolated or multiple muscular VSDs.
blood flow may be balanced, increased or decreased. These are best seen in the apical or subcostal four chamber
views. A restrictive VSD may be seen as an anatomically
Investigations small defect with turbulent flow and causes LVOT
obstruction. The degree of restriction may be assessed by
Electrocardiogram shows right ventricular hypertrophy doppler echocardiography.14
and in some cases biventricular hypertrophy. Conduction In the parasternal short-axis view, the features are
abnormalities may be found.9 simultaneous imaging of both great arteries in an anterior
Chest X-ray findings vary widely depending on the type of location and lack of a clockwise wrap around of the aorta by
DORV. At one end of the spectrum, radiological features may the right ventricular outflow tract. A double-circle appearance
resemble that of VSD with moderate enlargement of the heart of the great arteries may be seen. The great arteries may be
with varying degree of increased vascularity. At the other end, side-by-side, D-malposed or L-malposed.15
the heart may be 'boot-shaped' with decreased vascularity Transesophageal echocardiography (TEE) would furnish
resembling TOF. In DORV with L-malposition, the left upper extra details about the position of the VSD and its relationship 597
8
to the great arteries. Longitudinal planes would delineate Angiographic Illustrations
the right and left ventricular outflow tracts and the great
arteries. These views demonstrate the typical features of There are 16 possible variations of DORV based on the great
the predominant commitment of both great arteries to the artery relationships and the location of the VSD and it may be
RV. Additional defects of the AV valves and their chordal associated with pulmonary stenosis or with pulmonary artery
attachments may also be delineated well by TEE. hypertension (Figures 7A and B). The various illustrations
Fetal echocardiography: Careful visualization of the four include a case of dextrocardia with situs inversus with DORV
chamber view and outflow tracts in fetal echocardiography (Figures 8A and B).
is diagnostic.16 The VSD is almost always seen in the four The side-by-side relationships of the great arteries with
chamber view. While viewing the outflow tracts, both the subaortic VSD is the most frequently encountered type of
great vessels are seen arising from the RV and are often seen DORV (Figure 9A). The aorta is to the right of the pulmonary
to be side-by-side (Figure 6). 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
Figure 6: Fetal echocardiography outflow tract view shows double differentiate this type from the Taussig-Bing anomaly because
outlet right ventricular with subpulmonary ventricular septal defect on the lateral view of the RV this VSD is high, anterior,
(Taussig-Bing). Ao = Aorta; LV = Left ventricle; PA = Pulmonary artery;
RV = Right ventricle; VSD = Ventricular septal defect. superior and directly related to both semilunar valves. It is
A B
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
598 great arteries with dilatation of pulmonary artery due to pulmonary hypertension. Ao = Aorta; LV = Left ventricle; MPA = Main pulmonary artery;
PA = Pulmonary artery.
41

A B
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.
A B
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 The relationship of the great arteries may be observed i.e.
pulmonary valve or to both semilunar valves. aorta right and anterior or aorta to the right of pulmonary valve,
The DORV with remote VSD, as a case with multiple VSDs aorta anterior to the pulmonary valve, aorta left and anterior
not committed to both the great arteries, is illustrated in Figure to the pulmonary valve.10 In DORV with L-malposition,
12. The angiographic findings other than the great artery aortography shows left sided anterior ascending aorta with
relationships, are not different from those observed with side- right coronary artery passing anterior to the pulmonary
by-side great arteries and remote VSD. The malposition of the valve.7
aorta can be seen in both frontal and lateral views (Figure 13 A Computed tomography angiography and magnetic
and B). The left ventricular angiogram also demonstrates that resonance imaging: The spatial relationship between semilunar
the VSD is the only outlet from the left ventricle. valves and VSD can be accurately assessed by CT angiography
599
8
Figure 10: Right heart catheter through atrial septal defect entered Figure 11: Left ventricle (LV) angiogram in left anterior oblique view
left ventricle (LV). The LV angiogram in left lateral view shows the illustrates subpulmonic ventricular septal defect opacifying dilated
ventricular septal defect committed to the aorta (Ao) 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 B
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

A
Figure 14: Computed tomographic angiogram illustrates double outlet

right ventricle with aorta anterior and side by side with pulmonary B C
artery
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
(Figure 14) and magnetic resonance imaging (MRI) and could between the PV and Tric. V so that the pathway from the ventricular
provide additional information to the conventional imaging in septal defect (VSD) to the aorta is unobstructed. B. When PV is very
the assessment of VSD. MRI would provide accurate additional close to Tric. V a Rastelli repair may be appropriate. PV lies within
the baffle necessiating division and oversewing of main pulmonary
anatomic information, which would be helpful in presurgical artery. C. Separation of the Tric. V and PV is less than the diameter of
planning and in follow-up of patients.17 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
Management from reference 21.
There is no specific medical management for DORV.

Those infants who are having congestive heart failure need repair will be possible. In extremely unroutable VSD’s, a
decongestive therapy. single Fontan correction may be used if the pulmonary artery
size and vascular resistance permits.
Surgery for Double Outlet Right Ventricle9,18-21
Double Outlet Right Ventricle Subaortic VSD
Surgery for DORV has got two requirements—closure of Without Pulmonary Stenosis
the VSD and unobstructed outflow from the corresponding
ventricles to the great arteries. An adequately sized ventricle An intraventricular tunnel repair is possible in most patients.
is a necessary caveat for a biventricular repair in DORV. The patch forms a tunnel and in essence forms a part of the
Since both great arteries arise from the RV, the outflow path LVOT and so has to be liberal so as to not cause subaortic
will necessarily have to be through the VSD. The position stenosis. Initial inspection should be done and the possibility
of the VSD (in relation to the great arteries) is the primary of transposing any obstructing tricuspid chordae has to be
determinant of the hemodynamic status of the child. The status planned. If the VSD is small, suitable enlargement by excision
of the pulmonary arteries are also to be considered. of the superior and lateral margins are done, to avoid the
A subaortic VSD with pulmonary stenosis acts like a TOF conduction system. A suitable patch or portion of a tube graft
and if there is no pulmonary stenosis, it behaves like a VSD. A is used to construct a nonobstructive tunnel. If the generous
subpulmonic VSD makes the child behave like a transposition patch were to cause RVOT obstruction, then augmentation of
with a VSD. A doubly committed and a non-committed VSD the RVOT with a patch may be required.
will behave depending on how the blood streams to the
great arteries. Apart from the VSD, the relation of the great Double Outlet Right Ventricle Subaortic VSD with
arteries, outflow tract obstructions, chordal connections of the Pulmonary Stenosis
tricuspid valve and the distance between the pulmonary valve
and the tricuspid valve will also determine the management. If the pulmonary artery size is inadequate then the child may
The tricuspid–to–pulmonary annulus distance has been shown need an aortopulmonary shunt to enable growth of the pulmo
to be a useful predictor for the feasibility of intraventricular nary arteries to enable intracardiac repair later.
baffle repair (Figure 15).21 The size of the ventricles will also This can be equated to a TOF repair. If the override is not 601
determine whether a biventricular repair or a univentricular excessive and the RV infundibular narrowing is not excessive,
8
a liberal VSD patch and if required RVOT patching to allow mortality and in the current era associated arterial switch
unobstructed right ventricular outflow, can be done. If the has reduced the mortality by reducing the complexity of the
override is excessive and there is annular narrowing, then a tunnel. A DORV with subaortic VSD has a current mortality
transannular patch or an RV to pulmonary artery conduit (all of that of a VSD or a tetralogy repair. The introduction of the
the more if there are major coronaries crossing the RVOT) arterial switch for the Tausig-Bing anomaly has reduced the
may need to be implanted. mortality from as high as 50 percent to 5–15 percent.
Double Outlet Right Ventricle with Conclusion

Doubly Committed VSD
The prognosis of DORV with pulmonary stenosis resembles
These cases can usually be managed like a DORV with a that of TOF. In the Taussig-Bing type of DORV, course of
subaortic VSD. events are worse than TGA with large VSD. A number of
surgical maneuvers have achieved satisfactory anatomical
Double outlet right ventricle with a subpulmonic VSD repair and long-term survival.The precise timely diagnosis is
The Taussig-Bing anomaly presents a unique problem, very important.
where the pulmonary valve is interposed between the aorta
and the VSD necessitating a circuitous patch as described The physician's highest calling, his only calling, is to make
by Kawashima (especially, if the great vessels are side- sick people healthy -- to heal, as it is termed.
to-side), after resecting the subpulmonic infundibulum to — Samuel Hahnemann
allow reaching the aorta which may necessitate closing the
pulmonic orifice at times with an RV to pulmonary artery Acknowledgment
conduit, if the distance between the pulmonary valve and
the tricuspid valve is not sufficient to allow an unobstructed I would like to express my thanks to Dr Bhushan Chavan for
pathway. More commonly the subpulmonic VSD is converted his help in completion of this chapter and Ms Sujatha for her
into a “subaortic” VSD by performing an arterial switch and secretarial help.
now the intraventricular tunnel is shorter, the probability of
subaortic stenosis is reduced and the need for a conduit is References
avoided.
1. Obler D, Juraszek AL, Smoot LB, et al. Double outlet
right ventricle, etiologies and associations. J Med Genet.
Double Outlet Right Ventricle with an Uncommitted VSD
2008;45:481-97.
The repair is dictated by the position of the VSD. A circuitous 2. Walters HL 3rd, Mavroudis C, Tchervenkov CI, et al.
tunnel repair may be needed and an arterial switch may be Congenital Heart Surgery Nomenclature and Database Project:
double outlet right ventricle. Ann Thorac Surg. 2000;69:
combined to make the baffle less circuitous. Attention to the
S249-63.
conduction system needs to be kept in mind during the baffling 3. Angelini P, Leachman RD. The spectrum of double outlet
procedure. Multiple patches to create the circuitous baffle right ventricle: An embryologic interpretation. Cardiovasc
has been described by Barbero Marciel. In complex DORV, Dis. 1976;3:127-149.
where routing may not be easy or impossible, a variation of 4. Angelini P. Embrology and congenital heart disease. Tex Heart
the Fontan operation may be adopted. Inst J. 1995;22:1-12.
5. van den Hoff, Moorman AFM. Cardiac neural crest: the holy
Complications grail of cardiac abnormalities? Cardiovasc Res. 2000 ;47:212-
6.
Severe hemolysis can occur due to the circuitous patch. 6. Wilkinson J. Double outlet right ventricle. Orphanet
Residual VSDs, heart blocks and late onset of LVOT obstruction Encyclopedia, Feb 2005.
can occur. Damage to the septal arteries and left anterior 7. Lincoln C, Anderson RH, Shinebourne EA, et al. Double outlet
right ventricle with L-malposition of the aorta. Br Heart J.
descending artery can occur during enlargement of a restrictive
1975;37:453-63.
VSD. Patients with RVOT conduits are exposed to all the late
8. Belli E, Serraf A, Lacour-Gayet F, et al. Double-outlet right
complications related to conduit implantation and stenosis. ventricle with non-committed ventricular septal defect. Eur J
Cardiothorac Surg. 1999;15:747-52.
Results 9. Lacour-Gayet F, Haun C, Ntalakoura K, et al. Biventricular
repair of double outlet right ventricle with non-committed
Double outlet right ventricle being a wide spectrum has ventricular septal defect (VSD) by VSD rerouting to the
602 a differing mortality. Uncommitted VSD’s have a higher pulmonary artery and arterial switch. Eur J Cardiothorac Surg.
2002;21:1042-8.
41
10. Guo W, Lin ML, Gu ZQ, et al. Double outlet right ventricle, 16. Kim N, Friedberg MK, Silverman NH. Diagnosis and progno-
a clinical-roentgenologic-pathologic study of 28 consecutive sis of fetuses with double outlet right ventricle. Prenat Diagn.

patients. Chest. 1984;85:526-32. 2006;26:740-45.
11. Uemura H, Yagihara T, Kawashima Y, et al. Coronary arterial 17. Beekmana RP, Roest AA, Helbing WA, et al. Spin Echo MRI
anatomy in Double-outlet right ventricle with subpulmonary in the evaluation of hearts with a double outlet right ventricle:
VSD. Ann Thorac Surgery. 1995;59:591-97. Usefulness and limitations. Magn Reson Imaging. 2000;18:245-
12. Ewing S, Silverman NH. Echocardiographic diagnosis of 53.
single coronary artery in double-outlet right ventricle. Am J 18. Harvey JC, Sondheimer HM, Williams WG, et al. Repair of double
Cardiol. 1996;77:535-9. outlet right ventricle. J Thorac Cardiovasc Surg. 1977;73:611-15.
13. Hagler DJ, Tajik AJ, Seward JB, et al. Double outlet right 19. Brawn WJ, Mee RB. Early results for anatomic correction of
ventricle: wide-angle two dimensional echocardiographic transposition of the great arteries and for double outlet right
observations. Circulation. 1981;63:419-28. ventricle with subpulmonary ventricular septal defect. J Thorac
14. Hagler DJ. Double-Outlet Right Ventricle and Double-Outlet Cardiovasc Surg. 1988;95:230-38.
Left Ventricle. In Moss and Adams' Heart Diseases in Infants, 20. Delius RE, Rademecker MA, de Leval MR, et al. Is a high risk
Children and Adolescents: Including the Fetus and Young biventricular repair always preferable to conversion to a single
Adults, 7th edition. Allen HD, Driscoll DJ, Shaddy RE, Feltes ventricle repair? J Thorac Cardiovasc Surg. 1996;112:1561-69.
TF (Eds). Lippincott Williams and Wilkins. 2008.pp.1101-27. 21. Sakata R, Lecompte Y, Batisse A, et al. Anatomic repair of
15. DiSessa TG, Hagan AD, Pope C, et al. Two dimensional ventriculoarterial connection associated with ventricular septal
echocardiographic characteristics of double outlet right defect. I: Criteria of surgical decision. J Thorac Cardiovasc Surg.
ventricle. Am J Cardiol. 1979;44:1146-54. 1988;95:90-95.
603
C hapter
42 Truncus Arteriosus
INTRODUCTION development, tissue swellings (anterior and posterior

cushions) appear inside the side walls of the truncus arteriosus
Truncus arteriosus is a rare cyanotic heart disease classified and form the ‘spiral septum’ separating truncus arteriosus into
as one of the conotruncal anomalies and is characterized by the aorta and main pulmonary artery. The twisting descent of
i. A common arterial trunk originating from base of the the spiral septum accounts for twisting of the great arteries
heart ii. The common arterial trunk gives rise to the aorta, between themselves. Spiral septum also contributes to the
pulmonary artery and coronary arteries.1 Truncus arteriosus is formation of conal septum below the semilunar valves. Failure
thought to result from failure of septation of the conotruncus of formation of spiral septum leads to truncus arteriosus. Since
portion of the heart tube during embryonic development. this is a defect of spiral septum, the resultant VSD is in the
Truncus arteriosus is most commonly associated with a conal septum and does not involve the membranous septum.
large ventricular septal defect (VSD) in the conal septum. Occasionally, the membranous septum may also be deficient.
Pulmonary arteries originate from the common arterial trunk. But typically, the VSD in truncus arteriosus is a conal septal
In most clinical series, truncus arteriosus accounts for VSD. As a result, tricuspid valve annulus is separated from
less than 1 percent of all congenital heart defects. However, the edge of VSD by a small portion of ventricular septum that
it constituted 2.8 percent of autopsy cases, as seen in Boston forms the posteroinferior portion of septomarginal band.
Cardiac Registry.2 Even a higher incidence of 7 percent was Aortic arch, patent ductus arteriosus and pulmonary
reported from an earlier autopsy series from the same institution.3 arteries are derived form from 3rd, 4th and 6th branchial or
Variability in incidence probably reflects the nature of the study aortic arches with contributions from other primitive arteries
subjects, clinical vs autopsy and the institution. Overall, truncus such as seventh intersegmental artery. As a consequence,
arteriosus remains a rare congenital heart defect. there can be associated defects involving all these vessels
Truncus arteriosus was first reported by Wilson in 17984 and including coronary arteries. There is also a suggestion that
the features were confirmed in the next century by Buchanan main pulmonary artery is not only formed by separation of the
in 1864.5 Lev and Saphir proposed basic morphologic criteria truncus by spiral septum, but also by additional contribution
defining the anomaly in 1942.1 Collett and Edwards6 proposed from 6th branchial arches, that extend into proximal portions
a classification in 1949, based on previously published reports. of left and right pulmonary arteries.
An alternative classification was proposed by van Praagh in Theories on development of truncus arteriosus include the
1965.7 He later revised his own classification in 1975.8 following:
In this chapter, we will discuss embryology, genetics, 1. Abnormal flow during the bilocular stage of the heart
pathologic features, classification, natural history, clinical tube: There is spiraling of blood flow returning from
features, differential diagnosis, noninvasive and invasive inferior (IVC) and superior (SVC) vena cavae, when the
evaluation, management and outcome of treatment of truncus heart is in the bilocular stage. Disturbance of this flow may
arteriosus. predispose to abnormal or lack of development of spiral
septum.
EMBRYOLOGY 2. Abnormal migration of cardiac neural crest cells from
the occipital region to the primitive truncus and 3rd,
Primitive truncus arteriosus is a segment in the heart tube 4th and 6th branchial arches areas: If the number of
between the ventricles and branchial arches. During normal cardiac neural crest cells fall below a certain critical value,
42
the spiral septum does not develop. Ablation of cardiac originate separately and directly from the common arterial
neural crest cells in chick embryos has resulted in high trunk. Several classifications have been proposed based on the
Truncus Arteriosus
incidence of persistent truncus arteriosus.9 nature of pulmonary artery anatomy and are discussed below.
3. Cardiac neural crest cells express PAX3 gene: PAX3
gene mutation may be responsible for development of Ventricular Septal Defect
truncus arteriosus. However, the basis of the types of
truncus arteriosus cannot be explained with this theory, at Conal septal or infundibular VSD is the rule. In echocardio
this time.10 Several other candidate genes have also been gram, it appears as though the single truncal valve overrides
proposed as etiology for truncus arteriosus. the ventricular septum. The septal band is intact and so, is part
VSD accompanies truncus arteriosus in almost all cases, of the membranous ventricular septum. Therefore, typically
except for very rare reports.7 Typically the VSD in truncus this is a conal septal VSD—just as in tetralogy of Fallot.
arteriosus is a conal septal defect and is large in size. The Distal infundibular septum is defective resulting in a large
ventricular septum appears malaligned in an echocardiogram, VSD. The right posterior/inferior division and left anterior/
due to the single truncal valve overriding the VSD. Typically, superior division of the septal band form the inferior border of
the VSD does not involve the membranous portion of the the VSD. There have been only two of 47 cases, reported by
ventricular septum. This portion of ventricular septum is van Praagh,7 which did not have a VSD.
usually intact leaving a piece of ventricular septum separating
the edge of the conal septal VSD and tricuspid valve annulus. Pulmonary Arteries
There may be associated abnormalities of tricuspid valve
including its anterior leaflet and medial papillary muscle, The main pulmonary artery (PA) usually arises from the left
coronary arteries, pulmonary arteries and aortic arch branches. posterolateral portion of the common arterial trunk (as in
type I). The right and left pulmonary arteries may arise from
GENETIC ASSOCIATIONS back (as in type II) or side (as in type III) of common arterial
trunk directly. When the right and left pulmonary arteries have
Conotruncal anomaly is one of the better-studied areas separate origins, one of the pulmonary arteries may be absent;
of cardiovascular developmental genetics. There is a seen in 16 percent cases in one series.15 In the Mayo clinic
high association with DiGeorge syndrome with 22q11 series, in 80 percent of cases with single pulmonary artery, the
microdeletion identified using fluorescent in situ hybridization pulmonary artery was absent on the side of aortic arch. This
(FISH) technique. Reviewed by multiple authors,11-14 22q11 is in contradistinction to what is noted in tetralogy of Fallot,
microdeletion is noted in 20 to 33 percent of patients with where when a PA is absent, it will be on the side opposite from
truncus arteriosus. There is a high association with right that of aortic arch.
aortic arch. Of the 251 patients who were screened for 22q11, Pulmonary artery after its origin may criss-cross in cases of
microdeletion was positive in 50 percent of patients with truncus arteriosus coexisting with interrupted aortic arch, i.e.
interrupted aortic arch, 35 percent of truncus arteriosus and left PA originates to the right of right PA and crosses to the left
16 percent of tetralogy of Fallot.14 Similarly, five of 15 (33%) side.16
consecutive patients with truncus arteriosus were positive for
22q11 detection.11 Associated features in DiGeorge syndrome Truncal Valve
include dysmorphic facies, thymic and parathyroid hypoplasia,
skeletal and renal abnormalities and developmental delay. Most commonly, truncal valve has three leaflets (67%).
Velocardiofacial syndrome is another genetic association Quadricuspid truncal valve occurs in 24 percent of cases.
characterized by presence of facial features including cleft lip Bicuspid truncal valve is noted in 7 percent. Unicuspid
and palate, learning difficulties and heart defect. truncal valve has been rarely reported. When there are three
or four leaflets, they are usually similar in size. Truncal valve
PATHOLOGY regurgitation is more common, while truncal valve stenosis
is rare.7
Common Arterial Trunk
Coronary Ostial Anomalies
Presence of a single arterial trunk originating from base of
the heart is the hallmark of this defect. The pulmonary artery Location of the coronary ostia may be abnormal; the most
originates from the common arterial trunk either as a common common abnormality being a high-origin of the coronary
(main) pulmonary artery first and then branch into right and artery and location above the wrong commissure or cusp.
left pulmonary arteries or the right and left pulmonary arteries Rarely, coronary ostial stenosis has been noted.
605
8
Aortic Arch Table 1

Incidence of associated anomalies in truncus arteriosus.
Right aortic arch is present in 33 percent of cases.2,7 (Compiled from Kirklin and Barrat-Boyes,18 Russell HM, et al,19
Bohuta, et al20 and Goldmunz12.
Conduction System Associated anomaly %

Anomalous origin of right or left subclavian artery or 10%
Sinoatrial (SA) and atrioventricular (AV) nodes are in their innominate artery
usual location. AV bundle passes to the left of the central
Interrupted aortic arch ~ 10%
fibrous body. Left bundle courses posterior to the membranous
ventricular septum along the left side of the ventricular septum. Left superior vena cava to coronary sinus 6%
Right bundle travels along the ventricular septal summit usually ASD (moderate or large) 10%
intramyocardially—somewhat deeper from the edge of VSD Additional VSD 4%
and becomes subendocardial at the level of moderator band. Mitral valve anomalies (hypoplasia, stenosis or 10%
This is the case when membranous ventricular septum is intact. double-orifice)
However, when the VSD involves both membranous septum and Complete atrioventricular septal defect 2%
conal septum, the right bundle usually travels subendocardially,
Extracardiac anomalies 10%
along the left side of posterior-inferior rim of VSD and is
vulnerable to injury during surgical closure of VSD.17 DiGeorge syndrome 33%
Ventricles
therefore, there is partial separation of aorta and main PA.
Right ventricular (RV) hypertrophy and enlargement are Distal to the origin of main PA from the common arterial
always present. Left ventricular (LV) outflow is usually trunk, both aorta and main PA are identifiable. Short segment
normal. VSD usually is large. However, in rare occasions, of main PA gives rise to both branch pulmonary arteries.
VSD can be restrictive. If the overriding truncal valve is This type is seen in 48 to 68 percent of cases. Type II—no
committed primarily to the right ventricle, thus resembling main PA is present. Branch pulmonary arteries arise from the
a posterior deviation of the ventricular septum, there is a back portion of the common arterial trunk very close to each
potential to develop LV outflow tract obstruction when VSD other. This type is seen in 29 to 48 percent. Type III—no main
is closed. Such VSD may need enlargement during surgical PA is noted. The two branch pulmonary arteries arise from
repair. Significant truncal valve regurgitation is also a reason the side of the common arterial trunk. This type is seen in
for LV enlargement. 6 to 10 percent of cases.21 Type IV—there is no main PA.
Branch pulmonary arteries arise from different parts of the
Associated Defects aorta. This type is also called pseudotruncus and is thought to
be part of pulmonary atresia with VSD.21 Commonly the left
Associated cardiac defects include right aortic arch, interrupted PA originates from the undersurface of the arch and right PA
aortic arch, atrial septal defect, persistent left SVC and others originates from mid-thoracic descending aorta, approximately
(Table 1).11,18-20 Normal pulmonary venous return was seen from the level of lung hilum.
in all, but one of 47 cases in Van Praagh series.7 Associated
noncardiac defects occurred in approximately 21 percent of Classification 2 (1965)
cases, as seen in Van Praagh series.7
Van Praagh classification7 is somewhat more complex.
CLASSIFICATION Initially, truncus arteriosus is classified on the basis of
presence or absence of VSD; type A—with VSD. Type
Even though several classifications exist, two classifications B—without VSD. Since there have been very rare reports
of truncus arteriosus have been commonly followed. Collett of truncus arteriosus without VSD, type B is practically
and Edwards6 classification is more widely used than that of nonexistent, except for the rare, single cases reported in the
Van Praagh.7,8 literature. Type A is subdivided into four subtypes (Figure 1,
middle). A1—main PA arises from the common arterial trunk
Classification 1 (1949) and then, bifurcates into branch pulmonary arteries (similar
to type I of Collette and Edward classification). A2—absence
Collett and Edward classification6 is based on the degree of of main PA. Branch pulmonary arteries arise directly from
main PA development and of the origin of pulmonary arteries the common arterial trunk. Type A2 includes type II and
606 (Figure 1, top): Type I—the spiral septum is partially formed, III of Collette and Edward classification. Type A3—left 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 ‘Simplified’19. See text for detailed description
originates from aortic arch. Right PA originates from the Classification 4 (2011)
common arterial trunk. Type A4 —truncus arteriosus with
interrupted aortic arch. Descending aorta receives blood flow Very recently, a simplified categorization of common arterial
from a persistent ductus arteriosus. trunk has been proposed by the surgical group in Chicago, in
Types A1 to A3 display well-developed branchial arch four collaboration with Prof RH Anderson.19 This group proposes to
and poorly developed arch six. This results in absent Patent classify truncus arteriosus into only two categories, namely aortic-
ductus arteriosus (PDA). Type IV displays a poorly developed dominant or pulmonary-dominant types (Figure 1, bottom). This
arch four and well-developed arch six leading to hypoplasia, is based on the observation that among the 28 autopsy specimens
coarctation, or interruption at the level of aortic isthmus and a examined, 20 specimens were aortic-dominant. Pulmonary-
large PDA. Since type A4 is rare, presence of PDA in truncus dominance was less common and was associated with presence
arteriosus is an uncommon finding. Overall, PDA was present of a discrete aorta, which was hypoplastic and a PDA supplied
in 30 percent of cases with truncus arteriosus. However, PDA majority of flow to the descending aorta. In addition, only in the
is commonly noted, when there is associated arch hypoplasia, pulmonary-dominant category, did the pulmonary arteries arise
coarctation or interruption of aorta. Thus, when there is a from the side of common truncus and the aortic component is
large aorta present, PDA is usually absent (91%). Conversely, identifiable as a discrete structure within the pericardial cavity.
PDA was present in all cases with small aorta with or without Incidence was similar in 42 clinical case series from Chicago, in
coarctation or interruption.7 which 38 were aortic-dominant type and four were pulmonary-
dominant type. Even though this classification is simplified, it is
Classification 3 (2000) fairly new and has not come into clinical use.
Figure 1 summarizes the above classifications. The
Congenital Heart Surgery Nomenclature and Database Project, preference of the authors of this chapter is Collett and
200022 proposes a unified classification (Figure 1, middle). Edwards’ classification.
607
8
Clarification of Related Terminology respiratory distress occurs due to bronchial compression
from dilated common trunk, especially when associated
Pseudotruncus is a term introduced by Bharati and associates with interrupted aortic arch (usually right main bronchus) or
in 1974.21 The term refers to type IV truncus in Collett and between anteriorly placed left pulmonary artery and posterior
Edwards’ classification, in which pulmonary arteries originate portion of aortic arch (usually left upper lobe bronchus). Babies
from descending thoracic aorta. This also refers to the subtype with interrupted aortic arch or coarctation of aorta may present
of pulmonary atresia with VSD, where pulmonary arteries precipitously when the ductus arteriosus closes in the neonatal
are discontinuous and arise from aortic arch and descending period. Such patients may constitute approximately 10 percent
thoracic aorta, respectively. These may be aortopulmonary of the patients with truncus arteriosus. Manifestations would
collateral arteries rather than native pulmonary arteries. Use of include circulatory collapse, metabolic acidosis, respiratory
this term is discouraged in the nomenclature project paper.22 distress and cyanosis. Absent femoral pulse will be part of the
Hemitruncus refers to a condition with origin of a physical finding.
pulmonary artery from ascending aorta. Again, use of this Mild cyanosis may be present from decreased pulmonary
term is discouraged in preference to more specific description blood flow due to either pulmonary artery ostial stenosis or high
of the lesion. This also probably is a subtype of pulmonary pulmonary vascular resistance, that is usual in neonatal period.
atresia with VSD with major aortopulmonary collateral Cyanosis resolves when the pulmonary vascular resistance
arteries rather than a subtype of truncus arteriosus. decreases with transition to neonatal circulation. Features of
Use of both pseudotruncus and hemitruncus are also increased pulmonary blood flow and heart failure will develop
strongly discouraged by the authors of this chapter due to lack as the baby gets older, unless severe anatomic stenoses of
of developmental basis for these terms. pulmonary arteries keep the pulmonary blood flow at a low
level. Recurrent respiratory infections and failure to thrive
NATURAL HISTORY occur just as with other infants with large left-to-right shunting.
In older children, cyanosis develops again as Eisenmenger
Natural history for survival without intervention is poor syndrome occurs with development of pulmonary vascular
in children with truncus arteriosus. Without surgical repair, obstructive disease.
only 50 percent survive beyond 1 month, 30 percent survive
beyond 3 months, 18 percent survive beyond 6 months and Physical Examination
12 percent survive beyond 1 year.18 Cause of death during
neonatal period is congestive heart failure from large left Large volume pulse due to diastolic reversal of flow in the
to right shunting and/or truncal valve regurgitation. Some aorta from continued diastolic flow into the pulmonary arteries
patients develop endocarditis or brain abscess, causing their may easily be detected. Hyperdynamic precordium occurs.
death.6 Children who survive to 1 year of age do so, because Precordial bulge occurs due to right ventricular enlargement
of pulmonary artery stenosis and therefore, partial or complete and hypertrophy. Signs of respiratory distress occur with large
protection of the pulmonary vasculature from exposure to left-to-right shunting. However, if the pulmonary blood flow
systemic arterial pressure and consequent decreased risk for is normal or diminished due to anatomic pulmonary artery
development of pulmonary hypertensive vascular changes. stenosis or persistence of high pulmonary vascular resistance,
Therefore, there is low mortality after 1 year in this subgroup the child will present without features of heart failure or
of patients. Very few patients survive infancy and early respiratory distress. There may be mild cyanosis, however.
childhood with significant left-to-right shunting and yet, not Auscultation reveals normal to loud S1. Systolic click will
develop pulmonary vascular disease. This constitutes half of be present from truncal valve abnormalities or dilated common
survivors beyond 1 year or <5 percent of all infants born with arterial trunk. Second sound will be single. Systolic ejection
truncus arteriosus.23 When pulmonary vascular obstructive murmur with or without a thrill from pulmonary artery stenosis
disease (pulmonary vascular resistance > 9 Woods units m2) or truncal valve stenosis may be present. Similar murmur is also
develops during infancy or later, there is good chance for such heard when there is increased pulmonary blood flow through
patients to survive into their teens without surgical repair.24 nonstenotic branch pulmonary arteries. With severe pulmonary
However, pulmonary vascular occlusive disease develops artery stenosis, this murmur may be continuous. Presence of a
gradually and Eisenmenger syndrome eventually occurs, high frequency, early diastolic decrescendo murmur indicates
leading to death. truncal valve regurgitation. This is a discrete murmur although,
may be very low in intensity. This should not be confused
CLINICAL FEATURES with a diastolic rumble from increased pulmonary blood flow,
due to increased flow across the mitral valve; this is a mid-
Presenting symptoms include features of heart failure in the diastolic event. In rare cases of restrictive VSD, VSD murmur
608 first few weeks of life consisting of tachypnea, tachycardia, may be heard. Liver enlargement is present with heart failure,
irritability, poor feeding and poor weight gain. Rarely, secondary to a large left-to-right shunt.
42
DIFFERENTIAL DIAGNOSIS BASED side. In older children with pulmonary vascular disease,
ON CLINICAL FEATURES cardiomegaly and pulmonary plethora diminish with time.
Truncus Arteriosus
Infants with Heart Failure Electrocardiogram
Infants with heart failure usually have mild cyanosis and Normal QRS axis (rightward or normal quadrant) and RV
the differential includes transposition of great arteries with hypertrophy are noted early. LV hypertrophy develops later.
VSD, double outlet right ventricle, tricuspid atresia with large Often, biventricular hypertrophy is present at the time of
VSD (with or without transposition of great arteries), single diagnosis. P pulmonale develops later. Thus, none of the ECG
ventricle without pulmonary stenosis and total anomalous features are diagnostic in truncus arteriosus.25
pulmonary venous return (TAPVR). In tricuspid atresia,
left axis deviation and LV dominance are noted in the ECG. Echocardiography
Paucity of LV forces may be present in ECG in TAPVR.
Absent pulmonary artery segment in chest X-ray will support Echocardiography is the most important study that provides
either truncus or transposition of great arteries. However, the diagnosis, as well as most of the information necessary
there can be a normal-appearing pulmonary artery segment in for surgical planning. In neonates and infants, no further
type I truncus arteriosus, where the small common pulmonary investigations are necessary, unless there were specific
artery segment may produce a PA segment shadow on chest unanswered questions exist after echocardiography.
X-ray. Right aortic arch supports the diagnosis of truncus Objectives of echocardiography include demonstration of
arteriosus. Echocardiographic features are diagnostic for each single great artery from the ventricles, conal septal VSD, over
of the conditions mentioned above. riding truncal valve, truncal valve anatomy, pulmonary arteries,
PDA and other associated anomalies including interrupted
Older Infant and Children with Continuous Murmur and aortic arch, anomalies of the origin of aortic arch branches,
Evidence of Increased Pulmonary Blood Flow abnormalities of coronary artery origins, persistent left SVC,
additional VSDs, tricuspid and mitral valve anomalies,
Aortopulmonary window or PDA should be considered in if any. It is important to differentiate truncus arteriosus
the differential. Mild cyanosis is present in the children from pulmonary atresia with VSD and aortopulmonary
with truncus and may be too subtle to be recognized. Small window.26 Echo findings should enable determination of the
or absent PA segment, if present in chest X-ray will support type of truncus arteriosus and its physiology. Systematic
truncus arteriosus. Echocardiographic features are distinctive. echocardiographic evaluation of truncus arteriosus is well-
described in multiple echocardiography text books such as by
Children with Cyanosis Snider and Ritter.27
Parasternal long-axis view (Figure 2) shows the characteristic
In cyanotic children, differential diagnosis will include conal septal VSD with apparent overriding of aorta (truncus).
tetralogy of Fallot, pulmonary atresia with VSD, tricuspid Inability to show the second outflow tract and valve
atresia, atrioventricular septal defect with pulmonary stenosis (pulmonary valve) is a feature that helps to distinguish this
and double-outlet right ventricle with pulmonary stenosis. entity from tetralogy of Fallot. Anteriorly, the common arterial
Echocardiographic findings are diagnostic. trunk does not have continuity with infundibular septum.
Posteriorly, there is fibrous continuity between truncal valve
NONINVASIVE EVALUATION and mitral valve. The branch pulmonary arteries will be seen
to arise from the posterior and leftward aspect of the common
Chest X-ray arterial trunk. Color Doppler study will provide an assessment
of truncal valve stenosis and regurgitation.
Marked cardiomegaly and pulmonary plethora are present Parasternal short-axis view helps to evaluate truncal valve
in most infants. In type I truncus, there may be a normal PA anatomy regarding number of valve leaflets (Figure 3), stenosis
segment visible. In other types, the PA segment is diminutive or regurgitation. Pulmonary valve is undetectable. Location
or absent, giving the appearance of a narrow superior of the VSD should also be confirmed. Characteristically,
mediastinum. Right aortic arch is noted in approximately the membranous ventricular septum is intact with the conal
33 percent of truncus arteriosus patients. Comma sign in septal area deficient (between 12 O’clock and 2 O’clock in
left upper mediastinal border indicating high origin or high parasternal short-axis view (Figures 4A and B). Overriding
arching of left pulmonary artery may be recognizable in type of the common truncal valve may be unequal across the
III truncus.2 Absent unilateral pulmonary artery from truncus ventricular septal defect creating an impression of anterior
may cause pulmonary oligemia and smaller thorax on that or posterior deviation of the ventricular septum. Posterior 609
8
A B
Figures 4A and B: A. Parasternal short-axis view showing the
Figure 2: Parasternal long-axis view showing common arterial trunk ventricular septal defect (VSD) (arrow). VSD is conal septal VSD
(TA), ventricular septal defect (arrow) and truncal valve overriding with intact membranous portion of the ventricular septum (arrow);
ventricular septum. LV = Left ventricle; RV = Right ventricle 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
Figure 3: Parasternal short-axis view showing the cross-sectional view

of truncal valve. In this example, the truncal valve has three, dysplastic, A B
moderately thickened leaflets. LA = Left 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
deviation of ventricular septum towards the LV has the arteries; B. Color Doppler imaging shows nonturbulent flow in both
potential to develop LV outflow tract obstruction after repair. pulmonary arteries. RCA = Right coronary artery
Therefore, should be looked for. Coronary arteries will arise
from the common trunk.
Branch pulmonary arteries can be assessed further in this to refer to it as type 1.5! In type III, branch pulmonary arteries
view (Figures 5A and B). In type I truncus, the main pulmonary arise separately from either sides of the common arterial
artery will arise from the left side of the common trunk and trunk. Frequently, these origins are far apart such that they
branches into right and left pulmonary arteries. In type II truncus, may not be seen in one frame. A combination of parasternal
the two branch pulmonary arteries arise from the posterior short- axis view and suprasternal views may have to be used to
aspect of common arterial trunk. When the appearance of demonstrate each of the two branch pulmonary arteries.
pulmonary artery branching is difficult to distinguish between Apical and subcostal views confirm the findings regarding
610 type I and II, it has become an unrecognized clinical practice VSD (Figure 6), truncal valve anatomy and function.
42
Truncus Arteriosus
A B
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
Figure 6: Apical four-chamber view demonstrating a conal septal demonstrate main pulmonary artery (MPA) originating from the left
VSD (ventricular septal defect) with an overriding truncal (T) valve. side of the truncus arteriosus (TA) and bifurcating into right (RPA) and
Differential diagnosis for this appearance would include both truncus left (LPA) pulmonary arteries
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
Objectives of Catheterization
Objectives of catheterization include definition of aortic

These views may confirm the inability to demonstrate arch and its branches, identification of pulmonary artery
pulmonary valve and demonstrate branch pulmonary arteries anatomy, coronary anatomy if necessary and hemodynamic
(Figures 7A and B). In newborn, subcostal sagital view state—quantification of pulmonary blood flow and pressures
may also help to evaluate aortic arch. Suprasternal notch and estimation of pulmonary vascular resistance and its
view is useful in assessing aortic arch anatomy, sidedness reversibility in older infants and children.15
and its branches, PDA and branch pulmonary arteries. PDA
is absent in majority of cases. When PDA is present with Catheter Course
interrupted aortic arch, this may be lead an inexperienced
echocardiographer to mistake the large PDA for an aortic In current clinical practice, the diagnosis of truncus arteriosus
arch and miss the diagnosis of interrupted aortic arch. Paying is usually known at the time of catheterization. The catheter
careful attention to presence or absence of head and neck usually passes easily from RV to truncus arteriosus and into
branches may help to avoid such misstep. Right aortic arch either branch pulmonary arteries or via PDA into descending
and interrupted aortic arch are the common associations. aorta. Pitfalls in interpretation of the catheter passage include
lack of recognition of either an aortopulmonary window in
Magnetic Resonance Imaging which the catheter may have passed through the window from
main PA to aorta or a truncus arteriosus with interrupted aortic
Magnetic resonance imaging (MRI) is noninvasive and is useful arch in which the catheter has passed from truncus via PDA
in the following situations in truncus arteriosus management— into descending aorta. Cannulating each branch pulmonary
definition of pulmonary artery origins, definition of aortic artery for pressure measurement is necessary to evaluate any
arch and branching pattern, etc. when echocardiography stenosis at their origin. If cannulating each branch pulmonary
cannot determine the exact anatomy. Differentiation from artery is difficult using the venous catheter via RV, this can be
aortopulmonary window may be easier. Compared to cardiac accomplished using the retrograde, arterial catheter.28
catheterization, MRI also spares use of radiation.
Hemodynamic Evaluation
Catheterization and Angiography
Measurement of pulmonary artery pressures is important in
In neonates and infants, cardiac catheterization is only the overall evaluation. Evaluation of pulmonary vascular 611
required when echo and MRI do not provide the information resistance and demonstration of its reversibility becomes a
necessary for surgical planning. crucial entity in older unoperated children being considered
8
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 aorto-
pulmonary 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 Figure 8: Selected cine frame in anteroposterior view of an angiogram
pulmonary blood flows. In order to estimate relative blood from the truncus arteriosus (TA) demonstrating the origin of the main
flow to each of the lungs, nuclear quantitative lung perfusion pulmonary artery (MPA) and dividing into right (RPA) and left (LPA)
pulmonary arteries. The features are consistent with Collett and
scans may be used. However, this technique has not been Edwards type I truncus
formally studied or validated for this application.
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
A B
arteriosus, pulmonary artery relationships and probably
origins and coronary arteries. When a common pulmonary Figures 9A and B: Selected cine frames in (A) anteroposterior
artery is present, it is usually noted at the leftward and view and (B) left anterior oblique view of an angiogram from the
truncus arteriosus (TA). Note: The origin of right (RPA) and left (LPA)
posterior part of the common arterial trunk. Figures 8 and 9 pulmonary arteries from posterior aspect of TA, consistent with Collett
illustrate angiographic features of type I and type II (Collett and Edwards type II truncus
and Edwards) truncus.
Diagnosis of Aortic Interruption observations made from echocardiography and during the
catheterization itself.
Diagnosis of aortic interruption can be difficult with
angiography. Attention must be paid to each branch of the Thoracic Aortogram
aortic arch. A large PDA may be mistaken for aortic arch and
the ascending aorta for innominate artery. Confirming the This will show any aortopulmonary collateral arteries to the
position of each of the aortic arch branches helps to correctly lungs—especially, only one PA is identified to originate from
interpret aortic arch anomalies. aorta or truncus.
Selective Pulmonary Angiograms Pulmonary Venous Wedge Angiogram

Special views may be needed if origins of the pulmonary Pulmonary venous wedge angiogram may become necessary
arteries are to be shown. The ideal camera angles will vary to identify native pulmonary arteries when these are not
612 in each patient and need to be determined based on various 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. 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
Surgical Management ventricle (RV) via a valved conduit, which is usually a homograft.
Ventricular septal defect closure, which is part of this surgery is not
Palliative procedure, if necessary, will be pulmonary artery shown in this figure. LV = Left ventricle; RA = Right atrium
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 Postoperative Management
largely abandoned in the current day management. In addition to the usual postoperative care, immediate post
Surgical repair upon diagnosis is the usual approach in operative treatment includes management of episodes of
the current era. Exact timing of surgery may vary depending pulmonary hypertensive crises. Considerable precautions
upon the specific features in each patient. Since the only are taken to avoid pulmonary hypertensive crisis by keeping
approximately 10 percent of patient survive first year without the baby sedated with ample analgesics and sedatives. Some
surgery and there is a risk of rapid development pulmonary institutions routinely use muscle relaxants at least for the first
vascular obstructive changes, surgical repair usually is night of surgery. Nitric oxide is used as needed. Ventilatory
performed in early infancy if not as newborn. strategy to maintain alkalosis and avoiding hypoxia and
Principles of surgery include closure of VSD, separation hypercarbia is instituted.
of the pulmonary arteries from the common arterial trunk and There is also significant morbidity from pulmonary artery
connecting them to RV-PA conduit and closing the defect in stenosis, usually at the distal anastamosis of the conduit—
the common arterial trunk (Figure 10). Usually, truncal valve in the postoperative period. Such stenosis may need cardiac
does not require any surgical intervention, unless there is catheterization and angiography to demonstrate the stenosis.
significant stenosis or regurgitation. Stenting of the distal RV-PA conduit or proximal branch
When there is associated interrupted aortic arch, surgical pulmonary arteries (Figures 11 and 12) is an option in this
repair has to be performed as newborn after initial stabilization period. Balloon angioplasty of such conduit/pulmonary artery
on prostaglandin infusion. Surgical mortality is relatively high, stenosis is not advisable due to fresh suture lines.
when a combined repair of truncus arteriosus and interrupted
aortic arch need to be performed. Presence of truncal valve Outcome of Treatment
regurgitation at presentation greatly worsens the prognosis for
surgical outcome and survival. Surgical options include truncal Early Surgical Outcome
valve repair, truncal valve replacement using homografts or
mechanical valves; these have not produced good results, but In a recent review of Society of Thoracic Surgeons database
may be necessary. between 2000 and 2009 in 63 centers, 572 surgeries had been
613
8
Long-term Surgical Outcome
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
A B were for replacement of RV-PA conduits; freedom from RV-
Figures 11A and B: Bilateral branch pulmonary arteries stenosis pre- PA conduit replacement was 85 percent at 1 month, 63 percent
vented recovery during postoperative period in this newborn after repair at 3 years, 40 percent at 5 years , 11 percent at 10 years and 0
of truncus arteriosus. Stenosis of right (RPA) and left (LPA) pulmonary percent at 15 years. Some patients also required surgery of the
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
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. Twenty-
three 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 follow-
up of 10 years.31 Patients operated between 1987 and 1997 were
Figure 12: Lateral view freeze frame of stents placed at the origin studied. There were 46 patients in the cohort with a median
of both RPA and LPA in the baby shown in Figure 11. Relief of
bilateral branch pulmonary artery stenosis enabled weaning from age of 62 days and a median weight of 3.4 kg at operation.
positive pressure ventilator and postoperative recovery in this infant. Among associated anomalies, coronary anomalies were the
PA = Pulmonary artery 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
performed at a median age of 12 days.29 Surgical mortality for arch) and one death at 4 months after surgery. No late deaths
truncus arteriosus repair was 10 percent. Truncus arteriosus were reported. Freedom from RV-PA conduit reoperation at
repair along with truncal valve repair was performed in 37 five years was 43 percent when aortic homograft was used
babies. Mortality for this group was higher at 30 percent. and 73 percent when pulmonary homograft was used.
Repair of truncus arteriosus and interrupted aortic arch was The predictor of reoperation among the patients was use of a
performed in 38 babies in whom a mortality of 60 percent smaller homograft size.32 Also, presence of preoperative truncal
was noted. In four babies, valve surgery was performed as regurgitation at moderate or higher level, need for truncal valve
second surgery after an initial truncus repair. None of these repair and concomitant repair of interrupted aortic arch were
four babies survived.29 Single center experience of combined predictors of poor outcome—both short-term and long-term.
repair of truncus arteriosus and interrupted aortic arch Successful pregnancies have occurred in patients who have
from Melbourne, Australia in a cohort of 16 patients, who had truncus repair in the past—especially when the individual
underwent surgery between 1985 and 2007 revealed an early is in good functional state. Prepregnancy counseling
mortality of 12.5 percent.20 should include checking the status of 22q11 microdeletion.
614
42
Depending upon the results, appropriate counseling of the risk range 0.53–0.83) was associated with higher re-intervention
of the genetic and associated defect in the offspring must be rate. Freedom from conduit reoperation at 1 year was 92
Truncus Arteriosus
provided. Follow-up with specialist cardiologist during and percent and at 2 years, 76 percent. Development of PA stenosis
after pregnancy should be done. was considered secondary to surgery rather than preoperative
reason, because the pulmonary arteries were adequate in size
Alternative Surgical Approaches prior to surgery.34
We utilize balloon angioplasty and/or stenting of branch
In a series of 32 patients, 17 had conventional RV-PA conduit and pulmonary arteries and/or the conduit (Figures 13 to 15) to
13 had a conduit created using LA appendage and monocuspid relieve the right ventricular outflow tract obstruction and
valve.33 Mortality rates were similar between these two groups. attempt to reduce the right ventricular pressure to less than
However, reintervention rate at a mean follow-up of 40 months half systemic level. Balloon angioplasty35 and stents36,37
was significantly lower in the ‘non-conduit’ group; five of 11 appear to prolong the life of the conduit and lengthen the
in conduit group had conduit replacement, while only two interval between conduit replacements.
of nine in ‘non-conduit’, group required replacement. Lesser Recently, older candidates with conduit stenosis and/or
RV outflow gradient and better growth of branch pulmonary regurgitation have an option of transcatheter valves such as
arteries were also noted in the ‘non-conduit’ group. Whether Bonhoeffer,38 Melody® (Medtronic, Inc. USA)39 or Edwards
or not this advantage at short-term follow-up33 holds up at a Sapien® (Edward Lifesciences Inc)40 valves. Short-term
longer-term follow-up remains to be seen. results are encouraging for these valves. While transcatheter
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 Children’s 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 A B
consisting of balloon dilatation and/or stent placement in RV- Figures 13A and B: Selected cineangiographic frames in a sitting-
PA conduits (n = 29), pulmonary arteries (N = 31) and both (N up (15-degree left anterior oblique and 30-degree cranial) view
= 13). Thirty-six children required surgical reintervention for demonstrating severe stenosis of the junction of the conduit with the
pulmonary artery (arrow in A). Following stent implantation (arrow in B)
replacement of RV-PA conduit. Freedom from reintervention at the right ventricular pressure decreased and the gradient across this
1 year was 68 percent and at 2 years, 48 percent. In multivariate region abolished. Note: Normal sized right (RPA) and left (LPA) branch
analysis, use of smaller conduit size (hazard ratio 0.66/mm; pulmonary arteries. MC = Marker pig-tail catheter; RV = right ventricle
A B C
615
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
8
conclusion
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
Figure 15: Selected cineradiographic frame in the posterior-anterior counseling should be provided to prospective mothers with
view demonstrating stents in both right (RPA) and left (LPA) pulmonary
arteries. There was no significant conduit obstruction at the time of
repaired truncus arteriosus.
placement of RPA and LPA stents
The physician should look upon the patient as a besieged
city and try to rescue him with every means that art and
valve implantations will avoid need for surgical valve science place at his command.
replacement, it remains to be seen how much of an influence —Alexander of Tralles
that these transcatheter valve implantation procedures have in
the life-time of a given patient. REFERENCES
Truncal Root Dilatation and Truncal Valve Regurgitation 1. Lev M, Saphir O. Truncus arteriosus communis persistens. J
Pediatr. 1942;20:74.
Truncal root dilatation and truncal valve regurgitation occur 2. Calder L, van Praagh R, van Praagh S, et al. Truncus arteriosus
communis. Clinical, angiographic and pathologic findings in
in most of the patients. In a recent study of a cohort of 78
100 patients. Am Heart J. 1976;92:23.
patients, the mean truncal root diameter Z-score was 5.1 ± 3. Tandon R, Hauck AJ, Nadas AS. Persistent truncus arteriosus.
2.3. No dissection or rupture occurred. However, six patients A clinical, hemodynamic, and autopsy study of nineteen cases.
underwent aortic root surgery for aortic root dilatation Circulation. 1963;28:1050-60.
associated with truncal valve regurgitation and LV dilatation.41 4. Wilson J. A description of a very unusual malformation of the
human heart. Philos Trans R Soc London [Biol]. 1798;18:346.
Myocardial Dysfunction 5. Buchanan A. Malformation of the heart. Undivided truncus
arteriosus. Heart otherwise double. Trans Pathol Soc Lond.
Myocardial Dysfunction may develop from repeated surgical 1864;15:89.
6. Collett RW, Edwards JE. Persistent truncus arteriosus: A
procedures, conduit dysfunction, delayed surgery and myo-
classification according to anatomic types. Surgical Clinics of
cardial ischemia. North America. 1949;29:1245.
7. van Praagh R, van Praagh S. The anatomy of common
Arrhythmias aorticopulmonary trunk (Truncus arteriosus communis) and its
embryologic implications. Am J Cardiol. 1965;16:406-25.
Arrhythmias though rare can occur, also an important disorder 8. Van Praagh R. Editorial: Classification of truncus arteriosus
after surgical repair. communis (TAC). Am Heart J. 1976;92:129-32.
9. Kirby ML. Contribution of neural crest to heart and vessel
morphology. In: Richard P Harvey, Nadia Rosenthal (Eds). Heart
Progressive Pulmonary Vascular Disease Development. San Diego, CA: Academic Press. 1999.pp.179-93.
10. Conway SJ, Henderson DJ, Copp AJ. Pax3 is required for
In patients with delayed detection, pulmonary vascular
616 obstructive disease may develop.
neural crest migration in the mouse: evidence from the splotch
(Sp2H) mutant. Development. 1997;124:505-14.
11. Momma K, Ando M, Matsuoka R. Tuncus arteriosus 28. Rudolph M. Congenital heart diseases of the heart: Clinical-
42
communis associated with 22q11 deletion. J Am Coll Cardiol. physiologic considerations. 2nd edition. Armonk, NY. Futura
Truncus Arteriosus
1997;30:1067-71. Publishing Co. Inc. 2001.pp.737-61.
12. Goldmuntz E, Clark BJ, Mitchell LE, et al. Frequency of 29. Russell HM, Pasquali SK, Jacobs JP, et al. Outcomes of repair
22q11 deletions in patients with conotruncal defects. J Am Coll of common arterial trunk with truncal valve surgery: a review
Cardiol. 1998;32:492-8. of the society of thoracic surgeons congenital heart surgery
13. Emanuel BS, Budarf ML, Scambler PJ. The genetic basis database. Ann Thorac Surg. 2012;93:164-69.
of conotruncal defects: The chromosome 22q11.2 deletion. 30. Rajasinghe HA, McElhinney DB, Reddy VM, et al. Long-term
In: Heart Development. (Eds). Richard P Harvey and Nadia follow-up of truncus arteriosus repaired in infancy: a twenty-
Rosenthal. San Diego, CA. Academic Press. 1999.pp.463-78. year experience. J Thorac Cardiovasc Surg. 1997;113:869-78.
14. Goldmuntz E. Deciphering the genetic etiology of conotruncal 31. Urban AE, Sinzobahamyya N, Brecher AM, et al. Truncus
defects. In: Artman M, Woodrow Benson D, Srivatsava D, arteriosus: ten-year experience with homograft repair in
Nakazawa M. Malden, MA. Blackwell Futura. 2005.pp.238-41. neonates and infants. Ann Thorac Surg. 1998;66:S183-S8.
15. Mair D, Ritter D, Davis G. Selection of patients with truncus 32. Williams JM, de Leeuw M, Black MD, et al. Factors associated
arteriosus for surgical correction: Anatomic and hemodynamic with outcomes of persistent truncus arteriosus. J Am Coll
considerations. Circulation. 1974;49:144-51. Cardiol. 1999;34:545-53.
16. Butto F, Lucas R, Edwards J. Persistent truncus arteriosus: 33. Raisky O, Ali WB, Bajolle F, et al. Common arterial trunk
Pathologic anatomy in 54 cases. Pediatr Cardiol. 1986;7:95- repair: with conduit or without? Eur J Cardiothorac Surg.
101. 2009;36:675-82.
17. Thiene G, Bortolotti U, Gallucci V. Anatomical study of 34. Lund AM, Vogel M, Marshall AC, et al. Early reintervention
truncus arteriosus communis with embryological and surgical on pulmonary arteries and right ventricular outflow tract after
considerations. Br Heart J. 1976;38:1109-23. neonatal or early infant repair of truncus arteriosus using
18. Kirklin JW, Barratt-Boyes BG. Truncus arteriosus. In: Kirklin homograft conduits. Am J Cardiol. 2011;108:106-13.
JW, Barratt-Boyes BG (Eds). Cardiac Surgery 2nd edition. 35. Rao PS. Balloon dilatation of stenotic bioprosthetic valves. In:
New York: Churchill livingstone. 1992.pp.1131-52. Rao PS (Ed). Transcatheter Therapy in Pediatric Cardiology.
19. Russell HM, Jacobs ML, Anderson RH, et al. A simplified New York, NY: Wiley-Liss. 1993.pp.255-74.
categorization for common arterial trunk. J Thorac Cardiovasc 36. Powell AJ, Lock JE, Keane JF, et al. Prolongation of RV-
Surg. 2011;141:645-53. PA conduit life span by percutaneous stent implantation:
20. Bohuta L, Hussein A, Fricke TA, et al. Surgical repair of intermediate-term results. Circulation. 1995;92:3282-8.
truncus arteriosus associated with interrupted aortic arch: 37. Rao PS. Stents in the management of congenital heart
Long-term outcomes. Ann Thorac Surg. 2011;91:1473-7. disease in the pediatric and adult patients. Indian Heart J.
21. Bharati S, McAllister HA Jr, Rosenquist GC, et al. The surgical 2001;53:714-30.
anatomy of truncus arteriosus communis. J Thorac Cardiovasc 38. Bonhoeffer P, Boudjemline Y, Saliba Z, et al. Percutaneous
Surg. 1974;67:501-10. replacement of pulmonary valve in a right-ventricle to
22. Jacobs ML. Congenital heart surgery nomenclature and pulmonary-artery prosthetic conduit with valve dysfunction.
database project: Truncus arteriosus. ATS. 2000;69:S50-S5. Lancet. 2000;356:1403-5.
23. Juaneda E, Haworth SG. Pulmonary vascular disease in 39. McElhinney DB, Hellenbrand WE, Zahn EM, et al. Short- and
children with truncus arteriosus. Am J Cardiol. 1984;54:1314. medium-term outcomes after transcatheter pulmonary valve
24. Marcelleti C, McGoon DC, Mair DD. The natural history of placement in the expanded multicenter US Melody® valve
truncus arteriosus. Circulation. 1976;54:108. trial. Ciculation. 2010;122:507-16.
25. Victorica BE, Krovetz LJ, Elliott CP, et al. Persistent truncus 40. Kenny D, Hijazi ZM, Kar S, et al. Percutaneous implantation
arteriosus in infancy. Am Heart J. 1969;77:13. of the Edwards SAPIEN transcatheter heart valve for conduit
26. Hagler DJ, Tajik AJ, Seward JB, et al. Wide-angle two- failure in the pulmonary position: Early phase I results from
dimensional echocardiographic profiles of conotruncal an international multicenter clinical trial. J Am Coll Cardiol.
abnormalities. Mayo Clinic Proc. 1980;55:73. 2011;58:2248-56.
27. Snider AR, Serwer GA, Ritter SB. Pesistent truncus arteriosus. 41. Carol WF, McKenzie ED, Slesnick TC. Root dilatation
In: (Eds) Echocardiography in pediatric heart disease. 2nd in patients with truncus arteriosus. Congenit Heart Dis.
edition. St Louis: Mosby. 1997.pp.289-96. 2011;6:228-33.
617
C hapter
43 D-transposition of Great Arteries
Suresh Rao, Swati Garekar
Introduction aortic valve anteriorly and to the right. At the same time the
subpulmonary infundibulum fails to develop. TGA is usually
Transposition of the great arteries (TGA) is the most common an isolated defect. Complex TGAs are more likely to be
cause of a cyanotic newborn. Its management has been one of associated with extracardiac anomalies. An Italian multicenter
the amazing success stories as far as the treatment of various study found a 10 percent recurrence risk of congenital heart
complex congenital heart defects in the last two decades is disease (CHD) in families with a child with TGA. This study
concerned. The advances in medical science has converted looked at 370 consecutive patients with TGA. The most
a lesion with a very high mortality if left untreated, to one common CHDs reported were D-TGA, L-TGA, tetralogy of
where the child with TGA today can look forward to having Fallot and VSD.1 The finding of congenitally corrected TGA
a reasonably normal lifestyle and hopefully longevity. This (L-TGA or double discordance) in family members suggest a
treatise will discuss pure or isolated transposition of the common causative gene for these defects. This is against the
great arteries, i.e. a lesion with atrioventricular concordance, traditional classification of D-TGA under conotruncal defect
ventriculoarterial discordance, two good sized ventricles and L-TGA under looping defects.
and atrioventricular valves, with either an atrial septal The genetic mechanisms and several mutations have
defect (ASD), ventricular septal defect (VSD) or patent been implicated as the cause of discordant ventriculoarterial
ductus arteriosus (PDA) as a single associated anomaly or a connections.The genes which maybe involved are the growth
combination of anomalies. differentiation factor-1 gene, the thyroid hormone receptor-
Transposition of the great arteries means that the origin associated protein-2 gene and the gene encoding the cryptic
of the great arteries from the heart is reversed. In simple protein.2
terms, the aorta originates from the right ventricle (RV) and
the pulmonary artery originates from the left ventricle (LV), Incidence
while the atrioventricular (AV) connections are normal (AV
concordance with ventriculoarterial (VA) discordance). Transposition of great arteries is a common form of congenital
Specifically, D transposition of the great arteries implies heart anomaly occurring in 1:2000 to 4500 births and
that the aortic valve is ‘D’ related to the pulmonary valve accounting for 7 to 8 percent of all congenital heart defects.
(to the right and anterior) in the setting of ventriculoarterial Male to female ratio is 2:1, increasing to more than 3:1 for
discordance. However, VA discordance with variable TGA with intact ventricular septum.3,4
semilunar valve relationship has been described. As long as
the pathophysiology and the management pathway is the same ETIOPATHOGENESIS
as classic D-TGA, these variations are still called transposition
of the great arteries. The exact etiology of this disease is still unknown. The
associated risk factors, namely gestational diabetes
Embryology and Inheritance mellitus, maternal exposure to rodenticides, herbicides, and
maternal use of antiepileptic drugs have been postulated.2
Transposition of great arteries is believed to be due to Isolated TGA is called a simple TGA. It could be
abnormal presence and growth of the subaortic infundibulum. associated with a large VSD (up to 45% of cases). The types
This is absent in normal hearts. This infundibulum pushes the of VSDs seen are commonly perimembranous, muscular
and malalignment (30% each). When coarctation or arch Clinical Presentation 43
interruption is associated with TGA it is called a complex
TGA. About 20 percent of isolated TGAs have some form Simple transposition of great arteries usually presents in
d-transposition of great arteries

of left ventricular outflow tract obstruction (LVOTO) and the neonatal age group with severe cyanosis. The pulse
this is usually dynamic. TGA with VSDs have a 30 percent oximetry reading may show values of less than 40 percent.
incidence of LVOTO and this is usually fixed. The common This extremely low saturation can be confirmed by an arterial
causes include mitral valve tissue; posterior deviation of blood gas. In a simple TGA, reverse differential cyanosis
the conal septum and accessory tricuspid valve tissue will be present: the postductal saturation will be higher than
protruding in from the VSD.5 the preductal one. On auscultation, the S1 may be loud; S2
Other rarer defects of the heart like a hypoplastic ventricle, appears single. There may be a soft 2/6 ejection systolic
an aortopulmonary window, total anomalous pulmonary murmur along the upper sternal border. There is no diagnostic
venous connection, complete atrioventricular septal defects or auscultatory finding unfortunately. For the pediatrician
valvular deformities may also be seen.3,4 Coronary anomalies handling a neonate presenting with severe cyanosis, the other
are also very common in complex TGA. The most common differential diagnosis are pneumonia and/or sepsis. Absence
variation is origin of the circumflex artery from the right of respiratory distress, clear lung fields on chest radiograph
coronary artery (16% incidence). and absence of septic markers will make cyanotic CHD
the number one differential. Presence of a VSD is not an
Pathophysiology insurance against cyanosis, as flow of blood across the VSD
will be predominantly unidirectional.
Because of the reversed connections, the venous blood The neonate, who escapes detection of cyanosis will present
(deoxygenated blood) returning from the body goes back in infancy/early childhood with failure to thrive. If there is
to the body as the RV leads out to the aorta. Similarly, the subpulmonary valvar obstruction, a murmur may be the
oxygenated or pure blood returning from the lungs via the presenting sign. In complex TGAs with increased pulmonary
left atrium and LV goes back to the lungs via the pulmonary blood flow, the infant presents with signs and symptoms of
artery (circulation in parallel). This form of circulation is congestive heart failure.
incompatible with life after the baby is born, unless there The one who survives to early and mid childhood have
is mixing at the atrial, ventricular or arterial level. Of degrees of pulmonary stenosis (PS) and become increasingly
these three, the atrial level mixing is the most effective cyanotic as the PS progresses with growth and suffer the
in getting some left atrial blood out to the aorta and also complications of polycythemia and hyperviscosity syndromes.
some deoxygenated right atrial blood out to the pulmonary
artery. TGA is a circulation where the net pulmonary Natural History
blood flow is increased (presence of bronchopulmonary
collateral circulation). Hence, children with TGA and with A neonate with untreated TGA and insufficient mixing channels
the associated hypoxia, develop accelerated pulmonary (PDA/ASD/VSD) will succumb to hypoxia. The ones with
vascular disease if left untreated. The several anatomic and sufficient mixing will show a retarded physical and mental
functional factors and the extent of intercirculatory mixing growth and succumb to ill effects of hypoxia and polycythemia.
(Box 1), influences the clinical manifestations and course of Overall, approximately 30 percent of neonates will have expired
the disease.5 by age 1 month and 90 percent by age 1 year.6
Diagnosis
Box 1: Physiological – Clinical classification in In the current era, TGA is diagnosed by transthoracic
transposition of great arteries5 echocardiography. Almost all anatomic features and even
TGA (IVS or small VSD) with increased PBF and small coronary arterial anomalies may be picked up by this imaging
intercirculatory shunting modality. With improvements in fetal echocardiographic
TGA (large VSD) with increased PBF and large intercirculatory techniques, TGA may be diagnosed with certainty in the
shunting fetus as early as 14 weeks of gestation. On echocardiography,
TGA (VSD and LVOTO) with restricted PBF a detailed and complete segmental analysis is essential
TGA (VSD and PVOD) with restricted PBF (Figures 1A to C). Attention to AV valve annulus size,
ventricular size, description of the kind (if any) of
IVS = Interventricular septum; LVOTO = Left ventricular outflow
obstruction; PBF = Pulmonary blood flow: PVOD = Pulmonary subpulmonary obstruction, morphology of the semilunar
vascular obstructive disease; TGA = Transposition of great arteries; valves (especially the pulmonary valve-the future aortic
VSD = Ventricular septal defect. valve), size discrepancy of the main pulmonary artery versus
619
8
A B
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
C ventricle; PA = Pulmonary artery; RV = Right ventricle
the ascending aorta, coronary artery anatomy (low parasternal assess pulmonary artery pressure and response to vasodilators
window) helps to avoid surprises on the operating table. An in cases of late presentation when a palliative repair is being
anomalous coronary artery can be suspected if in any view, a comtemplated. The derived value of pulmonary vascular
coronary is seen coursing posterior to the pulmonary artery. resistance is fraught with assumptions. Computed tomography/
A few classifications for description of the coronary artery magnetic resonance imaging (CT/MRI) maybe useful and
anatomy exist. We describe the coronary arteries in terms of indicated in those rare cases where an abnormal aortic arch
arising from sinus 1 (leftward sinus) and sinus 2 (rightward (coarctation or interruption) is not visualized to satisfaction.
sinus). The normal coronary artery arrangement would thus A chest radiograph in the neonate with TGA will show a clear
be described as 1LC× 2R. A description in words of what is lung field, normal heart size and a narrow superior mediastinum
seen on echocardiography most often conveys the anatomy (as the great arteries lie on top of each other) (Figure 2). In the
better than complicated classification systems. This is infant, increased pulmonary vascularity and mild cardiomegaly
especially true, when images are suboptimal and there is a will be seen (Figure 3). In fact, severe cyanosis accompanied
suspicion of anomalous coronary. A mention must be made of by (paradoxically) increased pulmonary vascular markings on
any intramural course or juxtacommissural origin. chest radiograph is a pointer to the diagnosis.
It is indeed very rare that cardiac catheterization is done for An electrocardiogram in the neonate may appear normal.
TGA. The indication for cardiac catheterization in TGA is to Gradually, right ventricular hypertrophy manifests as upright
assess LV and RV pressure and suitability for arterial switch in T waves in the right precordial leads along with right axis
patients who present late and noninvasive assessment shows deviation. There may be absence of q waves in the precordial
620 borderline LV size. The only practical indication seems to be to leads (Figure 4).
43

Figure 2: Chest radiograph of a neonate with transposition of great Figure 3: Chest radiograph of an infant with transposition of great
arteries and intact interventricular septum arteries and a large ventricular septal defect
Figure 4: Twelve lead electocardiogram of a neonate with transposition of great arteries
Management of Transposition of infusion is begun if the atrial level communication is not

Great Arteries effective in maintaining peripheral saturation around 75
percent and higher. If this does not help, balloon atrial
The management of transposition of great arteries in a neonate septostomy is performed on an emergency basis. An
is surgical. adequate balloon atrial septostomy enables one to stop the
All treatments and other modalities of interventions are prostaglandin drip thereby preventing its side effects (apnea,
performed to make the neonate a better candidate for surgery. peripheral edema, tissue edema, rash). Occasionally, giving
Neonatal care involves ensuring that the peripheral oxygen to the neonate may improve oxygenation as well.
circulation is preserved. Monitoring and maintenance of The aim is to regulate the pulmonary and systemic vascular
peripheral temperature, pulses, capillary refill time and circuits so that adequate mixing is achieved.
urine output is essential. Laboratory tests to assess brain The surgical corrective procedure of choice in the neonatal
(ultrasound), kidneys (blood urea nitrogen, creatinine) and period and early infancy in simple and most of the complex
liver function tests should be performed. Prostaglandin transpositions is the arterial switch operation (ASO). 621
8 Arterial Switch Operation shaped LV cavity in cross-section (interventricular septum
bowing into the LV cavity); posterior wall thickness of less
Jatene arterial switch operation is an open heart surgical than 0.3 cm and LV mass less than 35 g/m2.7 Suitability for
correction, where the VA discordance is restored to normal. arterial switch surgery is therefore based on LV cavity being
The ascending aorta and the main pulmonary artery are atleast D shaped in systole and LV posterior wall thickness
transected and then anastomosed to the semilunar valve of the being atleast 0.3 cm in diastole. The mass of the LV on 2D
correct ventricle. The coronary artery origins from the original echocardiography is as calculated from the formula:
aortic valve sinuses are mobilized as buttons (ostia surrounded LV mass=1.05 {[5/6A1 (L+t)] – [5/6 A2 L]}
by sinus tissue) and then translocated to a new place on the where 1.05 is the specific gravity of the myocardium. L=long
neoaorta. The Lecompte maneuver brings the main pulmonary axis length of the ventricular cavity obtained from the 4
artery anterior and the ascending aorta posteriorly. Other chamber apical view. t=calculated mean LV wall thickness.
associated lesions like ASD, VSD, PDA and in few cases, t=√(A1/Π) – √(A2/ Π) where A1 is the total area enclosed by
left ventricular outflow obstructions like coarctation, arch the LV epicardium in short axis end diastolic frame. A2 is the
hypoplasia or interruption are also corrected. total area enclosed by the LV endocardium in short axis end
In effect, the arterial switch operation is a very good diastolic frame.
“functional” correction, though not strictly anatomical in In cases of TGA with a large VSD or PDA, the LV does
nature as thought so earlier, as the altered semilunar valve not regress as it remains at a high pressure. Hence in these
relationships, such as being anteroposterior in nature persists situations, ASO could be delayed to around a month or two,
even after the correction. This has a role to play in long-term when the indication would be increasing pulmonary blood
morbidities seen after this corrective surgery. flow and failure to thrive.
In the subset with LVOTO and those found fit for an ASO,
ATRIAL SWITCH OPERATION the LVOTO serves to forestall LV regression and allows an
elective ASO to be carried out.
The other alternative corrective procedures—Senning or There are reports of stretching the age limit of primary
Mustard are the “atrial switch” operations. This is so called ASO in TGA with intact ventricular septum to 3 to 6 months
as the circulatory correction is done at the atrial level, so that of age. These would be instances where the presentation of
the venous blood from the vena cava reaches the pulmonary the infant is late. The risks and mortality are higher and so
artery via the mitral valve and the LV and the pulmonary is the need for some form of left ventricular support for a
venous blood reaches the aorta via the tricuspid valve and time period postoperatively. The long-term behavior of these
the RV. The RV with the tricuspid valve is the systemic ventricles is unknown at the present time. It is hoped that they
ventricle and the mitral valve with the LV is the pulmonary adapt like the neonatal LVs, unlike those “trained” LVs, where
ventricle. Though this serves to correct the hypoxia of TGA, long-term dysfunction is common.
the unphysiological VA relationships give problems in the For the older patients with TGA and large VSD with
long-term in terms of tricuspid valvular regurgitation and pulmonary hypertension, it has been the experience of
systemic ventricular dysfunction along with varieties of the authors that children upto 2 to 3 years of age can be
atrial arrhythmias related to suture lines in the atria. operated upon expecting a low morbidity and mortality post
operatively. For the slightly older children, it has been our
Timing of Surgery practice to measure pulmonary artery pressure directly in the
cardiac catheterization laboratory and see the response of the
In a child with TGA with intact septum, in the normal course pressure to oxygen. A fenestration in the atrial or ventricular
of progression after birth, the LV, which had an equal mass septum is placed in borderline cases. Use of oral pulmonary
with the RV at birth, undergoes regression commensurate with vasodilators (sildenafil, bosentan) postoperatively. has helped.
the fall in the pulmonary vascular resistance. This renders the
LV incapable of supporting the systemic circulation and face Contraindications for an Arterial Switch Operation
the systemic vascular resistance, leading to its failure. Hence,
it mandates that the ASO be performed before the regression
Absolute
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 1. Pulmonary annular stenosis.
is done, the better for the child with TGA and an intact 2. Subvalvar LVOTO, which cannot be resected (non-
septum. It has been observed that babies with small atrial accessory mitral valve tissue).
level communications have better preserved LV myocardium. 3. A deformed pulmonary valve other than a plain bicuspid
This is probably due to the LV seeing more volume of blood valve.
as compared to a situation where there is a large ASD. On 4. A regressed LV seen beyond infancy.
622 echocardiogram, regression of the LV manifests as a banana- 5. Hypoplasia of ventricles.
Relative correcting the TGA physiology by an atrial switch operation 43
or an ASO leaving the VSD untouched could convert them to
Complex coronary artery anatomy. an Eisenmengerized VSD situation, removing the unfavorable

hemodynamics of a TGA in the process. This results in better
Other Options oxygenation and may probably retard the pulmonary vascular
disease progression once the hypoxic and polycythemic stimuli
In a TGA with intact ventricular septum, with a regressed LV have been removed. Use of oral pulmonary vasodilators
in infancy, a rapid two staged ASO could be attempted with (sildenafil and bosentan) may help as well.
success. A preliminary pulmonary artery banding to train the
LV with ASO a week later is performed.4 Result
More recently, there have been reports of ductal dilatation
and stenting to keep the LV prepared by subjecting the LV Currently the results of surgery for TGA is most gratifying
to volume overload and increasing its afterload due to the in both early and late periods.8 A lesion with a 100 percent
ensuing pulmonary arterial hypertension.8 mortality, if untreated has been converted to one with a near
However, in children beyond infancy with a regressed 100 percent chance of success after surgical correction with a
LV, an atrial switch repair in the form of a Senning operation good quality of life and growth in these children.10
could be performed successfully with low risk and a good More than 95 percent of children with simple transposition
palliation. can be corrected by an ASO successfully with predictable
In TGA with fixed LVOTO in the form of subvalvar, results.
valvar, annular or suprannular stenosis with a VSD, a Rastelli The mortality of complex transposition after surgical repair
procedure with VSD routing to aorta and establishment of too is below 10 percent currently in most large series.
RV—pulmonary arterial (PA) continuity with a conduit is the Atrial switch operation (Senning) operation has a reported
usual norm. Many modifications of this procedure in the form mortality of around 2 percent.
of aortic translocation and/or pulmonary translocation have Actuarial survival after an ASO is reported to be 98 percent,
been described. 93 percent and 91 percent at 1, 3 and 5 years respectively across
Another option in infants with TGA/VSD and LVOTO has all forms and severity of TGA. Freedom from reoperation was
been the REV operation which routes the VSD to the aorta 95 percent, 90.5 percent and 83 percent at the same points.
and establishes RV–PA continuity without a conduit. Residual The presence of a VSD adversely affected survival. Predictors
pulmonary regurgitation in varying degrees is seen after this of reintervention included VSD, coronary anomalies, aortic
form of repair.9 coarctation, LVOTO or moderate PS.9
What is the Place of Balloon Atrial Septostomy Long-Term Issues postcorrection

in Current Practice?
The arterial switch operation too, which was considered a
Balloon atrial septostomy (BAS) is regarded as one of the “cure” and an “anatomical correction” in the early era, has
procedures that changed the face of survival in neonates with certain inherent flaws that may cast a shadow in the long-
TGA. It helps to promote mixing across the interatrial septum term.
and improves the effective pulmonary blood flow and the Even though the ASO has a better long-term survival
oxygenation leading to survival. when compared with the atrial level corrections, freedom
Despite the initial benefits, recent reports of embolism from reoperation in the long-term is inferior to the Senning
have dampened the enthusiasm to use this procedure.9 operation for simple transpositions in some reports.10
Also, the ability to do the ASO successfully soon after The long-term issues identified are as follows:
birth has also limited the indications for a balloon atrial 1. Compromised neurodevelopmental, behavioral and
septostomy. neuropsychiatric outcomes: These manifest as gross and
fine motor and language developmental delay, learning
Current Indications disabilities, hyperactivity and attention deficit disorders.
This is seen in a minority of patients.
1. To stabilize preoperatively before an ASO. 2. Suprapulmonary valvar and bifurcation stenosis: 10 to 30
2. To stabilize before transfer to a higher center. percent incidence; particularly in those with TGA, VSD and
aortic arch anomalies. On echocardiography, the branch
Palliative Surgery pulmonary arteries are seen straddling the ascending aorta
on either side. It is easy to appreciate how the “straddled
In those cases of TGA with a large VSD presenting at a very position” hampers the growth of the bifurcation of the
late stage with fixed elevated pulmonary vascular resistance, pulmonary arteries. 623
8 3. Neoaortic regurgitation: Approximately 5 to 10 percent, References
the incidence rises over the years. The grade is trivial to
mild in the majority of patients. It is more likely to be 1. Digilio M, Casey B, Marino B, et al. Complete transposition
severe in patients with complex TGA and in those, who of the great arteries. Patterns of Congenital Heart Disease in
Familial Precurrence. Circulation. 2001;104:2809-14.
have had prior pulmonary artery banding procedure.
2. Martins P, Castela E. Transposition of the great arteries.
4. Coronary artery issues, symptomatic/asymptomatic: Orphanet J Rare Dis. 2008;13:3-27.
Approximately 5 percent. Some centers perform coronary 3. Kouchoukos N, Blackstone E, Hanley F, et al. Cardiac Surgery
angiograms periodically (every 5 years) to assess the growth 3rd edn. Churchill Livingstone, Elsevier; 2003.
and anatomy. Apart from the concern of ischemia, another 4. Sellke Frank, Pedro del NIdo, Scott J Sullivan. Sabiston and
aspect is the disruption of autonomic nervous supply and its Spencer Surgery of the Chest, 8th edn. Saunders Elsevier;
long term impact on vasodilatory capacity during exertion. 2010.
Lifelong follow-up is essential and a thorough annual 5. Wernovsky G. Transposition of the great arteries. In:
physical examination coupled with a 12 lead ECG and a complete Moss and Adams’ Heart Disease in Infants, Children,
and Adolescents: Including the Fetus and Young Adults,
echocardiogram is recommended. At an appropriate age, an
7th edn. Allen HD, Driscoll DJ, Shaddy RE, Feltes TF
exercise stress test should be made an annual requirement. (Eds). Lippincott Williams & Wilkins, Philadelphia; 2008.
pp.1039-87.
Conclusion 6. Liebman J, Belloc NB, et al. Natural history of transposition of
the great arteries. Anatomy and birth and death characteristics.
Isolated TGA as a congenital anomaly can be treated surgically Circulation. 1969;40:237-62.
today with a high degree of success. However, the excitement 7. Lacour-Gayet F, Piot D, Planche C, et al. Surgical
of the arterial switch operation being a “cure” has been management and indications of left ventricular retraining
dampened by the long-term issues being seen as the follow in arterial switch for transposition of the great arteries
with intact ventricular septum. Eur J Cardiothorac Surg.
up has increased. Not withstanding these issues, children with
2001;20(4):824-29.
TGA after the ASO, particularly for simple TGA, can look 8. Sivakumar K, Francis E, Krishnan P, et al. Ductal Stenting
forward to a life of normal growth, activity, with a very good retrains the left ventricle in TGA with IVS. J Thorac Cardiovasc
quality of life and in sinus rhythm, much unlike those with Surg. 2006;132:1081-86.
the atrial switch operations. Recognizing the long-term issues 9. Richard A Jonas. Comprehensive Surgical Management of
encountered, it is mandatory to keep operated children under Congenital Heart Disease. JR Soc Med. 2004;97(8):407-08.
lifelong follow-up. 10. Horer J, Schreiber C, Cleuziou J, et al. Improvement in
long-term after hospital discharge but not in freedom from
There are in fact two things, science and opinion; the former reoperation after the change from atrial to arterial switch
for transposition of great arteries. Thorac Cardiovasc Surg.
begets knowledge, the later ignorance
2009;137:347-54.
—Hippocrates
624
C hapter
Congenitally Corrected Transposition

44 of the Great Arteries
English C Flack, Neeru Kaushik, Thomas P Graham
Introduction
to a right sided atrium), L-looped ventricles (the morphologic
Congenitally corrected transposition of the great arteries LV with mitral valve positioned on the right) and L-transposed
(ccTGA) is a complex defect remarkable for its significant great arteries (aorta arising off the left-sided morphologic RV
anatomic abnormalities that nonetheless result in hemo and therefore situated anterior and leftward of the pulmonary
dynamically stable physiology. It is a rare defect that combines artery). The RV serves as the systemic ventricle and in the
atrioventricular (AV) discordance with ventriculoarterial absence of other defects, oxygen saturation is normal. The
discordance. In ccTGA the atria are connected to the opposite most common positions of the heart in the chest are levocardia
ventricle (left atrium to right ventricle via a tricuspid valve) (apex to the left) or mesocardia (midline). Patients with levo-or
and the ventricles are connected to the discordant great artery mesocardia and visceral situs inversus have a high likelihood
(right ventricle to aorta). Thus oxygen rich, systemic blood of ccTGA and therefore must carefully be assessed for atrial,
is circulated by the morphologic right ventricle (RV) and ventricular and arterial concordance. Dextrocardia, in which
deoxygenated blood returns to the right atrium to be pumped the apex of the heart is to the right, occurs in approximately 20
out the morphologic left ventricle (LV) to the lungs (Figure 1). percent of patients.1 In cases of dextrocardia with mirror-image
The defect is therefore ‘corrected’ because of the physiologic anatomy the anatomic designation is {I, D, D}.
flow of blood through the body. For the purposes of this review,
univentricular hearts, those with common AV valves and those Associated Defects
with aortic atresia will not be discussed.
The most common associated defects in ccTGA are ventricular
Incidence and Genetics septal defects (VSDs), which occur in 60 to 80 percent of cases,
pulmonary stenosis (PS) in 30 to 50 percent and tricuspid
The incidence of ccTGA in patients with congenital heart valve (TV) anomalies in 14 to 56 percent. The VSDs are
disease (CHD) is approximately 0.5 percent with a slight usually large, perimembranous and subpulmonary in location.
male predominance.1,2 Although a specific genetic defect is Muscular inlet defects as well as multiple VSDs may also be
yet to be defined for ccTGA, the recurrence risk of either type seen. Pulmonary stenosis, more appropriately referred to as
of transposition (corrected or non-corrected) for siblings of left ventricular outflow tract obstruction (LVOTO), may be
ccTGA patients is 2.6 percent. The overall recurrence risk for caused by fibromuscular tissue, valvar stenosis, or aneurysmal
any type of congenital heart defect is 5.2 percent in siblings of tissue of the membranous ventricular septum. The associated
ccTGA patients.2 This recurrence risk of more than 5 percent combination of LVOTO and VSD represents the largest group
is higher than expected, given that the typical recurrence risk of ccTGA patients. TV anomalies can occur along a varied
for unaffected parents to have an additional child with CHD is spectrum. Ebsteinoid malformations of the TV generally
thought to be 1 to 3 percent.3 represent the most clinically severe form. Furthermore, as the
TV is subjected to systemic pressures, even normally formed
Anatomy valves display progressive regurgitation with age. Less
common defects occurring in association with ccTGA include
The most common segmental alignment in ccTGA is that of atrial septal defect, patent ductus arteriosus, pulmonary
{S, L, L}, representing atrial and visceral situs solitus (right-sided atresia, double outlet RV, aortic regurgitation, mitral valve
inferior and superior vena cavae returning deoxygenated blood abnormalities and subaortic stenosis.1,4,5
8 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 (right-
sided) 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
Figure 1: Congenitally corrected transposition of the great arteries.
have connections to the ventricles. Patients with appropriate
IVC = Inferior vena cava; LA = Left atrium; LV = Left ventricle; MPA alignment of the atrial and ventricular septae may be more
= Main pulmonary artery; RA = Right atrium; RV = Right ventricle; likely to have two AV nodes with corresponding conduction
SVC = Superior vena cava. 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
Coronary Arteries and Cardiac Veins correlating ECG findings of complete heart block, suggesting
fibrotic invasion is involved in the development of AV
The coronary arteries are inverted in ccTGA, as described by block.8,10
Ismat et al.6 Just as the morphologic LV is situated on the
right side of the heart, the morphologic left coronary artery Natural History and Outcome
arises from the right aortic sinus. The morphologic right
coronary artery similarly arises from the left posterior aortic The natural history of ccTGA depends largely on the presence
cusp and supplies the left-sided morphologic RV. The right- of associated defects. Patients under 5 years of age who also
sided coronary (the morphologic left main coronary artery) have a VSD, LVOTO and/or TV abnormalities represent the
bifurcates into the anterior descending artery, which lays in the highest frequency of non-surgical deaths. However, patients
interventricular groove and the circumflex branch that courses with isolated ccTGA (no associated lesions) may survive
posterior to the heart in the right AV sulcus. Additional rare into their 4th and 5th decades.11,12 Nevertheless, many of
anomalies have been described, in which both main coronaries these patients will demonstrate one or more complications
arise from a single ostia or one main coronary gives rise to the including rhythm disturbances, tricuspid regurgitation (TR)
other (i.e. anterior descending off the right coronary artery).4,6 and congestive heart failure (CHF). Approximately 2 to 4
The cardiac veins generally correspond to ventricular and percent of ccTGA patients have ventricular pre-excitation
coronary anatomy as described in a pathological series by (Wolff-Parkinson-White syndrome) and should undergo
Bottega et al.7 In their series, prominent venous collaterals radiofrequency ablation of accessory pathways in cases of
were commonly noted on ccTGA specimens allowing symptomatic re-entrant tachycardia. Atrial tachycardias such
the morphologic LV to drain via Thebesian veins into the as atrial fibrillation and flutter often occur with increasing age,
coronary sinus. The coronary sinus then emptied as normal atrial enlargement and following surgical repair where suture
into the right atrium. These venous structures are often dilated lines and scars may support focal re-entrant circuits.
which can be of benefit in providing access to both ventricles Prieto et al13 suggests that outcome is dependent on
in some percutaneous procedures.7 morphology of the TV (the systemic AV valve), as this was the
only predictor of severe regurgitation and RV dysfunction in
Conduction System a cohort of ccTGA patients described after mean follow-up of
20 years. The authors concluded that severe TV insufficiency
Conduction system abnormalities are common in ccTGA. leading to RV dysfunction has the greatest impact on long-
The conduction system often consists of dual AV nodes and term survival in both operated and unoperated patients. In
626 inversion of AV bundles. An increasing incidence of AV block, patients who underwent surgical intervention for ccTGA,
20-year survival rate was 90 percent for patients with competent Prenatal Diagnosis 44
TVs, whereas survival was only 35 percent for patients with
severe TV insufficiency. Furthermore, patients who were Fetal diagnosis in CHD continues to improve. However,
Congenitally Corrected Transposition of the Great Arteries

diagnosed with severe TV insufficiency demonstrated a rapid the fetus with ccTGA and mild or no additional intracardiac
deterioration in clinical status with RV failure occurring on anomalies may be overlooked by routine ultrasound screening.
average 5 years after onset of insufficiency.13 By 45 years Distinct features notable on prenatal ultrasound that may
of age 67 percent of ccTGA patients with associated defects improve detection of ccTGA are the parallel course of the
will have developed CHF, as shown in Figure 2, whereas great arteries in combination with dextrocardia, abnormal
only 25 percent of ccTGA patients without associated lesions insertion of the papillary muscles and/or an abnormal TV.18-20
will have progressed to CHF by this age.14 In some cases A retrospective review by Wan et al. found no difference in the
patients may remain relatively asymptomatic through early number of cardiac interventions, timing of surgery or survival
and mid-adulthood. However, the frequent development of between a cohort of ccTGA patients diagnosed prenatally
complications in the 4th and 5th decades often culminates in (n = 14) and postnatally (n = 26). However, because 70
the progressive development of RV (systemic) dysfunction percent of this cohort required cardiac intervention prior
and heart failure, requiring aggressive medical management to 3 years of age, the authors suggest prenatal diagnosis is
and possible surgical intervention.12 important for preparation and counseling of the family.21
It is well-established that compensatory hypertrophy A recent review of 11 cases of fetal ccTGA diagnoses
of the systemic RV leads to overall decreased capillary describes the use of four-dimensional echocardiography
density with myocardial perfusion defects.15,16 However, and spatiotemporal image correlation (STIC), in which the
to what degree these perfusion defects commonly lead to relationship of the great arteries can be assessed in several
myocardial infarction and scarring in patients with systemic different orthogonal planes by placement of a reference
RV is unclear.17 Additional evaluation is required to further dot on images reconstructed from acquired volume data
determine the association between impaired coronary flow, sets.22
perfusion defects, and resulting myocardial dysfunction,
which may reside at the level of the cardiac myocyte. It is Early Presentation and Diagnosis
possible that ccTGA patients with preserved systemic RV
function may have more favorable microcirculation and Diagnoses in infants and children often occur during
coronary arterial reserve allowing adequate perfusion in times evaluation for a murmur, as VSDs are commonly associated
of increased metabolic demand. lesions. In cases of large VSDs or severe TV regurgitation,
some infants may present in CHF with diaphoresis, pallor,
Diagnosis tachypnea, inability to gain weight, hepatomegaly and a gallop
on examination. Auscultation of the ccTGA patient may also
Just as the natural history is largely dependent on defects reveal a loud, single second heart sound (S2) at the left second
associated with ccTGA, so is timing of presentation. 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.
Late Presentation and Diagnosis

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
Figure 2: Freedom from congestive heart failure (CHF) in group I over 18 years of age when diagnosed and 17 percent of the
(associated lesions, n = 125) and group II (no significant associated cohort was over 60 years of age at the time of diagnosis.
lesions, n = 50) as a function of increasing age. p = .0013. Courtesy: Common reasons for referral in such patients included
Reprinted from Journal of the American College of Cardiology,
abnormal electrocardiograms (ECGs) and cardiomegaly 627
number 36, volume 1, long-term outcome in congenitally corrected
transposition of the great arteries: a multi-institutional study, pp. 255- on chest radiographs as well as complete heart block and
61, copyright 2000 with permission from Elsevier murmurs.12,28
8 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 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
a large VSD and significant left to right shunt. A CXR with border is straightened because of the leftward-positioned ascending
impressive cardiomegaly and left atrial enlargement may also aorta. The thymic shadow is seen over the right mediastinum.
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. activation. As discussed previously, the conduction system
Overall, the degree of cardiomegaly and amount of visible in ccTGA consists of inverted AV bundles. Therefore, the
pulmonary vascularity is dependent on the presence and septum is activated from right to left, demonstrated by the
direction of shunting, as well as the severity of LVOTO.29 presence of septal Q waves in the right precordial leads (QR
pattern in leads V4R and V1) and absence of Q waves in the
Electrocardiogram left precordial leads (rS pattern in lead V6) (Figure 4). In fact,
undiagnosed ccTGA patients with such a pattern on ECG have
The electrocardiogram (ECG) in patients with ccTGA is been incorrectly diagnosed with remote inferior infarcts.25,30
most significant for a superior QRS axis and atypical septal 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
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
Figure 3A: Chest X-ray of a 6-year-old child with ccTGA and complete is usually anterior and to the left of the PA. Once the diagnosis
heart block. There is levocardia and abdominal situs solitus. The
upper-left cardiac border is straightened secondary to the leftward-
of ccTGA is made through demonstration of discordance
628 between atria and ventricles as well as ventricles and great
positioned ascending aorta. A permanent pacemaker is present with a
transvenous lead situated in the ventricle. arteries, several anatomic objectives should be defined in the
44

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 V5–V6), 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.
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.
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,
Figure 5: Transthoracic echocardiogram (apical four-chamber view) in and valve regurgitation prior to surgery (Figures 6A to D).
ccTGA shows the inferior hinge point of the left-sided atrioventricular
valve (TV) opening into a morphological right ventricle (RV). In Most interesting, however, is the adult patient who presents
comparison, the superior level of the right-sided atrioventricular valve with ischemic heart disease and is discovered on cardiac
(MV) hinge point is seen as well as valvar attachments to a papillary catheterization to have ccTGA after abnormal catheter passes
muscle within the morphologic left ventricle (LV) or inversion of coronary arteries on angiography.25
Cardiac Magnetic Resonance Imaging

TTE evaluation. Semilunar and AV valve morphology as well as
presence and severity of regurgitation warrant full description. Cardiac magnetic resonance imaging (cMRI) is now used in
Coronary origins should be identified and their proximal many types of CHD to further define anatomy and to quantify
courses described. The degree of LVOTO is important as well ventricular function and volume (Figure 7). For initial diagnosis,
as any additional defects present, as these will impact whether cMRI may be helpful in patients with restricted TTE windows, 629
8
A B
C D
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.
to define visceroatrial situs, and to delineate complex associated be a useful modality for evaluation of ccTGA patients not only
defects. In patients with interruption of the inferior vena cava, as an adjunct to TTE for initial diagnosis, but also for assessment
systemic return from the lower body can be difficult to delineate prior to surgical repair or for serial follow-up of the systemic RV.
by echocardiography, but is well-defined by cMRI. Because If the presence of a cMRI-incompatible pacemaker or prosthetic
echocardiographic evaluation of RV function in ccTGA patients valve precludes assessment by cMRI, computed tomography
is limited by geometric assumptions, cMRI has become the gold (CT) scans can depict anatomy, but cannot yield functional data
standard for RV function and volume assessment. TV morphology in the manner of a cMRI.33,34
can often be clarified through cMRI. Prior to performing
anatomic surgical repair in a ccTGA patient beyond infancy, Exercise and Stress Testing
cMRI can be useful in evaluation of the LV, with delineation
of mass, volume and ejection fraction. Furthermore, if there are Cardiopulmonary exercise testing by treadmill is an important
concerns about the degree of LV dysfunction, perfusion studies adjunct for ccTGA patient evaluation and management. In
with delayed enhancement MRI may be performed to directly those patients able to perform treadmill tests, exercise capacity
investigate scarring of the LV myocardium prior to committing is determined through minute ventilation, carbon dioxide
630 this ventricle to systemic workload. Cardiac MRI may therefore production and oxygen consumption. Impaired exercise
therapy for optimal CHF treatment in patients with systemic 44
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
Figure 7: Axial oblique, T2-weighted cardic magnetic resonance conduction delay from 137 to 37 ms and improved the patient’s
image (cMRI) of the cardiac four-chamber view in a ccTGA patient with CHF symptoms from New York Heart Association (NYHA)
levocardia. The right atrium (RA) empties into a right-sided, smooth-
class III to NYHA class II over a period of 6 months.44 A
walled, morphologic left ventricle (LV). A star (*) labels the entrance
of a left pulmonary vein into the left atrium (LA), which empties into a significant limitation in cardiac resynchronization therapy
trabeculated, left-sided, morphologic right ventricle (RV) includes difficulty in percutaneous lead delivery, although
this has successfully been accomplished even in ccTGA cases
of dextrocardia.45
capacity in ccTGA patients has been shown to correlate
with diastolic dysfunction and elevated RV filling pressures Surgical Management
as estimated by tissue Doppler imaging.35 Cardiopulmonary
exercise testing in combination with gadolinium-enhanced Indications for surgical ccTGA management in patients of all
MRI has been utilized to demonstrate RV myocardial fibrosis ages continues to evolve and most often is determined on a
hypothesized to be responsible for RV dysfunction.36 Systemic case-by-case basis. Beauchanese et al. described a cohort of
RV function can also be evaluated by dobutamine stress testing, 44 unrepaired adult ccTGA patients. Of these, the 30 patients
in which cMRI is performed at baseline and with dobutamine who required surgical intervention had significantly larger
infusion. Objectively defining the capacity of the systemic pre-operative cardiothoracic ratios on chest radiographs and had
RV to respond to stress may guide treatment on both initial moderate to severe or severe systemic AV valve regurgitation.
and follow-up evaluations.37,38 Sequential testing, performed The difference in ejection fraction of the systemic ventricle
either by cardiopulmonary exercise testing or by dobutamine between the operated and unoperated groups was not statistically
stress test, is useful to assess overall cardiopulmonary function significant.28 As discussed previously and depicted in Figure
and response to medical or surgical therapy. 2, nearly 2/3 of unrepaired ccTGA patients with associated
defects will have developed CHF by the age of 45 years.14
Management 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
Medical Management
of ccTGA for the majority of patients is eventual RV dysfunction
Medical mangement of CHF in the ccTGA patient with a and TV regurgitation. It is postulated that progression to failure
systemic RV has been extrapolated from CHF therapy for in a systemic RV is unavoidable because the RV and TV are
LV failure. This primarily includes β-adrenergic receptor not anatomically suited to withstand the systemic pressure for
blockade (β-blockers), diuretics and afterload-reducing which the LV and MV are intended. One mechanism thought
agents with an angiotensin-converting enzyme (ACE) to contribute to progressive RV decompensation is worsening
inhibitor.39 Digoxin may also be useful for its inotropic TR from annular dilation and/or displacement of the septal
and antiarrhythmic effects. Angiotensin receptor blockade leaflet of the TV as the RV remodels to accommodate systemic
with losartan was evaluated in a multicenter, randomized, afterload. Depending on the age of presentation and extent of
placebo-controlled clinical trial by Dore and colleagues, associated lesions, surgical repair may include one or more
but was found to have no improvement on exercise capacity of several approaches, which can be divided into the ‘classic’
and no reduction in neurohormonal levels in patients with or ‘physiologic’ repair or a more anatomic repair, typically
systemic right ventricles.40 In general, evidence-based referred to as the ‘double switch’ operation (Table 1). 631
8 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 + Univentricular repair
• Straddling AV valves • Systemic to pulmonary artery shunt
• Hypoplastic RV • Bidirectional Glenn
• Unbalanced AVSD • 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
Tricuspid regurgitation 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 demonstrated the greatest survival whereas patients requiring

TV replacement at their initial operation exhibited the shortest
In patients with a VSD and no LVOTO, ‘classic’ or ‘physiologic’ survival. Risk factors for death in the VSD group with or without
repair may include VSD closure only. Specific techniques must be PS relief included preoperative RV end diastolic pressure
employed in ccTGA patients to avoid damage to the conduction greater than 17 mm Hg and complete heart block. Survival rates
system during VSD closure. Because the AV conduction at 1-, 5-, 10, and 15-years for patients who underwent classic
bundle descends along the anterior rim of the VSD and travels repair were 84 percent, 75 percent, 68 percent and 61 percent,
along the septal side of the right-sided morphologic LV, it is respectively, although 17 of the 113 patients in this subgroup
recommended to suture the VSD patch along the morphological underwent Fontan and achieved 100 percent survival in short-
right ventricular aspect of the septum. The surgical approach term follow-up (Figure 8). In patients for whom biventricular
should be via a right atriotomy and right-sided mitral valve. repair was contraindicated, such as patients with straddling
Ideally the VSD patch will lie partially on the morphologic AV valve tissue, inaccessible or multiple VSDs or unbalanced
LV septal aspect (to avoid damage to the TV superiorly) and complete AV canals, the univentricular pathway with Fontan
partially on the morphologic RV aspect of the septum inferiorly was chosen.50 More recently Bogers et al. confirmed that a
(to avoid damage to the main conduction bundle).47 Physiologic classic repair in which the RV remains the systemic ventricle
repair may also include relief of PS, which sometimes requires results in significant incidence of reoperation and overall
placement of a conduit between the LV and PA. There is, suboptimal survival.51
however, the possibility that decreasing LV pressure by VSD
closure and/or PS relief may allow the ventricular septum to Anatomic Repair ‘Double Switch’ Operation
realign towards the LV, resulting in displacement of the TV
septal leaflet and increasing TR.48,49 In a cohort of 123 patients The ‘anatomic’ or ‘Double Switch’ (DS) operation was
with ccTGA presenting for classic biventricular repair over 33 developed in response to unsatisfactory outcomes after the
632 years, the surgical group undergoing repair of VSD plus PS classic repair. Components of the DS include arterial switch
44

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
with coronary artery transfer, VSD closure if necessary, standard for age of PAB placement in this setting, it is
and interatrial baffle by Senning or Mustard procedure. apparent that candidacy for LV training with PAB beyond
The Senning and Mustard operations, referred to as an ‘atrial adolescence is questionable. LV dysfunction and failure can
switch,’ serve to direct systemic venous flow to the TV and RV occur immediately or within days or weeks following PAB
and pulmonary venous flow to the MV and LV. By restoring placement if the band is too restrictive. Reports of late LV
the LV and MV to the systemic circulation, the DS operation dysfunction in ccTGA patients who underwent DS operation
offers the opportunity to improve long-term outcome. Before even after successful LV retraining by PAB placement are
committing the LV to the systemic workload, however, various also of concern.56
criteria must be met that afford the LV the greatest likelihood The combination of progressive systemic RV dysfunction
of success. This includes preoperative LV pressure that is 80 and TR has lead to the consideration of a variation in DS
to 100 percent systemic and normal LV wall thickness and operation for patients with LVOTO. Rather than combining
function for a systemic LV.52,53 In the absence of LVOTO, the atrial and arterial switches, the Senning or Mustard atrial
pulmonary hypertension or an unrestrictive VSD, the switch procedure is combined with a Rastelli operation, in
morphologic LV requires training prior to committing it to the which the LV outflow is baffled from the LV through a large
systemic ventricle in the DS. LV training has been performed VSD to the aorta and a conduit is placed from the RV to the
by placement of a pulmonary artery band (PAB) which is PA. This operation is technically challenging and subject to the
then serially tightened until the pressure load for the naïve LV need for conduit replacements as well as possible reoperation
nears systemic pressure. Median banding time for the purpose for interatrial or interventricular baffle obstructions. Specific
of LV retraining has been reported on average to be 13 to to the Senning/Rastelli operation, risk factors associated with
14 months53-55 although can be considerably less in younger death include longer cardiopulmonary bypass and aortic
patients. Morphologic LV reconditioning with PAB in patients cross-clamp times and there is an increased risk of complete
with systemic RV after atrial switch for dextrotransposition heart block and ventricular dysfunction if the existing VSD
of the great arteries (dTGA) has been described by Poirier requires enlargement.57,58 Nevertheless, intermediate results
et al.53 PAB was performed in this population prior to in a small group of ccTGA patients with VSD and LVOTO
anatomic correction or as bridge to transplant, and the success who underwent this form of anatomic repair suggest good
rate of completing adequate LV retraining was significantly biventricular function and mild or no AV valve insufficiency
less in patients beyond 12 years of age (20 percent of patients up to 17 years postoperatively.59 Aortic root translocation
over 12 years completed the protocol, whereas 62 percent in combination with the atrial switch has also been reported
of patients less than 12 years were able to complete the for anatomic repair in patients with LVOTO.60 After atrial
PAB protocol, p = 0.02).53 While there is no well-defined rerouting, the aortic root is harvested, obstruction in the LVOT 633
8 is relieved, LeCompte maneuver of the pulmonary arteries is (median age 1.1 years, range 0–12 years). Eleven of the 14
performed, and the aortic root is reanastomosed to the original patients had an increase in LV pressure of ≥ 2/3 systolic RV
location of the pulmonary artery. A conduit or pericardial pressure with PAB and demonstrated significantly decreased
patch is then used to reconstruct the RVOT. This variation TR as the LV geometry became more spherical and the
of anatomic repair, commonly referred to as the Nikaidoh interventricular septum shifted toward the RV. Patients who
procedure, may be suitable for patients with restrictive VSD underwent classic ccTGA repair with procedures that reduced
not amenable to the Rastelli operation.61 LV pressure below that of the RV, such as VSD closure with
An additional variation in the DS for patients with severe LV to PA conduit placement, demonstrated significantly
RV dysfunction, hypoplasia of the RV or abnormal right increased TR postoperatively.48
atrial anatomy includes a modified atrial switch termed the
‘hemi-Mustard/bidirectional Glenn,’ which is performed Outcomes: Physiologic vs Anatomic Repair
in combination with either an arterial switch or a Rastelli
procedure. In this operation only the IVC return is baffled to the Alghamdi and associates66 published a meta-analysis of 11
TV. The SVC is reimplanted into the pulmonary artery creating non-randomized studies totalling 124 ccTGA patients and
a cavo-pulmonary Glenn shunt and the SVC portion of the compared in-hospital mortality between physiologic and
RA is oversewn. Midterm outcomes from the hemi-Mustard/ anatomic repair. Patient age at time of repair ranged from 3
Glenn as reported by Malhotra et al.62 are favorable and hold months to 55 years with 41 percent of patients undergoing
several advantages over the traditional Senning or Mustard definitive repair prior to 1995. Thirty patients underwent
atrial switch. The authors report a prolonged lifespan of the RV physiologic repair, 69 underwent Rastelli-type anatomic
to PA conduit due to volume-unloading of the RV, increased repair, and 25 received anatomic repair with the standard
intra-atrial space for pulmonary venous return (and therefore double switch operation. The Rastelli-type anatomic repair
less risk of pulmonary venous obstruction) and less risk for had significantly lower hospital mortality, while operation
arrhythmia with the reduction in intra-atrial suture lines.62 It before 1995 demonstrated an increased mortality risk.66 A
remains to be seen if the hemi-Mustard/bidirectional Glenn large risk analysis performed by Shin’oka et al.58 combined
variant of the DS will prove favorable in long-term studies. ccTGA patients with a group of systemic RV patients with
discordant AV connections, (n = 189) and compared long-
Tricuspid Regurgitation term results of definitive surgical repair with respect to
hospitalization, late mortality and reoperation. Risk factors
Although it is reasonable to medically manage mild TR for hospital death included preoperative moderate TR and
with anticongestive therapy and afterload reduction, surgical intraoperative cardiopulmonary bypass time of over 240
intervention is indicated in cases of moderate or moderate to minutes. The presence of TR was also a risk factor for late
severe TR. TV repair for ccTGA patients is rarely successful, mortality. Risk for reoperation was highest in patients with
and most patients require valve replacement. This can prove preoperative cardiomegaly (cardiothoracic ratio of > 0.6)
problematic in young children because of the relatively large at least a moderate degree of TR, operative need for VSD
prosthesis needed to allow for growth. Palliation with PAB enlargement, and weight less than 10 kg. Although survival of
may therefore be reasonable in infants and young children, patients undergoing classic repair without TR was satisfactory
since it has been shown that severe TV insufficiency in comparison to anatomic repair, patients with ccTGA and
leading to RV dysfunction has the greatest impact on long- discordant AV connections with TR demonstrated improved
term survival.13,48 Several groups have concluded that TV survival with anatomic repair.58 More recently Lim and
replacement should be considered at the earliest sign of colleagues67 report results from a multicenter study including
RV dysfunction and recommend operation before systemic 167 patients who underwent biventricular ccTGA repair. Of
ventricular ejection fraction (EF) decreases below 40 to the patients studied, 123 underwent physiologic repair (ASD
44 percent, as low preoperative systemic EF has been shown or VSD closure, TV surgery and/or pulmonary ventricle to
to correlate with poor outcome.63,64 PA conduit placement), and 44 underwent anatomic repair
As an additional alternative, Metton and associates (atrial + arterial switch or atrial + interventricular rerouting
advocate the use of PAB in asymptomatic ccTGA neonates procedure) over the years 1983 to 2009. Long-term results
and infants with intact ventricular septum to maintain rather of biventricular repair revealed an estimated survival of
than train the LV.65 In Metton’s group the TV was not repaired 83.3 percent ± 0.05 percent at 25 years. The incidence of
at PAB placement, as it was thought that PAB placement complete heart block was lower for the anatomic repair
(with subsequent elevation in LV pressures and alteration of group and there was a late mortality of 5.9 percent after
the septal geometry) may improve TR that was present prior physiologic repair in comparison to 0 percent after anatomic
to banding.54 This mechanism is described by Kral Kollars repair. Freedom from systemic AV valve and ventricular
et al.48 in 14 patients who underwent PAB for LV retraining dysfunction was significantly higher after anatomic repair.
634
The authors concluded that anatomic repair is superior to Conclusion 44
physiologic repair in patients with two adequately sized
ventricles. However high risk groups such as those patients The debate continues over efficacy and long-term follow-up in

with RV dysfunction or the need for LV training warrant physiologic vs anatomic repair for ccTGA. Recent outcomes
careful selection prior to undergoing anatomic repair.67 data is leaning in favor of anatomic correction, in which
Taken together, these outcomes favor anatomic over classic/ systemic function is restored to the LV. However, the age and
physiologic repair with careful preoperative assessment of eligibility of pulmonary artery banding for LV retraining is
TR for the purpose of risk stratification. yet to be standardized as is the optimal timing for anatomic
correction. In the asymptomatic infant, pulmonary banding for
Follow-up and Special Considerations maintenance of LV function bears further evaluation as well.
Thus the complex combination of factors in the management
Patients with ccTGA require lifelong outpatient follow-up and of ccTGA patients requires individualized assessment of
should be seen by a pediatric or adult congenital cardiologist each patient with incorporation of multiple modalities for
every 1 to 2 years. Evaluation should include an ECG at each assessment and follow-up.
visit to monitor for AV block with periodic Holter monitor
evaluation as well. Cardiopulmonary exercise testing is “As to diseases, make a habit of two things—to help, or at least,
performed to assess overall function as well as response to to do no harm.”
medical or surgical therapy. RV function in the unrepaired —Hippocrates
or physiologically repaired ccTGA patient must be closely
monitored by echocardiography even in asymptomatic References
patients.46 Cardiac MRI with cine data used to quantify RV
volume, mass and ejection fraction is the best modality to 1. Graham TP, Markham LW. Congenitally corrected
serially quantify RV function and should be performed every transposition of the great arteries. In: Gatzoulis MD, GD Webb
3 to 5 years. (Eds). Diagnosis and Management of Adult Congenital Heart
Disease. Edinburgh: Churchill Livingstone; 2010. pp. 371-77.
2. Piacentini G, Digilio MC, Capolino R, et al. Familial
Pregnancy
recurrence of heart defects in subjects with congenitally
Pregnancy in the ccTGA patient is generally well tolerated corrected transposition of the great arteries. Am J Med Genet
except in the presence of maternal NYHA class III-IV A. 2005.137:176-80.
symptoms, moderate or severe AV valve regurgitation, or 3. Van der Bom T, Zomer AC, Zwinderman AH, et al. The
changing epidemiology of congenital heart disease. Nat Rev
poor ventricular function (EF < 40 percent). Evaluation of
Cardiol. [Review]. 2011;8:50-60.
pregnancy outcome in 22 women with ccTGA revealed 50
4. Hornung TS, Calder L. Congenitally corrected transposition of
live births in 60 total pregnancies (83 percent). However,
the great arteries. Heart. [Review]. 2010;96:1154-61.
the rate of miscarriage in the ccTGA mothers was higher
5. Van Praagh R, Papagiannis J, Grunenfelder J, et al.
than the general population.68 A recent cohort of patients by Pathologic anatomy of corrected transposition of the great
Gelson and colleagues69 revealed high maternal and neonatal arteries: medical and surgical implications. Am Heart J.
morbidity in women with systemic RVs with a significant 1998;135:772-85.
number of babies born small for gestational age. Although 6. Ismat FA, Baldwin HS, Karl TR, et al. Coronary anatomy in
cyanosis in women with ccTGA has been shown to be a risk congenitally corrected transposition of the great arteries. Int J
factor for miscarriage, the women in the cohort of Gelson et Cardiol. 2002;86:207-16.
al. were normally saturated.69,70 The risk of congenital heart 7. Bottega NA, Kapa S, Edwards WD, et al. The cardiac
defects in the offspring of mothers with ccTGA has not been veins in congenitally corrected transposition of the great
defined. arteries: delivery options for cardiac devices. Heart Rhythm.
2009;6:1450-56.
Heart Transplant 8. Daliento L, Corrado D, Buja G, et al. Rhythm and conduction
disturbances in isolated, congenitally corrected transposition of
Heart transplantation may be considered in patients who the great arteries. Am J Cardiol. [Research Support, Non-U.S.
have end-stage RV failure, significant LV dysfunction Gov’t]. 1986;58:314-18.
and pulmonary valve abnormalities precluding successful 9. Huhta JC, Maloney JD, Ritter DG, et al. Complete
DS operation or uncontrollable arrhythmia.52 For patients atrioventricular block in patients with atrioventricular
undergoing surgical intervention, poor preoperative EF of the discordance. Circulation. 1983;67:1374-77.
systemic ventricle has been shown to predict the eventual need 10. Anderson RH, Becker AE, Arnold R, et al. The conducting
for transplantation.28 tissues in congenitally corrected transposition. Circulation.
1974;50:911-23. 635
8 11. Hoffman JIE. Congenitally Corrected Transposition of 25. Jennings HS, 3rd, Primm RK, Parrish MD, et al. Coronary
the Great Arteries. In: Hoffman JIE (Ed). The Natural and arterial revascularization in an adult with congenitally corrected
Unnatural History of Congenital Heart Disease. Oxford: transposition. Am Heart J. [Case Reports]. 1984;108:598-600.
Wiley-Blackwell; 2009. pp. 206-17. 26. Orchard EA, Ormerod O, Myerson S, et al. Congenitally corrected
12. Presbitero P, Somerville J, Rabajoli F, et al. Corrected transpo transposition of the great arteries presenting in a nonagenarian.
sition of the great arteries without associated defects in adult Circulation. [Case Reports]. 2010;122:e441-44.
patients: clinical profile and follow-up. Br Heart J. [Multicent 27. Scardi S, Knoll P, Pandullo C. Corrected transposition of
er Study]. 1995;74:57-59. the great vessels and situs inversus viscerum in a 65-year-
13. Prieto LR, Hordof AJ, Secic M, et al. Progressive tricus old oligosymptomatic woman. Circulation. [Case Reports].
pid valve disease in patients with congenitally corrected 1999;100:777.
transposition of the great arteries. Circulation. 1998;98: 28. Beauchesne LM, Warnes CA, Connolly HM, et al. Outcome
997-1005. of the unoperated adult who presents with congenitally
14. Graham TP, Jr Bernard YD, Mellen BG, et al. Long-term out corrected transposition of the great arteries. J Am Coll Cardiol.
come in congenitally corrected transposition of the great ar 2002;40:285-90.
teries: a multi-institutional study. J Am Coll Cardiol. [Com 29. Carey LS, Ruttenberg HD. Roentgenographic Features of
parative Study Multicenter Study Research Support, Non-U.S. Congenital Corrected Transposition of the Great Vessels:
Gov’t]. 2000;36:255-61. A Comparative Study of 33 Cases with a Roentgenographic
15. Hornung TS, Bernard EJ, Celermajer DS, et al. Right Classifiction Based on the Associated Malformations and
ventricular dysfunction in congenitally corrected transposition Hemodynamic States. Am J Roentgenol Radium Ther Nucl
of the great arteries. Am J Cardiol. 1999;84:1116-9, A10. Med. 1964;92:623-51.
16. Hornung TS, Bernard EJ, Jaeggi ET, et al. Myocardial perfusion 30. Warnes CA. Transposition of the great arteries. Circulation.
defects and associated systemic ventricular dysfunction in [Review]. 2006;114:2699-709.
congenitally corrected transposition of the great arteries. Heart. 31. Oechslin E. Physiologically “Corrected” Transposition of the
[Case Reports]. 1998;80:322-26. Great Arteries. In: Lai WW, Mertens LL, Cohen MS, Geva T
17. Fratz S, Hauser M, Bengel FM, et al. Myocardial scars (Eds). Echocardiography in Pediatric and Congenital Heart
determined by delayed-enhancement magnetic resonance Disease: From Fetus to Adult. Oxford: Wiley-Blackwell; 2009.
imaging and positron emission tomography are not common in pp. 439-55.
right ventricles with systemic function in long-term follow-up. 32. Caso P, Ascione L, Lange A, et al. Diagnostic value of
Heart. 2006;92:1673-77. transesophageal echocardiography in the assessment of
18. McEwing RL, Chaoui R. Congenitally corrected transposition congenitally corrected transposition of the great arteries in
of the great arteries: clues for prenatal diagnosis. Ultrasound adult patients. Am Heart J. [Clinical Trial Comparative Study
Obstet Gynecol. [Case Reports]. 2004;23:68-72. Multicenter Study]. 1998;135:43-50.
19. Paladini D, Volpe P, Marasini M, et al. Diagnosis, characteriz 33. Schmidt M, Theissen P, Deutsch HJ, et al. Congenitally corrected
ation and outcome of congenitally corrected transposition of transposition of the great arteries (L-TGA) with situs inversus
the great arteries in the fetus: a multicenter series of 30 cases. totalis in adulthood: findings with magnetic resonance imaging.
Ultrasound Obstet Gynecol. [Multicenter Study]. 2006;27:281- Magn Reson Imaging. [Case Reports]. 2000;18:417-22.
85. 34. Teo LL, Hia CP. Advanced cardiovascular imaging in
20. Shima Y, Nakajima M, Kumasaka S, et al. Prenatal diagnosis congenital heart disease. Int J Clin Pract. 2011;65:17-29.
of isolated congenitally corrected transposition of the great 35. Tay EL, Frogoudaki A, Inuzuka R, et al. Exercise intolerance
arteries. Arch Gynecol Obstet. [Case Reports]. 2009;279:557- in patients with congenitally corrected transposition of the
59. great arteries relates to right ventricular filling pressures. Int J
21. Wan AW, Jevremovic A, Selamet Tierney ES, et al. Comparison Cardiol. [Research Support, Non-U.S. Gov’t]. 2011;147:219-
of impact of prenatal versus postnatal diagnosis of congenitally 23.
corrected transposition of the great arteries. Am J Cardiol. 36. Giardini A, Lovato L, Donti A, et al. Relation between right
[Comparative StudyMulticenter Study]. 2009;104:1276-79. ventricular structural alternans and markers of adverse clinical
22. Zhang Y, Cai A, Sun W, et al. Prenatal diagnosis of fetal outcome in adults with systemic right ventricle and either
congenitally corrected transposition of the great arteries. congenital complete (after Senning operation) or congenitally
Prenat Diagn. 2011;31:529-35. corrected transposition of the great arteries. Am J Cardiol.
23. Friedberg DZ, Nadas AS. Clinical profile of patients with 2006;98:1277-82.
congenital corrected transposition of the great arteries. A study 37. Dodge-Khatami A, Tulevski, II, Bennink GB, et al. Compar
of 60 cases. N Engl J Med. 1970;282:1053-59. able systemic ventricular function in healthy adults and
24. Chang HY, Yin WH, Hsiung MC, et al. A heart reversed patients with unoperated congenitally corrected transposition
triply: situs inversus totalis with congenitally corrected using MRI dobutamine stress testing. Ann Thorac Surg.
transposition of the great arteries in a middle-aged woman. [Comparative Study Research Support, Non-U.S. Gov’t].
Echocardiography. [Case Reports]. 2009;26:617-21. 2002;73:1759-64.
636
38. Fratz S, Hager A, Busch R, et al. Patients after atrial switch 50. Hraska V, Duncan BW, Mayer JE, et al. Long-term outcome of 44
operation for transposition of the great arteries can not increase surgically treated patients with corrected transposition of the
stroke volume under dobutamine stress as opposed to patients great arteries. J Thorac Cardiovasc Surg. [Comparative Study].

with congenitally corrected transposition. Circ J. [Comparative 2005;129:182-91.
Study]. 2008;72:1130-35. 51. Bogers AJ, Head SJ, de Jong PL, et al. Long-term follow-up
39. Winter MM, Bouma BJ, Groenink M, et al. Latest insights after surgery in congenitally corrected transposition of the
in therapeutic options for systemic right ventricular failure: a great arteries with a right ventricle in the systemic circulation.
comparison with left ventricular failure. Heart. [Comparative J Cardiothorac Surg. 2010;5:74.
Study Research Support, Non-U.S. Gov’t Review]. 52. Duncan BW, Mee RB. Management of the failing systemic
2009;95:960-63. right ventricle. Semin Thorac Cardiovasc Surg. 2005;17:
40. Dore A, Houde C, Chan KL, et al. Angiotensin receptor 160-69.
blockade and exercise capacity in adults with systemic right 53. Poirier NC, Yu JH, Brizard CP, et al. Long-term results of left
ventricles: a multicenter, randomized, placebocontrolled ventricular reconditioning and anatomic correction for systemic
clinical trial. Circulation. [Multicenter Study Randomized right ventricular dysfunction after atrial switch procedures. J
Controlled Trial Research Support, Non-U.S. Gov’t]. Thorac Cardiovasc Surg. [Clinical Trial Comparative Study
2005;112:2411-416. Controlled Clinical Trial Multicenter Study]. 2004;127:
41. Diller GP, Okonko D, Uebing A, et al. Cardiac resynchronization 975-81.
therapy for adult congenital heart disease patients with a 54. Ly M, Belli E, Leobon B, Kortas C, et al. Results of the double
systemic right ventricle: analysis of feasibility and review switch operation for congenitally corrected transposition of the
of early experience. Europace. [Research Support, Non-U.S. great arteries. Eur J Cardiothorac Surg. [Evaluation Studies].
Gov’t]. 2006;8:267-72. 2009;35:879-83; discussion 83-4.
42. Janousek J, Tomek V, Chaloupecky VA, et al. Cardiac 55. Winlaw DS, McGuirk SP, Balmer C, et al. Intention-to-treat
resynchronization therapy: a novel adjunct to the treatment analysis of pulmonary artery banding in conditions with a
and prevention of systemic right ventricular failure. J Am morphological right ventricle in the systemic circulation with a
Coll Cardiol. [Evaluation Studies Research Support, Non-U.S. view to anatomic biventricular repair. Circulation. [Evaluation
Gov’t]. 2004;44:1927-31. Studies]. 2005;111:405-11.
43. Kordybach M, Kowalski M, Hoffman P. Heart failure in a 56. Quinn DW, McGuirk SP, Metha C, et al. The morphologic left
patient with corrected transposition of the great arteries. When ventricle that requires training by means of pulmonary artery
is biventricular pacing indicated? Acta Cardiol. [Case Reports]. banding before the double-switch procedure for congenitally
2009;64:673-76. corrected transposition of the great arteries is at risk of late
44. Takemoto M, Nakashima A, Muneuchi J, et al. Para-Hisian dysfunction. J Thorac Cardiovasc Surg. [Comparative Study].
pacing for a pediatric patient with a congenitally corrected 2008;135:1137-44, 44 e1-2.
transposition of the great arteries (SLL). Pacing Clin 57. Gaies MG, Goldberg CS, Ohye RG, et al. Early and
Electrophysiol. [Case Reports]. 2010;33:e4-7. intermediate outcome after anatomic repair of congenitally
45. Malecka B, Bednarek J, Tomkiewicz-Pajak L, et al. Resyn corrected transposition of the great arteries. Ann Thorac Surg.
chronization therapy transvenous approach in dextrocardia and [Comparative Study]. 2009;88:1952-60.
congenitally corrected transposition of great arteries. Cardiol J. 58. Shin’oka T, Kurosawa H, Imai Y, et al. Outcomes of definitive
[Case Reports]. 2010;17:503-08. surgical repair for congenitally corrected transposition of the
46. Bos JM, Hagler DJ, Silvilairat S, et al. Right ventricular great arteries or double outlet right ventricle with discordant
function in asymptomatic individuals with a systemic right atrioventricular connections: risk analyses in 189 patients. J
ventricle. J Am Soc Echocardiogr. [Controlled Clinical Trial]. Thorac Cardiovasc Surg. 2007;133:1318-28, 28 e1-4.
2006;19:1033-037. 59. Horer J, Haas F, Cleuziou J, et al. Intermediate-term results
47. Jonas RA. Congenitally corrected transposition of the of the Senning or Mustard procedures combined with the
great arteries. In: Jonas RA (Ed). Comprehensive Surgical Rastelli operation for patients with discordant atrioventricular
Management of Congenital Heart Disease London: Hodder connections associated with discordant ventriculoarterial
Arnold; 2004. pp. 483-96. connections or double outlet right ventricle. Cardiol Young.
48. Kral Kollars CA, Gelehrter S, Bove EL, et al. Effects of 2007;17:158-65.
morphologic left ventricular pressure on right ventricular 60. Kwak JG, Lee CH, Lee C, Park CS. Aortic root translocation
geometry and tricuspid valve regurgitation in patients with with atrial switch: Another surgical option for congenitally
congenitally corrected transposition of the great arteries. Am J corrected transposition of the great arteries with isolated
Cardiol. 2010;105:735-39. pulmonary stenosis. J Thorac Cardiovasc Surg. 2010;139:
49. Said SM, Burkhardt HM, Schaff HV, et al. Congenitally 1652-53.
Corrected Transposition of the Great Arteries: Surgical Options 61. Morell VO, Jacobs JP, Quintessenza JA. The role of aortic
for the Failing Ventricle and/or Severe Tricuspid Regurgitation. translocation in the management of complex transposition of
World Journal for Peditratic and Congenital Heart Surgery. the great arteries. Semin Thorac Cardiovasc Surg Pediatr Card
2011;2:64-79. Surg Annu. 2004;7:80-4. 637
8 62. Malhotra SP, Reddy VM, Qiu M, et al. The hemi-Mustard/ 66. Alghamdi AA, McCrindle BW, van Arsdell GS. Physiologic
bidirectional Glenn atrial switch procedure in the double- versus anatomic repair of congenitally corrected transposition of
switch operation for congenitally corrected transposition the great arteries: meta-analysis of individual patient data. Ann
of the great arteries: rationale and midterm results. J Thorac Thorac Surg. [Comparative Study Meta-Analysis]. 2006;81:
Cardiovasc Surg. 2011;141:162-70. 1529-35.
63. Mongeon FP, Connolly HM, Dearani JA, et al. Congenitally 67. Lim HG, Lee JR, Kim YJ, et al. Outcomes of biventricular repair
corrected transposition of the great arteries ventricular function for congenitally corrected transposition of the great arteries. Ann
at the time of systemic atrioventricular valve replacement Thorac Surg. [Comparative Study]. 2010;89: 159-67.
predicts long-term ventricular function. J Am Coll Cardiol. 68. Connolly HM, Grogan M, Warnes CA. Pregnancy among
[Comparative Study Research Support, Non-U.S. Gov’t]. women with congenitally corrected transposition of great
2011;57:2008-17. arteries. J Am Coll Cardiol. 1999;33:1692-95.
64. Van Son JA, Danielson GK, Huhta JC, et al. Late results of 69. Gelson E, Curry R, Gatzoulis MA, et al. Pregnancy in women
systemic atrioventricular valve replacement in corrected with a systemic right ventricle after surgically and congenitally
transposition. J Thorac Cardiovasc Surg. 1995;109:642-52; corrected transposition of the great arteries. Eur J Obstet
discussion 52-3. Gynecol Reprod Biol. 2011;155:146-49.
65. Metton O, Gaudin R, Ou P, et al. Early prophylactic pulmonary 70. Therrien J, Barnes I, Somerville J. Outcome of pregnancy in
artery banding in isolated congenitally corrected transposition patients with congenitally corrected transposition of the great
of the great arteries. Eur J Cardiothorac Surg. [Evaluation arteries. Am J Cardiol. 1999;84:820-24.
Studies]. 2010;38:728-34.
638
C hapter
45 Common Atrium
Kiran VS, Sunita Maheshwari
common atrium entering ipsilateral sides of the common atrium separate from
the inferior vena cava (IVC) attachment. Anomalies of the
Virtual absence of atrial septum is a rare congenital anomaly, pulmonary venous return occur in nearly all cases of right
which may occur in isolation or as a part of complex isomerism. If the veins return to the atrium, it is usually to
heterotaxy syndromes. It occurs in less than 1 percent of a common collector in the roof of the common atrium. The
all congenital heart diseases (CHDs).1 In 1907, Young and coronary sinus is usually absent in such situations. When there
Robinson described this entity as a part of their series on the is a persistent left superior vena cava (SVC), it drains directly
malformations of human heart.2 into the left upper corner of the common atrium. Also, the
coronary venous blood drains directly into the left side of the
IS IT SAME AS SINGLE ATRIUM? common atrial cavity. This partly explains the mild desaturation
that is commonly encountered in such instances.8,9
The terms common atrium and single atrium have been used
interchangeably in the literature. Some authors suggest that Left Isomerism
single atrium is to be applied to the defects with complete
absence of atrial septum, absence of interventricular Common atrium occurs in almost one-third of left isomerisms.
communication and absence of malformations of the This complex is usually associated with polysplenia, interrupted
atrioventricular (AV) valves, while common atrium is to be IVC (which sometimes pose serious problems in determining
applied to the defects with complete absence of the atrial atrial situs) and anomalous pulmonary venous connection to
septum with malformations of the AV valves.7 both sides of the common atrium. 8,9
These semantic confusions3-5 were sorted out and now
both the terms refer to the complete absence of the interatrial SYNDROMES ASSOCIATED WITH COMMON ATRIUM
septum.6
In this chapter, we will focus on both common atrium Ellis van Creveld syndrome: A strong association between
and single atrium, avoiding detailed overlap with AV single atrium and postaxial hexadactyly (Figures 1A and B)
malformations and heterotaxy syndromes, which are dealt has been reported10 and indicates a diagnosis of Ellis van
separately in Chapter 20 and 10 respectively. Creveld syndrome.
Ivemark syndrome consists of intracardiac anomalies,
COMMON ATRIUM AND ISOMERISMS abnormal lobation of the lungs and abdominal heterotaxy.11
In an interesting observation, Spencer and colleagues
The complex heterotaxy syndromes are usually associated reported common atrium in two pairs of conjoint twins.12
with common atrium.
CLINICAL MANIFESTATIONS
Right Isomerism
Here, we shall concentrate on the single atrium without
There is an almost 50 percent incidence of common atrium associated lesions. In common atrium with complex lesions,
in right isomerisms. This complex is usually associated with the symptoms and findings of coexisting complex lesions
asplenia, midline liver with both right and left hepatic veins supersede that of the atrial component.
8
A B
Figures 1A and B: Ellis-Van Creveld syndrome: A. Postaxial hexadactyly of the hands with hypoplastic nails; B. Peg teeth and malocclusion
When the entire atrial septum is virtually absent, there is murmur. This will add to the overall volume load on heart.
a mandatory admixture of blood received from systemic and
pulmonary circulations into the atrial cavity. This explains the INVESTIGATIONS
mild desaturaion that can be noticed. However, in the setting
of right isomerism, the degree of desaturation may be higher After a meticulous clinical examination, one should proceed
for reasons explained earlier. to the basic battery of investigations, which would add to the
Symptoms of high pulmonary blood flow predominate diagnosis and management decisions.
in infancy. As in any non-restrictive atrial septal defect, the
compliance of the corresponding ventricles will determine the Electrocardiography
direction and magnitude of the flow out of the single atrial
cavity. The presenting features include dyspnea on exertion, The 12-lead electrocardiography (ECG) shows same pattern
fast breathing, failure to thrive, suck-rest-suck cycles and as partial AV canal defect or a primum ASD. Rhythm is
excessive sweating. As a general rule, the symptoms occur usually sinus, but in the setting of an abnormal situs, one may
earlier and progress faster than isolated atrial septal defects come across various degrees of conduction blocks including
(ASD) or primum defects. When the pulmonary vascular complete heart block. The P waves in lead II, III and AVF can
resistance is normal, precordium appears active. Apical be both tall and broad. Prolongation of PR interval is noted
impulse would be prominent and of right ventricular type. in upto two-thirds. This is a manifestation of increased intra-
Second heart sound would reveal a wide split and no change atrial conduction time.13 The mean QRS axis may show left
with respiratory cycle. The extent of pulmonary hypertension axis or superior axis, ranging from minus 30 degrees to minus
would determine the loudness of the pulmonary component 120 degrees. The QRS can be notched in the inferior leads
of second heart sound. Precordial auscultation would reveal and a typical rsR’ pattern is observed in V1. QRS pattern may
an ejection systolic murmur with its typical crescendo- suggest volume overload of right ventricle. However, with
decrescendo quality at the left upper sternal border. The same advancing age, it may also show pressure overload pattern due
murmur can be appreciated at the back and sometimes in the to increasing pulmonary vascular resistance. In the presence
axillae. One can also appreciate a mid-diastolic murmur in of normal pulmonary vascular resistance and right ventricular
left lower sternal border. This murmur has a soft-quality and function, even a significant MR is unlikely to show a left
is often described as ‘absence of silence’. The mid-diastolic ventricular volume overload pattern in the ECG (Figure 2).
murmur is due to the increased blood flow across the tricuspid
valve when the pulmonary vascular resistance and the right Chest Radiograph
ventricular functions are normal. Not infrequently, common
atrium is associated with an abnormal mitral valve. Clefts A well taken chest radiograph in posteroanterior projection is
in the mitral valve leaflets are common in such settings. The an invaluable tool in management decisions. Cardiomegaly is
640 resultant mitral regurgitation (MR) can produce a pansystolic 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 Figure 4: Echocardiography in four-chamber view showing complete
with dilatation of right atrium and right ventricle 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;
RV = Right ventricle.
are usual, even in the presence of significant MR. Pulmonary abnormal patterns of pulmonary and systemic veins. Apical
vascularity pattern may help in deciding the operability. four chamber is diagnostic (Figure 4).
Plethoric lung fields suggest clear operability, whereas If the IVC is uninterrupted, a long, redundant eustachian
oligemic lung fields are against it. However, one should not valve tissue might be seen wandering in the common atrial
confuse pulmonary venous congestion with plethoric lung cavity. It should not be confused with residual septal tissue.
fields (Figure 3). Apical four-chamber view is useful in assessing the
ventricular cavities and the av valves. When one of the
Echocardiography ventricles looks unusually small, measuring the annuli of AV
valves and comparing them against the Z-score charts would
Subcostal imaging is best suited to make an accurate diagnosis. be useful in deciding feasibility of two-pump repair. The view
Both coronal and sagital planes help in delineating the absence also provides good 2D assessment of AV valve morphology. 641
of interatrial septum and also in establishing the normal and Color-Doppler assessment of the AV valves will help in
8
quantifying the regurgitation and the direction of jet, details pulmonary vascular pressures, the right ventricular compliance
of which are very useful in planning a surgical strategy. Color- is much superior to that of left ventricle. In consequence, the
Doppler of the pulmonary veins with scales set to optimal pulmonary blood flow (Qp) is higher than systemic (Qs). The
Nyquist limit will help in quantifying the venous return, ratio would reduce in the same proportion as pulmonary to
which is an indirect marker of operability. systemic vascular resistance increases. With advancing age,
Every echocardiographic examination should also encompass the likelihood of operability comes down.
all the other views to rule out any other coexisting anomaly. It is
not uncommon to find cases in which a coexisting large ductus Cardiac Computed Tomography and Magnetic
or aortopulmonary window was missed. Hence, even after Resonance Imaging
establishing the diagnosis from subcostal and apical views, it is
still important to do a meticulous evaluation via parasternal and Cardiac computed tomography (CT) evaluation with contrast
suprasternal windows to determine the presence and absence of study is useful in delineating the systemic and pulmonary
coexisting anomalies. venous courses. However, CT cannot delineate the intracardiac
Role of 3D echocardiography: The utility of 3D- defect, nor can it assess the volumetrics. However, MRI of
transthoracic and 3D-transesophageal echocardiography heart can provide data that 2D-echocardiography cannot. MRI
(TEE) are well established in the evaluation of atrial septal can indicate the lack of atrial septum, amount of shunting, size
defects, especially in deciding the utility of transcatheter and function of both ventricles, along with anatomical details
device closures. However, the same cannot be extrapolated of pulmonary and systemic veins and coexisting lesions.15
for single atrium. With some effort, additional information With all these faculties up its sleeve, MRI may serve as the
can be obtained regarding the venous drainages. With primary imaging modality in the future.
advanced software, volumetrics can be assessed using 3D
echocardiography enabling the shunt calculations. TREATMENT
Cardiac Catheterization and Angiography Once the diagnosis is confirmed, the objective is to get the
anatomical repair early, preferably by 6 to 12 months of life.
Development of pulmonary vascular obstructive disease It is pertinent to make use of any modality of investigation
in single atrium is much faster than that in isolated which helps surgical decision making. An asymptomatic child
secundum ASD or partial AV canal defect of primum with normal pulmonary artery pressures need not be given any
variant. Whether development of early pulmonary medication other than watchful observation. Judicious use of
vascular disease in some common atrium patients is due diuretics and angiotensin converting enzyme inhibitors can
to a genetic predisposition (related to coexisting abnormal be advocated in symptomatic children, more so if av valve
substrate in the lung or congenital abnormalities in the regurgitation is an issue. Digoxin is best avoided, especially
pulmonary arterial vasculature) or an association with when the status of the sinus node is unclear.16 For those
idiopathic pulmonary hypertension is unknown. Due to with postoperative pulmonary artery hypertension, targeted
the rarity of condition and the eventual paucity of data therapy for pulmonary hypertension may be beneficial.14 The
on the natural history of common atrium and pulmonary surgical results are termed ‘good’ to ‘excellent’ by most of the
vascular disease, determining which patients with common authors.17,18 Even advanced age is not a contraindication to
atrium will develop early pulmonary vascular obstructive operation.19
disease remains challenging.14 Hence, the threshold for Splenic status is an important determinant of outcome. In
operability testing is low in many centers. However, with asplenia or reduced splenic function, use of irradiated blood,
advent of better echocardiographic techniques and non- special precautions to ensure sepsis free handling, dedicated
invasive volumetrics assessment by magnetic resonance staffing, judicious isolation and limitation of visitors in the
imaging (MRI) and 3D echocardiography the need for perioperative period would add to the success of the procedure.
catheterization studies has significantly come down. Since Common atrium can present technical challenges to the
the developing countries may still see many unevaluated surgeon, even when the anatomical details are well delineated.
and untreated grown-up CHD patients, catheterization It should be remembered that the surgeon is not just closing
studies may become essential to get the correct picture. an ASD here, but is actually reconstructing the entire atrial
The mixing of pulmonary and systemic venous returns septum. The most common material used to achieve this
is near complete due to lack of any interface between them. is pericardium. This patch is usually diverted leftward to
However, the relative flow of this mixture via AV valves incorporate the left SVC orifice on the right side of the
depends on the individual compliances of corresponding patch. Issues like absence of coronary sinus take away the
ventricles, which is determined by the vascular resistances landmark of conduction system for the surgeon on the table.
642 of the distal vascular beds. Hence, in the presence of low This compels the surgeon to take the sutures on the tricuspid
45
valve posteriorly to be carried on to right atrial wall beyond 4. Rastelli GC, Rahimtoola SH, Ongley PA, et al. Common
the tricuspid annulus. Some surgeons have used the base of atrium: anatomy, hemodynamics, and surgery. J Thorac
Common Atrium
the mitral valve to anchor sutures.20 Cardiovasc Surg. 1968;55:834-41.
A well reconstructed interatrial septum does very well 5. Gerbode F. Endocardial cushion defects. In: Wu YK, Peters
RM (Eds). International Practice in Cardiothoracic Surgery.
in the postoperative period.17 The decision to continue
Beijing: Science Press; 1985. p. 751.
medications would depend upon the postoperative normaliz
6. Behrendt DM. Atrial septal defect. In: Mavroudis C, Backer
ation of hemodynamics. However, it should be noted that CL (Eds). Pediatric cardiac surgery, 2nd edition. St Louis;
all children with altered splenic function should receive Mosby, 1994. pp. 193-200.
life-long prophylaxis and vaccination against encapsulated 7. Levy MJ, Salomon J, Vidne BA. Correction of single and
bacteria and preferably, annual influenza vaccine. This should common atrium, with reference to simplified terminology.
be emphasized to parents at the time of discharge and re- Chest. 1974;66:444-46.
emphasized during follow up visits. It is useful to get all this 8. Anderson RH,Webb S, Brown NA. Defective lateralisation in
practical information on patient care printed on a handy card children with congenitally malformed hearts. Cardiol Young.
1998;8:512-31.
and issued to the parents for their reference.
9. Van Praagh S, Santini F, Sanders SP. Cardiac malpositions
with special emphasis on visceral heterotaxy (asplenia and
Conclusion polysplenia syndromes). In: Fyler DC (Ed). Nadas’ pediatric
cardiology. Philadelphia’ Hanley and Belfus; 1992. pp. 589-608.
Common atrium and single atrium are two different 10. Digilio MC, Marino B, Giannotti A, et al. Single atrium,
terminologies and there should not be any nosological atrioventricular canal/postaxial hexadactyly indicating Ellis
confusion. Common atrium is a part of complex coexisting van Creveld syndrome. Hum Genet. 1995;96:251-53.
anomalies, whereas single atrium is isolated. Syndromic 11. Gutgesell HP. Cardiac malposition and heterotaxy. In: Garson
associations are well known. Presentation is similar to that of A, Bricker JT, Fisher DJ, Neish SR (Eds). The science and
practice of pediatric cardiology. 2nd edition. Baltimore:
ASD, albeit earlier and with evidence of cyanosis. Evaluation
Williams and Wilkins; 1998. pp. 1539-61.
should consist of a careful search for coexisting anomalies,
12. Spencer R, Robichaux WH, Superneau DW, et al. Unusual
especially of the pulmonary, systemic venous drainage and cardiac malformations in conjoint twins. Pediatr Cardiol.
the AV valves. Early surgical correction around 1 year of age 2002;23:631-38.
is recommended. Surgical results are good and age should not 13. Fournier A, Young ML, Garcia OL, et al. Electrophysiologic
be a deterrent as long as the patient is operable. 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
“Wherever the art of medicine is loved, pulmonary vascular disease. Pediatr Cardiol 2011;32:595-98.
15. Piaw CS, Kiam OT, Rapaee A, et al. Use of non-invasive phase
there is also a love of humanity”
contrast magnetic resonance imaging for estimation of atrial septal
—Hippocrates
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
Acknowledgment patients with left atrial isomerism. Pacing Clin Electrophysiol.
2001;24:1631-38.
We wish to thank Dr IB Vijayalakshmi, Professor of Pediatric 17. Murphy JG, Gersh BJ, McGoon MD, et al. Long-term outcome
Cardiology, for providing all the images. 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
References survival and low incidence of arrhythmias, stroke and heart failure
long-term after surgical ASD closure at young age. A prospective
1. Campbell M. Incidence of cardiac malformations at birth and
follow-up study of 21–33 years. Eur Heart J. 2003;24:190-97.
later and neonatal mortality. Br Heart J. 1973;35:189-200.
19. Inoue T, Kawamura J, Takeda M, et al. An elder case of
2. Young AH, Robinson A. Some malformations of the human
common atrium: surgical repair in a 56-year-old man [in
heart. M Chron. 1907/1908;47:96.
Japanese]. Kyobu Geka. 1991;44:793-96.
3. Campbell M, Nissen GAK. Endocardial cushion defects,
20. Pan-Chih, Chen-Chun. Surgical treatment of atrioventricular
common atrioventricular canal and ostium primum. Br Heart
canal malformations. Ann Thorac Surg. 1987;43:150-54.
J. 1957;19:403.
643
C hapter
46 Single Ventricle
Devananda NS, Maitri Chaudhuri
IntroduCtIon attempted to clarify the confusion surrounding these hearts by

dividing them into the following:
As early as 1699, Chemineau1 described a heart composed of 1. Univentricular heart of the left ventricular (LV) type:
two auricles, but only one ventricle. The univentricular heart Where dominant chamber is of LV morphology and
has since then fascinated the medical community. Unique rudimentary chamber had morphologic features of RV
in its complexity and scope, the univentricular heart has trabecular zone (Figure 4).
sparked intense debates about embryology and nomenclature, 2. Univentricular heart of the right ventricular (RV)
challenged our understanding of cardiovascular physiology type: Where dominant chamber is of RV morphology and
and hemodynamics and inspired some of the most creative rudimentary chamber had morphologic features of LV
surgical and interventional approaches in human history. trabecular zone.
They also proposed that a chamber must receive greater than
nomenClature, hIStory and ConSenSuS or equal to 50 percent of an inlet to be classified as a ventricle
defInItIon whereas the chamber need not have an outlet to qualify as
same. Chambers receiving < 50 percent of inlet were termed
The nomenclature of the univentricular heart is still a ‘rudimentary chambers’. Rudimentary chambers possessing
controversy. The terms single and common ventricle were used an outlet were called ‘outlet chambers’, whereas those only
interchangeably by Abbott, Taussig and Edwards.2-4 Maurice having a trabecular zone were termed ‘trabecular pouches’.
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
Figure 1: The figure shows an extremely rare congenital malformation:
to only one ventricle, which is well-developed and dominant. The true single ventricle, which has both a double inlet and double
The debate started with the use in classical descriptions of outlet. The apical trabeculations are extremely coarse and the
the term ‘single ventricle’. As pointed out by Van Praagh,8 the ventricular morphology is indeterminate. The inset shows the bizarre
conduction system with a sling of conduction axis connecting dual
so called univentricular heart also has an additional incomplete
atrioventricular nodes, and giving rise to a solitary strand, which
or rudimentary ventricle that lacks a proper atrioventricular activates the ventricular mass. Courtesy: Reprinted with permission
connection. In late 1970s and early 1980s, Anderson et al9 from reference 16
Subsequently, Van Praagh10 and colleagues protested 46
against this arbitrary definition of ventricles and challenged
the term ‘univentricular heart’ as in reality these hearts had
Single Ventricle
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
Figure 2: The figure shows a morphological RV, which is tripartite: an tricuspid and mitral valves or a common atrioventricular
inlet, apical trabecular and outlet portions. The apical trabeculations valve. So, this definition excludes tricuspid and mitral atresia.
are coarse. The solid red line indicates the atrioventricular junction,
Anderson’s system likewise emphasizes the nature of the
while the dotted red line indicates the ventriculoarterial junction.
Courtesy: Reprinted with permission from reference 16 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
Figure 3: The figure shows a morphological LV, which is also tripartite.
hearts with double inlet atrioventricular connection,
In contrast to Figure 2, the apical trabeculations are smooth. The solid both double inlet left ventricle (DILV) and double inlet
red line indicates the atrioventricular junction, while the dotted red right ventricle (DIRV), hearts with absence of one
line indicates the ventriculoarterial junction. Courtesy: Reprinted with atrioventricular connection (mitral atresia and tricuspid
permission from reference 16
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
Figure 4: The left hand panel shows a double inlet and double double outlet right ventricle (DORV), may at times be
outlet from morphological left ventricle (LV), which is the functional best managed in a fashion similar to that which is used to
single ventricle. The right hand panel demonstrates the presence of
treat univentricular hearts. However, we are not going to 645
a rudimentary right ventricle (RV), identified from its coarse apical
trabeculations. Courtesy: Reprinted with permission from reference 16 discuss the latter group or HLHS in this chapter.
8 With this short history, we recommend the readers to follow
their own preferred school of morphology. We have tried
to follow Professor Anderson’s method of describing these
cyanotic Heart diSeaSeS
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 Figure 5: This long axis section of a heart with double inlet left ventricle
defect (VSD) where treatment strategy is similar to that of (DILV) shows the relative position of the rudimentary right ventricle and
ventricular septum with respect to inlets. The incomplete RV is located
univentricular hearts. superior to dominant LV. The two inlet valves (yellow arrows) leading
to LV are posteroinferior to the ventricular septum (star). Courtesy:
anatomICal deSCrIptIon of unIVentrICular Reprinted with permission from reference 16
heartS
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 Figure 6: This long axis section of a heart with double inlet right
apical components for the morphologically right and left ventricle (DIRV) shows the opposite relationship to Figure 5. Here the
rudimentary LV is located posteroinferiorly. The yellow arrow shows
ventricles as proposed by Christoffels14 et al. the atrioventricular valve which is anterosuperior to the ventricular
septum (star). Courtesy: Reprinted with permission from reference 16
hearts with one Big and another rudimentary
Ventricle15-17
Question II: Which is the Dominant Ventricle?
Most of the univentricular hearts belong to this group. There
are two important morphological aspects to be understood: This decision is based on morphology of the ventricle and not
on position. The first morphologic principle states that left
Question I: Does the Rudimentary Chamber Really Matter? ventricles have relatively smooth internal walls and lack chordal
attachments of the atrioventricular valves to the rudimentary
Identification of ventricular morphology is the first-step septal surface. Right ventricles are more heavily trabeculated
in determining the type of atrioventricular connections and generally have chordal attachments of the atrioventricular
and eventually the ventricular function. This also helps in valve to the septal surface. The second principle states that
determining the location of ventricular septum and orientation the ventricular chamber that includes an infundibulum giving
646 of conduction tissues. This is important for the surgeon during rise to a great artery represents the morphologic right ventricle.
preoperative planning (Figures 5 and 6). As a corollary, the ventricular chamber having a direct arterial
connection without an intervening infundibulum represents GenetICS21-24 46
a morphologic left ventricle. Rarely, we find ventricles with
primitive or indeterminate morphology. Excluding HLHS, the other subtypes of univentricular heart
Single Ventricle
Additionally, each class of univentricular heart may have including DILV, single inlet, common inlet and complex single
associated abnormalities of atriovisceral situs, of one or both ventricle heterotaxy syndromes are thought to be polygenic in
atrioventricular valves, of one or both semilunar valves and nature, with recurrence and transmission risks far below that
of the relations (transposition or malposition) of the great expected from Mendelian inheritance. The risk to siblings and
arteries. All these have been diagrammatically summarized in offspring of affected individuals is generally in the order of 2
the Figure 7. to 5 percent.
epIdemIoloGy18-20 natural hIStory25,26

Accepting the lack of uniform nomenclature and classification In the largest series of unoperated patients (n = 83) Moodie
system, a New England registry in 1980 reported the incidence et al reported that 70 percent with dominant single left
of univentricular heart to be 54 cases per million live births. ventricles died before age 16, with an annual attrition rate of
Recent estimates are still higher. The commonest subtype was 4.8 percent. The natural history is even bleaker for patients with
HLHS, followed closely by tricuspid atresia. The Figure 8 univentricular hearts of right ventricular morphology, with 50
diagrammatically summarizes the approximate prevalence of percent survival 4 years after diagnosis. The most common causes
common types of single ventricles. of mortality were arrhythmias, congestive heart failure (CHF)
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
647
8
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 become critical as the ductus closes. In patients with mild
their experience with 13 unoperated adults with univentricular to moderate pulmonary stenosis, they present like tetralogy
hearts to determine, which characteristics permitted long-term of Fallot. They may be relatively asymptomatic,with mild
survival. 11 patients had DILV with transposed great arteries, to moderate cyanosis, clubbing and attain adulthood with
1 patient had DILV with normally related great arteries and 1 retarded growth.
patient had tricuspid atresia. The oldest patient was 66 years
old. All had either moderate-to-severe pulmonary stenosis or The LV type of single ventricle patients have a LV type
pulmonary hypertension. The left ventricular ejection fraction of apical impulse. It can be hyperdynamic in patients with
was normal (n = 11) or mildly depressed (n = 2) and no patient increased PBF. There can be a visible, palpable impulse
had more than mild atrioventricular valve regurgitation. in the third left intercostal space (due to inverted outlet
Twelve patients reported good functional capacity and worked chamber). The second heart sound is loud and palpable
full- or part-time. Thus, despite the overall grim prognosis in (anterior aorta). The systolic thrill at left sternal border is
unoperated patients, some adults with DILV, transposition of indicative of subaortic stenosis. The single ventricle of RV
the great arteries and well-balanced circulations may survive type have a subxiphoid RV impulse. There is no impulse in
into their seventh decade with acceptable functional capacity the third left intercostal space as there is no underlying outlet
and preserved ventricular function. chamber.
Clinical features Aortic component of S2 is loud due to the anterior aorta.

The second heart sound is single or narrow split or normally
The clinical features,timing and type of presentation of single split. In patients with pulmonary hypertension there is no
ventricle, depends on the associated lesions and degree of split and it may appear as single S2. The systolic murmur
outflow obstruction. The most frequent presenting symptom is is audible along the mid or lower left sternal border. The
cyanosis since birth. They can also present for heart murmurs, systolic murmur is decrescendo in patients with increased
CHFand neonatal shock. The patients with single ventricle PBF. A systolic ejection murmur is present in those with
with increased pulmonary blood flow (PBF) present in early subpulmonary stenosis. The murmur vary inversely in length
infancy with signs and symptoms of typical of large left to and loudness according to the degree of stenosis. The diastolic
right shunts like CHF and failure to thrive. Cyanosis may not murmurs can be heard in patients with single ventricle with
be very obvious if the patient has increased PBF. In patients increased PBF. There can be an apical mid diastolic rumble
with associated aortic obstruction, the CHF is worsened. due to increased flow across the left atrio ventricular valve.
In patients with pulmonary hypertension, Graham Steell early
In neonates with single ventricle and subpulmonary stenosis/ diastolic murmur of pulmonary regurgitation may be present
atresia marked cyanosis, metabolic acidosis develops and they along the upper left sternal border.
648
eChoCardIoGraphIC dIaGnoSIS of atrioventricular Connections31 46
unIVentrICular heart27-29
Atrioventricular connections can be of the following three types:
Single Ventricle
type of univentricular heart a. Double inlet.
b. Absence of an atrioventricular connection.
As we have discussed before, the univentricular hearts c. Straddling atrioventricular valves.
can be of LV dominance, RV dominance or primitive/
Indeterminate morphology. The best view having to evaluate Double Inlet Connections
this is parasternal short-axis view. The Table 1 and Figure 9
summarizes the findings. The most common univentricular hearts have double inlet
connection, which is usually due to both atrioventricular
Ventriculoarterial Connections valves draining into a common ventricular chamber (88%)
or rarely by a common atrioventricular valve (12%). Usually
The different connections possible are concordant, common atrioventricular valve is associated with heterotaxy
discordant, double outlet from main or outlet chamber and syndromes (asplenia or polysplenia).
single outlet. However, certain combinations are seen more The double inlet is best visualized in short axis and four
frequently. chamber echocardiographic views (Figure 10). In DILV, there
For example, nearly 86 percent of univentricular hearts with is no intervening inlet septum between the right and left
LV dominance30 have discordant ventriculoarterial connections. atrioventricular valves; therefore these valves may actually touch
We have to carefully exclude outflow tract obstruction of the one another when they open in diastole (kissing atrioventricular
great artery arising from the outlet or rudimentary chamber. valves) and both valves are in continuity with posterior great artery.
Only 14 percent of DILV hearts have normally related great
arteries called ‘Holmes heart’. Absence of an Atrioventricular Connection9
In univentricular hearts of RV dominance, the common
pattern is DORV from main chamber or single outlet with Either the right or left atrioventricular connection is absent. In
pulmonary atresia.9 absent connection, the floor of the atrium is entirely muscular

table 1
Echocardiographic diagnosis of univentricular hearts
Type Relation of rudimentary chamber Orientation of trabecular septum AV valves

to main chamber
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
649
Figure 9: Guide for echocardiographic diagnosis of univentricular hearts
8
Figure 10: An apical four-chamber echocardiographic view of double Figure 11: An echocardiogram in apical four-chamber view showing
inlet left ventricle (LV) showing both mitral and tricuspid valves atretic tricuspid valve (*), concordant left atrioventricular connection
draining into morphological LV which is dominant. The star (*) shows and mild mitral regurgitation. Left ventricle (LV) is dominant
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 a B
of the heart. Absence of an atrioventricular connection is more Figures 12a and B: The figures represent autopsy specimens of
common than imperforate atrioventricular valve. 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.
Common Inlet Ventricle9 Courtesy: Reprinted with permission from reference 16
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 a B
the main ventricular chamber feeds blood to the rudimentary Figures 13a and B: A subcostal four-chamber view showing complete
outflow chamber. If the chamber supports the pulmonary AV canal defect with common atrioventricular valve (*), common
flows like situation in Holmes heart, then restriction of the atrium (CA), unbalanced ventricles with dominant left ventricle (LV)
and relatively hypoplastic right ventricle (RV)
bulboventricular foramen restricts PBF. However, in majority
650
of instances since the rudimentary outflow chamber supports SurGICal manaGement of SInGle VentrICle 46
the aortic circulation, restriction of bulboventricular foramen
results in subaortic obstruction. In general, the surgical management of hearts with single
Single Ventricle
Matitiau32 et al reported a method to calculate the area of ventricle anatomy involves a combination strategy based
bulboventricular foramen. Since the foramen is almost never upon palliative and physiologically corrective procedures
circular in shape, its diameter was measured in two orthogonal (Figure 15).
planes (short- and long-axis views: diameter 1 and diameter Palliative procedures are those which correct the imbalance
2 respectively) and then the area was calculated from this between pulmonary and systemic blood flows, without
formula: separating the two circulations. Physiologically, corrective
procedures are those that completely separates the pulmonary
π × diameter 1 × diameter 2 and systemic circulations (creating in series circulations),
Area =
4 thus achieving the goal of unloading the systemic ventricle
and maintaining near normal systemic arterial saturation.
When the area of the bulboventricular foramen is greater
than 2 cm2/m2 BSA, the foramen is always considered as non- hemodynamICS of SInGle VentrICle
restrictive. In patients with area lesser than 1 cm2/m2 BSA, and fontan CIrCuIt33
during the initial palliation, the restrictive bulboventricular
foramen may need to be enlarged. In patients with area of A normal postnatal cardiovascular system consists of a
bulboventricular foramen between 1 to 2 cm2/m2 BSA, a double—pulmonary and systemic—circuit, connected in
guarded waiting policy is justified. In patients, in whom the series, powered by a double pump—the ‘right’ and ‘left’ heart.
bulboventricular foramen is anatomically smaller though non- However, in a univentricular heart, the single ventricle
restrictive by Doppler recordings, a close echocardiographic has to maintain both the systemic and pulmonary blood
watch is justified. circulations, which are not connected in series but in parallel.
There are two main disadvantages: 1. arterial desaturation and
Assessment of the Systemic Veins 2. chronic volume overload to the single ventricle. Such a
chronic volume overload has significant effects on the single
In every patient with univentricular circulation, it is ventricle namely:
mandatory to be precise about the systemic and pulmonary • Dilatation of atrium and ventricle
venous anatomy before planning the surgery. Systemic venous • Eccentric hypertrophy
anomalies commonly present as bilateral superior vena cava • Spherical remodeling with reorientation of wall fibers
or as interrupted inferior vena cava (IVC) as in left isomerism. • Annular dilatation causing progressive atrioventricular
valve regurgitation.
Assessment of the Pulmonary Veins Thus, the hemodynamic problems in univentricular hearts
arise from:
Anomalies of pulmonary venous return are also common • Inherent mechanics of a single ventricle (lack of
anomalies in single ventricular patients, especially in the interventricular coupling and volume overload to single
setting of heterotaxy syndromes. These anomalies have ventricle)
serious repercussions on the outcomes of Glenn shunt • Mechanics of morphological RV versus morphological LV
and extracardiac Fontan surgeries. In single ventricular • Morphology and functional state of atrioventricular valves
physiology with reduced PBF, the anomalous pulmonary • Degree of mixing within single ventricle
venous drainage may not show florid signs since the • Pulmonary vascular resistance (PVR)
pulmonary venous drainage will also be proportionately • Presence and degree of pulmonic or subaortic stenosis
low. The echocardiographer should make serious attempts In 1971, Francis Fontan’ from Bordeaux, France,
to trace all the pulmonary veins meticulously and ensure reported a new approach to the operative correction of these
that no individual pulmonary vein drains anomalously into a malformations. In a ‘Fontan circulation’, the systemic
chamber other than the atria. In case of confusion, one should venous return is connected to the pulmonary arteries without
not hesitate to obtain an angiogram to confirm the pulmonary an interposing ventricle and all shunts at venous, atrial,
venous pathway. ventricular and arterial levels are interrupted. In such a circuit,
To summarize, the check list while doing an echocardiogram the postcapillary energy is no longer ‘wasted’ into the systemic
of univentricular heart is represented in the following veins, but collected and used to push the blood through the lungs.
schematic diagram given in Figure 14. Advantages of a ‘Fontan circuit’ are (near) normalization
651
8
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 and Baudet in 1971. It diverted the systemic venous return to the
overload at the cost of chronic systemic venous hypertension pulmonary artery (PA) and included the insertion of an aortic or
and congestion. The cardiac ouput is decreased as compared to pulmonary homograft valve, at both the inflow and outflow of
normal subjects, both at rest and during exercise. Typically, the the right ventricle. Some time later, Kreutzer35 and colleagues
cardiac output is no longer determined by the heart, but rather described in a simple way the use of pulmonary valve at the
by transpulmonary flow (itself regulated by PVR). Thus, the connection of the right atrium to the PA. These operations
circuit runs on ‘autopilot’, with little interference possible by collectively called as Atriopulmonary plexy were based on
the clinician. Cardiac output can be increased by improving the principle that the right atrium can act as the pump for the
flow to and into the lungs or by bypassing the lungs with a pulmonary circulation. This concept was later questioned.
fenestration. The effect of pulmonary vasodilators is usually In 1987, de Leval36 et al proposed a major variation that
very modest (Figures 16A to C). consisted of an end-to-side direct anastomosis of the superior
vena cava to the undivided right PA and using a conduit that
Is every fontan Circuit alike? is created inside the atrium, the IVC is also drained to the
652 PA: Lateral Tunnel Technique. In the majority of cases,
The Fontan operation (Figures 17A to C) was first used in 1968 the lateral tunnel is created by insertion of a semicylindrical
for the repair of tricuspid atresia and was described by Fontan34 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 extracardiac conduit–inferior vena cava transition. Usually a
lateral tunnel can be created by autologous material from slightly oversized conduit is required in younger children to
the interatrial septum. Its advantages are decreased risk of allow for vessel growth in relation to somatic growth. Our
thrombosis, decreased blood stasis and exposure of a limited institutional protocol is to perform it at a minimum age of
portion of right atrium to the high venous pressures, thus around 3 years and weight of about 15 kg.
reducing the risk of arrhythmias. In addition, the coronary The latter two procedures namely Lateral Tunnel
sinus remains in the low-pressure atrium allowing unimpeded technique and Extracardiac conduits are named as Total
myocardial venous drainage. Cavopulmonary Connection (TCPC). TCPC surgeries offer
Marcellati 37 in 1990 popularized the use of an extracardiac laminar blood flows and are hydraulically more efficient than
interposition graft between the transected IVC and PA: older versions.
Extracardiac Fontan. It allows for better preservation In patients with infrahepatic interruption of the IVC (as
of ventricular and pulmonary function because it requires in left isomerism), only the hepatic veins drain into the right
minimal or no cardiopulmonary bypass. In addition, it avoids atrium. Blood from the lower body reaches the superior caval
right atrial incisions and extensive atrial suture lines. This vein via the azygos vein. In these patients, a bidirectional
reduces the risk of injury to the sinus node and the incidence cavopulmonary anastomosis (Kawashima operation)38 will
of postoperative arrhythmias. However, since the extracardiac result in an almost complete Fontan palliation, redirecting
tunnel is created either by homograft or conduit, it has no blood from the superior vena cava as well as from the azygos
growth potential and is at risk for obstruction by thrombus vein to the pulmonary arteries and leaving only the hepatic
formation or neointimal hyperplasia. The usual size of veins draining into the systemic circulation (Figures 18 653
conduit used is 18 mm and above. This is to allow a uniform and 19).
8
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
the West zones. The paradox in the Fontan circulation is the

coexistence of systemic venous hypertension and pulmonary
c arterial hypotension. It should be emphasized that the driving
force of the circulating blood volume between systemic and
Figures 16a to c: This schematic diagram depicts the hemodynamics pulmonary veins is the pressure gradient between central
of single ventricle and Fontan surgery. A. The normal cardiovascular
circulation. The pulmonary circulation (P) is connected in series with venous pressure and the left atrium, assisted mechanically by
the systemic circulation (S). The right ventricle maintains the right the thoracic muscles and the respiratory function.
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 Ideal patient for fontan operation
connected in parallel, with a considerable volume overload to the single
ventricle (V). The width of the line reflects the degree of volume load. The original criteria for the Fontan operation, set by
There is complete admixture of systemic and pulmonary venous blood, Choussat40 and his colleagues for patients with tricuspid
causing arterial oxygen desaturation; C. The Fontan circulation. The atresia, were particularly strict.
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 Original Criteria Proposed for Fontan Completion
expected for body surface area. In the absence of fenestration, there is
no more admixture of systemic and pulmonary venous blood, but the
(Ten Commandments)
systemic venous pressure is notably elevated. Ao = Aorta; LA = Left
atrium; LV = Left ventricle; RV = Right ventricle. Courtesy: Reprinted • Age greater than or equal to 4 to lesser than 15 years
from reference 34 • Normal sinus rhythm
• Normal systemic venous return
• Normal right atrial volume
paradox of fontan Circulation39 • Mean PA pressure lesser than or equal to 15 mm Hg
In a normal circulation, a good hemodynamic state is • Pulmonary arteriolar resistance lesser than 4 Wood units/
characterized by low pressures, especially in the IVC (< 10 mm m2 body surface area
Hg), with the mean PA pressure being at least 15 mm Hg in order • Pulmonary artery to aortic diameter ratio greater than or
654 for the pulmonary vascular network to be patent according to equal to 0.75
46
Single Ventricle
Figure 18: This subcostal sagittal echocardiographic view shows Figure 20: This suprasternal echocardiogram in a post Glenn child
interrupted IVC with azygos continuation (Az) posterior to descending shows the laminar flow in Glenn shunt (SVC connected to RPA with
aorta (D Ao) 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
Figure 19: This schematic diagram shows Kawashima’s modification
in patients of univentricular heart with interrupted inferior vena cava
(IVC). Ao = Aorta; HV = Hepatic vein; PV = Pulmonary veins; SVC = Cardiac Catheterization for pre-fontan evaluation41,42
Superior vena cava.
The focus of cardiac catheterization for pre-Fontan evaluation
is on the following:
1. Patency of the Glenn shunt with analysis of PA anatomy
• Left ventricular ejection fraction greater than or equal to (Figures 20 to 22): PA size and distortion, confluence
0.60 stenosis (stenosis > 50% as compared to adjacent segment),
• Competent mitral valve presence or absence of anomalously draining pulmonary
• Absence of PA distortion. veins in levophase and any significant decompressing
With increasing experience, the criteria have become more venovenous collaterals (> 2 mm).
flexible. Preoperatively impaired ventricular function and 2. Inferior vena cava angiogram (Figure 23) to rule out
elevated pulmonary arterial pressures are currently considered interrupted IVC/ stenosis/duplication of IVC and drainage 655
as the two most important commandments. pattern of hepatic veins.
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?

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.
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 Sequelae of fontan operation43-45
with a significant descending venovenous collateral decompressing
the Glenn shunt 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
Figure 23: This antegrade venous catheterization was done as part was 92.9 percent plus or minus 1.9 percent. 95.2 percent of
of Pre-Fontan evaluation showing an uninterrupted IVC draining into survivors were in NYHA class I.
heart. IVC = Inferior vena cava; L = Liver; S = Spine.
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
3. Ventriculogram to detect ventricular contractility, atrioven- use of extracardiac circulation, use of fenestration, preliminary
tricular valve regurgitation, systemic outflow obstruction, volume unloading operations like bidirectional Glenn shunt
presence or absence of antegrade flow from ventricle to and concomitant clamping of any aortopulmonary collaterals.
pulmonary artery. Data shows that the extracardiac conduit procedure
4. Hemodynamic evaluation: PA systolic, diastolic and provides superior hemodynamics compared to the intra-
mean pressures, PVR and ventricular end-diastolic pres- atrial lateral tunnel technique. This hemodynamic advantage
sures. is markedly enhanced by the use of conduit–superior vena
If one assumes a pulmonary venous oxygen saturation of cava offset, particularly at high physiologic flow rates as in
656 96 percent and normal systemic blood flow, the arterial oxygen exercise. These data suggest additional justification for the
saturation reflects total PBF. As a rule of thumb, values greater use of extracardiac conduit procedures for final completion of
• Pulmonary vein bed congestion 46
• Thromboembolic episodes
• Worsening cyanosis due to:
Single Ventricle
– Existence of surgically created communication (fenes-
tration)
– 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
Figure 24: This schematic diagram depicts a lateral tunnel procedure
• Significant regurgitation of the atrioventricular connection
with fenestration (arrow). Ao = Aorta; LT = Lateral tunnel; LPA = Left
pulmonary artery; RPA = Right pulmonary artery; SVC = Superior vena • NYHA class III/IV before surgery.
cava.
Complications post-fontan operation
the Fontan circulation. Functional Status and Exercise Tolerance49
In a subgroup of patients at increased risk (young
age at operation, increased mean PA pressure and PVR, More than 90 percent of all hospital survivors are in NYHA
raised ventricular end-diastolic pressures and significant functional class I/II. Most patients do well educationally and
atrioventricular valve regurgitation) a small fenestration can can pursue a variety of professional careers. However, with
be created in the intra-atrial tunnel at the time of TCPC to time there is a progressive decline of functional status in some
allow a protective right-to-left shunt (Figure 24). The potential subgroups.
benefits are a lower central venous pressure and better single
ventricle preload, albeit at the expense of a right-to-left shunt Ventricular Function33
and mild cyanosis. These benefits were found to be greatest in
the immediate postoperative period when, as a consequence All studies reported the ventricle of a functionally univentricular
of cardiopulmonary bypass and myocardial ischemia, heart to be dilated, hypertrophic and hypocontractile. It can be
myocardial function was impaired and elevated PVR was a caused by the congenital malformation itself, previous surgical
problem. This modification has improved operative survival interventions or the very abnormal working conditions of the
rates among high risk patients and shortened duration of ventricle at various stages of palliation, both before and after
pleural effusions and length of hospital stay.46 A considerable Fontan.
percentage of small fenestrations will close spontaneously During the first month after birth, the ventricle is always
later on. In patients with persistently patent fenestration and volume overloaded. This leads to dilatation and spherical
mild cyanosis it remains controversial whether interventional configuration, cardiac overgrowth and eccentric hypertrophy.
occlusion is required later. In patients with increasing By performing Fontan operation, the preload is reduced to
cyanosis during exercise, transcatheter device occlusion of levels well below normal for BSA (50–70%) and even more
fenestration is recommended in the presence of appropriate when expressed in relation to ventricular size (25–70%). The
hemodynamics.47 It should not be done in patients with ventricle thus undergoes a transition from volume overloaded
preoperative risk factors, residual PA distortion or anastomotic and overstretched, to overgrown and severely underloaded.
stenosis, significant atrioventricular regurgitation and signs of Thus, the Fontan ventricle shows systolic and diastolic
systemic ventricular dysfunction. dysfunction. It may enter into a vicious cycle whereby the
On the other hand, the main factors associated with long- low preload leads to remodelling, reduced compliance, poor
term morbidities are: ventricular filling and eventually declining cardiac output.
• Progressive ventricular dysfunction This phenomenon of progressive ‘disuse hypofunction’ occurs
• Systemic venous hypertension at a chronic preload of less than 70 percent of the “due” 657
• Right atrial distension preload.
8 The congenital malformation may itself predispose to Types
ventricular dysfunction. The morphological LV with its
ellipsoid shape and complex fiber orientation is tuned to handle The commonest arrhythmias are sinus node dysfunction
systemic pressure for a lifetime. But the morphological RV (prevalence 13–16%), intra-atrial re-entrant tachycardia
and even more the indeterminate primitive ventricle fails after (Figure 25) or atrial flutter. They are usually refractory to
few years of systemic loading. Futhermore, a tricuspid valve anti-arrhythmics and in the acute setting, quickly deteriorate
or common atrioventricular valve poorly tolerates the initial to clinical cardiac failure. Cardioversion with direct current
volume overload and starts regurgitating shortly. The treatment (DC) shock is the safest immediate therapy. Subsequently, the
of ventricular dysfunction in the setting of Fontan circuit is clinician should obtain a complete hemodynamic evaluation
very frustating for a cardiologist. Several studies, both acute in every patient with new tachycardia, as this may be the first
and chronic, have shown little impact of inotropes, afterload manifestation of pathway obstruction. Full anticoagulation
reducers, vasodilators and beta-blockers, as these have no should also be started. Long-term treatment involves
impact on the reduced preload which is the main limiting factor. medication and ablation. The best long-term treatment is
conversion of the older Fontan types to an extracardiac
arrhythmia50-52 cavopulmonary connection, together with a right atrial maze
and a reduction plasty (combined with dual chamber epicardial
The incidence of arrhythmias post-Fontan surgery ranges pacemaker if indicated). In refractory atrial tachyarrhythmias,
between 10 to 40 percent and reported even up to 10 years later. but no other indication for surgical revision, transcatheter
ablation approach may be tried with repeat procedures as
Etiology required.
Ventricular arrhythmias are extremely rare and usually
Many older Fontans have atrial wall incorporated into the caused by severe ventricular dysfunction.
circuit causing progressive atrial dilatation and wall stress;
furthermore, most of them also had atriotomy and possible Severe hypoxemia: post fontan53-56
injury to the sinus node or innervation. The lateral tunnel
technique per se is a risk factor, leading to the development Patients with a Fontan circulation are slightly desaturated
of arrhythmias due to the suture lines placed inside the with baseline pulse oximetry values 94 percent plus or minus
atrium. Heterotaxy syndromes are also prone to rhythm 2 percent. This is because the hepatic veins and coronary sinus
disorders. Bradyarrhythmias have also been observed in still drain into the atrial chambers. However, in the setting
patients undergoing the extracardiac tunnel technique. Atrial of severe desaturation, the following anatomical substrates
pacing has been suggested in order to avoid moderate degree should be ruled out: a large fenestration, intrapulmonary
bradyarrhythmias. arteriovenous fistulae and abnormal systemic venous channels
658
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
draining into the pulmonary venous atrium (for example, a left Ventricular failure57 46
superior caval vein to the left atrium). Detailed angiography
of supra and infradiaphragmatic systemic veins should be Ventricular failure is mostly seen around 8 years after the initial
Single Ventricle
done. These connections can be occluded percutaneously in Fontan surgery, although it has been reported both earlier
the majority of cases. and later. The etiology is multifactorial like morphology of
The development of pulmonary arteriovenous malforma- dominant ventricle, valve regurgitation, etc. But the unique
tions is described in up to 25 percent of patients post-Glenn shunt feature is the combination of decreased preload and increased
leading to progressive cyanosis and exercise intolerance. The afterload (as systemic and pulmonary circulation are again in
probable etiology is exclusion of hepatoenteric flow (Factor series) in a Fontan circuit.
X) from the pulmonary circulation. These malformations Even asymptomatic patients demonstrate abnormal cardio-
are often multiple and diffuse. Recent reports noted the respiratory response to exercise which is best unmasked by
reversal of pulmonary arteriovenous malformations following Dobutamine stress test.
redirection of hepatic venous flow to the pulmonary circulation As we have discussed before in the hemodynamics
(Figures 26A and B). section, the role of inotropes, vasodilators and beta-blockers
is limited. Prompt repair of structural anomalies like
residual left-to-right Shunt atrioventricular valve regurgitation, relief of outflow tract
obstructions, correction of PA stenosis are helpful. In end-
Residual left-to-right shunt can happen due to large stage situations, orthotopic heart transplantation is the only
aortopulmonary collaterals, persistent antegrade flow from answer.
ventricle to pulmonary artery and failed occlusion of previous
shunts. A large left-to-right shunt produces volume overload thromboembolic events58,59
and stress on the single ventricle. The rule of thumb is that
if angiography of a systemic vessel gives rise to pulmonary Symptomatic systemic venous and arterial thromboembolisms
capillary blush and opacification of pulmonary veins, it should have a reported incidence of 3 to 20 percent. Literature
be occluded percutaneously. review reveals a bimodal peak of increased incidence of
a B
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. 659
Courtesy: Reprinted from reference 51
8 lymphatic dysfunction60,61
Pathogenesis
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
Figure 27: Subcostal echocardiographic view of the right atrium (RA)
long-term follow-up. Leakage of chyle into the bronchus leads
in a patient with a modified classic Fontan for D-transposition of the
great arteries, multiple muscular ventricular septal defects, a functional to plastic bronchitis, most frequently diagnosed at necropsy.
single ventricle and atrial tachyarrhythmias. The arrow indicates a well-
delineated thrombus in the dilated right atrium. Courtesy: Reprinted
from reference 51
Clinical Presentation of PLE
The common clinical manifestations are edema, ascites,
immunodeficiency, fatigability and hypocalcemia. The
thromboembolism: one at 1½ year and another around 10 diagnosis is confirmed by low serum albumin and positive
years postsurgery. fecal α1 antitrypsin. In an international multicenter study of
Increased systemic venous pressure, low velocity flow 3029, patients with Fontan repair between 1975 and 1995,
within the systemic venous atrium and pulmonary circulation, PLE occurred in 3.8 percent. The prognosis is very poor with
low cardiac output and dehydration contribute to the risk of 5 and 10 year survival rates of 59 and 20 percent, respectively.
thrombus formation. In addition, liver dysfunction (Protein C,
Protein S and antithrombin III deficiency), increased platelet Etiology
reactivity and PLE may alter the balance between pro- and
anticoagulant factors (Figure 27). Problems in Fontan circuit (gradient at connection, poor
Massive pulmonary thromboembolism is the most common design), problems of pulmonary vasculature (increased
cause of sudden out-of-hospital death in patients with a Fontan PVR, hypoplasia, distorted PA anatomy) or cardiac problems
circuit. Chronic multiple pulmonary microemboli may lead to (atrioventricular valve regurgitation, myocardial dysfunction)
pulmonary vascular obstructive disease, which may appear are frequently identified. An autoimmune or inflammatory
late but is particularly lethal in a Fontan circulation. cause, sometimes triggered by an infection, has also been
There is no consensus, however, regarding the postopera- isolated in some cases. Hypoxemia induced pulmonary
tive mode and duration of prophylactic anticoagulation, since vasoconstriction was reported to be associated with PLE in
no large scale randomized control studies have been per- patients living at high altitudes.
formed. Routine anticoagulation with coumadin is performed
by some institutions irrespective of the type of the modified Treatment Strategies
Fontan procedure and potential risk factors. Many centers,
however recommend aspirin for uncomplicated patients and Clinical resolution of PLE is rare (< 1%). The following
full anticoagulation34 in presence of previous thrombi, low therapies have been tried:
cardiac output (frequently associated with spontaneous con- 1. A diet high in calories, high protein content and medium
trast on echo), congestion, dilation of venous or atrial struc- chain triglyceride fat supplements with low salt content
tures and arrhythmia, PLE, etc. is usually recommended.
Keeping in mind the bimodal presentation of thrombo- 2. Diuretics for peripheral edema.
embolism, our protocol is to administer oral anticoagulants 3. Protein infusions (albumin, globulin) on a weekly or
for 1 year postsurgery, then switch over to oral antiplatelets monthly basis.
and finally restart oral anticoagulants from 10 years post 4. In some patients, specific anti-infection measures are
surgery onwards. necessary (chronic antibiotics, vaccines).
660
5. Inotropes or systemic vasodilators fail to improve output, limited exercise tolerance, relapsing tachycardia, 46
ventricular function. PLE and/or plastic bronchitis. As explained before, treatment
6. Corticosteroids, heparin and octreotide have been with inotropes, vasodilators, and diuretics show little
Single Ventricle
occasionally useful. result. A more aggressive approach aimed at optimising the
7. Resection of the most affected part of the gut. Fontan circuit (stenting of stenosis, embolising collaterals,
8. Surgical correction of stenosed anastomotic sites, leaking conversion of older Fontans to TCPC, right atrial maze for
atrioventricular valves, late takedown, etc. carries a high intractable arrhythmias, creation of fenestration, etc.) is
mortality. needed. In refractory cases, heart transplantation is the only
9. Cardiac transplantation with consequent immunosup- option.
pressive therapy has been tried in refractory cases. This
often cures the PLE, but also has its own significant dis- SuGGeSted folloW-up of poSt-fontan patIentS
advantages.
10. Catheter interventions: Balloon dilatation/stent implan- Post-Fontan patients should be followed up by a specialist
tation of residual PA stenosis, embolization of left-to- team and the observation parameters in our institute are:
right shunts and fenestration of Fontan circuit has been • Clinical assessment including blood pressure and resting
tried in PLE. Of these, fenestration almost always impulse oximetry
proves PLE, but with the risk of progressive cyanosis. • 12 lead electrocardiogram
• Echocardiogram with color Doppler (Figures 28 and 29)
plastic Bronchitis and Tissue Doppler imaging
• Blood for complete blood count, prothrombin time (PT)
Plastic bronchitis is a very rare, but potentially lethal and INR (International Normalized ratio), liver function
complication occurring weeks to months after Fontan tests
surgery causing obstruction of major airways with solid • Exercise tolerance with Treadmill test
fibrinomucoid material. Persistent segmental atelectasis, • Holter monitoring if arrhythmias
large airway obstruction or expectoration of tenacious mucoid • Additional work-up include: Transesophageal
material should prompt early diagnostic and therapeutic echocardiography, cardiac MRI, cardiac catheterization
bronchoscopic lavage. Treatment is very difficult and similar and Electrophysiological study (EPS).
to PLE.
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
Figure 28: Subcostal echocardiogram showing laminar flow in
because of persistent congestion with edema, low cardiac extracardiac Fontan conduit (arrow). V = Inferior vena cava
661
8 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.
Circulation 2007 (reference 49). Our endeavor was to look

at univentricular heart and Fontan surgery from a practical
Figure 29: The echocardiogram in apical four-chamber view in a and clinical point of view. The interested readers are invited
patient of tricuspid atresia status post-Fontan surgery shows the
Fontan tunnel (T) with arrow showing mosaic flow through the
to go through the individual reference articles for a more
fenestration in Fontan circuit 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.
ConCluSIon
referenCeS
The long-term results of the Fontan operation performed
in low risk patients show good overall results: hypoxia is 1. Peacock TB. Malformations of the heart. In: Peacock TB (Ed).
eliminated, volume overload is abolished and chronic sys- On Malformations of the Human Heart: With Original Cases.
temic venous hypertension is usually tolerated. Survival of London: John Churchill; 1858. pp. 10-102.
2. Abbott ME. Atlas of congenital cardiac disease. New York:
patients undergoing a completion TCPC in the current era is
American Heart Association; 1936. pp. 50-2.
excellent. However, various common and uncommon mor- 3. Taussig HB. Cardiovascular anomalies: a single ventricle with
bidities gradually deteriorate the quality of life. Preliminary a diminutive outlet chamber. J Tech Methods. 1939;19:120.
unloading of the single ventricle by bidirectional Glenn shunt 4. Edwards JE. Congenital malformations of the heart and great
gives an overall better result of ultimate Fontan completion. vessels. In: Gould SE (Ed). Pathology of the heart, 2nd edition.
However, every clinician should remember that a Fontan Springfield: Charles C Thomas; 1960. p. 335.
operation remains an imperfect solution for a complex 5. Lev M, Liberthson RR, Kirkpatrick J, et al. Single (Primitive)
cardiovascular problem. Ventricle. Circulation. 1969;39.
6. Marin-Garcia J, Tandon R, Moller JH, et al. Common (single)
ventricle with normally related great vessels. Circulation.
It is health that is real wealth and not
1974;49:565-73.
pieces of gold and silver 7. Anderson RH, Becker AE, Wilkinson JL. Proceedings:
— Mahatma Gandhi morphogenesis and nomenclature of univentricular hearts. Br
Heart J. 1975;37:781-2.
aCKnoWledGment 8. Van Praagh R, Ongley PA, Swan HJ. Anatomic types of
single or common ventricle in man: morphologic and
We sincerely thank Professor Robert Anderson for permission geometric aspects of 60 necropsied cases. Am J Cardiol.
to reprint from his exhaustive collection of morphological 1964;13:367-86.
images of single ventricle. In addition, we thank him for 9. Anderson RH, Tynan M, Becker AE. Echocardiography of
the univentricular heart. In: Lundstrom N-R (Ed). Pediatric
allowing us to deliberate and realize the true meaning echocardiography – cross sectional, M-mode, and Doppler,
of functional single ventricle. We also acknowledge the Amsterdam; 1980, Elsevier/North – Holland Biomedical.
contribution of Dr Gewellig towards establishing an 10. Van Praagh R, David I, Van Praagh S. What is a ventricle? The
explanation of hemodynamics of single ventricle. His single ventricle trap, Ped Cardiol. 1982;2:79.
article (reference 33) is a must read item for any student of 11. Anderson RH, et al. The univentricular atrioventricular con-
662 pediatric cardiology. We also acknowledge the beautiful nection: getting to the root of a thorny problem, Am J Cardiol.
review on univentricular heart published by Khairy et al in 1984;54:822.
12. Jacobs ML, Mayer JE, Jr. Congenital Heart Surgery Nomencla-
ture and Database Project: single ventricle. Ann Thorac Surg.
great arteries: influence on initial palliative operation and rate
of growth, J Am Coll Cardiol. 1992;19:142.
46
2000;69(4 Suppl):S197-S204. 33. Gewillig M. The Fontan Circulation. Heart. 2005;91:839-46.
Single Ventricle
13. Wilkinson JL, Becker AE, Tynan M, et al. Nomenclature of the 34. Fontan F, Baudet E. Surgical repair of tricuspid atresia. Thorax
univentricular heart. Herz 1979;4:107-12. 1971;26:240-8.
14. Christoffels VM, Habets PEMH, Franco D, et al. Chamber 35. Kreutzer G, Galindez E, Bono H, et al. An operation for the
formation and morphogenesis in the developing mammalian correction of tricuspid atresia. J Thorac Cardiovasc Surg. 1973;
heart. Devel Biol. 2000;223:266-78. 66:613-21.
15. Cook AC, Anderson RH. The functionally univentricular 36. DeLeval MR, Kliner P, Gewillig M, et al. Total cavopulmonary
circulation: anatomic substrates as related to function. Cardiol connection: a logical alternative to atriopulmonary connection
Young. 2005;15(Suppl. 3):7-16. for complex Fontan operations. J Thoracic Cardiovasc Surg.
16. Anderson RH, Becker AE, Freedom RM, et al. Sequential 1988;96:682-95.
segmental analysis of congenital heart disease. Pediatr Cardiol. 37. Marcelletti C, Corno A, Giannico S, et al. Inferior vena cava-
1984;5:281-7. pulmonary artery extracardiac conduit. A new form of right
17. Anderson RH, Ho SY. Sequential segmental analysis – heart bypass. J Thorac Cardiovasc Surg. 1990;100:228-32.
description and categorization for the millennium. Cardiol 38. Kawashima Y, Kitamura S, Matsuda H, et al. Total cavo-
Young. 1997;7:98-116. pulmonary shunt operation in complex cardiac anomalies: a
18. Fyler DC, Buckley LP, Hellenbrand WE, et al. Report of the new operation. J Thorac Cardiovasc Surg. 1984;87:74-81.
New England Regional Infant Cardiac Program. Pediatrics. 39. de Leval MR. The Fontan circulation: a challenge to William
1980;65:375-461. Harvey? Nat Clin Pract Cardiovasc Med. 2005;2:202-8.
19. Hoffman JI, Kaplan S. The incidence of congenital heart 40. Choussat A, Fontan F, Besse B, et al. Selection criteria for
disease. J Am Coll Cardiol. 2002;39:1890-1900. Fontan’s procedure. In: Anderson RH, Shinebourne EA (Eds).
20. Van Praagh R, Ongley PA, Swan HJ. Anatomic types of single Paediatric Cardiology. New York: Churchill Livingstone;
or common ventricle in man: morphologic and geometric
1978. pp. 559-66.
aspects of 60 necropsied cases. Am J Cardiol. 1964;13:367-86.
41. Lock JE, Keane JF, Fellows KE. The use of catheter intervention
21. Gill HK, Splitt M, Sharland GK, et al. Patterns of recurrence
procedures for congenital heart disease. J Am Coll Cardiol.
of congenital heart disease: an analysis of 6,640 consecutive
1986;7:1420-3.
pregnancies evaluated by detailed fetal echocardiography.
42. Nakanishi T. Cardiac catheterization is necessary before
bidirectional Glenn and Fontan procedures in single ventricle
22. Weigel TJ, Driscoll DJ, Michels VV. Occurrence of congenital
physiology. Pediatr Cardiol. 2005;26:159-61.
heart defects in siblings of patients with univentricular heart
43. Stamm C, Friehs I, Mayer JE Jr, et al. Long-term results of
and tricuspid atresia. Am J Cardiol. 1989;64:768-71.
23. Burn J, Brennan P, Little J, et al. Recurrence risks in offspring the lateral tunnel Fontan operation. J Thorac Cardiovasc Surg.
of adults with major heart defects: results from first cohort of 2001;121:28-41.
British collaborative study. Lancet. 1998;351:311-6. 44. Earing MG, Cetta F, Driscoll DJ, et al. Long-term results of the
24. Shapiro SR, Ruckman RN, Kapur S, et al. Single ventricle Fontan operation for double-inlet left ventricle. Am J Cardiol.
with truncus arteriosus in siblings. Am Heart J. 1981;102(3 Pt 2005;96:291-8.
1):456-59. 45. Gentles TL, Mayer JE, Gavreau K, et al. Fontan operation
25. Moodie DS, Ritter DG, Tajik AJ, O’Fallon WM. Long-term in five hundred consecutive patients: factors influencing
follow-up in the unoperated univentricular heart. Am J Cardiol. early and late outcome. J Thorac Cardiovasc Surg. 1997;114:
1984;53:1124-8. 376-91.
26. Ammash NM, Warnes CA. Survival into adulthood of patients 46. Bridges ND, Mayer JE, Lock JE, et al. Effect of baffle
with unoperated single ventricle. Am J Cardiol. 1996;77:542-4. fenestration on outcome of the modified Fontan operation.
27. Rigby M, et al. Two-dimensional echocardiographic categoriza- Circulation. 1992;86:1762-9.
tion of the univentricular heart: ventricular morphology, type and 47. Sommer RJ, Recto M, Golinko R, et al. Transcatheter coil
mode of atrioventricular connection. Br Heart J. 1981;46:603. occlusion of surgical fenestration after Fontan operation.
28. Freedom RM, et al. The atrioventricular junction in the univen- Circulation. 1996;94:249-52.
tricular heart: a two-dimensional echocardiographic analysis, 48. Mair D, Puga F, Danielson G. Late functional status of
Ped Cardiol. 1982;3:105. survivors of the Fontan procedure performed during the 1970s.
29. Huhta JC, et al. Two-dimensional echocardiographic spectrum Circulation. 1992;86:106-09.
of univentricular atrioventricular connection, J Am Coll 49. Khairy P, Poirier N, Mercier LA. Univentricular Heart.
Cardiol. 1985;5:149. Circulation. 2007;115:800-12.
30. Bevilacqua M, et al. Double – inlet single left ventricle: 50. Shirai LK, Rosenthal DN, Reitz BA, et al. Arrhythmias and
echocardiographic anatomy with emphasis on the morphology thromboembolic complications after the extracardiac Fontan
of the atrioventricular valves and ventricular septal defect. J operation. J Thorac Cardiovasc Surg. 1998;115:499-505.
Am Coll Cardiol. 1991;18:559. 51. Cohen MI, Wernovsky G, Vetter VL, et al. Sinus node function
31. Shiraishi H, Silverman NH. Echocardiographic spectrum after a systematically staged Fontan procedure. Circulation.
of double inlet ventricle: evaluation of the interventricular 1998;98(suppl II):352-8.
communication. J Am Coll Cardiol. 1990;15:1401. 52. Fishberger SB, Wernovsky G, Gentles T, et al. Factors that
32. Matitiau A, et al. Bulboventricular foramen size in infants with influence the development of atrial flutter after the Fontan
double – inlet left ventricle or tricuspid atresia with transposed operation. J Thorac Cardiovasc Surg. 1997;113:80-6. 663
8 53. Gatzoulis MA, Shinebourne EA, Redington AN, et al.
Increasing cyanosis early after cavopulmonary connection
by transthoracic echocardiography after the Fontan operation.
caused by abnormal systemic venous channels. Br Heart J. 60. Mertens L, Hagler DJ, Sauer U, et al. Protein-losing enteropathy
1995;73:182-6. after the Fontan operation: an international multicenter study.

54. McElhinney DB, Reddy M, Tworetzky W, et al. Incidence PLE study group. J Thorac Cardiovasc Surg. 1998;115:
and implications of systemic to pulmonary collaterals after 1063-73.
bidirectional cavopulmonary anastomosis. Ann Thorac Surg. 61. Powell AJ, Gauvreau K, Jenkins KJ, et al. Perioperative
2000;69:1222-8. risk factors for development of protein-losing enteropathy
55. Stümper O, Wright JGC, Sadiq M, et al. Late systemic following a Fontan procedure. Am J Cardiol. 2001;88:1206-9.
desaturation after total cavopulmonary shunt operations. Br 62. Khairy P, Ouyang DW, Fernandes SM, et al. Pregnancy
Heart J. 1995;74:282-6. outcomes in women with congenital heart disease. Circulation.
56. Kaulitz R, Ziemer G, Paul Th, et al. Fontan-type procedures: 2006;113:517-24.
residual lesions and late interventions. Ann Thorac Surg 2002; 63. Canobbio MM, Mair DD, van der Velde M, et al. Pregnancy
74:778-85. outcomes after the Fontan repair. J Am Coll Cardiol. 1996;28:
57. Kaulitz R, Hofbeck M. Current treatment and prognosis in 763-7.
children with functionally univentricular hearts. Arch Dis 64. Mavroudis C, Backer CL, Deal BJ, et al. Total cavopulmonary
Child. 2005;90:757-62. conversion and maze procedure for patients with failure of
58. Balling G, Vogt M, Kaemmerer H, et al. Intracardiac thrombus the Fontan operation. J Thorac Cardiovasc Surg. 2001;122:
formation after the Fontan operation. J Thoarc Cardiovasc 863-71.
Surg. 2000;119:745-52. 65. Morales DL, Dibardino DJ, Braud BE, et al. Salvaging the
59. Fyfe DA, Kline CH, Sade RM, et al. Transesophageal failing Fontan: lateral tunnel versus extracardiac conduit. Ann
echocardiography detects thrombus formation not identified Thorac Surg. 2005;80:1445-51.
664
C hapter
47 Hypoplastic Left Heart Syndrome
P Syamasundar Rao, Srilatha Alapati
INTRODUCTION supply adequate coronary blood flow in a retrograde fashion.

Coarctation of the aorta may be present in a significant number
The term hypoplastic left heart syndrome (HLHS), initially of patients with HLHS,3,6-8 but interrupted aortic arch is rare.
proposed by Noonan and Nadas,1 describes a spectrum of The right heart (i.e. right atrium, right ventricle, pulmonary
cardiac abnormalities characterized by marked hypoplasia of arteries) is markedly enlarged.
the left ventricle (LV) with atresia or severe stenosis of aortic The left atrium is small reflecting limited blood flow in
and/or mitral valves (MV) and hypoplasia of the ascending utero. The atrial septum is usually thickened and there is
aorta and aortic arch. The ventricular septum is usually anomalous attachment of septum primum to the left atrium
intact. The left atrium is small and a patent foramen ovale or and this makes the foramen ovale to be small and restrictive.
secundum atrial septal defect is usually present. A large patent The septum primum is usually deviated more posteriorly
ductus arteriosus supplies blood to the systemic circulation. It and to the left.9,10 Rarely, there may be intact atrial septum
is associated with coarctation of the aorta in most cases. This is (Figure 1) and the condition of these patients is usually
the same disorder characterized as hypoplasia of the aortic tract much more critical at birth. Ventricular septal defect is not
complex by Lev.2 Prior to 1980’s, 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.
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 Figure 1: Subcostal echocardiographic view of the atrial septum with
color flow imaging in an infant with hypoplastic left heart syndrome
unicuspid or bicuspid with severe stenosis or atretic. The demonstrating intact atrial septum. The flow in the superior vena cava
ascending aorta is usually hypoplastic and measures 2 to 3 mm (SVC) is shown and no patent foramen ovale is seen. LA = Left atrium;
or less in diameter. Though it is very small, it is sufficient to RA = Right atrium
8 considered to be an integral part of HLHS, although it may ventricular output to go to the lungs instead of the body.
be present in the syndrome of mitral atresia with normal Although increased pulmonary blood flow results in higher
aortic root. A patent ductus arteriosus is usually present and is oxygen saturation, systemic blood flow is compromized.
CyanotiC Heart diseases
required for survival. When the systemic blood flow decreases below a critical
Severely hypoplastic LV may also be present in hearts with level, the perfusion becomes poor and metabolic acidosis
double-outlet RV with mitral atresia, unbalanced complete and oliguria may develop. There is also decreased flow to
atrioventricular canal and other complex heart defects; in the coronary arteries and brain, with a risk of myocardial or
some studies, these variants constitute as many as 25 percent cerebral ischemia respectively. Alternatively, if pulmonary
of HLHS cases.11,12 vascular resistance is significantly higher than systemic
vascular resistance, there will be hypoxemia.
PRENATAL CIRCULATION In summary, the postnatal circulation in HLHS depends on
three major factors:
In a normally formed fetus, highly saturated inferior vena 1. Adequacy of interatrial communication.
caval blood is preferentially shunted into the left atrium via 2. Patency of the ductus arteriosus.
the patent foramen ovale and from there into the LV and aorta. 3. Level of pulmonary vascular resistance.
The superior vena caval blood containing desaturated blood
is directed towards the tricuspid valve (TV), and RV and EPIDEMIOLOGY
from there into the pulmonary arteries, ductus arteriosus and
descending aorta. By contrast, in HLHS the oxygenated blood The incidence of HLHS is 0.16 to 0.36 per 1,000 live
from the placenta is returned to the inferior vena cava (IVC) births.15 It comprises 1.2 to 1.5 percent of all congenital heart
and instead of shunting across the patent foramen ovale into defects.16, 17 HLHS accounts for 7 to 9 percent of all congenital
the left atrium, it mixes with the superior vena caval blood heart disease diagnosed in the first year of life.12 Before
in the right atrium. The pulmonary venous drainage from left surgical treatment was available, HLHS was responsible
atrium gets shunted across the atrial septum into the right for 25 percent of cardiac deaths in the neonatal period.12
atrium because of MV obstruction. Right ventricle receives The recurrence risk of HLHS in families with one affected
a mixture of vena caval and pulmonary venous and coronary child is 0.5 percent and the recurrence risk for other forms of
sinus blood.13,14 congenital heart disease in families is 2.2 to 13.5 percent.18-20
Because of widely patent ductus arteriosus and high Bicuspid aortic valve was identified in 5 to 11 percent of
pulmonary vascular resistance in the fetus, only a small portion first-degree relatives of affected probands. The incidence of
of the blood from the RV enters the lungs. Most of the blood HLHS is higher in patients with Turner syndrome, Noonan
is directed into the aorta via the ductus. Once in the aorta, syndrome, Smith-Lemli-Opitz syndrome and Holt-Oram
the blood gets distributed into the brachiocephalic vessels, syndrome. Certain chromosomal duplications, translocations
ascending aorta and descending aorta. The quantitative and deletions are also associated with HLHS.
distribution into these different vascular beds depends on their
relative vascular resistances. The ascending aortic blood flows GENDER
in a reverse direction and supplies the coronary arteries.
The HLHS is more common in males than in females, with a
POSTNATAL CIRCULATION 55 to 70 percent male preponderance.
The newborn infant with HLHS has a complex cardiovascular AGE AT PRESENTATION
physiology. Fully saturated pulmonary venous blood
returning to the left atrium cannot flow into the LV because Babies with HLHS typically present within the first 24 to
of atresia, hypoplasia, or stenosis of the MV. Therefore, 48 hours of life. Presentation occurs as soon as the ductus
pulmonary venous blood must cross the atrial septum. This arteriosus begins to constrict, which decreases the systemic
blood mixes with desaturated systemic venous blood in the blood flow, producing shock and, without intervention, causes
right atrium and from there transmitted into the RV. The RV death. Infants with pulmonary venous obstruction (absent or
then must pump this mixed blood to both the pulmonary and restrictive patent foramen ovale) may present even sooner.
the systemic circulations that are connected in parallel, rather Very rarely, an infant with persistence of high PVR and widely
than in series, by the ductus arteriosus. Blood exiting the RV open ductus arteriosus may present later, because of balanced
may flow into the lungs via the branch pulmonary arteries or pulmonary and systemic circulations.
into the body via the ductus arteriosus.
The relative flows to the pulmonary and systemic circuits MORTALITY/MORBIDITY
depend on the relative resistances of the two vascular beds.
666 Following birth, pulmonary vascular resistance (PVR) Without surgery, HLHS is uniformly fatal, usually within the
decreases, this allows a higher percentage of the right first 2 weeks of life. As alluded to above, survival for a longer
period occurs rarely and is related to persistence of the ductus infants, significant obstruction to pulmonary venous return 47
arteriosus along with balanced systemic and pulmonary (a congenitally small or absent (Figure 1) patent foramen
circulations. ovale) is usually present.
HypoplastiC leFt Heart syndrome

Following the Norwood procedure, overall success
(survival to hospital discharge) is approximately 75 percent.12 PHYSICAL FINDINGS
Success rates are higher (85%) in patients with no or low
number of preoperative risk factors and lower (45%) in Before the initiation of PGE1 infusion to reestablish patency
patients with important and/or multiple risk factors. The risk of the ductus arteriosus, infants may exhibit signs of
factors for poor result include prematurity and major non- cardiogenic shock, including the following: hypothermia,
cardiac malformations. Other identified risk factors include tachycardia, respiratory distress, central cyanosis and pallor,
surgery in older infants, significant tricuspid regurgitation and poor peripheral perfusion with weak pulses in all extremities
pulmonary venous hypertension. High Aristotle scores are and hepatosplenomegaly.
also associated with poor prognosis. After re-establishment of systemic blood flow via the
Orthotopic heart transplantation results in early and long- ductus arteriosus, signs of shock resolve, with the infant in
term success similar to that of staged reconstruction. Among more stable condition, but with tachycardia, tachypnea, and
low-risk patients who undergo staged reconstruction or mild central cyanosis. If coarctation of the aorta is present,
transplantation, actuarial survival at 5 years is approximately arterial pulses in the legs may be more prominent than those
70 percent. in the arms, particularly the right arm. Other findings are
Most studies report neurodevelopmental disabilities in prominent right ventricular impulse, normal first heart sound
a significant number of patients who survive either staged and a loud, single second heart sound. Usually no murmur is
surgical reconstruction (Norwood/bidirectional Glenn/Fontan) noted; however, a nonspecific, soft, systolic ejection murmur
or cardiac transplantation. along the left sternal border; high-pitched holosystolic
murmur at the lower left sternal border, indicating tricuspid
CLINICAL FEATURES regurgitation and diastolic flow rumble over the precordium,
indicating increased right ventricular diastolic filling may be
heard.
History
The fetus grows and develops normally because the fetal Laboratory Studies
circulation is not significantly altered.11,21 Pregnancies are
typically uncomplicated. Most neonates are born at term and
Chest X-ray
initially appear normal.
In the current era, especially in the developed countries, The findings on chest X-ray are generally nondiagnostic, but
most of HLHS cases are diagnosed prenatally with an reflect the volume of pulmonary blood flow and degree of
abnormal four-chamber view in the screening obstetric atrial level shunting. With restrictive atrial shunt there will
ultrasound.22 Prenatal diagnosis of the disease allows adequate be evidence of pulmonary edema, while with nonrestrictive
time for parental counseling and as well as delivery planning atrial level shunt, there will be cardiomegaly and increase
at a tertiary care hospital, which also avoids transport-related pulmonary vascular markings (Figure 2).
morbidities. Following delivery, patient should be started
on prostaglandin E1 (PGE1) to maintain ductal patency and Electrocardiogram
should have an echocardiogram to confirm the prenatal
diagnosis of HLHS and to assess the adequacy of the atrial The electrocardiogram may not be diagnostic in neonates.
septal communication. Right axis deviation and right ventricular hypertrophy are
In neonates with no prenatal diagnosis of HLHS, the time common, but not distinctly different from the electrocardiogram
of presentation depends on degree of atrial level restriction, of the normal neonate. Decreased left ventricular forces may
ductal patency and the level of PVR. Most neonates are born be noted in the left precordial leads.
at term and initially appear normal. As the ductus arteriosus
begins to close (normally over the first 24–48 hours of life), Echocardiogram
symptoms of cyanosis, tachypnea, respiratory distress, pallor,
lethargy, metabolic acidosis, and oliguria develop. Without Echocardiography is the test of choice for diagnosing HLHS.
intervention to reopen the ductus arteriosus, death rapidly Two dimensional imaging readily shows the hypoplastic
ensues. Similar symptomatology may be expected if a LV and aorta (Figures 3A and B) and enlarged right atrium,
precipitous drop in PVR occurs. RV and main pulmonary artery (Figures 3 and 4). The
Occasionally, respiratory symptoms and profound degree of hypoplasia of the left heart structures is variable,
cyanosis are apparent at birth (2–5% of cases). In these 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

Magnetic resonance imaging (MRI) and computed tomo-
graphy (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
Figure 2: Chest roentgenogram in an infant with hypoplastic left heart central nervous system abnormality and abdominal ultrasound
syndrome demonstrating cardiomegaly and increased pulmonary to evaluate for renal anomalies are performed prior to the
vascular markings Norwood procedure or heart transplantation.
a B
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
668 atrium
47

a B
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)
a B C
d e F
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
8
a B
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
a B
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
670 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 Cardiac catheterization is also a standard procedure before 47
the Fontan conversion operation. Hemodynamic data to
Complete blood count (CBC) count, WBC count with dif- calculate PVR and transpulmonary gradients are obtained to

ferential, electrolytes, blood urea nitrogen (BUN)/creatinine, assess the suitability for next stage procedure. Angiograms are
liver function tests, arterial blood gases, lactic acid and karyo- obtained in similar fashion to pre-Glenn catheterization. The
type may be performed as indicated. pulmonary artery angiograms are done via superior vena cava
(Figure 9). Coil embolization of collateral vessels (Figures 10
CARDIAC CATHETERIZATION AND ANGIOGRAPHY and 11) is usually done at this time.
As indicated above, cardiac catheterization is rarely necessary for CATHETER INTERVENTIONS

diagnostic purposes in the newborn period; it may be performed
in cases with markedly restrictive interatrial communication or In the neonate, obstruction at the level of patent foramen
intact atrial septum. In these cases, transcatheter opening of the ovale may be relieved by balloon/blade atrial septostomy.23-25
atrial septum23-25 is undertaken to create an atrial septal defect In most cases, balloon/blade atrial septostomy is not possible
to relieve left atrial hypertension and pulmonary edema before because of hypoplastic left atrium; static dilation of the atrial
the stage I surgical (Norwood procedure). septum with a balloon angioplasty catheter can be done to
Routine cardiac catheterization at age 6 months prior to relieve the obstruction.25-27 If the atrial septum is extremely
bidirectional Glenn or hemi-Fontan operations is performed. thick with a markedly restrictive atrial septum, stent (Figures
This is to obtain hemodynamic data, to calculate PVR, to 12A and B) implantation25,28,29 to keep the atrial septum open
evaluate the size and pressures in the pulmonary arteries and may become necessary.
to assess the suitability for next stage procedure. Angiograms In some patients, the atrial septum may be intact or have
are obtained to assess the right ventricular function, tricuspid a very small patent foramen ovale that may not even allow
regurgitation and also to assess the branch pulmonary passage of a catheter. In such situations, puncture of the atrial
artery anatomy (Figures 8A and B) and to rule out recurrent septum by a Brockenbrough technique30,31 or by radiofrequency
aortic coarctation and aortopulmonary collateral vessels. If perforation32 followed by static balloon atrial septal dilatation
significant collateral vessels are found they may be occluded or, preferably, stent implantation25,28,29 may be performed.
with coils at the same time. Similarly, balloon angioplasty of In patients with hypoxemia due to clotted Blalock-Taussig
aortic coarctation is performed as indicated. (BT) shunts after stage I palliation and if the patient is not
a B
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 671
(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
8 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
Figure 9: Selected frame from superior vena caval cineangiogram in an bronchitis or protein-losing enteropathy.45 In these patients,
infant with hypoplastic left heart syndrome following Norwood procedure
with subsequent bidirectional Glenn procedure demonstrating right
following exclusion of obstructive lesion in the Fontan circuit,
(RPA) and left (LPA) pulmonary arteries and no obstruction at the puncture of the conduit wall by a Brockenbrough technique
superior vena cava (SVC) pulmonary artery junction. A stent placed followed by static balloon dilatation or stent implantation
previously for relieving interatrial obstruction is seen in the background. may be beneficial. In patients with fenestrated Fontan, the
ASD = Atrial septal defect
fenestration may be closed by transcatheter methods.46-48
a B
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
672
47

a B
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)
a 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
8 NATURAL HISTORY the infusion rate may be gradually decreased to a dose of
0.02 mcg/kg/minute. One should strive to maintain ductal
The natural history of untreated patients with hypoplastic left patency with the lowest effective PGE1 dose to minimize the
heart syndrome is uniformly poor. If untreated more than 95 dose-dependent side effects of PGE1 such as hypotension,
percent infants with HLHS die within the first month of life. prompting volume resuscitation and apnea and respiratory
HLHS accounts for 25 percent of deaths due to cardiac reasons depression, requiring mechanical ventilatory support.
in the first week and 15 percent of cardiac deaths during The PVR of a newborn is slightly less than the systemic
first month of life. If pulmonary and systemic resistances vascular resistance and begins to fall soon after birth. In
are balanced, survival for 4 to 6 years has been reported the patient with HLHS, decreased PVR causes progressive
sporadically. The patients usually die from congestive heart increase in pulmonary blood flow with a concomitant decrease
failure, myocardial ischemia and pulmonary vascular disease. in systemic blood flow. When severe, this results in systemic
hypoperfusion, metabolic acidosis and shock.
MANAGEMENT After establishing ductal patency, maneuvers should be
used to minimize systemic vascular resistance and maximize
A thorough explanation of different treatment approaches— PVR. It should be noted that maneuvers to increase PVR have
supportive care, multistage surgical palliation, cardiac been more efficacious. Intubation and mechanical ventilation
transplantation, including their advantages and disadvantages, with sedation and paralysis permits hypoventilation to
should be provided to the parents. Occasionally, some anatomic elevate the partial pressure of carbon dioxide (PaCO2). The
features favor one choice over the others. In the presence of chief metabolic factor that appears to influence pulmonary
severe TV or pulmonary valve anomalies, the multistage resistance in patients with HLHS is arterial PCO2 and should
surgical approach is not likely to be beneficial; cardiac be maintained in the range of 45 to 50 mm Hg. Metabolic
transplantation is the only surgical choice. In most cases, the acidosis should be corrected with sodium bicarbonate. The
choice of treatment is based on the parents’ preference. While hematocrit should be maintained between 40 to 45 percent
such a decision is being made, the infant should be stabilized to provide adequate oxygen carrying capacity and to increase
as discussed in the next section. the blood viscosity; the latter may also serve to elevate PVR.
If supportive care is chosen by the parents, they need strong Supplemental oxygen to increase the oxygen saturations
emotional support, because the condition is fatal without should be avoided.
active treatment. Subambient oxygen (FIO2 of 15–19%) with supplemental
nitrogen or carbon dioxide may be used to elevate PVR;
Preoperative Medical Care although this is an attractive concept, it should not be pursued
for long periods, because severe pulmonary hypertension may
In situations where prenatal diagnosis of HLHS by fetal complicate the postoperative course. However, this does not
echocardiography is made, it is advisable to have the baby seem to adversely affect the pulmonary vasculature on long-
deliver at an institution, where tertiary care, including term follow-up.50
neonatal cardiac surgery, is performed routinely. There was Because of obstruction at the mitral valve, pulmonary
some suggestion in the past that elective cesarean delivery venous blood must cross the atrial septum via a patent
may provide better outcomes. A recent study examining this foramen ovale (PFO) and mix with desaturated systemic
issue found that there was no hemodynamic advantage for venous blood in the right atrium. In some patients, the PFO
elective cesarean delivery section over vaginal delivery.49 may be restrictive. Mild restriction is acceptable and may be
Successful preoperative management encompasses address- beneficial in that it may maintain high PVR and promote good
ing three main aspects: systemic flow. Severe restriction may cause severe hypoxemia
1. Providing adequate systemic flow. and pulmonary edema. Periodic monitoring by echo-Doppler
2. Limiting pulmonary overcirculation. studies is recommended. In contrast to other patients with
3. Provide adequate egress of pulmonary venous return from HLHS, the patients with severe obstruction at PFO and
the left atrium. patients with intact septum do not show diastolic flow reversal
In HLHS, the blood flow to systemic circulation (coronary in the ductus arteriosus. When severe restriction develops,
arteries, brain, liver and kidneys) mainly depends on the transcatheter interventions to enlarge the atrial septal defect
patency of ductus arteriosus. Treatment with PGE1 should be may be performed. While Rashkind balloon septostomy and
initiated immediately after HLHS is diagnosed or suspected, Park blade septostomy are conventional methods to open atrial
to establish ductal patency and ensure adequate systemic septum, these may not be feasible because of hypoplastic left
perfusion. The patient’s physiologic state often directs initial atrium. Static dilatation of the atrial septum25-27 with a balloon
PGE1 dosing. For patients who present in shock with suspected angioplasty catheter may be used, which may not only relieve
ductal closure or a restrictive duct, initial dose will range from the obstruction, but also keep some restriction such that there
674 0.05 to 0.1 mcg/kg/minute. Once ductal patency is ensured, is no rapid fall in the pulmonary vascular resistance. Rarely
stent implantation25,28,29 may become necessary. Sometimes, 3. Anastmosis of the main pulmonary artery to the aorta with 47
it may be impossible to stabilize them medically or in the or without homograft material in order to provide systemic
cardiac catheterization laboratory and such patients may blood flow.

require emergency surgery. 4. Addressing aortic coarctation, if present and
Infants should remain in room air with acceptable oxygen 5. Aorta-to-pulmonary artery shunt, most commonly, a
saturation (by pulse oximetry) in the low 70s. Ventilation with modified BT shunt to provide pulmonary blood flow.
high fraction of inspired oxygen (FiO2) should be completely Some surgeons have modified the procedure further by
avoided, as supplemental oxygen decreases the PVR resulting insertion of a Gore-Tex graft in the right ventricular outflow
in increased pulmonary blood flow and decreased systemic tract, connecting it to the pulmonary artery (instead of conven-
perfusion. In these settings, even though the peripheral blood tional modified BT shunt) as initially described by Sano and his
oxygen saturation is higher, oxygen delivery to the tissues is colleagues.58,59 The perceived advantage of Sano shunt is the
lower and metabolic acidosis ensues. The exception to this avoidance of aorto-pulmonary runoff resulting in higher coro-
is the infant with severe hypoxemia caused by pulmonary nary and systemic perfusion pressures, which may potentially
venous hypertension. lessen the incidence of ventricular ischemia. Early hemodynam-
Inotropic support is indicated only in severely ill neonates ic studies60,61 documented higher diastolic perfusion pressures.
with concurrent sepsis or profound cardiogenic shock and However, both single institutional61 and multi-institutional62
acidosis. The administration of inotropes can adversely studies comparing the two techniques have not demonstrated
affect the balance between pulmonary and systemic vascular significant advantage of one technique over the other.
resistance and should be weaned off as soon as the baby is
stabilized. While overall cardiac output may be increased, Postoperative management: It begins in the operating room
peripheral perfusion can decrease with inotropic support and with separation from cardiopulmonary bypass. If there is no
may become deleterious. Diuretics can be used to manage umbilical arterial catheter, a peripheral indwelling arterial line
pulmonary overcirculation before surgery. should be inserted. Milrinone is started at maintenance dose
It is important to recognize that the status of PVR can of 0.05 mcg/kg/min in the operating room. Inotropic support
change rapidly and close monitoring of the patients, until is initiated and the patient is weaned from cardiopulmonary
Norwood procedure with interventions several times a day support, with adjustment of inotropic support as necessary.
may become necessary. Renal and hepatic failure due to poor Temporary epicardial atrial and ventricular pacing wires
perfusion should be recognized and treated. are placed. In patients with excessive myocardial edema,
cardiopulmonary instability or mediastinal bleeding, the
Surgical Care/Multistage Surgery chest is left open, with a patch of silicone elastomer sutured
to the skin for coverage of the incision.63,64 After stabilizing
Sinha,21 Caylor51 and Dotty52 and their associates proposed the patient hemodynamically, closure of the chest may be
various palliative operations; however, significant survival performed in the intensive care unit. If the chest is open,
was not achieved, until Norwood and associates3,4 mechanical ventilation and milrinone is continued until
demonstrated that a multistage operative approach could chest closure and then, they may be weaned. The ventilator
be used to treat HLHS. The concepts and procedures settings commonly used in immediate postoperative period
described by Fontan,53 Kreutzer,54 de Leval55 and others56,57 are pressure regulated, volume controlled mode and positive
initially to address tricuspid atresia were extended to treat end expiratory pressure of 3 to 5 mm Hg.
other cardiac defects with a functionally single ventricle, In the intensive care unit, infants are usually monitored with
including HLHS. surface electrocardiograms, pulse oximetry, central venous
The purpose of surgical reconstruction of HLHS is to pressures and near infrared spectroscopy. Arterial blood
eventually separate the pulmonary and systemic circulations gases and echocardiograms are usually done intermittently
to achieve a ‘Fontan’ circulation. The right ventricle becomes as needed. The usual problems encountered in immediate
systemic ventricle, while the flow to the lungs is via the Fontan postoperative period are:
connections. The multistage reconstruction is accomplished in 1. Low cardiac output: It can occur usually in the first 24 to
the three stages: 48 hours after Norwood procedure. Typical findings are
tachycardia, hypotension, oliguria and metabolic acidosis.
Norwood Procedure (Stage I) In these particular situations, the arterial and mixed venous
saturation difference can be a sensitive predictor of low
Norwood procedure is performed in the first week of life systemic blood flow. The potential causes of low systemic
following stabilization in the neonatal intensive care unit. The cardiac output are:
Norwood procedure3,4 consists of: a. Globally decreased ventricular function.
1. Atrial septectomy to provide unrestricted blood flow across b. Elevated pulmonary systemic flow ratio (Qp : Qs),
the atrial septum. adequate saturation with maldistribution of flow. 675
2. Ductal ligation. c. Atrioventricular (AV) valve regurgitation.
8 The combination of AV oxygen saturation difference and systemic pressures. In the presence of aortic obstruction, the
echocardiographic evaluation of ventricular function and right ventricular systolic function may decrease rapidly. The
AV valve regurgitation is important in establishing the physical examination and femoral pulses can be misleading in
cause and initiation of treatment. Infant with decreased these cases, because of obligatory runoff through the systemic
ventricular function may benefit from increasing the to pulmonary artery shunt.
inotropic support, where as infants with adequate function, The incidence of interstage mortality is 5 to 15 percent.65
but high QP : QS benefit from maneuvers to increase the The presence of a restrictive atrial communication, aortic arch
PVR and/or by lowering the systemic vascular resistance. obstruction, obstructed shunt flow, pulmonary artery distortion
2. Cyanosis: The possible reasons for cyanosis include, and AV valve insufficiency are associated with interstage
a. Pulmonary venous desaturation from lung pathology mortality.65 Commonly acquired childhood gastrointestinal
(pneumothorax, pleural effusion, pneumonia, infection, or respiratory diseases, which result in hypovolemia and/
pulmonary edema) or acute hypoxemia have also been implicated as causes for
b. Systemic venous desaturation (anemia, low systemic interstage death.65 After successful stage I palliation, any
cardiac output) of the above-mentioned pathologic processes can lead to
c. Decreased pulmonary blood flow (elevated PVR, increased metabolic demands and an unfavorable oxygen
pulmonary venous hypertension, restrictive the atrial supply/demand relationship, placing the infant with minimal
septal defect, distortion of pulmonary arteries, small or myocardial reserve at even greater risk for mortality, until
occlusion of systemic to pulmonary artery shunt). progression to cavopulmonary anastomosis. Therefore,
Pulmonary venous desaturation is evaluated typically transitioning infants to home after stage I palliation warrants
with chest radiograph and auscultation. Systemic venous ongoing vigilance well beyond the initial early postoperative
desaturation can be evaluated by mixed venous oxygen period. Careful home surveillance and optimal nutrition with
saturation and hemoglobin and hematocrit. Sometimes good growth may reduce inter-stage mortality.66,67
cardiac catheterization may be necessary to identify the
anatomic (shunt related) or physiologic (PVR related) Bidirectional Glenn Procedure (Stage II)
causes of decreased QP : QS ratio.
3. High oxygen saturation: Infants with high oxygen Bidirectional Glenn procedure is usually performed 6 months
saturations more than 90 percent, typically have low PVR following Norwood procedure. Prior to bidirectional Glenn,
and pulmonary blood flow in excess of systemic blood cardiac catheterization is performed to assess right ventricular
flow. Also, evaluation for arch obstruction is important, function, pulmonary artery size and anatomy, PVR and
since distal obstruction will force more blood through the coarctation of the aorta. Transcatheter occlusion of collateral
shunt and increase the Qp at the expense of Qs. vessels, balloon angioplasty/stent of branch pulmonary artery
In the intensive care unit, the management mainly depends stenosis and balloon angioplasty of aortic coarctation are
on optimizing the cardiac output (inotropic and lusitropic performed as indicated.
support) and optimizing the nutrition as soon as possible and The bidirectional Glenn procedure consists of performing
removing the unnecessary indwelling catheters early. Since an anastomosis between the SVC and the right pulmonary
the babies with HLHS may not have been fed orally prior to artery, end-to-side, so that venous return from the upper part
surgery, suck and swallow coordination may be delayed. of the body flows directly into both lungs. If a persistent
left SVC is present, especially in the absence of or a small
Follow-up: Upon hospital discharge, most infants receive bridging innominate vein, bilateral bidirectional Glenn shunts
digoxin to augment cardiac function, minimal diuretics to help should be performed. In the hemi-Fontan, the SVC-right atrial
manage right ventricular volume overload and aspirin to prevent junction is either closed with a patch or SVC is constricted
thrombosis of the shunt. If significant tricuspid regurgitation is with polydioaxanone thread that is reopened during the next
present, afterload reduction with captopril11 should be used. stage. Blood from the IVC continues to drain into the right
Caution should be exercised in patients receiving diuretic atrium. The BT or Sano shunt that was placed at stage I is
therapy to avoid intravascular volume depletion that might liagated.
reduce total cardiac output, as well as increase the risk of Repair of pulmonary artery narrowing, if present and
shunt thrombosis owing to hyperviscosity. Oxygen saturation addressing TV regurgitation, restrictive atrial septum and
is typically 70 to 80 percent in room air and should not be any other abnormalities should be undertaken at the time of
of concern. Periodic (every 4 week or as clinically indicated) bidirectional Glenn.
cardiology evaluations are essential for detection of potential
complications such as aortic arch obstruction, adequacy of Follow-up after stage II: The follow-up after bidirectional
the BT or Sano shunt, atrial septal defect obstruction and Glenn is also necessary, although the infants are more stable
significant tricuspid regurgitation. In patients with HLHS after than after Norwood. Interstage mortality68 also exists, but not
676 Norwood, the RV is volume overloaded and has to generate as high as seen between stages I and II.
Fontan Procedure (Stage III) in total cavopulmonary connections. Obstructed pulmonary 47
outflow pathways, persistent shunts and systemic venous
Fontan procedure is performed approximately 12 months after congestion including protein-losing enteropathy45,74 may

the bidirectional Glenn or an approximate patient weight of occur. Symptoms and signs indicative of obstruction to Fontan
15 kg. Again, prior to the Fontan procedure, cardiac pathways should be promptly scrutinized. Poor echo windows
catheterization is performed to examine the same issues outlined make non-invasive evaluation difficult and therefore, cardiac
in bidirectional Glenn section. Transcatheter interventional catheterization and angiography may become necessary.
procedures should be performed, as necessary. The need Identified obstructive lesions should be treated with balloon
for occlusion of collateral vessels is more frequent prior to angioplasty, stenting,75 or even surgery, as necessary. A
Fontan than prior to bidirectional Glenn. We routinely perform persistent shunt, secondary to intentional fenestration should
descending aortic and selective left and right subclavian artery be closed46,75-77 six to 12 months after fenestrated Fontan
cineangiograms to detect collateral vessels. surgery, preferably by a transcatheter device (Figures 13A and
In Fontan procedure, blood flow from the IVC is B). Test occlusion of the fenestration is desirable to ensure
directed to the pulmonary arteries either via a lateral tunnel that adequate cardiac output is maintained after occlusion.
procedure55 or via an extracardiac conduit.69 Extracardiac Sometimes, systemic venous to left heart collateral vessels
conduit diversion of inferior vena caval blood into the right cause arterial desaturation and these should be closed by coils
pulmonary artery is currently preferred by most surgeons. or devices (Figures 14A and B), as appropriate.
To address the growth issue related to extracardiac Fontan, Protein-losing enteropathy,45,74 though less commonly seen
some surgeons use autologous pericardial roll grafts. At the than in the past, carries a high (75%) mortality. It appears to be
conclusion of the procedure, systemic venous blood returns to related to loss of protein in the bowel by lymphatic distention
the lungs passively without passing through a ventricle. secondary to increased systemic venous pressure, although this
Fenestrated Fontan: Choussat et al70 devised criteria for can occur in patients with reasonably ‘normal’ pulmonary artery
successful Fontan operation. Many cardiologists and surgeons pressures for the Fontan procedure; however the cause of protein-
have modified these criteria. These factors should be identified losing enteropathy is unknown. Symptoms include diarrhea,
at the time of preoperative evaluation and include elevated edema, ascites and pleural effusion. Decreased albumin in the
pulmonary artery pressure (mean pressure >18 mm Hg) or serum and increased a1-antitrypsin in the stool are present. If there
resistance (> 4 Wood units/m2), distorted or small (McGoon is evidence for obstruction of the Fontan pathway, it should be
ratio of 1.8 or less) pulmonary arteries, poor ventricular relieved. Medium-chain triglyceride diet and parenteral albumin
function (end-diastolic pressure above 12 mm Hg), significant supplementation may help to stabilize the situation. A number of
tricuspid regurgitation and others. Patients violating these treatment options have been explored and include prednisone,
criteria are at a higher risk for poor prognosis following regular high-molecular-weight heparin, low-molecular-weight
Fontan operation than patients within the set limits. In this heparin, an elementary diet, calcium replacement, somatostatin,
high-risk group, a concept of leaving a small atrial septal high-dose spironolactone, sildenafil and resection of localized
defect open to facilitate decompression of the right atrium was intestinal lymphangiectasia (if demonstrated), all with variable
proposed. Billingsley, Laks and their associates71,72 advocated success. Because protein-losing enteropathy appears to be a fatal
closure of the atrial defect by constricting the preplaced complication of the Fontan procedure, aggressive management
suture in the postoperative period, while Bridges et al73 used is suggested. In these patients with so called ‘failed Fontan,’
a transcatheter closure techniques. Improvement in cardiac after excluding and addressing obstructions and residual shunts
index, decreased postoperative pleural effusions and systemic apart from other conventional treatment, consideration for;
venous congestion and possibly shorter hospitalization 1. Reduction of conduit pressure by creation of defect in the
have been observed after fenestration, but at the expense of conduit to allow right-to-left shunt.75,78
systemic arterial hypoxemia. Although the fenestrated Fontan 2. Atrioventricular sequential pacing.79,80
was initially conceived for high-risk patients, it has since been 3. Cardiac transplantation81,82 should be given.
used in patients with modest or even low risk. However, most patients do well after the Fontan procedure.
Follow-up after Fontan: Periodic follow-up after Fontan is
recommended. Inotropic and diuretic medications should Surgical Care/Cardiac Transplantation
be weaned. Afterload reduction with an angiotensin-
converting enzyme inhibitor is presumed to be beneficial and Heart transplantation is another surgical option,5 used as an
recommended. We use platelet-inhibiting doses of aspirin to alternative to multistage surgery. The infant should receive
prevent development of thrombi in the conduit, while some continuous infusion on PGE1 to keep the ductus arteriosus
cardiologists utilize warfarin anticoagulation. While most patent, while waiting for a donor heart to become available.
patients do well after the multistage surgery, several problems Nearly 20 percent of infants listed for cardiac transplantation
have been observed during follow-up. die, while waiting for a suitable donor organ. Furthermore,
Arrhythmias which were common problems in patients with following successful heart transplantation, all patients require 677
atriopulmonary connection type of Fontan are less frequent multiple medications for immune modulation and prevention
8
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 bidirectional Glenn shunt performed. This appears to shift
rejection early and multiple hospitalizations for treatment of some of the early mortality of Norwood to stage II. This is
infection and suspected rejection. Periodic endomyocardial followed by Fontan conversion with an extracardiac conduit.
biopsy is required for more precise monitoring. However, Although reduction of early mortality is theoretically feasible,
the long-term survival following both surgical approaches is larger experience with this approach than is currently available
similar. At most institutions heart transplantation is no longer is necessary prior to general adaptation of this method of
the first option for management of HLHS patients. management of all HLHS patients. Some comparisons of
hybrid with conventional Norwood84,85 did not demonstrate
EMERGING THERAPIES significant difference. Other new approaches such as double
shunt technique for hybrid palliation86 are being attempted.
Hybrid Approach to Hypoplastic Left Heart Syndrome
Prevention by Fetal Intervention
Banding of both the branch pulmonary arteries via median
sternotomy and implanting stent in the ductus arteriosus is Fetal echocardiographic studies have shown development of
performed initially.83 At the time of the second stage, aortic HLHS in fetuses initially found to have severe/critical aortic
678 arch is reconstructed, atrial septectomy carried out and stenosis. Fetal intervention to relieve aortic valve stenosis
47

a B
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 actuarial survival rate after staged reconstruction is 70 percent
development of the LV.87 Further experience/research into this at 5 years. Neurodevelopmental prognosis is not known; how-
type of approach is needed. ever, abnormalities are reported.91,92 Approximately 20 percent
of infants listed for cardiac transplantation die, while waiting for
Catheter-assisted Fontan a donor heart. After successful transplantation, the survival rate
at 5 years is approximately 80 percent. When the preoperative
Konert et al88 proposed a staged surgical-catheter approach; mortality is considered, the overall survival rate after cardiac
they performed a modified hemi-Fontan procedure instead transplantation is approximately 70 percent, or similar to the re-
of bidirectional Glenn shunt that is later completed by sults for staged reconstruction.
transcatheter methodology. This reduces the total number of
operations required. This concept has not been tried for post- SUMMARY AND CONCLUSION
Norwood HLHS patients.
Hypoplastic left heart syndrome (HLHS) is an assortment
PROGNOSIS of left heart anomalies including a very small left ventricle
with under development of the mitral and aortic valves and
The survival rate of infants treated with both multistage a small and hypoplastic aorta. A patent foramen ovale and a
surgery and cardiac transplantation is similar to that of infants patent ductus arteriosus are usually present and are necessary
with other complex forms of congenital heart disease in which a for survival. Coarctation of the aorta may also be present.
two-ventricle repair is not possible. The major mortality is at the Pulmonary venous blood crosses the atrial septum and mixes
time of Norwood, stage I. Overall survival at hospital discharge with systemic venous blood in the right atrium and from there
after the Norwood procedure is nearly 75 percent.89 Success rates passed on into the right ventricle and the pulmonary artery.
are higher in uncomplicated cases and lower in cases in whom The pulmonary and the systemic circulations are connected
significant preoperative risk factors are present, such as age in parallel by the ductus arteriosus and the blood exiting the
greater than 1 month, significant tricuspid insufficiency, pul- right ventricle is distributed into the lungs via the branch
monary venous hypertension, associated major chromosomal pulmonary arteries and into body via the ductus arteriosus.
or noncardiac abnormalities, prematurity and high Aristotle HLHS comprises 1.2 to 1.5 percent of all congenital heart de-
scores (> 20).90 Survival after the bidirectional Glenn/hemi- fects and is a uniformly lethal unless it is promptly identified,
Fontan and Fontan operations is nearly 90 to 95 percent. The treated with PGE1 and surgically palliated. They are clinically 679
8 identified either by prenatal ultrasound or present after birth 10. Rychik J, Rome JJ, Collins MH, et al. The hypoplastic left
heart syndrome with intact atrial septum: atrial morphology,
with symptoms as the ductus begins to close. The time of
presentation depends on the degree of atrial level obstruction, pulmonary vascular histopathology and outcome. J Am Coll
ductal patency and the level of pulmonary vascular resistance. Cardiol. 1999;34:554-60.
11. Rao PS, Striepe V, Merrill WH. Hypoplastic left heart syndrome.
The diagnosis can usually made with echo-Doppler studies.
In: Kambam J (Ed). Cardiac Anesthesia for Infants and Children.
The initial management of HLHS is by prompt infusion of
St Louis, MO: Mosby-Year Book 1994. pp. 296-309.
PGE1 to keep the ductus open. Balancing the pulmonary and 12. Norwood WI Jr. Hypoplastic left heart syndrome. Ann Thorac
systemic circulation to maintain sufficient systemic perfusion Surg. 1991;52:688-95.
and ensuring adequacy of the patent foramen ovale for easy 13. Rudolph AM. Congenital Diseases of the Heart. Chicago: Year
egress of the left atrial blood while waiting for surgery are the Book Medical; 1974.
next tasks. 14. Rao PS. Fetal and neonatal circulation. In: Kambam J (Ed).
Surgical management is either by multistage surgical proce- Cardiac Anesthesia for Infants and Children. St Louis, MO:
dures, consisting of Norwood procedure (stage I) in the neonatal Mosby-Year Book; 1994. Chapter 2. pp. 10-19.
15. Fyler DC. Report of the New England Regional Infant Cardiac
period, hemi-Fontan or bidirectional Glenn procedure (stage II)
Program. Pediatrics. 1980;65:375-461.
at about six months of age, and Fontan conversion (stage III)
16. Freedom RM. Aortic atresia. In: Keith JD, Rowe RD, Vlad P.
one or more years later or by orthotopic heart transplantation. (Eds). Heart Disease in Infants and Children, 3rd edition. New
Currently, the actuarial survival rate of infants treated with these York: Mcmillian; 1978.
surgical approaches is 70 percent at 5 years and is similar to that 17. Fyler DC. Prevalence trends. In: Fyler DC. (Ed). Nadas‘
of infants with other complex forms of congenital heart disease Pediatric Cardiology, Philadelphia: Hanley and Belfus; 1992.
in whom a two-ventricle repair is not possible. Continued fol- 18. Holmes LB, Rose V, Child AH. Comment on hypoplastic left
low-up both after Fontan conversion and orthotopic heart trans- heart syndrome. In: Daniel Bergsma (Ed). Clinical Delineation
plantation is mandatory to address problems associated with of Birth Defects, Part 16: Urinary System and Others.
Baltimore: Williams and Wilkins; 1972. pp. 228-30.
both these modalities of treatment.
19. Nora JJ, Nora AH. Genetics and Counseling in Cardiovascular
Diseases. Springfield, IL: Charles C Thomas Publisher; 1978.
Disease is war with the laws of our being, and all war, as a 20. Boughman JA, Berg KA, Astemborski JA, et al. Familial
great general has said, is hell. risks of congenital heart defect assessed in a population-based
— Lewis G Janes epidemiologic study. Am J Med Genet. 1987;26:839-49.
21. Sihha SN, Rusnak SL, Sommers HM, et al. Hypoplastic left
ventricle syndrome. Analysis of 30 autopsy cases in infants
REFERENCES with surgical considerations. Am J Cardiol. 1968;21:166.
22. Galindo A, Nieto O, Villagra S, et al. Hypoplastic left heart
1. Noonan JA, Nadas AS. The hypoplastic left heart syndrome an syndrome diagnosed in fetal life: associated findings, pregnancy
analysis of 101 cases. Pediat Clinics North Am. 1958;5:1029. outcome and results of palliative surgery. Ultrasound Obstet
2. Lev M, Arcilla R, Rimoldi HJ, et al. Premature narrowing or Gynecol. 2009;33:560-66.
closure of foramen ovale. Am Hear J. 1963;65:638. 23. Rashkind WJ, Miller WW. Creation of an atrial septal defect
3. Norwood WI, Kirklin JK, Sanders SP. Hypoplastic left heart without thoracotomy. A palliative approach to complete trans-
syndrome: experience with palliative surgery. Am J Cardiol. position of the great arteries. 1966;196:991-92.
1980;45:87-91. 24. Park SC, Neches WH, Zuberbuhler JR, et al. Clinical use of
4. Norwood WI, Lang P, Hansen DD. Physiologic repair of blade atrial septostomy. Circulation. 1978;58:600-06.
aortic atresia-hypoplastic left heart syndrome. N Engl J Med. 25. Rao PS. Role of interventional cardiology in neonates: Part
1983;308:23-26. I. Non-surgical atrial septostomy. Congenital Cardiol Today.
5. Bailey L, Concepcion W, Shattuck H, et al. Method of heart 2007;5(12):01-12.
transplantation for treatment of hypoplastic left heart syndrome. 26. Shrivastava S, Radhakrishnan S, Dev V, et al. Balloon dilatation
J Thorac Cardiovasc Surg. 1986;92:01-05. of atrial septum in complete transposition of great artery—a new
6. Bharati S, Lev M. The surgical anatomy of hypoplasia of aortic technique. Indian Heart J. 1987;39:298-300.
tract complex. J Thorac Cardiovasc Surg. 1984;88:97-101. 27. Rao PS. Static balloon dilatation of the atrial septum. Am Heart
7. Von Rueden TJ, Knight L, Moller JH, et al. Coarctation of J. 1993;125:1826.
the aorta associated with aortic valvular atresia. Circulation. 28. Rao PS. Interventional pediatric cardiology: state of the art and
1975;52:951-54. future directions. Pediat Cardiol. 1998;19:107-24.
8. Jonas RA, Lang P, Hansen D, et al. First-stage palliation of 29. Atz AM, Feinstein JA, Jonas RA, et al. Preoperative
hypoplastic left heart syndrome. The importance of coarctation management of pulmonary venous hypertension in hypoplastic
and shunt size. J Thorac Cardiovasc Surg. 1986;92:6-13. left heart syndrome with restrictive atrial septal defect. Am J
9. Chin AJ, Weinberg PM, Barber G. Subcostal two-dimensional Cardiol. 1999;83:1224-28.
echocardiographic identification of anomalous attachment 30. Brockenbrough EC, Braunwald E, Ross J Jr. Transseptal left
of septum primum in patients with left atrioventricular valve heart catheterization. A review of 450 studies and description of
underdevelopment. J Am Coll Cardiol. 1990;15:678-81. an improved technique. Circulation. 1962;25:15-22.
680
31. Duff DF, Mullins CE. Transseptal left heart catheterization
in infants and children. Cathet Cardiovasc Diagn. 1978;4:
49. Peterson AL, Quartermain MD, Ades A, et al. Impact of mode of
delivery on markers of perinatal hemodynamics in infants with
47
213-23. hypoplastic left heart syndrome. J Pediatr. 2011;159:64-69.

32. Justino H, Benson LN, Nykanen DG. Transcatheter creation 50. Day RW, Barton AJ, Pysher TJ, et al. Pulmonary vascular
of an atrial septal defect using radiofrequency perforation. resistance of children treated with nitrogen during early
Catheter Cardiovasc Interv. 2001;54:83-87. infancy. Ann Thorac Surg. 1998;65:1400-04.
33. Fischer DR, Park SC, Neches WH, et al. Successful dilatation 51. Cayler GG, Smeloff EA, Miller GE. Surgical palliation of
of stenotic Blalock-Taussig anastomosis by percutaneous hypoplastic left side of the heart. N Engl J Med. 1970;282:780.
transluminal balloon angioplasty. Am J Cardiol. 1985;55: 52. Dotty DB, Knott HW. Hypoplastic left heart syndrome.
861-62. Experience with an operation to establish functionally normal
34. Rao PS, Levy JM, Chopra PS. Balloon angioplasty of stenosed circulation. J Thorac Cardiovasc Surg. 1977;74:624.
Blalock-Taussig anastomosis: role of balloon-on-a-wire in 53. Fontan F, Baudet E. Surgical repair of tricuspid atresia. Thorax.
dilating occluded shunts. Am Heart J. 1990;120:1173-78. 1971;26:240-48.
35. Ormiston JA, Neutze JM, Calder AL, et al. Percutaneous 54. Kreutzer G, Bono H, Galindez E. Una operacion para la
balloon angioplasty for early postoperative modified Blalock- correccion de la atresia tricuspidea. Ninth Argentine Congress
Taussig shunt failure. Cathet Cardiovasc Diagn. 1993;29: of Cardiology, Oct. 31-Nov. 6. Buenos Aires, Argentina, 1971.
31-34. 55. de Leval MR, Kilner P, Gewillig M, et al. Total cavopulmonary
36. Zahn EM, Chang AC, Aldousany A, et al. Emergent stent connection: a logical alternative to atriopulmonary connection
placement for acute Blalock-Taussig shunt obstruction for complex Fontan operations. Experimental studies and early
after stage I Norwood surgery. Cathet Cardiovasc Diagn. clinical experience. J Thorac Cardiovasc Surg. 1988;96:682-95.
1997;42:191-94. 56. Haller JA, Adkins JC, Worthington M, et al. Experimental
37. Tsounias E, Rao PS. Stent therapy for clotted Blalock–Taussig studies on permanent bypass of the right heart. Surgery.
shunts. Congenital Cardiol Today. 2010;8:01-09. 1966;59:1128-32.
38. Petit CJ, Gillespie MJ, Kreutzer J, et al. Endovascular stents 57. Hopkins RA, Armstrong BE, Serwer GA, et al. Physiological
for relief of cyanosis in single-ventricle patients with shunt or rationale for a bidirectional cavopulmonary shunt. A versatile
conduit-dependent pulmonary blood flow. Catheter Cardiovasc complement to the Fontan principle. J Thorac Cardiovasc Surg.
Interv. 2006;68:280-86. 1985;90:391-98.
39. Eicken A, Genz T, Sebening W. Stenting of stenosed shunts in 58. Sano S, Ishino K, Kawada M, et al. Right ventricle-to-pulmonary
patients after a Norwood-Sano operation. Catheter Cardiovasc artery shunt in first-stage palliation of hypoplastic left heart
Interv. 2006;68:301-03. syndrome. J Thorac Cardiovasc Surg. 2003;126:504-10.
40. Siblini G, Rao PS, Nouri S, et al. Long-term follow-up results 59. Sano S, Ishino K, Kado H, et al. Outcome of right ventricle-to-
of balloon angioplasty of postoperative aortic recoarctation. pulmonary artery shunt in first-stage palliation of hypoplastic
Am J Cardiol. 1998;81:61-67. left heart syndrome: a multi-institutional study. Ann Thorac
41. Rao PS, Balfour IC, Singh GK, et al. Bridge stents in the Surg. 2004;78:1951-57; discussion 1957-1958.
management of obstructive vascular lesions in children. Am J 60. Pizarro C, Malec E, Maher KO, et al. Right ventricle to
Cardiol. 2001;88:699-702. pulmonary artery conduit improves outcome after stage I
42. Rao PS. Stents in the management of congenital heart disease Norwood for hypoplastic left heart syndrome. Circulation.
in pediatric and adult patients. Indian Heart J. 2001;53:714-30. 2003;108:II155-II160.
43. Siblini G, Rao PS. Coil Embolization in the Management of 61. Ghanayem NS, Jaquiss RD, Cava JR, et al. Early postoperative
Cardiac Problems in Children. J Invasive Cardiol. 1996;8: hemodynamic comparison of the right ventricle to pulmonary
332-40. artery conduit and the innominate artery to pulmonary artery
44. Rao PS. Transcatheter embolization of unwanted blood vessels shunt for hypoplastic left heart syndrome: Results of a single
in children. In: Rao PS, Kern MJ (Eds). Catheter Based institution randomized prospective study. Ann Thorac Surg.
Devices for Treatment of Noncoronary Cardiovascular Disease 2006;82:1603-09.
in Adults and Children. Philadelphia, PA: Lippincott, Williams 62. Ohye RG, Sleeper LA, Mahony L, et al. Pediatric Heart
and Wilkins; 2003. pp. 457-73. Network Investigators. Comparison of shunt types in the
45. Rao PS. Protein-losing enteropathy following the Fontan Norwood procedure for single-ventricle lesions. N Engl J Med.
operation (Editorial). J Invasive Cardiol. 2007;19:447-48. 2010;362:1980-92.
46. Rao PS, Chandar JS, Sideris EB. Role of inverted buttoned 63. McElhinney DB, Reddy VM, Parry AJ, et al. Management and
device in transcatheter occlusion of atrial septal defects or outcomes of delayed sternal closure after cardiac surgery in
patent foramen ovale with right-to-left shunting associated with neonates and infants. Crit Care Med. 2000;28:1180-84.
previously operated complex congenital cardiac anomalies. 64. Tabbutt S, Duncan BW, McLaughlin D, et al. Delayed sternal
Am J Cardiol. 1997;80:914-21. closure after cardiac operations in a pediatric population. J
47. Rao PS. Transcatheter closure of atrial septal defects with Thorac Cardiovasc Surg. 1997;113:886-93.
right-to-left shunt. In: Rao PS, Kern MJ. (Eds). Catheter Based 65. Tweddell JS, Hoffman GM, Mussatto KA, et al. Improved
Devices for Treatment of Noncoronary Cardiovascular Disease survival of patients undergoing palliation of hypoplastic left
in Adults and Children. Philadelphia, PA: Lippincott, Williams heart syndrome: lessons learned from 115 consecutive patients.
and Wilkins; 2003. pp. 119-28. Circulation. 2002;106:82-89.
48. Rao PS. Catheter-based device closure of Fontan fenestrations 66. Hehir DA, Cooper DS, Walters EM, et al. Feeding, growth,
681
(Letter). Catheter Cardiovasc Interv. 2001;52:407. nutrition, and optimal interstage surveillance for infants with
8 hypoplastic left heart syndrome. Cardiol Young. 2011;21: 80. Estner HL, Kolb C, Schmitt C, et al. Long-term transvenous
59-64. AV-sequential pacing in a failing atriopulmonary Fontan
67. Hansen JH, Furck AK, Petko C, et al. Use of surveillance patient. Int J Cardiol. 2008;127:e93-95.
criteria reduces interstage mortality after the Norwood operation 81. Gamba A, Merlo M, Fiocchi R, et al. Heart transplantation in
for hypoplastic left heart syndrome. Eur J Cardiothorac Surg. patients with previous Fontan operations. J Thorac Cardiovasc
2012;41:1013-18. Surg. 2004;127:555-62.
68. Carlo WF, Carberry KE, Heinle JS, et al. Interstage attrition 82. Jayakumar KA, Addonizio LJ, Kichuk-Chrisant MR, et al.
between bidirectional Glenn and Fontan palliation in children Cardiac transplantation after the Fontan or Glenn procedure. J
with hypoplastic left heart syndrome. J Thorac Cardiovasc Am Coll Cardiol. 2004;44:2065-72.
Surg. 2011;142:511-16. 83. Galantowicz M, Cheatham JP. Lessons learned from the
69. Marcelletti C, Corno A, Giannico S, et al. Inferior vena cava- development of a new hybrid strategy for the management of
pulmonary artery extracardiac conduit. A new form of right hypoplastic left heart syndrome. Pediatr Cardiol. 2005;26:
heart bypass. J Thorac Cardiovasc Surg. 1990;100:313-14. 190-99.
70. Choussat A, Fontan F, Besse P, et al. Selection criteria for 84. Photiadis J, Sinzobahamvya N, Hraška V, et al. Does bilateral
Fontan procedure. In: Anderson RH, Shinebourne EA (Eds) pulmonary banding in comparison to Norwood procedure
Paediatric Cardiology. Edinburgh: Churchill Livingstone; improve outcome in neonates with hypoplastic left heart
1978. p. 559. syndrome beyond second-stage palliation? A review of the
71. Billingsley AM, Laks H, Boyce SW, et al. Definitive repair in current literature. Thorac Cardiovasc Surg. 2012;60:181-88.
some patients with pulmonary atresia with intact ventricular 85. Hsia TY, Cosentino D, Corsini C, et al. Modeling of Congenital
septum. J Thorac Cardiovasc Surg. 1989;97:746-54. Hearts Alliance (MOCHA) Investigators. Use of mathematical
72. Laks H, Pearl JM, Haas GS, et al. Partial Fontan: advantages modeling to compare and predict hemodynamic effects between
of an adjustable interatrial communication. Ann Thorac Surg. hybrid and surgical Norwood palliations for hypoplastic left
1991;52:1084-94. heart syndrome. Circulation. 2011;124(11 Suppl):S204-10.
73. Bridges ND, Lock JE, Castaneda AR. Baffle fenestration 86. Jatene MB, Oliveira PM, Moysés RA, et al. Double shunt
with subsequent transcatheter closure: Modification of the technique for hybrid palliation of hypoplastic left heart
Fontan operation for patients with increased risk. Circulation. syndrome: a case report. J Cardiothorac Surg. 2011;6:146.
1990;82:1681-89. 87. Tworetzky W, Wilkins-Haug L, Jennings RW, et al. Balloon
74. Rao PS, Turner DR, Forbes TJ. Hypoplastic Left Heart dilation of severe aortic stenosis in the fetus: potential for
Syndrome. eMedicine from WebMD. Updated September 22, prevention of hypoplastic left heart syndrome: candidate
2009. Available at: http://emedicine.medscape.com/article/ selection, technique, and results of successful intervention.
890196-overview. Circulation. 2004;110:2125-31.
75. Kreutzer J, Graziano JN, Stapleton G, et al. Late catheter 88. Konertz W, Schneider M, Herwig V, et al. Modified hemi-
interventions in hypoplastic left heart syndrome. Cardiol Fontan operation and subsequent nonsurgical Fontan
Young. 2011;21:65-76. completion. J Thorac Cardiovasc Surg. 1995;110:865-67.
76. Goff DA, Blume ED, Gauvreau K, et al. Clinical outcome of 89. Bove EL. Current status of staged reconstruction for hypoplastic
fenestrated Fontan patients after closure: the first 10 years. left heart syndrome. Pediatr Cardiol. 1998;19:308-15.
Circulation. 2000;102:2094-99. 90. Sinzobahamvya N, Photiadis J, Kumpikaite D, et al.
77. Boudjemline Y, Bonnet D, Sidi D, et al. Closure of extracardiac Comprehensive Aristotle score: implications for the Norwood
Fontan fenestration by using the Amplatzer duct occluder. Arch procedure. Ann Thorac Surg. 2006;81:1794-800.
Mal Coeur Vaiss. 2005;98:449-54. 91. Newburger JW, Sleeper LA, Bellinger DC, et al. (Pediatric
78. Jacobs ML, Rychik J, Byrum CJ, Norwood WI Jr. Protein- Heart Network Investigators). Early developmental outcome
losing enteropathy after Fontan operation: resolution after in children with hypoplastic left heart syndrome and related
baffle fenestration. Ann Thorac Surg. 1996;61:206-08. anomalies: the single ventricle reconstruction trial. Circulation.
79. Lopez JA. Transvenous right atrial and left ventricular 2012;125:2081-91.
pacing after the Fontan operation: long-term hemodynamic 92. Carotti A. Postoperative neurodevelopmental outcome of
and electrophysiologic benefit of early atrioventricular patients with hypoplastic left heart complex: hybrid versus
resynchronization. Tex Heart Inst J 2007;34:96-101. Norwood strategy. Eur J Cardiothorac Surg. 2012;42:40-41.
682
Sec t i on
Congenital
Cardiomyopathies
C hapter
48 Dilated Cardiomyopathy
Bhanu Duggal, Munde K
Cardiomyopathies are diseases of the heart muscle, char- Etiology

acterized by abnormal findings of chamber size and wall
thickness, or functional contractile (systolic or diastolic) The number of cardiac or systemic processes that can lead
dysfunction. In 1980, World Health Organization (WHO) de- to this condition is remarkably varied. Ischemia, valvular
fined cardiomyopathies as ‘heart muscle disease of unknown involvement, hypertension and congenital defects must be
cause’. However in clinical practice, the term has been used excluded in every case of dilated cardiomyopathy.
to define left ventricular (LV) dysfunction due to different Dilated cardiomyopathy can be primary, i.e. confined to
etiologies. Hence, the 1995 WHO/International Society and the heart muscle or secondary, i.e. one in which myocardial
Federation of Cardiology (IFSC) classification is based on involvement is secondary to a generalized systemic disorder.
global anatomic description of chamber dimensions in sys- A number of conditions lead to the dilated phenotype (Box
tole and diastole and the classification has been expanded to 1). In 50 percent of the patients no identifiable cause is found,
include all diseases affecting the heart muscle.1 hence the term ‘idiopathic’ dilated cardiomyopathy.5
American Heart Association (AHA) expert consensus panel Familial forms make up 30 percent of DCM. The phenotype
(2006) defined cardiomyopathies as a group of diseases of the in monogenetic forms is determined by the mutation itself,
myocardium associated with mechanical and/or electrical but it can be modified by the transmission mode, penetrance,
dysfunction, which usually exhibit inappropriate ventricular environmental influence, current or changing immune status,
hypertrophy or dilation, due to a variety of etiologies that polymorphism and other confounders and thus explains in
frequently are genetic.2 part the different functional status.6
The European Society of Cardiology (2007) position
statement however stated that cardiomyopathy is a heart Inflammatory and Postinfective Subtype
muscle disorder, in which heart muscle is structurally and
functionally abnormal in the absence of coronary artery Inflammatory and postinfective subtype are considered as
disease, hypertension, valvular disease and congenital heart secondary cardiomyopathies and .The World Health Federation
disease’. Thus, they confirmed the morphofunctional approach (WHF) updated the conventional Dallas classification by the
of WHO, but removed ischemic, hypertensive, valvular and introduction of immunohistochemical methods. Myocarditis
congenital etiologies and did not include electrical disorders.3 was defined as a process charecterised by an inflammatory
infilterate of the myocardium.The WHF committee choose
Definition a minimum of 14 infiltrating leukocytes/mm2. The most
common etiologies in Europe have shown an epidemiological
Thus, dilated cardiomyopathy (DCM) is defined as an ejection shift from enterovirus and adenovirus to parvovirus B19,
fraction of less than 55 percent, in some studies less than human herpesvirus 6 (HHV6), and cytomegalovirus (CMV).7
45 percent, in the presence of increased LV dimensions (end-
diastolic size more than 115 percent of that calculated for Pathophysiology
age and body surface area)3 or an increased end-diastolic
volume of more than 100 mL/m2, which cannot be explained Dilated cardiomyopathy represents the final common
by coronary artery disease, hypertension, or valvular disease.4 morphologic outcome of various biological insults. The
The right ventricle may also be dilated with reduced ejection etiology of the clinical phenotype of dilated cardiomyopathy
fraction, but this is not essential for the diagnosis. comprises genetic, autoimmune and viral factors. Most likely
9 Box 1: Causes of dilated cardiomyopathy
all three factors interplay to a different extent. Myocyte
injury due to various factors enlisted in Box 1, myocarditis,
• Ischemic cardiomyopathy (must be excluded) autoimmune mechanism triggered secondary to myocardial
Congenital cardiomyopathies
• Stress-induced cardiomyopathy inflammation or other environmental factors lead to myocyte

• Tachycardiomyopathy necrosis and fibrosis. Myocyte failure and cytoskeletal
• Infectious cardiomyopathy
uncoupling, cause the chambers to become dilated. According
– Viral cardiomyopathy
– Human immunodeficiency virus (HIV) infection to Laplace’s law, increased diameter increases wall stress and
– Chagas disease causes further mechanical disadvantage. The hypertrophied
– Lyme disease cells exposed to continued stress eventually become fibrotic
– Kawasaki disease and inadequate to maintain cardiac function (Figures 1A to D).
• Genetic causes of dilated cardiomyopathy Thus, myocardial dysfunction can cause a vicious cycle leading
– Inherited syndrome
– Hypertrophic cardiomyopathy (end-stage disease)
to more myocardial dysfunction in a process termed adverse
– Left ventricular non-compaction. ventricular remodeling. DCM is associated with complex
• Toxic causes of cardiomyopathy. remodeling of one or both ventricles, resulting in a change
– Drugs: Alcohol, cocaine of the ventricle shape and the architecture of the myocardium
– Medications: Chemotherapeutic agents (anthracycline), fibers. This eventually leads to a decreased cardiac output and
antiretroviral drugs, chloroquine. consequently activation of the neurohormonal axis (Figure 2).
– Trace elements.
• Electrolyte abnormalities—Hypocalcemia,
hypophosphatemia, uremia. Epidemiology
• Peripartum cardiomyopathy
• Metabolic: Endocrine diseases (e.g. hyperthyroidism, Dilated cardiomyopathy is a common and largely irreversible
hypothyroidism, myxedema, hyper and form of heart muscle disease with an estimated prevalence
hypoparathyroidism), diabetes mellitus.
of 1:2500.8 Dilated cardiomyopathy is the most common
• Collagen vascular disease: Systemic lupus erythematosus
(SLE), scleroderma, giant cell arteries. cardiomyopathy worldwide and accounts for 60 percent of all
• Infiltrative disorders: Hemochromatosis, amyloidosis, cardiomyopathies. It is the third most common cause of heart
glycogen storage disease. failure and the most frequent cause of heart transplantation.
• Nutritional deficiencies: Thiamine, carnitine, selenium. Intensive investigations can reveal a specific associated cause
• Obstructive sleep apnea. in 50 percent of the patients, remaining 50 percent are assigned
• Neuromuscular disorders—Duchenne dystrophy, myotonic
dystrophy.
the diagnosis of exclusion, idiopathic DCM.9
• Immunologic disorders: Serum sickness, transplant The prevalence in the general population remains undefined.
rejection. This disorder develops at any age, in either sex and in people
of any ethnic origin. In adults, DCM arises more commonly in
A C D
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
686 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
Dilated Cardiomyopathy
Figure 2: Neurohormonal activation in heart failure.
men than in women. In children, the yearly incidence is 0.47 In idiopathic DCM, 70 to 95 percent have frequent and
cases per 100,000 per year overall, but it is higher in boys complex ventricular premature complexes (VPCs) and 40 to
than in girls (1.32 vs 0.92 cases per 100,000, p < 0.001) and in 80 percent have unsustained ventricular tachycardia (VT). In
babies younger than 1 year than in children (8.34 vs cases per VHeFt study 25 to 30 percent of patients with unsustained VT
100,000, 95 percent confidence interval 7.21 to 9.61).10 did not have symptoms.12
Physical findings depend upon the severity of LV dysfunction
Clinical Features as well as right ventricular dysfunction. If cardiac output is
reduced, low arterial pressure, tachycardia and cool extremities
Patients may present in early childhood, though most present develop. Bilateral basal crepitations due to pulmonary venous
during the 4th and 5th decades of life. congestion may be evident in auscultation. The apex beat may
In general, symptoms are manifested when disease has be displaced laterally due to the dilated LV. Auscultation of the
progressed to end-stage with significant myocardial fibrosis. heart may reveal S3 and/or systolic murmur of MR secondary
Symptoms related to congestive heart failure such as dyspnea, to LV dilation. Right ventricle involvement presents with signs
fatigue, angina, pulmonary congestion and low cardiac output and symptoms of venous congestion and a murmur of tricuspid
are the usual presenting features. Suspicion of myocarditis regurgitation. Cachexia and peripheral edema typically arise
and postinfectious DCM may be raised by the presence of late in the course of the disease. Additionally, peripheral edema
chest pain, exertional dyspnea, fatigue, syncope, palpitations, and ascites are late signs in children.
ventricular tachyarrhythmias and conduction abnormalities or
by acute congestive heart failure/cardiogenic shock associated Thromboembolism
with LV dilation and/or segmental wall motion abnormalities
and ST-T changes on electrocardiogram (ECG). Angina is a Thromboembolism often complicates the clinical course of
feature frequently found in parvovirus B19-associated heart patients with DCM and could be the first presentation. At least
disease.11 11 to 13 percent patients experience embolic episodes. Emboli
The disease is usually progressive. Mitral regurgitation occur in order of decreasing frequency in pulmonary, renal,
and ventricular arrhythmias can develop in the course of spleen or cerebral circulations.13
the disease. MR is secondary to LV dilatation. Ventricular
arrhythmias have been associated with myocardial fibrosis Diagnosis
and hemodynamic stress, both of which contribute to
re-entry phenomenon critical to the development of Diagnosis is dependent on patient’s history, clinical examina-
arrhythmias. About 40 percent of DCM patients die suddenly. tion and imaging, i.e. echocardiography or cardiac magnetic
687
9 resonance imaging (MRI) features of DCM or heart failure also helps in assessing the severity of the disease.14 These
or both. features are included in Box 2.
Chest Radiographs Biomarkers

Chest radiographs often show cardiomegaly and increased Biomarkers include inflammatory markers C-reactive
pulmonary vascular markings that are consistent with protein, tumor necrosis factor (TNF), markers of oxidative
pulmonary edema. stress (oxidized low-density lipoproteins, myeloperoxidase),
extracellular matrix remodeling (matrix metalloproteinase,
Electrocardiography procollagen type I and III), neurohormones (brain natriuretic
peptide {BNP}, endothelin I), markers of myocyte injury
Electrocardiography, another standard diagnostic test, can (troponins) and myocyte stress (natriuretic peptides). For
show sinus tachycardia, ST-T wave changes, Q waves, a biomarker to be useful, accurate, repeated measurements
conduction disturbances, bundle-branch block, left atrial should be possible at a reasonable cost and its measurement
and ventricular hypertrophy or ectopy (Figures 3A and B), should help in guiding therapeutic management.15
including supraventricular tachycardia, atrial fibrillation or Horwich et al reported that cardiac troponin I was
ventricular arrhythmias. New onset left bundle branch block detectable (≥ 0.04 ng per milliliter) in approximately half of
(LBBB), wide QRS > 120 msec may be associated with poor 240 patients with advanced, chronic heart failure without is-
prognosis.13 chemia.16 In another study, cardiac troponin T levels greater
than 0.02 ng per milliliter in patients with chronic heart failure
Echocardiography were associated with a hazard ratio for death of more than
4.17 After adjustment for other variables associated with poor
Echocardiography is a Class I diagnostic test for DCM and prognosis, the presence of cardiac troponin I remained an
LV dilatation with depressed ejection fraction is required independent predictor of death.14 Logeart et al reported that,
for diagnosis (Figures 4A and B). Apart from the primary in patients hospitalized for decompensated heart failure, the
diagnostic criteria, secondary features on echocardiography 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,
Box 2: Echocardiographic parameters
they are relatively unstable in plasma and may be difficult to
in dilated cardiomyopathy
measure on a routine basis.
Left Ventricular Dilatation
• Assessment of left ventricular internal dimension (LVID) Endomyocardial Biopsy
• Left ventricular volumes
• Sphericity index (ratio of long axis to minor axis) Endomyocardial biopsy (EMB) is a procedure carrying
• Functional MR sufficient risk, which limits its use to patients in whom
• Left ventricular thrombus and spontaneous echo contrast
(SEC) may be seen (Figure 5A and B)
it has been shown to have therapeutic implications. A
thorough medical history regarding the onset and disease
LVEF: M-mode: EPSS and B-hump, 2D (Simpson’s, 3D Echo)
program is required. Rapidly progressive disease over 1
Left Atrial Dilatation
month (giant-cell myocarditis, lymphocytic myocarditis),
• Left atrial dimensions (indicator of raised left atrial filling
pressures) heart failure of less than 3 months duration with new onset
• Stasis of blood in left atrium conduction abnormalities (2nd or 3rd degree AV block
Pulmonary Hypertension or ventricular arrhythmias) or acute onset heart failure
• Tricuspid regurgitation with rapidly deteriorating ejection fraction and failure to
Right Ventricular Dilatation and Dysfunction stabilize the patient with conventional treatment, requires
LV Diastolic Dysfunction EMB. Other group of patients who are candidates for
Mitral E/A Ratio (Response to Valsalva)
EMB are those in whom laboratory investigations indicate
• Restrictive pattern indicates poor prognosis presence of autoimmune disease or if infiltrative and storage
Deceleration Time disorders are suspected and non-invasive test findings are
inconclusive.19 From EMB samples, identification of the
Annular Doppler Tissue Velocity
causative virus by its viral genome with PCR has been
E/e’
useful to establish the cause of acute myocarditis and has
EPSS = E point septal separation; LVEF = Left ventricular ejection clarified that some cases of dilated cardiomypathy are the
688 fraction.
result of chronic myocarditis. Additionally, this diagnostic
48
A
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
A B
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
9
A B
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 A cardiac MRI should also include late-enhancement
and accuracy of prognosis. images, which are important for tissue-characterization
and can help differentiate dilated ischemic CMP from non-
Magnetic Resonance Imaging ischemic DCM.
Functional changes in DCM are easily quantified using MRI. Treatment

MRI provides a valuable alternative to echocardiography
in the diagnostic work-up of patients with limited windows Aim of treatment is to alleviate the symptoms, prevent the
as well as in patients with right ventricular involvement. It disease progression to decompensated heart failure and
provides a more accurate delineation of the endocardial border complications of thromboembolism and sudden cardiac death.
and LV volumes and may be a useful tool for monitoring drug
therapy. In black blood images, the end-diastolic volumes of Angiotensin-converting Enzyme Inhibitors
DCM are more than 140 ml for LV and more than 150 ml
for RV; these figures may be more accurate, if indexed for All patients regardless of symptoms should be started on
body surface area. Pilot studies reveal that it could prove angiotensin-converting enzyme (ACE) inhibitors, because of
to be a useful tool in differentiating acute and chronic survival benefit. The drug is initiated in a low dose and the drug
alterations of the myocardium. Comparing global myocardial should be uptitrated once in every 1 or 2 weeks to achieve the
enhancement with skeletal muscle enhancement early after trial dose of these drugs. Renal function and serum potassium
gadolinium administration is of use to depict generalized should be assessed 1 or 2 weeks after initiation of the drug and
myocardial hyperemia, which can be found in patients with after uptitration. As there is an uncertainty of benefit with the
myocardial inflammation not only in the acute phase, but also drugs at lower doses, one tries to achieve this target endpoint,
in chronic forms of myocarditis.20,21 Besides, myocardial if tolerated, to maximize benefit.22,23
T1 mapping techniques are appealing for the depiction of
diffuse myocardial fibrosis and represent a valuable addition ß-blockers
to the late gadolinium enhancement (LGE) MRI technique.
Shortening of the myocardial T1 relaxation time is related to They upregulate b1-receptor density, blunt norepinephrine
the amount of myocardial collagen deposition. Performing and renin production and mitigate production of deleterious
fast gradient-echo sequences using multiple increasing cytokines. Large scale clinical trials have demonstrated about
inversion times (e.g. 50–1,000 ms) before and after contrast- 35 percent reduction in mortality. However, only 3 drugs, i.e.
medium administration at the blood/myocardium equilibrium bisoprolol, carvedilol and metoprolol have shown mortality
phase, allows the decay in myocardial signal intensity to be benefit in clinical studies and hence these are the drugs
measured and T1 maps to be generated with the use of curve recommended in heart failure. The ACC/AHA guidelines
690 fitting techniques. recommend the use of these β-blockers in heart failure,
excluding patients with relative contraindications to β-blocker Combination of Hydralazine and Nitrates 48
therapy, i.e. heart rate < 60 bpm, prolonged PR interval,
conduction system defects, reactive airways, peripheral arterial Nitrates increase nitric oxide production and hydralazine
disease as well as systemic hypotension and evidence of fluid sustains these levels. Hence, the combination is associated
retention. β-blockers with intrinsic sympathomimetic activity with vasodilatation and reduced afterload, but the mortality
and agents like bucindolol have not shown survival benefit.24,25 reduction is less than that of ACEIs and ARBs.25 In patients
Clinical trials have shown a dose dependent improvement with renal insufficiency, or persistent hypertension in the
in LV function and reduction in mortality and hospitalizations presence of optimal doses of β-blockers and ACE-inibitors
with β-blocker use. Thus, β-blocker dose should be started addition of a fixed dose isosorbide dinitrate (37.5 mg
in a very low dose and the dose should be doubled every 2 hydralazine and 50 mg isosorbide dinitrate) and hydralazine
weeks until the target dose is reached or symptoms become combination is associated with improved survival and
limiting. The patient should be informed that β-blockers may decreased hospitalization as seen in A-HeFt trial.29,30
lead to an increase in symptoms for 4 to 10 weeks before any
improvement. Though inpatient initiation is associated with Digoxin
a higher compliance, it should not be initiated on patients
with minimal evidence of fluid retention or those on recent Digoxin has a sympathoinhibitory effect and Digitalis
intravenous therapy. Investigation Group (DIG) trial has demonstrated a reduction
in hospitalization for heart failure. No mortality benefit was
Angiotensin Receptor Blockers seen and the benefit in women was less than that for men.
Hence, the addition of a low dose of the drug may benefit
A large meta-analysis of 24 randomized trials showed symptomatic patients and trough digoxin levels should be
superiority of angiotensin receptor blockers (ARBs) to checked to minimize the risk of toxicity.31
placebo in patients with intolerable side effects with ACE-
inhibitors and their non-inferiority to all cause mortality or Statins
hospitalizations when compared to ACE inhibitors. Valsartan
Heart Failure Trial (Val-HeFT) suggested that addition of Dilated cardiomyopathy is a multifactorial and progressive
valsartan in patients already receiving treatment with ACEIs disease indicating that important pathogenetic mechanism
and β-blockers was associated with a worse outcome. Thus, remain active and unmodified by currently available treatment.
neurohormonal blockade beyond a certain extent is not In view of probable role of cytokines and inflammation in
associated with any benefit, but may be harmful.26,27 DCM, statins with their pleiotropic effect may provide an
alternative treatment option in patients with this condition.
Aldosterone Antagonists In the universe (RosUvastatiN Impact on VEntricular
Remodeling, LipidS, and CytokinEs) study, high-dose
The elevated aldosterone levels seen in patients with heart rosuvastatin (40 mg/day) did not result in a significant
failure promote sodium retention, electrolyte imbalance improvement in LV ejection fraction relative to placebo.
as well as endothelial dysfunction leading to myocardial Attorvastatin 80 mg has been shown improvement in the LV
fibrosis. Both the selective agent eplerenone and non-selective function and excercise tolerence in DCM due to improvement
antagonist spironolactone significantly reduce the mortality in endothelial dysfunction and anti inflamatory effects.
and hospitalizations. These should be introduced in New York Candidates for statin therapy with DCM should be in New
Heat Association (NYHA) Class III and IV patients, but one York Heart Association Class II or III and should have normal
must monitor potassium levels carefully.28 or increased levels of lipid.32
Diuretics Complications
Goal of diuretic therapy is to eliminate clinical evidence of Complications such as arrhythmias and thromboembolic
fluid retention, such as elevated jugular pressure and peripheral events can be reduced with prophylactic medications. Rate
edema. The most commonly used loop diuretics is furosemide. control in atrial fibrillation can be achieved by β-blockers and
Bumetanide and torsemide are more potent and may be started. digoxin. Avoid calcium channel blockers. If symptoms persist,
Thiazide diuretics may be added for a synergistic effect, if then Class III antiarrhythmic drugs defetilide and amiodarone
clinically indicated. The diuretic dose needs to be carefully have been found to be safe and effective.33 Amiodarone is
adjusted as a higher dose can cause volume depletion and another medication that clinicians may use to treat arrhythmias,
precipitate ACE inhibitor-induced hypotension, while lower such as atrial fibrillation and supraventricular arrhythmias,
dosing can lead to recurrence of symptoms. Therefore, the there is no benefit in mortality in patients with ventricular
therapy has to be tailored to each patient and they should be arrhythmias.34 Reduction of thrombus formation within the 691
educated to daily monitor their weight and regulate the dose. dilated chambers may be necessary to prevent thromboembolic
9 events. Anticoagulants, such as warfarin, are indicated for adsorption and subsequent IgG substitution improved cardiac
patients with a history of previous thromboembolic events, function, hemodynamic parameters (cardiac and stroke
severe systolic dysfunction or ventricular dilatation, though volume index) and systemic vascular resistance .
the benefits for warfarin treatment must outweigh the risks. The tailored immunosuppressive inflammatory cardio-
myopathy (TIMIC-immunosuppressive therapy in patients
Immune-Mediated Therapy with virus-negative inflammatory cardiomyopathy) study37
was the first randomized, placebo-controlled trial in which
Controversy continues about the immune mediated therapy all EMB were studied for inflammation by histological and
for myocarditis. In view of the chronic inflammatory immunohistological criteria. Molecular biological analyses
nature of the disease and the effects of the immune were performed in all biopsy specimens to exclude viral
system, immunomodulatory therapy might be beneficial. infection. A significant improvement of LV ejection fraction
However, non-selective therapy has not proved useful. One and a decrease in LV dimensions resulted from immuno
of the largest randomized, controlled treatment trials, the suppressive therapy with prednisone and azathioprine.37
Myocarditis Treatment Trial35 failed to show the benefit Patients with fulminant viral myocarditis and hemodynamic
from immunosuppressive therapy additional to heart compromise at presentation are more likely to experience
failure therapy. There was neither a difference in mortality complete recovery than patients with acute myocarditis,81 if
nor an improvement of LV ejection fraction after 1 year of aggressive pharmacological and/or mechanical circulatory
treatment with prednisone and with either azathioprine or support is initiated early during the fulminant phase.38 In
cyclosporine versus placebo. These results might be due to patients with cardiac sarcoidosis or giant cell myocarditis,
a lack of consensus in interpretation of EMB findings. No prognosis depends probably on an early initiated treatment
immunohistology for the detection of inflammatory cells and (immunosuppressive therapy or heart transplantation).39
no molecular biological analyses of EMB were used for the
detection of infectious agents. Device Therapy in Heart Failure
Better efforts are required to distinguish viral from non-
infectious autoimmune forms of the disease in order to guide Device therapy is indicated in symptomatic patients on
appropriate treatment. Molecular biological detection of optimal drug therapy. Mechanical dyssynchrony, defined
cardiotropic viruses can be performed by nested polymerase as non-synchronous contraction between the walls of the
chain reaction (PCR)/real time-PCR from EMB. Finally, LV (intraventricular) or between the ventricular chambers
this contemporary diagnostic repertoire is essential for the (interventricular) impairs systolic function, adversely affects
selection of DCM patients who will likely to benefit from ventricular filling, increases wall stress and worsens mitral
immunosuppression or antiviral interferon (IFN) treatment. regurgitation. Dyssynchrony is defined by widening of
The molecular biological diagnosis of viral genomes comprises QRS complex on the ECG. The indications for cardiac
PCR for the qualitative evaluation, quantitative PCR (qPCR) resynchronization therapy (CRT) are summarized in Table 1.
for the determination of viral loads and sequencing for the This therapy has been shown to restore the coordination
analysis of viral genotypes. Treatment with IFN-beta in and relaxation of the cardiac chambers which results in
patients with myocardial enteroviral or adenoviral persistence favorable cardiac remodeling and improves survival in this
and LV dysfunction showed an elimination of viral genomes population.40 However, up to a third of patients do not have
in all patients and an improvement of LV function in 15 of 22 any clinical benefit with present recommended criteria.
patients.6 In the subsequent placebo-controlled, randomized, These patients could have identifiable reasons for a poor
double-blind, Europe wide multicenter Betaferon in patients response. Thus, their drug doses, compliance to medications
with chronic viral cardiomyopathy study, the treatment with and fluid restriction, underlying arrhythmias, LV lead
Betaferon significantly reduced the viral load (enteroviruses) position, optimization of atrioventricular timings must be
in the myocardium and significant improvement in NYHA reviewed.
class and patient global assessment was seen.36
Table 1

Immunoglobulin Treatment Indications for cardiac resynchronization therapy
The rationale to use immunoglobulin (Ig) in viral myocarditis RT indicated if all 3 criteria (below) are fulfilled.
C
results from their antiviral and immunomodulating effects. LVEF ≤ 35%
In recent onset of myocarditis or DCM, only children with QRS duration of > 120 msec
acute myocarditis showed an improvement of LV function and NYHA II-IV symptoms with optimal medical therapy
survival in the 1st year after treatment. Consider CRT if both criteria given below are fulfilled.
Virus negative inflammatory myocarditis, there is LVEF ≤ 35%
692 evidence that removal of circulating antibodies by immuno NYHA II-IV symptoms with frequent right ventricular pacing
Implantable Cardioverter-defibrillator non-ischemic disease remains problematic. For these reasons, 48
gene-based therapies such as gene therapy, stem-cell therapy
Sudden Cardiac Death (SCD) may occur in nearly 30 and targeted treatments are being investigated.
percent of patients with nonischemic dilated cardiomyopathy
(NICM).41 The risk is highest in patients with aborted SCD Stem Cell Therapy
and unexplained syncope. In a meta-analysis of 5 primary
and secondary trials a risk reduction of 31 percent in all cause Interest in the use of stem cell therapy as a treatment for end-
mortality was seen, however as mortality on optimal medical stage DCM has increased during the past decade. Several studies
therapy is as low as 7 percent, this figure translates to 2 percent have documented beneficial effects of stem cell transplantation
per year.42 Moreover, as implantable cardioverter-defibrillator in patients who have depressed left ventricular systolic
(ICD) does not cause any symptomatic improvement, patients dysfunction after myocardial infarction. However, concern has
in NYHA Class IV or with life expectancy of less than 6 grown that this approach might only result in paracrine growth
months are not candidates for the device. Thus, the ICD factor stimulation or improvement in myocardial scaffolding
treatment needs to be individualized. without generation of new myocardium.51,52
Cardiac transplantation is needed in extreme cases. At
Left Ventricular Assist Device present, transplants are reserved for patients with the most
severe disease those needing inotropes and usually mechanical
Studies have found that the left ventricular assist device (LVAD) ventilatory and mechanical device support.
normalises hemodynamics, improves progressive dysfunction
of the heart, improves exercise tolerance and allows patients to Lifestyle Management
become outpatients. On closer look, it was observed that patients
with non-ischemic DCM on optimal doses of ACE inhibitor
Exercise Training
and β-blocker therapy and shorter duration of disease process,
responded favorably to ventricular assist devices. Various Exercise training is recommended as an adjunctive treatment
ventricular assist devices exist at present; some are stationary, in patients with heart failure. HF-ACTION trial controlled
others ambulatory and some are fully implantable. Use of trial investigating outcomes of exercise training) investigated
ventricular assist devices has significantly improved survival of short and long-term outcomes of a supervised exercise
adults and children with DCM with end-stage disease who are program in heart failure and confirmed a decrease in mortality
awaiting heart transplant. The total artificial heart is used for and increase in patient’s sense of well-being in these patients,
destination therapy (use of long-term mechanical circulatory however, in the presence of acute myocarditis one must
support in patients with end stage heart failure, without the abstain from active sport. The duration of abstinence advised
intention of eventual heart transplantation).43,44 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 Obstructive sleep apnea is associated with periods of hypoxia
medical treatment and not eligible for device implantation. and adrenergic surge and hence, is an independent predictor
However, the surgical option should be offered before patient of worsening of heart failure. Treatment with nocturnal
becomes inotrope dependent as at this stage surgical outcome is continuous positive airway pressure (CPAP) improves
not good. Severe functional MR patients undergo surgical mitral 6 minutes walk test and improved ejection fraction.55
valve annuloplasty as well as Maze procedure, if indicated.45 Although improved outcomes in DCM and heart failure
The mortality benefit outcome remains controversial. Results have been achieved, improving outcomes for patients with
of the AMADEUS46 and CARILLON47 trials also show non-ischemic disease remains problematic. For these reasons,
feasibility of percutanoues mitral valve annuloplasty, with gene-based therapies such as gene therapy, stem-cell therapy
a decrease in functional mitral regurgitation. The Batista and targeted treatments are being investigated.
procedure12 or partial left ventriculotomy, is useful in patients
with end-stage dilated cardiomyopathy.48 Other interventions Prognosis
include surgical ventricular restoration by recreation of the
elliptical shape of the LV by volume reduction with a sizing Predictors of increased likelihood of death or need for
balloon, achieving a volume of 55 to 60 mL per m2 body- cardiac transplantation include syncope, right ventricular
surface area. Favorable benefits have been seen in patients systolic dysfunction, elevated pulmonary artery pressure, and
undergoing a volume reduction of the left ventricle by at least advanced NYHA functional class. Elevated levels of Fas, Fas
30 percent with a goal to improve the biophysics of the LV and ligand, TNF, and IL-10 as well as immunohistologic signs
reduce the stimulus for unfavorable remodelling.49,50 of inflammation (CD3 and/or CD68), are also predictors 693
Although improved outcomes in DCM and heart failure of increased risk of death. The Seattle Heart Failure Model
have been achieved, improving outcomes for patients with incorporates a broader range of patients along with multiple
9 clinical predictors, laboratory data, and medical therapy, is a conduction system disorder. 18 percent of patients less
correlates well with 1-, 2-, and 3-year survival, similar to the than 10 years of age had delayed intracardiac conduction.
Framingham Coronary Heart Disease Risk Model and is able 92 percent of patients presenting at more than 30 years of
to predict the mode of death in heart failure: pump failure vs age had conduction system disease and 44 percent required
SCD.56 Less information is available on the natural history of pacemaker placement. In early stages, they have an ECG
myocarditis in children. Other clinical risk factors in patients with low amplitude P waves, prolonged PR interval and
with suspected myocarditis are low systolic, diastolic and relatively normal QRS complex.59 Subsequently they
mean arterial blood pressures as well as high heart rate. A develop atrial fibrillation and DCM. A high incidence of
prolonged QRS duration > 120 ms has also been shown to thromboembolic events has been noted in 30 percent these
predict for cardiac death or heart transplantation in patients patients. Presence of conduction system disease indicates
with suspected myocarditis. progressive fibrosis. Meune et al implanted ICDs in 19
patients who had lamin A/C mutations and indications for
Specific Cardiomyopathies pacemaker and found that 42 percent patients received
shocks. As the data are controversial about appropriateness
of shocks.60 Knowledge of patient’s family history of SCD
Peripartum Cardiomyopathy
indicates a low threshold for SCD41 which is associated
Peripartum cardiomyopathy is a disorder, in which initial LV with conduction system disease. The mechanisms that are
systolic dysfunction and symptoms of heart failure develop responsible for the development of this disease, conduction
between the late stages of pregnancy and early postpartum system abnormalities and skeletal myopathy are being
period, typically within 1 month of predelivery and 5 months established.
postdelivery.57 Its causes and pathogenesis are poorly
understood. The disorder is common in some countries and rare Fetal Cardiomyopathy
in others. In most patients with this disorder, molecular markers
of an inflammatory process are identified. Affected women Systolic and diastolic fetal cardiac function have become part
generally present clinically with typical signs and symptoms of the routine evaluation of the fetal heart. In series of neonates
of heart failure; signs of thromboembolism are also frequent. and infants, cardiomyopathy was observed in about 2 to 7
Conventional heart-failure treatment is typically used. Effective percent, but probably during the fetal life the prevalence is higher
treatment reduces mortality rates and increases the number of 6 to 11 percent. The high intrauterine loss, occurring in
women who fully recover LV systolic function. Outcomes for one-third of affected fetuses, likely accounts for these
subsequent pregnancies after peripartum cardiomyopathy are differences. Fetal echocardiography, B and M-mode is the
better for women who have fully recovered heart function main diagnostic tool and it is useful for the therapeutic
compared with those who have persistent LV dysfunction. orientation and to determine the neonatal outcome. A
hemodynamic evaluation can be performed by Doppler
Left Ventricular Non-compaction mode. Cardiomyopathies can be isolated or associated with
other cardiac and non-cardiac malformations. All the studies
Left ventricular non-compaction has been discussed in confirm a great variability of DCM in the fetal age as for the
Chapter 49. anatomical and functional forms, etiology and hemodynamic
impact with different final outcome. Genetic, metabolic,
Familial Dilated Cardiomyopathy infective and cardiac diseases may present with DCM.
Ventricular dysfunction may be progressive in utero and after
Familial dilated cardiomyopathy is now thought to account birth, but possibility of improvement or even normalization
for upto 50 percent of idiopathic dilated cardiomyopathy of the LV. dysfunction is known in all forms of DCM,
(IDC). Most of these cases (>90%) are thought to have idiopathic, postinfective or in non-compaction of LV. The
autosomal dominant inheritance, although X-linked and outcome is worse in presence of fetal hydrops, significant
autosomal recessive forms have been identified. This requires atrioventricular valve regurgitation, for the earlier age at
a sufficient family history to identify at least two first-degree presentation and when diastolic dysfunction is associated
family members with IDC. This is difficult as the disease is with systolic dysfunction. Unfortunately, a poor outcome
variable with age dependent penetrance even within the family. is observed in most, particularly in DCM, with only a few
Although up to 50 percent patients with IDC may have familial therapeutic options available. Detailed evaluation of fetal
DCM (FDC) by history, a genetic test may identify the disease and maternal condition provide prognostic information for
in only 10 percent causes.58 prenatal counselling and may lead to improved outcome.61
Lamin A/C Mutation Conclusion

694
Lamin A/C mutation is thought to be the cause in 10 Dilated Cardiomyopathy appears to be the most common
percent of FDC cases. The earliest finding in this disease form of cardiomyopathy in children. Dilated cardiomyopathy
represents a common expression of myocardial damage that 13. Ciaccheri M, Castelli G, Cecchi F, Nannini M, Santoro G, 48
has been produced by a variety of yet unestablished myocardial Troiani V, et al. Lack of correlation between intracavitary
insults. The demographics and underlying causes have been thrombosis detected by cross sectional echocardiography and
difficult to ascertain, particularly in children. Arrhythmias form systemic emboli in patients with dilated cardiomyopathy. Br
Heart J. 1989;62:26-9.
an important mode of death. ACE-inhibitors and β-blockers
14. Armstron WF, Ryan T. Feigenbaum’s Echocardiography:
along with diuretics are the mainstay of the therapy. Device
Lippincott Williams and Wilkins; 2010. pp. 9507.
therapy is now useful in symptomatic patients but in end stage 15. Braunwald E. Biomarkers in heart failure. N Engl J Med 2008;
disease, cardiac transplantation is the only option. 358:2148-59.
16. Horwich TB, Patel J, MacLellan WR, Fonarow GC. Car-
The greatest mistake in the treatment of diseases is that diac troponin I is associated with impaired hemodynam-
there are physicians for the body and physicians for the soul, ics, progressive left ventricular dysfunction, and increased
although the two cannot be separated. mortality rates in advanced heart failure. Circulation. 2003;108:
—Plato 833-8.
17. Hudson MP, O’Connor CM, Gattis WA, Tasissa G, Hasselblad
V, Holleman CM, et al. Implications of elevated cardiac tro-
References ponin T in ambulatory patients with heart failure: a prospective
analysis. Am Heart J. 2004;147:546-52.
1. Richardson P, McKenna W, Bristow M, Maisch B, Mautner 18. Logeart D, Thabut G, Jourdain P, Chavelas C, Beyne P,
B, O'Connell J, et al. Report of the 1995 World Health Beauvais F, et al. Predischarge B-type natriuretic peptide
Organization/International Society and Federation of assay for identifying patients at high risk of re-admission after
Cardiology Task Force on the Definition and Classification of decompensated heart failure. J Am Coll Cardiol. 2004;43:635-
cardiomyopathies. Circulation 1996;93:841-2. 41.
2. Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, 19. Lambert A, Lapyere AC 3rd, Cooper LT: Current role of Endo
Arnett D, et al. Contemporary definitions and classification of myocardial biopsy in the management of Dilated Cardiomy-
the cardiomyopathies: an American Heart Association Scientific opathy and Myocarditis. Mayo Clin Proc: 2001;76:1030-8.
Statement from the Council on Clinical Cardiology, Heart 20. Ismail TF, Prasad KS, Pennell DJ. Prognostic importance
Failure and Transplantation Committee; Quality of Care and of late gadolinium enhancement cardiovascular magnetic
Outcomes Research and Functional Genomics and Translational resonance in cardiomyopathy. Heart. 2012;98:438-42.
Biology Interdisciplinary Working Groups; and Council on 21. Slavich M, Florian A, Bogaert J. The emerging role of magnetic
Epidemiology and Prevention. Circulation 2006; 113:1807-16. resonance imaging and multidetector computed tomography
3. Elliott P, Andersson B, Arbustini E, Bilinska Z, Cecchi F, in the diagnosis of dilated cardiomyopathy. Insights Imaging.
Charron P, et al. Classification of the cardiomyopathies: a 2011;2:453-69.
position statement from the European Society Of Cardiology 22. The SOLVD Investigators. Effect of enalapril on survival in
Working Group on Myocardial and Pericardial Diseases. Eur patients with reduced left ventricular ejection fractions and
Heart J 2008;29:270-6. congestive heart failure. N Engl J Med. 1991;325:293-302.
4. Ramani GV, Uber PA, Mehra MR. Chronic Heart Failure: 23. Rogers WJ, Johnstone DE, Yusuf S, Weiner DH, Gallagher P,
Contemporary Diagnosis and Management: Mayo Clin Proc:. Bittner VA, et al. Quality of life among 5,025 patients with
2010;85:180-95. left ventricular dysfunction randomized between placebo and
5. Towbin JA, Lowe AM, Colan SD, Sleeper LA, Orav EJ, enalapril: the Studies of Left Ventricular Dysfunction. The
Clunie S et al. Incidence, causes, and outcomes of dilated SOLVD Investigators. J Am Coll Cardiol. 1994;23:393-400.
cardiomyopathy in children. JAMA. 2006;296:1867-76. 24. Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB,
6. Taylor MR, Carniel E, Mestroni L. Cardiomyopathy, familial Gilbert EM, et al. The effect of carvedilol on morbidity and
dilated. Orphanet J Rare Dis. 2006;1:27. mortality in patients with chronic heart failure. US Carvedilol
7. Mestroni L, Gilbert EM, Lowes BD, Bristow MR: Dilated Heart Failure Study Group. N Engl J Med 1996;334:1349-55.
Cardiomyopathy In Fuster V, Walsh RA, Harrington RA (Eds): 25. Hernandez AF, Hammill BG, O’Connor CM, Schulman
Hurst’s The Heart. The Tata McGraw-Hill Co; 2011. pp. 82. KA, Curtis LH, Fonarow GC. Clinical effectiveness of beta-
8. Jefferies JL, Towbin JA: Dilated cardiomyopathy: Lancet blockers in heart failure: findings from the OPTIMIZE-HF
2010;375:752-762 (Organized Program to Initiate Lifesaving Treatment in
9. Rakar S, Sinagra G, Di Lenarda A, Poletti A, Bussani R, Hospitalized Patients with Heart Failure) Registry. J Am Coll
Silvestri F, et al. Epidemiology of dilated cardiomyopathy. A Cardiol. 2009;53:184-92.
prospective post-mortem study of 5252 necropsies. The Heart 26. Cohn JN, Tognoni G; Valsartan Heart Failure Trial Investigators.
Muscle Disease Study Group. Eur Heart J. 1997;18:117-23. A randomized trial of the angiotensin-receptor blocker valsartan
10. Wilkinson JD, Landy DC, Colan SD, Towbin JA, Sleeper LA, in chronic heart failure. N Eng J Med. 2001;345:1667-75.
Orav EJ, et al. The Pediatric Cardiomyopathy Registry and 27. Burnier M, Brunner HR. Angiotensin II receptor antagonists.
Heart Failure: Key Results from the First 15 Years. Heart Fail Lancet. 2000;355:637-45.
Clin. 2010;6:401-13. 28. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et
11. Towbin JA, Bowles NE. The failing heart. Nature. 2002;415: al. The effect of spironolactone on morbidity and mortality in
227-233. patients with severe heart failure. Randomized Spironolactone
12. Luk A, Ahn E, Soor GS, Butany J. Dilated Cardiomyopathy: A 695
Evaluation Study Investigators. N Engl J Med. 1999;341:
review: J Clin Path 2008;62:219-225. 709-17.
9 29. Ferdinand KC. Isosorbide dinitrate and hydralazine
hydrochloride: a review of efficacy and safety. Exp Rev
45. Tulner SA, Steendijk P, Klautz RJ, Tops L, Bax JJ, Versteegh
MI, et al. Clinical efficacy of surgical heart failure therapy by
Cardiovasc Ther. 2005;3:993-1001. ventricular restoration and restrictive mitral annuloplasty. J
30. Taylor AL, Ziesche S, Yancy C, Carson P, D'Agostino R Card Fail. 2007;13:178-83.
Jr, Ferdinand K, et al. Combination of isosorbide dinitrate 46. Siminiak T, Hoppe UC, Schofer J, Haude M, Herrman JP,
and hydralazine in blacks with heart failure. N Engl J Med. Vainer J, et al. Effectiveness and safety of percutaneous
2004;351:2049-57. coronary sinus-based mitral valve repair in patients with
31. Digitalis Investigation Group. The effect of digoxin on dilated cardiomyopathy (from the AMADEUS trial). Am J
mortality and morbidity in patients with heart failure.N Engl J Cardiol. 2009;104:565-70.
Med.1997;336:525-33. 47. Schofer J, Siminiak T, Haude M, Herrman JP, Vainer J, Wu JC,
32. Bielecka-Dabrowa A, Mikhailidis DP, Hannam S, Aronow WS, et al. Percutaneous mitral annuloplasty for functional mitral
Rysz J, Banach M. Statins and dilated cardiomyopathy: do we regurgitation: results of the CARILLON Mitral Annuloplasty
have enough data?. Expert Opini Investig Drugs. 2011;20:315- Device European Union Study. Circulation. 2009;120:326-33.
23. 48. Abe T, Fukada J, Morishita K. The Batista procedure: fact,
33. Kopecky SL MD, Litin SC. Clinical Pearls in Cardiology. fiction and its role in the management of heart failure. Heart
Concise review for Physicians. Mayo Clin Proc. 2010;85: Fail Rev. 2001;6:195-9.
473-8. 49. Koyama T, Nishina T, Ono N, Sakakibara Y, Nemoto S, Ikeda
34. Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau T, et al. Early and mid-term results of left ventricular volume
R et al. Amiodarone or an implantable cardioverter-defibrillator reduction surgery for dilated cardiomyopathy. J Card Surg.
for congestive heart failure. Sudden Cardiac Death in Heart 2005;20:S39-42.
Failure Trial (SCD-HeFT) Investigators. N Engl J Med. 50. Isomura T. Surgical treatment for heart failure: left ventricular
2005;352:225-37. restoration for cardiomyopathy. Circ J 2009;73 suppl A:A 6-12.
35. Mason JW, O’Connell JB, Herskowitz A, Rose NR, McManus 51. Stamm C, Choi YH, Nasseri B, Hetzer R. A heart full of
BM, Billingham ME, et al. A clinical trial of immunosuppressive stem cells: the spectrum of myocardial progenitor cells in the
therapy for myocarditis. The Myocarditis Treatment Trial postnatal heart. Ther Adv Cardiovasc Dis. 2009;3:215-29.
Investigators. N Engl J Med 1995;333: 269-75. 52. Liu J, Sluijter JP, Goumans MJ, Smits AM, van der Spoel T,
36. Kindermann I, Barth C, Mahfoud F, Ukena C, Lenski M, Nathoe H, et al. Cell therapy for myocardial regeneration. Curr
Yilmaz A et al. Update on myocarditis. J Am Coll Cardiol. Mol Med. 2009;9:287-98.
2012;59:779-92. 53. O’Connor CM, Whellan DJ, Lee KL, Keteyian SJ, Cooper
37. Frustaci A, Russo MA, Chimenti C. Randomized study on the LS, Ellis SJ, et al. Efficacy and safety of exercise training in
efficacy of immunosuppressive therapy in patients with virus- patients with chronic heart failure: HF-ACTION randomized
negative inflammatory cardiomyopathy: the TIMIC study. Eur controlled trial. JAMA. 2009;301:1439-50.
Heart J. 2009;30:1995-2002. 54. Flynn KE, Piña IL, Whellan DJ, Lin L, Blumenthal JA, Ellis
38. McCarthy RE 3rd, Boehmer JP, Hruban RH, Hutchins SJ, et al. Effects of exercise training on health status in patients
GM, Kasper EK, Hare JM, et al. Long-term outcome of with chronic heart failure: HF-ACTION randomized controlled
fulminant myocarditis as compared with acute (nonfulminant) trial. JAMA. 2009;301:1451-9.
myocarditis. N Engl J Med. 2000;342:690-5. 55. Wang H, Parker JD, Newton GE, Floras JS, Mak S, Chiu KL, et
39. Wu LA, Lapyere AC 3rd , Cooper LT. Current Role of al. Influence of obstructive sleep apnea on mortality in patients
Endomyocardial Biopsy in the Management of dilated with heart failure. J Am Coll Cardiol. 2007;49:1625-31.
Cardiomyopathy and Myocarditis. Mayo Clin Proc 2001;76: 56. Mozaffarian D, Anker SK, Anand I, Linker DT, Sullivan MD,
1030-8. Cleland JG, et al. Prediction of mode of death in heart failure:
40. Mullens W, Grimm RA, Verga T, Dresing T, Starling RC, the Seattle Heart Failure Model. Circulation 2007;116:392-8.
Wilkoff BL, et al. Insights from a cardiac resynchronization 57. Hilfiker-Kleiner D, Sliwa K, Drexler H. Peripartum
optimization clinic as part of a heart failure disease management cardiomyopathy: recent insights in its pathophysiology. Trends
program. J Am Coll Cardiol. 2009;53:765-73. Cardiovasc Med. 2008;18:173-179.
41. Kadish A, Dyer A, Daubert JP, Quigg R, Estes NA, Anderson 58. Mestroni L, Rocco C, Gregori D, Sinagra G, Di Lenarda A,
KP, et al. Prophylactic defibrillator implantation in patients Miocic S, et al. Familial dilated cardiomyopathy: evidence for
with nonischemic dilated cardiomyopathy. N Engl J Med. genetic and phenotypic heterogeneity. Heart Muscle Disease
2004;350:2151-8. Study Group. J Am Coll Cardiol. 1999;34:181-190.
42. Desai AS, Fang JC, Maisel WH, Baughman KL. Implantable 59. Hershberger RE, Hanson E, Jakobs PM, Keegan H, Coates K,
defibrillators for the prevention of mortality in patients with Bousman S et al. Novel lamin A/C mutation in a family with
nonischemic cardiomyopathy: a meta-analysis of randomized dilated cardiomyopathy, prominent conduction system disease,
controlled trials. JAMA. 2004;292:2874-9. and need for permanent pacemaker implantation. Am Heart J.
43. Miller LW, Pagani FD, Russel SD, ohn R, Boyle AJ, Aaronson 2002;144:1081-6.
KD, et al. Use of a continuous-flow device in patients awaiting 60. Meune C, Van Berlo JH, Anselme F, Bonne G, Pinto YM,
heart transplantation. N Engl J Med 2007;357:885-96. Duboc D. Primary prevention of sudden death in patients with
44. Rose EA, Gelijns AC, Moskowitz AJ, Heitjan DF, Stevenson lamin A/C gene mutations. N Engl J Med. 2006;354: 209-10.
LW, Dembitsky W et al. Long-term mechanical left ventricular 61. Fesslova V, Mongiovì M, Pipitone S, Brankovic J, Villa L.
assistance for end-stage heart failure. N Engl J Med. 2001;345: Features and outcomes in utero and after birth of fetuses with
696
1435-43. myocardial disease. Int J Pediatr. 2010. pp. 628-51.
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 Nomenclature
of endomyocardial morphogenesis with trabeculations that
are increased in prominence and number, with excessive Numerous synonyms have been used to describe this
intramyocardial spaces communicating with the ventricular abnormality, like spongy myocardium, spongiform cardiomyo
cavity.1 It represents an arrest of the normal maturation pathy, non-compaction, hypertrabeculation or persisting
process of the myocardium, which could be considered myocardial sinusoids. The recently recognized myocardial
an atavistic throwback, since it is the normal anatomy of malformation more commonly known as ventricular non-
the reptile heart. This congenital cardiomyopathy carries compaction is a fascinating disorder, characterized by the
a high risk of morbidity and mortality due to malignant presence of an extensive trabeculated myocardial layer
arrhythmias, thromboembolic episodes and pump failure of reinforcing the luminal aspect of the compact portion of the
the heart.2 Non-compaction of the ventricular myocardium ventricular wall. According to the World Health Organization
is the morphological hallmark of a rare familial or sporadic (WHO) definition, cardiomyopathies are classified by the
unclassified heart disease of heterogeneous origin. It results dominant pathophysiology or if possible, by etiological or
presumably from a congenital developmental error and has pathogenetic factors.6 Although the cause of isolated ventricular
been traced back to single point mutations in various genes, non-compaction is not fully elucidated, the disease is thought to be
especially, mutation in the b-myosin heavy chain gene.3 a morphogenetic abnormality involving an arrest of compaction
Spongy myocardium has almost invariably been associated of the loose myocardial meshwork during fetal ontogenesis.
with other congenital cardiac malformations.4 This implies that isolated ventricular non-compaction should
be present at birth in all patients, a notion supported by two
Morphology previous reports.7,8 Since isolated ventricular non-compaction
has so far lacked a pathophysiological characterization, this
The ventricular walls of both ventricles in the normal heart are congenital anomaly has been unspecifically assigned to a
made up predominantly of a compacted layer of myocardial heterogeneous group of ‘unclassified cardiomyopathies’. The
fibers set in a matrix of supporting connective tissue.5 The non- classification serves to bridge the gap between ignorance and
compaction of the left ventricle (LV) consists of a meshwork knowledge. This type of congenital cardiomyopathy has not
of numerous prominent muscle bands called trabeculations in been fully understood so far and remains unclassified by the
the left ventricular apex and to a variable extent the apical WHO, although it is thought to have some individual features.
aspect of the left ventricular free wall with deep intertrabecular In 2006, the American Heart Association classified this entity as
recesses (Figure 1). These trabeculae account for more than a primary cardiomyopathy of genetic origin.9
half of the wall thickness in the affected areas. Typically,
the two-layered appearance of the myocardium is an outer Incidence
thin compact layer and a non-compact trabeculated thick
endocardial layer, with deep intertrabecular spaces, mostly Left ventricular non-compaction (LVNC) was once considered
near the right and left ventricular apex, below the papillary a rare form of myocardial disorder.10-13 The morphological
muscle level and also the apical portion of the septum. The pattern of LVNC has been seen both as an isolated finding and
9
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
also in association with other congenital anomalies. Iso- the ventricle during intrauterine development are absent.
lated LVNC is now being recognized with increasing fre- In particular, various forms of semilunar valve obstruction
quency, with various echocardiographic studies reporting or left ventricular outflow tract obstruction have to be ruled
its finding in between 0.05 percent and 0.24 percent.7,8,14-17 out. A similar persistence of non-compacted myocardium is
Ritter et al15 suggested that the incidence is 0.05% in frequently reported in patients with congenital left or right
adults. Pignatelli et al17 from the Texas Children’s Hos- ventricular outflow tract obstruction and is referred to as ‘spongy
pital, reviewed about 50,000 echocardiograms performed myocardium’ or ‘persisting sinusoids’ that communicate with
in over 26,000 patients from 1997 to 2002 and found the coronary arteries.4,21-26 (Figure 2A) By contrast, isolated
36 patients with the isolated form of the malformation. Over ventricular non-compaction is a genetically heterogeneous
this period, the same group diagnosed 344 cases of cardiomy- congenital disorder characterized by a pattern of excessively
opathy, and/of which non-compaction accounted for one-tenth prominent trabecular meshwork and deep intertrabecular
of their cases of cardiomyopathy, a proportion very similar to recesses in the absence of other structural heart diseases.2,27,28
that calculated by Nugent et al in Australia.18 Oechslin et al16 Furthermore, while the persisting sinusoids are enlargements
estimated that isolated LVNC was seen in 0.0014 of all pa- of the coronary vessels (comparable with hemangioma), the
tients referred to their department of echocardiography over a recesses in isolated ventricular non-compaction have no
period of 14 years. Although these contemporary data suggest connection with the coronary circulation.16,23 (Figure 2B). In
that isolated LVNC is an extremely rare form of cardiomyo- fact they are recesses covered by endocardial lining continuous
pathy, we must now accept that it is being recognized with with the ventricular cavity, predisposing to local thrombus
increasing frequency, so we may need to revise our views in formation.
the light of emerging findings.
If ventricular non-compaction does not coexist with other Historical review
cardiovascular pathologies it is called ‘isolated’ ventricular
non-compaction. Although the LV is most commonly Although described as early as 1932, the disorder was
affected (62%), both ventricles can be influenced in some largely unrecognized until the widespread availability of
cases (22–38%).19 In a study, 22 patients (76%) had isolated echocardiography, which has enhanced the detection. It was
ventricular non-compaction and only the LV was affected in Dusek et al4 who provided one of the earliest substantial
all of them.20 descriptions of the entity that probably represents what
698 In isolated ventricular non-compaction, coexisting cardiac we now call ventricular non-compaction. They called
anomalies that cause excessively high pressure exposure of it postnatal persistence of spongy myocardium with an
49
Non-compaction of the Ventricles

A B
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 G4.5 in one family with severe X-linked LVNC, but without the
described for the first time, morphologically underdeveloped other usual findings of Barth syndrome.34 Pauli et al39 identified
papillary muscles and non-compacted internal myocardial deletion of chromosome 5q in a child with previously repaired
layers, consisting of more than 50 percent of the ventricular congenital heart disease, facial dysmorphism and LVNC. Vatta
wall thickness in their patients.8 Though described as highly et al40 in contrast, have shown that in some patients with either
fatal in early childhood, it has been reported in as old as dilated cardiomyopathy or LVNC, a mutation in Cypher-Zasp,
94-year-old patient.29 a gene encoding a protein i.e. a component of the Z-line in
However ‘non-compacted apex’ in which non-compaction both skeletal and cardiac muscle, may be causal. It may also
of both right and left ventricular apexes and septum is be pertinent that mice lacking FKBP12 have normal skeletal
extremely rare and hardly reported in the literature. Robert muscle, but have a severe dilated cardiomyopathy and a
Anderson says, this is what is known to happen in the ‘chicken condition suggestive of LVNC.41 Clinical studies suggest
heart’, but thus far there has been no evidence to suggest a that LVNC is often familial with predominantly autosomal
similar mechanism in human. Hence, its cause, development, dominant inheritance. It has been linked to mutations in several
clinical course and treatment are fields of further research genes including ZASP,40 a dystrobrevin36 and tafazzin.36,42
in future. The disease can present throughout life with progressive left
ventricular systolic dysfunction.
Genetics Left ventricular non-compaction is certainly known
also to be a part of various syndromes, including the Barth,
Analysis of genetic linkage and mutation has revealed that Noonan, Roifman, Melnick-Needles, Nail-patella, Toriello-
mutations in the gene G4.5, which encodes tafazin and maps to Carey and other uncommon syndromes.14,37,38,43-51 Analysis
chromosome Xq28, are responsible for this myocardial disorder of the Roifman syndrome, characterized by a constellation
in some patients being allelic with Barth syndrome.30-36 In this of antibody deficiency, spondyloepiphyseal dysplasia, facial
regard, G4.5 was initially identified as the gene responsible for dysmorphism, growth retardation and retinal deficiency,
Barth syndrome, an X-linked mitochondrial disease affecting suggested an X-linked pattern of inheritance.45 The etiology
cardiac and skeletal muscle.37,38 These mutations produce a of the Toriello-Carey syndrome, first reported in 1988,
wide phenotypic spectrum of cardiomyopathies, including is unknown, but both X-linked and autosomal recessive
dilated cardiomyopathy, X-linked infantile cardiomyopathy, inheritance have been suggested.46,51 In one case, a 3-year-
and X-linked endocardial fibroelastosis.36 Ichida et al7 found old boy was diagnosed both with the Toriello-Carey syndrome
a mutation in α-dystrophin in some of their patients. Chen and non-compaction, with ultrasound confirming a similar 699
et al. found a novel splice acceptor site mutation of intron 8 of constellation in his unborn sibling.51
9 Embryology the trabecular cardiomyocytes. In support of the cellular
recruitment mechanism, proliferative activity is consistently
The heart is the first organ to form and function in the vertebrate higher within the compact myocardium, as there is a gradient
embryo.52-61 In this respect, Kirby58 has written—“Heart of decreasing proliferation and increased differentiation
development in all vertebrates from fish to humans follows from the outside of the heart toward the lumen and trabecular
the same general pattern: fusion of the myocardium and side.70-73 This balance of proliferation and differentiation
endocardium in the ventral midline to form a simple tubular is critical to the formation of a functionally competent
heart”. ventricular wall. The hypertrabeculation is likely to be the
Before the fifth week of intrauterine life, the myocardium result of altered regulation in cell proliferation, differentiation
forms a loose network of fibers and sinusoids, which are in and maturation during ventricular wall formation.
continuity with the ventricular cavity. Subsequently, the The fetal heart muscle has a non-compacted appearance
meshwork of fibers become ‘compacted’ and the sinusoids between the 4th and 18th week of development and this
disappear. Pathological arrest of this compaction process leads is important for the nutrition of its cells. The spongy
to the persistence of ventricular hypertrabeculation, so called myocardium is supplied predominately by diffusion of blood
spongy myocardium or LVNC.62 In 1990, Chin et al described in the heart that flows into the spaces between the muscle
a group of eight patients with non-compaction, which was bands. Later and simultaneously with the development of the
not associated with other congenital cardiac abnormalities.8 coronary arteries, which will eventually take over carrying
But recently the childhood form of non-compaction was first blood to the heart muscle, development of the muscle bands
described in association with other congenital abnormalities appears to go backwards. The thickness of the compacted
such as cyanotic congenital heart disease, coronary artery wall and the mass of the heart muscle is then increasing
anomalies and both right and left ventricular outflow tract and hence the pumping function is increasing too. The final
obstruction.4,15,26 Furthermore, it may be associated with appearance is that of a compacted muscular wall of the
neuromuscular abnormalities. Others suggest that it is more heart with minor muscle bands close to its inner surface.
common and that its prognosis is better than expected.63 Therefore ventricular walls of both ventricles in the normal
During mammalian embryonic heart development, heart are made up predominantly of a compacted layer of
the ventricles undergo a series of morphogenetic myocardial fibers set in a matrix of supporting connective
developments.64-66 Ventricular trabeculation and compaction tissue.5 Rana et al in their study on fertilized chicken egg
are two of the many essential steps for generating a state that component ballooning from the initial linear heart
functionally competent ventricular wall.67 Simplistically, tube is destined to become the LV, the ventricular septum
development of the ventricular wall has four distinct stages. and the adjacent trabeculations. Most importantly, their
Stage I, is the formation of single-cell layered myocardium study shows that the RV, in essence, has comparable origins
at an early developmental stage. Following induction via in mammals and birds, allowing direct extrapolation of
adjacent endoderm, lateral mesoderm gives rise to an early findings in birds to mammalian cardiac development.74 It is
tubular heart. The heart at this stage is composed of one cell of interest to note that, in the evolution of the vertebrates,
layer of myocardium and one cell layer of endocardium lining myocardial non-compaction is advantageous and indeed
the lumen.64,68 Stage II, is the formation of a trabeculated and necessary, for the circulatory function of some fish and yet
compact myocardium at the early mid-gestation stage. As the its presence is decidedly disadvantageous for man.23,75,76
myocardium thickens, cardiomyocytes along the inner wall Ventricular non-compaction, a genetically heterogeneous
form sheet-like protrusions into the lumen to give rise to the disorder,77 may affect both ventricles and apical septum,
trabecular myocardium, while the outside layer of myocardium may be associated with many diverse forms of congenital
becomes organized into compact myocardium. Ventricular cardiac malformations. This apical non-compaction entity
trabeculation has been suggested to facilitate oxygen and was detected in the fetus of 24 weeks gestation with
nutrient exchange and to enhance force generation to match muscular ventricular septal defect (VSD) (Figure 3). This
the increasing blood flow in developing embryos.64,67 Stage patient came back to us after delivery and the infant did have
III, myocardial compaction, occurs at the late mid-gestation apical non-compaction along with a large VSD and patent
stage. As development proceeds, the trabecular myocardium ductus arteriosus.
becomes compacted towards the myocardial wall and
contributes to forming a thicker, compact ventricular wall. Clinical Findings
Stage IV, is the formation of a mature and multilayered spiral
myocardium during the late fetal and neonatal stage.66,69 Patients with LVNC may have normal ventricular function,
Following the formation of primitive trabecular ridges hemodynamics and may lead a normal life. Patients may
the myocardium undergoes extensive expansion either by present at any age from infancy to older than 94 years.29
recruitment of cardiomyocytes from the myocardial wall The clinical manifestations may include heart pump failure,
700 into the trabecular ridges or via cellular proliferation within arrhythmias and thromboembolic events.14
Diagnosis 49
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.
Figure 3: Fetal echocardiography in a 24 weeks gestation fetus shows
midmuscular ventricular septal defect with apical non-compaction Echocardiography
The diagnosis of non-compaction is mostly based on the
Ichida et al7 suggest that this difference may be accounted morphologic features of the left ventricle.81,82 Echocardiography
for by the fact that LVNC in their patients was detected has been the routine initial non-invasive diagnostic test to detect
incidentally during a screening study of an entire population LVNC and is still the diagnostic test of choice.83,84 There is
of Japanese children. Whether the extent or degree of little consensus on the diagnostic criteria of non-compaction.
hypertrabeculation has a role in determining the timing of The extent of non-compaction has also been adopted as a
presentation and severity of clinical course, is also uncertain, diagnostic criterion for non-compaction. Several authors have
although this has been suggested.8,78 Because of the known stipulated diagnostic thresholds using various measures of non-
genetic heterogeneity,79 it is yet to be determined if a specific compaction.8,16,77,85 A number of echocardiographic definitions
genetic marker may contribute to either the severity or timing for the diagnosis of LVNC have been proposed (Table 1). Two
of presentation. In 27 percent of cases, extracardiac diseases are based on an analysis of fewer than 45 patients with what
mainly mental and motor retardation were found in a study. appeared to be a common phenotype; the third is extrapolated
The most common complaints at admission were due to heart from a post-mortem study examining the number of prominent
failure (69%). The mortality rate was 21 percent and death trabeculations.8,85,86 Although all definitions attempt to describe
was caused by cardiac failure and sepsis.20 the morphology of the condition, they differ substantially in
 Table 1
Diagnostic criteria for left ventricular non-compaction
Author Criteria
Chin et al8 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.
Jenni et al85 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
9 their approach. The method proposed originally by Chin et al8 conspicuous is the trabecular recesses that penetrate deep into
evaluates the size of trabeculations in relation to the thickness the ventricles. The echocardiographic pattern is characteristic
of the compacted wall in different echocardiographic views and and diagnostic.87,88 Echocardiography, nonetheless, is less
at different levels of the LV in end-diastole. In this study to than perfect for the diagnosis of non-compaction, since the
quantify the depth of penetration of the intertrabecular recesses adequacy of the investigation depends very much on the
with two-dimensional echocardiography, X to Y ratio has been experience and knowledge of the investigator. Non-compaction
developed (Figure 4). This ratio quotient is of the distance of the apex and the septum are seen as Swiss cheese appearance
between the epicardial surface and trough of a trabecular (Figure 5).
recess (represented by X) and the distance between epicardial Transthoracic echocardiography (TTE) is also useful in
surface and peak of the trabeculae (represented by Y). LVNC is detecting associated lesions like multiple muscular VSDs
defined when the ratio of X/Y ≤ 0.5. The schematic diagram of and supramitral ring along with non-compaction (Figures 6
diagnostic features of biventricular non-compaction with Swiss and 7). A case of probable apical non-compaction in young
cheese interventricular septum is shown in Figure 4. Jenni and man with biventricular non-compaction associated with
coworkers85 have proposed a method that relies on the detection VSD and having undergone surgery at the age of two years
of the two myocardial layers, non-compact and compact, for coarctation of aorta, who presented with heart failure is
in short-axis views of the LV in end-systole. LVNC, in this reported.89 The evidence of non-compacted myocardium in
instance, is defined by the ratio > 2 between non-compacted to both left and right ventricular apex was made with intracardiac
compacted layers. The third definition, proposed by Stollberger echocardiography performed during the electrophysiologic
et al.86 determines the number of prominent trabeculations study for arrhythmia is reported. This method has allowed the
visible in the apical views of the LV in diastole. diagnosis of non-compaction of the ventricular myocardium
The diagnosis of spongy myocardium is challenging, as it due to its high resolution. Color Doppler showed trabecular
has to be differentiated from muscle bundles. Discrete muscle recesses in communication with the ventricular cavity that
bundles, more than 2 millimeter in diameter, that stand out could not be identified with transthoracic echocardiography.90
against the background of the left ventricular endocardium, has Thromboembolic events have been reported in 21 percent to
been reported in 68 percent of normal hearts and are virtually 38 percent of patients with non-compaction and chest pain in
always two to three or less in number. In contrast, in non- 19 percent.8,15,16 The thrombus can be detected in LV (Figure
compaction, there are numerous prominent trabeculations and 8A) or thrombus could be in RV. One of our patient with
702 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 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;
RV = Right ventricle. A
Figure 6: 8 years old asymptomatic boy with multiple muscular ven-

tricular 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. B
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.
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
A B trabeculated nature of the RV itself and secondly, due to
Figures 7A and B: A. Apical four-chamber view in a 3-year-old boy problems with echocardiographic access to the RV behind the
shows large midmuscular ventricular septum defect, non-compaction sternum. Previous echocardiographic studies have reported
of left ventricle, septum and right ventricle. There is a thin epicardial right ventricular involvement in less than half of patients with
layer and an extremely thickened endocardial layer with prominent unequivocal non-compaction of the LV.15,62,93,94 In our own
trabeculations and deep recesses; B. Color Doppler imaging shows
blood flow through ventricular septum defect and from the ventricular experience based on cardiac magnetic resonance imaging, some
cavity into the deep recesses 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
biventricular non-compaction with severe aortic stenosis with insertion of the apex of the RV, as viewed in the horizontal long-
biventricular dysfunction had multiple, mobile soft clots in axis view. This phenomenon can also be recognized in several 703
the RV (Figure 8B). previous publications describing non-compaction.17,95,96
9 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 Figure 9: Right ventricular angiogram in a 2-year-old boy with situs

inversus, dextrocardia, double outlet right ventricle with severe
Left ventriculography is rarely required today to make the infundibular stenosis showing non-compaction of the apex, septum
and left ventricle
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.
Magnetic Resonance and Computed

Tomographic Imaging
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 tunnel-
like septal defect (Figure 10) but MRI was more useful.
Sometimes prominent muscular trabeculations with deep
intertrabecular recesses in the apex is well demonstrated by Figure 10: Transthoracic echocardiography in parasternal long-
cardiac MRI of both the ventricles. The Swiss cheese VSD in axis view with color Doppler shows long track like ventricular septal
defect. AO = Aorta; LV = Left ventricle; RV = Right ventricle; VSD =
both TTE and MRI resemble the delta of the river (Figures 11A Ventricular septal defect.
to C).
Magnetic resonance cine imaging, by using so-called steady
state free precession sequence (SSFP), is increasingly used internally by an interrupted layer of tissue. The trabeculations
because of its ability to clearly visualize the compacted and hang from this layer towards the compacted layer, appearing
non-compacted layers.77 This technique shows a wider extent like a cascading necklace. It has also been suggested that the
of disease and a greater ratio of non-compacted to compacted delayed hyperenhancement technique might be able to visualize
myocardium, when compared to echocardiography in cases with the necrotic or fibrotic myocardium that could be the focus
704 LVNC.77 Interestingly, the non-compacted layer is demarcated of the ventricular arrhythmia.95 Another advantage of MRI
49

A B C
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.
A B
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 tissue. The abnormal non-compacted myocardium is thickest
assessment of all cardiac segments. Sequences based on the use in the apex. It extends to the atrioventricular junction along
of contrast then allow the assessment of myocardial perfusion the free wall, while the basal one-third of the septum is not
and the evaluation of myocardial fibrosis.100 This modality involved.
also allows visualization of left ventricular thrombus.101,102
Computed tomography, however, is of limited value, because it Differential diagnosis
is not possible to assess regional and global ventricular function
and furthermore, the technique depends on the use of radiation. Once the dilated and hypertrophic variants of cardiomyopathy
The utility of electrographically gated CT, nonetheless should are excluded from consideration, there are relatively few
be investigated. Cine MRI in four-chamber and two-chamber further potential diagnosis for myocardial non-compaction.
views shows an interrupted layer of tissue delineating the It is, of course, necessary to exclude the false diagnosis of
non-compacted layer of myocardium from the left ventricular ‘normal’ left ventricular trabeculations as non-compaction, as
cavity. The trabeculations are seen as fine strands extending we discussed earlier. It is also necessary to distinguish non-
from the compacted myocardium towards the thin layer of compaction from the acquired changes seen in the setting 705
9 of lesions such as pulmonary atresia with intact ventricular non-compaction seem less troubled with severe disturbances
septum. Another potentially misleading condition is the of rhythm.
appearance of layered mural thrombus of the LV simulating Cerebrovascular accidents certainly contribute to co-
non-compaction.14 It has also been suggested that mycotic morbidity in patients with isolated LVNC, the unusual
invasion of the heart can produce the appearance of abnormal hypertrabeculations not only reducing ventricular
trabeculations,103,104 while rarely an intramyocardial hematoma function, but also creating a nidus for formation of mural
may mimic isolated LVNC.105 The question has also been thrombus.7,8,14-17,98,110-115 It is difficult, however, precisely to
asked as to whether LVNC can be a cardiac manifestation determine the incidence of adverse neurological events. It has
of Fabry disease.106 In this respect, while the appearances of been suggested that patients should at least be placed on a
hypertrophic cardiomyopathy are well-documented in patients protocol of oral anticoagulation once the diagnosis of isolated
with Fabry disease, to the best of our knowledge there is no LVNC is made. Of course, if a patient has sustained and
data supporting unequivocally the association of this inborn unequivocal thromboembolic event, then full anticoagulation
metabolic disorder with LVNC. with low-molecular-weight heparin is advised.7,8,16,17 The
The WHO classification of cardiomyopathies should successful interventions for the associated lesions, which
reconsider, inclusion of isolated ventricular non-compaction could be a ray of hope in these patients with pump failure and
as a distinct cardiomyopathy. This would improve not only the reduce the morbidity and postpone the mortality. The balloon
knowledge, but also the awareness of this disorder and thus, dilatation can be done for critical aortic stenosis and coarctation
facilitate its diagnosis, as even a skilled echocardiographer’s of aorta. In our series of cases of apical non-compaction, two
eye sees better, while knowing what to look for.85 situs inversus dextrocardia patients underwent successful
interventions. One 4 year old boy underwent aortic balloon
outcome valvuloplasty (Figure 12 A and B) and another 8 years old
girl’s mid-muscular VSD was closed with Amplatzer duct
Many of the early clinical reports emphasized the dismal occluder II (Figure 13 A and B). Non-compaction of the
outcomes of patients with isolated LVNC,7,8,14-17,62,85,98, ventricle with associated aorto-left ventricular tunnel closed
107-115 focusing on the egregious nature of the often malignant by Amplatzer duct occluder is reported for the first time in
accompanying arrhythmias. Increasing clinical experience world literature.122 This patient had hemolysis for five days.
has modified to some extent this bleak outlook.17,98 In some Hemolysis probably can be minimized if a custom made
asymptomatic patients, isolated LVNC has been found as an device is used to fit the anatomy of the tunnel. Aorto-right
incidental finding.116,117 In others it has been recognized in the ventricular tunnel in biventricular non-compaction has
sixth and seventh decades of life and beyond. Yet the disorder been closed with Amplatzer duct occluder II.123 Associated
certainly has the potential for a poor outcome. Even for those multiple VSDs can be closed by device to reduce the volume
patients presenting in the first year of life with depressed left overload and pump failure in ventricular non-compaction
ventricular contractility, with some recovery of ventricular (Figures 14 A and B). Surgery in ventricular non-compaction
function, recovery can be transient. with associated lesions carry high risk. Therefore non-surgical
In 27 percent of cases in a study, extracardiac diseases, transcatheter interventions are better options for post surgical
mainly mental and motor retardation were found. The most residual VSDs.
common complaints at admission were due to heart failure
(69%). The mortality rate was 21 percent and death was FUTURE
caused by cardiac failure and sepsis.20
The currently increased awareness of the condition has
MANAGEMENT recently led to frequent reports in the medical literature
of people having the features of non-compaction, but
A variety of medical therapies have been utilized in those the clinical significance of this has to be evaluated with
symptomatic patients with congestive heart failure, including caution. High priority should be given to establishing
cardiac glycosides, diuretics, inhibitors of angiotensin standard nomenclature and diagnostic criteria for future
converting enzyme and afterload reducing agents. In those research.82,124,125 Genetic testing of the most clinically
suspected of having an underlying mitochondrial myopathy, affected individuals, echocardiographic or cardiac MRI
a ‘metabolic’ cocktail has been used.17 Beta-blockers has also screening of all first degree relatives and obtaining family
been used with some success.118 Some patients have needed history for at least three generations, need to be implemented
cardiac transplantation.119 Disturbances of rhythm have in clinical practice, to further understand the influence of
been treated in standard fashion, while some have implanted genetic mechanisms in this disorder. Finally, the clinicians,
defibrillators for severe ventricular arrhythmias recognized as imaging specialists, geneticists and pathologists all need to
predisposing to sudden death.120,121 Surprisingly, patients with contribute their scientific knowledge to define this elusive
706 complex congenital cardiac malformations coexisting with entity called ‘ventricular non-compaction’.126-128
49

A B
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
A B
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 perhaps more common in children. The entity has now been
recognized in the fetus and also in the octogenarian, with
Ventricular non-compaction, a genetically heterogeneous many patients presenting or identified in adults. The peculiar
disorder,78 may affect both ventricles, may be isolated or may association of LVNC with many kinds of neuromuscular
be associated with many diverse forms of congenital cardiac disorders is well-established, but the reasons for this
malformations. It has been identified in patients with a variety association have not been clarified. The prognosis for the
of syndromes. When confined to the LV, patients may present symptomatic patient is generally poor, with progression to
like those with idiopathic dilated cardiomyopathy or less chronic cardiac failure and death. Some patients with isolated 707
frequently with restrictive physiology, this latter physiology LVNC will die suddenly due to arrhythmias, thromboembolism
9 and left ventricular dysfunction. The recently recognized cardium: a rarity or missed diagnosis? Circulation. 2002;106:
myocardial malformation with non-compaction of both the E22-E23.
ventricular apex and septum is almost always associated 14. Stöllberger C, Finsterer J. Left ventricular hypertrabeculation/
with other hemodynamically significant congenital cardiac noncompaction. J Am Soc Echocardiogr. 2004;17:91-100.
malformations, which worsen the pump failure, pre-existing 15. Ritter M, Oechslin E, Sutsch G, et al. Isolated noncompaction
of the myocardium in adults. Mayo Clin Proc. 1997;72:26-31.
with the non-compaction. Non-surgical interventions or
16. Oechslin EN, Attenhofer Jost CH, Rojas JR, et al. Long-
surgical correction of associated lesions though difficult is term follow-up of 34 adults with isolated left ventricular
feasible and can reduce the morbidity and possibly postpone noncompaction: a distinct cardiomyopathy with poor
mortality. Some symptomatic patients may benefit from prognosis. J Am Coll Cardiol. 2000;36:493-500.
orthotopic cardiac transplantation, if medical therapy fails to 17. Pignatelli RH, McMahon CJ, Dreyer WJ, et al. Clinical
stabilize the condition. characterization of left ventricular noncompaction in children:
a relatively common form of cardiomyopathy. Circulation.
Life is short, the art long, opportunity fleeting, experiment 2003;108:2672-8.
treacherous, judgment difficult. 18. Nugent AW, Daubeney PE, Chondros P, et al. The epidemiology
of childhood cardiomyopathy in Australia. N Engl J Med.
—Hippocrates
2003;348:1639-46.
19. Ulusoy RE, Ku¨çu¨karslan N, Kırılmaz A, et al. Noncompaction
References of ventricular myocardium involving both ventricles. Eur J
Echocardiogr. 2006;7:457-60.
1. Junga G, Kneifel S, Von Smekal A, et al. Myocardial ischaemia 20. Ozgur S, Senocak F, Arman Orun U, et al. Ventricular non-
in children with isolated ventricular non-compaction. Eur compaction in children: clinical characteristics and course.
Heart J. 1999;20:910-6. Interact Cardiovasc Thorac Surg. 2011;12(3):370-3.
2. Jenni R, Goebel N, Tartini R, et al. Persisting myocardial 21. Grant RT. An unsusual anomaly of the coronary vessels in the
sinusoids of both ventricles as an isolated anomaly: malformed heart of a child. Heart. 1926;13:273-83.
echocardiographic, angiographic and pathologic anatomical 22. Bellet S, Gouley BA. Congenital heart disease with multiple
findings. Cardiovasc Intervent Radiol. 1986;9:127-31. cardiac anomalies: report of a case showing aortic atresia,
3. Budde BS, Binner P, Waldmuller S, et al. Noncompaction fibrous scar in myocardium and embryonal sinusoidal remains.
of the ventricular myocardium is associated with a de novo Am J Med Sci. 1932;183:458-65.
mutation in the beta-myosin heavy chain gene. PLoS One. 23. Angelini A, Melacini P, Barbero F, et al. Evolutionary
2007;2(12):e1362. persistence of spongy myocardium in humans. Circulation.
4. Dusek J, Ostadal B, Duskova M. Postnatal persistence of 1999;99:2475.
spongy myocardium with embryogenic blood supply. Arch 24. Davignon AL, DuShane JW, Kinacaid OW, et al. Pulmonary
Pathol. 1975;99:312-7. atresia with intact ventricular septum: report of two cases
5. Anderson RH. Anatomy. In: Anderson RH, Baker E, Macartney studied by selective angiocardiography and right heart
F, Rigby ML, Shinebourne EA, Tynan M (Eds). Pediatric catheterization. Am Heart J. 1963;62:690-7.
Cardiology, 2nd edn. Churchill Livingstone, London. 2002. pp. 25. Elliot LP, Adams PJ, Edwards JE. Pulmonary atresia with
37-55. intact ventricular septum. Br Heart J. 1963;25:489-501.
6. Richardson P, McKenna W, Bristow M, et al. Report of the 26. Lauer RM, Fink RM, Petry EL, et al. Angiographic
1995 World Health Organization/International Society and demonstration of intramyocardial sinusoids in pulmonary-
Federation of Cardiology task force on the definition and clas- valve atresia with intact ventricular septum and hypoplastic
sification of cardiomyopathies. Circulation. 1995;93:841-2. right ventricle. N Engl J Med. 1964;271:68-72.
7. Ichida F, Hamamichi Y, Miyawaki T, et al. Clinical features of 27. Gerull B, Sasse-Klaassen S, Oechslin E, et al. Isolated
isolated noncompaction of the ventricular myocardium: long- ventricular noncompaction of the myocardium is a genetically
term clinical course, hemodynamic properties, and genetic heterogeneous disorder.[abstract] Circulation. 1999;100:I-818.
background. J Am Coll Cardiol. 1999;34:233-40. 28. Tsang JC, Chiu RC. The phantom of “myocardial sinusoids”: a
8. Chin TK, Perloff JK, Williams RG, et al. Isolated historical reappraisal. Ann Thorac Surg. 1995;60:1831-35.
noncompaction of left ventricular myocardium: a study of 29. Sato Y, Matsumoto N, Matsuo S, et al. Isolated noncompaction
eight cases. Circulation. 1990;82:507-13. of the ventricular myocardium in a 94-year-old patient:
9. Sarma RJ, Chana A, Elkayam U. Left Ventricular Noncompac- depiction at echocardiography and magnetic resonance
tion . Prog Cardiovasc Dis. 2010;52:264-73. imaging. Int J Cardiol. 2007;119:e32-e34.
10. Wong SP, Oldfield M, Ko AP, et al. Ventricular non-compaction: 30. Gedeon AK, Wilson MJ, Colley AC, et al. X linked fatal
a rare cause of heart failure. Intern Med J. 2003;33:262-3. infantile cardiomyopathy maps to Xq28 and is possibly allelic
11. Baumhakel M, Kindermann I, Kindermann M, et al. Isolated to Barth syndrome. J Med Genet. 1995;32:383-8.
noncompaction of ventricular myocardium syndrome: a rare 31. Matsuda M, Tsukahara M, Kondoh O, et al. Familial isolated
structural heart disease. Dtsch Med Wochenschr. 2003;128:562-7. noncompaction of ventricular myocardium. J Hum Genet.
12. Buonanno C, Variola A, Dander B, et al. Isolated noncompaction 1999;44:126-8.
of the myocardium – an exceedingly rare cardiomyopathy: a 32. Bleyl SB, Mumford BR, Brown-Harrison MC, et al. Xq28-
case report. Ital Heart J. 2000;1:301-5. linked noncompaction of the left ventricular myocardium:
708 13. McCrohon JA, Richmond DR, Pennell DJ, et al. Images in prenatal diagnosis and pathologic analysis of affected
cardiovascular medicine. Isolated noncompaction of the myo- individuals. Am J Med Genet. 1997;72:257-65.
33. Bione S, D’Adamo P, Maestrini E, et al. A novel X-linked
gene, G4.5 is responsible for Barth syndrome. Nat Genet.
52. Icardo JM. Developmental biology of the vertebrate heart. J
Exp Zool. 1996;275:144-61.
49
1996;12:385-9. 53. Sanchez-Quintana D, Garcia-Martinez V, Climent V, et al.

34. Chen R, Tsuji T, Ichida F, et al. Mutation analysis of the G4.5 Morphological changes in the normal pattern of ventricular
gene in patients with isolated left ventricular noncompaction. myoarchitecture in the developing human heart. Anat Rec.
Mol Genet Metab. 2002;77:319-25. 1995;243:483-95.
35. Bleyl SB, Mumford BR, Thompson V, et al. Neonatal, lethal 54. Moore KL (Ed). Cardiovascular system. In: The Developing
noncompaction of the left ventricular myocardium is allelic Human: Clinically Oriented Embryology. Philadelphia: WB
with Barth syndrome. Am J Hum Genet. 1997;61:868-72. Saunders Co;1982;pp.262-76.
36. Ichida F, Tsubata S, Bowles KR, et al. Novel gene mutations 55. Torry TW. Morphogenesis of the Vertebrates. John Wiley and
in patients with left ventricular noncompaction or Barth Sons, New York, 1962;pp.407-69.
syndrome. Circulation. 2001;103:1256-63. 56. Hyman LH. Comparative Vertebrate Anatomy. Chicago:
37. Neustein HB, Lurie PR, Dahma B, et al. An X-linked recessive University of Chicago Press; 1970.p.544.
cardiomyoapthy with abnormal mitochondria. Pediatrics. 57. Van Mierop LHS, Kutsche LM. Comparative anatomy and
1979;64:24-9. embryology of the ventricles and arterial pole of the vertebrate
38. Barth PG, Scholte HR, Berden JA, et al. An X-linked heart. In: Nora JJ, Takao A (Eds). Congenital Heart Disease.
mitochondrial disease affecting cardiac muscle, skeletal muscle Causes and Processes. NY: Futura Publishing Co.; Mt. Kisco.
and neutrophil leucocytes. J Neurol Sci. 1983;62:327-55. 1984;pp.459-74.
39. Pauli RM, Scheib-Wixted S, Cripe L, et al. Ventricular 58. Kirby ML. Molecular embryogenesis of the heart. Pediatr
noncompaction and distal chromosome 5q deletion. Am J Med Develop Pathol. 2002;5:516-43.
Genet. 1999;85:419-23. 59. Wessels A, Markwald R. Cardiac morphogenesis and
40. Vatta M, Mohapatra B, Jimenez S, et al. Mutations in Cypher/ dysmorphogenesis. 1. Normal development. In: Tuan RS, Lo CW
ZASP in patients with dilated cardiomyopathy and left (Eds). Methods in Molecular Biology, Vol. 136. Developmental
ventricular non-compaction. J Am Coll Cardiol. 2003;42: Biology Protocols. Totowa: Humana Press; NJ, 2000;pp.239-59.
2014-27. 60. Davis CL. Development of the human heart from its first
41. Shou W, Aghdasi B, Armstrong DL, et al. Cardiac defects and appearance to the stage found in embryos of twenty paired
altered ryanodine receptor function in mice lacking FKBP12. somites. Carneg Inst Contrib Embryol. 1927;107:245-83.
Nature. 1998;391:489-92. 61. Gittenberger-de Groot AC. Mannheimer Lecture. The
42. Kenton AB, Sanchez X, Coveler KJ, et al. Isolated left quintessence of the making of the heart. Cardiol Young. 2003;
ventricular noncompaction is rarely caused by mutations in 13:175-83.
G4.5, alpha-dystrobrevin and FK Binding Protein-12. Mol 62. Zambrano E, Marshalko SJ, Jaffe EL, et al. Isolated noncom-
Genet Metab. 2004;82:162-6. paction of the ventricular myocardium: clinical and molecular
43. Amann G, Sherman FS. Myocardial dysgenesis with persistent aspects of a rare cardiomyopathy. Lab Invest. 2002; 82:117-22.
sinusoids in a neonate with Noonan’s syndrome. Pediatr Pathol. 63. Murphy RT, Thaman R, Blanes JG, et al. Natural history
1992;12:83-92. and familial characteristics of isolated left ventricularnon-
44. Wong JA, Bofinger MK. Noncompaction of the ventricular compaction. Eur Heart J. 2005;26:1144-5.
myocardium in Melnick–Needles syndrome. Am J Med Genet. 64. Bartman T, Hove J. Mechanics and function in heart
1997;71:72-5. morphogenesis. Dev Dynam. 2005;233(2):373-81.
45. Mandel K, Grunebaum E, Benson L. Noncompaction of the 65. Moorman AF, Christoffels VM, et al. The heart-forming fields:
myocardium associated with Roifman syndrome. Cardiol one or multiple? Philos Trans R Soc Lond Ser B Biol Sci.
Young. 2001;11:240-3. 2007;362(1484):1257-65.
46. Toriello HV, Carey JC. Corpus callosum agenesis, facial 66. Taber LA. Mechanical aspects of cardiac development. Prog
anomalies, Robin sequence, and other anomalies: a new Biophys Mol Biol. 1998;69(2–3):237-55.
autosomal recessive syndrome? Am J Med Genet. 1988;31: 67. Sedmera D, Pexieder T, et al. Developmental patterning of the
17-23. myocardium. Anat Rec. 2000;258(4):319-37.
47. Yamatogi Y, Ohtahara S. Early infantile epileptic encephalopathy 68. Brutsaer DL, Andries LJ. The endocardial endothelium. Am J
with suppression-bursts, Ohtahara syndrome; its overview Physiol. 1992;263(4 Pt 2):H985-H1002.
referring to our 16 cases. Brain Dev. 2002;24:13-23. 69. Mikawa T, Gourdie RG, et al. Induction and patterning of the
48. Ohtahara S, Yamatogi Y. Epileptic encephalopathies in early Purkinje fibre network. Novartis Found Symp. 2002;250:142-
infancy with suppression-burst. J Clin Neurophysiol. 2003;20: 53; discussion 153-6.
398-407. 70. Icardo JM. Heart anatomy and developmental biology.
49. Finsterer J, Stöllberger C, Kopsa W. Noncompaction on Experientia. 1988;44(11–12):910-9.
cardiac MRI in a patient with Nail–Patella syndrome and 71. Icardo JM, Fernandez-Teran A. Morphologic study of
mitochondriopathy. Cardiology. 2003;100:48-9. ventricular trabeculation in the embryonic chick heart. Acta
50. Happle R, Daniels O, Koopman RJJ. MIDAS syndrome Anat (Basel). 1987;130(3):264-74.
(micropthalmia, dermal aplasia, and sclerocornea): an X-linked 72. Pasumarthi KB, Field LJ. Cardiomyocyte cell cycle regulation.
phenotype distinct from Goltz syndrome. Am J Med Genet. Circ Res. 2002;90(10):1044-54.
1993;47:710-3. 73. Rumyantsev PP, Krylova MI. Ultrastructure of myofibers and
51. Lacombe D, Creusot G, Battin J. New case of Toriello–Carey cells synthesizing DNA in the developing and regenerating
709
syndrome. Am J Med Genet. 1992;42:374-6. lymph-heart muscles. Int Rev Cytol. 1990;120:1-52.
9 74. Rana MS, Horsten NC, Tesink-Taekema S, et al. Trabeculated
right ventricular free wall in the chicken heart forms by
92. Chung T, Yiannikas J, Lee LC, et al. Isolated noncompaction
involving the left ventricular apex in adults. Am J Cardiol.
ventricularization of the myocardium initially forming the 2004;94:1214-6.
outflow tract. Circ Res. 2007;100:1000-7. 93. Corrado G, Santarone M, Miglierina E, et al. Isolated
75. Victor S, Nayak VM, Rajasingh R. Evolution of the ventricles. noncompaction of the ventricular myocardium: a study in an
Tex Heart Inst J. 1999; 26:168-75. adult male and literature review. Ital Heart J. 2000;1:372-5.
76. Steiner I, Hrubecky J, Pleskot J, et al. Persistence of spongy 94. Koo BK, Choi D, Ha JW, et al. Isolated noncompaction of
myocardium with embryonic blood supply in an adult. the ventricular myocardium: contrast echocardiographic
Cardiovasc Pathol. 1996;5:47-53. findings and review of the literature. Echocardiography.
77. Petersen SE, Selvanayagam JB, Weismann F, et al. Left ventri 2002;19:153-6.
cular non-compaction: insights from cardiovascular magentic 95. Korcyk D, Edwards CC, Armstrong G, et al. Cardiac-enhanced
resonance imaging. J Am Col Cardiol. 2005;46:101-5. cardiac magnetic resonance in a patient with familial isolated
78. Wald RM, Veldtman GR, Golding F, et al. Determinants of ventricular non-compaction. J Cardiovasc Magn Reson. 2004;
outcome in isolated ventricular noncompaction in childhood. 6:569-76.
Am J Cardiol 2004;94:1581-4. 96. Weiss F, Habermann CR, Lilje C, et al. MRI in the diagnosis of
79. Digilio MC, Marino B, Bevilacqua M, et al. Genetic non-compacted ventricular myocardium (NCVM) compared to
heterogeneity of isolated noncompaction of the left ventricular echocardiography. Rofo. 2003;175:1214-9.
myocardium. Am J Med Genet. 1999;85:90-1. 97. Chung T, Yiannikas J, Lee LC, et al. Isolated noncompaction
80. Freedom RM, Yoo SJ, Perrin D, et al. The morphological involving the left ventricular apex in adults. Am J Cardiol.
spectrum of ventricular noncompaction. Cardiol Young. 2004 1;94:1214-6.
2005;15:345-64. 98. Ali SKM, Godman MJ. The variable clinical presentation and
81. Ramaraj R, Sorrell VL, Marcus F, et al. Recently defined cardio outcomes for noncompaction of the ventricular myocardium
myopathies: a clinician’s update. Am J Med. 2008;121:674-81. in infants and children, and under-diagnosed cardiomyopathy.
82. Kohli S, Pantazis AA, Shah JS, et al. Diagnosis of left- Cardiol Young. 2004;14:409-16.
ventricular non-compaction in patients with left-ventricular 99. Hamamichi Y, Ichida F, Hashimoto I, et al. Isolated
systolic dysfunction: time for a reappraisal of diagnostic noncompaction of the ventricular myocardium: ultrafast
criteria? Eur Heart J. 2008;29:89-95. computed tomography and magnetic resonance imaging. Int J
83. Frischknecht B, Attenhofer Jost CH, Oechslin EN, et al. Valida- Card Imaging. 2001;17:305-14.
tion of noncompaction criteria in dilated cardiomyopathy, and 100. Gebker R, Paetsch I, Wahl A, et al. Ventricular non-compaction.
valvular and hypertensive heart disease. J Am Soc Echocardi- Eur Heart J. 2004;25: Cover Image.
ogr. 2005;18:865-72. 101. Barkhausen J, Hunold P, Eggebrecht H, et al. Detection and
84. Tamborini G, Pepi M, Celeste F, et al. Incidence and characterization of intracardiac thrombi on MR imaging. Am J
characteristics of left ventricular false tendons and trabeculations Roentgenol. 2002;179:1539-44.
in the normal and pathologic heart by second harmonic 102. Petersen SE, Timperley J, Neubauer S. Left ventricular thrombi
echocardiography. J Am Soc Echocardiogr. 2004;17:367-74. in a patient with left ventricular non-compaction – visualisation
85. Jenni R, Oechslin EN, Attenhofer Jost C, et al. Echocardiographic of the rationale for anticoagulation. Heart. 2005;91:e4.
and pathoanatomical characteristics of isolated left ventricular 103. Stöllberger C, Preiser J, Finsterer J. Histological detection
noncompaction: a step towards classification as a distinct of intramyocardial abscesses in Candida sepsis mimicking
cardiomyopathy. Heart. 2001; 86:666-71. left ventricular noncompaction/hypertrabeculation on echo
86. Stollberger C, Finsterer J, Blazek G. Left ventricular cardiography. Mycoses. 2004;47:72-5.
hypertrabeculation, noncompaction and association with 104. Stöllberger C, Preiser J, Finsterer J. Candida sepsis with

additional cardiac abnormalities and neuromuscular disorders. intramyocardial abscesses mimicking left ventricular
Am J Cardiol. 2002;90:899-902. noncompaction. Eur J Echocardiogr. 2004;5:76-8.
87. Vijayalakshmi IB, Sumangala BV, Chitra N. Echo in aorto- 105. Stöllberger C, Finsterer J, Waldenberger FR, et al.

ventricular tunnel with non-compaction of Ieft ventricle. Journal Intramyocardial hematoma mimicking abnormal left ventricular
of the Indian Academy of Echocardiography. 2001;7: 238. trabeculation. J Am Soc Echocardiogr. 2001;14: 1030-2.
88. Vijayalakshmi IB. ‘Role of Echocardiography in Rarest 106. Stöllberger C, Finsterer J, Voigtlander T, et al. Is left ventricular
Congenital Heart Disease’ in Journal of Indian Academy of hypertrabeculation/noncompaction a cardiac manifestation of
Echocardiography. 2003;7:509-12. Fabry’s disease? Z Kardiol. 2003;92:966-9.
89. Tatu-Chitoiu A, Bradisteanu S. A rare case of biventricular 107. Jenni R, Rojas J, Oechslin E. Isolated noncompaction of the
non-compaction associated with ventricular septal defect and myocardium. N Engl J Med. 1999;340:966-7.
descendent aortic stenosis in a young man. Eur J Echocardiogr. 108. Weiford BC, Subbarao VD, Mulhern KM. Noncompaction of
2008;9:306-8. the ventricular myocardium. Circulation. 2004;109:2965-71.
90. Ficili S, Pandozi C, Galeazzi M, et al. Noncompacted 109. Oechslin E, Jenni R. Guest editorial. Isolated left ventricular
ventricular myocardium: characterization by intracardiac echo. non-compaction: increasing recognition of the distinct, yet
J Cardiovasc Med (Hagerstown). 2011;12:294-6. “unclassified” cardiomyopathy. Eur J Echocardiogr. 2002;3:
91. Moon JC, Fisher NG, McKenna WJ, et al. Detection of apical 250-51.
hypertrophic cardiomyopathy by cardiovascular magnetic 110. Halbertsma FJ, van’t Hek LGEM, Daniels O. Spongy
resonance in patients with non-diagnostic echocardiography. cardiomyopathy in a neonate. Cardiol Young. 2001;11:458-
710
Heart. 2004;90:645-9. 60.
111. Neudorf UE, Hussein A, Trowitzsch E, et al. Clinical features
of isolated noncompaction of the myocardium in children.
120. Celiker A, Kafali G, Dogan R. Cardioverter defibrillator
implantation in a child with isolated noncompaction of the
49
Cardiol Young. 2001;11:439-42. ventricular myocardium and ventricular fibrillation. Pacing

112. Kohl T, Villegas M, Silverman N. Isolated noncompaction of Clin Electrophysiol. 2004;27:104-8.
ventricular myocardium detection during fetal life. Cardiol 121. Seres L, Lopez J, Larrousse E, et al. Isolated noncompaction
Young. 1995;5:187-9. left ventricular myocardium and polymorphic ventricular
113. Winer N, Lefevre M, Nomballais MF, et al. Persisting spongy tachycardia. Clin Cardiol. 2003;26: 46-8.
myocardium: a case indicating the difficulty of antenatal 122. Vijayalakshmi IB, Chitra N, Prabhu Deva AN. Use of a

diagnosis. Fetal Diagn Ther. 1998;13:227-32. Amplatzer Duct Occluder for closing an aortico-left ventricular
114. Moura C, Hillion Y, Daikha-Dahmane F, et al. Isolated
tunnel in a case of noncompaction of left ventricle. Pediatr
non-compaction of the myocardium diagnosed in the Cardiol. 2004;25:77-9.
fetus: two sporadic and two familial cases. Cardiol Young. 123. Vijayalakshmi IB, Chitra N, Ashish A . Closure of Aorto-right
2002;12:278-83. ventricular tunnel with Amplatzer Duct Occluder II. Accepted
115. Guntheroth W, Komarniski C, Atkinson W, et al. Criterion for for publication in Journal of Invasive Cardiology on September
fetal spongiform cardiomyopathy: restrictive pathophysiology. 21st 2012.
Obstet Gynecol. 2002;99:882-5. 124. Lurie PR. The perspective of ventricular noncompaction as
116. Tsui KL, Chan KK, Leung TC, et al. Isolated ventricular non- seen by a nonagenarian. Cardiol Young. 2008;18:243-9.
compaction presenting with ventricular tachycardia. Hong 125. Anderson RH. Ventricular noncompaction—a frequently

Kong Med J. 2003;9:137-40. ignored finding? Eur Heart J. 2008;29:10-1.
117. Elshershari H, Okutan V, Celiker A. Isolated noncompaction 126. Stollberger C, Finsterer J. Pitfalls in the diagnosis of left

of ventricular myocardium. Cardiol Young. 2001;11: ventricular hypertrabeculation/noncompaction. Postgrad Med
472-5. J. 2006;82:670-83.
118. Toyono M, Kondo C, Nakajima Y, et al. Effects of carvedilol 127. Nair SB, Khattar RS. Isolated left ventricular non-compaction:
on left ventricular function, mass and scintigraphic an emerging cause of heart failure in adults. Postgrad Med J.
findings in isolated left ventricular non-compaction. Heart. 2009;85:202-7.
2001;86:e4. 128. Engberding R, Yelbuz T, Breithardt G. Isolated noncompaction
119. Stamou SC, Lefrak EA, Athari FC, et al. Heart transplantation of the left ventricular myocardium. A review of the literature
in a patient with isolated noncompaction of the left ventricular two decades after the initial case description. Clin Res Cardiol.
myocardium. Ann Thorac Surg. 2004;77: 1806-8. 2007;96:481-8.
711
C hapter
50 Restrictive Cardiomyopathy
Bhanu Duggal, Neeraj Raghani
Restrictive cardiomyopathy (RCM) is a clinical and Associated History

hemodynamic syndrome resulting from an infiltrative
process involving the myocardium and/or subendocardium. A detailed history should be taken to rule out an underlying
It is characterized by restrictive filling and reduced diastolic disorder or potential causes of RCM.
volume of either one or both the ventricles with normal or near History: Drug treatment (long-term chloroquine treatment,6
normal systolic function. In such cases the input of a normal or L-tryptophan, anthracycline, doxorubicin), radiation for a
small volume of blood into the affected ventricle is followed previous malignancy, history of diabetes, hepatic problems,
by a disproportionate increase in intracavitary pressure, i.e. arthritis for hemochromatosis, weight loss, renal or hepatic
the ventricle compliance curve is shifted to the left.1 problems for amyloidosis, pulmonary problems for scleroderma;
It may occur due to endomyocardial fibrosis (EMF), idiopathic allergic rhinitis or nasal polyps for Churg-Strauss syndrome;
interstitial myocardial fibrosis or as a cardiac manifestation muscle weakness and wasting for neuromuscular disorders
of systemic disease such as scleroderma, amyloidosis, Churg- should be elicited.
Strauss syndrome, cystinosis, sarcoidosis, lymphoma, Gaucher Family history: RCM has an autosomal dominant pattern
disease, hemochromatosis, Fabry disease, hypereosinophilic in desminopathy, Noonan syndrome and unspecified skeletal
syndrome and various neuromuscular disorders.2 myopathy. It is an autosomal recessive disorder associated
with musculoskeletal abnormalities. Familial occurrence of
Prevalence the idiopathic variety has also been reported.
Physical examination: Reveals systemic and pulmonary
Restrictive cardiomyopathy is much less frequent than dilated venous congestion. The most common signs are jugular
or hypertrophic cardiomyopathy. A nationwide epidemiologic venous distension (52%), systolic murmurs (49%), pulmonary
survey in Japan found a crude prevalence of 0.2 per 100,000 rates (18%), ascites (15%) and edema (15%). The jugular
people.3 It is the cause of less then 3 percent cases of diastolic venous pressure (JVP) is elevated (52%) with prominent ‘y’
heart failure in adults and 5 percent in children.4 descent. A low pulse volume due to reduced stroke volume and
tachycardia, can be seen in severe cases. The apical impulse is
Clinical Features 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
Symptoms
and pedal edema are common clinical findings.
As the ventricles are stiff and have restrictive filling, the Other clinical findings to rule out associated clinical disorders
ventricular diastolic and resultant atrial, jugular and pulmonary include skin fibrosis and Raynaud’s phenomenon in scleroderma,
venous pressures are increased. This produces symptoms hyperpigmentation in hemochromatosis; macroglossia and
of pulmonary and/or systemic venous congestion (dyspnea, hepatosplenomegaly in amyloidosis and storage disorders;
orthopnea, edema, abdominal distension) depending on the skeletal abnormalities in Gaucher disease, myeloma; muscle
affected ventricle. The under filled ventricles cause symptoms weakness and wasting in neuromuscular disorders.
of decreased cardiac output like dyspnea on exertion, chest pain Chest radiography usually shows cardiomegaly as atrial
and easy fatigability. The patient may give history of palpitations enlargement and pericardial effusion can produce an enlarged
or syncope due to associated arrhythmias or conduction defects, cardiac silhouette (Figure 1). A double shadow because of
which are often observed in these disorders.5 enlargement of left atrium and pulmonary artery trunk may be
seen. Pulmonary venous congestion appears in nearly all the Atrial and ventricular arrhythmias and conduction 50
patients (86%).7 disturbances are frequent (Figure 2). Atrial fibrillation is
common in idiopathic restrictive cardiomyopathy. ST-T
restrictive cardiomyopathy
Electrocardiography abnormalities are seen in 80 percent cases, atrial fibrillation
74 percent, intraventricular conduction delay (19%) and the
Electrocardiography (ECG) is abnormal in 98 percent of the ECG is only rarely normal (2%). Atrioventricular block or
patients. The ECG findings corroborate with the enlargement a tachybrady syndrome requiring pacemaker implantation
or hypertrophy of the particular chambers. It usually shows suggests RCM due to neuromuscular disorders such as
evidence of atrial enlargement. Criteria for ventricular hyper desminopathy, myofibrillar myopathy, distal myopathy with
trophy may be seen. Repolarization abnormalities especially rimmed vacuole, chloroquine myopathy or an unspecified
notched and biphasic T waves, obliquely elevated and late myopathy. Familial RCM has been associated with
peaking ST segments, which may prolong the QT interval atrioventricular blocks.8
are seen especially in children. Amyloidosis is a contrasting
example with low voltage ECG seen in all the leads. Blood Test
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
Figure 1: Chest X-ray posteroanterior view shows cardiomegaly,
which they remain normal. It is also a useful prognostic
double shadow due to right atrial (RA) enlargement and pericardial marker as it increases with right heart failure.9
effusion (PE) beyond the RA and left ventricle (LV) border (arrows)
713
Figure 2: Electrocardiogram showing sinus rhythm, biventricular hypertrophy, prolonged QTc, biphasic T wave in chest leads
9
A B
Figure 3A and B: Transthoracic echocardiography with color Doppler shows left ventricular hypertrophy secondary to amyloidosis in a 2-year-
old 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
Figure 4: Apical four-chamber view showing biatrial enlargement
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 Doppler
motion as well as increased dimensions of the right ventricle Mitral and tricuspid regurgitation (TR) is often seen
and right ventricular outflow tract. (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
2D Echo pulmonary hypertension (Figure 6B). The flow through the mitral
and tricuspid valves, depending on which ventricle is damaged,
Systolic function is normal till late stages of the disease. presents as practically forming one peak in protodiastole (the
Ventricular volumes are normal. There may be increased E wave) with an acute reduction in declaration time (DT < 160
wall thickness and a characteristic speckled appearance is ms) and a short isovolumic relaxation time (IVRT < 70 ms)
seen in certain infiltrative disorders. Biatrial enlargement is (Figure 7), followed by a greatly reduced A wave (E/A ratio of
ubiquitous in this disease state (Figure 4), along with dilated mitral inflow > 2.0) (Figure 8). This indicates a pattern of rapid
non-collapsing inferior vena cava (Figure 5), hepatic veins inflow immediately after valve opening followed by an abrupt
714 and pulmonary veins. cessation due to reduction in distensibility.
There is no respiratory variation in the filling patterns. 50
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 7: Modified apical four-chamber view showing calculation of

Doppler Tissue Imaging isovolumic relaxation time (IVRT), from closure of aortic valve to opening
of mitral valve (Patient has a junctional rhythm, and sweep velocity of
Doppler Tissue imaging of the mitral annulus or proximal tissue Doppler is 50 mm/sec
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 Figure 8: Pulse wave Doppler at mitral valve level showing tall E
variation (IVC Plethora) wave, E/A ratio is > 2:1, DT < 150 msec
A B
Figures 6A and B: A. Transthoracic echocardiography in an 11-year-old girl of restrictive cardiomyopathy in apical four-chamber view shows 715
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.
9
Figure 9: Pulse wave Doppler at pulmonary vein Figure 11: Color M-mode: Doppler flow propagation velocity (Vp)
showing systolic (S), diastolic (D) waves (D > S) 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 less than 1/3rd of the RV systolic pressure (Figure 12). The
measured. One is the slope of transition from color to no early dip, rapid rise, and abrupt plateau gives rise to a ‘square
color as measured from tip of mitral leaflets to apex of LV and root’ sign, similar to constrictive pericarditis. The ventricular
second is the slope of the first aliasing velocity from the tip of diastolic pressure rise may be followed by a more sustained
the mitral leaflets to a position 4 cm distal into the LV(Vp). In rise, a mid-diastolic ventricular pressure rather than a true
RCM, Vp is less than 4 cm/s (Figure 11). plateau. This dip and plateau in the diastolic pressure waveform
Restrictive cardiomyopathy is often a global process is represented by a rapid Y descent followed by a rapid rise and
and similar pathology can be noted in the right ventricle, plateau in the atrial pressure tracing (Figure 13). The descent
including varying degrees of hypertrophy and infiltration and of V wave becomes more prominent in inspiration. A higher
abnormalities of tricuspid inflow and hepatic vein flow as seen LV than RV filling pressure (> 6 mm Hg) strongly favors the
on the left side.10 diagnosis of restrictive cardiomyopathy.1,11
Cardiac Catheterization Endomyocardial Biopsy

The cardiac index is often decreased. The early portion of left For a definitive diagnosis of RCM, Endomyocardial biopsy
and right ventricular pressure tracing in diastole is characterized (EMBx) is needed in many cases to establish the diagnosis
716 by a sharp dip (deep and rapid early decline in ventricular as well as to differentiate from constrictive pericarditis.
pressure) and then a precipitous rise in the rapid filling phase. In RCM due to amyloidosis, myocardial biopsy shows
The right ventricular end diastolic pressure (RVEDP) is usually interstitial amyloid deposits. Immunohistochemical staining
hypotension. Patients of cardiac amyloidosis may be very 50
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
Figure 13: Right atrial pressure tracing showing a rapid Y descent diastolic dysfunction and a hypertensive response to exercise.
Anticoagulation should be considered because of significant
risk of thromboembolic complications. Therapies directed
determines the type of amyloid. In idiopathic RCM, at specific forms of this condition include chelation therapy,
endomyocardial biopsy demonstrates interstitial fibrosis. phlebotomy, bone marrow transplantation, salt restriction and
Immunofluorescent straining, immunohistochemical studies implantable cardioverter defibrillator placement. In children,
and electron-microscopy may be needed for the diagnosis. RCM is primarily idiopathic and transplantation is the
In storage disorders like Gaucher and Fabry disease, EMBx treatment of choice. This is often required within 4 years of
can be diagnostic. Although not required for diagnosis in diagnosis.
hemochromatosis, it may be required to monitor the response
to therapy.12 Specific Cardiomyopathies
Treatment Strategies Hypereosinophilic Syndromes

• Diuretics Endomyocardial fibrosis (EMF) is an endemic heart disease
• Angiotensin converting enzyme (ACE) inhibitors or other in several tropical countries. It is characterized by deposition
vasodilators of fibrotic tissue covering the endocardium initially at the
• Calcium channel blockers apex and then proceeding towards the atrioventricular plane.
• Beta-blockers The outflow tract is mostly free of the fibrotic tissue. The
• Anticoagulation involvement of chordae tendinae is frequent and causes
• Surgery mitral and tricuspid regurgitation. The endocardial thickening
• Implantable cardioverter defibrillator and myocardial involvement leads to decrease ventricular
• Transplantation. distensibility and impairment of filling. Symptoms are mainly
of diastolic impairment depending upon which ventricle is
Treatment of Specific RCM involved.
Amyloidosis: Immunosuppression (minor benefits). Diagnostic Studies

Sarcoidosis: Steroids.
Loeffler Hypereosinophilic syndrome: Steroids, interferon Hypereosinophilia may be present. Chest X-ray shows varying
alpha, Anticoagulants. degrees of cardiomegaly. Right atrial enlargement is seen in
Hemochromatosis: Chelation therapy. right sided EMF, left atrial enlargement is seen in patient with
Fabry disease: Recombinant human alpha-galactosidase left-sided involvement and biatrial enlargement in biatrial
replacement. EMF. Pulmonary venous congestion is seen with left-sided
Gaucher disease: Enzyme replacement therapy. involvement. Occasionally myocardial calcification is seen.
Treatment of restrictive cardiomyopathy is difficult because 2D echo shows the characteristic findings of apical
the underlying processes usually do not respond to interventions. obliteration of the involved ventricle with gross enlargement
Diuretics are often useful in relieving the congestive of the atrium. Pericardial effusion may be present.
symptoms. Their dose needs to be monitored carefully as they
may cause a decline in the preload and lead to hypotension. Hemodynamics
Arteriolar and balanced vasodilators are not useful because
excessive afterload is not a problem. Venous vasodilators may A dip and plateau curve with high diastolic pressure is seen in 717
decrease congestive symptoms, but can provoke significant the corresponding ventricle.
9 Angiography Cardiac Amyloidosis
Characteristic obliteration of the apex of the involved This is the prototype of infiltrative heart disease with
ventricle with varying degrees of atrioventricular valve increased wall thickness. Amyloidosis is a systemic disorder
regurgitation is seen in all patients with left or biventricular characterized by interstitial deposition of linear, rigid, non-
EMF. Endomyocardial biopsy showed fibrous thickening branching, amyloid protein fibrils in multiple organs (e.g.
of the endocardium made up of collagen without classic heart, liver, kidney, nerve). However, absence of extracardiac
fibers. amyloid does not exclude the presence of amyloid heart disease
Treatment: Endarterectomy with atrioventricular valve Currently, 5 subtypes of amyloidosis have been recognized.
replacement of the diseased ventricle has been done with Cardiac involvement is common in all types of amyloidosis
mixed outcome. Cavopulmonary connection has been done in and is the most frequent cause of morbidity and mortality.
some patients.13
Clinical Features
Idiopathic Hypereosinophilic Syndrome
Amyloid deposits can be interstitial and widespread causing
Idiopathic hypereosinophilic syndrome is characterized by RCM, or localized to:
prolonged overproduction of eosinophils of unknown cause i. Conduction tissues resulting in heart block or ventricular
in addition to specific organ damage due to eosinophil derived arrhythmias.
protein toxicity. Its prognosis is correlated with development ii. Cardiac valves causing valvular regurgitation.
of restrictive cardiomyopathy. iii. Pericardium producing constriction.
Usually a disease affecting men of temperate climate and iv. Coronary arteries causing ischemia and
the diagnostic criteria for this disease are: v. Pulmonary vasculature causing pulmonary hypertension.
1. Blood eosinophila of 1,500/uL (1.5 × 10.9/L) or higher Diagnostic studies: The cardiac silhouette can be normal
lasting more than 6 months. or enlarged on the chest X-ray.
2. No parasitic, allergic or known cause of eosinophilia. Electrocardiography (ECG) typically shows decreased
3. Signs or symptoms of cardiac, hematological, pulmonary, voltage, a pseudoinfarction pattern and conduction distur-
neurologic and cutaneous involvement. bances predominate the clinical course.
Cardiac involvement has 3 phases: M-mode echo reveals symmetrical wall thickness
i. Endocardial damage and eosionophilic infiltration of involving the RV and LV, a small or normal LV cavity, variable
the myocardium. (often depressed) systolic function, left atrial enlargement
ii. Thrombosis of damaged endocardium. and small pericardial effusion. 2D Echo findings include
iii. Progressive fibrosis and scarring of the endocardium thickening of the ventricular myocardium with a speckled
leading to RCM. appearance, the interatrial septum and the valves. LV wall
Because this is an eosinophil mediated damage, aim is thickness is an important prognostic variable. In one study
to reduce peripheral blood eosinophila and reduce cardiac patients with biopsy proven amyloidosis and wall thickness
infiltration. Corticosteroids and hydroxyurea are widely of greater than 15 mm had a median survival of 0.4 years
used to reduce eosinophil count and have improved whereas those with wall thickness less than 12 mm had a
survival in hypereosinophilic syndrome. In some patients survival of 2.4 years. Doppler characteristics of restrictive
where a favorable response is not seen with these drugs, physiology are DT less than 150 msec and an increased
interferon alpha has been used to reduce the eosinophil E/A transmitral ratio, which are strong predictors of cardiac
count, but reduction of organ damage still remains death.17
controversial. Case reports of high doses of interferon- The infiltrative pathology associated with amyloidosis
alpha causing a definite improvement in the disease are can be detected by tissue characterization using magnetic
present. 14 resonance imaging (MRI). In a recent study, qualitative
global and subendocardial enhancement of the myocardium
Churg-Strauss Syndrome associated with faster gadolinium clearance from the blood
pool was higher in patients with cardiac amyloidosis than
This is primarily a disease of young women with a history of hypertensive controls. Treatment is often unrewarding.18
allergic rhinitis and bronchial asthma. The presence of four Immunosuppressive therapy with melphalan and prednisolone
of the following six criteria provides a diagnostic sensitivity is the established treatment regimen for primary amyloidosis.
of 85 percent-asthma, eosinophilia greater than 10 percent Autologous stem cell infusion reduces the monoclonal
of white blood cells (WBC) differential count; mono or gammopathy, but has little effect on existing infiltrative
polyneuropathy; non-fixed pulmonary infiltrate on chest amyloid deposits. Orthotopic cardiac transplantation is
718 X-ray; paranasal sinus abnormality; biopsy containing a blood generally not recommended because of systemic nature of the
vessel with extravascular eosinophils.15,16 disease and possibility of recurrence in the transplant.19
Hemochromatosis familial. Familial phenotypes may include an associated skeletal 50
myopathy with or without conduction abnormalities. A proper
It represents an iron overload disorder or iron storage disease family history should be taken and a genetic screening should
characterized by accumulation of excessive iron within the be done. Children may present with reactive airway disease,
cells of various internal organs. It may result from a genetic recurrent respiratory infections, breathlessness on exertion, or
defect (hereditary hemochromatosis) or from secondary causes more ominously with palpitations, syncope or sudden death.
(e.g. multiple blood transfusions as in thalassemia major Most of these are manifestations are of increased left-sided
(ineffective erythropoiesis). Iron accumulates in the heart, filling pressures and decreased myocardial reserve. Exercise
pancreas, skin, liver, anterior pituitary, gonads. The myocardial stress testing, Holter monitoring and serial BNP measurements
iron deposition usually produces dilated cardiomyopathy, but can may be useful to monitor the disease progression. Presence of
produce RCM, congestive heart failure, conduction abnormalities LVS3/LVS4 is a ubiquitous finding on physical examination.
like supraventricular and ventricular arrhythmias occur in one- ECG is universally abnormal with biatrial enlargement and
third of patients. Bronze diabetes, hepatic dysfunction are non-specific ST-T changes. Echocardiography will show
commonly associated. Echocardiography may show granular diagnostic features of RCM.23
sparkling, atrial enlargement, but these are not specific. Ultrasonic
analysis of integrated backscatter has been used experimentally Natural History
to detect changes in echocardiographic reflectivity of the
myocardium with iron deposits. Computed tomography (CT) This is a progressive disease with a mortality rate of 50 percent
and MRI can demonstrate subclinical cardiac involvement and in 2 years from diagnosis.24,25 Children with RCM should be
tissue characterization can be possible with MRI. Liver biopsy is followed closely for progression of pulmonary hypertension.
the definitive test for iron overload. Endomyocardial biopsy can Those with elevated but reversible pulmonary hypertension are
be confirmatory and reveals stainable iron in the heart. It is more at an urgent need for cardiac transplant, while those with mildly
useful to monitor the therapy. elevated, pulmonary artery pressures may remain stable for
Repeated phlebotomy is recommended for primary years and may not require urgent listing for transplant. Children
hemochromatosis and chelating agent desferrioxamine is presenting with chest pain and syncope and ECG or Holter
beneficial in secondary hemochromatosis. Combinations evidence of ischemia are at risk of sudden cardiac death. The
with oral active chelator deferiprone have been successful use of beta blocker, implantable cardioverter defibrillator and
in Europe. Deferasirox is a novel, orally active agent with urgent listing of cardiac transplant is indicated for these patients.
a single oral dosing. An extensive clinical trial has shown
its efficacy in adults and children and it has a safety profile, Genetic cardiomyopathies in children
which is manageable with regular clinical monitoring.20,21
Cardiac transplantation can be considered in selected cases. These can be classified into four categories, which are not
mutually exclusive.26
Sarcoidosis 1. Inborn errors of metabolism.
2. Malformation syndromes.
Systemic granulomatous disease of unknown etiology. It 3. Storage disease: Pompe disease, Gaucher disease, Fabry
affects young adults between 10 to 40 years of age and presents disease.
with bilateral hilar lymphadenopathy, reticular pulmonary 4. Disorders of energy metabolism that produce suspected
opacities, joints, eyes and skin involvement (erythema cardiotoxic intermediary metabolites.
nodosum). Cardiac involvement occurs in 5 percent and heart
failure can be due to restrictive or dilated cardiomyopathy and Diagnostic Approach
has a progressive course.22
Patients with inborn errors of metabolism often have signs of
Restrictive cardiomyopathy in Children multiple organ dysfunction. The indications to screen for a
biochemical abnormality are onset of acute/chronic encepha-
Restrictive cardiomyopathy in children is far less common lopathy, hypotonia, growth retardation, failure to thrive, etc.
(3–5%) than in adults. Median age of presentation is 9 years Patients with storage diseases who cannot degrade certain
(range 1 month–16 years). The etiology tends to be different in structural components of cells typically develop coarse or
children than adults. While the latter often have RCM associated dysmorphic facial features, organomegaly, short stature or
with amyloidosis or varieties of endocardial fibroelastosis or chronic encephalopathy with a degenerative course. Skeletal
idiopathic or familial; in children, it is exposure to radiation muscle weakness without encephalopathy is usually due to a
or anthracyclines. While in infants evaluation for congenital primary neuromuscular and rarely due to inborn error of me-
metabolic syndromes like Gaucher or Hurler is required, tabolism. Here skeletal muscle weakness precedes the cardiac
many pediatric cases remain idiopathic with upto a third being involvement. 719
9 Metabolic Cardiomyopathies affected, though the onset is in later age (average: 29 years)
and is milder. The disease causes severe renal, cardiac and
Glycogen Storage Diseases cerebrovascular disease. The onset is in childhood and
adolescence and includes intermittent pain in the extremities

Pompe disease: An autosomal recessive disorder caused (acroparesthesias), episodic ‘Fabry crisis’ of acute pain lasting
by deficiency of lysosomal enzyme acid-alpha-glucosidase. for hours, characteristic skin lesions (angiokeratomas), corneal
Classic infantile onset disease, characterized by cardiomegaly opacities, hypohidrosis, mild proteinuria and gastrointestinal
and profound weakness, leads to death in the year of life manifestations. Cardiovascular manifestations include left
from cardiorespiratory failure. ECG is diagnostic with ventricular hypertrophy, mitral regurgitation (MR), ascending
short PR interval and gigantic QRS complexes. Reversal of aorta dilatation, coronary artery disease and secondary
cardiomyopathy and improved motor function has been seen conduction defects. By adulthood, end stage renal disease has
in clinical trials of enzyme alpha-glucosidase replacement set in. Cerebrovascular manifestations include early stroke,
therapy (ERT).27 hemiparesis, diplopia, dysarthria, nystagmus, etc. Disease is
diagnosed by alpha-galactosidase A activity in plasma and
Lysosomal Storage Disease peripheral leukocytes.
Gaucher disease: Most common inherited lysosomal Cardiac Troponin Mutations

storage disorder caused by deficiency of glucocerebroside
in lysosomes of macrophages. Children present with Often found to be the causative factor in idiopathic RCM in
hepatosplenomegaly, anemia and thrombocytopenia. It is children. A strong family history is usually present.30
divided into 3 types depending on the severity and onset of
neurological symptoms. Cardiac involvement includes RCM, Differentiating Restrictive Cardiomyopathy
cardiomegaly, thickening and calcification of aortic and mitral from Chronic Constrictive Pericarditis
valves and annulus.
Fabry disease: X-linked recessive lysosomal storage The differentiation of restrictive and constrictive pericarditis
disease, hence a male predominant disease, usually mani can be a difficult task at times and in the rare case has rarely
festing at 11 + 7 years.28,29 Rarely, female carriers are led to exploratory thoracotomies31-33 (Table 1).
Table 1

Difference between restrictive cardiomyopathy and constrictive pericarditis
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 Raised there is prominent rapidly collapsing y
y descents present in early stages and prominent descent combined with a normally prominent x
y descent only will persists in later stages due to descent results in M or W shaped pattern .
atrial dysfunction.
Kussmaul’s sign Absent Seen in 80%
Pulsus paradoxus Absent Present in 20%
Extra sounds in diastole Loud diastolic filling sound S3 (late), rarely S4, Pericardial knock—high-frequency sound
a low frequency sound
Mitral or tricuspid May have a murmur of mitral or tricuspid Usually a quiet heart
regurgitation insufficiency
Chest X-ray Often have cardiomegaly with biatrial Normal cardiac silhouette, presence of
enlargement, pulmonary vascular redistribution pericardial calcification is pathognomonic
(20–30%), tubercular infiltrates in the lung
fields
Contd...
720
Contd... 50
ECG P waves reflect right/left atrial enlargement. P waves reflect intra-atrial conduction delay.
Atrioventricular or intraventricular conduction Conduction defects are rare.
defects are not unusual. LVH is more common, RVH and right axis deviation are more
e.g. LVH with T-wave inversion in an infant common.
with endocardial fibroelastosis
Features RCM31,32 CCP
Brain natriuretic peptide levels Increased Normal
Echocardiography
Interventricular septal Abrupt septal movement in early diastole seen Abrupt septal movement (“notch”) in early
movement in diastole only occasionally 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 Occasional Usually marked

and tricuspid flow velocity
Pulmonary vein flow Blunted S/D ratio, prominent atrial reversal S/D ratio = 1
No respiratory variation of D wave Prominent inspiratory decrease of S and D
waves.
Tissue Doppler Lateral and diastolic e’ velocities of < 8 cm/s Usually normal (e' >8 cm/s) as myocardium is
have been accepted as a cutoff for RCM. not affected (mitral annular calcification may
W wave may also be reduced to < 5 cm/s reduce sensitivity)
Color M-mode Slow flow propogation (< 45 cm/s) Rapid flow propagation (> 100 cm/s)
Speckle tracking imaging Endocardial dysfunction, hence abnormal Pericardial constraint affects circumferential and
longitudinal mechanics twist mechanics
Myocardial velocity gradients Low due to uniform affection of myocardium High due to preserved endocardial motion but
decreased epicardial motion
Cardiac catheterization
Ventricular diastolic pressure Helpful if unequal diastolic pressures Equalization of diastolic

(> 6 mm Hg) pressures (< 5 mm Hg).
LV and RV diastolic pressure The LV diastolic pressure will exceed RV Diastolic gradients rise equally or even
gradient diastolic pressure by > 5 mm Hg if volume decrease with these stresses
infusion, leg elevation or exercise is done
Dip and plateau End-diastolic pressure often less than one- End-diastolic pressure more than one-third of
waveform in the right third of the systolic pressure the systolic pressure in most cases
ventricular pressure waveform
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 May detect thickening, less sensitive to
on MR is suggestive of myocardial infiltrative calcium. Cine MR can detect septal bounce
disease. and real-time Cine MR can detect respiratory
variation seen on echo
EM biopsy Findings vary according to the etiology Normal

721
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.
9 Conclusion 14. Hassan WM, Fawzy ME, Al Helaly S, et al. Pitfalls in diagnosis
and clinical echocardiographic and hemodynamic findings in
Restrictive cardiomyopathy is a relatively rare form of endomyocardial fibrosis. Chest. 2005;128:3985-92.
cardiomyopathy in which diastolic function is abnormal 15. Baratta L, Afeltra A, Delfino M, et al. Favorable response to
high-dose interferon Alpha in idiopathic hypereosinophilic
due to the stiff ventricles. The most common cause of RCM
syndrome with restrictive cardiomyopathy. Angiology.
in adults is amyloidosis, whereas in children, the cause is
2002;53:465-70.
unknown. At present, medical therapy remains supportive 16. Alvarez-Sala R, Prados C, Armada E, et al. Congestive cardio-
and appears to be ineffective and the development of myopathy and endobronchial granulomas as manifestations of
pulmonary hypertension is common. The prognosis for Churg-Strauss Syndrome. Postgrad Med J. 1995;71:365-6.
RCM in infants and children is very poor and cardiac 17. Shanks M, Ignaszewski AP, Chan SY, et al. Churg-Strauss
transplantation is recommended soon after the diagnosis is syndrome with myocarditis manifesting as acute myocardial
made. infarction with cardiogenic shock: case report and review of
the literature. Can J Cardio. 2003;19:1184-8.
18. Cueto-Garcia L, Reeder G, Kyle R, et al. Echocardiographic
In this sick room, ten cents’ worth of human understanding
findings in systemic amyloidosis: spectrum of cardiac involvement
equals ten dollars’ worth of medical science.
and relation to survival. J Am Coll Cardiol. 1985;6:737-43.
—Martin H Fischer 19. Maceira AM, Joshi J, Prasad SK, et al. Cardiovascular magnetic
resonance in cardiac amyloidosis. Circulation. 2005;111:186-93.
References 20. Gertz MA, Lacy MQ, Lust JA, et al. Prospective randomized trial
of melphalan and prednisolone versus vincristine, carmustine,
1. Benotti JR, Grossman W. Restrictive cardiomyopathy. Annu. melphalan, cyclophosphamude and prednisone in the treatment
Rev. Med. 1984;35:113-25. of primary systemic amyloidosis. J Clin Oncol. 1999;17:262-7.
2. Stollberger C, Finsterer J. Extracardiac medical and neuromus- 21. Kontoghiorghes GJ. Future chelation monotherapy and
cular implications in restrictive cardiomyopathy. Clin Cardiol. combination therapy strategies in thalassemia and other
2007;30:375-80 conditions. Comparison of deferiprone, deferoxamine ICL
3. Hirotay Shimizu G, Kita Y, et al. Spectrum of restrictive 670, GT56-252, L1NAll and starch deferoxamine polymers.
Hemoglobin. 2006;30:329-47.
cardiomyopathy: report of the national survey in Japan. Am
22. Cappellini MD, Pattoneri P. Oral iron chelators. Annu Rev
Heart J. 1990;120:188-94.
Med. 2009;60:25-38.
4. Shaddy RE. Cardiomyopathies in adolescents: dilated,
23. Poppi NT, Reis MV, Aiello VD. A 20 years old man with heart
hyper trophic and restrictive. Adolesc Med. 2001;12(1): failure due to restrictive cardiomyopathy. Arq Bras Cardiol.
35-45. 2009;92:461-8.
5. Hoit BD, Gupta S. Restrictive, Obliterative and Infiltrative 24. Hayashi T, Tsuda E, Kurosaki K, et al. Electrocardiographic
Cardiomyopathies. In: Fuster V, O’ Rourke R, Walsh RA, and clinical characteristics of Idiopathic Restrictive cardio
Poole-Wilson P, (Eds). Hurst’s the heart 12th edition. McGraw myopathy in children. Circ J. 2007;71:1534-9.
Hill. Inc. 2007;851. 25. Ammash NM, Seward JB, Bailey KR, et al. Clinical profile and
6. Lee JH, Chung WB, Kang JH, Kim HW, et al. A case of outcome of idiopathic restrictive cardiomyopathy. Circulation.
chloroquine—induced cardiomyopathy that presented as sick 2000;101:2490-6.
sinus syndrome. Korean Circ J. 2010;40:604-10. 26. Guertl B, Neohammer C, Heofler G. Metabolic cardiomyopa-
7. Cetta F, O’ Leary PW, Seward JB, et al. Idiopathic restrictive thies. Int J Exp Pathol. 2000;81:349-72.
cardiomyopathy in childhood: Diagnostic features and clinical 27. Schwartz ML, Cox GF, Lin AE, et al. Clinical approach to genetic
course. Mayo Clin Proc. 1995;70:634-40. cardiomyopathy in children. Circulation. 1996;94:2021-38.
8. Zangwill S, Hamilton R. Restrictive Cardiomyopathy. Pacing 28. Case LE, Hanna R, Frush DP, et al. Fractures in children with
Clin Electrophysiol. 2009;32:S41-S43. Pompe’s disease: a potential long term complication. Pediatr
9. Sengupta PP, Krishnamoorthy VK, Abhayaratna WP, et al. Radiol. 2007;37:437-45.
Comparison of usefulness of tissue Doppler imaging versus 29. Desnick RJ, Brady R, Barranger J, et al. Clinical Guidelines
Brain natriuretic peptide for differentiation of constrictive Fabry disease, an under-recognised multisystem disorders:
pericardial disease from restrictive cardiomyopathy. Am J expert recommendations for diagnosis, management and enzyme
Cardiol. 2008;102:357-62. replacement therapy. Ann Intern Med. 2003 Feb 18;138:338-46.
10. Vijayaraghavan G, Davies J, Sadanandan DS, et al. 30. Peters FP, Vermeulen A, Kho TL. Anderson-Fabry disease:
Echocardiographic features of tropical endomyocardial disease alpha galactosidase deficiency. Lancet. 2001;357:138-40.
in South India. Br Heart J. 1983;50:450-9. 31. Parvatiyar MS, Pinto JR, Dweck D, et al. Cardiac troponin
11. Gaudalajara JF, Vera-Delgado A, Gaspar-Hernandez J, et al. mutations and restrictive cardiomyopathy. J Biomed
Echocardiographic aspects of restrictive cardiomyopathy: Biotechnol. 2010:2010:350706. Epub 2010 Jun 8.
their relationship with pathophysiology. Echocardiography. 32. Hancock EW: Cardiomyopathy differential diagnosis of
1998;15:297-314. restrictive cardiomyopathy and constrictive pericarditis. Heart
12. Chatterjee K. Primary diastolic heart failure. Am J of Geriatr 2001;86:343-9.
Cardiol. 2002;11:178-87. 33. Anderson PA. Diagnostic Problem: constrictive pericarditis or
722
13. Przybojewski JZ. Endomyocardial biopsy: a review of restrictive cardiomyopathy? Cathet Cardiovasc Diagn. 1983;9:
literature. Cathet Cardiovas Diagn. 1985;11:287-330. 01-07.
C hapter
51 Hypertrophic Cardiomyopathy
Krishnan MN
Introduction children (~2%).9 The deaths are almost exclusively sudden.

About 3 percent of patients with HCM progress to a dilated
Hypertrophic cardiomyopathy (HCM), the most common of phase called end-stage (ES) HCM associated with progressive
genetically mediated heart muscle disorder, characterized by systolic dysfunction ((LVEF) < 0.5).9 These patients show
thickened non-dilated left ventricle (in the absence of other progressive cavity dilatation, LV wall thinning and diffuse
cardiac or systemic conditions) and myocyte disarray.1-5 gadolinium enhancement on magnetic resonance imaging
In about two-thirds of the cases, dynamic left ventricular indicating extensive fibrosis. They often present with atrial
(LV) obstruction of varying degrees exists. Although a fibrillation (AF) or congestive heart failure (HF). Progression
relatively benign condition, it can cause atrial and ventricular to intractable HF and sudden cardic death (SCD) are frequent
arrhythmias, sudden cardiac death (SCD) or progressive LV (10% per year). The most reliable risk marker of progression
dilatation leading to congestive heart failure. It is characterized to ES is family history of ES HCM.
by variable penetrance, heterogeneous clinical expression and
variable natural history. It is the commonest cause of sudden Genetics10,11
cardiac death in the young.
Although the disease entity was reported by French Hypertrophic cardiomyopathy is a genetic disorder of
pathologists in 19th century, the first contemporary reports sarcomeric proteins of cardiomyocyte. It is transmitted as
came from Russell Brocks, a British cardiac surgeon in 1957 Mendelian dominant pattern of inheritance with variable
and Donald Teare, a pathologist from London in 1958.6 Teare penetrance. The seminal report of the R403Q mutation in
described the autopsy findings of nine young patients who died MYH7 in a family with HCM by Seidman’s group in 1990
suddenly in a paper entitled ‘Asymmetrical Hypertrophy of the unraveled the genetic enigma of HCM.11 The discovery led
Heart in Young Adults’.7 In the 60’s, Goodwin laid foundation subsequently to identification of more than 150 mutations of
to clinical details of the condition and Braunwald elucidated 11 sarcomeric proteins as causing the disease (Box 1). About
the concept of dynamic obstruction of the LV outflow tract 80 percent of the cases are accounted by b-myosin heavy
(LVOT). Many names have been ascribed to this condition; chain and myosin-binding protein C.
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 Box 1: Genetic mutations in HCM
now accepted as the all inclusive name, and hypertrophic
Disease of sarcomeric protein. Dominant inheritance with
obstructive cardiomyopathy (HOCM) in cases with LV
variable penetrance:
outflow obstruction. 1. Alpha and beta-myosin heavy chain.
Epidemiological studies have estimated a prevalence of 2. Myosin-binding protein C.
the HCM phenotype at 0.2 percent or 1 in 500 live births;8 3. Troponin I and T.
considering a much lower occurrence of the disease in 4. Alpha tropomyosin.
cardiology practice, it can be inferred that most affected 5. Myosin light chain (essential and regulatory).
6. Titin.
individuals are asymptomatic and do not come to clinical
7. Alpha-cardiac actin.
attention. The overall annual mortality of HCM has been 8. Muscle LIM protein (MLP).
estimated to be 1 percent although somewhat higher in
9 Non-sarcomere protein mutations like Fabry disease, ventricular volume or decrease systolic arterial pressure
PRKAG2, lysosome-associated membrane protein 2 (LAMP2) augment the gradient and vice versa. Accordingly, exercise,
cardiomyopathies mimic HCM clinically. isoproterenol or dobutamine infusion increases the gradient;
beta-blocking drugs reduce it. Valsalva maneuver, standing up

Morphology from squatting, blood loss or dehydration by reducing volume
of LV increases the gradient; isometric handgrip, squatting
Left ventricular hypertrophy in HCM is diverse in pattern or phenylephrine administration reduces the obstruction by
including dissimilar phenotypes in relatives. Wall thickness elevating systolic blood pressure.
of LV can range from normal to massive. Any degree of
or pattern of hypertrophy is compatible with clinical and/ Diastolic Dysfunction
or genetic diagnosis of HCM. Typically the hypertrophy is
asymmetric and transition to normal abrupt. Non-contiguous Abnormal filling of LV due to impaired relaxation is present
patterns of hypertrophy and extension to right ventricle in vast majority of patients with HCM and contributes to
are common. Hypertrophy of LV is frequently diffuse with effort dyspnea, although parameters of diastolic dysfunction
involvement of septum and free wall; however in sizable by echocardiography do not predict symptoms, prognosis or
minority it may be confined to septum only (asymmetric septal therapeutic response. Diastolic dysfunction is not directly
hypertrophy) or apical regions (apical HCM) characterized related to severity of hypertrophy. The abnormal diastolic
by spade deformity of LV cavity and deep T inversions in properties are consequent to hypertrophy, replacement fibrosis
electrocardiogram. There is no evidence to suggest that any and myocellular disarray and is the fundamental mechanism
specific pattern of hypertrophy correlates with outcome. The for HF symptoms in HCM.
hypertrophy commonly develops over time with dramatic
increase in thickness and distribution through adolescence. Autonomic Dysfunction
Structural abnormalities of the mitral valve apparatus
represent a primary morphologic alteration in HCM; the valve During exercise, approximately 25 percent of patients with HCM
may be twice as much as normal due to elongation of both have an abnormal blood pressure response defined by either a
leaflets. In a small subset of patients, anomalous insertion of failure of systolic blood pressure to rise by 20 mm Hg or a fall in
anterolateral papillary muscle to anterior mitral leaflet causes systolic blood pressure. The presence of this finding is associated
midventricular obstruction. with a poorer prognosis. The inability to augment and sustain
In HCM the cardiomyocytes show abnormal shape and size systolic blood pressure during exercise is caused by the dynamic
with grossly disorganized patterns of oblique and perpendicular left ventricular outflow tract obstruction (LVOTO) in the wake
angles (myocyte disarray) and replacement fibrosis. Abnormal of systemic vasodilatation during exercise. It is speculated that
intramural coronary arteries with thickening of walls and autonomic dysregulation is present in patients with HCM and that
narrowing of lumen are seen in 80 percent of cases, leading the fall in BP associated with bradycardia may be an abnormal
to ischemia, necrosis and replacement fibrosis. These areas reflex response to obstruction.
of fibrosis act as a substrate for ventricular arrhythmias and
sudden death. Clinical Features12,13
Pathophysiology Symptoms
Symptoms of HCM include dyspnea on effort, fatigue, angina
Left Ventricular Outflow Tract Obstruction
and syncope/presyncope. Dyspnea is predominantly due to
About 70 percent of hospital-based patients with HCM have diastolic dysfunction and may be compounded by LVOTO.
LV outflow tract obstruction (gradient ≥ 30 mm Hg). In most Severity of symptoms often varies day-by-day. Symptoms are
patients the obstruction is due to systolic anterior movement more after a large meal or alcohol ingestion, which increases
(SAM) of the mitral valve and midsystolic contact with the gradient. Angina occurs due to myocardial ischemia on
septum caused by drag effect on the anterior mitral leaflet. The exertion. Syncope usually occurs during exertion although it
magnitude of the gradient is directly related to the duration of may present itself on sudden standing from supine posture.
the contact. Mitral regurgitation (MR) may occur secondary The syncope is explained by several mechanisms including
to the SAM and is usually directed posteriorly. The outflow arrhythmias and increase in outflow obstruction. CHF is rarely
gradient imposes increased wall stress and oxygen demand seen in HCM in normal sinus rhythm, but it may be seen with
and is a predictor of progression to HF. However, there is no severe obstruction to outflow, severe systolic or diastolic
consistent relation between the magnitude of gradient and risk dysfunction or advent of AF. History of palpitations may also
of sudden death. Outflow gradient is dynamic with spontaneous be there during tachyarrhythmia and may be associated with
724 variability. Interventions that increase contractility, reduce syncope.
Physical Findings Table 1
 51
Differences in the physical findings of HOCM and valve aortic
Left ventricular involvement is reflected by a variably displaced stenosis
Hypertrophic Cardiomyopathy
and forceful LV impulse. Patients with non-obstructive HCM
Clinical parameter HOCM Valvar aortic stenosis
have no murmur and manifest only as forceful apical impulse
and palpable and audible fourth heart sound. Carotid pulse Jerky/bisferiens Delayed low volume,
carotid shudder
In patients with significant obstruction, the carotid pulse is
usually flicking or jerky and at times bisferiens character may JVP Prominent ‘a’ Prominent ‘a’ wave
wave, if RV may be present
be present. Apex is variably displaced and forceful. Sometimes
involvement (Bernheim effect)
a double systolic impulse may be felt over the apex. A fourth (Broady’s effect)
heart sound may also be palpable causing a ‘triple ripple’. The
Apex beat Double or triple, Heaving, S4 may be
first heart sound is usually normal. The second heart sound may forceful palpable
be normal, fused or paradoxically split with increasing severity
Thrill Rare Common
of obstruction. A fourth heart sound is usually audible over the
apex. The mid systolic murmur of LVOTO is usually 2/6 or S2 Single or reverse Single or reverse
3/6, best audible over the 3rd left intercostal space; it is seldom Ejection click No Commonly present
associated with a thrill. There may be, in addition, an apical Outflow murmur 3rd left space; no 2nd right space;
systolic murmur of mitral regurgitation. Patients with mid- carotid radiation radiates to carotids
ventricular obstruction may also have an apical systolic murmur MR Common No
although it is usually softer than with subaortic obstruction. There
HOCM = Hypertrophic obstructive cardiomyopathy; JVP = Jugular venous
may be at times a very distinctive long diastolic murmur caused pressure
by mid-ventricular narrowing and asymmetric relaxation. A
mid systolic clicking sound of mitral leaflet septal contact may DIAGNOSIS/INVESTIGATIONS
be rarely heard. The murmur of subaortic obstruction varies
significantly with maneuvers. Valsalva maneuver, standing Electrocardiography14,15
from squatting position or amyl nitrite inhalation increases the
gradient and the intensity of murmur; squatting or isometric The 12-lead electrocardiogram (ECG) is abnormal in 90
handgrip decreases the gradient and murmur. Postectopic percent of patients of HCM (Figure 1). The most common
beat causes an increase in the obstruction and murmur, while abnormalities include tall R waves, deep narrow Q waves, ST-T
being associated with a smaller pulse volume as a result of abnormalities and left atrial enlargement. Sometimes the ECG
increase in contractility due to postextrasystolic potentiation. pattern is very bizarre. The deep Q waves may at times
The differential physical findings in HCM versus valvar aortic mimic myocardial infarction. About 25 percent of cases have
stenosis are depicted in Table 1. left anterior hemiblock. Deep negative T in lateral leads is
725
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.
9 characteristic of apical form of HCM. Normal ECG is seen
Box 2: Conditions causing left ventricular hypertrophy
in five percent of cases and predict a favorable cardiovascular or thickened interventricular septum
course, but is not predictive of SCD. The ECG does not
distinguish between obstructive and non-obstructive forms of 1. Sigmoid septum.

HCM. 2. Hypertensive hypertrophy.
3. Athelete’s heart.
4. Aortic stenosis.
Echocardiography16 5. Infants of diabetic mothers.
6. Tumors of septum.
Left Ventricular Hypertrophy 7. Layered clot over the septum.
A characteristic feature of HCM is hypertrophy of LV

septum disproportionate to free wall hypertrophy. Septal
Box 3: Genetic diseases associated
thickness to posterior wall thickness ratio of 1.5 is with left ventricular hypertrophy
characteristic (Figures 2A to C). Although asymmetric
septal hypertrophy (ASH) is very characteristic of HCM, 1. Fabry disease.
other patterns like diffuse hypertrophy, disproportionate 2. Friedreich’s ataxia.
3. Noonan syndrome.
posterior wall hypertrophy and apical hypertrophy are not
4. Pompe disease.
uncommon. Anterior septal hypertrophy is seen in majority 5. PRKAG2 mutation.
of patients and in 40 percent cases more than one segment 6. Lysosome-associated membrane proteins-2 (LAMP2)
is affected. The LV is not dilated and systolic cavity size cardiomyopathy (Danon disease).
is markedly reduced. Characteristically the septum fails
to thicken during systole. Left ventricular hypertrophy
(LVH), even asymmetric is not specific for HCM and can (Table 2). Presence of wall thickness ≥ 30 mm is seen in
be found in several other conditions (Box 2 and Box 3). about 10 percent of patients and correlated with higher risk
Various indices for assessment of LVH have been developed of SCD.
A B
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
 51
Indices for echocardiographic assessment of left ventricular hypertrophy by echocardiography
Index Description Score
Wigle Thickness of basal septum in mm 15–19 : 1
20–24 : 2
25–29 : 3
≥ 30 : 4
Spirito’s score Left ventricular hypertrophy extent 1 segment—mild
2 segments—moderate
3 or more—severe
Spirito-Maron index Left ventricular hypertrophy Sum of maximum thickness of all 4
extent and severity 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 Systolic anterior motion of the mitral valve may also
gross phenotypic expression and clinical profile of HCM occur in conditions other than HCM (pseudo SAM). Mitral
may occasionally be identified in infants and young children, annulus is an integral part of LV; motion exhibited by mitral
marked LVH is rarely documented during the 1st year of valve may be related to motion of mitral annulus and/or left
life. Rapid changes in LV morphology often occur during ventricular wall. Any condition in which posterior LV wall
adolescence, when LV wall thickness may increase rapidly. motion is exaggerated can lead to SAM. In true SAM the peak
Genetic studies among large families demonstrated that leaflet anterior motion is complete before the peak posterior
morphological LVH reaches a plateau at the third decade of wall movement; in pseudo SAM the peak of AML movement
life in myosin heavy-chain and in tropomyosin mutations, occurs after the peak of PW movement. SAM may be produced
whereas it increases continuously though life in cardiac by various parts of the mitral valve apparatus like anterior
myosin-binding protein C mutations. mitral leaflet alone, anterior and posterior leaflets or chordae
alone. SAM is thought to be produced by venturi effect of
Left Ventricular Outflow Obstruction blood flowing across the hypertrophied septum or malposition
of papillary muscles. The aortic valve motion may show a mid
A common accompaniment to hypertrophy in HCM is systolic closure of the anterior leaflet indicating alteration in
dynamic obstruction of the LVOT. Up to one-third of patients aortic blood flow (Figure 3B).
with HCM will have obstruction under basal (resting) Spectral Doppler echocardiography helps in determining
conditions (defined as gradients ≥ 30 mm Hg). Another one- the presence and severity of LVOTO. The classic continuous
third or more of patients will have labile, physiologically wave Doppler recording shows relatively slow increase in
provoked gradients (< 30 mm Hg at rest and ≥ 30 mm Hg velocity in early systole and peaks in late systole producing
with physiologic provocation). The final one- third of patients a dagger-shaped velocity envelope (Figure 4). Color Doppler
will have the non-obstructive form of HCM (gradients < 30 helps to identify the location of the obstruction and also the
mm Hg at rest and with provocation). The echocardiographic presence and severity of MR (Figure 5). The jet of MR is
hallmark of obstruction is SAM of the mitral valve (Figure directed laterally and posteriorly and predominates during mid
3A). The anterior mitral leaflet moves anteriorly toward and late systole. An anteriorly directed jet should suggest an
the interventricular septum (IVS) shortly after the onset intrinsic abnormality of the mitral valve. The mitral diastolic
of systole and returns to its normal position just before the filling pattern is usually indicative of impaired relaxation with
onset of diastole. The finding is best seen with M-mode E/A reversal or restrictive filling pattern. In mid ventricular
echocardiography. There is close correlation between the obstruction blood may actually flow from apex to the body
severity of obstruction and the duration of mitral leaflet— of the ventricle during diastole producing a high velocity
septal contact. The gradient is given by the equation: diastolic flow.
LVOT gradient = (Septal contact time/Time from onset of
SAM to septal contact) × 25 + 25 mm Hg. Hemodynamic Evaluation and Ventriculography17
Systolic anterior motion of mitral valve and obstruction are
classically dynamic and may not be always present at rest, but Pull-back tracings from left ventricle will show gradient at
may appear on provocation such as Valsalva maneuver, amyl the LVOT in those with resting obstruction. The aortic tracing
nitrite inhalation or intravenous isoproterenol. may show ‘spike and dome’ pattern in those with significant 727
9
A B
Figures 3A and B: M mode in echocardiogram showing: A. SAM (arrow); B. Aortic valve presystolic closure (arrow)
Figure 4: Doppler in left ventricular outflow tract showing dagger Figure 5: Color Doppler showing left ventricular outflow tract (LVOT)
shaped velocity profile turbulence (arrow) and mitral regurgitation (MR). Ao = Aorta; LA = Left
atrium; LV = Left ventricle.
gradients; this represents the rapid early systolic ejection show hypertrophied ventricle with near obliteration of cavity
followed by slowing of the ejection beyond midsystole in systole, SAM and MR.
in the wake of progressive obstruction in the mid systole
characteristic of HOCM (Figure 6). Postextrasystolic aortic Cardiac Magnetic Resonance Imaging19-21
tracing shows decrease systolic pressure and pulse pressure
in the beat after the pause with an increase in the LV pressure In the last few years, cardiovascular magnetic resonance
and the gradient. During the long diastole, although increase (CMR) has emerged not only as a diagnostic tool, but also as
in the LV volumes tend to reduce the obstruction, the a study with prognostic valve, by characterizing myocardial
postextrasystolic increase in contractility (postextrasystolic fibrosis with great accuracy in HCM patients. Additionally,
potentiation) over-rides this effect and causes greater obstruc CMR identifies the type of hypertrophy, analyses the
tion (Brockenbrough-Braunwald-Morrow sign) (Figure 7).18 ventricular function, estimates the intraventricular gradient
The LV and right ventricular end diastolic pressures are and allows the determination of differential diagnosis.
usually elevated, so also the left atrial (LA) mean pressure. Mild Magnetic resonance is more sensitive and accurate to assess
elevation of PA pressure may be present. Tall V waves in the hypertrophy and LV mass than echocardiography. European
728 pulmonary artery wedge pressure tracing represent significant and American Societies of Cardiology recently accepted
MR or elevated LA pressures. Left ventriculography will CMR as the primary modality of imaging in suspected HCM.
respect any specific coronary territory and in the majority 51
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 athlete’s 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
Figure 6: Left ventricle (LV) and aortic tracing showing gradient and septal thickness of 13 to 15 mm can be seen in about 2 percent
spike and dome aortic tracing of highly trained male athletes. The major differentiating
points between HCM and athlete’s 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 Athlete’s heart
Parameter HCM Athlete’s heart

Family history May be present Absent
Reversibilty once Not reversible Reversible
Figure 7: Brockenbrough sign—shows increase in left ventricle (LV) stopping excercise
systolic pressure, a decrease in ascending aortic systolic pressure LVIDD < 45 mm > 55 mm common
and increase in the gradient between the LV and ascending aorta in
the post-ectopic beat. Ao = Aorta; LA = Left atrium; VPC = ventricular Involvement Asymmetric septal Diffuse hypertrophy
premature complex. hypertrophy
Septal thickness Thickness >13 mm Almost never > 11
mm in females and
One of the major contributions of CMR, besides the > 15 in males
anatomical and functional data and geometric indices, is the SAM Yes Never
delineation of myocardial fibrosis in HCM, which follows Abnormal LV filling Yes No
specific patterns. The presence of myocardial fibrosis pattern
increases the diagnostic accuracy and insight on the prognosis. MRI LGE Normal
About 80 percent of patients with HCM have been detected
to have myocardial fibrosis by late gadolinium enhancement
LGE = Late gadolinium enhancement; LVIDD = Left ventricular internal 729
dimension in diastole; MRI = Magnetic resonance imaging; SAM = Systolic
(LGE). The myocardial hyperenhancement in HCM does not anterior motion.
9 3. To provoke gradients in those who have resting gradient each of the HCM risk factors has a low positive predictive
<30 mm Hg. values (approx 10–20%) and modest negative predictive
Invasive coronary angiography is indicated in patients value (approx 85–95%). Multiple risk markers in individual
who complain of angina-like chest pain with intermediate patients may not indicate higher risk; the vast majority of
likelihood for coronary artery disease (CAD), prior to surgical patients with more than one risk marker will not experience
septal myectomy (SSM) or percutaneous transluminal septal SCD.29 The number of risk factors did not correlate with the
myocardial ablation (PTSMA). Assessment of coronary rate of subsequent appropriate ICD discharges. Data suggest
anatomy with computed tomographic angiography is that the presence of a single risk marker may be sufficient
reasonable for patients with HCM with chest discomfort and to warrant ICD placement in most patients; however these
a low likelihood of CAD to assess for possible concomitant decisions have to be individualized with regard to age,
CAD. Assessment of ischemia or perfusion abnormalities strength of the risk factor and the risk benefit of lifelong ICD
suggestive of CAD with single photon emission computed therapy.
tomography or positron emission tomography myocardial The usefulness of the following potential SCD risk
perfusion imaging (because of excellent negative predictive modifiers is unclear but might be considered in selected
value), is reasonable in patients with HCM with chest patients with HCM for whom risk remains borderline after
discomfort and a low likelihood of CAD to rule out documentation of conventional risk factors:
concomitant CAD. a. CMR imaging with LGE.
b. Double and compound mutations (i.e. > 1).
Risk Stratification27,28 c. Marked LVOT obstruction. Invasive electrophysiologic
testing as routine SCD risk stratification for patients with
Assessment of risk of SCD is an integral part of the patients HCM should not be performed.
with HCM. Table 4 outlines the major risk factors for SCD in
HCM. Treatment
Several studies investigated the risk of SCD with
combination of major risk factors. The combination of history Treatment strategies in HCM are tailored along:
of syncope with family history is a significant risk factor for 1. Control of symptoms.
SCD. Patients with 2 or more risk factors have an estimated 2. Prevention of sudden cardiac death.
annual SCD risk of 4 to 5 percent. 3. Prevention and management of atrial fibrillation.
A minority of HCM patients have increased risk for SCD 4. Management of dilated phase of HCM.
with a rate of above 1 percent per year. Other than cardiac arrest, 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
Table 4
 the disease process and to screen the first degree relatives.
Risk factors for sudden cardiac death in hypertrophic
cardiomyopathy They should be advised to avoid strenuous physical activity
or competitive athletics. Risk stratification of SCD should be
Parameter Definition performed in all patients irrespective of symptoms. Hydration
1. A
borted sudden cardiac Documented cardiac arrest and avoidance of situations where vasodilatation may occur
arrest or VF are important in patients with resting or provocable LV-
2. Spontaneous sustained VT VT lasting for > 30 s or OT obstruction. High dose diuretics and vasodilators and
requiring cardioversion inotropes should be avoided.
3. Family history of premature SCD is first degree relatives Beta-blockers are the mainstay of pharmacologic therapy
SCD less than 40 years and the first line agents because of their negative inotropic
4. Unexplained syncope Syncope without a known effects and ability to attenuate adrenergic induced tachycardia.
causal factor, ≥2 episodes in They act by reducing LVOT obstruction and myocardial
the previous year ischemia and improving diastolic filling of LV.
5. Nonsustained VT on Holter > 3 consecutive ventricular In patients, who cannot tolerate beta blockers or
complexes at a rate of > 120 unresponsive to beta blockers, non-dihydropyridines calcium
beats per minute channel blockers (CCB) may provide symptomatic relief by
6. Extreme LV wall thickness Maximum LV wall thickness their negative inotropic and rate lowering effects. Verapamil
more than or equal to 30 mm or diltiazem should be cautiously given in patients with
7. A
bnormal exercise BP Failure to increase by at least severe obstruction, elevated LA pressure and low systemic
response 20 mm or a drop of ≥ 20 mm blood pressure because a drop in the blood pressure may
during effort trigger severe outflow obstruction and precipitate pulmonary
730 BP = Blood pressure; LV = Left ventricle; SCD = Sudden cardiac death; VF edema. Dihydropyridine class of CCB should not be used in
= Ventricular fibrillation; VT = Ventricular tachycardia. obstructive HCM.
Those who remain symptomatic despite use of beta repair, in addition to myectomy, may be most appropriate for 51
blockers and CCB alone or in combination may benefit from selected patients with severe MR caused by primary valvular
disopyramide due to its negative inotropic effect. The use of disease. Septal myectomy is established as a proven approach
disopyramide alone without beta blockers or verapamil is for reversing the consequences of HF by providing permanent
potentially harmful in the treatment of HCM with AF because amelioration of obstruction (and relief of MR) and restoring
it may enhance atrioventricular conduction and increase the functional capacity and an acceptable quality of life at any
ventricular rate. Oral diuretics in patients with non-obstructive age. The procedure results in excellent long-term survival of
HCM may be administered when dyspnea persists despite the 90 percent at 10 years, superior to non-operated patients, and
use of beta blockers and/or verapamil. reduces the incidence of SCD.
The use of angiotensin converting enzyme inhibitors or
receptor blockers in HCM with preserved systolic function is Percutaneous Transluminal Septal
not well established and these drugs should be used cautiously Myocardial Ablation31
in patients with LVOT obstruction.
Alcohol septal ablation is a catheter-based procedure in
Septal Reduction Therapy which 96 percent alcohol is injected through a major septal
artery supplying the basal hypertrophied septum (Figures 8A
Septal reduction therapy (SRT) involves invasive methods of and B). The eligibility is same as SSM; however, at present
reducing the septal thickness viz. SSM and PTSMA. Septal the procedure is reserved for those who are poor surgical
reduction therapy is indicated in eligible (those with septal candidates or those who refuse surgery. Ideal PTSMA
hypertrophy and SAM) patients with LVOTO (gradient basal candidate is subaortic SAM-related LVOT obstruction ±
> 30 mm Hg and/or provocable > 50 mm Hg) with drug- SAM-related MR with basal septum thickness > 18 mm,
refractory symptoms. but < 30 mm; while those with marked elongation of AML,
severe MR due to MV abnormalities, markedly thick and
Surgical Septal Myectomy30 fibrotic septum, abnormal insertion of papillary muscles are
poor candidates for the procedure. After measurement of basal
The first choice of septal reduction therapy in HCM is SSM. gradient, the septal branch is wired; the distribution area of
Surgical septal myectomy, when performed in experienced the septal branch is ascertained using myocardial contrast
centers, can be beneficial for the majority of eligible patients echocardiography using Levovist through an over the wire
with HCM with severe drug-refractory symptoms and LVOT balloon in the septal branch; the balloon is inflated and a small
obstruction. In the hands of experienced operators the success quantity of contrast is injected to rule out back-leak; 1 to 2 mL
rate is around 95 percent, surgical mortality < 1 percent and of alcohol is then slowly injected keeping the balloon inflation.
major complications 2 to 3 percent. A rectangular trough Echocardiographic control is extremely important as the septal
of septum from below the aortic valve to the distal septum branches have highly variable area of supply; misplacement
beyond the septal contact (or up to the insertion of papillary of alcohol into wrong branch could not only be ineffective,
muscle in extended myectomy) is removed. Mitral valve but could cause remote infarction with serious complications.
A B
731
Figures 8A and B: Coronary angiogram before (A) and after (B) Percutaneous transluminal septal myocardial ablation (PTSMA)
9 The area of myocardium undergoes chemical necrosis and prevention ICDs was 3 to 4 times more frequent than in other
later scarring. A final angiography control excludes left patients in that registry (10.3% per year compared with 2.6%
coronary artery damage and verifies septal branch occlusion per year).33 Alternatively, incidence of sustained ventricular
while hemodynamic measurements confirm the immediate arrhythmias after surgical myectomy is extremely low (0.2–
result of septal ablation. Contraindications include the failure 0.9% per year).
of myocardial contrast echocardiography to identify a target
septal branch, the echocardiographic contrast opacification of Dual Chamber Pacing34
any cardiac structure other than the target septal area, or insecure
balloon positioning that bears the risk of alcohol reflux during A small number of patients with HOCM may draw symptomatic
injection. Furthermore, alcohol injection should be avoided benefit from dual chamber pacing. Pacing the right ventricular
if there is any suspicion of collateral flow that could lead to apex with maintenance of atrioventricular synchrony results
infarction far from the target septal area. About 90 percent of in a decrease in the LVOT gradient and improvement of
patients will have significant reduction in the gradient, which symptoms in a subset of patients. The exact mechanism of
will continue to decrease over time. Symptomatic improvement improvement with pacing remains unknown; the decrease in
parallels the hemodynamic changes. gradient may be caused by alteration in the timing of septal
Complications of PTSMA include bundle branch block, contraction. Although there was an initial enthusiasm for
complete heart block (CHB) and reflux of alcohol into left dual-chamber pacing as a primary treatment for patients with
anterior descending artery. Right bundle branch block obstructive HCM, subsequent data demonstrated long-lasting
occurs in about 50 percent of patients after septal ablation. beneficial results in only a small minority of patients, whereas
In approximately half of patients undergoing alcohol septal most perceived improvement was judged to be placebo effect.
ablation, temporary complete atrioventricular block occurs
during the procedure. The incidence of persistent CHB used to Prevention of Sudden Cardiac Death35,36
be > 10 percent in the earlier series of PTSMA; however with
myocardial contrast echocardiographic control and limited The only treatment modality, which has been proven to
use of alcohol (< 2 mL), the incidence has come down to < reduce SCD in HCM is implantation of ICD. The decision
5 percent almost equaling that of SSM. The block usually to place an ICD should include application of strength of
occurs within 48 hours of the procedure although it may be as evidence, benefits, risks and individual clinical judgment. The
late as 10 days; patients with pre-existing left bundle branch indications for ICD implantation is outlined in Table 5.
block are more prone to CHB. Approximately 5 percent of The usefulness of ICD is uncertain in HCM with isolated
patients have sustained ventricular tachyarrhythmia during non-sustained ventricular tachycardia (NSVT) or abnormal
hospitalization. In-hospital mortality is now < 1.5 percent. blood pressure response with exercise. The complications
A most feared complication is iatrogenic reflux of alcohol of ICD in HCM include inappropriate discharge (25%), lead
into the left anterior descending artery, causing vessel complications (6–13%), device infection (4–5%) and bleeding
occlusion and anterior wall myocardial infarction. This can be and thrombotic complications (2–3%). Dual chamber ICDs are
avoided, however, by the routine use of a slightly oversized reasonable for patients with elevated resting outflow gradient
balloon compared to the septal artery diameter, and by (> 50 mm Hg) and significant heart failure symptoms.
keeping the balloon inflated for at least 10 minutes after the
last alcohol injection. Management of Atrial Fibrillation37
Long-term results of PTSMA are encouraging with
sustained abolition of gradient and persistent symptomatic Atrial fibrillation in patients with HCM usually causes
improvement. Recently published data from a larger cohort hemodynamic deterioration due to fast ventricular rate and
of 347 patients has shown 94 percent survival after 5 years withdrawal of atrial booster action. Ventricular rate control can be
and 87 percent after 10 years, which is comparable to the achieved with high doses of beta blockers or non-dihydropyridine
results of large myectomy studies. Many studies have raised CCB. Disopyramide and amiodarone can be given to prevent the
the concern over the occurrence of ventricular tachyarrhythmia recurrences in paroxysmal AF. Radio frequency ablation may
and SCD among patients who have undergone PTSMA. The be considered in those who have refractory symptoms or who
presence of a scar in the septum may act as a substrate for are unable to take antiarrythmic drugs. Maze procedure with
arrhythmias. In a selected subset of 42 patients with an ICD closure of LA appendage is reasonable either during SSM or as
or permanent pacemaker that enabled detection of device- an isolated procedure in selected patients.
stored electrograms, the annualized event rate (ventricular
tachycardia, ventricular fibrillation, and/or appropriate ICD Physical Activity38
discharge) was 4.9 percent per year.32 Similarly, the multicenter
HCM ICD registry of 506 patients demonstrated that the rate of It may be reasonable for patients with HCM to indulge in
732 appropriate ICD therapy among ablation patients with primary low-intensity sports or recreational activities. They should
Table 5
 51
Indications for implantable cardiac defibrillator in hypertrophic cardiomyopathy
Definite:
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, Future

sex, race, presence or absence of LVOT obstruction, prior
septal reduction therapy, or implantation of ICD. The last decades have seen major steps forward in the under
standing of natural history, clinical features, risk assessment
Pregnancy39 and medical management of HCM. Future efforts should
focus on precise risk assessment of SCD and indications for
Women with HCM can safely undergo pregnancy and labor ICD implantation.
with minimal documented risks. The maternal mortality rate Mechanistic studies suggest that cardiac hypertrophy
is exceedingly low and is limited to those with advanced in HCM is secondary to activation of various hypertrophic
disease. However careful evaluation of the functional and signaling molecules and hence is potentially reversible.42

hemodynamic status is of paramount importance. Usually The hypothesis is supported by the results of genetic and
special medical precautions are unnecessary; cesarean pharmacological interventions in animal models. The results
delivery is dictated by obstetric indications. However women have shown potential beneficial effects of angiotensin II
with advanced disease, like marked LVOT obstruction, receptor blocker losartan, mineralocorticoid receptor blocker
progressive heart failure, ventricular arrhythmias and severe spironolactone, 3-hydroxy-3-methyglutaryl-coenzyme-A
diastolic dysfunction will require regular monitoring and reductase inhibitors simvastatin and atorvastatin and most
specialized care. Those who are well controlled with medical recently, N-acetylcysteine (NAC) on reversal or prevention
therapy should continue to take the medications. It is of great of hypertrophy and fibrosis in HCM. The most promising
importance that genetic counseling be given to any woman of results have been obtained with NAC, which through multiple
child bearing age with HCM. thiol-responsive mechanisms completely reversed established
cardiac hypertrophy and fibrosis in three independent studies.
End-stage HCM40 The results in animal models have firmly established the
reversibility of established cardiac hypertrophy and fibrosis
Patients who develop systolic dysfunction with an EF less in HCM and have set the stage for advancing the findings
than or equal to 50 percent should be treated with angiotensin in the animal models to human patients with HCM through
converting enzyme inhibitors, angiotensin receptor blockers, conducting large-scale efficacy studies.
beta blockers, and other indicated medications. Other
concomitant causes (such as CAD) should be looked for and Conclusion
treated appropriately. An ICD may be considered in these
patients (with EF < 50%) even though it is not otherwise HCM is a fascinating disease entity that has intrigued
indicated. Negative inotropic agents may be discontinued. cardiologists for decades. It is a unique hereditary disease in
Digoxin may be used for control of ventricular rate in atrial which there is an abnormal increase in the thickness of the
fibrillation. Patients with ES HCM who are not responsive heart muscle. The cause of HCM is said to be due to a gene
to any form of medical therapy should be considered for mutation with Mendelian dominant pattern of inheritance
heart transplantation. Symptomatic children with restrictive with variable penetrance. It is a highly heterogeneous disease,
physiology and unresponsive/inappropriate for other forms with diverse pathology, pathophysiology, and clinical course.
of interventions also may be considered for transplantation.41 The appropriate therapies can be given for improvement of 733
9 symptoms and to identify those patients who may be at risk for 13. Wigle ED, Rakowski H, Kimball BP, et al. Hypertrophic
SCD. In the future, genetic testing and identification of genes cardiomyopathy. Clinical spectrum and treatment. Circulation.
will continue to help clarify the treatment and management of 1995;92:1680-92.
patients with HCM. 14. Montgomery JV, Harris KM, Casey SA, et al. Relation of
electrocardiographic patterns to phenotypic expression and
clinical outcome in hypertrophic cardiomyopathy. Am J
Temperance and labor are the two real physicians of man.
Cardiol. 2005;96:270.
—Jean Jacques Rousseau 15. McLeod CJ, Ackerman MJ, Nishimura RA, et al. Outcome
of patients with hypertrophic cardiomyopathy and a normal
Acknowledgment electrocardiogram. J Am Coll Cardiol. 2009;54:229.
16. Losi M, Nistri S, Galderisi M, et al. Echocardiography in
I wish to thank Professor Dr B Ramesh and Dr AC Nagamani, patients with hypertrophic cardiomyopathy: usefulness of old
Associate Professor of Cardiology at Sri Jayadeva Institute and new techniques in the diagnosis and pathophysiological
of Cardiovascular Institute of Sciences and Research for their assessment. Cardiovascular Ultrasound. 2010;8:7-26.
17. Grossman W. Profiles in dilated (congestive) and hypertrophic
contribution of the images in this chapter.
cardiomyopathies. In: Grossman W, (Ed). Cardiac cath
eterization and angiography. Philadelphia: Lea and Febiger;
References 1986. pp. 420-21.
18. Brockenbrough EC, Braunwald E, Morrow AG. A hemo
1. Gersh BJ, Maron BJ, Bonow RO, et al. 2011ACCF/AHA dynamic technic for the detection of hypertrophic subaortic
Guideline for the Diagnosis and Treatment of Hypertrophic stenosis. Circulation. 1961;23:189-94.
Cardiomyopathy.A Report of the American College of 19. Shiozaki AA, Kim RJ, Parga JR, et al. Cardiovascular magnetic
Cardiology Foundation/American Heart Association Task Force resonance in hypertrophic cardiomyopathy. Arq Bras Cardiol.
on Practice Guidelines. Circulation. 2011;124:e783-e831. 2007;88(2):243-48.
2. Alcalai R, Seidman JG, Seidman CE. Genetic basis of 20. Moon JC, Fisher NG, McKenna WJ, et al. Detection of apical
hypertrophic cardiomyopathy: From bench to the clinics. J hypertrophic cardiomyopathy by cardiovascular magnetic
Cardiovasc Electrophysiol. 2008;19:104. resonance in patients with non-diagnostic echocardiography,
3. Maron BJ, Towbin JA, Thiene G, et al. Contemporary Heart. 2004;90:645-49.
definitions and classification of the cardiomyopathies. An 21. Rickers C, Wilke NM, Jerosch-Herold M, et al. Utility of
American Heart Association Scientifi Statement. Circulation. cardiac magnetic resonance imaging in the diagnosis of
2006;113:1807. hypertrophic cardiomyopathy. Circulation. 2005;112:855-61.
4. Bos JM, Towbin JA, Ackerman MJ. Diagnostic, prognostic, 22. Cheng TO. Hypertrophic cardiomyopathy vs athlete’s heart.
and therapeutic implications of gene testing for hypertrophic International Journal of Cardiology. 2009;131:151-5.
cardiomyopathy. J Am Coll Cardiol. 2009;54:201. 23. Maron BJ, Savage DD, Wolfson JK, et al. Prognostic
5. Maron BJ, Seidman CE, Ackerman MJ, et al. What’s in a significance of 24 hours ambulatory electrocardiographic
name? Dilemmas in nomenclature characterizing hypertrophic monitoring in patients with hypertrophic cardiomyopathy: a
cardiomyopathy and left ventricular hypertrophy. Circ prospective study. Am J Cardiol. 1981;48:252-7.
Cardiovasc Genet. 2009;2:8. 24. Monserrat L, Elliott PM, Gimeno JR, et al. Non-sustained
6. Ross J Jr, Shabetai R, Curtis G, et al. Nonobstructive and ventricular tachycardia in hypertrophic cardiomyopathy: an
obstructive hypertrophic cardiomyopathies West J Med. independent marker of sudden death risk in young patients, J
1979;130:325-49. Am Coll Cardiol. 2003;42:873-9.
7. Teare D. Asymmetrical hypertrophy of the heart in young 25. Sadoul N, Prasad K, Elliott PM, et al. Prospective prognostic
adults. Br Heart J. 1958;20:1-8. assessment of blood pressure response during exercise in
8. Maron BJ, Gardin JM, Flack JM, et al. Assessment of the patients with hypertrophic cardiomyopathy, Circulation.
prevalence of hypertrophic cardiomyopathy in a general 1997;96:2987-91.
population of young adults: Echocardiographic analysis of 26. Olivotto I, Maron BJ, Montereggi A, et al. Prognostic value
4111 subjects in the Cardia Study. Circulation. 1995;92:785. of systemic blood pressure response during exercise in a
9. Maron BJ. Hypertrophic cardiomyopathy: A systematic review. community-based patient population with hypertrophic
JAMA. 2002;287:1308. cardiomyopathy. J Am Coll Cardiol. 1999;33:2044-51.
10. Bos JM, Towbin JA, Ackerman MJ. Diagnostic, prognostic, 27. Elliott PM, Poloniecki J, Dickie S, et al. Sudden death in
and therapeutic implications of genetic testing for hypertrophic hypertrophic cardiomyopathy: identification of high risk
cardiomyopathy. J Am Coll Cardiol. 2009;54:201-11. patients. J Am Coll Cardiol. 2000;36:2212-8.
11. Tanigawa G, Jarcho JA, Kass S, et al. A molecular basis for 28. Maron BJ. Contemporary insights and strategies for risk
familial hypertrophic cardiomyopathy: an alpha/beta cardiac stratification and prevention of sudden death in hypertrophic
myosin heavy chain hybrid gene. Cell. 1990;62:991-8. cardiomyopathy. Circulation. 2010;121:445-56.
12. Maron BJ, Bonow RO, Cannon RO, et al. Hypertrophic 29. Maron BJ, Spirito P, Shen WK, et al. Implantable cardioverter
cardiomyopathy: interrelations of clinical manifestations, patho defibrillator and prevention of sudden cardiac death in
physiology, and therapy. N Engl J Med. 1987;316:780-9, 884- hypertrophic cardiomyopathy. JAMA. 2007;298;405-12.
52.
734
30. Ommen SR, Olivotto I, Betocchi S, et al. The effect of
surgical myectomy on survival of patients with hypertrophic
38. Pelliccia A, Fagard R, Bjornstad HH, et al. Recommendations
for competitive sports participation in athletes with cardio
51
cardiomyopathy. J Am Coll Cardiol. 2004;43(Suppl)A:215 A. vascular disease: a consensus document from the Study
31. Rigopoulos AG, Panou F, Kremastinos DT, et al. Alcohol Group of Sports Cardiology of the Working Group of
Septal Ablation in Hypertrophic Obstructive Cardiomyopathy. Cardiac Rehabilitation and Exercise Physiology and the
Hellenic J Cardiol. 2009;50:511-22. Working Group of Myocardial and Pericardial Diseases of
32. Noseworthy PA, Rosenberg MA, Fifer MA, et al. Ventricular the European Society of Cardiology. Eur Heart J. 2005;26:
arrhythmia following alcohol septal ablation for obstructive 1422-45.
hypertrophic cardiomyopathy. Am J Cardiol. 2009;104:128-32. 39. Autore C, Conte MR, Piccininno M, et al. Risk associated with
33. Maron BJ, Spirito P, Shen WK, et al. Implantable cardioverter pregnancy in hypertrophic cardiomyopathy. J Am Coll Cardiol.
defibrillators and prevention of sudden cardiac death in 2002;40:1864-69.
hypertrophic cardiomyopathy. JAMA. 2007;298:405-12. 40. Harris KM, Spirito P, Maron MS, et al. Prevalence, clinical
34. Vatasescu R, Evertz R, Mont L, et al. Biventricular/Left Ven- profile, and significance of left ventricular remodeling in the
tricular Pacing in Hypertrophic Obstructive Cardiomyopathy: end-stage phase of hypertrophic cardiomyopathy. Circulation.
An Overview Indian Pacing and Electrophysiology Journal. 2006;114:216-25.
2012;12(3):114-23. 41. Towbin JA. Cardiomyopathy and heart transplantation in
35. Maron BJ, Spirito P, Shen WK, et al. Implantable cardioverter- children. Curr Opin Cardiol. 2002;17:274-79.
defibrillators and prevention of sudden cardiac death in 42. Marian AJ. Experimental Therapies in Hypertrophic Cardio-
hypertrophic cardiomyopathy. JAMA. 2007;298:405-12. myopathy. J Cardiovasc Transl Res. 2009;2(4):483-92.
36. Maron BJ, Spirito P. Implantable defibrillators and prevention
of sudden death in hypertrophic cardiomyopathy. J Cardiovasc Other Suggested Reading
Electrophysiol. 2008;19:1118-26. 1. Braunwald’s Heart Disease: A Textbook of Cardiovascular
37. Olivotto I, Cecchi F, Casey SA, et al. Impact of atrial fibrillation Medicine. 9th Ed. pp. 1582-94.
on the clinical course of hypertrophic cardiomyopathy. 2. Hurst. The Heart. 13th Ed. pp. 837-64.
Circulation. 2001;104:2517-24.
735
C hapter
52 Endocardial Fibroelastosis
Mishra SS, Mishra BR
Introduction Fulminating Type

Endocardial fibroelastosis (EFE) is a rare entity, encountered When the presentation is sudden and severe, it is known as
in clinical practice. This rare congenital anomaly is seen in ‘fulminating type’ of EFE. It manifests as acute congestive
infancy and early childhood. It is characterized by thickening heart failure.
of the endocardium due to fibroelastotic proliferation, with a
pearly white appearance. It leads to progressive heart failure Chronic Type
and generally has a poor prognosis. In 1943, Weinberg and
Himmelfarb for the first time described the disease and When the presentation is insidious and it runs a protracted
coined the term EFE.1 This condition should not be confused course, it is known as ‘chronic type’ of EFE. It manifests with
with endomyocardial fibrosis, which is a distinctly separate slow and progressive chronic congestive heart failure.
acquired heart disease.
Incidence
Classification
EFE is a rare disease, with occurrence of 1 to 2 percent in
Endocardial fibroelastosis (EFE) is classified into two types: the list of all congenital heart diseases.8 In recent years, the
incidence of EFE has decreased considerably,9 compared
Primary Endocardial Fibroelastosis to the earlier reported incidence of 1 in 5,000 live births,10
possibly due to better antenatal scanning and decreased
When there is no identifiable congenital anomaly, it is known incidence of mumps.11 There is no sex predilection with
as primary EFE.2,3 Primary EFE is again divided into two equal affection of both sexes. In 80 percent of cases, clinical
types depending upon the size of left ventricle (LV). presentation is within the first 3 to 6 months of age. It is one of
a. Dilated type: When the LV is dilated it is called the ‘dilated the causes of non-immune hydrops fetalis.12 Survival beyond
type’. 2 years is unusual.2 This is extremely rare in adolescents
b. Contracted type: When the LV size is normal or small, it is and adults. Although the disease is sporadic, familial cases
called the ‘contracted type’. with an X-linked pattern are also seen in about 10 percent of
cases.13
Secondary Endocardial Fibroelastosis
etiology
When EFE is associated with other congenital anomalies, it is
known as secondary type of EFE. The common associations The fibroelastic process is thought to be secondary to various
are hypoplastic left heart syndrome,4 aortic stenosis,5 endocardial stimulation in fetal life.14 Histological and
coarctation of aorta6 and anomalous left coronary artery from molecular studies substantiated viral etiology particularly
pulmonary artery.7 Coxsackie B virus and mumps infection.11 This is also linked
to presence of maternal anti-Ro and anti-La antibodies.15
Clinical Classification Autosomal recessive and X-linked recessive inheritance
pattern of EFE were also reported including mutation of
There are two types of EFE according to the clinical presentation:3 gene 4.5 (tafazzin).16 Other possible etiological factors are
impaired lymphatic drainage, systemic carnitine deficiency, In EFE, thickened endocardium limits the contraction 52
neonatal lupus and subendocardial ischemia. and relaxation of the LV myocardium producing a splinting
In secondary type of EFE, increased wall tension, cardiac action causing both systolic and diastolic dysfunction.
Endocardial Fibroelastosis
hypertrophy leading to myocardial oxygen demand and Impaired contraction and relaxation together with MR leads to
supply mismatch, resulting in subendocardial injury, which is increased left ventricular end-diastolic pressure (LVEDP) that
thought to be the trigger to produce EFE. EFE is also seen leads to increased mean LA pressure and pulmonary venous
after myocardial infarction.17 hypertension (PVH), PVH is responsible for symptoms of
dyspnea and leads to development of pulmonary arterial
Pathophysiology hypertension (PAH), which ultimately gives rise to right
heart failure. In fetal life, it may lead to development of non-
Normal endocardium is thin and transparent. In EFE, endo immune hydrops fetalis.12 In contracted type, PAH develops
cardium is diffusely thicked upto 1 to 2 mm due to proliferation early and is more severe. Abnormal endocardium with
of collagen and elastic tissue and deposition of extracellular global hypokinesia sets the stage for mural thrombosis with
matrix. The characteristic appearance of endocardium in consequent systemic embolization.19
EFE is described as pearly white or milky white, glistening
and opaque. In the dilated type of pimary EFE, both LV Clinical Features
and left atrium (LA) are dilated. LV assumes a spherical
shape. Endocardial thickening also affects mitral valve
Symptoms
and other cardiac chambers.18 LV dilatation along with
abnormal origin of papillary muscles; poor LV function leads Infants present with dyspnea, wheezes, tacyhpnea, feeding
to mitral regurgitation (MR) of various grades. High origin of difficulties and failure to thrive. In some neonates, presentation
papillary muscles together with short and thick chordae results is acute (acute LVF) and the condition of the infant rapidly
in improper coaptation of mitral leaflets in systole. Aortic deteriorates. It is the fulminant presentation of EFE.20 It is
valve is also involved in 50 percent of cases. Myocardial one of the causes of sudden death in infancy.21 In other cases,
thickness remains normal. Aorta and coronary arteries are not presentation is more insidious. Sometimes the infant presents with
involved.8 diaphoresis, abdominal pain or with recurrent chest infection.
In contracted type, the LV endocardium resembles the
dilated type, but the LV remains normal or hypoplastic Signs
(Figure 1). Similar morphologic changes in endocardium occur
in secondary type of EFE, but they are more often patchy.9 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
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
Figure 1: Opened out left ventricular inflow tract shows small size of unless PAH is seen producing a right axis. P wave indicate
the left ventricle (LV) with smoothened out trabeculae and pearly white
LA enlargement or biatrial enlargement. In dilated type, 737
endocardium. The mitral valve (MV) is dysplastic. Note the presence of
patent foramen ovale (PFO) (arrow). Courtesy: Dr. Pradeep Vaideeshwar left ventricular hypertrophy is usually present with narrow
9 ‘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 Figure 2: Echocardiography in endocardial fibroelastosis (done in
EFE is one of the causes of massive cardiomegaly in newborns 1987 in a 4 months baby) showing bright echogenic endocardium of
and infants. Although there is marked cardiomegaly in dilated left ventricle, mitral valve, papillary muscles seen in parasternal long-
type, the aorta and pulmonary trunk remains normal, which axis view. Right ventricle is dilated. The mother had mumps in the first
trimester
helps in differentiating EFE from other congenital heart
diseases.
finding is bright echogenic thickened endocardium seen on
Echocardiography 2D echocardiography and M-mode (Figures 2 and 3A).24
LV shows global hypokinesia and MR is detected by
In echocardiography, LV and LA are dilated, LV dilatation is color Doppler (Figure 3B) and its severity can be graded.
accompanied by increased wall thickness. The characteristic In presence of severe MR, the LA may be hugely dilated.
A B
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
738 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
Echocardiography also helps in assessing pulmonary Infiltrating and Storage Disease 52
arterial pressure. In contracted type, LV cavity is small
with hypertrophied myocardium and bright echogenic Infiltrative and storage disease like Pompe disease, glycogen
endocardium. PAH is particularly common in contracted storage disease and mucopolysaccharidosis may present with
type as determined from tricuspid regurgitation jet, which is similar findings, but marked generalized thickening of the
usually present. Intrauterine detection is also possible by fetal cardiac structures including right ventricular free wall along
echocardiography.25 Doppler echocardiography study is the with other systemic findings help to differentiate it from
tool of choice for diagnosis and follow-up. EFE.32
Other Imaging Modalities Management

In some cases, echo findings may be equivocal or non- Treatment is supportive, there is no medical or surgical
diagnostic. In such cases, newer imaging like magnetic cure as yet developed. Nutrition and hydration are to be
resonance imaging (MRI)26 and electron beam computed maintained. Concurrent infections particularly chest infection
tomography27 are helpful. MRI using perfusion and delayed and anemia should be treated promptly. Decongestive
enhancement demonstrate endocardial surface as a rim of therapy with conventional regimen with digoxin, diuretic
hypointense signal in perfusion sequences and a rim of and ACE inhibitors are prescribed.33 Rapid digitalization
hyperintense signal in the myocardial delayed enhancement was prescribed earlier is seldom used now. Digoxin is useful
sequence. in atrial fibrillation. Beta blockers like carvedilol34 are of
Cardiac catheterization and angiocardiography does particular help in reducing heart rate when sinus tachycardia
not help much as they do not add further to non-invasive is marked. Some infants do respond to medical management.
modalities. But others remain refractory in spite of medical management.
Treatment should be continued indefinitely even after
Differential Diagnosis symptomatic improvement and reduction of heart size.
Role of steroid remains controversial. Dexamethasone was
Congenital anomalies giving rise to CHF in neonates and shown to prevent conduction delay in case of EFE associated
infancy with cardiomegaly comes in the differential diagnosis with maternal anti-Ro and anti-LA antibodies.35 Those with
of EFE.28 mural thrombi or episode of thromboembolism, will require
anticoagulation initially with heparin and then with oral
Congenital Mitral Regurgitation vitamin K antagonist. Cardiac transplant is recommended in
refractory cases.36
In congenital MR, LA and LV are dilated in the presence of
MR and CHF. In congenital MR, the murmur of MR is quite Prognosis
prominent unlike EFE. Echo demonstration of abnormal mitral
apparatus with preserved contractility and absent endocardial The overall prognosis in primary EFE is ominous. Dilated
thickening differentiates it from EFE.29 EFE with fulminating presentation and contracted type
are generally fatal. Even in chronic type, the disease
Myocarditis and Dilated Cardiomyopathy progresses relentlessly with 30 to 40 percent mortality
rate. Survival beyond 2 years is rare. Sudden death may
In myocarditis and dilated cardiomyopathy there is LV occur. Severe the symptom and younger the patient, poorer
dilatation, MR and CHF. But marked myocardial and is the prognosis.37
endocardial thickening is absent. Viral serological tests,
molecular tests, nuclear perfusion imaging and endocardial Conclusion
biopsy help in establishing diagnosis.30
Endocardial fibroelastosis is characterized by diffuse
Anomalous Left Coronary Artery from Pulmonary Artery thickening of the ventricular endocardium due to proliferation
of fibrous and elastic tissue and impaired cardiac function.
ALCAPA is also responsible for cardiomegaly and CHF in It is most commonly seen in young children and rarely in
neonates. ECG evidence of myocardial infarction pattern adults. It is often associated with congenital heart anomalies,
in left coronary artery territory, wall motion abnormality in infection or gene mutation. Treatment is supportive with
echo and demonstration of origin of left coronary artery from decongestive therapy and sustained refractory ventricular
pulmonary artery differentiates it from EFE.31 tachycardia might be an end-stage disease that requires
739
9 mechanical support and heart transplantation. The overall for the role of mumps virus as an etiologic agent. Circulation.
1997;95:133-9.
prognosis is gloomy; survival beyond two years of age is
rare. 12. Rodriguez MM, Bruce JH, Jimenez XF, et al. Nonimmune
hydrops fetalis in the liveborn: series of 32 autopsies.

The purpose of medicine is to prevent significant disease, Pediatr Dev Pathol. 2005;8:369-78. Epub 2005 Jul 14.
to decrease pain and to postpone death... Technology 13. Rafinski T, Folenia A, Wozneiwicz B, et al. Familial endocardial
has to support these goals-if not, it may even be fibroelastosis. J Pediatr. 1967;10:574-6.
14. Carceller AM, Maroto E, Fouron JC. Dilated and contracted
counterproductive.
forms of primary endocardial fibroelastosis: A single fetal
—Dr Joel J Nobel
disease with two stages of development. Br Heart J. 1990;63:
311-13.
Acknowledgment 15. Nield LE, Silverman ED, Smallhorn JF, et al. Endocardial
fibroelastosis associated with maternal anti-Ro and anti-La
The authors thank Dr Pradeep Vaideeswar, Professor antibodies in the absence of atrioventricular block. J Am Coll
(Additional), Department of Pathology (Cardiovascular and Cardiol. 2002;40:796-802.
Thoracic Division), Seth GS Medical College, Mumbai, 16. Chen S, Thompson MW, Rose V. Endocardial fibroelastosis:
India for the pathological image and Dr IB Vijayalakshmi, family studies with special reference to counseling. J Pediatr.
Professor of Pediatric Cardiology for the echocardiographic 1971;79:385-92.
images. 17. Hutchins G, Bannayan GA. Development of endocardial
fibroelastosis following myocardial infarction. Arch Pathol.
References 1971;91:113-18.
18. Lynfield J, Gasul BM, Luan LL, et al. Right and left heart
1. Weinberg T, Himelfarb AJ. Endocardial fibroelastosis. Bull. catheterization and angiocardiographic findings in idiopathic
Johns Hopkins Hosp. 1943;72:299-308. cardiac hypertrophy with endocardial fibroelastosis.
2. Andersen DH, Kelly J. Congenital endocardial Fibroelastosis. Circulation. 1960;21:386-400.
II, A clinical and pathologic investigation of those cases 19. Branch CL, Castle RF. Thromboembolic complications in
without associated cardiac manifestations including report of primary endocardial fibroelasosis. J Pediatr. 1966;69:250-8.
two familial instances. Pediatrics. 1956;18:539-55. 20. Thomas WA, Randall RV, Bland EF, et al. Endocardial
3. Moller JH, Lucas RV, Adams P, et al. Endocardial fibroelastosis. fibroelastosis: A factor in heart disease of obscure etiology: A
Circulation. 1964;30:759-82. study of 20 autopsied cases in children and adults. N Eng J
4. Noonan JA, Nadas AS. The hypoplastic left heart syndrome. Med. 1954;251:327-8.
Pediatr Clin North Am. 1958;5:1029-56. 21. Valdes-Dapena M, Gilbert-Barness E. Cardiovascular causes
5. DuShane JW, Edwards JE. Congenital aortic stenosis in for sudden infant death. Pediatr Pathol Mol Med. 2002;21:195-
association with endocardial sclerosis of the left ventricle. Proc 211.
Staff Meet Mayo Clin. 1954;29:102-8. 22. Sellers FJ, Keith JD, Manning JA. The diagnosis of primary
6. Oppenheimer EH. Association of adult type coarctation of endocardial fibroelastosis. Circulation. 1964;29:49-59.
aorta with endocardial fibroelastosis in infancy. Bull Johns 23. Schryer MJT, Karnauchow PN. Endocardial fibroelastosis:
Hopkins Hosp. 1953;93:309-19. Etiologic and pathogenetic considerations in children. Am
7. Noren GR, Raghib G, Moller JH, et al. Anomalous origin of Heart J. 1974;88:557-65.
the left cornary artery from the pulmonary trunk with special 24. Tannouri F, Rypens F, Peny MO, et al. Fetal endocardial
reference to the occurence of mitral insufficiency. Circulation. fibroelastosis: ultrasonographic findings in two cases. J
1964;30:171-8. Ultrasound Med. 1998;17:63-6.
8. Keith JD, Rose V, Manning JA. Endocardial fibroelastosis. 25. Weiner Z, Shalev E. Doppler fetal echocardiography in
In: Keith JD, Rowe RD, Vlad P (Eds). Heart Disease in Infancy endocardial fibroelastosis. Obstet Gynecol. 2001;98:
and Childhood. 3rd edition New York (NY): MacMillan. 1978. 933-5.
pp.941-57. 26. Stranzinger E, Ensing GJ, Hernandez RJ. MR findings of
9. Lurie PR. Changing concepts of endocardial fibroelastosis. endocardial fibroelastosis in children. Pediatr Radiol.
Cardiol Young. 2010;20:115-23. Epub 2010 Mar 29. 2008;38:292-6. Epub 2008 Jan 3.
10. Moller JH, Lucas RV, Adams P, et al. Endocardial fibroelastosis: 27. Wang IJ, Chen SJ, Wang JK, et al. Electron beam computed
a clinical and anatomic study of 47 patients with emphasis on its tomography appearance of endocardial fibroelastosis EBCT
relationship to mitral insufficiency. Circulation. 1964;30:759- appearance of endocardial fibroelastosis. Int J Cardiovasc
82. Imaging. 2003;19:85-90.
11. Ni J, Bowles NE, Kim YH, et al. Viral infection of the 28. Satpathy M. Primary endocardial fibroelastosis, Satpathy M,
myocardium in endocardial fibroelastosis. Molecular evidence Mishra BR, (Eds), Clinical Diagnosis of Congenital Heart
740
Disease, 1st edition. Jaypee Brothers Medical Publishers. for management of heart failure in children. J Heart Lung 52
2008,pp.71-3. Transplant. 2004;23:1313-33.
29. Ahmed MI, McGiffin DC, O’Rourke RA, et al. Mitral 34. Blume ED, Canter CE, Spicer R, Gauvreau K, Colan S,
regurgitation. Curr Probl Cardiol. 2009;34:93-136. Jenkins KJ. Prospective single-arm protocol of carvedilol
30. Bohn D, Benson L. Diagnosis and management of pediatric in children with ventricular dysfunction. Pediatr Cardiol.
myocarditis. Pediatr Drugs. 2002;4:171-81. 2006;27:336-42.
31. Scholz TD, Reinking BE. Congenital heart disease. In: 35. Mevorach D, Elchalal U, Rein AJ. Prevention of complete
Gleason CA, Devaskar S, (eds). Avery’s Diseases of the heart block in children of mothers with anti-SSA/Ro and
Newborn. 9th edition. Philadelphia, Pa: Saunders Elsevier; Curr Opin Rheumatol. 2009;21:478-82.
2011,pp. 762-88. 36. Netz H, Bauer JJ, Scheld HH, et al. Cardiac Transplantation in
32. Chen SC, Balfour IC, Jureidini S. Clinical spectrum of restric a Neonate with Endocardial Fibroelastosis, Tex Heart Inst J.
tive cardiomyopathy in children. J Heart Lung Transplant. 1990;17:122-5.
2001;20:90-2. 37. Ino T, Benson LN, Freedom RM, et al. Natural history and
33. Rosenthal D, Chrisant MR, Edens E, et al. International Society prognostic risk factors in endocardial fibroelastosis. Am J
for Heart and Lung Transplantation: Practice guidelines Cardiol. 1988;62:431-44.
741
Sec t i on
10
Congenital Heart Disease

in Adults
C hapter
Transitional Care in Congenital

53 Heart Disease
Mary M Canobbio, Reema Chugh
INTRODUCTION Box 1: Seven key elements of an effective transfer

program from childhood to adulthood
As the survival of children born with congenital heart disease
(CHD) into adulthood continues to increase, the need for an • Timing of transfer to adult care in order to form a policy
effective transition plan is becoming an important clinical based on the individual’s maturity, chronological age and
concern. In 2003, the American Academy of Pediatrics/ social factors, that is carried on during a period of medical
American College of Physicians presented a consensus statement stability
on health care transition for young adults with special heath care • Educational programs coordinated by nurse specialists in
pediatric and adult teams to prepare patients and their
needs.1 A similar report was published in the UK addressing
families to navigate the adult health care system
the needs for the emerging population of young adults.2 The • A coordinated transfer process with transfer summaries
term transitional care is a multifaceted, dynamic process that from the pediatric to adult clinics
attends to the medical, psychosocial and educational/vocational • Health passport for the patient to carry—a snapshot of
needs of adolescents as they move from a child-focused to congenital heart defects, procedures, surgeries, medical
an adult-focused health care system.3 The overall goal is to conditions, medications, allergies, pertinent diagnostic
provide uninterrupted health care that is patient centered, age test results and an outline of the plan of care
and developmentally appropriate and comprehensive.4,5 The • Selection of an appropriate Adult Congenital Heart
structured plan should be introduced in the pediatric cardiology Disease Center or specialists that is geographically and
financially feasible for the patients and their families
setting, in order to allow an efficient and caring transfer to the
• Involvement of primary care providers and administrative
adult setting. The following highlights key elements that should support to ensure continuous quality improvement process
be included in a transitional plan of care in order to ensure an • Ongoing consultation with the pediatric team/referring
effective transfer program from childhood into adulthood pediatric cardiologist after the transfer is complete
(Box 1).
COMPREHENSIVE MEDICAL CARE

proposes adult cardiologists as primary providers since they
The overall goal of transitional care is the transfer of care from are well prepared to deal with acquired diseases and address
the pediatric setting to an adult-focused model.6 Despite the adult issues. However, the main problem here is that they lack
recent attention given to transitional care, the actual transfer is training in the area of CHD and the management of long-term
often unsuccessful because of a number of identified barriers residua and sequelae after surgery. Adult-centered care is also
beginning with who is best qualified provider to take care of more patient-centered and disease oriented thus it takes for
the adult with CHD.7,8 granted that the patient has the necessary skills to self-manage
The first model is that pediatric cardiologists can provide his/her care.
continuity of care well into adulthood, based on the virtue Additionally, regardless of the setting, it is important to
that they are better informed on CHD and are more family- recognized that as adults, most CHD patients will at some point
centered. The main problem with this model is that pediatric require a number of non-cardiac health referrals.9,10 These
providers lack the experience of handling acquired heart may vary from routine preventive health care to non-cardiac
diseases and addressing adult care issues. A second model surgery. Throughout childhood, the pediatric cardiologist
10 has served, in most cases, not only as the cardiologist, but EMPLOYABILITY
as the primary care provider. As the child grows, parents
need to be encouraged to identify a primary care physician Adults with CHD have been able to find comparatively steady
Congenital Heart Disease in Adults
(general physician) who assumes not only the responsibility employment, although the type of employment for some
of coordinating the care, but is also willing to work closely is inferior compared to the general population. Obtaining
with cardiology and other subspecialities.9 suitable employment has historically been a serious concern
Particular attention must be given when the patient requires for the young adult with CHD.17 While less so today, full-time
non-cardiac surgery.10,11 Perioperative safety can be assured or part-time employment has been reported to occur in only
if the risks inherent in each individual case are anticipated. 71 percent of adults with CHD as compared with 84 percent
The surgical team must be informed as to the relative risk of healthy people.15,18,19 The rate of employment tends to be
of operation, including risks of bleeding, hypotension, higher among those with milder and acyanotic forms of CHD.17
hypovolemia and infective endocarditis. Relative risk is One possible explanation for this high unemployment rate is the
dependent upon the type of defect and any residual effects misunderstanding and the lack of knowledge or misperception
of CHD including rhythm disturbances, ventricular failure, regarding CHD by employers with respect to the individual’s
acquired medical problems or comorbidities such as diabetes future health prospects. Over the years, legislation in many
or hypertension. Cyanotic CHD with or without pulmonary parts of the world has been enacted to reduce employment
vascular disease presents with the highest risk and should be discrimination of individuals with preexisting disabilities. It
carefully evaluated prior to any surgical procedure. is therefore important for health care providers to give career
For females, gynecologic and reproductive issues are the and vocational counseling that assists the patient in selecting a
leading non-cardiac health issues that health care providers career. This should combine not only personal interests, but is
must address. A number of gynecologic issues such as in keeping with clinical limitations that the young person with
menstrual complaints and contraception frequently present CHD might have.20,21 In this way, we may provide them with
in adolescents and require age appropriate counseling and skills that are appropriate for achieving occupational success.
referral.12
FINANCIAL COSTS OF HEALTH CARE AND
EDUCATION AND CAREER COUNSELING INSURABILITY
While early studies reported that CHD had a negative Access to specialized care for the adult with CHD is not
impact on school progress, later studies have demonstrated uniformly available in all parts of the world. Even in developed
that with early surgical intervention and improved countries, patients and their families often have to travel long-
medical management, patients have attained educational distances for specialized care and follow-up. While most
milestones similar to those of healthy peers.13-15 Recent countries have national health care systems that will provide
studies focusing on neurodevelopmental outcomes have care to this special population, many of these centers are not
reported that while the majority of the children have within the patients reach. In the United States (USA), access
normal intelligence, a subgroup have demonstrated slightly to health care requires some form of insurance coverage and
lower scores on standardized tests of cognitive ability insurability. Infants and children are either covered by their
and academic achievement than those for the general parents’ insurance carrier or by a state health care coverage.
population.16,17 Specifically, children with complex CHD For adults with CHD, lack of insurance is one of the major
such as d-transposition of the great arteries, hypoplastic barriers to long-term follow-up and therefore discussions with
left heart syndrome and other functional single-ventricle parents and adolescent must be introduced, while they are still
lesions have a higher incidence of problems with academic covered by the parents or before the child’s state heath care
performance, behavioral abnormalities, hyperactivity and coverage is terminated, which is usually at 21 years or at 26
the ability to perform executive functions such as visual- years for students.18,20,22 Patients with complex CHD, who are
motor integration.16 Despite these findings, today the often more at risk, should be directed to explore policies that
majority of young adults with CHD achieve educational tend to have fewer restrictions such as group policies obtained
goals similar to that of the general population and should be through their employment.
encouraged to believe that they will grow up to be healthy
and able to work. Career counseling and vocational guidance SEXUALITY AND REPRODUCTIVE ISSUES
should be offered in middle and high schools so that based
upon their intellectual abilities and interests, adolescents are Sexual maturity is a major developmental milestone of
encouraged to achieve higher education and skills necessary adolescence. For many adolescents with CHD, discussion
for employment in occupations that are manageable based surrounding issues of human sexuality and reproduction are
on their work capacity. often avoided or ‘postponed’ by the parent and provider.
746
As a result many patients enter adulthood with a series of Table 1
 53
misconceptions and fears about their sexuality or their ability Informational needs for the young with congenital health disease
to conceive and bear children. There is limited emerging data
Transitional Care in Congenital Heart Disease

indicating that the majority of patients with CHD engage in Learning need Topic
sexual practices similar to the general population.23,24 For some, Defect-specific Discussion of treatment:
however, there remains some hesitation in disclosing their learning
CHD for fear of rejection. It is important, therefore, to permit • Surgical interventions
frank and open discussion on sexuality, childbearing and • Invasive/interventional cardiac
procedures
contraception for females. For males there may be concerns
• Medications and allergies/intolerance
regarding the emotional impact of intercourse on their heart • Exercise, sports and limitations
condition and the risk transmission of CHD to their offspring. • Diet/nutrition
Introducing the topic early in the transition process sends the Medical follow-up:
message to both teenagers and their parents that these are safe
• Adult CHD specialist or Pediatric
and welcome topics to discuss as part of their clinic visit. Cardiologist
• Primary care physician/health care
INFORMATIONAL NEEDS providers
Preventive Dental Health: Brushing, flossing, and
The ability to assume responsibility for their own health Health cleaning to prevent plaque formation,
care is an important developmental task for adolescents with Practices gingivitis and bacteremia
CHD. However, there are continuing reports unveiling the Indications for endocarditis prevention/
young adult’s lack of knowledge about their defect, treatment prophylaxis:
and need for follow-up. Many enter adulthood believing that • Dental hygiene or procedures
they are cured.25 One study found that while the majority of • Elective surgery/medical procedures
patients (80%), from 18 to 46 year-of-age, with CHD were • Tattooing/body piercing
able to correctly identify treatment plans, only 50 percent Risk Behaviors:
of this study group was able to identify the frequency of • Tobacco use
recommended follow-up medical/dental care and knowledge • Alcohol
about pregnancy risks.26 • Substance abuse: Marijuana, cocaine,
Thus, as the children enter their teenage years, health care street drugs
• Unprotected sex
providers must continuously assess their patients’ knowledge
of the condition and begin to provide age appropriate Counseling Educational and career development
Employment counseling
education.26 The adolescent should be given time, without his
Insurance coverage: Medical, dental and life
or her parents present, to ask questions not only about their insurance
heart condition, but also to establish a trusting relationship
Reproduction:
so that sensitive issues about sexuality, self-esteem may be
explored and addressed. The level of discussion should be • Females: Contraception, pregnancy and
gynecological issues
based on the patient’s physical, psychosocial development • Males: Childbearing and supporting a
and the information should be presented in a manner that is family
culturally and age appropriate.27 Topics to be included in a • Genetic transmission
structured educational plan are listed in Table 1. 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 with CHD enter teenage years, they should be educated
for developing endocarditis, it is prudent for patients at risk to about the risks of infection associated with body piercing and
understand the behaviors that can serve as portals for infection. tattooing. The patients should be made aware of questions
These include poor dental care, body piercing and tattooing. to ask with respect to needle sterilization before getting the
Early studies reported that only 50 percent of their population tattoos. While the standards of needle sterilization and safety
could name one situation considered at risk for acquiring techniques have improved, the frequency of procedure-
endocarditis.28 Thus discussions emphasizing the importance related infections remains a concern.29 There is small risk of
of maintaining regular good dental health and indications for bleeding and topical infections. Permanent tattooing should
antibiotic prophylaxis should be introduced early in childhood be discouraged in patients with CHD at risk for developing
to the parents and their children with CHD. These discussions endocarditis due to episodes of transient bacteremia or in
should be continued through adolescence. When the children those taking oral anticoagulants. 747
10 Exercise Counseling maturity of the teenager and her commitment to adhering to the
prescribed contraceptive choice. Although oral contraceptives
While the majority of available information on exercise are effective when used by teenagers, it is estimated that 13
supports the benefits of exercise for children and adolescent percent of teen users between ages of 15 to 17 years will miss an
CHD patients, it is important to counsel this growing average of three pills per month.34 Similar results are reported
population on appropriate recreational activities. This topic for patches and vaginal rings.34 Long-term contraceptives,
is discussed in more detail in the chapter on exercise and such as, implantable devices or IUDs, are safe for use in
sports in CHD. As adolescents enter high school and look young patients and carry a higher level of compliance.
to participate in higher level or competitive sports, exercise Injectables which are also safe still require regular return
testing is helpful in gauging safety. Over the years, the visits thus placing a certain level of responsibility on the teen
American Heart Association and others have published to return to clinic. Additionally, depomedroxyprogesterone
recreational and sport recommendations for young persons acetate (PMPS), known as Depo Provera carries a risk of
with heart disease.30-32 These guidelines have been the osteoporosis associated with the amenorrhea that occurs in
basis for outlining activities allowances and recommended long-term users.35 Therefore, teen use should be carefully
workloads for a number of postoperative defects and can be monitored especially in females who are extremely thin,
helpful to guide competitive and recreational activities that suffer from anorexia nervosa or have a comorbidity of
are safe. chronic renal disease36
Contraception and Preconception Counseling THE HEALTH PASSPORT

for Young Females
The American College of Cardiology/American Heart
Discussion on reproductive issues should be available to Association along with Adult Congenital Heart Association
females as they enter menarche. It should be presented in a (ACHA), which is a patient advocacy group in the United
sensitive and culturally appropriate manner that is in alignment States, have developed a booklet called ‘The Heath
with their individual level of emotional maturity and the value Passport’ which provides a comprehensive, summarized
system of their society. The initial discussions can take place account of patient information.37 The Health Passport can
in presence of the patient’s mother or a female family member be downloaded from the ACHA website at (http://www.
with whom she is comfortable with, but if there are family or achaheart.org/Portals/0/pdf/ACHAPassport.pdf). Its goal
cultural barriers associated with premarital sexual activity, is to outline routine health care recommendations and
the adolescent must be made aware that the provider is there specific information on diagnoses, procedures, operations,
for her to seek confidential counsel. It is important for health medications, allergies, endocarditis prophylaxis, exercise,
care providers to proactively address questions and concerns contraception and the recommended frequency of medical
regarding their sexuality, the ability to conceive/bear children, and dental follow-up. Patients are asked to carry it with
the safety and availability of contraceptives based upon their them at all times so that this information is available during
underlying defects.33 Once a young female becomes sexually emergency or unscheduled visits to hospitals or providers
active she should be referred to a gynecologist, preferably who are not familiar with the patient’s condition. They
one who works with adolescents, to ensure appropriate use should also carry a list of their cardiologist/health providers
of contraception and discussion and/or detection of sexually and personal emergency contacts.
transmitted diseases. Therefore, such a summary is referred to as a health
passport in that it is similar to a travel passport, because it
Contraceptives carries vital information to ensure safe health care when
one is away from his/her own providers. Patients are also
The prevention of unplanned pregnancy in adolescent/young encouraged to carry scanned copies of their medical reports
adult requires a collaboration between providers, patients and on a password encrypted flash drive so that more detailed
sometimes, their parents. Additionally, the adolescent health medical records are readily available during unforeseen
care provider should be familiar with the relation between circumstances.
oral contraception, particularly the estrogenic type and venous On their respective websites, the ACHA (www.achaheart.
thromboembolism that makes this form of contraception org), and the International Society of Congenital Heart Defects
hazardous for females who are cyanotic and/or in those with (ISACHD-www.isachd.org) have a list of some of the adult
conditions such as right-to-left shunts, pulmonary vascular CHD programs in the United States and around the world.
disease, prosthetic valves/conduits. Even though this list is not complete, through these contacts
A number of contraceptive methods are available to more information can be sought at the local and regional levels
teens.33 It is important, however, to consider the level of by the health care providers and then passed on to the patients.
748
CONCLUSION 12. Canobbio MM, Rapkin A, Perloff JK. Gynecologic Health of
females with congenital heart disease. Intl J Cardiol. 2004;98:
53
In this chapter an attempt has been made to provide an 379-87F.
Transitional Care in Congenital Heart Disease

overview of the transitional care issues that must be addressed 13. Ferencz C, Wiegmann FL Jr, Dunning RE. Medical knowledge
with the adolescent/young adult with CHD and his/her family. of young persons with heart disease. J Sch Health. 1980;50:
133-6.
These measures are to ensure a smooth transition into the
14. Kanoch MJ, Collins-Nakai RL, Medwid SM, et al. Adult
adult heath care system and avoid the complications resulting
patients’ knowledge about their congenital heart disease.
from lack of proper long-term care. Canadian Journal of Cardiology. 1997;13:641-50.
15. Simko LC, McGinnis KA, Schembri J. Educational needs
Be sober and temperate, and you will be healthy. Be in of adults with congenital heart disease. J Cardiovasc Nurs.
general virtuous, and you will be happy. 2006;21:85-94.
—Benjamin Franklin 16. Wernovsky G. Current insights regarding neurological and
(1706-1790) developmental abnormalities in children and young adults with
complex congenital cardiac disease. Cardiol Young. 2006;16
(suppl 1):92-104.
REFERENCES
17. Sable C, Foster E, Uzark K, et al. Best Practices in Managing
1. American Academy of Pediatrics, American Academy of Transition to Adulthood for Adolescents With Congenital Heart
Family Physicians, American College of Physicians–American Disease: The Transition Process and Medical and Psychosocial
Society of Internal Medicine. A consensus statement on health Issues. Circulation. 2011;123:1454-85.
care transitions for young adults with special health care needs. 18. Celermajer DS, Deanfield JE. Employment and insurance
Pediatrics. 2002;110:1304-6. for young adults with congenital heart disease. Br Heart J.
2. Report of the British Cardiac Society Working Party. Grown-up 1993;69:539-43.
congenital heart (GUCH) disease: current needs and provision 19. Kamphuis M, Vogels T, Ottenkamp J, et al. Employment in
of service for adolescents and adults with congenital heart adults with congenital heart disease. Arch Pediatr Adolesc
disease in the UK. Heart. 2002;88:i1–i14. Med. 2002;156:1143-8.
3. Rosen DS, Blum RW, Britto M, et al. Transition to adult health 20. Hellstedt LF. Transitional care issues influencing access to
care for adolescents and young adults with chronic conditions: health care: employability and insurability. Nurs Clin North
Position paper of the Society for Adolescent Medicine. J Am. 2004;39:741-53.
Adolesc Health. 2003;33;309-11. 21. McGrath KA, Truesdell SC. Employability and career
4. Skorton DJ, Garson A Jr, Allen HD, et al. Task force 5: Adults counseling for adolescent and adults with congenital heart
with congenital heart disease: access to care. J Am Coll Cardiol. disease. Nurs Clin of N Amer. 1994;29:319-33.
2001;37:1193-8. 22. Canobbio MM. Health care issues facing adolescents with
5. Knauth A, Verstappen A, Reiss J, et al. Transition and transfer congenitl heart disease. J of Ped Nurs. 2001;16:363-70.
from pediatric to adult care of the young adult with complex 23. Trends in the prevalence of sexual behaviors: National
congenital heart disease. Cardiol Clin. 2006;24:619-29. Youth Risk Behavior Survey: 1991–2009. US Department of
6. Foster E, Graham TP Jr, Driscoll DJ, et al. Bethesda Conference. Health and Human Services, Centers for Disease Control and
Task Force 2: special health care needs of adults with congenital Prevention, National Center for Chronic Disease Prevention
heart disease. J Am Coll Cardiol. 2001;37:1176-83. and Health Promotion, Division of Adolescent and School
7. Reiss JG RW, Walker LR. Health care transition: Youth, family, Health. 2009.
and provider perspectives. Pedatric. 2005;15:112-20. 24. Reid GJ, Siu SC, McCrindle BW, et al. Sexual behavior and
8. Reid GJ, Irvine MJ, McCrindle BW, et al. Prevalence and reproductive concerns among adolescents and young adults
correlates of successful transfer from pediatric to adult health with congenital heart disease. Int J Cardiol. 2008;125:332-8.
care among a cohort of young adults with complex congenital 25. Veldtman GR, Matley SL, Kendall L, et al. Illness
heart defects. Pediatrics. 2004;113:e197-205. understanding in children and adolescents with heart disease.
9. Deanfield J, Thaulow E, Warnes C, et al. Task Force on Heart. 2000;84:395-7.
the Management of Grown Up Congenital Heart Disease, 26. Moons P, De Volder E, Budts W, et al. What do adult patients
European Society of Cardiology; ESC Committee for Practice with congenital heart disease know about their disease,
Guidelines. Management of grown up congenital heart disease. treatment, and prevention of complications? A call for
Eur Heart J. 2003;24:1035-84. structured patient education. Heart. 2001;86:74-80.
10. Warner MA, Lunn RJ, O’Leary PW, et al. Mayo Perioperative 27. Day MJ. Educational assessment of the adult with congenital
Outcomes Group. Outcomes of noncardiac surgical procedures heart disease. The Nursing Clinics of North America.1994;29:
in children and adults with congenital heart disease. Mayo Clin 299-312.
Proc. 1998;73:728-34. 28. Cetta F, Warnes CA. Adults with congenital heart disease:
11. Webb GD, Burrows, FA. The risk of noncardiac surgery. Patient knowledge of endocarditis prophylaxis. Mayo Clinic
Jounral of Amer Coll Cardiol. 1991;18:311-42. Proceedings. 1995;70:50-4.
749
10 29. Cetta F, Graham LC, Lichlenberg RC, et al. Piercing and 34. Balassone ML. Risk of contraceptive discontinuation among
adolescents. J Adolesc Health Care. 1989;10:527-33.
tattooing in patients with congenital heart disease: Patient
and physician perspectives. Journal of Adolescent Health. 35. Cundy T, Evans M, Roberts H, et al. Bone density in women
1999;24:160-2. receiving depot medroxyprogesterone acetate for contraception

30. Gutgesell HP, Gessner IH, Vetter VL, et al. Recreational and BMJ. 1991;303:13-6.
occupational recommendations for young patients with heart 36. Cromer BA, Blair JM, Mahan JD, et al. A prospective
disease: a statement for physicians by the Committee on comparison of bone density in adolescent girls receiving
Congenital Cardiac Defects of the Council on Cardiovascular depot medroxyprogesterone acetate (Depo-Provera),
Disease in the Young, American Heart Association. Circulation. levonorgestrel (Norplant), or oral contraceptives. J Pediatr.
1986;74:1195A-8A. 1996;129:671-6.
31. Bar-Mor G, Bar-Tal Y, Krulik T, et al. Self-efficacy and physical 37. Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA
activity in adolescents with trivial, mild, or moderate congenital 2008 guidelines for the management of adults with congenital
cardiac malformations. Cardiol Young. 2000;10:561-6. heart disease: a report of the American College of Cardiology/
32. Mitchell JH, Haskell W, Snell P, et al. Task Force 8: American Heart Association Task Force on Practice Guidelines.
classification of sports. J Am Coll Cardiol. 2005;45:1364-7. J Am Coll Cardiol. 2008 Dec 2;52:e143-263 or in Circulation.
33. Canobbio MM. Contraception for the adolescent and young 2008;118:2395-451.
adult with congenital heart disease. Nursing Clinics of North
America. 2004;39:769-85.
750
C hapter
Management Issues in Adults

54 with Congenital Heart Diseases
Reema Chugh
INTRODUCTION successful intracardiac operation with the help of his newly

designed heart-lung machine “Model II”, for closure of an
The tale of how adult congenital heart disease (ACHD) atrial septal defect in an 18-year-old girl. This set the stage for
became as subspecialty of cardiology is fascinating, especially the advent of cardiac surgeries assisted by artificial circulation
when eloquently told by Dr Joseph Perloff (USA) and Dr Jane (bypass machine).
Somerville (UK), the founders of this field in the western In the same era, Dr Paul Wood, a dynamic cardiologist
hemisphere. with his passion for physical examination of the heart and
Only just over a 100 years ago, William Osler, often his deep interest in congenital heart disease (CHD) attracted
honored as the ‘Father of modern medicine’ in North America students from near and far to “drink up the new medicine”
wrote a book entitled “The Principles and Practice of as described by his disciple, Dr Jane Somerville. Born in
Medicine: Designed for the Use of Practitioners and Students India and raised in Australia, Dr Wood became well-known
of Medicine”, first published in 1892. He devoted only a 5 for describing the Eisenmenger syndrome and for writing the
page chapter (out of 1,079 pages) to ‘Congenital Affections first single author cardiology textbook, “Diseases of the Heart
of the Heart’. In his times, congenital heart defects were and Circulation”. Deeply influenced by the chapters from this
considered as hopeless futilities. Little did he know then that book on “Physical examination” and “Congenital affections
two of his female disciples would generate a new wave in the of the heart” another disciple, Dr Joseph Perloff went on to
field of medicine. write individual textbooks on these two topics. Dr Paul Wood
Maude Abbott, initially barred from studying medicine did not know, what his two students would do in the future.
because she was a woman, with her undying persistence and Dr Somerville collaborated Sir Magdi Yacoub, a world
perseverance acquired medical knowledge from universities reknown pioneering CHD surgeon and a dedicated team at
around the world. She returned to Montreal, Canada where the Royal Brompton Hospital, London to establish, a new
she soon became the curator of the McGill Pathological subspecialty that will be known as grown-up congenital heart
Museum in 1901. Her chapter on “Congenital Heart Disease” disease (GUCH) in Europe.
in Dr Osler’s text “Modern Medicine” in 1908 was very well Dr Joseph Perloff partnered with a brilliant cardiologist,
received. Ironically, she was awarded an honorary medical Dr John Child whose phenomenal clinical skills and talent
degree in 1910. Categorizing in detail the various congenital for mental 3D reconstruction led to his expertise in imaging
heart defects over the course of decades, she published CHD and a niche in “Echocardiography in CHD”. Joined
her work in the “Atlas of Congenital Cardiac Disease” by Dr Hillel Laks, a CHD surgeon par excellence, diligent
in 1936. Her contributions have served as a foundation for nurse specialists, Mary Canobbio, Pamela Miner and a
understanding the pathology of congenital heart disease. multidisciplinary team at UCLA Medical Center in Los
Osler’s other student, who was barred from receiving her Angeles, they established the first center for ACHD in North
medical degree alongside her classmates, since she was a America.
woman, was Helen Taussig. She led the pioneering “blue baby
operation” along with Vivien Thomas and Alfred Blalock in Why Adult Congenital Heart Disease
1944. This surgery changed the future of cyanotic congenital should be a subspecialty of cardiology?
heart disease.
In 1953 Dr John Gibbons, a surgeon and inventor at the Advances in all aspects of medicine and surgery have allowed
Jefferson Medical College in Philadelphia, performed the first the majority of the infants born with congenital heart defects,
10
who have access to healthcare, to survive into adulthood. slit-shaped tunnel-like defect in the atrial septum, residual from
While most individuals born with congenital heart defects are the fetal circulation, due to the failure of the primum and the
Congenital Heart Disease in aDults
diagnosed in infancy and childhood, some go undiagnosed secundum atrial septum to fuse postnatally, is often associated
until adulthood. Other than the exceptional case of an early with another defect of atrial morphogenesis called atrial
surgically ligated, isolated patent ductus arteriosus with no left septal aneurysm (ASA). An ASA may be associated with one
ventricular enlargement or dysfunction, all adults with CHD or multiple PFO in 50 to 85 percent of the cases. The ASA is
have postoperative residual and sequelae that need follow-up characterized by a redundant, undulating, interatrial membrane
throughout their lives. in the region of the fossa ovalis, with the diameter of the base
There has been organized global effort to integrate exceeding 15 mm and the amplitude of the interatrial septum
multidisciplinary services devoted to this special population. excursion up to 10 to 15 mm.7 Presence of a concomitant ASA
Many clinics/centers for Adult Congenital Heart Association increases the likelihood of thrombus formation on the left atrial
(ACHD) GUCH have sprouted around the world. The side of the aneurysm. Besides an ASA, the other proposed high-
International Society for Adults Congenital Heart Disease risk factors for cerebral embolic events associated with a PFO are
(ISACHD) has been instrumental in bringing together experts Eustachian valve anatomy favoring right-to-left shunt, presence
from all over the world (www.isachd.org). Over the past decade, of venous thrombus or hypercoagulable states. Both PFO and
the American College of Cardiology,1 European Society ASA are undetectable on physical examination (Table 1).
of Cardiology2 and the Canadian Cardiovascular Society Over the past two decades, the PFO has caught clinical
Consensus Conferences,3-6 published guidelines to establish interest for potentially contributing to paradoxical embolism,
standards of care for the adult with CHD. In the United States, especially in adults < 55 years old with cryptogenic stroke. In
the ACHA provides patient support and advocacy (www. most studies, the clinical diagnosis of paradoxical embolism
achaheart.org). Currently there are several professional and was presumptive and was based on the presence of a right-
patient-centered organizations assisting in the universal goal to to left shunt in the absence of a left-sided thromboembolic
improve quality of life and care of the adults with CHD. source. Its association with migraines is still open to question.
While there is a detailed discussion of embryology, The question also arose, whether transcatheter device closure
pathology, genetics, natural history, clinical presentation, of PFO really ‘shut the door’?8
diagnosis and management of individual defects in other In a multicenter European study with 581 patients who had
chapters of this book, the aim of this chapter is to provide an ischemic stroke, an association of recurrent stroke rate for
a concise overview regarding salient management issues patients with ASA and PFO was 15.2 percent compared with
encountered while caring for an adult with CHD. 4.2 percent in the absence of these 2 defects.9 A prospective
population-based study, Patent foramen ovale In Cryptogenic
DEFECT SPECIFIC MANAGEMENT Stroke Study (PICSS), suggested that after correction for age
ISSUES IN ADULTS WITH CHD 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
SHUNT LESIONS
not truly representative of the PFO patient population with
ischemic stroke. The quest for an answer to whether “to close
Patent Foramen Ovale or not to close” the PFO in adults with cryptogenic stroke
One of the most common indications for performing a younger than 55 years by a percutaneous device is still on. A
transesophageal echocardiogram is to rule out cardiac source recent randomized trial (Closure I) did not detect any benefit
of emboli in an adult patient with a cerebrovascular event of closure over medical treatment alone.11-13
(stroke or transient ischemic attack). Besides looking for an With respect to selection of antiplatelet versus
obvious intracavitary thrombus, clot in the left atrial appendage anticoagulant therapy, the data continues to be controversial.
or atheromas in the ascending limb of the aortic root or arch, In the Warfarin-Aspirin Recurrent Stroke Study (WARSS),
the cardiologist is expected to rule out the possibility of a 2,206 patients were randomized to aspirin or warfarin (INR
paradoxical embolus through an interatrial communication 1.4 to 2.8) with no significant benefit from either treatment
with a right-to-left shunt, such as a patent foramen ovale (PFO) at 2 years.14 The present opinion based on observational and
or an atrial septal defect with a bidirectional shunt or shunt randomized data from 9 studies that compared the medical
reversal. An adequate Valsalva maneuver is essential, while therapies is consistent and suggests that anticoagulants are
assessing the presence of a right-to-left shunt by an agitated superior to antiplatelets for preventing stroke recurrence.11,15
saline contrast study with transthoracic or transesophageal While the search for the optimal management continues,
echocardiogram. patients with large PFO, especially in the setting of an atrial
It is the most common CHD, with an autopsy–derived septal aneurysm, may receive low dose aspirin for primary
752 incidence for a probe-patent PFO of around 27 percent. This prevention of thromboembolic events.
54

table 1
Shunt lesions
ManageMent issues in aDults witH Congenital Heart Diseases

Heart defect Cardiac examination Residual and sequelae Associated defects
(common)
Patent foramen None Paradoxical embolus Atrial septal aneurysm

ovale stroke
Secundum atrial septal Prominent right ventricular Atrial arrhythmias Anomalous pulmonary
defect impulse Right heart failure venous return
Wide fixed splitting of S2 Pulmonary hypertension
Pulmonary ejection systolic Left ventricular dysfunction
murmur at left upper sternal Paradoxical embolism/stroke
edge
Accentuated P2
Ventricular septal defect Pansystolic murmur Infective endocarditis Atrial septal defects (ASDs)
Precordial thrill Pulmonary hypertension Aortic valve regurgitation
Accentuated P2 (in Left ventricular dysfunction Aortic root dilatation
pulmonary hypertension) Conduction defects
(heart block)
Aortic insufficiency
Tricuspid regurgitation
Patent ductus arteriosus Continuous ‘machinery’ Infective endocarditis/ Occurs in association with
murmur at the left upper endarteritis several congenital heart
sternal border with radiation Pulmonary hypertension defects
to the back Left ventricular heart failure Accounts for 10% of all
Aneurysmal congenital heart defect
Calcification (CHD)
Rupture
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 for ASD closure. A sinus venosus defect with associated
anomalous pulmonary venous return is suspected, when there
One in six individuals born with an atrial septal defects (ASDs) is right heart enlargement in the absence of a clearly defined
is likely to be first diagnosed in adulthood. Palpitations due to interatrial shunt. Further evaluation with a transesophageal
atrial arrhythmias and dyspnea are the most common presenting echocardiogram is recommended in these cases and in all cases
symptoms. An ASD is a direct communication between the prior to ASD closure to rule out concomitant congenital heart
cavities of the atrial chambers that permits shunting of blood. defects. Possible reasons for clinical deterioration in adults with
Associated defects occur in nearly 30 percent of patients with unclosed ASD are listed in Box 1.
a secundum ASD (the most common form). Characteristic The consensus is to close defects in symptomatic patients
physical findings are a prominent right ventricular parasternal and in those with right heart enlargement. Percutaneous
lift, persistent or wide fixed splitting of the second heart sound transcatheter device closure is presently the method of choice
and a pulmonary systolic ejection murmur, at the left upper for defects within the fossa ovalis with an adequate rim
sternal edge due to increased pulmonary flow. Pulmonary of at least 4 to 5 mm (in order to avoid distortion of these
hypertension leads to an accentuation of the pulmonary surrounding structures), between the ASD and the aortic valve
component of the second heart sound. Electrocardiogram (ECG) annulus, atrioventricular (AV) valves, pulmonary and systemic
may show sinus rhythm or atrial fibrillation, right axis deviation veins. In the presence of pulmonary hypertension, the defect
(left axis deviation in primum ASD) and a bifid notch on the may be safely closed if pulmonary artery systolic pressure
ascending limb of the R wave in inferior leads (‘crochetage’).16 is less than 50 percent of the systemic arterial pressure.
Transthoracic echocardiography establishes the diagnosis in Right heart catheterization to assess the pulmonary vascular
most cases by demonstrating a discontinuity of the interatrial resistance may be required for those with higher pulmonary
septum on two-dimensional echocardiogram and an intracardiac artery pressures. In general, all defects should be considered
shunt at the atrial level with color Doppler. Long-standing for early closure unless there are specific contraindications.
significant left-to-right shunt causes right heart enlargement Endocarditis/endarteritis prophylaxis is recommended for 6 753
and elevated pulmonary artery pressures, which is an indication months after device closure.1
10
Box 1: Causes for clinical deterioration in adults Victor Eisenmenger in 1897 described a bidirectional or
reversed (right-to-left) shunt through the large VSD leading
with unclosed asD

to severe pulmonary hypertension. It was later defined by
• Age-related decrease in left ventricular compliance may Dr Paul Wood in 1958 as Eisenmenger syndrome with its
lead to augmentation of the left-to-right shunt
• Heart failure may be precipitated by atrial arrhythmias
distinctive clinical and physiologic characteristics.19
• Persistence of left-to-right shunt may lead mild to In patients with a supracristal (subpulmonic) VSD there
moderate pulmonary hypertension, consequent right is progressive aortic regurgitation, due to prolapse of the
ventricular pressure and volume overload aortic valve leaflet into the defect resulting from the ‘venturi
• Delayed closure has been shown to be associated with a effect’. Closure of the VSD along with aortic valve repair is
higher likelihood of long-term complications: recommended to avoid progressive left ventricular dilatation and
– Atrial arrhythmias dysfunction from worsening aortic regurgitation. Endocarditis/
– Pulmonary hypertension
– Right heart failure
endarteritis prophylaxis is recommended for 6 months after
– Paradoxical embolism and stroke surgical closure for an isolated VSD and should be continued
lifelong if there is concomitant valve surgery or residual shunt.1
Ventricular Septal Defect Patent Ductus Arteriosus

While some small ventricular septal defects (VSDs) close Adults with a small patent ductus arteriosus (PDA) are usually
spontaneously in childhood (10%), others persist into adulthood asymptomatic, while those with a moderate to large PDA may
with a 25 percent likelihood of serious complications.17 The present with dyspnea or palpitations. Patent ductus arteriosus
VSD is a communication between the two ventricles resulting is a residual fetal communication between the proximal left
from the failure of the components of the interventricular pulmonary artery and the descending aorta distal to the left
septum to fuse, with the perimembranous VSD being the subclavian artery. During fetal life, it allows the diversion of
most common form. Residual shunts are sometimes seen in blood from the right ventricle to the descending aorta, thus
patients with larger VSDs, who have undergone surgery or bypassing the pulmonary circulation. Physical examination
percutaneous closure. Although aware of a murmur all through is remarkable for a continuous machinery murmur at the left
their lives, many asymptomatic individuals are only diagnosed upper sternal border with radiation to the back. In others, PDA
in adulthood. Physical examination is characteristic of a is only detectable on an echocardiogram. After several decades,
pansystolic murmur (and sometimes precordial). The pulmonic PDA may get calcified and become visible on a chest X-ray.16
component of the second heart sound may be accentuated in the The long-term residua, sequelae and the type of intervention
presence of pulmonary hypertension. Late closure of a VSD depend upon the size and shape of the PDA. The risk of
predisposes to long-term residua and sequelae in adulthood.16 endarteritis is present in all patients, therefore antibiotic
Echocardiography defines its location, degree of shunt prophylaxis and early closure are recommended. Heart failure
and associated defects and most long-term issues depend on and pulmonary hypertension are likely to develop with a
these parameters. The most important clinical issue is the risk moderately sized or larger PDA. Device closure is preferred
of endocarditis seen in around 11 percent of the adult with for the majority of the patients.20 Surgical closure is indicated,
a VSD.17 Meticulous dental hygiene, skin care, antibiotic when PDA is too large and not amenable to device closure
prophylaxis before dental procedures and early treatment of or in the presence of a ductal aneurysm. Patients, who have
infection are strongly recommended. increased pulmonary vascular resistance at the time of closure
Common long-term complications of persistent VSD are may present with late pulmonary hypertension. Presence of
heart failure, pulmonary hypertension and arrhythmias,17 that severe, irreversible pulmonary vascular disease is a contra-
depend on the volume and pressure load. The direction and indication for PDA closure, as it is for all shunt lesions.
the volume of an interventricular shunt are dictated by the size Endocarditis/endarteritis prophylaxis is recommended for 6
of the defect and the ratio of pulmonary vascular resistance months after device closure and lifelong for residual PDA.1
to the systemic vascular resistance. The left heart experiences
volume load and depending on the size of the defect, the right VALVULAR DEFECTS
heart may experience a pressure load. In a small, restrictive
VSD, right ventricular systolic pressure is less than half of CONGENITAL PULMONARy VALVE LESIONS
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 Pulmonary Stenosis
the two chambers. This leads to near systemic pressures in This is the most common form of a right sided obstruction,
754 the pulmonary arteries that causes irreversible pulmonary resulting from fusion of valve leaflets that may occur as an
vascular disease and pulmonary hypertension.18 isolated heart defect in up to 10 percent of patients with CHD.
54
Pulmonary stenosis (PS) has been associated with maternal The physical examination in an adult with moderate to
rubella, Noonan’s syndrome, William’s syndrome and Alagille severe PS is significant for a prominent right ventricular

syndrome. impulse palpable at the left sternal border (with or without a
Most patients with mild PS are asymptomatic and at low- thrill), normal first and widely split second heart sound with
risk of getting infective endocarditis. Patients with the ‘dome- normal respiratory variation, a harsh crescendo-decrescendo
shaped’ valve are likely to have fusion of the leaflets with systolic murmur that becomes louder with inspiration and is
increasing stenosis and calcification in adulthood. There is a heard best at the left upper sternal border.16
higher likelihood of pulmonary artery dilatation and aneurysms Echocardiography confirms the diagnosis and assesses
due to an associated connective tissue disorder.21 In contrast, the the severity of the transvalvular gradient, right ventricular
dysplastic pulmonary valve with thickened leaflets is not usually systolic pressure, right ventricular size, function and associated
associated with pulmonary artery dilatation. Other forms are defects (Table 2). Based on the peak systolic gradient on
unicuspid, bicuspid, tricuspid, quadricuspid or their variations. transvalvular Doppler, the severity of PS is graded as mild

table 2
Valvular defects
Heart defect Salient findings on Residua and sequelae Associated defects

cardiac examination (common)
Pulmonary stenosis Widely split second heart sound Pulmonary regurgitation Patent foramen ovale (PFO)
with normal respiratory variation Pulmonary artery dilatation/ Atrial septal defect (ASD)
Harsh crescendo-decrescendo aneurysm Ventricular septal defect (VSD)
systolic murmur radiating to the Right ventricular hypertrophy Peripheral pulmonary stenosis
back and louder with inspiration— Right heart failure
best heart at the left upper sternal Sudden cardiac death
border
Pulmonary regurgitation Widely split second heart sound Right heart enlargement Pulmonary valve abnormality-
(absent if rudimentary or absent Right heart failure isolated
valve tissue) Tetralogy of fallot
Crescendo-decrescendo, short
diastolic murmur—best heard in the
second or third intercostal space
Ebstein’s anomaly Widely split first heart sound, split Atrial arrhythmias- fibrillation/ PFO–very common
second heart sound, soft, early flutter—25–30% ASD–over 30%
systolic murmur that increases Supraventricular tachycardia Wolf-Parkinson-White
with inspiration— best heard at the Right heart failure syndrome—5–25%
lower left sternal border Left heart failure Congenitally corrected
Cyanosis transposition of the great
Sudden cardiac death arteries (CCTGA)
Paradoxical emboli VSD
Patent ductus arteriosus (PDA)
Left heart abnormalities
including left ventricular non-
compaction (LVNC)—40%
Pulmonary stenosis or atresia
Tetralogy of Fallot
Bicuspid aortic valve Systolic ejection click Infective endocarditis Coarctation of aorta
Early peaking systolic flow murmur Aortic dissection Aortic root dilatation
Aortic stenosis Sub and supra-aortic stenosis
Aortic insufficiency VSD
Mitral valve prolapse Apical mid to late systolic clicks Mitral regurgitation Secundum ASD
(MVP) Late systolic murmur with Atrial arrhythmias Holt-Oram syndrome
radiation to the apex due to mitral Endocarditis Ebstein’s anomaly
regurgitation MVP syndrome Marfan syndrome
Heart failure Ehlers-Danlos syndrome
Infective endocarditis Osteogenesis imperfecta
Syncope (related to orthostatic 755
hypotension)
Sudden cardiac death—rare
10
(25–49 mm Hg), moderate (50–79 mm Hg) and severe (over 80 enlargement occurs with long-standing severe pulmonary
mm Hg). In order to avoid adverse effects from long-standing regurgitation. The interventricular septum is dyskinetic due to
significant PS, percutaneous balloon valvuloplasty should right heart volume overload and the left ventricle may appear
be performed, when the peak transvalvular gradient is over D-shaped on the parasternal short-axis view.
50 mm Hg, even when the patient is asymptomatic.22 Severe Pulmonary valve replacement is indicated in patients
PS can lead to marked right ventricular hypertrophy, right heart with severe pulmonary regurgitation, who are symptomatic
failure and risk of sudden cardiac death. Surgical valvotomy or have early signs of right heart enlargement with impaired
or pulmonary valve replacement is considered, when there is ventricular function.1
significant calcification, a thickened stiff dysplastic valve and/
or concomitant pulmonary artery aneurysm. Pulmonary valve CONGENITAL TRICUSPID VALVE DEFECTS
replacement (transcatheter or surgical) is indicated for severe
pulmonary regurgitation before it affects the right ventricular
Ebstein’s Anomaly
function.1
Ebstein’s anomaly is an abnormality of the tricuspid valve
Pulmonary Regurgitation characterized by the tethering of the septal leaflet to the
ventricular septum that gives an impression of apical
Clinically insignificant trace to mild pulmonary regurgitation displacement of the tricuspid valve. It is associated with
(PR) is seen in individuals with structurally normal hearts.23 discontinuity of the central fibrous body, which lends itself to
It rarely occurs as an isolated defect. Most adults present creating a substrate for accessory pathways and type B Wolf-
with significant PR in association with tetralogy of Fallot and Parkinson-White (WPW) syndrome in 5 to 25 percent of the
rarely with other malformations. Significant PR may occur in cases. These patients are therefore predisposed to having
the presence of morphologically abnormal pulmonary valves supraventricular tachycardia.25
or when there is total absence of the pulmonary valve. While On physical examination, the characteristic signs are a
most adults tolerate low pressure PR, a small group may palpable impulse in the left third intercostal space (due to an
develop right heart enlargement and right heart failure due to enlarged infundibulum). On auscultation, the first heart sound
long-standing severe PR.24 Pulmonary hypertension (primary is widely split due to a delayed loud tricuspid component
or secondary) can contribute to progression of PR. (caused by the increased excursion of the elongated anterior
Isolated PR is incidentally diagnosed because of the murmur, leaflet of the tricuspid leaflet that delays closure of the
in association with a dilated pulmonary trunk noted on a chest valve). In the presence of a right bundle branch block, the
X-ray or as an incidental finding on an echocardiogram. second heart sound is also split due to delayed closure of the
On clinical examination, patients with right heart failure pulmonary valve. A quadruple rhythm may be heard due to
will have prominent A and V waves of the jugular venous third and fourth heart sounds. There is a soft, early systolic
pulse. On palpation, in patients with severe PR, there is a murmur that increases with inspiration and is best heard at the
hyperdynamic pulse at the left sternal border and subxiphoid lower left sternal border.16
area. Dilated pulmonary artery may generate prominent The characteristic finding on the electrocardiogram of the
pulsations in the second left intercostal space. On auscultation, tall, peaked ‘Himalayan’ p waves (described by Dr Helen
a normal first heart sound is usually followed by a widely Taussig) occur primarily due to prolonged aberrant conduction
split second heart sound (usually associated with increase through the markedly enlarged right atrium.26 PR interval may
capacitance of the pulmonary vascular bed and slow elastic be prolonged in 50 percent of the cases except, when there
recoil) that decreases with inspiration in the absence of right is preexcitation (demonstrated by an intermittent delta wave)
heart failure. The second heart sound is absent, when there due to type B WPW syndrome in nearly 25 percent of the
is rudimentary or absent valve tissue. Patients with moderate cases. Additionally, there is right bundle branch block pattern
to severe PR have a distinctive crescendo-decrescendo, short and deep Q waves in the inferior leads, as well as in V1-4.25
diastolic murmur that is best heard in the second or third Chest X-ray is notable for a narrow vascular pedicle due to
intercostal space.16 lack of pulmonary artery border and a narrow ascending aortic
Two-dimensional echocardiogram defines the anatomy of shadow. A ‘box-like’ appearance of the cardiac silhouette is
the pulmonary valve, the size of the main pulmonary artery, due to a very prominent right atrial border contributing to the
proximal right and left branches, size and contractility of the right heart convexity and a dilated infundibulum contributing
right ventricle. Pulmonary regurgitation is primarily graded to left heart convexity.16
by color Doppler. An important point to note is that the right Echocardiogram defines the morphology of the tricuspid
ventricular outflow tract may have pulsatile motion in the case valve and allows assessment of the right atrial size, biventricular
of low pressure severe pulmonary regurgitation, even when size, function and associated defects (Table 3). The tricuspid
756 the color Doppler is not too impressive. Significant right heart valve is characterized by apical displacement due to tethering
54

table 3
Complex congenital heart defects

Coarctation of aorta Thrill in the suprasternal notch Hypertension Bicuspid aortic valve
Loud aortic closure sound Infective endocarditis/endarteritis Aortic aneurysm
Recoarctation Intracranial aneurysms
Aortic aneurysm Subaortic stenosis
Premature coronary artery Mitral stenosis
disease
Tetralogy of Fallot post Right ventricular heave (due to Impaired right and left ventricular Patent foramen ovale (PFO)
repair right ventricular hypertrophy) function, Atrial septal defect (ASD)
Single S2 (aortic component Pulmonary regurgitation Muscular VSD
only) Tricuspid regurgitation Right aortic arch
PR -crescendo-decrescendo Aortic regurgitation Coronary artery abnormalities-
harsh to-and-fro diastolic Aortic root dilatation commonest is left anterior
murmur loudest at the second Right ventricular outflow tract descending (LAD) originating from
intercostal space (RVOT) obstruction obstruction/ right coronary sinus crossing the
AR - grade 1-2/4 soft diastolic aneurysm RVOT
murmur heard best in the left Ventricular arrhythmias- Hypoplastic pulmonary arteries
lower sternal border monomorphic VT-nonsustained
TR Sudden cardiac death
Residual ventricular septal Residual ventricular septal defect
defect—pansystolic murmur at (VSD)
the left lower sternal border Conduit (Rastelli) obstruction
Signs of right heart failure–
elevated jugular venous
pulsations, pedal edema,
ascites
Dextro-transposition of Single and loud S2 (due to Systemic ventricular dysfunction VSD

the great arteries anterior position of the aortic Baffle leak PFO/ASD
(D TGA) valve) Baffle obstruction Patent ductus arteriosus (PDA)
post atrial switch repair Heart murmurs depending on Tachyarrhythmias AV septal defect
associated valvular disease Bradyarrhythmias
Pulmonary hypertension Abnormal origin of the coronary
Sudden cardiac death arteries coarctation of aorta
(COA)—5%
Left ventricular outflow tract
(LVOT) obstruction (subpulmonic
stenosis)—25%
RVOT obstruction(subaortic
narrowing)
D TGA Diastolic murmur due to neo- Coronary artery fibrosis—18% As noted above
post arterial switch aortic valve regurgitation Sudden cardiac death—ischemia/
repair Pulmonary ejection murmur if sustained ventricular tachycardia
conduit stenosis is present Neoaortic valve regurgitation
Mild aortic root dilatation
Pulmonary artery stenosis at the
valvar, supravalvar or peripheral
levels—5–25%
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
Pulmonary hypertension 757
Contd...
10
Contd...

D TGA post-Rastelli Pulmonary ejection murmur if Reoperations for conduit As noted in the previous page
repair conduit stenosis is present obstruction
Diastolic murmur if conduit Arrhythmias-atrial and ventricular
regurgitation is present Heart block
Sudden cardiac death
Left ventricular dysfunction
—25%
Right ventricular dysfunction
Endocarditis
Congenitally corrected Loud usually single second Systemic ventricular dysfunction Ventricular septal defect (60–80%)
transposition of the heart sound (A2), soft P2. Heart failure Pulmonary stenosis
great arteries Systolic murmur at the left Systemic AV valve (tricuspid) Tricuspid valve abnormality
sternal border or apex due to regurgitation (Ebstein/Ebstein-like
systemic AV valve regurgitation, Complete heart block abnormality or dysplastic)
other murmurs depending upon Emboli stroke Patent foramen ovale
the associated defects Endocarditis Atrial septal defect
Conduit stenosis (in Rastelli LVOT obstruction-subaortic or
repair) supravalvular stenosis
Aortic regurgitation Coronary artery anomaly (inverted
Sudden cardiac death due to ventricular inversion)
Tricuspid atresia post Usually, quiet heart sounds Heart failure Univentricular heart/single ventricle
Fontan operation Single second heart sound Systemic (usually left) ventricular physiology with a hypoplastic right
Holosystolic murmur radiating dysfunction ventricle
to the apex due to mitral Atrial arrhythmias
regurgitation. Thrombus in the right atrium Atrial septal defect
Protein losing enteropathy Ventricular septal defect
Endocarditis Transposition of the great arteries
Pacemaker
Atrioventricular valve regurgitation
Conduit obstruction—Obstruction
of the Fontan connection—usually
right pulmonary vein compression
with enlarged right atrium or
conduit obstruction
of the septal leaflet, over 2 cm in adults, in relation to the saturation with activity. Severe tricuspid regurgitation and
septal attachment of the mitral valve. In contrast, the anterior increased degree of apical displacement of the tricuspid valve
leaflet appears elongated and large with ‘sail-like’ motion. The predisposes to right heart failure. Eventually, left heart failure
right atrial size appears larger due to ‘atrialization’ of the right may develop due to prolonged cyanosis, interventricular
ventricle, with relatively small right ventricle. Color Doppler dependence and left heart fibrosis.
is used to assess the severity of tricuspid regurgitation and Cyanosis occurs, when high filling pressures of the volume-
rule out an interatrial communication such as a patent foramen overloaded right ventricle instigate right-to-left shunting at the
ovale or an atrial septal defect. atrial level. These patients are at risk for paradoxical emboli
Clinical presentation in adults with Ebstein’s anomaly or cerebral abscess because of the interatrial communication
depends upon the severity of morphological tricuspid valve (PFO or ASD). Atypical chest pain, the etiology of which is
abnormality, the functional status (degree of regurgitation) not clearly understood, but sometimes attributed to sternal
of the tricuspid valve and the presence of associated defects. compression of the enlarged right heart, is also seen in some.
Adults with mild abnormality of the tricuspid valve with no Uncontrolled arrhythmias cause hemodynamic deterioration,
associated defects may remain asymptomatic for most of progressive cyanosis and syncope. The risk of sudden
their lives. The most common clinical issues in adulthood cardiac death may be increased by sustained tachycardias
are atrial arrhythmias such as atrial fibrillation/flutter and such as atrial fibrillation/flutter with rapid ventricular rates.
supraventricular tachycardia. Dyspnea and decreased exercise Atrial arrhythmias should be managed with medications.
758 tolerance occurs due to an inadequate increase in pulmonary Radiofrequency ablation (RFA) should be considered when
blood flow and a decrease in systemic arterial oxygen there is an accessory pathway, even though it is associated
54
with relatively low success rates.27 Right heart catheterization Although aortic root dilatation is most commonly associated
should be avoided since stimulation of the atrialized right with Marfan’s syndrome, in absolute numbers there are more

ventricle may produce ventricular tachycardia or ventricular people, who have aortic dilation associated with BAV (since
fibrillation. BAV is a more common defect). The aortic root dimensions
Surgical repair or replacement of the abnormal tricuspid should be followed on serial echocardiograms. Computerized
valve and concomitant defects should be performed in tomography (CT) scan or magnetic resonance imaging (MRI)
adults, who have poor functional capacity despite medical is required, when aneurysm of descending aorta is suspected
therapy28,29 and/or have right heart failure or progressive in patients with coexistent coarctation of aorta.
cyanosis. Valve repair is preferred over replacement, but it Calcification leads to stenosis of the BAV at an earlier age
can be very challenging due to the severity of tricuspid valve in men than in women, with an average increase of 18 to 27
abnormality. A bioprosthetic valve is preferred when valve mm Hg in the aortic valve gradient for each decade of life.
replacement needs to be performed. Anatomy of the cusps and acquired risk factors affect the rate
Although endocarditis is rare in isolated Ebstein’s anomaly, of progression. In patients with left ventricular dysfunction, the
probably because of the low velocity tricuspid regurgitant jet, valve gradients may underestimate the degree of stenosis. Risk
it is prudent to offer endocarditis prophylaxis, especially in factors for atherosclerosis such as hyperlipidemia, hypertension,
the presence of concomitant defects.1 obesity and smoking may also contribute to the age-related
deterioration of the aortic valve. Intensive cardiovascular risk
CONGENITAL AORTIC VALVE DEFECTS 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
Bicuspid Aortic Valve
regurgitation. Concomitant aortic root surgery is performed
Infective endocarditis is often the clinical scenario in which with the aortic root dimensions are over 4 cm. Emergent surgery
undiagnosed adults with bicuspid valves present, whether is required in those presenting with infective endocarditis and
or not it may have led to severe aortic regurgitation due to new onset severe aortic regurgitation or an aortic root abscess.1
damaged valve tissue. Due to a very high incidence of endocarditis and its asso-
Bicuspid aortic valve is defined as an aortic valve with ciated complications, antibiotic prophylaxis is recommended
(effectively) two instead of three valve leaflets, with many in all patients, even in the absence of associated stenosis or
variations in the pattern. It most commonly presents with regurgitation.
fusion of the right and left aortic valve cusps. On physical
examination, there may be a systolic ejection click and an CONGENITAL MITRAL VALVE DEFECTS
early peaking systolic flow murmur (Table 3).
The diagnosis is confirmed by an echocardiogram. In the
Mitral Valve Prolapse
parasternal short axis view, a bicuspid aortic valve (BAV)
opens as an oval (American football) in contrast to the Mitral valve prolapse (MVP) is a very common connective
triangle of a trileaflet valve that appears like the ‘Mercedez tissue abnormality of the mitral valve frequently associated
Benz sign’ when closed. A transesophageal echocardiogram with mitral regurgitation (MR) and endocarditis in adults
may be required when the aortic valve morphology cannot with otherwise structurally normal hearts. It often occurs in
be visualized clearly in the parasternal short axis view on association with other CHD and connective tissue disorders.
a transthoracic echocardiogram. Approximately 9 percent Clinical symptoms of increasing dyspnea and decreasing
patients with BAV will have an autosomal-dominant pattern exercise tolerance may be related to severe mitral regurgitation
of inheritance with incomplete penetrance and variable with or without atrial fibrillation, heart failure and/or
expression that may affect several family members. Therefore, pulmonary hypertension. Endocarditis prophylaxis should be
echocardiographic screening of first-degree relatives is offered, especially to those with significantly myxomatous
recommended to look for BAV.30 mitral valves and associated regurgitation. Acute rupture of
A complete echocardiographic examination should define the chordae may occur in severe MVP leading to acute severe
morphology, degree of aortic stenosis and aortic regurgitation mitral regurgtitation and heart failure. Stroke probably from
and assessment of associated defects (seen in 20–50% of the an embolic phenomenon may occur due to platelet aggregation
patients). on markedly myxomatous disrupted endocardial surface.
Due to inherent aortic structural wall abnormalities, BAV Mitral valve prolapse syndrome may occur in some adults
has an associated risk of aortic root dilatation and aortic (especially in women) with atypical chest pain/pressure,
dissection.21 The risk is markedly increased, when BAV palpitations, anxiety, orthostatic hypotension (probably due to
is associated with coarctation of aorta. Progression of the autononic dysfunction).31 Management of the MVP syndrome
ascending aortic dimensions may be achieved by controlling is primarily supportive with increased hydration, reduced 759
hypertension, avoiding heavy weights and isometric exercises. caffeine intake, aerobic activity, beta blockers, adequate dietary
10
potassium and magnesium intake. Significant orthostatic Hence, closure of ASD will help reduce pulmonary blood
hypotension in the absence of heart failure, may respond to flow and the risk of developing pulmonary hypertension.
volume expansion with good hydration, high sodium intake Echocardiography defines the morphological defect, left
and the use of fludrocortisone acetate (Florinef USP). It is tip mobility, papillary muscle anatomy and examines for
a synthetic adrenocortical steroid, which produces marked presence of a supravalvular fibrous membrane. The severity
sodium retention and increased urinary potassium excretion, of mitral stenosis is assessed by pressure half-time based
because of its mineralocorticoid effects. This leads to a rise in calculation of valve area, mean gradient and estimated of
blood pressure, because of the effects on electrolyte levels. It the right ventricular systolic pressure that is a surrogate
is usually prescribed as a daily oral dose of 0.1 mg. for pulmonary artery pressures. In double orifice valve or
On physical examination, although apical mid to late supravalvular membrane with multiple orifices, the area of the
systolic clicks (due to sudden tension in the subvalvular individual orifices is added to give a total orifice area. Medical
apparatus when the leaflets prolapse) have been reported, the management includes diuretics, beta blockers and arrhythmia
more frequent auscultatory findings are a late systolic murmur control. In case of severe symptomatic stenosis, surgery is
with radiation to the apex due to mitral regurgitation. ECG may performed.33
demonstrate nonspecific ST and T wave abnormalities that can
cause false positive treadmill stress tests. Two-dimensional Coarctation of Aorta
or three-dimensional, transthoracic or transesophageal echo-
cardiography are the most accurate diagnostic methods.32 While moderate to severe coarctation of aorta (COA) is
Afterload reduction with angiotensin converting enzyme usually diagnosed in infancy or childhood, the diagnosis is
(ACE) inhibitors or angiotensin receptor blockers is suspected in a person presenting with secondary hypertension
recommended in hypertensive adults with mitral regurgitation. in adulthood. Severe left ventricular hypertrophy by voltage
Mitral valve repair should be considered early in symptomatic criteria on an electrocardiogram or by echocardiographic
patients with preserved left ventricular size and function. criteria in a young adult should raise an alarm.
Although mitral valve replacement is less desirable, it Coarctation of aorta is congenital narrowing of the aorta at
may be the only option for those with very friable, heavily the junction of the distal aortic arch and the descending aorta,
myxomatous valves with severe prolapse. below the origin of the left subclavian artery. It comprises up to
8 percent of all CHD. The discrete coarctation is not just limited
Cleft Mitral Valve to focal stenosis, but is one variant of a diffuse arteriopathy and
associated structural abnormalities of the great arterial walls.16
Besides MVP, congenital MR may occur in association with A brachial and femoral blood pressure recording demonstrates
a cleft mitral valve, usually seen in association with Down upper-body arterial hypertension. There are decreased arterial
syndrome or rarely as an isolated defect. The management pulsations and blood pressure in the left upper extremity when
in adults with mitral regurgitation is guided by the criteria there is interrupted blood flow into the left subclavian artery
outlined for acquired mitral regurgitation.33 (with compensatory blood flow via collaterals). Accurate
blood pressure recordings are obtained from the right arm in
Congenital Mitral Stenosis these individuals. Characteristic physical findings are weak,
delayed femoral pulses, prominent left ventricular impulse,
A diverse group of congenital mitral valve anomalies can a loud aortic closure sound, thrill in the suprasternal notch
cause obstruction to left atrial flow and that leads to mitral and vascular murmur between the shoulder blades beginning
stenosis. Although rare in adults, the diagnosis is confirmed in mid systole and persisting beyond the second heart sound.
by transthoracic or transesophageal echocardiogram. Continuous murmurs due to collaterals may be present.
Most adults have had mitral valve replacement, since the Echocardiography demonstrates the gradient across the
severe cases are usually diagnosed in childhood. It is rare aortic arch and defines the commonly associated defects -
for an adult to present with Shone’s complex, characterized bicuspid aortic valve in 75 to 85 percent of the cases, aortic
by a supravalvular membrane or ring, parachute mitral root dilatation/aneurysm, VSD, mitral valve abnormalities
valve, subaortic stenosis and coarctation of aorta.16 Usually (Table 3) and allows assessment of left ventricular mass
presenting as a stable lesion, the supravalvular mitral ring and function. MRI is useful for delineating aneurysms in
may also be seen in association with a VSD, PDA, AV septal postoperative cases and also shows site of the stenosis, the
defects or double outlet right ventricle (DORV). extent and degree of narrowing, pressure gradient across the
Clinical presentation is similar to rheumatic mitral stenosis, stenosis, aortic arch anatomy, and aortopulmonary collaterals.
with the additive effect from associated defects. When Patients with COA are at increased risk for aortic
congenital MS occurs in association with an ASD, there may aneurysms and dissection. Hypertension often persists after
760 be an increase in left atrial pressure and left-to-right shunt. surgery and ambulatory blood pressure monitoring may
54
detect uncontrolled hypertension in those, who appear to
be normotensive at rest during office visits. Adequate blood Box 2: surgeries for tetralogy of Fallot

pressure control decreases the incidence of common long-term
complications such as premature coronary artery disease and Palliative surgical procedures
heart failure that are unfortunately common in these patients • Blalock-Thomas-Taussig (BTT) shunt: Classic shunt-
and the cause of early morbidity and mortality.34,35 subclavian to pulmonary artery anastomosis (end to side)
• Modified BTT shunt: subclavian to ipsilateral pulmonary
Surprisingly, intracranial aneurysms occur even in
artery
normotensive patients with COA, presenting as headaches • Waterston shunt-ascending aorta to main or right
or even hemorrhage due to rupture.36 All patients with COA pulmonary artery
must receive endocarditis prophylaxis, since they are at risk • Potts shunt-descending aorta to left pulmonary artery
for endarteritis and endocarditis involving associated lesions. (side-to-side)
Resection of the COA with end-to-end anastomosis is the • Brock procedure-closed pulmonary valvotomy
procedure of choice in most adults. Early operation reduces Intracardiac repair
long-term complications. Angioplasty with/without stenting
Salient features of a complete intracardiac repair are the
is an option for coarctation, recoarctation or residual stenosis
following:
in the absence of any paracoarctation aneurysms.1 Since • Ventricular septal defect (VSD) patch repair—When
ambulatory hypertension, occurs, even after intervention or more than half of the aortic valve is connected to the
surgery it should be treated aggressively to reduce long-term right ventricle, the surgery is more complex since a larg-
morbidity and mortality.37 er patch is required across the VSD in order to connect
the aorta to the left ventricle.
• Right ventricular outflow tract (RVOT) surgery—Depend-
Tetralogy of Fallot
ing upon the anatomical variations, the following are the
This is the most common cyanotic CHD accounting for more commonly performed surgeries for the RVOT.
– Pulmonary valvotomy—Previously known as the
nearly 10 percent of all CHDs with slightly higher male
Brock procedure (closed pulmonary valvotomy), it is
preponderance. Most adults have undergone palliative now performed at the time of intracardiac repair for
surgeries and intracardiac repair. Unoperated adults with pulmonary stenosis (PS).
tetralogy of Fallot (TOF) have high morbidity. They may – RVOT obstruction
present with progressive cyanosis, atrial arrhythmias, impaired - Previous surgical approach was to relieve obstruction
biventricular function causing heart failure, paradoxical by infundibular muscle resection and/or by using
emboli through intracardiac shunts leading to thromboembolic a patch across the RVOT or a right ventriculotomy
events and cerebral abscesses. They are considered inoperable incision followed by and transannular patch
in adulthood if irreversible pulmonary vascular disease/severe - Current surgical approach is a transatrial/
transpulmonary incision involving closure of the
pulmonary hypertension have developed. Without definitive
VSD, relief of RVOT obstruction through the right
surgery, a high mortality of 25 percent in the first year of life, atrium and pulmonary artery.
40 percent by the 3rd year, 70 percent by 10th year and 95 – Extracardiac conduit from right ventricle to pulmonary
percent by 40 years of life has been reported.38 artery (RV to PA ) conduit is indicated in the following
cases:
Palliative Procedures - Pulmonary atresia/severe stenosis of RVOT
- Coronary artery abnormality with the left anterior
Some adults have only had palliative procedures in the past descending (LAD) from right coronary cusp crossing
with the purpose of increasing blood flow to the lungs and to the RVOT
– Concomitant surgeries for associated defects include
normalize the growth of the pulmonary arteries restricted due
the following:
to varying degree of infundibular stenosis. The major problems - Atrial septal defects and patent foramen ovale
with long-standing shunts are pulmonary hypertension (most (ASD/PFO) closure
commonly occurs with the Waterston shunt) and stenosis with - Aortic regurgitation repair
narrowing or kinking (most often occurs with Waterston or - Dilated aortic root (wider than 4 cm)—augmentation
Potts shunts). Although the surgical approach has evolved with Goretex or Dacron
over the years, the basic palliative procedures and intracardiac - Hypoplastic pulmonary arteries—patch augmentation
repairs are discussed in the Box 2. The long-term residua and or angioplasty of the main or branch pulmonary
sequelae after a palliated shunt are the following: arteries.
• Progressive cyanosis and complications associated with
prolonged cyanosis
• Persistent interatrial shunt • Pulmonary or subpulmonary stenosis 761
• Progression of pulmonary vascular disease • Left ventricular dysfunction
• Pulmonary arteriovenous fistulae • Atrial or ventricular arrhythmias
10
• Endocarditis 10 to 15 years, cardiologists often try to minimize the number
• Paradoxical thrombo-embolism through interatrial right- of surgeries required in a lifetime by appropriately timing and
to-left shunt. sometimes delaying the redo surgeries.

Early repair ensures much better long-term outcomes
Intracardiac Repair for individuals born with TOF. In adults with repaired TOF,
the main surgical issue is impaired exercise performance,
The main purpose of the surgery is to close the VSD supraventricular or ventricular arrhythmias, increasing
and correct the overriding of the aorta, relieve the right tricuspid regurgitation, right ventricular dilatation and failure.
ventricular outflow tract obstruction and the pulmonary valve A timely reoperation may protect from these adverse outcomes
abnormality. Follow-up of operated adults with TOF depends and therefore it is important to determine the appropriate
upon a host of factors including the nature of previous timing of pulmonary valve replacement.39
procedures/surgeries. All patients need follow-up preferably twice a year for
The main issues with intracardiac repairs are usually related early detection and management of common residua and
to an older surgical approach with right ventriculotomy incision/ sequelae noted in Table 3. The more commonly reported
transannular patch that predisposes to progressive PR due to loss clinical symptoms are exertional dyspnea, palpitations
of integrity of the pulmonary valve annulus. The hemodynamic (atrial arrhythmias), pedal edema, ascites (due to passive
burden of wide open PR on the postventriculotomy scar/the liver congestion in advanced right heart failure), presyncope
transannular patch, generates an electrical nidus for mono- and syncope (may be due to ventricular arrhythmias).
morphic ventricular tachycardia. In addition it leads to right Characteristic physical findings are related to multivalvular
ventricular dilatation and impaired ventricular function. disease (regurgitation of the pulmonary, tricuspid and aortic
Ideally, a redo intracardic repair with removal of the scar/ valves). ECG and echocardiogram should be performed every
aneurysm at the site of the transannular patch followed by 12 to 18 months unless indicated sooner due to any change in
pulmonary valve replacement (PVR) is recommended before clinical status. On a routine ECG the presence of right bundle
right heart enlargement and impairment of right ventricular branch block (RBBB)) is a universal finding post repair in
function occurs. Progressive tricuspid valve regurgitation an adult with tetralogy of Fallot (Figure 1). The key points
due to stretching of the annulus may also predispose to heart to review on serial electrocardiograms are QRS duration,
failure and atrial arrhythmias. PVR is often delayed until early since QRS prolongation is associated with an increased risk
adulthood, since the valve size cannot keep up with individual of ventricular arrhythmias.40 Other abnormalities are QT
growth during childhood and adolescence. Additionally, prolongation, varying degree of heart blocks, atrial fibrillation
since the bioprosthetic valves have a limited life span of 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
54
Holter test and/or treadmill stress testing should be requested as seen with Marfan syndrome, bicuspid aortic valve and
in a patient presenting with palpitations or presyncope, since coarctation of aorta. It is not uncommon to see patients remain

these tests help determine exercise-induced tachyarrhythmias, stable with aortic roots around 5 cm.
chronotropic insufficiency/bradyarrhythmias and very frequent
premature ventricular complexes (PVCs). More than 30 PVCs TRANSPOSITION OF THE GREAT ARTERIES
per hour have a high correlation with nonsustained ventricular
tachycardia.
Dextro or d-Transposition of the Great Arteries
Routinely, a tranthoracic echocardiogram is performing to
follow-up long-term residual and sequelae, especially biven- Most adults with d-Transposition of the great arteries (D TGA)
tricular size, function, pulmonary and aortic valve regurgita- have had a previous atrial switch (Mustard or Senning) repair.
tion. Severe pulmonary regurgitation is also associated with The younger adults who have undergone an arterial switch
propensity for ventricular arrhythmias and timely pulmonary (Jatene) repair are now presenting in the adult CHD clinics. In
valve replacement may reduce this risk.41 A stress echocardio- D TGA, there is ventriculoarterial discordance with the aorta
gram may be performed to assess the impact of exercise on arising from the right ventricle and the pulmonary artery arising
the ventricular function, pulmonary artery pressures and valve from the left ventricle. Instead of a normal circulation with a
gradients. single series circuit, the ventriculo-arterial discordance makes
Impaired left ventricular dysfunction develops partly the blood circulate in two separate parallel circuits, without
because of biventricular interdependence and progressive allowing oxygenation of the systemic blood. Infants born with
aortic regurgitation from poor coaptation of the aortic leaflets in an isolated D TGA have a very poor survival with up to 90
patients with aortic root dilatation. Congestive heart failure and percent mortality in infancy.46 Survival is only possible after
sudden cardiac death due to arrhythmias are the main causes of birth when there is mixing of the blood through an intracardiac
morbidity and mortality. The causes of congestive heart failure shunt (ASD, VSD or PDA). Other associated defects are listed
on TOF post repair are multifactorial and include the following: in Table 3.
• Long-standing shunts In a normal heart, the ascending aorta is posterior and
• Prolonged cyanosis in patients with late repair runs crisscross in relation to the main pulmonary artery.
• Poor myocardial preservation during multiple surgeries Characteristics findings on an echocardiogram in DTGA
• Right heart failure due to severe pulmonary regurgitation. are that the two great arteries are parallel to each other. The
Although, larger longer-term studies are needed to ascending aorta is anterior and rightward in relation to the
determine if ACE inhibitors are beneficial in improving main pulmonary artery. This finding is best appreciated in the
ventricular remodelling and clinical outcomes, a recent study parasternal short axis view at the level of the great vessels or in
reported that ramipril improves biventricular function in a modified long axis view.
patients with operated TOF.42
Sudden cardiac death related to monomorphic ventricular Palliative Procedures
tachycardia originating from the postventriculotomy scar
has been documented in many cases. The predictors of high Balloon septostomy of the atrial septum performed soon after
mortality in TOF are late age at repair, right heart failure and birth allows adequate shunting between the two circuits, so
impaired biventricular function. Left ventricular longitudinal that there is an adequate supply of oxygenated blood to the
dysfunction has also been associated with greater risk of vital organs until a definitive arterial switch repair is performed
sudden cardiac death/life-threatening ventricular arrhythmias. (usually after the first two weeks of life in the current era). In
It may be considered as a useful adjunct to established the past atrial switch repair was performed after 6 months of
markers such as QRS duration in determining the prognosis in life. Meanwhile, the balloon septostomy allowed the infants
operated TOF.43 to survive on 50 to 80 percent oxygenation resulting from the
Atrial fibrillation or flutter occurs in nearly 30 percent of intermixing of blood.
the cases, usually in adults with long-standing systemic to
pulmonary artery shunts, late intracardiac repair or severe Atrial Switch Repairs (Mustard or Senning Operations)
tricuspid regurgitation. Dual chamber pacemakers are indicated
in patients with advanced heart blocks (trifascicular or complete These definitive repairs were usually performed in the first
heart block) due to discontinuity of the bundle of His by a large year of life. Dr A Senning described the atrial switch operation
VSD. Pulmonary artery dilatation and aneurysm formation in 195947 and Dr WT Mustard described another version of the
may occur due to intrinsic tissue abnormality.44 Aortic root atrial switch operation in 1964 in Toronto.48 These operations
dilatation is primarily due to structural abnormalities of the fundamentally involve directing the deoxygenated blood from
great arterial walls associated with TOF.45 However, the aortic the superior and inferior vena cava through a baffle into the
root in tetralogy of Fallot is not as vulnerable to dissection left ventricle, that pumps the blood into the pulmonary artery. 763
10
The oxygenated blood returning from the lungs passes through to keep up with the increasing blood supply requirements,
the pulmonary veins, via another baffle into the right ventricle leading to perfusion defects. Progressive systemic AV
that pumps the blood through the aorta into the systemic (tricuspid) valve regurgitation behaves in a similar way like
circulation. Hence, the morphological right ventricle is the mitral regurgitation affects a structurally normal heart.50-52
systemic ventricle and the morphological left ventricle is the
subpulmonic ventricle. Systemic AV Valve Regurgitation
The major difference between the Senning and the Mustard (Tricuspid Regurgitation)
operations is the material used for the baffle. In the Senning There is an increased predisposition for systemic AV valve
operation, the baffle is created from the patient’s tissues regurgitation, due to the altered geometry of the systemic right
(right atrial wall and part of the atrial septum).47 The Mustard ventricle in D TGA. The tricuspid annular dilatation, globular
operation uses pericardium and synthetic material to make the shape of the enlarging right ventricle and displaced chordal
baffle.48 attachments of the systemic AV valve leads to progressive
The long-term residua and sequelae experienced by the regurgitation. The systemic AV valve regurgitation then
patient’s, who underwent an atrial switch operation are listed leads to further right ventricular enlargement and worsening
in Table 4. Most common causes of morbidity and mortality in systemic RV function.
this population are heart failure due to progressive impairment
of systemic right ventricular, not designed to withstand the Baffle Problems—Obstruction or Leaks
pressure load of lifelong pumping into the systemic circulation. Baffle leaks usually occur along suture lines and most
Most patients demonstrate decreasing systemic ventricular commonly along the superior limb of the systemic venous
function by the second to third decade of life. Bradyarrhythmias baffle, in 25 percent of the individuals, who have undergone
due to chronotropic incompetence from sick sinus syndrome atrial switch repair. Fortunately, not all leaks are clinically
and atrial arrhthymias related to atrial surgical incisions and significant. A left-to-right shunt through the baffle leak is
baffle construction affect many young adults. hemodyamically more significant, when it has the potential
for volume overloading of the systemic ventricle. Right-
Rastelli Repair to-left shunts are clinically more significant if they are
contributing to worsening systemic arterial oxygenation and
Dr Rastelli, at the Mayo Clinic described this surgery in cyanosis.
1969.49 In patients with D TGA and pulmonary outflow tract Obstruction of the superior limb of the systemic venous
obstruction who have a large, subaortic VSD, a Rastelli repair Mustard baffle is more common (5–10%) than that of the
is performed utilizing a conduit to direct the blood from the inferior limb (1–2%). Pulmonary venous baffle obstruction
right ventricle (via the VSD) to the aorta. The blood from the may occur in around 2 percent of the cases. Transesophageal-
left ventricle is directed to the aorta thereby making the left guided transcatheter intervention with stent implantation may
ventricle the systemic ventricle. These patients are relieved relieve the obstruction in most cases. In other cases of severe
of the long-term issues related to atrial repair, but may need obstruction, surgical correction may be needed.
further re-operations for the conduit.
While a Rastelli repair in early infancy protects from Arrhythmias
prolonged cyanosis, the infant-sized conduit needs more re- Bradyarrhythmias—Resting sinus bradycardia with a slow
operations for replacement over a lifetime. Biventricular junctional escape rhythm is common with progressive
dysfunction may occur due to long-standing conduit obstruction sinus node dysfunction occurring in 50 percent of patients
or volume overload. Long-term issues in the postsurgical postoperatively over time. Many patients will need pacemakers
patient with D TGA and Rastelli repair are listed in Table 3. after their third decade of life.
Tachyarrhythmias—Incisional atrial re-entry tachycardia
Long-term Issues with Atrial Switch Repair (atypical atrial flutter) occurs in 50 percent of the adults post
atrial switch repair (Figures 2A and B). Electrophysiological
Systemic Ventricular Dysfunction and Heart Failure studies and radio frequency ablation (RFA) may help 75
The right ventricle is unable to keep up with the demands of percent of the patients, but the incidence of high grade AV
pumping into the systemic circulation long-term and begins to block requiring a pacermaker is very high.53-55
deteriorate in the third decade of life. The degree of deterioration
is multifactorial, but primarily depends on the right ventricular Pulmonary Vascular Disease
morphology and demand-supply mismatch from right Pulmonary hypertension is more common in patients who
ventricular hypertrophy. The right coronary artery is unable have long-standing shunts and underwent late repairs.
764
54

a
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 Dr Antoine Jatene first described the arterial switch operation
arrhythmogenic due to ventricular tachycardia or fibrillation. in 1975.56 For optimal long-term results, this operation is
The exact mechanisms are not clearly known. ideally performed between the ages of 2 weeks and 6 weeks.
765
10
Delay in performing this surgery may result in long-term Unfortunately on echocardiography, it is not too uncommon
left ventricular failure, since there is disuse atrophy of the for the systemic AV valve to be mistaken, as the mitral valve
subpulmonic left ventricle due to low pressure load. In this in an undiagnosed case of CCTGA. At times, an embarrassing
operation, the aorta and the pulmonary artery are transected situation may occur when a cardiac surgeon opens the chest
at the level above the coronary sinus and the coronaries are to operate on the mitral valve and is shocked to find the
dissected from the aortic sinuses with a ‘button’ of tissue around morphological tricuspid valve on the left side of the heart. If
them and sutured into the neo-aorta. The main pulmonary there is no CHD surgeon available to help out, he/she may
artery is repositioned anterior to the neo-aorta and the two end up closing the chest without performing the surgery. The
great arteries are sutured into their anatomically corrected patient in this situation is so emotionally traumatized for
positions. The most important feature of this operation is that having undergone an unfruitful open-heart surgery that he/
it allows the left ventricle to function as the systemic ventricle, she may refuse to undergo another surgery to fix the severely
thereby reducing the risk of early morbidity or mortality from regurgitating AV valve.
systemic ventricular dysfunction and heart failure. Long-term While reading echocardiograms one must look carefully
outcomes are reviewed in Table 3.57 Coronary arterial fibrosis at the morphology of the ventricles. The AV valves follow
leading to potential ischemia appears to be the major long- their respective ventricle, hence the systemic AV valve
term issue in this population.58 (morphologic tricuspid valve) that is more apically placed
than the mitral valve (Figure 4) is on the same side of the heart
Congenitally Corrected Transposition of the as the right ventricle.
Great Arteries Standard heart failure management is recommended with
the use of carvedilol, ACE I/ARB and aldactone titrated to
Patients with congenitally corrected transposition of the maximum tolerated dose. Digoxin may be added if tolerated.
great arteries (CCTGA) with no associated defects may go Exercise training has miraculous effects on cardiovascular
undiagnosed into adulthood. They most commonly present conditioning in disciplined individuals, who can persistently
with heart failure when the morphological right ventricle, perform at least 45 minutes of daily aerobic activities. Surgical
which is the systemic ventricle, begins to fail. Nearly 25 percent management and the role systemic AV valve surgery are
patients develop heart failure by 45 years of age.59 Although discussed in the chapter on congenitally corrected transposition
the atria are in the normal position, there is double discordance of the great arteries.
with transposition of the great arteries, and ventricular
inversion. Although these two wrongs try to make a right by Univentricular Heart (Single Ventricle Physiology)
attempting to establish a physiologically correct circulation, with Fontan Operation
the major caveat is that the morphologically right ventricle
functions as the systemic ventricle, and pumps into the aorta. In 1971, Dr Francois Fontan performed a new surgical
The blood from the superior and inferior vena cavae flows procedure in patients with tricuspid atresia that would be
into the right atrium that drains into the left ventricle through later become known as the classic Fontan operation. The
the morphological mitral valve. The left ventricle pumps the goal of this surgery is to improve blood flow to the lungs
blood into the pulmonary artery. The oxygenated blood returns by connecting the right atrium to the pulmonary artery.63
from the lungs returns via the pulmonary veins into the left Tricuspid atresia is the commonest form of atrioventricular
atrium and then flows through the morphological tricuspid atresia with complete absence of the tricuspid valve or
valve into the morphological right ventricle which pumps into imperforate tricuspid tissue. Majority of the cases have a
the aorta. Associated defects lead to varying presentations concordant ventriculoarterial connection, while in nearly one-
and diagnosis is usually made early in life. Cyanosis may be third cases there is transposition of the great arteries. There
seen in patients with significant left ventricular outflow tract may be a restrictive VSD connecting the left ventricle to the
(LVOT) obstruction associated with a VSD. Other long-term hypolastic right ventricle.
residua and sequelae are reviewed in Table 3. Some patients have to undergo palliative surgeries in
On physical examination, there is usually a loud single childhood, such as a bidirectional Glenn to improve pulmonary
second heart sound (A2). Sometimes a soft P2 may be heard. blood flow (especially in the setting of severe pulmonary
Patients with systemic AV valve regurgitation will have a systolic stenosis) and then later have a conversion to the Fontan
murmur at the left sternal border or apex. Other murmurs may be operation to improve oxygenation.64 Although, cyanotic
audible depending upon the associated defects. An adult with no patients become acyanotic and have improved quality of life
associated defects/signs of heart failure may go undiagnosed. and longevity after the Fontan operation, there are long-term
The ECG is often misinterpreted as showing a previous issues such as progressive ventricular dysfunction, atrial
myocardial infarction, because there are Q waves in the arrhythmias, recurrence of cyanosis, elevated pulmonary
766 anterior leads due to ventricular inversion60 (Figure 3). vascular resistance and protein-losing enteropathy, which
Coronary artery anatomy is also inverted.61,62 can result in heart failure, thromboembolism and stroke. The
54

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
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:
Arrhythmias
There is higher probability of atrial arrhythmias in patients
Figure 4: Transthoracic echocardiogram in the apical four-chamber
with a classic Fontan due to markedly enlarged right atrium
view showing crux anatomy. Note that the tricuspid valve (apically
displaced) is on the left side along with the morphological right ventricle and higher atrial pressures. In addition, mitral/systemic
(with the prominent moderator band). LA = Left atrium; LV = Left atrioventricular valve regurgitation predisposes to left atrial
ventricle; MV = Mitral valve; MB = Moderator band; RA = Right atrium; enlargement and atrial fibrillation. Suture lines in the atria from
RV = Right ventricle; TV = Tricuspid valve;
prior surgeries may be also trigger arrhythmias. Medications
such as beta blockers or calcium channel blockers, with
recurrence of cyanosis may be due to fenestrated atrial septum, or without digoxin are used for rate control. Amiodarone is
pulmonary arteriovenous fistulae and other causes. Many the antiarrhythmic of choice, when atrial fibrillation/flutter
patients may also need revision of the Fontan operation. Over persists. The lowest dose should be used and it should be
the years, the Fontan operation has undergone modifications carefully monitored for adverse pulmonary effects, thyroid and 767
with the total cavopulmonary connection (TCPC) achieved liver function tests.
10
Sometime intractable arrhythmias are a sign of a failing enteropathy (PLE) by 10 years was 13.4 percent and 5-year
Fontan. In these cases a revision of the Fontan or relief of the survival after the diagnosis was 46 percent. Hemodynamic
conduit obstruction is indicated. Electrophysiology assessment data showed an increased systemic venous pressure, decreased
is indicated, when poorly controlled arrhythmias cause further cardiac index, increased pulmonary vascular resistance and
deterioration of the hemodynamics. Unfortunately, lateral increased ventricular end-diastolic pressure. Factors related
and extracardiac conduits limit catheter access for ablating to PLE were ventricular anatomy, increased preoperative
arrhythmias even though the likelihood of arrhythmias in these ventricular end-diastolic pressure, longer operative bypass time,
patients is expected to be lower than in the classic Fontan. increased length of hospital stay and postoperative renal failure.
Intra-atrial re-entrant tachycardia (atypical atrial flutter) is Patient selection and perioperative factors seem to predispose
common and often difficult to treat. to PLE.65 The management options are limited and primarily
supportive. These include a special diet, unfractionated
Heart Failure heparin, corticosteroids and somatostatin analogs. Some
patients benefit from decreased systemic venous pressure and
Management of ventricular dysfunction is challenging. passive hepatic congestion by transcatheter fenestration of the
Afterload reduction/vasodilators may not be well-tolerated in atrial septum. Fontan revision and heart transplantation have
the Fontan patient. sometimes showed temporary improvement of the protein
losing enteropathy.
Antiplatelet Versus Anticoagulation Therapy
Endocarditis Prophylaxis
Classic Fontan puts patients at a very high-risk for thrombus
formation (Figure 5). The role of antiplatelet versus Appropriate dose of antibiotics is advised for endocarditis
anticoagulation therapy remains controversial and needs to be prophylaxis in all Fontan patients.
individualized.
CONCLUSION
Protein-losing Enteropathy
Long-term follow-up and appropriate management are essential
This is the most serious complication post Fontan characterized to ensure improved quality of life and longevity in adults with
by increasing ascites, edema, pleural effusions and malnutrition. CHD. Antibiotic prophylaxis for bacterial endocarditis should
The diagnosis is confirmed by low serum albumin levels and be prescribed when indicated, especially in high-risk patients
increased fetal alpha antitrypsin. Feldt et al. showed that with complex CHD, conduits, pacemakers, defibrillators,
the cumulative risk for the development of protein-losing 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
REFERENCES
Figure 5: Transesophageal echocardiogram confirming a right atrial 1. Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA
768 thrombus in a 38-year-old woman with tricuspid atresia with history of a 2008 guidelines for the management of adults with congenital
classic Fontan operation (right atrium to pulmonary artery connection) heart disease: a report of the American College of Cardiology/
54
American Heart Association Task Force on Practice Guidelines. foramen ovale in prevention of recurrent neurological events
J Am Coll Cardiol. 2008;52(23):e143-263 or in Circulation. after presumed paradoxical embolism. JACC Cardiovasc

2008;118:2395-451. Interv. 2012;5(7):777-89.
2. Baumgartner H, Bonhoeffer P, De Groot NM, et al. Task Force 16. Perloff JK, Marelli AH. In: Perloff’s Clinical Recognition
on the Management of Grown-up Congenital Heart Disease of of Congenital Heart Disease. 6 edn. Philadelphia, PA: WB
the European Society of Cardiology (ESC). ESC Guidelines Saunders; 2012.
for the management of grown-up congenital heart disease (new 17. Ammash NM, Warnes CA. Ventricular septal defects in adults.
version 2010). Eur Heart J. 2010;31(23):2915-57. Epub 2010 Ann Intern Med. 2001;135:812-24.
Aug 27. 18. Neumayer U, Stone S, Somerville J. Small ventricular septal
3. Silversides CK, Marelli A, Beauchesne L, et al. Canadian defects in adults. Eur Heart J. 1998;19(10):1573-83.
Cardiovascular Society 2009 Consensus Conference on the 19. Wood P. The Eisenmenger syndrome or pulmonary hypertension
management of adults with congenital heart disease: executive with reversed central shunt. Br Med J. 1958;2(5099):755-62.
summary. Can J Cardiol. 2010;26(3):143-50. 20. Magee AG, Huggon IC, Seed PT, et al. Association for
4. Silversides CK, Dore A, Poirier N, et al. Canadian European Cardiology Transcatheter coil occlusion of the
Cardiovascular Society 2009. Consensus Conference on the arterial duct; results of the European Registry. Eur Heart J.
management of adults with congenital heart disease: shunt 2001;22(19):1768-89.
lesions. Can J Cardiol. 2010;26(3):e70-9. 21. Niwa K, Perloff JK, Bhuta SM, et al. Structural abnormalities
5. Silversides CK, Kiess M, Beauchesne L, et al. Canadian of great arterial walls in congenital heart disease: light and
Cardiovascular Society 2009 Consensus Conference on the electron microscopic analyses. Circulation. 2001;103(3):
management of adults with congenital heart disease: outflow 393-400.
tract obstruction, coarctation of the aorta, tetralogy of Fallot, 22. Chen CR, Cheng TO, Huang T, et al. Percutaneous balloon
Ebstein anomaly and Marfan’s syndrome. Can J Cardiol. valvuloplasty for pulmonary stenosis in adolescents and adults.
2010;26(3):e80-97. N Engl J Med. 1996;335(1):21-5.
6. Silversides CK, Salehian O, Oechslin E, et al. Canadian 23. Choong CY, Abascal VM, Weyman J, et al. Prevalence of val-
Cardiovascular Society 2009 Consensus Conference on the vular regurgitation by Doppler echocardiography in structur-
management of adults with congenital heart disease: complex ally normal hearts by two-dimensional echocardiography. Am
congenital cardiac lesions.Can J Cardiol. 2010;26(3):e98-117. Heart J. 1989;117:636-42.
7. Chugh, R. Caring for the adult with congenital heart 24. Hamby RI, Gulotta SJ. Pulmonary valvular insufficiency:
disease: management of common defects. Perm J. 2007 etiology, recognition, and management. Am Heart J. 1967;74:
Spring;11(2):40-6. 110-25.
8. Anzola GP, Morandi E, Casilli F, et al. Does transcatheter closure 25. Bialostozky D, Horowitz S, Espino-Vela J. Ebstein malfor-
of patent foramen ovale really “shut the door”? A prospective mation of the tricuspid valve. A review of 65 cases. Am J
study transcranial Doppler. Stroke. 2004;35(9):2140-4. Cardiol. 1972;29:826-36.
9. Mas JL, Arquizan C, Lamy C, et al. Patent Foramen Ovale and 26. Kaushik ML, Sharma M, Kashyap R. “Himalayan” p wave. J
Atrial Septal Aneurysm Study Group Recurrent cerebrovascular Assoc Physicians India. 2007;55:856.
events associated with patent foramen ovale, atrial septal 27. Cappato R, Schluter M, Weiss C, et al. Radiofrequency current
aneurysm, or both. N Engl J Med. 2001;345(24):1740-6. catheter ablation of accessory atrioventricular pathways in
10. Homma S, Sacco RL, Di Tullio MR, et al. PFO in Cryptogenic Ebstein’s anomaly. Circulation, 1996;94:376-83.
Stroke Study (PICSS) Investigators Effect of medical 28. Barber G, Danielson GK, Heise CT, et al, Cardiorespiratory
treatment in stroke patients with patent foramen ovale: patent response to exercise in Ebstein’s anomaly. Am J Cardiol.
foramen ovale in Cryptogenic Stroke Study. Circulation. 1985;56:509-14.
2002;105:2625-31. 29. Driscoll DJ, Mottram CD, Danielson GK. Spectrum of
11. Kitsios GD, Dahabreh IJ, Abu Dabrh AM, et al. Patent foramen exercise intolerance in 45 patients with Ebstein’s anomaly and
ovale closure and medical treatments for secondary stroke pre- observation on exercise tolerance in 11 patients after surgical
vention: a systematic review of observational and randomized repair. J Am Coll Cardiol. 1988;11:831-6.
evidence. Stroke. 2012; 43(2):422-31. Epub 2011 Dec 15. 30. Braverman AC, Guven H, Beardslee MA, et al. The bicuspid
12. Furlan AJ, Reisman M, Massaro J, et al. Closure I Investigators. aortic valve. Curr Probl Cardiol. 2005;30(9):470-522.
Closure or medical therapy for cryptogenic stroke with patent 31. Devereux RB, Kramer-Fox R, Brown WT, et al. Relation
foramen ovale. N Engl J Med. 2012;366(11):991-99. between clinical features of the mitral prolapsed syndrome and
13. Wahl A, Jüni P, Mono ML, et al. Long-term propensity score- echocardiographically documented mitral valve prolapsed. J
matched comparison of percutaneous closure of patent foramen Am Coll Cardiol. 1986;8:763-72.
ovale with medical treatment after paradoxical embolism. 32. Freed LA, Levy D, Levine RA, et al. Prevalence and clinical
Circulation. 2012;125(6):803-12. Epub 2012 Jan 11. outcome of mitral-valve prolapse. N Engl J Med. 1999;341:1-7.
14. Mohr JP, Lazar RM, Thompson JLP, et al. Warfarin-Aspirin 33. Bonow RO, Carabello BA, Chatterjee K, et al. 2008 focused
Recurrent Stroke Study Group A comparison of warfarin and update incorporated into the ACC/AHA 2006 guidelines for
aspirin for the prevention of recurrent ischemic stroke. N Engl the management of patients with valvular heart disease: a
J Med. 2001;345(20):1444-51. report of the American College of Cardiology/American Heart
15. Agarwal S, Bajaj NS, Kumbhani DJ, et al. Meta-analysis Association Task Force on Practice Guidelines. J Am Coll 769
of transcatheter closure versus medical therapy for patent Cardiol. 2008;52(13):e1-142.
10
34. Oliver JM, Gallego P, Gonzalez A, et al. Risk factors for aortic 51. Millane T, Bernard EJ, Jaegii E, et al. Role of ischemia and
complications in adults with coarctation of the aorta. J Am Coll infarction in later right ventricular dysfunction after atrial
Cardiol. 2004;44(8):1641-7. repair of transposition of the great arteries. J Am Coll Cardiol.

35. Toro-Salazar O, Steinberger J, Thomas W, et al. Long-term 2000;35:1661-68.
follow-up of patients after coarctation of the aorta repair. Am J 52. Park SC, Neches WH, Mathews RA, et al. Hemodynamic
Cardiol. 2002;89(5):541-7. function after the Mustard operation for transposition of the
36. Connolly HM, Huston J, 3rd, Brown RD, et al. Intracranial great arteries. Am J Cardiol. 1985;55:1238-9.
aneurysms in patients with coarctation of the aorta: a 53. Puley G, Siu S, Connelly M, et al. Arrhythmia and survival
prospective magnetic resonance angiographic study of 100 in patients >18 years of age after the Mustard procedure for
patients. Mayo Clin Proc. 2003;78(12):1491-9. transposition of the great arteries. Am J Cardiol. 1999;83:1080-4.
37. Pedersen TA, Munk K, Andersen NH, et al. High long-term 54. Gillette PC, Kugler JD, Garson A Jr, et al. Mechanisms of
morbidity in repaired aortic coarctation: weak association cardiac arrhythmias after Mustard operation for transposition
with residual arch obstruction. Congenit Heart Dis. 2011;6(6): of the great arteries. Am J Cardiol. 1980;45:1225-30.
573-82. 55. Kanter RJ, Papagiannis J, Carboni MP, et al, Sanders
38. Betranou EG, Blackstone EH, Hazelrig JB, et al. Life WE, Wharton JM. Radiofrequency catheter ablation of
expectancy without surgery in tetralogy of Fallot. Am J supraventricular tachycardia substrates after Mustard and
Cardiol. 1978; 42:458-66. Senning operations for d transposition of the great arteries. J
39. Davlouros PA, Karatza AA, Gatzoulis MA, et al. Timing and Am Coll Cardioll. 2000;35:428-41.
type of surgery for severe pulmonary regurgitation after repair 56. Jatene AD, Fontes VF, Paulista PP, et al. Anatomic correction
of tetralogy of Fallot. Int J Cardiol. 2004;97 Suppl 1:91-101. of transposition of the great arteries. J Thorac Cardiovasc Surg.
40. Gatzoulis MA, Balaji S, Webber SA, et al. Risk factors 1976;72:364-70.
for arrhythmia and sudden cardiac death late after repair 57. Losay J, Touchot A, Serraf A, et al. Late outcomes after
of tetralogy of Fallot: a multicentre study. Lancet. arterial switch operation for transposition of the great arteries.
2000;356(9234):975-81. Circulation. 2001;104 (suppl I):121-6.
41. Therrien J, Siu SC, Harris L, et al. Impact of pulmonary valve 58. Bonhoeffer P, Bonnet D, Piechaud JF, et al. Coronary artery
replacement on arrhythmia propensity late after repair of obstruction after the arterial switch operation for transposition
tetralogy of Fallot. Circulation. 2001;103(20):2489-94. of the great arteries in the newborns. J Am Coll Cardiol.
42. Babu-Narayan SV, Uebing A, Davlouros PA, et al. Randomised 1997;29:202-6.
trial of ramipril in repaired tetralogy of Fallot and pulmonary 59. Graham TP Jr, Bernard YD, Mellen BG, et al. Long-term
regurgitation: the APPROPRIATE study (Ace inhibitors for outcome in congenitally corrected transposition of the great
Potential PRevention Of the deleterious effects of Pulmonary arteries: a multi-institutional study. J Am Coll Cardiol. 2000
Regurgitation In Adults with repaired Tetralogy of Fallot). Int J Jul;36(1):255-61.
Cardiol. 2012;154(3):299-305. 60. Anderson R, Becker A, Arnold R, et al. The conducting
43. Diller GP, Kempny A, Liodakis E, et al. Left ventricular tissues in congenitally corrected transposition. Circulation.
longitudinal function predicts life-threatening ventricular 1974;50:811-23.
arrhythmia and death in adults with repaired tetralogy of fallot. 61. Dabizzi RP, Barletta GA, Caprioli G, et al. Coronary artery
Circulation. 2012;125(20):2440-6. Epub 2012 Apr 11. anatomy in corrected transposition of the great arteries. JACC
44. Bédard E, McCarthy KP, Dimopoulos K, et al. Structural 1988;12:486-91.
abnormalities of the pulmonary trunk in tetralogy of Fallot and 62. Chiu IS, Wu SJ, Chen SJ, et al.Sequential diagnosis of coronary
potential clinical implications: a morphological study. J Am arterial anatomy in congenitally corrected transposition of the
Coll Cardiol. 2009;54(20):1883-90. great arteries. Ann Thorac Surg. 2003;75:422-9; discussion 429.
45. Niwa K, Siu SC, Webb GD, et al. Progressive aortic root 63. Fontan F, Baudet E. Surgical repair of tricuspid atresia.Thorax.
dilatation in adults late after repair of tetralogy of Fallot. 1971 May;26(3):240-8.
Circulation. 2002;106(11):1374-8. 64. Aboulhosn JA, Shavelle DM, Castellon Y, et al Fontan
46. Liebman J. Cullum L, Belloc NB. Natural history of operation and the single ventricle. Congenit Heart Dis. 2007
transposition of the great arteries: anatomic and birth and death Jan-Feb;2(1):2-11.
characteristics. Circulation. 1969; 40:237-62. 65. Feldt RH, Driscoll DJ, Offord KP, et al. Protein-losing
47. Senning A. Surgical correction of transposition of the great enteropathy after the Fontan operation. J Thorac Cardiovasc
vessels. Surgery. 1959;45:966-80. Surg. 1996 Sep;112(3):672-80.
48. Mustard WT. Successful two-stage correction of transposition 66. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective
of the great vessels. Surgery. 1964;55:469-72. endocarditis: guidelines from the American Heart Association.
49. Rastelli GC, Wallace RB, Ongley PA. Complete repair of Circulation. 2007 Oct 9;116(15):1736-54. Epub 2007 Apr
transposition of the great arteries with pulmonary stenosis. A 67. Child JS. Echo-Doppler and color-flow imaging in congenital
review and report of a case corrected by using a new surgical heart disease. Cardiol Clin. 1990 May;8(2):289-313. Review.
technique. Circulation. 1969;39(1):83-95. 68. Hiratzka LF, Bakris GL, Beckman JA, et al. ACCF/AHA/
50. Hurwitz RA, Caldwell RL, Girod DA, et al. Right ventricular AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for
systolic function in adolescents and young adults after Mustard the diagnosis and management of patients with thoracic aortic
770 operation for transposition of the great arteries. Am J Cardiol. disease. J Am Coll Cardiol. 2010;55(14):e27-e129. (Key
1996;77:294-7. algorithm is on page e83)
C hapter
Caring for the Adults with Cyanotic

Reema Chugh
INTRODUCTION outflow tract obstruction. The pulmonary outflow tract

obstruction/pulmonary stenosis is actually a boon in patients
Inspired by the impact of high altitude physiology on Peruvians with large shunts, since it offers protection from excessive
residing in the high Andes,1 Dr Joseph Perloff embarked on a blood flow going to the lungs, which could lead to severe
lifetime of research to study the effects of cyanosis in adults pulmonary vascular disease or Eisenmenger syndrome (severe
with congenital heart disease (CHD). He began drawing pulmonary hypertension with reversal of the shunt).6
correlations between these two populations, exposed to a Cyanotic CHD is a multisystem disorder that results
lifetime of chronic low oxygen saturations and unraveled the from long-term effects of the deoxygenated blood flow to
long-term impact of hypoxemia and erythrocytosis that makes all organs of the body (Table 1). Cyanotic CHD accounts for
cyanotic congenital heart disease in adults a multisystem approximately 25 percent of all congenital heart defects, with
disorder.2-4 the most common one being tetralogy of Fallot. Before the
advent of early interventions and surgical operations, many
CYANOTIC CONGENITAL HEART DISEASE—A adults with the manifestations of cyanotic CHD were seen
MULTISYSTEM DISORDER in clinics all over the world. In the past 20 years, we have
thankfully noticed a diminishing population of cyanotic CHD
The term cyanosis comes from the color cyan, which is in the United States (US) due to timely palliative procedures
derived from kyanos, the Greek word for blue. Individuals and surgical repairs. Unfortunately, some people will continue
born with cyanotic CHD appear ‘blue’, due to intermixing of to be cyanotic with CHD as long as there is limited access to
higher concentrations of venous deoxygenated blood (carrying pediatric and surgical care. This may also happen when early
deoxyhemoglobin over 2.5 g/dL) with the arterial oxygenated interventions/surgeries are denied by the patients or their
blood, resulting in persistent systemic arterial desaturation families because of their belief system or fears.
(usually below 85%). Central cyanosis is usually visible in the
oral mucosa making the lips appear blue. The bluish discoloration Hematologic Manifestations
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, In his teachings, Dr Perloff has made it very clear that there is
ventricular or arterial level (atrial or ventricular septal defects a difference between polycythemia and erythrocytosis, since
or a patent ductus arteriosus) through a right-to-left shunt or these two terms are often used incorrectly and interchangeably
a bidirectional shunt. It may also occur by intermixing of by the medical community worldwide. Patients with cyanotic
the blood in univentricular hearts, in congenital/palliative CHD have secondary erythrocystosis as a physiological
surgical connections or in patients with intrapulmonary adaptive response to chronic low systemic arterial oxygen
shunts. Palliative connections include surgically created saturation. This involves an isolated increase in the red
systemic arterial to pulmonary artery shunts for augmenting blood cell (RBC) mass. The RBC production is stimulated
the restricted pulmonary blood flow in order to improve by erythropoietin that is released from the renal cortex in
cyanosis. These aortopulmonary shunts may be complicated response to hypoxemia.
by pulmonary vascular disease, if they are too large.5
The communications between the systemic and pulmonary The term ‘polycythemia’ refers to an increase in more than
circulation may sometimes be associated with pulmonary one (generally all) of the formed elements in blood (from the
10
normal. All the major clinical manifestations are a result
Greek polys, ‘many’) and the designation is not appropriate
of exposure of multiple organs to prolonged chronic
for the isolated increase in red cell mass that characterizes

the hematologic response in patients with cyanotic congenital hypoxemia and secondary erythrocytosis.4
heart disease. Joseph K Perloff7 2. Iron deficient rigid microspherocytes: The iron
balance is very important in adults with cyanotic CHD.
Secondary erythrocystosis in cyanotic CHD is very Iron deficiency decreases muscle strength and exercise
different from polycythemia rubra vera, which is a malignant tolerance. Most of the patients with cyanotic CHD are
clonal stem cell disorder that involves all three cell lines often iron deficient due to repeated phlebotomies or chronic
leading to an increase in RBC mass, along with an increase in blood loss such as from menstrual bleeding that occurs
white blood cells (WBC) and platelets.4 especially in premenopausal women. Iron deficiency is
The two major determinants of increased whole blood often unrecognized in this population since hemoglobin
viscosity that affect patients with cyanotic CHD are: and hematocrit levels are not reflective of the true degree
1. Secondary erythrocytosis: Since, the principal function of iron deficiency and therefore serum ferritin levels need
of the erythrocytes is to carry oxygen, in cyanotic CHD to be assessed. The serum ferritin concentration directly
the secondary erythrocytosis is an appropriate adaptive correlates with the level of total body iron stores making
response to decreased tissue oxygenation. Low tissue it a sensitive and specific indicator of the iron status. The
oxygenation causes the renal release of erythropoietin peripheral blood smear is also helpful in early detection of
leading to an increase in RBC mass. The platelet counts microcytic, hypochromic RBC that are indicative of iron-
are in the low range of normal and the WBC counts are deficient 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 Structural abnormalities of the walls
coronaries with paucity of Effect of erythrocytosis
atherosclerosis Nitric oxide (NO)
Hyperbilirubinemia
Hypocholesterolemia
Thrombocytopenia
Pulmonary Pulmonary hemorrhage Extrapulmonary bleeding
Pulmonary embolism Main or branch pulmonary thrombosis
Central nervous system 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 Platelet derived growth factor and transforming
Elevated urate levels growth factor-beta
Metabolism of bilirubin and glucose Bilirubin stones Hyperbilirubinemia
Gout Hyperuricemia
False hypoglycemia on blood tests Glycolysis by secondary erythrocytosis
Rheumatological digits and long Clubbing Platelet-derived growth factor (PDGF) and
bones Hypertrophic osteoarthropathy transforming growth factor-beta
Vascular endothelial growth factor
Gynecological Menstrual disorders Abnormal hemostasis
Infertility Prolonged cyanosis
772
55
Iron deficiency may lead to microcytic and hypochromic
Box 1: Symptoms of hyperviscosity syndrome
erythrocytes with decreased oxygen carrying capacity of
Caring for the Adults with Cyanotic Congenital Heart Diseases

the blood because of reduced mean corpuscular hemoglobin Neurological symptoms
concentration in the RBC. There is reduced deformability • Headaches
• Lightheadedness or dizziness
of the iron deficient RBC and they become into rigid
• Faint
microspherocytes. Unlike the biconcave, iron-replete • Irritability
RBCs that are more flexible in their passage through the • Impaired concentration
microcapillaries, these iron-deficient, rigid microspherocytic • Numbness—perioral and digital
RBCs are prone to sludging in the microcapillaries and • Tinnitis
aggregate readily thereby promoting hyperviscosity. Careful Visual symptoms
iron repletion is needed to correct this problem as discussed • Blurring or double vision
• Scotoma
later in this chapter.
Bleeding disorders
Firstly, is there compensated or decompensated • Bruising
erythrocytosis? In compensated erythrocyosis, there is a • Bleeding gums
proportionate rise in the hematocrit levels in response to • Nose bleeds
elevated erythropoietin stimulated by tissue hypoxemia. • Coughing up or vomiting blood
This is a physiologic adaptation to tissue hypoxemia. • Excessive bleeding after trauma or surgery
Hyperviscosity symptoms are usually mild, if the hematocrit Musculoskeletal symptoms
is over 70 percent and resolve when hematocrit is less than 65 • Muscle pains and weakness
• Long bones pain
percent.8 • Joint pains and swelling
In decompensated erythrocytosis, as described by Rosove Gynecological symptoms
et al. there is pronounced rise in the hematocrit in response • Menorrhagia
to tissue hypoxemia. The hematocrit continues rise in an General symptoms
exaggerated manner beyond the physiological needs even after • Fatigue
normalizing serum iron, serum ferritin levels and achieving • Lethargy
an appropriate RBC mass. Hyperviscosity symptoms are
moderate to severe and recurrent in these patients.8
Hyperviscosity Syndrome hot weather spells or dehyration resulting from gastrointestinal

disorders, they may present with symptoms of hyperviscosity
Exacerbated by dehydration, adults with cyanotic CHD when oral intake cannot match the physiological demands. In
may present with symptoms of hyperviscosity syndrome these cases, the hyperviscosity syndrome promptly responds
(Box 1). Severe secondary erythrocytosis causes increased to an intravenous infusion with 1 liter of isotonic saline.
plasma viscosity and impairment of the microcirculation. This Iron replacement therapy: Providers need to be cautious and
compromises tissue delivery and usually occurs in the setting avoid over treatment.10 The indications for iron replacement
of volume depletion or dehydration. When a patient presents therapy are as follows:
with symptoms suggestive of hyperviscosity syndrome, it • Serum ferritin less than 30 microgram/mL
is also important to examine the differential diagnosis that • Serum ferritin less than 50 microgram/mL with transferrin
includes, but is not limited to, hypovolemia, hypothyroidism, saturation less than 15 percent
depression, brain abscess and gout. • No history of intolerance to oral iron.
Symptoms of hyperviscosity usually respond to hydration. One of the preferred protocol for oral therapy is to prescribe
Once the hematocrit is less than 65 percent, the symptoms an iron formulation containing 66 mg of elemental iron once
resolve but persist if there is iron deficiency. daily, with an incremental increase in the dose, as tolerated,
The management of hyperviscosity syndrome involves to three times daily over a course of 3 months. Follow-up
mainly hydration and long-term iron repletion.9 Laboratory laboratory testing for iron stores should be performed monthly
tests should be performed after adequate hydration and and the complete profile should be checked in 3 months.
these include a complete blood count, serum ferritin levels If there is history of intolerance to oral iron, one may
and transferrin saturation. Phlebotomy should be avoided, if consider giving parenteral therapy with an infusion of
symptoms of hyperviscosity improve. Hydroxyurea has a very intravenous iron sucrose 200 mg at one time then reassess
limited role as discussed later in this chapter. serum ferritin levels and transferrin saturation in 1 month to
Hydration: All patients with cyanotic CHD are constantly determine the need for future doses.10
reminded to drink enough water and fluids to remain adequately The most common side effects of oral iron replacement
hydrated. However, due to excessive insensible losses during therapy are abdominal pain, constipation or diarrhea. If the 773
10
therapy is well tolerated and the patient completes the course, interferes with the production of DNA precursors required
the benefits include a significant increase in iron stores, mean for cell replication and maturation. The treatment must be
corpuscular volume (MCV) and hemoglobin concentration guided by a hematologist and reserved for selected cases of
within 3 months. There is also an increase in exercise capacity refractory hyperviscosity syndrome. In these cases, despite all
and an improvement in quality of life. measures, including iron repletion, the symptomatic patients
Phlebotomy: The age old practice of phlebotomy has a continue to have high hematocrits and are at increased risk for
very limited role now and can be detrimental in most cases. adverse events. Potential serious side effects associated with
The indications for therapeutic phlebotomy in patients hydroxyurea treatment are neutropenia and thrombocytopenia
with polycythemia rubra vera cannot be applied to patients that usually resolve when the treatment is stopped.11
with cyanotic CHD as these two disorders have completely
different pathophysiology. Unfortunately, this fundamental Hemostatic Abnormalities
misconception caused too many inappropriate and often
harmful phlebotomies in cyanotic CHD patients for several Cyanotic CHD patients are vulnerable to bleeding that may vary
years. Phlebotomies have sometimes been fatal and at other from mild to serious and sometimes fatal bleeding. Epistaxis,
times exacerbated hyperviscosity syndrome by causing bruising, petechial and gingival bleeding are examples of mild
more sludging in the microcapillaries, by the iron deficient bleeding. Bleeding associated with trauma or surgery can
microspherocytes. be serious. Hemoptysis can be minor to fatal. Many factors
Phlebotomy should only be considered in an iron replenished associated with bleeding tendency include erythrocytosis with
patient, if the hematocrit continues to remain above 65 and hematocrit over 65 percent, thrombocytopenia, shortened
there are persistent symptoms of the hyperviscosity syndrome, platelet lifespan, clotting factor deficiencies and abnormal
even after receiving adequate hydration. prothrombin time.12,13 Some patients may have congenital
Phlebotomy should be performed with utmost care hematologic disorders (such as in von Willebrand disease)
only when it is strongly indicated.4,5 In the absence of iron associated with CHD.12
deficiency or dehydration, the main indications are: During cardiac surgery many patients will have excessive
a. Persistence hyperviscosity symptoms when the bleeding due to further reduction in platelet counts and
hematocrit is above 65 percent despite adequate function. Coagulation factor deficiencies, heparin-induced
hydration. thrombocytopenia, disseminated intravascular coagulation,
b. Preoperative phlebotomy if the hematocrit is above excessive fibrinolysis may also be contributing factors.
65 percent despite adequate hydration, for reducing Clinically, all patients with cyanotic CHD should avoid
perioperative bleeding complications and/or for saving taking antiplatelet agents such as clopidogrel, Aspirin and other
autologous blood for potential transfusions. nonsteroidal anti-inflammatory drugs (NSAIDs). They should
Phlebotomy is performed as an outpatient procedure, also avoid anticoagulation with low molecular weight heparin or
with admission to an observation unit with cardiac and non- warfarin as far as possible. When warfarin is strongly indicated
invasive hemodynamic monitoring. The following protocol is for persistent atrial fibrillation, the presence of a mechanical
recommended: prosthetic valve, deep vein thrombosis or pulmonary embolus,
• Continuous cardiac electrocardiographic monitoring careful monitoring should be done to maintain the International
• Blood pressure, pulse rate and pulse oximetry checks every Normalized Ratio (INR) between 2 and 2.5.
15 minutes When bleeding occurs, fresh frozen plasma and vitamin
• Remove no more than 1 pint of blood slowly and replete K (for patients taking warfarin) may help. Appropriate
with equal or more volume of isotonic saline management of the cause, platelet transfusion, repletion of
• Observe for 4 hours and reassess symptoms any deficient factors may also be required. Desmopressin may
• Observe for improvement in symptoms help in some situations especially in raising von Willebrand
• Assess for orthostatic hypotension before discharging the factor concentrations. Platelet transfusions, fresh frozen
patient. plasma, vitamin K, cryoprecipitate and desmopressin can be
When performed appropriately and carefully, phlebotomy used to treat severe bleeding.12
should result in favorable clinical effects within 24 hours by
improving the stroke volume, the systemic blood flow and Cardiovascular Issues
the oxygen transport in these patients. The primary goal of
phlebotomy is to provide temporary relief from moderate to Hypoxemic erythrocytotic residents of high altitudes lack
severe symptoms of hyperviscosity syndrome. coronary atherosclerosis and have low cholesterol levels.
Use of hydroxyurea in hyperviscosity syndrome: Hydroxyurea It was postulated that hypoxemic erythrocytotic adults with
cyanotic congenital heart disease might be analogous.
(hydroxycarbamide) is an S-phase specific chemotherapeutic
774 Joseph K Perloff
agent that inhibits ribonucleotide reductase, and thus
55
Prolonged cyanosis and erythocytosis may have an shunt. Other situations with lower benefits from oxygen
unusual effect on the coronary circulation. While coronary supplementation in cyanotic CHD are fixed pulmonary

atherosclerosis is a ubiquitous phenomenon that plagues our vascular resistance or fixed obstruction in the outflow tract of
modern civilization, adults with cyanotic CHD appear to have the subpulmonic ventricle.
some protection from obstructive coronary artery disease. While intermittent use of oxygen may be helpful especially
We studied extramural coronary arteries by reviewing in acute situations, chronic use may result in drying of the nasal
angiograms in 59 adults with cyanotic CHD from two medical mucosa predisposing to epistaxis and potential pulmonary
centers (UCLA and Washington University in St Louis), and toxicity.4
coronary histopathology in 6 adults from one medical center
(UCLA). The mean systemic arterial oxygen saturations were Pulmonary Thrombosis
79 percent and the mean hematocrit measurement was 67, in
these 25 women and 34 men between the ages of 34 and 56 Pulmonary embolus due to thrombosis poses a therapeutic
years. The coronaries were aneurysmal, dilated and tortuous dilemma in cyanotic CHD. In Eisenmenger syndrome,
in 86 percent of the patients with paucity of atherosclerosis.14 female patients and/or those with lower oxygen saturations
On histopathology examination after special stainings, the are at the highest risk of developing thrombosis.20 It can be
dilated ectatic tortuous coronary arteries demonstrated the segmental or massive to occlusive disease causing death. The
following features: proximal pulmonary artery thrombus can migrate to cause
a. Loss of medial smooth muscle cells an intrapulmonary embolus, which may lead to pulmonary
b. Increased medial collagen infarction. This in turn may cause intrapulmonary hemorrhage
c. Duplication of internal elastic lamina and as well as a hemorrhagic pleural effusion. In acute situations,
d. Fibromuscular intimal hyperplasia.14 the benefits of the chosen therapy for thrombosis must outweigh
These findings have been attributed to persistent the hemorrhagic risks. Due to the increased bleeding tendency
erythrocytosis in cyanotic CHD that causes increased in these patients, the role of anticoagulation treatment needs to
laminar endothelial shear stress leading to upregulation of be determined. Intravenous heparin may be used cautiously. It
nitric oxide (NO) synthase by a cascade of interactions that is short-acting and its anticoagulant effect wears off within an
result in vasodilatation.15 Prostaglandins that contribute to hour when it needs to be turned off. Low molecular heparin
vasodilatation are also believed to be released in response to should be avoided due to its longer half life in case there are
increased endothelial shear stress. hemorrhagic complications.
The paucity of atherosclerosis seen in cyanotic CHD There is no proven role for using thrombolytics in patients
may be due to hypocholesterolemia that persists after with chronic thrombi. Nonsteroidal anti-inflammatory drugs
surgical elimination of the cyanosis.16 In addition to (NSAIDs) are to be avoided as far as possible since they
hypocholesterolemia, other independent coexisting anti put the patient at risk for catastrophic hemorrhage. Oral
atherogenic factors are hypoxemia, hyperbilirubinemia, anticoagulation is avoided as far as possible and when it is
upregulated nitric oxide (NO) and low platelet counts. mandated, careful monitoring is essential to maintain the INR
The basal coronary flow is significantly increased and the between 2 and 2.5.4,21
remodeling of the microcirculation is based upon coronary
arteriolar length, volume as well as surface densities, that Pulmonary Hemorrhage
contribute to preservation of flow reserve.17-19
Since the hemorrhage due to cyanotic CHD is intrapulmonary,
Pulmonary issues there is limited role for bronchoscopy, which sometimes can
be dangerous in these patients. Hospitalization with supportive
care and volume repletion is recommended.4
Oxygen Supplementation
Very commonly cyanotic CHD patients are offered oxygen Cerebrovascular events
supplementation in response to low oxygen saturation (SaO2)
especially in emergency rooms/casualty wards. This comes The neurological manifestations in cyanotic CHD include
more from a physician’s reflex action rather than for a medical headaches, syncope, strokes/transient ischemic attack and
indication. cerebral hemorrhage.
Oxygen supplementation has more psychological than
physiological benefits in cyanotic CHD. It may only help Syncope
marginally, since there is a larger volume of deoxygenated
blood that may not reach the alveolar circulation for Besides the neurological symptoms such as headaches that are
oxygenation due to intermixing through a large right to left commonly associated with hyperviscosity syndrome, cyanotic 775
10
CHD patients often experience presyncope or syncope due herniation) or intravenous mannitol (for severe brain edema).
to inappropriate vasodilatation of systemic vascular bed. It Some patients may require interventions such as aspiration of
probably occurs because of the increased nitric oxide levels the abscess24 and placement of a ventriculostomy catheter for
may play a central role in regulating vascular tone. In addition cerebrospinal fluid drainage, to relieve intracranial pressure
to adequate hydration, these patients should avoid hot showers and/or abscess excision.27 Seizures are a frequent complication
or prolonged exposure to hot weather. of brain abscess and anticonvulsants may be needed.27
Bacterial endocarditis prophylaxis and early detection
Stroke and treatment may prevent high morbidity and mortality
associated with brain abscesses.
The residents of high altitudes with secondary erythrocytosis
do not have a high incidence of stroke. However, strokes are a Cerebral Arterial Thrombosis
major cause of morbidity in cyanotic CHD population even in
the absence of classical cardiovascular risk factors. In patients For many years, adults with cyanotic CHD were inappropriately
with cyanotic CHD lesions, the prevalence of stroke is over phlebotomized for elevated hematocrit levels because of an
10-fold above the average.22 assumed risk of cerebral arterial thrombotic stroke caused
Most episodes appeared to be embolic and usually occur by hyperviscosity/sludging. Although the cerebrovascular
in cyanotic CHD patients with or without Eisenmenger accidents due to thromboses of the intracranial venous sinuses
syndrome. Cerebral hemorrhage may be precipitated by and veins have been associated with iron deficient secondary
problems with hemostasis or the use of anticoagulant therapy. erythrocytosis in children,4 there is no established correlation
between secondary erythrocytosis and cerebral arterial
Paradoxical Emboli thrombotic stroke in adults.28
In other studies, the reported incidence of strokes
Cyanotic CHD predisposes to an increased risk of stroke that in cyanotic CHD was up to 14 percent.29,30 Microcytic
may occur due to paradoxical emboli. Passage of thrombotic spherocytes caused by iron deficiency remains the strongest
or particulate matter can occur from the pulmonary to independent predictor for cerebrovascular accidents, even
systemic circulation (cerebral circulation), without allowing when patients with the two other strong independent risk
the blood to filter through the lungs. This risk can be reduced factors are excluded—hypertension and atrial fibrillation.30
by implementing prophylactic measures against deep venous Therefore, inappropriate phlebotomies should be avoided
thrombosis (DVT) and by introducing air filters in all since they exacerbate iron deficiency, which then leads to
intravenous lines. an increased risk of stroke in cyanotic patients.
Brain Abscess Renal

Cyanotic CHD poses a risk of developing a brain abscess, In cyanotic CHD, renal issues can present as proteinuria,
which has been reported in 2 percent of the cyanotic patients.23 hyperuricemia or renal failure, which is an independent
However, in another study among 149 patients presenting predictor of mortality.21 Although hyperuricemia is common,
with a brain abscess, 69 percent had cyanotic CHD.24 patients with cyanotic CHD rarely develop urate nephropathy
A brain abscess is a focal, intracerebral infection that or uric acid stones.
develops into a collection of pus surrounded by a well- The structural renal abnormalities noted in cyanotic
vascularized capsule. Although brain abscesses are commonly CHD are vascular changes—hypercellular congestion and
known to originate from infection of contiguous structures dilatation of capillaries and hilar arteriole—that appear to
or following head trauma/surgery, in patients with cyanotic be due to nitric oxide. In addition, there are non-vascular
CHD they are mostly associated with hematogenous spread changes—prominence of juxta glomerular apparatus and
(bacteremia) that seeds a focal area of ischemia in the brain mesangium- that are attributed to stimulation of tissue by
(caused by sludging from the erythrocytotic blood). The most the platelet-derived growth factor and transforming growth
common organisms isolated in cyanotic brain abscess include factor beta cytokines released by the fragmentation of
Streptococcus viridans, microaerophilic streptococci and megakaryocytes that bypassed the pulmonary circulation due
anaerobic streptococci.25,26 to a shunt. These megakaryocytes are normally destined to
Brain abscess may present with a new or different headache breakdown in the pulmonary circulation to form platelets.31
or any neurological symptoms. Management should be guided The hypercellular and congested glomeruli eventually
by the infectious disease specialists and neurology to include become sclerotic.32
appropriate intravenous antibiotics, with adjunctive therapies Among the functional renal abnormalities, abnormal renal
776 such as corticosteroids when indicated (for impending cerebral clearance of urate results in elevated uric acid levels that may
55
predispose to gout and proteinuria due to increased glomerular Hyperuricemia
hydraulic pressure from secondary erythrocytosis.33

The important clinical implications of these findings are that In cyanotic patients, hyperuricemia occurs due to an increased
they result in a reduction of the glomerular filtration rate and production-breakdown of erythrocytes and decreased
increased creatinine level along with the proteinuria. Cyanotic clearance (abnormal urate reabsorption with inappropriately
patients undergoing cardiac catheterization or radiological low fractional uric acid excretion and not due to urate
procedures may encounter problems with radiopaque contrast overproduction).33 The prevalence of hyperuricemia correlates
material, leading to contrast-induced nephropathy especially with age and hematocrit as well as renal function in cyanotic
in the setting of dehydration. Similarly, they are at a risk for CHD.36-39
acute renal failure leading to uremia, oliguria and even anuria, Clinically as always, adequate hydration helps. These
after cardiopulmonary bypass or any condition that may cause patients should not be treated prophylactically with
hypoperfusion or hypotension.21,34 allopurinol for their absolute uric acid levels. Allopurinol
These patients should be well hydrated before procedures although commonly used in patients with a chronic history of
that involve contrast media. Providers should be aware of the gout has potential for serious side effects including a rare, life-
preoperative diagnosis of glomerulopathy. Gentle diuresis threatening dermatological condition called toxic epidermal
with monitoring is indicated when there is fluid overload. necrolysis syndrome (TENS).
Although not yet proven, there may be a role for long-term During an attack of acute gout that may occur infrequently,
use of angiotensin-converting enzyme (ACE) inhibitors for colchicine is the preferred medication of choice, given with
reducing proteinuria. plenty of food and water to reduce as well as overcome the
occurrence of gastrointestinal side effects (vomiting and
Metabolic disorders 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
Hyperbilirubinemia
or sulfinpyrazone. Nonsteroidal anti-inflammatory drugs such
Cyanotic patients have been observed to have a higher as ibuprofen and salicylates should be avoided even in low
incidence of gallstones (over 20%) as compared with the doses in cyanotic patients because of the risk of bleeding.
acyanotic patients with CHD and the general population, However salsalate which is not an antiplatelet agent may help
where the incidence is around 10 percent.35 While most of in management of pain in these patients without potentiating
gallstones are cholesterol stones (80%), the cyanotic patients hemorrhagic risks.4
have brown and black pigment stones made of calcium
bilirubinate. Rheumatological manifestations
Over time in long-standing chronic cyanotic CHD, an
increased breakdown of red blood cells from excessive
Clubbing
erythrocytosis results in the release of heme. Heme then
breaks down to release unconjugated bilirubin, which is water The most common clinically visible rheumatological
insoluble at physiological pH. Therefore, chronic cyanotic manifestation of cyanotic CHD is clubbing. It is characterized
patients are increased risk of calcium bilirubinate gallstones, by bulbous enlargement of the ends of fingers or toes, with
which are detected by an abdominal ultrasound. loss of the normal angle between the skin and nail plate along
Clinically, they may remain asymptomatic or present with excessive sponginess of the nail base.
with chronic biliary colic. The most common non-cardiac In cyanotic CHD, there is cell proliferation and tissue
surgery in cyanotic CHD patients is cholecystectomy. They formation in the digits because of the release of platelet derived
rarely have acute cholecystitis, but the presence of calcium growth factor and the transforming growth factor beta from
bilirubinate stones can set a substrate for gram negative the breakdown of the megakaryocytes in the end capillaries of
bacteremia, which can then lead to infective endocarditis or the digits rather than in the lungs (where the breakdown would
sepsis in these patients. have normally occurred in the absence of a large shunt). The
A recent study from the Chiba Cardiovascular Center platelet derived growth factor is known to cause increased
in Japan confirms that the prevalence of cholelithiasis and capillary permeability and connective tissue hypertrophy that
asymptomatic gallstones is significantly high in cyanotic appears to be the mechanism for clubbing.40-42
CHD patients regardless of cardiac repairs. In addition
to prolonged cyanosis in these patients, exposure to Hypertrophic Osteoarthropathy
frequent cardiopulmonary bypass during surgeries and
thrombocytopenia might influence gallstone formation in Cyanotic CHD patients may have joint pains of mild to
adults with CHD.35 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 bacterial endocarditis, since they have fragile spongy gums
ends of the metacarpals and metatarsals. Joint aches may be that bleed readily predisposing to bacteremia. Reducing the
accompanied with local tenderness. These symptoms are due risk of gingivitis by taking excellent care of gums can reduce
to hypertrophic osteoarthropathy seen in more than 30 percent this daily and ongoing risk.
of the patients with cyanotic CHD. Meticulous daily dental care and biannual dental hygiene
In hypertrophic osteoarthropathy, there appears to be a visits are strongly advocated in all individuals with cyanotic
chronic inflammatory process with active bone metabolism. CHD. In addition, bacterial endocarditis prophylaxis should
There is edema, round cell infiltration with lifting of the be prescribed in all cyanotic CHD patients, since endocarditis
periosteum and involvement of the structures in the joint is associated with the most detrimental outcomes in this
capsule with adjoining soft tissue. The vascular endothelial population.49 Dental procedures should be avoided for 6
growth factor appears to play a role in addition to other months after an operation, since endothelialization of the
circulating growth factors that are normally inactivated in the prosthetic structures (such as valves, conduits) or sutures
lungs.43 Bisphosphonates are generally effective for relieving needs to be complete in order to reduce the risk of seeding the
pain related to hypertrophic osteoarthropathy, when the pain surgical site with bacteria.
is disabling and refractory to conventional analgesics.44
Skin and Nail Care
Scoliosis
Skin is the largest and most vulnerable organ of the body. Cuts
Scoliosis occurs more frequently in patients with CHD. and wounds are portals for bacteremia, if they are not cleansed
The impact of cardiac surgery on possibility of developing immediately with soap and water following an injury. Careful
scoliosis was reviewed in 998 patients with congenital heart follow-up and appropriate wound care are essential to avoid
defects who were below the age of 16 years. In this Mayo cellulitis and abscess formation. Acne frequently affects the
clinic study, there was no correlation between scoliosis and young people with skin lesions on the face, neck and shoulders.
the presence of cyanosis probably because of early surgical These patients are advised to avoid picking on the ‘pimples’
correction of cyanosis.45 and follow good skin hygiene, hydration, reduced caffeine
intake, stress management, get adequate sleep and take
Pregnancy, contraceptive and medications recommended by dermatology. Body piercing,
gynecological issues tattoos and intravenous drug use are strongly discouraged.
Nail biting or picking adjacent soft tissues is another
Cyanosis is a recognized high risk factor to fetal growth and common habit that opens up portals for bacteremia, besides
development and impacts outcomes in pregnancy. There is being socially unappealing. I have always enjoyed Dr Perloff
increased maternal and fetal mortality that correlates with advising nail-biters to dip their fingers in hydrogen peroxide
the degree of cyanosis, impaired ventricular function and solution from time to time during the day, since it is not only
pulmonary artery pressures.46 Adverse fetal outcomes include a potent disinfectant but also tastes terrible!
fetal wastage (high incidence of miscarriages), preterm
delivery and intrauterine growth retardation. Health Passport and Medical Records
The use of contraceptives is important in avoiding high
risk and unplanned pregnancies in these women. Appropriate The health passport and carrying essential medical records is
guidance regarding choice of contraceptives is important, even more essential in patients with cyanotic CHD, especially
since estrogen increases the risk of thrombosis. Reproductive when they are traveling outside the vicinity of their home
issues including menstrual disorders and infertility challenge town. The details about the health passport are discussed in
most women with cyanotic CHD.47,48 the chapter on transitional care in congenital heart disease.
Pregnancy, contraception and gynecological issues are
discussed in more detail in the chapter relating to this topic. Travel Advice and Precautions
General considerations 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
Dental Care
hydrated, since they are prone to excessive insensible losses.
Infective endocarditis is more likely to result from daily Thirst is a poor indicator of dehydration, especially during air
activities, such as bacteremia caused by bleeding during travel. The cabin pressure during pressurized commercial air
brushing and flossing teeth rather than from bacteremia at the travel is usually well tolerated and permission to carry oxygen
778 time of dental procedures. Cyanotic CHD are at higher risk for in a compressor should be obtained well before embarking on
55
a flight.34,50 Although oxygen supplementation is not clearly work within acceptable limits. Inevitably some need to go on
indicated, it may help to reduce anxiety. disability due to the severity of their cardiac condition and

All precautions should be taken to reduce travel fatigue associated comorbidities.
with good planning, timely arrangements, and reduced
luggage. Medications and equipment for special needs should Psychosocial Challenges and Psychiatric Issues
be carried as hand luggage.4
Depression, anxiety and emotional difficulties are not
Hospitalizations and Non-cardiac Surgery uncommon in individuals with chronic medical conditions
including cyanotic CHD.34 Unfortunately, these may have
Cyanotic patients are at a higher risk for complications during a major impact on the quality of life and affect education,
any hospitalization or operation. Preventive management vocation and relationships. A recent study by Müller et al
strategies include reducing the risk of paradoxical emboli related reported that even minor depressive symptoms in patients
to air and particulate matter through the intravenous lines by with CHD may have a stronger impact on their quality of life
using a filter that is commonly available in pediatric wards. than on limited exercise capacity.53
These patients are prone to bleeding due to increased tissue This topic is discussed in more detail in the chapter
vascularity (potential effect of NO and prostaglandins), friable on Psychosocial Challenges and Psychiatric issues while
tissues (especially skin and gums) and thrombocytopenia Growing Up with Congenital Heart Disease.
with short platelet life span. Right-to-left shunts may deliver
whole megakaryocytes into the system arterial circulation, Smoking Cessation
bypassing the lungs (where megakaryocytic cytoplasm is
normally fragmented into platelets) thus reducing the platelet Both active and passive smoking are even more detrimental
production. The perioperative bleeding risk may be reduced in cyanotic CHD, since inhaled tobacco products stimulate
by preoperative phlebotomy, as discussed previously in this erythrocytosis (seen in chronic smokers) due to an increase in
chapter, since it may improve hemostasis. carboxyhemoglobin. The resulting carboxyhemoglobinemia
They are also more prone to thrombosis due to secondary impairs oxygen carrying capacity of the red blood cells and
erythrocytosis and precautions against DVT should be thereby stimulates secondary erythrocytosis. Young patients
implemented. Renal function also needs to be monitored.4,34 should be advised early on to refrain from smoking and those
who are smokers should be introduced to smoking cessation
Exercise programs and acceptable pharmacological options.4
It has been reported that despite similar cyanosis, patients Special precautions for laboratory testing
with Eisemenger syndrome show less exercise performance,
more ventilation-perfusion mismatch and a worse quality of For accurate measurement of hematological parameters,
life when compared to complex cyanotic CHD patients with special precautions are taken with blood drawn from patients
pulmonary stenosis who are protected from severe pulmonary with cyanotic CHD. The hematocrit level of their blood
vascular disease (due to decreased blood flow to the lungs samples should be calculated by an automated electronic
because of the pulmonary stenosis). The oxygen saturation particle counter because the microhematocrit centrifugation
at rest predicts exercise capacity and ventilatory efficiency in results in plasma trapping and falsely raised hematocrit.
these patients.51,52 Sodium fluoride should be added to the tube carrying
People with cyanotic CHD should avoid dehydration and the blood sample to avoid the false reading of marked
exercising in extremes of weather conditions. Competitive hypoglycemia due to increased in vitro glycolysis.4
sports should be avoided in cyanotic patients. Regular
aerobic exercise with slow warm up and slow cool down is CONCLUSION
encouraged.
Adults with cyanotic CHD have multisystem involvement
Work Restrictions with issues that need close follow-up and care by a
multidisciplinary team (Table 2). Fundamental preventive
Many people with CHD are only able to work for limited strategies, early detection and timely care can improve long-
work hours. In addition, the emotional and mental intensity term survival and quality of life in these special individuals.
involved in completion of the tasks and physical limitations
due to scoliosis or reduced muscle strength may hinder. Faith and knowledge lean largely upon each other in the
The physicians should be supportive in providing letters or practice of medicine.
documents to the employers that will allow these people to —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 Remind patients to stay well hydrated
erythrocytosis Hydrate well before considering phlebotomy and also
after phlebotomy
Nutrition Iron deficiency Monitored iron supplementation
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 Daily dental care—brushing teeth properly twice daily
gums—increased risk of infective with soft toothbrush, biannual dental hygiene visits
endocarditis 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 Avoid nail biting
plucking skin tags
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 Reasonable travel plans and minimize exertion
Access to medical care Research local medical options/facilities
Dehydration Adequate volume repletion and travel precautions
Non-cardiac surgery 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
Pregnancy High risk of miscarriage and preterm Preconception counseling
delivery Correction of the defect prior to pregnancy
Increased incidence of prematurity, Appropriate antenatal care with planned labor and
small for gestational age babies delivery at a specialized center
Postpartum risk of DVT DVT precautions
Immunization Immunocompromized Pneumovax
Higher risk for pulmonary infections Influenza vaccination
780
55
REFERENCES 19. Perloff JK. Cyanotic congenital heart disease the coronary
arterial circulation. Curr Cardiol Rev. 2012;8:1-5.

1. Ruth Porter (Editor), Julie Knight (Editor). In High Altitude 20. Silversides CK, Granton JT, Konen E, et al. Pulmonary
Physiology: Cardiac and Respiratory aspects. CIBA thrombosis in adults with Eisenmenger syndrome. J Am Coll
Foundation. 1971. Cardiol. 2003;42:1982-7.
2. Penaloza D, Arias-Stella J. The heart and pulmonary circulation 21. Silversides CK, Oechslin E, Schwerzmann M, et al. Canadian
at high altitudes: healthy highlanders and chronic mountain Cardiovascular Society 2009 Consensus Conference on
sickness. Circulation. 2007;115:1132-46. the management of adults with congenital heart disease:
3. Perloff JK. Systemic complications of cyanosis in adults with Complex congenital cardiac lesions. Can J Cardiol.
congenital heart disease. Hematologic derangements, renal 2010;26:e98-e117.
function and urate metabolism. Cardiol Clin. 1993;11:689-99. 22. Hoffmann A, Chockalingam P, Balint OH, et al. Cerebrovascular
4. Perloff JK, Child JS, Aboulhosn J (Editors). In Congenital Heart accidents in adult patients with congenital heart disease. Heart.
Disease in Adults, 3rd edition. Philadelphia: WB Saunders Co; 2010;96:1223-6.
2008 23. Fischbein CA, Rosenthal A, Fischer EG, et al. Risk factors
5. Oechslin E. Hematological management of the cyanotic adult of brain abscess in patients with congenital heart disease.
with congenital heart disease. Int J Cardiol. 2004;97:109-15. American Journal of Cardiology. 1974;34:97-102.
6. Wood P. The Eisenmenger syndrome or pulmonary hypertension 24. Takeshita M, Kagawa M, Yato S, et al. Current treatment of
with reversed central shunt. Br Med J. 1958;2:701-9. brain abscess in patients with congenital cyanotic heart disease.
7. Bridges ND. Risk of stroke in adults with cyanotic congenital Neurosurger. 1997;41:1270-8.
heart disease. Circulation. 1994;89:911. Comment on: Risk 25. De Louvois J. The bacteriology and chemotherapy of
of stroke in adults with cyanotic congenital heart disease brainabscess. Journal of Antimicrobial Chemotherapy. 1978;4:
[Circulation. 1993]. 395-413.
8. Rosove MH, Perloff JK, Hocking WG, et al. Chronic hypoxemia 26. Saez-Llorens XJ, Umana MA, Odio CM, et al. Brain abscess
and decompensated erythrocytosis in cyanotic congenital heart in infants and children. Pediatric Infectious Disease Journal.
disease. Lancet. 1986;2:313-5. 1989;8:449-58.
9. Perloff JK, Rosove MH, Child JS, et al. Adults with cyanotic 27. Mathisen GE, Johnson JP. Brain abscess. Clinical Infectious
congenital heart disease: hematologic management. Ann Intern Diseases. 1997;25:763-81.
Med. 1988;109:406-13. 28. Perloff JK, Marelli AJ, Miner PD. Risk of stroke in adults
10. Tay EL, Peset A, Papaphylactou M, et al. Replacement therapy with cyanotic congenital heart disease. Circulation 1993;87:
for iron deficiency improves exercise capacity and quality of 1954-9.
life in patients with cyanotic congenital heart disease and/or 29. Daliento L, Somerville J, Presbitero P, et al. Eisenmenger
the Eisenmenger syndrome. Int J Cardiol. 2011;151:307-12. syndrome. Factors relating to deterioration and death. Eur
Epub 2010 Jul 1. Heart J. 1998;19:1845-55.
11. Reiss UM, Bensimhon P, Zimmerman SA, et al. Hydroxyurea 30. Ammash N, Warnes CA. Cerebrovascular events in adult
therapy for management of secondary erythrocytosis in patients with cyanotic congenital heart disease. J Am Coll
cyanotic congenital heart disease. Am J Hematol. 2007;82:740- Cardiol. 1996;28:768-72.
3. 31. Perloff JK, Latta H, Barsotti P. Pathogenesis of the glomerular
12. Territo MC, Rosove MH. Cyanotic congenital heart disease: abnormality in cyanotic congenital heart disease. Am J Cardiol.
hematologic management. J Am Coll Cardiol. 1991;18:320-22. 2000;86:1198-204.
13. Lill MC, Perloff JK, Child JS. Pathogenesis of thrombo
32. Flanagan MF, Hourihan M, Keane JF. Incidence of renal
cytopenia in cyanotic congenital heart disease. Am J Cardiol.
dysfunction in adults with cyanotic congenital heart disease.
2006;98:254-8. Epub 2006 May 30.
Am J Cardiol. 1991;68:403-6.
14. Chugh R, Perloff JK, Fishbein M, Child JS. Extramural
33. Ross EA, Perloff JK, Danovitch GM, et al. Renal function and
coronary arteries in adults with cyanotic congenital heart
urate metabolism in late survivors with cyanotic congenital
disease. Am J Cardiol. 2004;94:1355-7.
heart disease.Circulation. 1986;73:396-400.
15. Han TH, Perloff JK, Liao JC. Nitric oxide metabolism in
34. Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA
adults with cyanotic congenital heart disease. Am J Cardiol.
2008 guidelines for the management of adults with congenital
2007;99:691-95. Epub 2007 Jan 9.
heart disease: a report of the American College of Cardiology/
16. Fyfe A, Perloff JK, Niwa K, et al. Cyanotic congenital heart
disease and coronary artery atherogenesis. Am J Cardiol. American Heart Association Task Force on Practice Guidelines.
2005;96:283-90. J Am Coll Cardiol. 2008;52:e143-263 or in Circulation.
17. Dedkov EI, Perloff JK, Tomanek RJ, et al. The coronary 2008;118:2395-451.
microcirculation in cyanotic congenital heart disease. 35. Shiina Y, Toyoda T, Kawasoe Y, et al. The prevalence and risk
Circulation. 2006;114:196-200. Epub 2006 Jul 10. factors for cholelithiasis and asymptomatic gallstones in adults
18. Brunken RC, Perloff JK, Czernin J, et al. Myocardial perfusion with congenital heart disease. Int J Cardiol. 2011;152:171-76.
reserve in adults with cyanotic congenital heart disease. Am J Epub 2010 Aug 1.
Physiol Heart Circ Physiol. 2005;289:H1798-806. Epub 2005 36. Somerville J. Gout in cyanotic congenital heart disease. Br
Heart J. 1961;23:31-4.
Jul 8. 781
10
37. Lewis JG, Gardner JE. The relation of serum uric acid to 46. Siu SC, Sermer M, Harrison DA, Risk and predictors for
hemoglobin level in patients with cardiac and respiratory pregnancy-related complications in women with heart disease.
disease. J Clin Pathol. 1960;13:502-5. Circulation. 1997;96:2789-94.

38. Cameron EA. Gout from cyanotic congenital heart disease. Br 47. Canobbio MM, Perloff JK, Rapkin AJ. Gynecological health
Med J. 1961;1:34-5. of females with congenital heart disease. Int J Cardiol.
39. Hayabuchi Y, Matsuoka S, Akita H, et al. Hyperuricemia in 2005;98:379-87.
cyanotic congenital heart disease. Eur J Pediatr. 1993;152: 48. Canobbio MM, Rapkin AJ, Perloff JK, et al. Menstrual patterns
873-6. in women with congenital heart disease. Pediatr Cardiol.
40. Dickinson CJ. The etiology of clubbing and hypertrophic 1995;16:12-5.
osteoarthropathy. Eur J Clin Invest. 1993;23:330-8. 49. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective
41. Dickinson CJ, Martin JF. Megakaryocytes and platelet clumps endocarditis: guidelines from the American Heart Association.
as the cause of finger clubbing. Lancet. 1987;2:1434-5. Circulation. 2007;116:1736-54. Epub 2007 Apr 19.
42. Border WA, Noble NA. Transforming growth factor-beta in 50. Harinck E, Hutter PA, Hoorntje TM, et al. Air travel and adults
tissue fibrosis. N Engl J Med. 1994;331:1286-92. with cyanotic congenital heart disease. Circulation. 1996;93:272-6.
43. Silveira LH, Martínez-Lavín M, Pineda C, et al. Vascular 51. Müller J, Hess J, Hager A. Exercise performance and quality
endothelial growth factor and hypertrophic osteoarthropathy. of life is more impaired in Eisenmenger syndrome than in
Clin Exp Rheumatol. 2000;18:57-62. complex cyanotic congenital heart disease with pulmonary
44. Pineda CJ, Guerra J Jr, Weisman MH, et al. The skeletal stenosis. Int J Cardiol. 2011;150:177-81. Epub 2010 May 1.
manifestations of clubbing: a study in patients with cyanotic 52. Sietsema KE, Cooper DM, Perloff JK, et al. Dynamics
congenital heart disease and hypertrophic osteoarthropathy. of oxygen uptake during exercise in adults with cyanotic
Semin Arthritis Rheum. 1985;14:263-73. congenital heart disease.Circulation. 1986;73:1137-44.
45. Reckles LN, Peterson HA, Weidman WH, Bianco AJ Jr. The 53. Müller J, Hess J, Hager A. Minor symptoms of depression in
association of scoliosis and congenital heart defects. J Bone patients with congenital heart disease have a larger impact on
Joint Surg Am. 1975;57:449-55. quality of life than limited exercise capacity. Int J Cardiol.
2012;154:265-69. Epub 2010 Oct 5.
782
Pregnancy, Contraception and
C hapter
56 Gynecological Issues in Women

with Congenital Heart Disease
Reema Chugh, Pamela D Miner, Mary M Canobbio
INTRODUCTION prophylaxis are among the other major topics addressed at

that time.
As women born with congenital heart diseases (CHD) mature Overall, women with unoperated complex or cyanotic CHD
into child bearing years, they are exposed to the risks of have a reduced cardiac reserve and decreased ability to tolerate
pregnancy that can vary widely among the specific types the cardiovascular demands of pregnancy, labor and delivery.
of CHD. All patients must be well informed of the risks of They are also at high-risk for cardiovascular complications and
pregnancy, associated with their condition and the available adverse fetal outcomes. As reported in most studies, maternal
options to avoid pregnancy when desired. Some women are outcomes are directly related to New York Heart Association
also faced with gynecological disorders that may be related (NYHA) functional class.2
to the underlying CHD. In this chapter, we have three sections Fetal outcomes directly depend on maternal health and
addressing these major issues—pregnancy, contraception and exposure to teratogens. Women with complex CHD are more
gynecological issues—in women with CHD. likely to have fetal wastage, prematurity, low birth weight and
CHD in the offspring.3
REGNANCY IN WOMEN WITH chd
P
By Reema Chugh, MD, FACC PRECONCEPTION ASSESSMENT FOR PREGNANCY RISK
ASSESSMENT IN WOMEN WITH congenital heart
In order to improve the outcomes in women with CHD, risk diseases
stratification is recommended before pregnancy. Unfortunately,
not all women present for preconception counseling and often A comprehensive clinical assessment is critically important
the process of risk stratification have to take place in early for identifying maternal status and directing appropriate
pregnancy. This is either due to lack of patient education or management (Box 1). It is important to obtain a detailed
resources, or when the patient is first diagnosed with CHD medical, surgical, social and family history. This should be
during pregnancy. followed by a thorough cardiovascular examination looking
According to the guidelines, pregnant women in the low- for status of the underlying defects, their residua and sequelae.
risk group can usually be managed in a community hospital In all women contemplating pregnancy, one must review
setting, while those who are at intermediate to high risk for the possibility of exposure to medications and potentially
complications should be managed in a high-risk perinatal teratogenic agents. The physician should prescribe an
unit by a multidisciplinary team that includes an obstetrician, alternative medication when necessary. Angiotensin-converting
perinatologist, cardiologist, high-risk anesthesiologist and enzyme inhibitors (ACE inhibitors) and angiotensin II receptor
a pediatrician.1 The team should meet early in the patient’s antagonists, atenolol and amiodarone are commonly used
pregnancy to develop a management plan after understanding cardiac medications that should be stopped before pregnancy.
the status of the cardiac lesion, potential issues during In women who need anticoagulation during pregnancy, an
pregnancy, labor and delivery. They should address specific alternative to warfarin should be offered to avoid fetal exposure
issues including the timing, mode of delivery, the type of to warfarin, especially in the first trimester (discussed later in
anesthesia, the level of monitoring before and after delivery. this chapter). Naturopathic medications or over-the-counter
Review of medications, discontinuation of teratogenic drugs, preparations should be avoided during pregnancy, unless
genetic counseling, fetal screening and the use of antibiotic approved by the health care providers. Preconception intake of
10 BOX 1: Preconception clinical assessment in women BOX 2: Cardiac diagnostic tests in pregnancy
with congenital heart diseases Electrocardiogram
History • Rate, rhythm and intervals (PR interval, QRS duration,

• Assessment of symptoms suggestive of cardiac issues: and QT intervals), axis, R wave progression
Dyspnea, chest pain/discomfort, palpitations, presyncope, • Left ventricular hypertrophy (LVH) or right ventricular
syncope, orthopnea, paroxysmal nocturnal dyspnea, hypertrophy (RVH)
peripheral edema • Sinus node function and conduction defects: Atrio
• Medical history with review of medical records relating to ventricular (AV) heart block, conduction blocks (bundle
CHD and obstetric history branch blocks)
• Cardiac surgery and interventional procedures—review • Wolff-Parkinson-White (WPW) syndrome
of operation notes Echocardiogram
• Substance use: Alcohol, tobacco and recreational drugs Establish normal findings in pregnancy114,115
• Inheritable disorders/CHD, coronary artery disease, Second trimester
diabetes, hypertension or stroke • Increase in size of the left and right ventricles and the
Medications and allergies left atrium
• Identify potentially teratogenic medications: Discontinue • Increased left ventricular (LV) volumes during both
them and replace with alternate ones when feasible systole and diastole
• Allergies/intolerance to medications, foods and • Increased left ventricular mass and wall thickness
environmental/seasonal substances • Increased cardiac globularity in the third trimester
• Recommend the use of prenatal vitamins: Folic acid Third trimester
supplements should be started early and prior to • Biventricular reduction in global and segmental longitudinal
conception for maximal beneficial effect deformation (compensatory change to accommodate the
Physical examination increase in cardiac dimensions during pregnancy)
• Assessment of vitals: Weight, blood pressure, heart rate • No change in ejection fraction
and rhythm, oxygen saturation on room air Study serial changes between the preconception echocardio
• Jugular venous pulsations, carotid pulsations and gram and those during pregnancy and postpartum
upstroke • Confirmation of the anatomy, situs, chamber size and
• Pulmonary: Position of the trachea and assessment of position (rule out ventricular inversion), valve disease,
breath sounds to rule out heart failure/asthma shunts
Cardiac examination • Systemic and pulmonic ventricular size and function
• Inspection of the chest wall: Scoliosis, kyphosis, pectus • Assessment of residual or recurrent lesions
excavatum, scars from previous surgeries • Assessment of pulmonary hypertension
• Palpation: Cardiac borders, apical impulse, thrill. Stress echocardiogram with treadmill stress test (precon
• Percussion ception)
• Auscultation: Heart sounds, murmurs, rubs and gallops • Baseline functional capacity: Exercise duration, workload
– Abdomen: Situs (position of the liver and gastric metabolic equivalents of task—METs
sounds), abdominal jugular reflux (AJR), palpable • Exercise induced symptoms, arrhythmias or ischemia
masses or pulsations, bowel sounds • Imaging for assessment of:
– Extremities: Pulses, edema, cyanosis, clubbing, – Contractile reserve: Response of systemic and
varicose veins pulmonic ventricle to exercise
– Pulmonary hypertension: Changes in estimated right
ventricular systolic pressure (RVSP) pre and post
multivitamins including folic acid decreases the incidence of exercise
CHD in the offspring.4 – Stenotic valve gradients, left or right ventricular outflow
tract gradient pre and post exercise.
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 underlying defects, operated or unoperated with their residua
when the mother is affected with CHD rather than the father. and sequelae, are assessed and managed accordingly in order
The risk of transmission can range from 3 to 15 percent for to reduce the risk of maternal and fetal complications during
most CHD and up to 50 percent for autosomal dominant pregnancy, labor and delivery (Box 2).
defects. Examples of autosomal dominant defects are: Marfan
syndrome, Noonan syndrome and the Holt-Oram syndrome. HEMATOLOGICAL AND HEMODYNAMIC CHANGES IN
Appropriate cardiac diagnostic tests are requested for PREGNANCY
assessment of the baseline exercise functional capacity,
784 determination of stress-induced arrhythmias and evaluation During pregnancy hemodynamic changes occur to sustain
of the systemic ventricular systolic function. The status of the intrauterine life and maintain maternal homeostasis (Table 1).
Table 1
 and an increase in heart rate. It rapidly rises after 12 weeks 56
Normal major hemodynamic and hematological changes in and peaks by the 20th to 24th weeks, remaining at that level,
pregnancy until late in pregnancy.11
Pregnancy, Contraception and Gynecological Issues in Women with Congenital Heart Disease
There is a modest decrease in systolic blood pressure
Systolic blood pressure Mildly decreased
(10–15 mm Hg) and a more significant drop in diastolic blood
Diastolic blood pressure Decreased pressure (20–25 mm Hg) that occurs in the first trimester
Pulse rate Increased by 15 to 20% resulting in widened pulse pressure by mid-pregnancy. Blood
Cardiac output Increased by 30 to 50% pressure during pregnancy is affected by maternal age over 35
Systemic vascular resistance Decreased
years and parity.12
The systemic vascular resistance (SVR) decreases during
Pulmonary vascular resistance Decreased
the first two months of pregnancy due to hormonal influences
Plasma volume Increased by 40 to 50% (estrogen, prolactin and progesterone), along with a decrease
RBC mass Increased by 20 to 40% in pulmonary vascular resistance (PVR). These changes
Hemoglobin/hematocrit Decreased 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
The maternal plasma volume progressively expands during dysfunction. The mean pulmonary artery pressures remain
pregnancy and rises by 40 to 50 percent of the pregestational similar to pre-gestational values.
volume by the 32nd week of gestation. A greater increase in Maternal position exerts a profound mechanical effect on
volume is noted in multigravidas (as compared to primigravidas) cardiovascular hemodynamics, particularly towards the end
and in twin pregnancies (as compared to a singleton of gestation, causing positional fluctuations in cardiac output
pregnancy).5,6 Distension of the atrial tissue may increase the by the 38th and 40th weeks. There may be compression of the
risk of atrial arrhythmias during pregnancy. Overall, the cardiac inferior vena cava by the gravid uterus in the supine position,
output increases by 30 to 50 percent and stroke volumes rises by which can decrease venous return, stroke volume and cardiac
18 to 25 percent. Since the uteroplacental blood flow is directly output.14 In the last trimester, approximately 8 percent of
dependant on the cardiac output, a decrease in cardiac output is women will experience light headedness and nausea. This
associated with intrauterine growth restriction (IUGR) and an ‘supine hypotensive syndrome’, can be relieved by placing
increased likelihood of preterm delivery.7 the patient in the lateral recumbent position.15 This is also the
The rise in red cell volume is around 20 to 40 percent of preferred position in late pregnancy, during labor and delivery.
the pre-gestational values, causing a relative reduction of the No changes in cardiac output are observed in this position. Of
maternal hemoglobin concentration, also known as dilutional note, the blood pressure taken in the supine position will be
anemia or physiological anemia of pregnancy.8 Most women higher than that taken in the left lateral position.10,16,17 The
may appear anemic with hemoglobin levels of 11 to 12 g/100 hemodynamic changes during pregnancy return to the baseline
ml and hematocrit levels as low as 33 to 38 percent during the values usually within 6 to 8 weeks postpartum.
second trimester.8,9 An increase in extravascular fluid is caused
by a rise in plasma aldosterone levels, which promotes sodium ANTEPARTUM ASSESSMENT
retention that leads to an increase in body water.6 Women often
encounter peripheral and generalized edema in late pregnancy. From the cardiovascular standpoint, pregnancy is usually
This is due to the additive effect of elevated venous pressure in well tolerated in the first trimester, since major hemodynamic
the lower extremities and the increase in extravascular fluid. changes do not occur until the second and third trimester
Pregnancy is a thrombogenic state as a consequence of of pregnancy. The most important change is an increase in
the changes in the coagulation cascade. This results from an cardiac output by 20 to 24 weeks, due to an increase in blood
increase in clotting factors and decreased fibrinolysis. There is volume and heart rate. These changes pose a burden on the
an additive effect of increased venous stasis. During pregnancy/ systemic ventricle and residual heart defects, which should be
postpartum period, women are at risk for developing deep identified and repaired before pregnancy, if possible.
venous thrombosis, especially when they are inactive or on Physicians and nurse specialists should be familiar with the
bed rest. Those with intracardiac shunts are at risk of having physiologic findings on cardiovascular examination during
transient ischemic attacks or stroke, due to paradoxical emboli. pregnancy. By the 12 to 20th week of gestation, there may be
The heart rate progressively rises by 10 to 20 bpm or 17 tachycardia with pulse rates 10 to 20 beats per minute above
percent over pregestational rates, with mean values ranging baseline, a widely split first heart sound due to early closure
from 78 to 89 beats per minute. Changes in body position of the mitral valve and a third heart sound. In addition, there
from supine to lateral may cause a decrease in heart rate.10 may be low intensity ejection systolic murmurs along the left
The cardiac output rises by 30 to 50 percent over nonpregnant sternal border due to a hyperdynamic circulation.18 In the last
levels, since it is the product of an increase in stroke volume trimester, a systolic murmur originating from the branches of 785
10 the internal thoracic (mammary) artery and a continuous bruit fetal defects may require a planned delivery at a tertiary care
originating in the veins of the breast may be heard.19 Women center, or in some cases, medical termination of pregnancy.
often have varicose veins and peripheral edema. Counseling should be offered to the parents of the offspring
Among the abnormal heart sounds during pregnancy are a and the involvement of a clinical social worker helps the
fixed splitting of the second heart sound, a fourth heart sound, family deal with the challenges.24
a loud systolic murmur (over grade 3/6) or the presence of any
diastolic heart murmurs. DETERMINING THE MATERNAL AND FETAL RISK
Early on and when indicated in pregnancy, medications
need to be reviewed for their safety data, as well as for Pregnancies in women with CHD without potential risk
potential teratogenic effects and prescribed only if necessary. factors are likely to carry low maternal and fetal morbidity/
More current information on the medications and their effects mortality. Pregnancy carries the highest risk in women with
during pregnancy can be obtained from certain websites at no Eisenmenger syndrome with the postnatal maternal mortality
charge or subscription (www.drugs.com). as high as 50 percent. Another high-risk scenario is a woman
Electrocardiograms and transthoracic echocardiograms with Marfan syndrome and a dilated aortic root over 4 cm,
can be performed safely as and when indicated. Stress testing which can be at high risk for an aortic dissection. This may
should be avoided whenever possible during pregnancy. A occur due to the impact that hemodynamic and hormonal
submaximal treadmill stress test (70% of the maximum age changes of pregnancy have on the aneurysmal aorta.
predicted heart rate on Bruce protocol) is performed only if Pregnancy is therefore contraindicated in these women.
strongly indicated. Exposure to radiation should be minimized Risk factors for maternal morbidity include poor maternal
and avoided unless absolutely necessary. Abdominal shielding functional class, poorly controlled arrhythmias, heart failure,
should be provided when the procedure is necessary and the cyanosis, significant left heart obstruction and a history of
risk versus benefit ratio is in favor of performing the procedure. cerebral ischemia. The common maternal risk factors are
The risk of radiation exposure to the fetus should be discussed listed in Box 3. Maternal health status, especially cyanosis
with the patient. When possible, the procedures should be and exposure to teratogenic drugs are the major risk factors
postponed, until late second or third trimester of pregnancy. for fetal and neonatal complications. Box 4 addresses the
One such case could be a woman with critical aortic stenosis or major fetal risk factors.
severe mitral stenosis who may need emergent valvuloplasty, Siu et al described a risk index scoring system to predict
if she is in heart failure due to progressive volume load during the risk of adverse maternal events.25 In order to calculate
pregnancy. the score, the risk index awards one point each for poor
functional status (New York Heart Association [NYHA] > II),
Screening for Congenital Heart Diseases in the Offspring cyanosis (oxygen saturation < 90%), left ventricular systolic
The incidence of CHD in offspring is estimated to be 0.8

box 3: Contraindications for pregnancy
percent in the general population. Irrespective of age, women
with CHD should be screened, since the risk of CHD in Absolute contraindications
their offspring could vary from 3 to 15 percent, although the • Eisenmenger syndrome
• Dilated aortic root in Marfan (over 4 cm)
offspring may not have the same defect.20
• Cyanotic congenital heart disease with decompensation
The maternal serum markers, alpha-fetoprotein in
due to unoperated defects
conjunction with pregnancy-associated plasma protein A
Relative contraindications
(PAPP-A), human chorionic gonadotropin, and unconjugated
• Severe obstructive lesions such as critical aortic stenosis
estriol, have improved detection rates of Down syndrome or left ventricular significant outflow tract obstruction,
and trisomy 18. Fetal nuchal translucency, the measurement severe mitral valve or pulmonary stenosis
of fluid collection size at the back of fetal neck between 11 • Symptomatic heart failure/systemic ventricular function
and 14 weeks of gestation, helps identify a broad range of with ejection fraction less than 40%
chromosomal, genetic and structural abnormalities as long as • Uncontrolled arrhythmias
the measurements are accurate.21 • History of transient ischemic attacks or cerebrovascular
Chorionic villus sampling or amniocentesis may be accidents
useful after discussion of the potential risks and benefits.
Amniocentesis more specifically detects chromosomal
defects. In a prospective clinical trial, amniocentesis carried a Box 4: Fetal risk factors
procedure-related fetal loss rate of 0.06 percent.22 • Maternal use of teratogenic drugs
Fetal echocardiography at 14 to 16 weeks gestation should • Maternal cyanosis
be performed on all women. This may be repeated at 18 to 22 • Maternal systemic ventricular dysfunction
786 weeks and closer to delivery. The sensitivity and specificity • Maternal uncontrolled arrhythmias
• Fetus with a significant or complex congenital heart disease
are operator dependent.23 The presence of moderate-to-severe
BOX 5: Risk score for predicting pregnancy-related
left interatrial shunt, with an increased risk of paradoxical 56
complications embolism and stroke, especially when it occurs along with an
atrial septal aneurysm.
• H istory of prior cardiac events such as arrhythmias, heart
Atrial septal defects (ASD), ventricular septal defects
failure, transient ischemic attack/stroke
• Prior arrhythmias such as symptomatic sustained (VSD) and patent ductus arteriosus (PDA) are common lesions
tachyarrhythmia or bradyarrhythmia requiring treatment with a left to right shunts.29,30 Women with unoperated or
• Poor functional class (New York Heart Association residual VSD or PDA are at high risk of developing infective
[NYHA] class > 2) endocarditis.31 Long-standing large shunts may predispose
• Cyanosis with low oxygen saturation of < 90% on room to pulmonary vascular disease and significant pulmonary
air hypertension. Eventually the rising right heart pressures may
• Significant valvular and outflow tract obstruction (aortic cause reversal of the shunt (right-to-left rather than left-to-
valve area < 1.5 cm2, mitral valve area < 2 cm2, or left
right shunt) leading to Eisenmenger physiology.
ventricular outflow tract peak gradient > 30 mm Hg)
Even after patch closure of an atrial septal defect, women
• Systemic ventricular ejection fraction < 40%
may have supraventricular arrhythmias during pregnancy.
The risk index score is the sum of the points (one point is
Postventriculotomy ventricular tachycardia or conduction
awarded for each risk factor listed above) that predicts the
percentage likelihood of adverse maternal events. Women block may occur following patch repair of a VSD. An early
with risk index of < 1, 1 and > 1, have a 5%, 27%, and 75% surgically ligated or divided PDA poses no additional hazard
likelihood of pregnancy-related complications (Adapted from to the mother or the fetus.
Siu et al)25.
Atrial Septal Defects
dysfunction, left heart obstruction and a history of cardiac In a study of pregnancies in women who have ASD and
events prior to pregnancy including arrhythmias, stroke, or no associated lesions, a higher risk of neonatal events was
pulmonary edema.25,26 A risk index score of 0 indicates an noted in women with unrepaired ASDs. The risk of cardiac
approximate risk of 5 percent, a risk index of 1 correlates with and obstetrical complications were comparable between
a 27 percent of adverse maternal events, whereas a woman the women with unrepaired and the repaired ASDs. Women
with a risk index greater than 1 has a 75 percent likelihood of with unrepaired ASDs had an increased incidence of pre-
adverse events (Box 5). eclampsia, small-for-gestational-age babies (less than the 10th
On the basis of these risk factors and the available data, percentile) and a higher fetal mortality (intrauterine death at
women can be stratified into low, intermediate, or high- or after 20 weeks of gestation). Cardiac arrhythmias, namely
risk categories. Unfortunately, most of the current data on nonsustained ventricular tachyarrhythmia and supraventricular
outcomes of pregnancy for individual defects are based arrhythmias (atrial fibrillation or supraventricular tachycardia)
on retrospective case series or case reports. Therefore occurred in 4.3 percent of the pregnancies, more often in older
decisions are often based on clinical experience.27,28 A women and in those with previous history of arrhythmias.
referral to a regional adult congenital heart disease (ACHD) One woman with an unrepaired ASD had a transient ischemic
clinic/tertiary care center is recommended for pregnant attack in the postpartum period, probably due to paradoxical
women who are at intermediate to high risk for maternal- embolism. Reduced exercise tolerance and mild heart failure
fetal complications. Included among the women identified were noted in around 3 percent women during pregnancy.32
as having a high risk score, are those with unoperated
or operated complex CHD, such as transposition of the Ventricular Septal Defects
great arteries postatrial switch repairs (Mustard/Senning
procedure) or univentricular hearts post-Fontan procedures. A recent study comparing outcomes of pregnancy in women
with unrepaired versus repaired VSDs showed a higher
CONGENITAL HEART DISEASES AND PREGNANCY incidence of pre-eclampsia (8.7%) in those with unrepaired
VSD, mostly occurring after 34 weeks of gestation. A higher
A brief overview of the potential maternal and fetal incidence of preterm labor was noted in women with repaired
management issues associated with simple and complex VSDs, probably related to a greater background risk with
CHD, most often encountered at a regional ACHD center, are relatively larger VSDs having undergone surgical repair. The
discussed below. mechanism of these observations is not clear. One woman with
an unrepaired VSD suffered Streptococcus viridans infective
Shunt Defects endocarditis involving a right heart valve in the postpartum
period, despite receiving antibiotics during an uncomplicated
Patent foramen ovale, although not always classified as a vaginal delivery. The incidence of recurrence of CHD was
CHD, is arguably the most common CHD with a right to 2 percent.33 Other studies have shown a lower incidence of 787
10 pre-eclampsia (1.8%) as reported in a literature review by The major maternal complications were hypertension-related
Drenthen et al.28 disorders noted in 15 percent of the women. Four pregnancies
were complicated by pre-eclampsia and two women had
Patent Ductus Arteriosus eclamptic seizures. These observations are unusual, because
the incidence of hypertension-related disorders and eclampsia
Depending on the size of the ductus and degree of shunt, there were much higher than seen in the general population.
is an increased risk for developing pulmonary hypertension, Thromboembolic events occurred in nearly 4 percent pregnant
congestive heart failure and bacterial endocarditis/endarteritis. women with pulmonary stenosis. Cardiac problems were
The maternal morbidity and mortality in unrepaired PDA is palpitations/arrhythmias in nine women and deterioration
low. Women with a ligated or divided isolated PDA carry no in functional class in two women persisting for one year
risk in the presence of normal left ventricular function and postpartum. Fetal complications were premature deliveries in
normal pulmonary arterial pressures.34 17 percent, fetal mortality in 4.8 percent and occurrence of
CHD in offspring 3.7 percent.38
Atrioventricular Septal Defects Although, there is no clear explanation for the higher
incidence of non-cardiac complications among these women
In atrioventricular septal defects (AVSD), the architecture undergoing pregnancy, early detection and close attention to
of the fibrous skeleton of the heart is structurally different risk factors for hypertension-related disorders and premature
from other septal defects and therefore, the clinical outcomes, birth are advocated to improve maternal and fetal outcomes.
surgical repair, residua and sequelae differ significantly. Due
to these complexities, pregnancy is not always well tolerated Bicuspid Aortic Valve
in women with AVSD.
In a multicenter study with 29 women who had 62 Bicuspid aortic valve (BAV) is one of the most common
pregnancies, including 12 miscarriages (19%) and two CHDs.29,30 Pregnancy with mild to moderate stenosis is well
elective abortions, cardiovascular complications occurred tolerated. However, severe stenosis encroaches upon the
in almost 40 percent of the term pregnancies. There was circulatory reserve (valve area less than 1 cm2) and valve
deterioration in functional class (NYHA) seen in 23 percent replacement/repair should be advised before pregnancy.
and worsening of pre-existing atrioventricular (AV) valvular Women proceeding with severe aortic stenosis (AS) are at
regurgitation in 17 percent. Cardiac arrhythmias occurred in risk for developing heart failure (44%),36 angina, syncope
19 percent and symptomatic heart failure in 2 percent of the and sudden cardiac death during pregnancy. The aortic root
women. Mortality was high among the children (6.3%), since should be monitored in women by echocardiography during
12 percent had complex CHD. Among the three children who pregnancy for dilatation/dissection.
died, two children had left-sided hypoplasia.35 In a study with 39 women who had congenital aortic
stenosis (AS) and carried 49 pregnancies, Silversides et
Obstructive Outflow Tract Defects al report that although more than one-half had severe AS,
most of them were asymptomatic before pregnancy. Early
Pulmonary Stenosis cardiac complications, including pulmonary edema and atrial
arrhythmias, occurred in three pregnancies. One of those cases
Pulmonary stenosis (PS), the most common form of a right- was a woman with critical aortic stenosis who required urgent
sided obstruction, may occur as an isolated heart defect.29,30 percutaneous aortic valvuloplasty at 12 weeks’ gestation.
The clinical presentation depends upon the severity of the The severity of AS dictated cardiac complications (10%
obstruction and can vary from being asymptomatic with good occurred in severe AS, compared to none in mild or moderate
long-term outcomes as seen with mild stenosis, to the presence AS). Fetal complications included prematurity (8%), small
of right ventricular hypertrophy, right heart failure and sudden for gestational age (2%) and neonatal distress respiratory
cardiac death in uncorrected cases of severe pulmonary syndrome (6%).39
stenosis. Balloon valvuloplasty is therefore recommended In a follow-up study on late outcomes after pregnancy with
when the resting gradient across the right ventricular outflow congenital AS, Tzemos and Silversides et al reported that
tract is over 50 mm Hg or when the patient is symptomatic prior women with moderate or severe AS who were symptomatic
to conception. It need not be performed during pregnancy in during pregnancy were at higher likelihood of requiring
women who are asymptomatic or mildly symptomatic. Most cardiac interventions late after pregnancy. There were also at
women will tolerate a vaginal delivery.36,37 risk of experiencing a higher frequency of late cardiac events
Surprisingly, an excessive rate of noncardiac complications than those who had not been pregnant (31% vs. 0%).40
was reported in one multicenter study with 51 women with In another multicenter study, Yap et al followed-up
corrected pulmonary stenosis, who had 108 pregnancies, 53 successful pregnancies in 35 women (from a total of
788 including 21 (19%) miscarriages and 6 elective abortions. 58 pregnancies resulting in three miscarriages and two
abortions). The most serious cardiac complications (9.4%) changes in pregnancy cause some women to suffer aortic 56
were heart failure (3.8%) and atrial arrhythmia (5.7%). rupture and dissection during pregnancy or postpartum.
Interestingly, noncardiac complications were far more Women with CoA have been reported to have a higher risk
common with obstetric issues occurring in 22.6 percent and of hypertensive complications of pregnancy in many series.
perinatal complications in 24.5 percent. Hypertension-related The incidence of pre-existing hypertension complicating
disorders (including one case of eclampsia) were noted in pregnancy and pregnancy-induced hypertension are both
six pregnancies (11.3%). Fetal complications were mainly increased in this population.44,45 In a study by Krieger et al,
premature births in 7 (13.2%) and small for gestational age hypertension occurred in 24.1 percent of all women with CoA
births in 7 (13.2%). They concluded that pregnancy in women during their pregnancies, and 13.9 percent of those who were
with severe AS was associated with an increased incidence previously considered normotensive were diagnosed with
of heart failure, premature labor, and shorter duration of hypertensive disorders during pregnancy.45 Although the
pregnancy, with a higher likelihood of perinatal events in guidelines for the care of ACHD recommend vaginal delivery
women over the age of 30.41 in most cases, except in the setting of an obstetric indication
Preconception counseling is very important in women for cesarean delivery, this study noted that women with CoA
with AS. The risk of late cardiac outcomes after pregnancy have a higher rate of delivery by cesarean section and longer
should be considered in those with moderate to severe aortic hospitalizations, than seen in the general population.45
stenosis. Balloon valvuloplasty or aortic valve replacement Beauchesne et al reported 118 pregnancies in 50 women
(bioprosthetic) should be recommended before pregnancy. with CoA and found a 34 percent incidence of hypertensive
During gestation, in severely symptomatic women who are complications.46 Women with unoperated coarctation of aorta
unresponsive to medical management (mainly diuretics), often become hypertensive in the third trimester of pregnancy.
early delivery should be considered once fetal lung maturity They may develop paracoarctation aortic aneurysm/dissection
is achieved (usually around 36 weeks of gestation), so that and should have resection with end-to-end repair before
the mother can then undergo intervention or aortic valve conception. Unfortunately, risks persist in some women even
surgery. Those who cannot deliver the baby may require early after having the operation. These include hypertension (not
termination of pregnancy or relief of stenosis by percutaneous related to age at the time of repair), aortic root dissection and
balloon valvuloplasty or surgery. Although percutaneous rupture of berry aneurysms that occur even in normotensive
balloon valvuloplasty carries a risk of fetal radiation (partially patients. The residual aortic gradient was associated with an
reduced by abdominal shielding), it is preferred over surgery increased risk for hypertensive complications of pregnancy.46,47
for aortic valve replacement, since the later carries higher risk All patients should have adequate blood pressure control and
of maternal morbidity and fetal loss. aortic root monitoring. The goal is to maintain a systolic blood
High risk anesthesiologists should assist with hemodynamic pressure between 100 to 120 mm Hg and a diastolic blood
monitoring during labor and delivery in patients with moderate pressure between 60 to 80 mm Hg.
and severe AS. Vaginal delivery with an assisted second stage Hypertension in pregnancy has also been linked to adverse
of labor is the preferred mode of delivery, with cautious use fetal outcomes, including higher incidence of preterm
of adequate regional anesthesia in order to avoid a decrease delivery, low birth weight for gestational age and admissions
in systemic vascular resistance that may be poorly tolerated. to a neonatal intensive care unit.48
General anesthesia is preferred in women with severe aortic
stenosis undergoing a cesarean delivery.42 Cyanotic Congenital Heart Disease
Coarctation of Aorta Tetralogy of Fallot

Coarctation of aorta (CoA) is not just limited to focal Tetralogy of Fallot (TOF) is the most common cyanotic
stenosis, but is a variant of diffuse arteriopathy and associated congenital heart defect.29 Women with unoperated tetralogy
structural abnormalities of the great arterial walls.43 The of Fallot may experience increased cyanosis as systemic
narrowing of the aorta usually occurs at the junction of the vascular resistance decreases during the pregnancy. In most
distal aortic arch and the descending aorta, below the origin series, cardiac (4.5% to 18%), obstetric (11% to 20%) and
of the left subclavian artery.29,30 This defect is thought to neonatal (16% to 27%) events occurred during completed
be intrinsically associated with a diffuse vasculopathy with gestations. Unrepaired tetralogy as well as the presence
vascular and endothelial dysfunction. In addition, there are of pulmonary atresia have been reported as independently
histopathologic abnormalities in great arterial walls43 leading predictive of fetal prematurity, dysmaturity, fetal wastage, and
to arterial stiffness, endothelial dysfunction and endothelium- low infant birth weight.49-53
independent vascular dysfunction that predispose to While complete intracardiac repair improves maternal
hypertension. These structural abnormalities of the aorta and fetal outcomes depending on the prepartum functional
hypertension, the added stress from hemodynamic, hormonal class and biventricular function, adverse maternal events 789
10 may be associated with left ventricular dysfunction, severe in these studies, probably because of caution on the part of
pulmonary hypertension and severe pulmonary regurgitation obstetricians in these more vulnerable mothers and babies. The
with impaired right ventricular function.49 rate of antenatal complications was reported as significantly
The postventriculotomy scar exacerbated by a mechano- higher in a study by Gelson et al.60 They noted a more frequent
electrical disturbance caused by severe pulmonary regurgita use of epidural anesthesia, shorter length of the second stage,
tion, can trigger monomorphic ventricular tachycardia.54 An with both spontaneous and assisted deliveries, in the women
echocardiogram should be performed during every trimester with repaired TOF. Women with moderate to severe pulmonary
or when indicated, to measure aortic root dilatation since regurgitation also had small-for-gestational-age offsprings.
dissection has been reported in individuals with markedly Preconception counseling is very important in this
enlarged aortic root.55,56 The occurrence of CHD in the population in order to review the circulation with particular
offspring is as high as 6 percent of livebirths. The 22q11 attention to severe right ventricular outflow tract obstruction,
deletion is associated with DiGeorge syndrome and tetralogy severe pulmonary regurgitation and right ventricular
of Fallot.49 dysfunction. Since pregnancy carries the risk of arrhythmias,
In a retrospective review of 40 deliveries in 25 patients right ventricular failure and endocarditis, an elective-induced
with repaired TOF, Kamiya et al reported that 17.5 percent delivery should be planned once fetal lung maturity is
pregnancies were complicated by cardiac events (mainly due attained. A plan for delivery should be agreed and documented
to decline in functional class and arrhythmias). The main by the team taking care of the patient. Close follow-up and
predictors of adverse outcomes were history of ablation and the management of heart failure and arrhythmias is important.
increased baseline cardiothoracic ratio on chest radiography. If right ventricular failure occurs, preterm delivery should
While left ventricular size and function did not change with be considered. Vaginal delivery with low-dose combined
pregnancy, the right ventricle was enlarged at 6 months after spinal-epidural analgesia and assisted second stage of labor
delivery and could potentially affect the long-term prognosis is recommended. When cesarean delivery is indicated for
of women with repaired TOF.57 obstetric reasons, a low-dose combined spinal with incremental
In another large retrospective international multicenter epidural anesthesia, or incremental spinal catheter anesthesia,
study of 157 pregnancies in 74 women with corrected are both suitable. General anesthesia is usually reserved for
TOF, Balci et al reported 123 completed pregnancies with emergency situations.61 Invasive hemodynamic monitoring is
associated maternal cardiac events in 8.1 percent and not recommended, since there is a higher risk of complications
obstetric complications in 58.9 percent. There were adverse and limited clinical benefits. Noninvasive hemodynamic
fetal outcomes in 33.9 percent. The mortality in the offspring monitoring with periodic blood pressure readings, continuous
was 6.4 percent. The most important predictors of adverse telemetry to check for arrhythmias and pulse oximetry for
maternal outcomes were the use of cardiac medications before oxygen saturations are recommended.
pregnancy, prior surgery for pulmonary valve replacement It is important to note that the radial pulse will not be
(PVR) and the occurrence of arrhythmias before pregnancy. palpable on the same side as the Blalock-Taussig shunt.
Previous history of PVR was associated with arrhythmias, and All women should receive prophylaxis against bacterial
in one pregnancy, there was pulmonary embolism along with endocarditis and deep venous thrombosis.
arrhythmias, while another pregnancy in the PVR group was
complicated by arrhythmias and heart failure.58 Dextro or d-Transposition of the Great Arteries
The use of cardiac medications before pregnancy was also
associated with birth of significantly small-for-gestational- In d-Transpostion of the great arteries (d-TGA), there
age babies. The reason for the association between adverse is ventriculoarterial discordance due to the transposed
maternal/fetal events and the use of cardiac medications pulmonary artery and the aorta.29 Most women with d-TGA
before pregnancy, may reflect a need based on less favorable have previously undergone an atrial switch repair (Mustard
baseline cardiac condition in terms of ventricular function and or Senning procedure) and their morphological right ventricle
history of arrhythmias. The use of cardiac medication before is the systemic ventricle that pumps into the aorta. Currently,
pregnancy was noted in 71 percent of women with PVR and more women with arterial switch repair (Jatene procedure)
right ventricular dysfunction, indicating late timing of PVR. are entering into their child-bearing years.
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 Atrial Switch Repair
A possible relation between severe pulmonary regurgitation In a multicenter study, Canobbio et al reported that in women
and symptomatic right heart failure has been noted in other with atrial switch repair (Mustard or Senning procedure), there
series.59 were cardiac complications, primarily heart failure and atrial
The threshold for performing cesarean delivery for arrhythmias, most often in the third trimester, in 36 percent
790 obstetric/offspring reasons appears to be lower than usual of the pregnancies. There were two maternal deaths after
delivery. The fetal complications seen in 39 percent included a events occurred during or after any pregnancy. Two women 56
high rate of fetal wastage, low birth weight and prematurity.62 with dilated aortic roots did not have progressive enlargement
Similar risks have been shown by other studies.63-66 The in pregnancy or postpartum. No maternal mortality was
systemic (morphologic right) ventricle is likely to become reported in this study nor were there any significant adverse
further dilated with volume load of pregnancy. The success of fetal outcomes other than one small-for-gestational-age baby
pregnancy is related to function of the systemic right ventricle born to a mother who had multiple comorbidities.68
prior to pregnancy, as well as the degree of aortic and tricuspid
insufficiency.65 Congenitally Corrected Transposition
A more recent study by Metz et al prospectively followed of the Great Arteries
the right ventricular function through pregnancy and the
postpartum period.67 There was a fall in the systemic right In congenitally corrected transposition of the great arteries
ventricular function in 89 percent women during pregnancy (CCTGA) there is transposition of the great arteries
and although there was an improvement in the postpartum (ventriculoarterial discordance) and ventricular inversion (AV
period, the baseline function was not regained completely. discordance). Although the circulation is physiologically)
The degree of tricuspid (left AV valve) regurgitation also corrected, the morphologic right ventricle is the subaortic
progressed, but improved after delivery. A unique observation sytemic ventricle. Commonly associated defects are
was the high rate of atrial baffle obstruction that occurred in ventricular septal defect and pulmonary stenosis.29
36 percent women during pregnancy, as compared with only Women with unoperated defects may have worsening
5 percent reported in the all patients after an atrial switch cyanosis, risk of stroke because of microcytosis, paradoxical
procedure. In all women, the superior limb of the systemic emboli and systemic emboli (with severe right ventricular
venous atrial baffle was obstructed significantly (and was cardiomyopathy). Heart failure occurs due to systemic
probably unmasked by the increased venous return that ventricular dysfunction and severe tricuspid regurgitation
occurs during pregnancy). The baffle obstructions required in both unoperated and operated cases.69,70 In those with
intervention in the postpartum period. 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
Arterial Switch Repair (6–27%) and the occurrence of CHD in the offspring varies
As the women with arterial repair for d-TGA plan to have from 2 to 18 percent.70
pregnancies, the potential long-term residual and sequelae of Management issues during pregnancy are usually related
this surgery have to be taken into account. Limited data are to heart failure or atrial arrhythmias. Fluid retention is treated
available regarding pregnancy in this population. with gentle diuresis. Rate control in atrial arrhythmias may be
Despite pulmonary artery banding before surgery to train achieved by using beta blockers (propranolol). Direct-current
the left ventricle to take over as the systemic ventricle, left (DC) cardioversion is safe when there is hemodynamic
ventricular function may still deteriorate gradually after instability. Ideally women with history of arrhythmias should
arterial switch operation in patients with d-TGA and an intact consider radiofrequency ablation (RFA) prior to carrying a
ventricular septum. Right ventricular outflow obstruction pregnancy. Women with unimpaired systemic ventricular
(subpulmonic stenosis/infundibular stenosis) is commonly function who are tolerating the pregnancy well may carry it
noted and may require intervention in 10 percent of the cases. to term and have an elective induced vaginal delivery with
Coronary events may occur in 7 percent due to an abnormal assisted second stage of labor under epidural anesthesia.
coronary anatomy or coronary ostial fibrosis at the site of the Those who are markedly symptomatic may need to deliver
reimplanted coronaries, or due to kinking, torsion or extrinsic as soon as fetal lungs are mature. Hemodynamic monitoring
compressions that require immediate surgery. should be noninvasive with blood pressure checks, telemetry
Tobler et al retrospective studied the prevalence of adverse to check for arrhythmia and pulse oximetry instead of invasive
maternal cardiac events during pregnancy in nine women monitoring.71
with arterial repair, who had 17 pregnancies. There were
four miscarriages. Five women had clinically important Ebstein Anomaly
valve lesions and one had left ventricular dysfunction prior
to pregnancy. Cardiac complications occurred in two women; Women with unoperated Ebstein anomaly of the tricuspid
nonsustained ventricular tachycardia was noted in one valve may develop increased cyanosis because of the right-
woman with impaired left ventricular systolic function and to-left shunt through an interatrial shunt. Right heart failure
postpartum valve thrombosis occurred in another woman may develop from severe tricuspid regurgitation and right
with a mechanical mitral (systemic atrioventricular) valve. ventricular dysfunction. Supraventricular tachycardia may
Although the left ventricular function deteriorated during occur because of an accessory pathway associated with Wolff-
pregnancy in two women, no pulmonary edema or ischemic Parkinson-White (type B) syndrome.12 791
10 In women with operated Ebstein anomaly, the outcomes Eisenmenger Syndrome
during pregnancy depend on baseline functional NYHA class,
adequacy of tricuspid valve repair or replacement, arrhythmias Eisenmenger syndrome (ES) is characterized by irreversible
related to an accessory pathway.72 pulmonary vascular disease and severe pulmonary

Women with an accessory pathway should be advised hypertension in the presence of reversal of a shunt (right to
to have RFA before planning a pregnancy, in order to left shunt).29 Interestingly, adults with ES have better survival
reduce the incidence arrhythmias or the use of medications and more favorable hemodynamics than those with idiopathic
needed to control them during pregnancy. Adenosine or DC pulmonary arterial hypertension.
cardioversion according to advanced cardiac life support Maternal mortality rates of 30 to 52 percent in ES are
protocol can be used to terminate SVT during pregnancy. largely due to the inability of the relatively fixed pulmonary
Overall, in the absence of significant maternal cyanosis vascular resistance to adjust to the cardiovascular demands
or arrhythmia, pregnancy is usually well tolerated. Fetal of pregnancy, delivery and puerperium. Death usually occurs
outcomes depend upon maternal cyanosis, since it contributes during delivery or most commonly in the 1st to 6th weeks
to an increased risk of prematurity and dysmaturity.73 post partum. Spontaneous abortions may occur in 40 percent.
The level of pulmonary arterial pressure before or in the early
Univentricular Heart stage of pregnancy is an important predictor of pregnancy
outcome.77,78 Fetal outcomes are poor, with prematurity in 55
The univentricular heart (single ventricle physiology) is char- percent, low birth weight in 30 percent and perinatal mortality
acterized by a large dominant ventricle (more commonly the in 28 percent.77
left ventricle) and a small rudimentary ventricle. Associated Despite medical advances, the prognosis of pregnancy
heart defects include atrioventricular (AV) valves defects, in women with ES remains dismal.78-82 Pregnancy is
transposition of the great arteries and intracardiac shunt contraindicated in women with Eisenmenger’s syndrome.
defects.29 Right ventricular hypoplasia with tricuspid atresia is Contraception should be offered to all women with ES during
the commonest form. Majority of the women have had a prior their child-bearing years. Combined oral contraceptives
Fontan procedure (classic Fontan involving a right atrium to carry an increased risk of thrombosis, while progesterone
pulmonary artery conduit, also called atriopulmonary con- only contraceptives have a high failure rate as noted in the
nection)74 or one of its modifications, such as direct connec- section on contraceptive issues. Laparoscopic sterilization
tion between the systemic venous return and the pulmonary with general anesthesia carries risk. The best options in
artery, also called the total cavopulmonary connection (TCPC). these women are the intrauterine coil and subdermal devices.
Long-term issues in women with Fontan procedure are related Medical termination of pregnancy should be addressed very
to low cardiac output, increased venous pressure and con- early, since procedures in later pregnancy carry a higher risk.
gestion. Exercise tolerance may be reduced due to impaired In women who choose to carry on with pregnancy despite
ventricular function and difficulty in increasing preload. having informed risks about high rates of mortality associated
Canobbio et al reported that the major maternal with pregnancy and ES, a detailed group discussion between
complications related to pregnancy are heart failure, atrial the medical/obstetric/clinical social worker team and the
arrhythmias (atrial fibrillation and flutter) and thromboembolic patient with her family should occur and be documented in
complications related to intracardiac thrombi formed despite the medical records.
antiplatelet therapy or anticoagulation.75 Arrhythmias, usually These women will require very close monitoring during
supraventricular, were reported in 26 percent of pregnancies their pregnancy with coordination between a multidisciplinary
and most often associated with the classic Fontan.76 team for early detection and treatment of pregnancy-induced
There is an increased risk of first trimester miscarriages complications. Heart failure during pregnancy is common
(33%) and occurrence of CHD in the offspring. Due to preterm and should be treated promptly with gentle diuresis. If the
rupture of membranes, premature labor and delivery between pregnancy lasts until the third trimester, hospitalization for bed
26 and 33 weeks, the fetal complications are prematurity and rest and supplemental oxygen is recommended and there is a
low birth weight. There is a significant risk of postpartum high likelihood of preterm delivery. Although these women are
hemorrhage.75,76 at high risk for thrombosis as well as hemorrhage, there are no
These women should avoid dehydration during pregnancy specified guidelines regarding the use of anticoagulation and it
and especially during labor and delivery, because volume remains controversial. Adequate hydration and antithrombotic
depletion can lower the central venous pressure and blood pumps with support hose stockings should be used to reduce
flowing through the cavopulmonary connection to the lungs. the risk of deep venous thrombosis.
In order to prevent aortocaval compression by the gravid Pulmonary vasodilators may be considered, other than the
uterus, the left lateral position is very important when lying use of endothelin antagonists, which are contraindicated in
down. General anesthesia should be avoided for a cesarean pregnancy. Inhaled nitric oxide may be useful, particularly
792 delivery, since positive pressure ventilation will decrease the in the peripartum period, since it increases pulmonary blood
pulmonary blood flow.61 flow and improves systemic arterial oxygen saturations in
patients with pulmonary hypertension.82 Invasive pulmonary Anticoagulation especially in the postpartum period may be 56
artery monitoring can be very dangerous should therefore prescribed to very high-risk patients.87
be avoided. The intravenous administration of pulmonary
vasodilators carries a risk of clinical deterioration despite Anticoagulation
theoretically improving the pulmonary hypertension, by
causing a fall in systemic vascular resistance, an increase in The biggest challenges in anticoagulation during pregnancy
right-to-left shunting, worsening hypoxemia, acidosis and are the mechanical prosthetic valves.88 In a study of 33 women
decreased coronary artery perfusion.83 with 82 pregnancies, the risk factors for valve thrombosis
An elective cesarean delivery is usually scheduled between were based on type (mechanical), position (mitral), number
30 and 34 weeks of pregnancy, when the fetus is viable and of prosthetic valves, arrhythmias, previous thrombosis
before the occurrence of maternal hemodynamic compromise. and adequacy of anticoagulation. All fetal complications,
General anesthesia should be avoided and low-dose sequential stillbirths, spontaneous and therapeutic abortions, occurred
combined spinal-epidural or incremental spinal anesthesia is in women taking warfarin (5 mg or higher). Low-molecular
recommended, since both allow slow titration with minimal weight heparin use was associated with intrauterine growth
effects on the peripheral circulation.61 Close monitoring is retardation in 22 percent of the offspring. No anticoagulation
carried into the postpartum, since there continues to be a very regimen conferred complete protection from thromboembolic
high incidence of maternal mortality. phenomena in pregnancy.89
The protocols for anticoagulation during pregnancy should
COMMON MANAGEMENT ISSUES IN PREGNANCY be individualized and based upon patient preference and risk
profile. Some prefer warfarin, except, in the first trimester and
Endocarditis Prophylaxis 2 weeks before delivery, during which period unfractionated
heparin or enoxaparin is used. Others advocate subcutaneous
The American College of Cardiology (ACC)/American Heart unfractionated heparin (UFH) or enoxaparin throughout
Association (AHA) guidelines in 2007 advocate intravenous pregnancy followed by a switch to intravenous heparin two
antibiotic prophylaxis, at the onset of labor, in women with days before elective delivery.90-94 For higher risk patients,
moderate to high risk CHD.84 This comprises all CHD except warfarin dose should be adjusted to keep International
for an isolated or repaired atrial septal defect (6 months Normalized Ratio (INR) 2.5 to 3.5 and they should receive
after closure), repaired ventricular septal defect with no an aspirin 81 mg oral daily when UFH or enoxaparin is given
residual shunt, surgically ligated patent ductus arteriosus and to maintain a trough anti-Xa levels more than or equal to 0.8
extracardiac, cardiac pacemakers and defibrillators. IU/ml and peak anti-Xa levels less than 1.5 IU/ml. The anti-
The standard dosage of antibiotics are ampicillin 2 gm Xa levels should be monitored every 2 weeks, since the body
intravenous (IV)/intramuscular (IM) and gentamicin 1.5 mg/ surface area and the drug volume of distribution are constantly
Kg initially and second dose of ampicillin 1 gm IV/IM or changing in pregnancy.
orally 6 hours later. Vancomycin (1 gm IV over 1–2 hours)
plus gentamicin are used if the patient is allergic to penicillin. Aortic Root in Pregnancy
Due to the low risk of bacteremia, the guidelines do not advocate
prophylaxis for an uncomplicated vaginal or cesarean delivery. Many CHDs are associated with structural abnormalities
Since it is not possible to predict obstetric complications, most of the great arterial walls that lead to dilatation of the aorta
centers prefer to administer antibiotics at time of the rupture and/or the pulmonary arteries.43 Progressive dilatation of the
of the membranes during a vaginal delivery, because of the aortic root can occur in women with a bicuspid aortic valve,
high morbidity or mortality associated with endocarditis. No coarctation of aorta, large ventricular septal defect, tetralogy
major toxicities have been reported with dosage for bacterial of Fallot/pulmonary atresia with ventricular septal defect and
endocarditis prophylaxis.85 Concerns about inappropriate in truncus arteriosus.
obstetrical use of antibiotics mainly apply to situations other The potential risk of forming an aneurysm or dissection
than for bacterial endocarditis prophylaxis.86 is the highest at the time of labor and delivery because of a
surge in the cardiac output. Due to estrogen withdrawal, the
Deep Venous Thrombosis risk may continue to be high in the postpartum period. An
elective cesarean delivery is recommended in women with a
All women are hypercoagulable during pregnancy and have an dilated aortic root that is progressively increasing in size. The
increased risk of deep venous thrombosis (DVT), pulmonary risk of rupture/dissection rises when the diameter reaches 5 to
embolism, paradoxical embolism and stroke depending upon 5.5 cm or if dilatation of the aortic root progresses at the rate
the associated underlying cardiac defects. These women of 1 cm or greater per year.95 Asymptomatic women should
should be educated about preventive measures such as regular consider undergoing prophylactic aortic root repair prior to
ambulation, adequate hydration and support stockings. conception, even though the surgical risk associated with 793
10 aortic root surgery averages around 2.5 percent.96 According be used for rate control in the second and third trimesters. Anti-
to the clinical practice guidelines for thoracic aortic disease, arrhythmic agents should be avoided during the first trimester,
operative repair is indicated in symptomatic patients with since there are limited data on the safety of their use in
aortic diameter over 4.4 to 5 cm and/or growth greater than pregnancy. Women with effective antitachycardia pacemakers
0.5 cm per year, in ascending aortic aneurysms associated with or implantable defibrillators, who take medications to reduce
Marfan syndrome, bicuspid aortic valve or other genetically- the frequency of overdrive pacing or discharge, can stop
medicated disorders that are at high risk for dissection. The antiarrhythmics during the first trimester. The preferred and
aortic root should be assessed annually if the diameter ranges safe method for terminating hemodynamically compromising
from 3.5 to 4.4 cm and semiannually if it is 4.5 to 5.5 cm.97 atrial arrhythmias during pregnancy is by DC cardioversion.100
Prior to conception, women undergoing an intracardiac
surgery for another indication should be considered for a Bradyarrhythmias
concomitant aortic root repair, if the aortic root is over 4 cm.
It is recommended that preconception transthoracic Women with pacemakers for sick sinus syndrome or
echocardiographic assessment of the aortic root dimensions30 chronotropic incompetence should have the lower rate limit
be performed, along with serial echocardiograms to document of the pacemakers increased to match the physiological heart
changes in aortic dimensions at 20 to 24 weeks of pregnancy rate increase during pregnancy. In women with re-entrant
and monthly thereafter until 4 to 6 weeks postpartum. type of arrhythmia potentially induced by premature atrial
beats, the lower rate limit of the pacemaker may be elevated
Arrhythmias to overdrive suppression of premature beats and decrease the
frequency of tachycardia.100
The severity and frequency of arrhythmias increases with The obstetric team should be aware that high doses of
hemodynamic changes in pregnancy. The relation between magnesium when used for treating pre-eclampsia or eclampsia
symptoms and cardiac arrhythmias was studied in 110 can increase pacing thresholds and this may lead to pacemaker
consecutive pregnant patients without evidence of heart failure to capture. This is especially important when there is
disease referred for evaluation of palpitations, dizziness and impaired renal function.
syncope. Holter monitoring showed an increased incidence
of mostly atrial and ventricular premature complexes (VPCs) Heart Failure
during pregnancy with a substantial reduction in the incidence
in the postpartum period. Although the number of simple Women with moderate or severely reduced systemic
and multifocal VPCs was higher in symptomatic patients, ventricular function and/or NYHA functional class III and
there was no significant correlation between the incidence of IV are at high risk for maternal complications and should be
arrhythmias and symptoms. Only 10 percent of symptomatic advised against pregnancy. There is cumulative effect of all
documented episodes correlated with the presence of pregnancies, including miscarriages and abortions, on the
arrhythmias.98 systemic ventricular function.101
Women with CHD are at increased risk of presenting for the In case of mild to moderate systemic ventricular
first time with a symptomatic arrhythmia during pregnancy or dysfunction, heart failure medications including angiotensin-
if previously diagnosed, are at the risk of recurrence of their converting enzyme (ACE) inhibitors and aldosterone
arrhythmias.99 In women with complex CHD, uncontrolled antagonists such as spironolactone, should be prescribed for
maternal arrhythmias can cause hypotension and decreased a year before considering pregnancy, with reassessment of
cardiac output, leading to poor perfusion of the placenta systemic ventricular function prior to conception. Since these
and fetus with possible premature deliveries of small-for- two medication classes are listed as pregnancy risk category
gestational-age babies. D, they should be stopped once the woman is planning
After considering the risk/benefit ratio for the mother and pregnancy. Other heart failure medications such as diuretics,
the fetus, antiarrhythmic therapy should be restricted for certain beta blockers (especially propranolol) and digoxin may
use in management of intolerable symptoms or intractable be continued during second and third trimester of pregnancy.
arrhythmias that may be potentially harmful to the fetus. Acutely decompensated heart failure in pregnant women
Based on the data from observational reports, most available requires admission to the cardiac care unit with 100 percent
antiarrhythmic drugs are classified as in pregnancy risk oxygen, diuretics and vasopressor support as indicated.
category C. Concerns regarding fetal safety should be set aside, while
trying to stabilize the mother. The patient should lie in the
Tachyarrhythmias left lateral position to improve her cardiac output. Invasive
monitoring is rarely indicated and should be avoided as far as
Adenosine may be used safely to diagnose or terminate a possible. Noninvasive methods of monitoring are preferred.
794 supraventricular tachycardia. Beta blockers and digoxin may Once stabilized, a woman in her third trimester, should be
considered for an induced delivery as soon as fetal lung may be adequate for anticoagulation in most cases, one may 56
maturity is achieved. require a higher dose of 2.5 to 3.0 for mechanical prosthetic
valve. Careful monitoring is required, since the volume
Common Cardiac Medications in Pregnancy of distribution of the drug is constantly changing during
pregnancy. Since fetal adverse effects are dose-related, women
Since none of the cardiac medications are absolutely safe for are advised to avoid dietary/supplemental intake of vitamin K,
the fetus during pregnancy, their use should be limited and so that daily dose of 5 mg oral or less may be required for
considered carefully only after reviewing the indications, adequate anticoagulation.91 It should be discontinued 2 weeks
safety data and pregnancy risk category classification before an elective delivery and replaced by unfractionated
(Table 2). Nursing mothers are advised to avoid feeding their heparin.
infants when the expected plasma concentration of the drugs
is the highest, even if no major clinical effects on infants have Side Effects
been reported for that particular medication.102
Some of the more commonly prescribed cardiac ‘Warfarin embryopathy’ is characterized by nasal hypoplasia
medications are discussed in this chapter. More up-to- and chondrodysplasia punctata that can occur in 6.4 percent
date information on cardiac medications in pregnancy live births.91 There is a potential effect on childhood growth
can be obtained from the US. Department of Health and and development.103 In addition, there is an increased risk of
Human Services, Office on Women’s Health (http://www. fetal hemorrhage and wastage.
womenshealth.gov/publications/our-publications/fact-sheet/
pregnancy-medicines.pdf) and from another website: www. Contraindications
drugs.com.
Warfarin should be avoided in the first trimester and its use
Warfarin should be restricted for anticoagulating mechanical valves in
second and third trimesters. An informed consent should be
Warfarin is classified as pregnancy category X. It inhibits obtained from the patient before prescribing it.
vitamin K-dependent coagulation factors, proteins C and S.
Low-molecular Weight Heparin
Standard Dosage
Enoxaparin is classified as pregnancy category B and is a
Dose is adjusted for the lowest INR required for adequate subcutaneously administered anticoagulant. It has a lower risk
anticoagulation for an indication. While a dose of 2 to 2.5 of osteoporosis than unfractionated heparin.104,105
Table 2

Classification of medications in pregnancy
Pregnancy Definition of the category Some commonly used medications in this category
category
A Controlled human studies showed no fetal risk Folic acid
B Controlled human studies have not shown fetal risk despite Amoxicillin
adverse findings in animal studies
or
Inadequate data from human studies, but animal studies
showed no fetal risk.
C Inadequate data in human and animal studies. More likely Most cardiac medications including low dose aspirin,
to have beneficial effects when used cautiously furosemide, digoxin, most beta blockers (except
atenolol), nitrates, hydralazine, adenosine, calcium
channel blockers and adenosine
D Data from human studies or subsequent use in humans Atenolol
demonstrates fetal risk Angiotensin-converting-enzyme (ACE) inhibitors
Drug may be rarely acceptable if needed in a life-
threatening situation or serious disease for which safer
drugs cannot be used
X Contraindicated in pregnancy Warfarin
Human and animal studies data show a very high risk of
adverse effects to the fetus 795
Based on the FDA system of classification: www.fda.gov
10 Standard Dosage for stroke prevention and as conjunctive therapy in high risk
mechanical valves. Its use should be stopped 2 weeks before
The dose is adjusted according to weight, creatinine clearance delivery to avoid bleeding, prolonged gestation/labor and
and depending upon the indication. It is usually injected premature closure of fetal ductus arteriosus.
subcutaneously every 12 hours and held for at least 8 hours
(ideally for 24 hours) before an invasive procedure. In order Standard Dosage
to ensure adequate anticoagulation, the antifactor Xa levels
should be checked biweekly, 4 to 6 hour after an injection Low dose aspirin, 75 to 162 mg oral daily.
and maintained between 1.0 to 1.2 U/ml.89,91
Main Side Effects
Side Effects
Bleeding, low birth weight.
Bleeding and hematomas.
Contraindications
Contraindications
Allergic rhinitis/nasal polyps, salicylate hypersensitivity.
Bleeding, heparin-induced thrombocytopenia (HIT), uncon-
trolled hypertension. Avoid intramuscular injections and use Diuretics
in labor/delivery, since hematoma and bleeding are major
complications.106 Loop diuretics such as furosemide are in pregnancy category
C and are used to decrease fluid retention by increasing
Unfractionated Heparin urinary sodium excretion. They provide rapid symptomatic
relief in heart failure.
Unfractionated heparin is in pregnancy class C. It mediates
antithrombotic properties through an interaction with Standard Dose
antithrombin III and does not cross the placenta.
The initial dose is 20 mg oral daily, which is titrated to
Standard Dosage increase urine output and decrease weight by 0.5 to 1 kg daily.
Excessive diuresis should be avoided, since low cardiac output
Subcutaneously injected with an average dose of 5,000 decreases uterine perfusion and leads to fetal hypoperfusion.
to 10,000 U every 8 to 12 hours adjusted to body weight, Rare teratogenicity effects are oligohydramnios, intrauterine
or may be given as continuous intravenous infusion that growth restriction, hypospadias, and neonatal death from
is titrated to achieve an activated partial thromboplastin renal failure.
level (APTT), which is 1.5 to 2.5 times the normal value.91
It should be stopped 2 hours before delivery (vaginal or Main Side Effects
cesarean) and resumed 4 hours after, if it there are no contra
indications. Hypotension, electrolyte depletion (hypokalemia) and
azotemia. Serum electrolytes and creatinine should be
Contraindications monitored regularly. Potassium should be replenished to
maintain serum potassium levels between 4 and 5 meq/L.
Thrombocytopenia, hemorrhage (except in disseminated
intravascular coagulation). Beta Blockers
Side Effects Most beta blockers are in pregnancy category C except

atenolol, which is listed in category D. They inhibit
Bleeding, heparin-induced thrombocytopenia (HIT), maternal adverse effects on the sympathetic nervous system in heart
osteoporosis. failure. Most of the data comes from their use in gestational
hypertension. Although carvedilol (alpha-1, beta-1 and -2
Aspirin adrenergic receptor blocker) is the most effective beta blocker
in stable heart failure, its use in pregnancy is limited. The
A low dose of aspirin belongs to pregnancy class C, while clinical responses may not be apparent, until after several
a full dose of 325 mg dose is considered as pregnancy class weeks of therapy.
D in the third trimester. Aspirin is a potent inhibitor of Propranolol has a longer safety record, but its use is
796 prostaglandin synthesis and platelet aggregation. It is used primarily limited to heart rate control in pregnant women
with atrial arrhythmias, valvular stenosis, or significant left Contraindications 56
or right outflow tract obstruction. Propranolol or labetalol
are used to reduce the hemodynamic stress on the dilated Digoxin use is avoided in patients with obstructive left ventricular
aorta, even though the evidence of benefit is limited in those outflow tract lesions, WPW syndrome, sinus node dysfunction,
without Marfan syndrome. conduction disease, and in the presence of renal impairment.
Since beta blockers cross the placenta, fetal bradycardia
and hypoglycemia may occur. Although teratogenicity is low, Hydralazine
preterm labor, prematurity and intrauterine grown retardation
may occur due to reduce uterine blood flow. Low birth- Hydralazine is in pregnancy class C and acts by direct
weight babies have been reported, especially with the use of arteriolar vasodilatation and may be used for management of
atenolol.107 heart failure and hypertension.
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.
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 Contraindications

daily for better rate control.
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 Isosorbide dinitrate is in pregnancy class C. It acts by
sugar levels should be monitored. relaxing the vascular smooth muscle through the endothelial-
independent pathway. Prolonged use of nitrates often causes
Contraindications tolerance and loss of the beneficial hemodynamic effects.
Limited data is available regarding its use during pregnancy.
Asthma or active bronchospasm, sinus node dysfunction, Isosorbide dinitrate has been associated with fetal heart rate
conduction disease, and florid pulmonary edema. decelerations in cases of maternal hypotension.
Digoxin Standard Dose

Digoxin belongs to pregnancy category C and since it crosses Isosorbide dinitrate initiated at 10 mg, titrated to 30 to 40 mg,
the placenta, it may cause prematurity and intrauterine growth three times daily along with hydralazine if tolerated.
retardation. It acts by inhibiting sodium-potassium adenosine
triphosphate and increasing the cardiac contractility. Treatment Main Side Effects
for 1 to 3 months can improve heart failure symptoms in
pregnancy. Headache, postural hypotension.
Standard Dose Contraindications

The average dose of digoxin is 0.125 to 0.25 mg daily when Hypotension, severe anemia or cerebral hemorrhage.
the renal function is normal. A loading dose is not necessary,
even if maternal serum levels are low. Adenosine
Main Side Effects Adenosine belongs to pregnancy class C and is the most
rapidly acting endogenous modulator of smooth muscle tone
Digoxin toxicity usually occurs in those with renal impairment that is often used to treat supraventricular tachycardia. No
and abnormal serum potassium levels. fetal adverse effects have been reported. 797
10 Standard Dose They have not been extensively studied for other indications
or in the first and second trimesters. Short-term use may be
A rapidly administered intravenous injection of 6 mg followed indicated for heart rate control in late pregnancy.
by 12 mg twice, if the desired effect is not achieved. Each

injection should be promptly followed by a bolus of 10 Cardiac Procedures in Pregnancy
ml of intravenous saline through the same site to flush the
medication rapidly through the circulation. Cardiac Catheterization and Interventions
Main Side Effects Due to the high likelihood of teratogenic effects, fetal demise
and increased risk of malignancy in late childhood, radiation
Bronchoconstriction may occur in asthmatics. Sinus exposure with fluoroscopic diagnostic/interventional cardiac
bradycardia or AV block are short-lasting and resolve procedures holds a major concern during the first trimester
spontaneously. of pregnancy and should be avoided. Abdominal shielding
is used for all procedures requiring fluoroscopy to minimize
Contraindications fetal radiation exposure.
Avoid in bypass tract-mediated narrow QRS supraventricular

tachycardia (may precipitate atrial fibrillation), high degree Valvuloplasty
AV block, sick sinus syndrome. If a woman has critical aortic or mitral stenoses, with recurrent
heart failure refractory to medical therapy, pregnancy may
Flecainide not be well tolerated due to volume overload, especially
during the late second and third trimesters. Balloon dilatation
Flecainide is a class I C antiarrhythmic agent that belongs to valvuloplasty may be performed after 24 weeks to allow her
pregnancy class C and is prescribed only by cardiologists/ to tolerate the remaining pregnancy. In case of critical aortic
electrophysiologists after careful risk assessment followed stenosis, the valvuloplasty serves only as a bridge to surgery.
by close monitoring. While efficient placental transfer can
cause adverse fetus effects, it is sometimes used to treat fetal
arrhythmias. Electrical Cardioversion
Synchronized electrical cardioversion may be performed when
Indications atrial tachyarrhythmias are not well tolerated and associated
with heart failure, syncope or suboptimal response to medical
Suppression of documented sustained ventricular tachycardia. therapy. There are potential risks of thromboembolism during,
anesthesia or conscious sedation. Although the likelihood of fetal
Standard Dose arrhythmias is rare, fetal electrocardiography monitoring should
be performed during the procedure and in early recovery. There is
100 mg every 12 hours, increase by 100 mg/day every 4 days a remote possibility of synchronized direct current shock falling
to a maximum of 400 mg/day with dose adjusted for renal or onto the vulnerable phase of the fetus’s action potential leading to
hepatic impairment. potentially life-threatening arrhythmias.
Anticoagulation prior to cardioversion is not required
Main Side Effects for supraventricular tachycardia or when atrial flutter is
documented to be of less than 24 hours in duration. A
Maternal hypotension, potentially proarrhythmic in CHD. transesophageal echocardiogram to exclude an intracardiac
Severe toxicity may easily occur with flecainide’s narrow thrombus can be performed just prior to the cardioversion, in
therapeutic index. hemodynamically stable patients at high risk of having a clot.
Energy doses required for monophasic/biphasic synchronized
Contraindications shock should be the same as those used for the general
population and according to the current Advanced Cardiac
Pre-existing high degree AV blocks, chronic atrial fibrillation, Life Support (ACLS) guidelines. The transthoracic impedance
systemic ventricular dysfunction. does not significantly change with pregnancy.100
Calcium Channel Blockers

Electrophysiological Procedures
Calcium channel blockers are pregnancy class C and their Whenever possible, the need for radiofrequency ablation (RFA)
798 use has been limited to late pregnancy for preterm labor. or device implantation should be assessed prior to pregnancy.
RFA may be performed for intractable arrhythmias such as one may lose both if maternal blood flow is not promptly 56
paroxysmal supraventricular tachycardia that are unresponsive restored.109,110
to pharmacological therapy and pose a significant maternal-
fetal risk. This procedure can be cautiously performed during
the late second or third trimesters, with maternal abdominal Surgical Procedures
shielding to minimize fetal radiation exposure. All nonobstetric surgical procedures, other than emergency
operations, are best avoided during pregnancy.
Pacemakers LABOR AND DELIVERY

Women with CHD, especially those with congenitally
corrected transposition of the great arteries, d-transposition of During labor, there is a surge of blood flow into the maternal
the great arteries, post-Fontan procedure, large atrioventricular circulation, with 300 to 500 ml being released with each
(AV) septal defect may have symptomatic bradyarrhythmias uterine contraction. This leads to nearly a 25 percent increase
during pregnancy. This may occur due to underlying sinus in cardiac output. In addition, pain and anxiety lead to a rise
node dysfunction, AV node dysfunction, high degree in blood pressure and heart rate, which in turn leads to another
conduction heart block such as second degree (Mobitz II) or rise in cardiac output by 40 to 50 percent. The cardiac output
third degree heart block. These conduction abnormalities may peaks an hour after delivery. Adequate analgesia and anesthesia
be unmasked by the higher heart rate demand and increased during the active labor and delivery is necessary to allay pain
cardiac output during pregnancy. Transvenous or epicardial or anxiety. Epidural anesthesia without epinephrine shows
pacemaker implantation can be performed with relatively hemodynamic stability throughout delivery with a small rise
low maternal and fetal risk. Abdominal shielding is used to in cardiac output.5 Women with residual intracardiac shunts
minimize fetal radiation exposure during fluoroscopy. Women should have intravenous particle filters to reduce the risk of
with complex cardiac lesions and/or arrhythmias resistant to paradoxical thromboembolic events.
conventional therapies should be referred to regional centers The left lateral position is favored during labor and
for consultation and management.100 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,
Automatic Implantable Cardiac Defibrillators there is an increase in venous return due to relief of inferior
Women with long QT syndrome with family history of sudden vena caval compression and a shift of blood from the uterus
cardiac death or palliated tetralogy of Fallot with monomorphic to the systemic circulation. The maximum volume shifts
ventricular tachycardia should have an automatic implantable occur in the first 48 to 72 hours leading to highest incidence
cardiac defibrillators (AICD) implanted before considering of major cardiovascular complications including heart failure,
pregnancy. No major maternal/fetal complications have been arrhythmias and maternal mortality. These women should be
reported with their use during pregnancy.108 monitored and discharged only when stable.
Mode of Delivery
Cardiopulmonary Resuscitation
Unfortunately, cardiac arrest occurs in 1:30,000 pregnancies. The preferred mode of delivery is vaginal, with a facilitated
Women with CHD have a higher risk of sudden death from second stage of labor.
postventriculotomy scar causing ventricular tachycardia, or An elective induced delivery is preferred in women with
from severe cardiomyopathy or aortic dissection. Other causes complex CHD or high risk factors, usually after 37 to 38
include amniotic fluid embolism, eclampsia, drug toxicity, weeks when fetal lung maturity is achieved. Nearly all women
massive pulmonary embolism and hemorrhage. with CHD should deliver at a center with high risk obstetrics,
Cardiopulmonary resuscitation should be performed neonatology, pediatric cardiology and adult CHD specialists.
according to the standard ACLS algorithms. The pregnant All patients need hemodynamic noninvasive monitoring
woman should be moved to the left lateral decubitus position of blood pressure, heart rate, pulse oximetry. Telemetry is
to relieve inferior vena caval compression, improve venous indicated if there is a likelihood of developing arrhythmias.
return, and increase her cardiac output. The chest compressions Cesarean delivery is mainly performed for obstetric
are higher on the sternum to adjust for the elevated diaphragm indications, or in women on anticoagulation therapy with
caused by the gravid uterus. Emergency hysterotomy should warfarin, in order to avoid the potential risk of fetal intracranial
be performed within 4 to 5 minutes of cardiac arrest if the hemorrhage, because of fetal head compression in the birth
fetus is older than 25 weeks gestation, since delivering the canal during contractions.
fetus may improve venous return and maternal-fetal survival. Relative indications for a cesarean delivery include a
Maternal resuscitation is the key to fetus resuscitation and dilated aortic root (over 4 cm), severe valvular stenosis, 799
10 severe left ventricular outflow tract obstruction and severe Adult survival and advances in pregnancy risk stratification
pulmonary hypertension. of women with moderate to complex CHD have opened up
In the United States, there have been concerns about the door to procreation like no other generation living with
the rising incidence of cesarean deliveries from 5.5 percent CHD. However, by eliminating the prohibition of pregnancy
in 1970 to 29.1 percent in 2004.111,112 There are significant for all, but a select few women with the most significant forms
associated risks including increased blood loss, delayed cardio/pulmonary disease, equal emphasis should be placed
ambulation and prolonged recovery. In addition, there is a on the importance of ‘planning’ a pregnancy, rather than
potential risk of scar rupture during labor and delivery with confronting an unplanned high risk pregnancy. Regrettably,
future pregnancies. After adjusting for possible confounding unplanned pregnancies are still the reality for almost half of
factors, the postpartum mortality is 3.6 times higher after all pregnancies,1 signifying a mismatch in either contraceptive
a cesarean delivery than a vaginal delivery, mainly due to counseling/access and/or contraceptive compliance. Kovacs
complications associated with anesthesia, puerperal infection and colleagues found that only 51 percent of women with
and venous thromboembolism.113 CHD recalled receiving information about birth control from
their health care provider.2 This reality makes effective,
Postpartum Care accessible, easy and safe contraception a mandate for this
complex population and ‘prepregnancy’ counseling is the
Women should be advised to resume contraception after responsibility of all ACHD providers.
delivery. They are often most receptive to procedures such Contraceptive options available today, provide women with
as permanent sterilization, if a future pregnancy is contra- CHD with many alternatives to prevent or postpone pregnancy.
indicated. Supportive care and education are usually well For women with complex congenital heart disease, they confront
received by the mothers. the highest risks with pregnancy, and therefore, a planned
pregnancy should always be approached as collaboration
DIET AND EXERCISE between the procreating couple, the fetus and the ACHD/high
risk obstetric team (comprising the cardiologist and nurse
A well-balanced diet with adequate fluid (preferably water) specialists in ACHD, a high risk obstetrician/perinatologist).
intake and minimized use of artificial sugar sweeteners is Part of that collaborative process usually entails a period of
advised in all women. Caffeine, alcohol intake and smoking time in which contraception is a necessity. The three biggest
are to be avoided during pregnancy. considerations in choosing optimal contraception are:
Prenatal vitamins should be started, while planning a a. The woman’s risk of thrombosis
pregnancy and continued while nursing or 6 months postpartum b. Contraceptive ease and efficacy
to replenish the iron and vitamin stores. Daily folic acid intake c. The degree of side effects. Choosing the lowest risk and
of over 400 micrograms reduces the incidence of neural tube most effective contraception can be a challenge for women
defects.4 Athough the daily intake of calcium should be over with the highest complexity of CHD.
1,500 mg (dietary and supplemental), no more than 600 mg The heterogeneity of congenital heart disease makes risk
should be taken at a time, to allow adequate absorption. stratification challenging. Some women have simple cardiac
Regular isotonic exercises and aerobic activity such as defects, which have little to no impact on their contraceptive
walking and swimming help with cardiovascular conditioning. and pregnancy decisions. However, for those women with
Jogging should be avoided during pregnancy. moderate to complex congenital heart disease, choosing a
safe contraceptive requires careful consideration of what their
CONCLUSIONs actual pregnancy risk is (moderate, high or prohibitive) and
what risks and benefits come with the preferred contraceptive
As more women with complex congenital heart defects are option. For example, women with a prohibitively high risk for
entering into their reproductive years, careful risk assessment pregnancy (Eisenmenger), the contraceptive option with the
and preconception counseling are becoming even more lowest possible failure rate (such as sterilization, intrauterine
important. Close follow-up with the perinatologists and devices [IUD], or contraceptive implants) might be
collaboration with a multidisciplinary team are essential for considered. On the other hand, a woman with complex CHD
favorable maternal and fetal outcomes. (such as double outlet right ventricle/Rastelli or transposition
of the great arteries/Mustard) may have a low risk for
ONTRACEPTIVE OPTIONS FOR WOMEN WITH
C thrombogenesis, but could confront dysfunctional menstrual
CONGENITAL HEART Diseases By Pamela bleeding or polycystic ovarian syndrome. The potential benefits
Miner, RN, MN, NP of a combined hormonal contraceptive such as a drospirenone
containing combined oral contraceptive (Yaz, Yasmin) might
Most children growing up with congenital heart disease in the be considered for both contraception and hormonal advantage.
800 21st century will live long enough to confront family planning. As this demonstrates, the decisions regarding contraception
can be more complicated than simply pregnancy prevention
Box 6: Contraindications for combined hormonal 56
and deserve comprehensive individualized evaluation and contraceptive use
treatment. Complicating matters is the paucity of published
General
data about contraceptive safety in women with CHD, since
Previous thromboembolic event or stroke
so much of our clinical decision making is based on data Inherited thrombophilia
regarding women with acquired cardiovascular disease and Smoking
perhaps more so by expert consensus. Even with the data Liver disease
published on contraceptive safety in women with other forms Pregnancy
of heart disease, the World Health Organization (WHO) and History of an estrogen-dependant tumor
the Centers for Disease Control, both emphasize the need Migraine headaches with aura
to take individual clinical circumstances into consideration Obesity
rather than holding firmly to published clinical guidelines.3 Age over 35
Cardiovascular
Hypertension
Contraceptive Options Coronary artery disease
Cerebrovascular disease
1. Combined hormonal contraceptives. Complicated valvular disease
2. Progestin-only contraceptives. Older-style mechanical valves (even on Coumadin)
3. Barrier methods/emergency contraception. Pulmonary hypertension
4. Intrauterine devices. Dilated cardiomyopathy with LVEF < 30%
5. Sterilization. Cyanotic congenital heart disease
6. Rhythm method/abstinence/abortion. Right-to-left shunting
History of Fontan procedures—highest risk with classic
Fontan (right atrium to pulmonary artery)/ or with a markedly
Combined Hormonal Contraceptives dilated right atrium.
Combined hormonal contraceptives contain both estrogen
and progestin and are highly effective at preventing
pregnancy (99.4%), when used correctly. They also have non- disease data. Thorne8 developed guidelines for contraceptive
contraceptive benefits, including reductions of menorrhagia, use in women with heart disease, including CHD. Their
dysmenorrhea, acne, hirsutism and ovarian cancers. The group categorized the highest risk groups from a thrombotic
evolution of these oral combined hormonal contraceptives standpoint to be those with older-style mechanical valves
in recent years has resulted in lower estrogen levels (20 to (even on Coumadin), pulmonary hypertension, and dilated
35 mcg) and new generations of progestin aimed at reducing cardiomyopathy with left ventricular ejection fraction (LVEF)
symptoms of menstrual syndromes. These changes have less than 30 percent. For these, the use of combined hormonal
resulted in fewer side effects and a reduction in thrombotic contraceptives was considered contraindicated. In addition,
complications.4,5 However, lower hormone levels in these patients with cyanosis (or right-to-left shunting) or Fontan
combined hormonal pills have resulted in higher susceptibility procedures were also considered to be at high risk for clot (or
to contraceptive failure if a single dose is missed in the first or at highest risk for complications related to clot) and cautioned
third week of hormones or the hormone free interval exceeds against the use of combined hormonal contraceptives. The
7 days, making back-up contraception a necessity, when these ACC/AHA guidelines for management of adults with CHD10
low estrogen oral preparations are used.6 shared some of the above concerns related to the highest risk
According to the WHO,7 the contraindications for using group, also warned against the use of estrogen containing
combined hormonal contraceptives include (Box 6): previous contraceptives in Fontan patients, pointing out that the highest
thromboembolic event or stroke or an inherited thrombophilia, risk Fontan patients appear to be those with older version, right
coronary artery disease or cerebrovascular disease, atrium to pulmonary artery (RA-PA), Fontans or massively
complicated valvular disease, women over age 35 who smoke, dilated right atriums. According to Thorne,8 treating the
liver disease, pregnancy, or a history of an estrogen dependent thrombotic risk in these patients with anticoagulation did not
tumor. In addition, special consideration of the thrombotic change the precautions against the use of combined hormonal
risks of combined oral contraceptives should be individually contraceptives. However, there are ACHD specialists who
assessed in the setting of hypertension, migraine headaches would consider using low estrogen oral contraceptives in
with aura, or in obese women over age 35. In women with women with newer version Fontans, total cavopulmonary
congenital heart disease, risk stratification is more challenging connection (TCPC), and no sustained atrial arrhythmias, or
due to lack of data regarding overall thrombogenicity and those who are consistently protected with anticoagulation.
ultimately rests on experiential inferences from those managing The risk of estrogen-provoked thrombus in women who are
adults with CHD8,9 and associations linked to acquired heart adequately anticoagulated is not known, so practice standards 801
10 in this regard are left to the treating physician. This is where systemic side effects of the other formulations of progestin
the experiential line is drawn, allowing for different practice (fluid retention, osteoporosis, etc.).
standards that each may hold merit, but make generalized
guidelines that fit all patients very difficult. Intrauterine Devices

Although the majority of combined hormonal contra
ceptives are administered orally, this method of administration Intrauterine devices are highly effective at preventing pregnancy
is associated with highest failure rates due to missed for upto 5 years. This is a safe long-term contraceptive option
doses or discontinuation among users. This has led to the for women at low risk for sexually transmitted diseases
development of other combined hormonal contraceptive (STDs). Historically, IUDs were associated with a higher
methods, including the vaginal ring and transdermal patch. rate of pelvic inflammatory disease, particularly in women
The vaginal ring (NuvaRing) is inserted by the women and exposed to Chlamydia or gonorrhea and therefore, carried a
stays in for 21 days and then is removed for 7 days. The slightly higher risk for endocarditis. However, this risk has
advantage of this method is easier compliance, they do not not been borne out in the newer generations of IUDs, as long
need to be fitted and can be inserted anywhere in the vagina, as their use is confined to women in mutually monogamous
and by avoiding gastrointestinal absorption, lower hormone relationships or those who also use condoms to prevent
doses are needed. In fact, systemic exposure to estrogen with STDs. The two types of IUDs commonly used are the copper
the ring was half that of the 30 mcg low estrogen combined IUD (Paragard) and the progestin-releasing IUD (Mirena).
hormonal contraceptive pill,11 however, a corresponding Although no study has proven a link between prophylactic
decrease in thrombotic risk has not yet been demonstrated. In antibiotic use at the time of IUD insertion and a decrease in
fact, recent studies indicate a slightly higher thrombotic risk the incidence of pelvic infections, it is reasonable to consider
in these “non-oral” hormonal contraceptives, specifically the prophylactic antibiotics in CHD patients at the highest risk for
vaginal ring and the combined hormonal transdermal patch endocarditis. Doxycycline or erythromycin are appropriate
(known as Ortho Evra in the United States).12,13 In addition, agents for this preventative purpose. The Mirena IUD would
failure rates for the patch are higher in heavier women be an appropriate contraceptive choice for women with CHD
(> 90 kg). at higher risk for thromboembolism and those who are at high
risk if they were to become pregnant. This provides long-term
Progestin-only Contraceptives effective contraception with very few side effects and the added
benefit of controlling any heavy menstrual bleeding issues.
Progestin-only hormonal formulations are the best non-
permanent contraceptive choice for women at higher risk Barrier Contraceptives/Emergency Contraception
for thromboembolism. These formulations include an oral
pill, injectable form, implantable form and local release from Barrier methods of birth control are associated with the highest
an intrauterine device. Oral progestin pills (‘mini pills’) are failure rates (15–32%) due to inconsistent and imperfect
prone to higher failure rates due to the need to take the pill utilization. These methods include condoms, diaphragms
each day at the same time. Variation of only a few hours can and cervical caps. Using a ‘double barrier’ method approach
reduce efficacy, since the primary contraceptive function of increases the efficacy considerably, which includes the use of
oral progestin is to reduce sperm penetration by changing the spermicide with any barrier method, or the combination of
consistency of cervical mucus. A more reliable formulation a diaphragm and condom. For purposes of preventing STDs
of progestin is the injectable depot medroxyprogesterone alone, the male or female condom should be used, even when
acetate (DMPA). This injection is administered by a health other forms of contraception are employed. Any woman with
care provider every 3 months and acts both on the cervical CHD can safely use a barrier method to prevent pregnancy,
mucus and on inhibiting ovulation. Implantable progestin is but women confronting the highest maternal or fetal risk with
available in the form of Implanon in the United States and pregnancy should never rely on a single-barrier method alone.
provides for 3 years of effective contraception via a single When a barrier method fails (broken condom) or is not
rod implanted in the under surface of the upper arm. All of used, emergency contraception is an option for women in the
these formulations of progestin are associated with higher first 72 hours after sexual intercourse. In the United States,
rate of breakthrough bleeding, but ultimately help to suppress Plan B (levonorgestrel) is available over the counter for
menstrual bleeding altogether. One last version of progestin women 18 years an older, or by prescription for those under
is available in an intrauterine device (IUD) called Mirena age 18. This is a progestin only drug and is taken in a single
and the advantage of this formulation is the highest efficacy 1.5 mg dose orally within 72 hours of unprotected intercourse.
of an IUD combined with only local release of progestin in Side effects include heavier menstrual bleeding, headache,
the uterus, which has the advantage of reducing or stopping lower abdominal pain and dizziness. This is a safe option
menstrual bleeding altogether without any of the potential for most women with CHD, in that it contains no estrogen.
802
However, emergency contraception should never be used as considered ‘contraception’, but provides the highest risk in 56
the primary form of contraception and it should also not be women with CHD, as an option to terminate a pregnancy
used if pregnancy is already suspected or if over 72 hours that puts them or their fetus at unacceptable risk. The risks
have passed since intercourse. of a therapeutic (surgical) abortion should be included in all
contraceptive counseling, so that the woman understands the
Sterilization potential risk of anesthesia, blood loss, infection, damage to
the uterus or cervix and psychological injury imposed by a
Sterilization provides for the most efficacious and permanent surgical abortion, thereby emphasizing the importance of
form of contraception. Options include vasectomy, surgical ‘preconception’ action to avoid pregnancy.
tubal ligation and intratubal occlusion (known as Essure in
the United States). It is reasonable to recommend this form of Risk Stratification for Contraceptive Use
contraception to women who would confront a prohibitively
high risk with pregnancy, such as women with pulmonary Risk stratification can be divided into two main considerations,
hypertension (Eisenmenger syndrome). Laparoscopic the risk of thrombosis and the risk of maternal/fetal morbidity/
surgical tubal ligation presents a small perioperative risk, mortality with pregnancy (Table 3). Often, those at highest
particularly to women with pulmonary hypertension. clot risk are also those in whom pregnancy would be the
A cardiac anesthesiologist should be present during the most hazardous. The majority if women with CHD are at low
procedure in high-risk women. Intratubal occlusion (Essure) thrombotic risk. This includes those with unoperated valve
is a less risky option for permanent contraception and can disease, small VSD, postoperative coarctation with controlled
be performed using local anesthesia. A coil-like device is blood pressure, postoperative valve repair or bioprosthetic
embedded in the fallopian tubes via a transvaginal procedure valve replacements, tissue valved pulmonary artery conduits,
and causes irritation and scarring in the surrounding tubes. transvenous pacemakers without right-to-left shunts, atrial and
Complete tubal occlusion needs to be confirmed with imaging arterial switch repairs, Marfan syndrome and postoperative
studies 3 months postcoil occlusion, so intermediate forms shunt repairs in the absence of pulmonary hypertension. Those
of contraception need to be used in those first 3 months. at moderate thrombotic risk include women with a known
Vasectomy is a reasonable option and avoids any potential thrombotic potential protected with antiplatelet therapy or
risk confronted by the woman with CHD. One could argue anticoagulation as indicated. This includes patients with
that the male partner may outlive the female partner with mechanical valve prostheses, total cavopulmonary Fontan
CHD and as such, may desire future procreation options, repairs, sustained atrial arrhythmias, unrepaired atrial septal
but in this instance, vasectomy can be reversed. Therefore, defect, or dilated cardiomyopathy with class I-II symptoms.
sterilization using vasectomy should not be easily dismissed The highest thrombotic risk group includes those women
from consideration. with CHD whose potential for clot cannot be effectively
prevented, or in whom the consequences of a clot presents
Rhythm Method/Abstinence/Abortion significant morbidity or mortality. This includes women
with pulmonary hypertension (Eisenmenger syndrome),
Rhythm method/abstinence/abortion are the least desirable cyanosis, atriopulmonary Fontan repairs, NYHA class III-
options for ‘family planning’. In the first half of the 20th IV heart failure with dilated cardiomyopathy, uncontrolled
century, prior to the era of birth control pills, the rhythm hypertension, inherited thrombophilia or documented past
method, withdrawal or abstinence were a woman’s only thrombotic tendency, obesity, or women over 35 years of age
choices for preventing pregnancy. The rhythm method is only who smoke.
marginally effective if a woman has very regular menstrual Women in the low thrombotic risk group are candidates
cycles and can precisely predict ovulation. Relying on this type for any form of contraception, including combined hormonal
of modification of one’s sexual relationship is unrealistic, as is contraceptives. Consideration must be given to those women
abstinence. Contraception is available to provide women with whose thrombotic risk may be low, but their pregnancy risks
choices that prevent pregnancy and provide more freedom in are high (such as severe aortic stenosis) and therefore, more
their sexual relationships. Fear and misinformation are often definitive contraception might be considered, such as an
the reason why a woman with CHD avoids entering into a IUD. For those with moderate thrombotic risk, nonestrogen
sexual relationship and this reflects a failure by the health care options for contraception should be considered first, but
provider to provide comprehensive contraceptive counseling. with individualized consideration towards modification of
This is both unfair to the woman and perhaps equally as thrombotic risk, one could consider a low estrogen containing
unfortunate as an unplanned pregnancy. Providers owe their combined hormonal contraceptive. This may be indicated if
patients accurate, understandable and accessible information a woman confronts considerable menstrual symptoms such
regarding their options for birth control. Abortion is not as heavy bleeding or polycystic ovaries. Clearly those at
803
10 Table 3

Risk stratification for contraceptive use
Thrombotic risk Recommended form of contraception

Low thrombotic risk Usually any form of contraception, including combined
Unoperated valve disease hormonal contraceptives
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
Moderate thrombotic risk
Thrombotic potental protected with antiplatelet therapy/anticoagulation First line are the nonestrogen options for contraception
such as in women with: Low estrogen containing combined hormonal
Mechanical valve prostheses contraceptive may be considered based on each
Total cavopulmonary connection Fontan repairs individual case
Sustained atrial arrhythmias
Unrepaired atrial septal defects
Dilated cardiomyopathy with class I-II symptoms.
High thrombotic risk
Pulmonary hypertension (Eisenmenger syndrome) Combined barrier methods
Cyanotic congenital heart disease Progestin-only options
Classic Fontan repair (atriopulmonary—right atrium to pulmonary artery) Intrauterine device (IUD)
NYHA class III-IV heart failure with dilated cardiomyopathy Sterilization
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 education regarding contraception. Young female patients
hormonal contraceptives and should be guided to progestin should be referred to such a specialist if available, if only
only options, IUD, sterilization or combined barrier methods, to begin the conversation and guide future questions when
depending on their pregnancy risks and future procreation appropriate to their level of interest or evolving sexuality.
potential. When contraceptive choices are considered ‘contraindicated’
for certain patients, alternatives must be provided. As outlined
Contraceptive Counseling in this review, multiple options are available to young women
today, who desire sexual activity without the risk of pregnancy.
Contraceptive counseling is often the most difficult subject to Clearly additional investigation is necessary to outline
address for pediatric cardiologists, although the best time to the contraceptive risks confronted by women with complex
begin addressing this in young women with CHD is when they CHD.
are entering puberty. These discussions need to be reassessed
over time, accounting for all non-cardiac risk factors for YNECOLOGICAL ISSUES IN WOMEN WITH CHD By
G
thrombosis and any changes in maternal cardiac status.14 The Mary M Canobbio, RN, MN, FAAN
only way contraceptive counseling can be deemed a “failure”
is when it never takes place. One study found that 43 percent Medical and surgical advancements have allowed most females
of women with CHD had not been counseled regarding with CHD to survive into and beyond their reproductive
contraception, and 48 percent had not been informed about years. As a result, gynecological and reproductive issues
pregnancy related risks by their treating physician.15 Many have emerged as one of the most common noncardiac health
large ACHD centers have skilled nurse specialists who are care issues, cardiologist and other health care providers must
804 experienced in providing this level of comprehensive patient address as part of their clinical management.
MENSTRUATION uncorrected CHD. The use of anticoagulation also appears to 56
increase the risk of metrorrhagia or menorrhagia, although no
Menarche significant causal relationship has been reported. In the general
population, the primary causes include systemic illness (e.g.
Menarche occurs in the normal female population at a mean hypothyroidism) and intrauterine lesions (e.g. myomas) or
age of 12.3 years. For females with acyanotic congenital heart endometriosis. Chronic metrorrhagia and menorrhagia can
disease, menarche occurs a little later at 13 years and for result in iron-deficient anemia. For females with cyanotic
females with cyanotic CHD, it occurs at the average age of CHD, who are usually erythrocytotic as result of an adaptive
13.9 years.1 While the menstrual patterns in acyanotic females response to systemic arterial hypoxemia, hematocrit must be
with CHD are similar to the general population, females carefully monitored if oral iron replacement is required. This is
with cyanotic CHD often will have menstrual irregularities because an increase in circulation erythropoietin predisposes
including shorter or longer cycle lengths, a greater frequency to a rapid and excessive rise in hematocrit.5
of menstrual irregularities, breakthrough bleeding, and/or Metrorrhagia can be managed in the short-term with high-
missed periods including amenorrhea. dose progestins or dilatation and curettage. For prolonged
Limited data is available on the postoperative menstrual menstrual suppression, Depo-Provera or the progestin-
patterns in women with CHD. An early study reported that secreting intrauterine device may be considered. For women
Fontan operation performed before the age of 10 years was in whom pregnancy is not desired or when the risks are
associated with menarche at the same age as the normal female prohibitive, endometrial ablation or hysterectoscopy may be
population, while Fontan operation performed after menarche considered.
was associated with resumption of normal menstrual patterns Regardless of cause, females with DUB require a thorough
within 6 months of surgery.2 gynecologic evaluation, which includes a detailed menstrual
A subset of patients who remained cyanotic beyond history supplemented by a pelvic examination and pap
menarche reported dysfunctional bleeding evidenced by smear. Medical treatment of DUB includes a combination
complaints of oligomenorrhea, metrorrhagia and amenorrhea oral contraceptive pills, however, the use of estrogen is
suggesting a possible relationship with the duration of contraindicated in women at risk for thromboembolism.
cyanosis after menarche, although the exact cause remains to Progesterone alone can be used to stabilize an immature
be elucidated.2 endometrium and is usually successful in the treatment of
women with anovulatory dysfunctional uterine bleeding.
Dysfunctional Uterine Bleeding The concern for anovulatory patients is that if left untreated,
chronic unopposed estrogen production can result in
Dysfunctional uterine bleeding (DUB) is defined as abnormal continuous endometrial stimulation and hyperplasia that
uterine bleeding in the absence of organic disease and is may be accompanied by a three-fold increase in the risk of
the most common cause of abnormal vaginal bleeding in endometrial cancer.6,7 Additional therapies that have proven
women of child-bearing age. It is a diagnosis of exclusion to be effective in reduction of DUB include the use of anti-
and approximately 90 percent of dysfunctional uterine fibrinolytic tranexamic acid, nonsteroidal anti-inflammatory
bleeding cases result from anovulation while 10 percent of drugs (NSAID’s).7-9
cases occur with ovulatory cycles.3 Dysfunctional bleeding is
characterized by a variety of menstrual complaints including MEDICAL TERMINATION OF PREGNANCY
irregular noncyclic bleeding, heavy bleeding (metrorrhagia,
oligomenorrhea or amenorrhea). In cases of unplanned pregnancy, in women with CHD who
In the general population, amenorrhea occurs in 0.1 percent are at high risk for maternal-fetal complications, medical
to 2.5 percent of the women as primary or secondary cause. termination of pregnancy is often recommended. The decision
The occurrence of secondary amenorrhea is higher in CHD to medically terminate a pregnancy must be a collaborative one
(10.3%), while only 0.7 to 3.0 percent of the women in the involving not only the patient, her spouse or partner, family,
general population report this menstrual cycle disturbance.4 obstetric/gynecology service, ACHD specialist, and clinical
Causes of amenorrhea are similar to general population and social worker to discuss the risks associated with pregnancy,
include hypothalamic dysfunction, endocrine disorders and as well as ensure that the choice is made with consideration to
uterine disease. Patients cyanotic prior to menarche appear the patient’s personal beliefs.
to be at greater risk of developing secondary amenorrhea. Once a decision to terminate a pregnancy has been made, it
Oligomenorrhea also appears to be common in women is important to act swiftly, because the choice of procedure is
with CHD and the number of surgical interventions prior determined by the stage of pregnancy. An ultrasound should be
to menarche may be a potential predictor, even though the performed if there is discrepancy between dates and uterine size.
comparative data of the general population is lacking. During the first trimester termination of pregnancy (first
Metrorrhagia has been mainly reported by patients with 12 weeks of gestation), the methods are either medical or 805
10 surgical. If performed within the first 7 weeks of gestation, these beneficial effects of HRT. The Women’s Health Initiative
medical abortion utilizing oral antiprogesterone agents (WHI) stopped the Heart and Estrogen/Progestin Replacement
such as RU486 (Mifepristone) and vaginally administered Study (HERS) trial of combined hormones/estrogen/progestin
misoprostol (prostaglandin E1 analog) are as effective as in women with an intact uterus, because of the increased risk
suction curettage.10-12 Because expulsion and bleeding of breast cancer, stroke and pulmonary embolism. The current
occur at home, the process is not controlled, so the systemic recommendation is neither to begin nor continue HRT for
vasodilation afforded by the PGE could potentially be risky primary or secondary prevention of cardiovascular disease.
for women with Eisenmenger syndrome/primary pulmonary Rather HRT should be limited to the treatment of menopausal
hypertension. Dilation and suction curettage under local symptoms at the lowest effective dosage over the shortest
anesthesia (paracervical block) is the most common method duration possible and continued use should be reevaluated on
employed for first trimester termination. It carries a very a periodic basis.14-16
low complication rate when performed by an experienced Currently, hormone replacement regimens include unop
obstetrician in an operating room rather than in an outpatient posed estrogen or combined estrogen/progestin therapies.15
setting. Unopposed estrogen is not recommended for women who
Dilatation and evacuation of fetus and placenta are have an intact uterus. A systemic estrogen is available in
more frequently used for termination of second-trimester oral or transdermal form with a starting dose of 0.625 mg
pregnancies. With introduction of a small dilator, called of conjugated estrogen or the equivalent recommended
Laminaria, the cervix is slowly dilated. Most of this occurs in dose. Lower doses of estrogen (0.45 mg of conjugated
the first 6 hours, with maximum dilation usually occurring in estrogen) when combined with a progestin (1.5 mg hydroxy-
12 to 24 hour followed by evacuation. The procedure carries a progesterone acetate) have been found to relieve vasomotor
low rate of complications. symptoms and prevent bone loss. The addition of cyclic or
Another method is the intrauterine instillation of of daily progestin administration is recommended for women
prostaglandin (E2 or F) and hypertonic urea that results in with an intact uterus to reduce risk of endometrial cancer.17
uterine contractions and expulsion of the fetus. However, the Progestin (medroxyprogesterone acetate or norethindrone
labor can take up to 20 hours, is painful and requires in-patient acetate) is usually prescribed in oral form, while progesterone
care. There is the risk of retention of the placenta, hemorrhage is available in other forms including oral (micronized), vaginal
and infection. or rectal suppositories.
The decision to prescribe HRT must consider the individual
MENOPAUSE needs of each patient weighing the benefits against the risks.
For the woman with CHD, the decision to prescribe HRT
Menopause is defined as the absence of menses for 12 must take into account her underlying cardiac defect, previous
consecutive months. The number of women with CHD history of surgeries and her present clinical status. Because
who are currently reaching menopause is increasing. As the the standard estrogen replacement dose, is approximately
population of adults continues to grow, the number of women one quarter of the estrogenic potency of the 20 mg of ethinyl
reaching menopause will also increase. Currently, there estradiol in an oral contraceptive pill, the majority of women
are no studies evaluating the patterns of menopause in this with CHD can safely receive these agents.
population, therefore most of our understanding of symptom However, WHI reports a 41 percent increase in stroke and
presentation and management is drawn on population-based a two-fold greater rate of venous thromboembolism (VTE), in
studies. women receiving estrogen plus progestin therapy. Therefore
While women may begin menopausal transition at about HRT use in women at high risk for thrombolic episodes is
47 years, for most women the menopause occurs between 50 discouraged.18 HRT should not be prescribed in women with
and 55 years with an average of 51.13 Symptoms commonly a history of thrombosis, embolism or bleeding.
associated with menopause may develop during this In the absence of clinical data, one should prescribe the
transitional period. Nulliparous women tend to experience lowest dose of systemic HRT that will address the vasomotor
menopause earlier than multiparous women. symptoms associated with estrogen deficiency. If there are
Health providers need to be sensitive to the emotional and residual complaints of vaginal dryness or dyspareunia due
physical effects of menopause and also assist in decisions to vaginal atrophy, the symptoms can be treated with vaginal
regarding hormone replacement therapy (HRT). Estrogen estrogen in the form of cream, tablets or ring. Estrogen doses
production begins to decline over a period of several years lower than 0.625 mg of conjugated estrogen are probably
before complete cessation. The principal goal of HRT is to as effective in reducing bone loss if combined with a
deliver the lowest effective dose of estrogen/progestin to progestin.19,20 For females with cyanotic CHD, or at risk for
relieve menopausal symptoms and to potentially reduce the thromboembolic events, HRT should be contraindicated. For
risk of osteoporosis. these women, over-the-counter phytoestrogens or selective
806 While earlier reports emphasized the benefits of HRT for serotonin reuptake inhibitors (SSRI) may be an alternative
prevention of coronary artery disease, later reports questioned to alleviate menopausal symptoms such as hot flashes.
There are mixed reports of their effectiveness from controlled Aangeboren Hartafwijking (ZAHARA) II study. Am Heart J.
2011;161:269-75.
56
trials. In the asymptomatic female, it is reasonable to avoid
HRT and utilize other agents such as bisphosphonates to 8. Pritchard J. Changes in the blood volume during pregnancy
and delivery. Anesthesiology. 1965;26:393-9.
prevent osteoporosis, unless the latter are contraindicated due
9. Kaneshige E. Serum ferritin as an assessment of iron stores
to reflux, hiatal hernia or impaired renal function. Transvaginal and other hematologic parameters during pregnancy. Obstet
estrogen may then be used for vaginal atrophy and SSRIs for Gynecol. 1981;57:238-42.
mood changes associated with the perimenopause or early 10. Ueland K, Hansen J. Maternal cardiovascular dynamics II:
menopause.19 posture and uterine contractions. Am J Obstet Gynecol. 1969;
101:1-7.
CONCLUSION 11. Ueland K, Metcalfe J. Circulatory changes in pregnancy.
Clinical Obstet Gynecol. 1975;18:41-50.
Gynecologic issues such as DUB, remains one of the 12. Christianson RE. Studies on blood pressure during pregnancy.
1. Influence on parity and age. Am J Obstet Gynecol.
commonest reasons for women with CHD to seek medical
1976;125:509-13.
attention. As the population of women with CHD increases, 13. Ueland K, Parer JT. Effects of estrogens on the cardiovascular
menopause will need to be addressed. Detailed work-up of system of the ewe. Am J Obstet Gynecol. 1966;96:400-6.
these patients along with counseling/education is needed 14. Kerr M. The mechanical effects of the gravid uterus in late
in order to establish a diagnosis and prescribe appropriate pregnancy. J Obstet Gynaecol Br Commonw. 1965;72:513-29.
management in the setting of their particular cardiac 15. Kinsella S, Lohmann G. Supine hypotensive syndrome. Obstet
physiology. Gynecol. 1994;83:774-88.
16. Ueland K, Hansen J. Maternal cardiovascular dynamics III:
A wise man should consider that health is the greatest of labor and delivery under local and caudal anesthesia. Am J
Obstet Gynecol. 1969;103:8-18.
human blessings, and learn how by his thought to derive
17. Ueland K, Novy M, Peterson E, et al. Maternal cardiovascular
benefit from his illnesses. dynamics IV: the influence of gestational age on the maternal
—Hippocrates cardiovascular response to posture and exercise. Am J Obstet
Gynecol. 1969;104:856-8.
REFERENCES 18. Cutforth R, MacDonald CB. Heart sounds and murmurs in
pregnancy. Am Heart J. 1966;71:741-7.
19. Hurst JW, Staton J, Hubbard D. Precordial murmurs during
Pregnancy in Women with CHD pregnancy and lactation. N Engl J Med. 1958;259:515-7.
20. Romano-Zeleka O, Hirsh R, Blieden L, et al. The risk of
1. Regitz-Zagrosek V, Blomstrom Lundqvist C, Borghi C,
congenital heart defects in offspring of individuals with
et al. ESC Guidelines on the management of cardiovascular
congenital heart defects. Clin Genet. 2001;59:325-9.
diseases during pregnancy: the Task Force on the Management
21. ACOG practice bulletin number 77. Obstet Gynecol.
of Cardiovascular Diseases during Pregnancy of the European
2007;109:217-27.
Society of Cardiology (ESC). Eur Heart J. 2011;32:3147-97.
22. Eddleman KA, Malone FD, Sullivan L, et al. Pregnancy loss
Epub 2011 Aug 26.
rates after midtrimester amniocentesis. Obstet Gynecol. 2006;
2. Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008
108:1067-72.
Guidelines for the Management of Adults with Congenital
23. Sharland G. Routine fetal cardiac screening: what are we
Heart Disease: Executive Summary: a report of the American
doing and what should we do? Prenat Diagn. 2004;24:
College of Cardiology/American Heart Association Task
1123-9.
Force on Practice Guidelines (writing committee to develop
24. Upham M, Medoff-Cooper B. What are the responses and
guidelines for the management of adults with congenital heart
needs of mothers of infants diagnosed with congenital heart
disease). Circulation. 2008;118:2395-451. Epub 2008 Nov 7.
disease? MCN Am J Matern Child Nurs. 2005;30:24-9
3. Presbitero P, Somerville J, Stone S, et al. Pregnancy in cyanotic
25. Siu S, Sermer M, Harrison D, et al. Risk and predictors for
heart disease. Circulation. 1994;89:2673-6.
pregnancy-related complications in women with heart disease.
4. Bailey LB, Berry RJ. Folic acid supplementation and the
Circulation. 1997;96:2789-94.
occurrence of congenital heart defect, orofacial clefts, multiple
26. Siu S, Sermer M, Colman J, et al. Prospective multi-center
births and miscarriages. Am J Clin Nutr. 2005. 81:1213 S-17S.
study of pregnancy outcomes in women with heart disease.
5. Metcalfe J, Ueland K. Maternal cardiovascular adjustments to
Circulation. 2001;104:515-21.
pregnancy. Progress in cardiovascular diseases. 1974;16:363-
27. Drenthen W, Boersma E, Balci A, et al. ZAHARA Investigators.
74.
Predictors of pregnancy complications in women with
6. Ueland K. Maternal cardiovascular dynamics VII:
congenital heart disease. Eur Heart J. 2010;31:2124-32. Epub
intrapartum blood volume changes. Am J Obstet Gynecol.
2010 Jun 28.
1976;126:671-7.
28. Drenthen W, Pieper PG, Roos-Hesselink JW, et al. ZAHARA
7. Balci A, Sollie KM, Mulder BJ, et al. Associations between
Investigators. Outcome of pregnancy in women with congenital
cardiovascular parameters and uteroplacental Doppler (blood)
heart disease: a literature review. J Am Coll Cardiol. 2007 Jun
flow patterns during pregnancy in women with congenital 807
19;49:2303-11. Epub 2007 Jun 4.
heart disease: Rationale and design of the Zwangerschap bij
10 29. Perloff JK, Marelli AJ. Perloff’s Clinical Recognition of
Congenital Heart Disease, 6th edition. Philadelphia: WB
47. Vriend JWJ, Drenthen W, Pieper PG, et al. Outcome of
pregnancy after repair of aortic coarctation. Eur Heart J. 2005;
Saunders; 2012. 26:2173-8.
30. Chugh R. Caring for the adult with congenital heart disease: 48. Roberts JM, Pearson GD, Cutler JA, et al. Summary of the
Management of common defects. The Permanente Journal. NHLBI Working Group on Research on Hypertension During
2007;11:40-6. Pregnancy. Hypertens Pregnancy. 2003;22:109-27.
31. Zuber M, Gautschi N, Oechslin E, et al. Outcome of pregnancy 49. Veldtman GR, Connolly HM, Grogan M, et al. Outcome
in women with congenital shunt lesions. Heart. 1999;81: of pregnancy in women with tetralogy of Fallot. J am Coll
271-5. Cardiol. 2004;44:174-80.
32. Yap SC, Drenthen W, Meijboom FJ, et al. ZAHARA 50. Singh H, Bolton PJ, Oakley CM. Pregnancy after surgical
investigators. Comparison of pregnancy outcomes in women correction of tetralogy of Fallot. Br Med J (Cl Res Ed.) 1982;
with repaired versus unrepaired atrial septal defect. BJOG. 285:168-70.
2009;116:1593-601. Epub 2009 Aug 13. 51. Neumayer U, Somerville J. Outcome of pregnancies in patients
33. Yap SC, Drenthen W, Pieper PG, et al. ZAHARA investigators. with complex pulmonary atresia. Heart. 1997;78:16-21.
Pregancy outcome in women with repaired versus unrepaired 52. Connolly HM, Warnes CA. Outcome of pregnancy in patients
ventricular septal defect. BJOG. 2010;117:683-9. Epub 2010 with complex pulmonic valve atresia. Am J Cardiol. 1997;79:
Feb 15. 519-21.
34. Actis Dato G, Cavaglia M, Aidala E, et al. Patent ductus 53. Drenthen W, Pieper PG, Zoon N, et al. Pregnancy after
arteriosus. Follow-up of 677 operated cases 40 years later. biventricular repair for pulmonary atresia with ventricular
Minerva Cardioangiol. 1999;47:245-54. septal defect. Am J Cardiol. 2006;98:262-6.
35. Drenthen W, Pieper PG, van der Tuuk K, et al. ZAHARA 54. Gatzoulis MA, Balaji S, Webber SA, et al. Risk factors for
Investigators. Cardiac complications relating to pregnancy arrhythmias and sudden cardiac death late after repair of tetral-
and recurrence of disease in the offspring of women with ogy of Fallot: a multicentre study. Lancet. 2000;356:975-81
atrioventricular septal defects. Eur Heart J. 2005;26:2581-7. 55. Kim WH, Seo JW, Kim SJ, et al. Aortic dissection late after
Epub 2005 Aug 17. repair of tetralogy of Fallot. Int J Cardiol. 2005;101:515-6.
36. Hameed A, Karaalp IS, Tummala PP, et al. The effect of valvular 56. Rathi VK, Doyle M, Williams RB, et al. Massive aortic
heart disease on maternal and fetal outcome of pregnancy. J root aneurysm and dissection in repaired tetralogy of Fallot;
Am Coll Cardiol. 2001;37:893-9. diagnosis of cardiac magnetic resonance imaging. Int J Cardiol.
37. Hameed AB, Goodwin TM, Elkayam U. Effect of pulmonary 2005;101:169-70.
stenosis on pregnancy outcomes—a case-control study. Am 57. Kamiya CA, Iwamiya T, Neki R, et al. Outcome of pregnancy
Heart J. 2007;154:852-54. Epub 2007 Sep 6. and effects on the right heart in women with repaired tetralogy
38. Drenthen W, Pieper PG, Roos-Hesselink JW, et al. Non-cardiac of Fallot. Circ J. 2012;76:957-63. Epub 2012 Jan 25.
complications during pregnancy in women with isolated 58. Balci A, Drenthen W, Mulder BJ, et al. Pregnancy in women
congenital pulmonary valvar stenosis. Heart. 2006; 92:1838- with corrected tetralogy of Fallot: occurrence and predictors of
43. adverse events. Am Heart J. 2011;161:307-13. Epub 2011 Jan
39. Silversides CK, Coleman JM, Sermaer M, et al. Early and 15.
intermediate-term outcomes of pregnancy with congenital 59. Meijer JM, Pieper PG, Drenthen W, et al. Pregnancy, fertility,
aortic stenosis. Am J Cardiol. 2003;91:1386-9. and recurrence risk in corrected tetralogy of Fallot. Heart.
40. Tzemos N, Silversides CK, Colman JM, et al. Late cardiac 2005;91:801-5
outcomes after pregnancy in women with congenital aortic 60. Gelson E, Gatzoulis M, Steer PJ, et al. Tetralogy of Fallot:
stenosis. Am Heart J. 2009;157:474-80. maternal and neonatal outcomes. BJOG 2008;115:398-402.
41. Yap SC, Drenthen W, Pieper PG, et al. ZAHARA investigators. 61. Naguib MA, Dob DP, Gatzoulis MA. A functional
Risk of complications during pregnancy in women with understanding of moderate to complex congenital heart disease
congenital aortic stenosis. Int J Cardiol. 2008;126:240-6. Epub and the impact of pregnancy. Part II: tetralogy of Fallot,
2007 May 4. Eisenmenger's syndrome and the Fontan operation. Int J Obstet
42. Elkayam U, Bitar F. Valvular heart disease and pregnancy part Anesth. 2010;19:306-12. Epub 2010 Jun 3. Review.
I: native valves. J Am Coll Cardiol. 2005;46:223-30. Review. 62. Canobbio MM, Morris CD, Graham TP, et al. Pregnancy
43. Niwa K, Perloff Jk, Bhuta SM, et al. Structural abnormalities outcomes after atrial repair for transposition of the great
of the great arterial walls in congenital heart disease: light and arteries. Am J Cardiol. 2006;98:668-72.
electron microscopic analyses. Circulation. 2001;103:393-400. 63. Clarkson PM, Wilson NJ, Neutze JM, et al. Outcomes of
44. Saidi AS, Bezold LI, Altman CA, et al. Outcome of pregnancy pregnancy after the Mustard operation for transposition of the
following intervention for coarctation of the aorta. Am J great arteries with intact ventricular septum. J Am Coll Cardiol,
Cardiol. 1998;82:786-8. 1994;24:190-3.
45. Kreiger EV, Landzberg MJ, Economy KE, et al. Comparison 64. Genoni M, Jenni R, Hoerstrup, et al. Pregnancy after atrial repair
of risk of hypertensive complications of pregnancy among for transposition of the great arteries. Heart. 1991;81: 276-7.
women with versus without coarctation of aorta. Am J Cardiol. 65. Guedes A, Mercier LA, Leduc L, et al. Impact of pregnancy on the
2011;107:1529-34. systemic right ventricle after a Mustard operation for transposition
46. Beauchesne LM, Connolly HM, Ammash NM, et al. of the great arteries. J Am Coll Cardiol. 2004; 44:433-7.
Coarctation of the aorta: Outcome of pregnancy. J Am Coll 66. Drenthen W, Pieper PG, Ploeg M, et al. Risk of complications
808
Cardiol. 2001;38:1728-33. during pregnancy after Senning or Mustard (atrial) repair of
complete transposition of the great arteries. Eur Heart J. 2005;
26:2588-95.
86. Pocock SB, Chen KT. Inappropriate use of antibiotic
prophylaxis to prevent infective endocarditis in obstetric
56
67. Metz TD, Jackson GM, Yetman AT. Pregnancy outcomes patients. Obstet Gynecol. 2006;108:280-5.
in women who have undergone an atrial switch repair for 87. Ellison J, Walker ID, Greer IA. Antenatal use of enoxaparin for
congenital d-transposition of the great arteries. Am J Obstet prevention and treatment of thromboembolism in pregnancy.
Gynecol. 2011;205:273.e1-75. Epub 2011 Jun 17. British Journal of Obstetrics and Gynaecology. 2000;107:
68. Tobler D, Fernandes SM, Wald RM, et al. Pregnancy outcomes 1116–21.
in women with transposition of the great arteries and arterial 88. Sadler L, McCowan, White H, et al. Pregnancy outcomes and
switch operation. Am J Cardiol. 2010;106:417-20. cardiac complications in women with mechanical, bioprosthetic
69. Connolly HM, Grogan M, Warnes CA, et al. Pregnancy among and homograft valves. BJOG. 2000;107:245-53.
women with congenitally corrected transposition of the great 89. Nassar AH, Hobeika EM, Abd Essamad HM, et al. Pregnancy
arteries. J Am Coll Cardiol. 1999;33:1692-5. outcome in women with prosthetic heart valves. Am J of Obstet
70. Therrien J, Barnes I, Somerville J. Outcome of pregnancy in Gynecol. 2004;191:1009-13.
patients with congenitally corrected transposition of the great 90. Seshadri N, Goldhaber SZ, Elkayam U, et al. The clinical
arteries. Am J Cardiol. 1999;84:820-4. challenge of bridging anticoagulation with low molecular-
71. Dobb DP, Naquib MA, Gatzoulis MA. A functional weight heparin in patients with mechanical valves : an evidence
understanding of moderate to complex congenital heart based comparative review focusing on anticoagulation
disease and the impact of pregnancy. Part I: the transposition options in pregnant and nonpregnant patients. Am Heart J.
complexes. Int J Obstet Anesth. 2010;19:298-305. Review. 2005;150:27-34.
72. Connolly HM, Warnes CA. Ebstein’s anomaly: Outcome of 91. Bates S, Greer IA, Hirsh J, et al. Use of Antithrombotic agents
pregnancy. J Am Coll Cardiol. 1994;23:1194-8. during pregnancy. Chest. 2004;126:627S-44S.
73. Donnelly JE, Brown JM, Radford DJ. Pregnancy outcome and 92. Elkayam U, Singh H, Irani A, et al. Anticoagulation in pregnant
Ebstein's anomaly. Br Heart J. 1991;66:368-71. women with prosthetic heart valves. J Cardiovasc Pharmacol
74. Fontan F, Baudet E. Surgical repair of tricuspid atresia. Thorax. Ther. 2004;9:107-15. Review.
1971;26:240-8. 93. Elkayam U, Goland S. The search for a safe and effective
75. Canobbio MM, Mair DD, Ven der Velde M, et al. Pregnancy anticoagulation regimen in pregnant women with mechanical
outcomes after Fontan repair. J Am Coll Cardiol. 1996;28: prosthetic heart valves. J Am Coll Cardiol. 2012;59:
763-7. 1116-8.
76. Drenthen W, Pieper PG, van der Tuuk K, et al. Pregnancy 94. Goland S, Elkayam U. Anticoagulation in pregnancy. Cardiol
and delivery in women after Fontan palliation. Heart. 2006; Clin. 2012;30:395-405.
92:1290-4. 95. Elefteriades JA. Natural history of thoracic aortic aneurysms:
77. Gleicher N, Midwall J, Hichberger D, et al. Eisenmenger’s indications for surgery, and surgical versus nonsurgical risks.
syndrome and pregnancy. Obstet Gynecol Surv. 1979;34: Ann Thorac Surg. 2002;74:S1877-80. (discussion S 1892-98).
721-41. 96. Davies RR, Goldstein LJ, Coady, et al. Yearly rupture
78. Katsuragi S, Yamanaka K, Neki R, et al. Maternal Outcome or dissection rates for dissection rates for thoracic aortic
in Pregnancy Complicated With Pulmonary Arterial aneurysms: simple prediction based on size. Ann Thorac Surg.
Hypertension. Circ J. 2012 Jun 13. 2002;73:17-27 (discussion 27-28).
79. Avila WS, Grinberg M, Snitcowsky R, et al. Maternal and fetal 97. Hiratzka LF, Bakris GL, Beckman JA, et al. ACCF/AHA/
outcome in pregnant women with Eisenmenger's syndrome. AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for
Eur Heart J. 1995;16:460-4. the diagnosis and management of patients with thoracic aortic
80. Weiss BM, Zemp L, Seifert B, et al. Outcome of pulmonary disease. J Am Coll Cardiol. 2010; 55:e27-e129.(Key algorithm
vascular disease in pregnancy: a systematic overview from is on page e83).
1978 through 1996. J Am Coll Cardiol. 1998;31:1650-7. 98. Shotan A, Ostrzega E, Mehra A, et al. Incidence of arrhythmias
Review. in normal pregnancy and relation to palpitations, dizziness, and
81. Wang H, Zhang W, Liu T. Experience of managing pregnant syncope. Am J Cardiol. 1997;79:1061-4.
women with Eisenmenger's syndrome: maternal and fetal 99. Baumgartner H. Reproductive issues in adults with congenital
outcome in 13 cases. J Obstet Gynaecol Res. 2011;37:64-70. heart disease: arrhythmias during pregnancy: importance,
82. Goodwin TM, Gherman RB, Hameed A, et al. Favorable diagnosis and therapy. Thorac Cardiovasc Surg. 2001;49:94-7.
response of Eisenmenger syndrome to inhaled nitric oxide during Review.
pregnancy. Am J Obstet Gynecol. 1999;180: 64-7. 100. Lee J CR, Wetzel G, Shannon K. Maternal arrhythmia
83. Rosenthal E, Nelson-Piercy C. Value of inhaled nitric oxide management during pregnancy in patients with structural
in Eisenmenger syndrome during pregnancy. Am J Obstet heart disease. Progress in Pediatric Cardiology. 2004;19:
Gynecol. 2000;183:781-2. 71-82.
84. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective 101. Chugh R. Management of pregnancy in patients with congenital
endocarditis: guidelines from the American Heart Association: heart disease and systemic ventricular failure. Progress in
a guideline. Circulation. 2007 Oct 9;116:1736-54. Epub 2007 Pediatric Cardiology. 2004;19:47-60.
Apr 19. Erratum in: Circulation. 2007;116:e376-7. 102. Frishman WH, Elkayam U, Aronow WS. Cardiovascular
85. Nahum GG, Uhl K, Kennedy DL. Antibiotic use in pregnancy drugs in pregnancy. Cardiol Clin. 2012;30:463-91. Epub 2012
and lactation. Obstet Gynecol. 2006;107:1120-38. Jun 5.
809
10 103. Wesseling J, van Driel D, Heymans HAS, et al. Coumarins
during pregnancy: long term effects on growth and
6. Centers for Disease Control and Prevention. U.S. Medical
Eligibility Criteria for Contraceptive Use, 2010. MMWR
development in school age children. Thromb Haemostas. Recomm Rep. 2010;59:1-86.
2001;85:609-13. 7. World Health Organization: Medical Eligibility Criteria for

104. Weitz JI. Low-molecular-weight heparins. N Engl J Med. Contraceptive Use, edition 3. Geneva, Switzerland: World
1997;337:688-98. Health Organization; 2004.
105. Casele HL, Laifer SA, Woelkers DA, et al. Changes in the 8. Thorne S, MacGregor A, Nelson-Piercy C. Risk of contraception
pharmacokinetics of the low molecular weight heparin and pregnancy in heart disease. Heart 2006;92:1520-5.
enoxaparin sodium during pregnancy. Am J Obstet Gynecol. 9. Miner P. Contraceptive choices for females with congenital
1999;181:1113–7. heart disease. Prog Pediatr Cardiol. 2004;19:15-24.
106. Maslovitz S, Many A, Landsberg JA, et al. The safety of low 10. Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008
molecular weight heparin therapy during labor. J Matern Fetal Guidelines for the Management of Adults with Congenital
Neonatal Med. 2005;17:39-43. Heart Disease: a report of the American College of Cardiology/
107. Lip GYH, Beevers M, Churchill D, et al. Effect of atenolol on American Heart Association Task Force on Practice Guidelines.
birth weight. Am J Cardio. 1997;79:1436-8. Circulation. 2008;118:e714-e833.
108. Schuler PK, Herrey A, Wade A, et al. Pregnancy outcome 11. Roumen FJ. The contraceptive vaginal ring compared with the
and management of women with an implantable cardioverter combined oral contraceptive pill: a comprehensive review of
defibrillator: a single centre experience. Europace. 2012;27. randomized controlled trials. Contraception. 2007;75:420.
[Epub ahead of print]. 12. Lidegaard O, Hougaard Nielsen L, Wessel Skovlund C, et al.
109. Cummins CO, Hazinski MF, Baskett PJF, et al. Cardiac arrest Venous thrombosis in users of non-oral hormonal contraception:
associated with pregnancy. Circ. 2005;112:150-3. follow-up study, Denmark 2001-2010. BMJ 2012;344:e2990.
110. Suresh MS, LaToya Mason C, Munnur U. Cardiopulmonary 13. Bakru A, Standwood N. Performance of contraceptive patch
resuscitation and the parturient. Best Pract Res Clin Obstet compared with oral contraceptive pill in a high-risk population.
Gynaecol. 2010;24:383-400. Epub 2010 Apr 24. Obstet Gynecol. 2006;108:378.
111. Resnik R. Can 29% cesarean delivery rate possibly be justified? 14. Silversides CK, Sermer M, Siu SC. Choosing the best
Obstet Gynecol. 2006;107:752-4. contraceptive method for the adult with congenital heart
112. National Institute of Health. National Institutes of Health disease. Currrent Cardiology Reports 2009;11:298-305.
State-of-the-Science Conference statemen: cesarean delivery 15. Vigl M, Kaemmerer M, Seifert-Klauss V, et al. Contraception
on maternal request, March 27-29, 2006. Obstet Gynecol. in women with congenital heart disease. Am J Cardiol. 2010;
2006;107:1386-97. 106:1317-21.
113. Deneux-Tharaux C, Carmona E, Bouvier-Colle MH, et al.
Postpartum maternal mortality and cesarean delivery. Obstet Gynecological Issues in Women with
Gynecol. 2006;108:541-8. Congential Heart Diseases
114. Naqvi TZ, Elkayam U. Serial echocardiographic assessment
of the human heart in normal pregnancy. Circ Cardiovasc 1. Canobbio MM, Rapkin AJ, Perloff JK, et al. Menstrual patterns
Imaging. 2012;5:283-5. in women with congenital heart disease. Pediatr Cardiol.
115. Savu O, Jurcuţ R, Giuşcă S, et al. Morphological and functional 1995;16:12-15.
adaptation of the maternal heart during pregnancy. Circ 2. Canobbio MM, Mair DD, Rapkin AJ, et al. Menstrual
Cardiovasc Imaging. 2012;5:289-97. Epub 2012 Mar 28. patterns in females after the Fontan repair. Am J Cardiol.
1990;66:238-40.
3. Pitkin J. Dysfunctional uterine bleeding. BMJ. 2007;334:
Contraceptive Options for Women with 1110-1.
Congenital Heart Diseases 4. Drenthen W, Hoendermis ES, Moons P, et al. Menstrual Cycle
1. Finer LB, Henshaw SK. Disparities in rates of unintended and its Disorders in Women with Congenital Heart Disease.
pregnancy in the United States, 1994 and 2001. Perpect Sex Congenital Heart Disease. 2008;3;277-83.
Reprod Health 2006;38:90. 5. Perloff JK, Rosove MH, Child JS, et al. Adults with cyanotic
2. Kovacs AH, Harrison JL, Colman JM, et al. Pregnancy and congenital heart disease: hematologic management. Ann Intern
Contraception in Congenital Heart Disease: What Women are Med. 1988;109:406-13.
Not Told. JACC vol 52, No. 7, 2008, August 12, 2008:577-86. 6. Kurman RJ, Kaminshi PT, Norris HJ. The behavior of
3. Guibert E. Black A, Dunn S, et al. Missed hormonal endometrial hyperplasia: a long-term study of ‘‘untreated’’
contraceptives: new recommendations. J Obstet Gynaecol Can. hyperplasia in 170 patients. Cancer. 1985;56:403-12.
2008;30:1050-62, 1063-77. 7. Casablanca Y. Management of dysfunctional uterine bleeding.
4. Van Hylckama Vlieg A, Helmerhorst FM, Vandenbroucke JP, Obstet Gynecol Clin North Am. 2008;35:219-34, viii.
et al. The venous thrombotic risk of oral contraceptives, effects 8. Bongergs MY, Mol BWJ, Brolmann HAM. Current treatment
of oestrogen dose and progestogen type: results of the MEGA of dysfunctional uterine bleeding. Maturitas. 2004;47:159-74.
case-control study. BMJ. 2009;79:182. 9. Hickey M, Higham J, Fraser IS. Progestogens versus oestro-
5. Lidegaard O, Lokkegaard E, Svensdsen AL, Agger C. gens and progestogens for irregular uterine bleeding associ-
Hormonal contraception and risk of venous thromboembolism: ated with anovulation. Cochrane Database Syst Rev. 2007; Oct
17CD001895.
810 national follow-up study. BMJ 2009;339:b2921.
10. Spitz IM, Bardin CV, Benton L, et al. Early pregnancy
termination with mifepristone and misoprostol in the Unives
16. Writing Group for the Women’s Health Initiative Investigators.
Risks and benefits of estrogen plus progestin in health
56
States. N Engl J Med. 1998;333:1242-7. postmenopausal women: principle results from the Women’s
11. ACOG. Clinical management guidelines of obstetrician- Health Initiative randomized controlled trial. JAMA.
gynecologists. Medical management of abortion. Obstet 2002;288:321-33.
Gynecol. 2005;106:871-82. 17. Furness S, Roberts H, Marjoribanks J, et al. Hormone therapy
12. Mischell DR. Family planning: contraception, sterilization, in postmenopausal women and risk of endometrial hyperplasia.
and pregnancy termination. In: Katz VL, Lentz GM, Lobo Cochrane Database of Systematic Rev 2009.(2):CD000402.
RA, Gershenson DM (Eds) Comprehensive Gynecology, 5th DOI: 10.1002/14651858.CD000402.pub3
edition. Philadelphia, PA: Mosby Elsevier; 2007. 18. The Women’s Health Initiative Steering Committee. Effects
13. Lund KL. Menopause and the Menopausal Transition. Medical of conjugated equine estrogen in postmenopausal women with
Clinics of North America. 2008;92:1253-71. hysterectomy. The Women’s Health Initiative randomized
14. Position Statement. The 2012 Hormone Therapy Position controlled trial. JAMA. 2004;291:1701-12.
Statement of The North American Menopause Society. 19. Sikon A, Thacker HL. Treatment options for menopausal
Menopause: The Journal of the North American Menopause hot flashes. Cleveland Clinic Journal of Medicine. 2004;71:
Society. 2012;19:257-71. 578-82.
15. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and 20. Utian WH, Shoupe D, Bachmann G, et al. Relief of vasomotor
benefits of estrogen plus progestin in healthy postmenopausal symptoms and vaginal atrophy with lower doses of conjugated
women: principal results From the Women’s Health Initiative equine estrogens and medroxyprogesterone acetate. Fertil
randomized controlled trial. JAMA. 2002;288:321-33. Steril. 2001;75:1065-79.
811
Exercise and Sports in
C hapter
57 Adolescents and Adults with

Congenital Heart Disease
Reema Chugh
INTRODUCTION with CHD. Functional status has been shown to be a reliable

predictor for perioperative and long-term cardiac events and can
Aerobic exercise is important for improving the general health be improved by regular organized exercise.1 Besides improving
and well-being of all people. Those born with congenital heart exercise tolerance, daily aerobic physical exercise has a positive
defects (CHD) are often overprotected and restricted from effect on emotional, mental and psychosocial well-being.
getting involved in any organized exercise, sports or training
programs. Patients with CHD may often have low exercise Types of Exercise
ability due to a combination of the underlying heart defects and
physician or self-imposed reduction in daily physical activity. Exercise is generally categorized into two forms and with some
Studies have shown that the exercise capacity is decreased overlap between the movements that are primarily of one type
on objective assessment even in self-reported asymptomatic or the other. The two types (Table 1) of exercise are:
adults with CHD and may be similar to that seen in patients 1. Isotonic exercise or dynamic
with chronic heart failure. Known contributing factors are 2. Isometric or static.2
blunted heart rate response to exercise (due to sinus node or
conduction diseases), impaired ventricular function, pulmo- Isotonic Exercise
nary hypertension, cyanosis and the propensity for develop-
ing exercise-induced arrhythmias. Poor functional capacity During isotonic exercise, a person uses a relatively small force
is associated with poor prognosis, risk for hospitalizations or to achieve changes in muscle length by rhythmic muscular
death. contractions, mainly leading to volume load of the heart.
Guidance to aspire towards achievable and obtainable Examples of this type of exercise are walking, jogging,
activities is extremely important for improving clinical cycling, swimming, water aerobics, yoga and Tai Chi. Cardiac
outcomes and the quality of life. patients are recommended this form of exercise for up to 30
to 45 minutes daily with a slow, long warm up and a slow
EXERCISE 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
Benefits of Exercise
an increase in stroke volume as well as in heart rate. These
Moderate physical activity is known to help us lose weight changes then lead to an increase in cardiac output and oxygen
and regulate our metabolism, thereby reducing the risk of consumption. The diastolic blood pressure may fall from a
developing hypertension, lipid disorders and diabetes. As decrease in peripheral vascular resistance.2-4
the population of adults with CHD ages, coronary artery
disease and metabolic disorders are becoming more prevalent. Isometric Exercise
Cardiovascular risk reduction plays an important role in
improving long-term outcomes, with diet and exercise being During isometric exercise, a person uses a large force with
the foremost recommendations. minimal or no change in muscle length leading to pressure
Regular exercise also improves the ability to tolerate load on the heart. The most common form of isometric
pregnancy in all women and this is even more so for women exercise is weight lifting. Isometric work involves lifting or

table 1 57
Types of exercise
ExErcisE and sports in adolEscEnts and adults with congEnital hEart disEasE
Type of exercise Isotonic Isometric
Effect on the heart Volume load Pressure load
Blood pressure Increase in systolic and decrease in Sudden increase is systolic blood
diastolic pressure 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 

table 2
exercise movement is called a repetition (or rep in short). A Classification of recreational activity
series of repetitions is called a set (or a set of reps in short). Category Level of exercise Types of activity
Light weights with more repetitions are preferred because
I No restrictions Athletics, contact sports,
they help in maintaining muscle mass, tone and bone strength.
endurance training
Heavy weight-lifting is discouraged when there is aortic
II Moderate exercise Regular physical education
root dilatation, since it may cause strain and progression of
classes, tennis
aneurysmal formation, especially in patients with connective
tissue disorders involving the great arterial walls.5 Other III Light exercise Jogging, cycling, golf and
recreational swimming
forms of isometric exercise are wrestling and gymnastics.
Heavy isometric exercise should also be avoided in individ- IV Moderate limitation Attending school or college,
avoiding organized sports or
uals with severe left ventricular outflow tract lesions such as physical education classes
significant aortic stenosis, subvalvular stenosis, hypertrophic
V Extreme limitation Homebound or activities of
obstructive cardiomyopathy or coarctation of aorta, because a
daily living only
surge in blood pressure and an uncontrolled increase in pres-
Adapted from Gutgesell et al. Circulation. 1986 Nov;74(5):1195A-1198A.
sure overload may occur during this form of exercise.2-4
Levels of Intensity and Duration of Exercise


table 3
Low intensity exercise is preferred in adolescents and adults Classification of occupational activity
with CHD who have ventricular volume overload at rest.
Category Level of exercise Type of activity
Depending upon the degree of volume overload, even isotonic
I Very heavy work Lifting objects over 45 kg and/
exercise of moderate to higher intensity may cause fatigue and
or frequent lifting/carrying
severe strain on the heart. Walking at a comfortable pace is objects over 23 kg
therefore preferred to running. By increasing both the pace
II Heavy work Lifting objects up to 45 kg and/
and the duration of the physical activity as tolerated, over or frequent lifting/carrying
time there will be an incremental increase in endurance and objects up to 23 kg
exercise tolerance. III Medium work Lifting objects up to 23 kg and/
Gutgesell et al.6 categorized the levels of recreational and or frequent lifting/carrying
occupational activity in a special report from the American objects up to 11 kg
Heart Association in 1986 as shown in Tables 2 and 3. This IV Light work Lifting objects up to 9 kg and/or
report emphasizes that the risks of brief periods of dizziness frequent lifting/carrying objects
or syncope can be more hazardous than the impact of severity up to 4.5 kg
of workload involved in a particular activity. Examples of V Sedentary work Lifting objects up to 4.5 kg
such cases are unsupervised swimming, construction work at and/or occasionally lifting and
high buildings and structures or flying an aircraft because of carrying small articles
the dangers of drowning and falls.6 Adapted from Gutgesell et al. Circulation. 1986 Nov;74(5):1195A-1198A.
813
10 ATHLETIC AND COmpETITIvE SpORTS Ambulatory Holter and Event Recording
The 36th Bethesda conference guidelines define the For arrhythmias that occur sporadically or are affected by
congEnital hEart disEasE in adults
competitive athlete “as one who participates in an organized changes in the hemodynamic status, serial electrocardiographic
team or individual sport that requires regular competition recordings may be required over time. Depending upon the
against others as a central component, places a high premium frequency and duration of these arrhythmias, an ambulatory
on excellence and achievement and requires some form of Holter monitor or transtelephonic event recorder may be
systematic (and usually intense) training.” These highly helpful.
intense organized competitive sports are likely to put heavy A recent study by Rodriguez et al showed that 15 percent
emotional and physical pressures on the athlete. In a person of the adults with CHD had arrhythmias on Holter monitoring.
with CHD, commitment to competitive sports may not allow Repeat Holter monitoring detected a new arrhythmia in
him/her to determine when it is prudent to terminate the 34 percent of the patients. The majority of the patients with
physical exertion if cardiac-related symptoms or warning arrhythmias were asymptomatic (76%). Among those with
signs occur.7 normal ECGs, arrhythmias were frequently detected on Holter
monitoring (26%).16
SUDDEN CARDIAC DEATH IN ATHLETES
Implantable Loop Recorder
The most commonly reported congenital heart or genetically-
linked lesions associated with sudden cardiac death (SCD) An implantable loop recorder is a small device to help identify
during sports participation are hypertrophic cardiomyopathy the causes of unexplained syncope. Under local anesthesia, it
(HCM), coronary artery anomalies, Marfan syndrome and is inserted under the skin below the clavicle, usually on the
aortic valve disease.8-10 left side with closer proximity to the heart. It continuously
Sudden cardiac death is less frequently linked with the records heart rhythm for up to 2 years. When syncope occurs,
underlying diagnosis of complex congenital heart defects such the device is activated to save the recording before, during
as tetralogy of Fallot, D-transposition of the great arteries, and after the episode. These recordings are then examined to
congenitally corrected transposition of the great arteries or determine if there are any tachy or bradyarrhythmias causing
defects associated with significant pulmonary hypertension. syncope.17
More often than not these individuals are prudent regarding
exercise prescriptions and restrictions. Treadmill Stress Testing
CARDIAC DIAGNOSTIC TESTING FOR SCREENING Treadmill stress testing allows objective assessment of the
functional capacity, exercise-induced arrhythmias and impact
Besides a good history and physical examination that are of of exercise on the QT interval. In addition, it is most commonly
utmost importance,11 the following cardiac tests may assist in used to evaluate ischemia. Regular organized exercise over
identifying individuals at higher risk for SCD. several months, in children and adolescents with CHD, has
beneficial effects on physical fitness and improves objectively
Electrocardiogram assessed functional capacity.18
Patients with coarctation of aorta (CoA) should have blood
For population-based preparticipation screening of cardio- pressure measurements checked in the right arm and leg before
vascular diseases in young athletes, the 12-lead ECG has been and after exercise. The resting systolic blood pressure readings
advocated as a practical and cost-effective tool.12 Although, the and resting systolic blood pressure difference between the
likelihood of ECG abnormality associated with HCM is high right arm and leg are not indicators for blood pressure response
(75–95%), other findings such as a prolonged QT in individuals during exercise. Exercise testing is very important in patients
with the long QT syndrome or ST and T wave abnormalities with CoA to unmask the exercise-induced hypertension.19,20
suggestive of coronary artery anomalies in the young or other Those with cyanotic CHD should have their oxygen
specific findings associated with inherited syndromes, may saturation checked at rest and after at treadmill stress test
not be consistently present on serial ECGs.13,14 ECGs may or before and after a six-minute walk test. Few centers
sometimes be helpful in identifying Brugada syndrome15 and have bicycle stress testing that may allow more convenient
other inherited syndromes that may place the person at a risk measurements of ECG, blood pressure and workload in people
for a high risk for SCD secondary to ventricular tachycardia/ with back problems, but this form of testing may be limited
fibrillation, under adrenergic stimulation. due to leg fatigue.
814
Echocardiography Stress Echocardiography 57
Transthoracic echocardiography (2-dimensional, color and In addition to the assessment of symptomatic and functional
spectral Doppler) is the principal diagnostic imaging modality response to exercise, stress echocardiography provides
for clinical identification of structural heart diseases and valuable information on exercise-induced changes in
serial follow-up of residua and sequelae in individuals with hemodynamics, ventricular function and pulmonary artery
unoperated or operated CHD.21,22 pressure in adolescents and adults with CHD.
The most common cause of sudden cardiac death in the Biventricular response to exercise, changes in pulmonary
young is hypertrophic cardiomyopathy (HCM). A heart pressure and hemodynamic severity of the underlying defect
murmur or abnormalities on ECG may be suggestive of classic before and after exercise offers an additional prognostic value
hypertrophic cardiomyopathy or its variants (Figures 1 and 2). for clinical management.
The diagnosis is usually confirmed by echocardiography.
The presence of unexplained asymmetric left ventricular Cardiopulmonary Exercise Testing
(LV) wall thickening with a maximal LV end-diastolic wall
thickness of 15 mm or more in an adult (two or more standard Where available and affordable, cardiopulmonary exercise
deviations from the mean relative to body surface area; z-score testing (CPET) may offer additional prognostic information by
of two or more in children) is considered diagnostic for comparing peak oxygen uptake (peak VO2) of the individual,
HCM.23,24 However, when an echocardiogram is performed in relation to the defined normal values that are greater than 90
in a person who has a mutant HCM gene, but is younger than percent of the predicted peak VO2.26
14 years of age, the left ventricular wall thickness may not Kempny et al. reviewed 23 publications, with 2286
meet the criteria for HCM because he or she is in the pre- patients from the Medline literature, describing exercise
hypertrophic phase of the disease process.23 Therefore, capacity in adults with CHD using CPET. They then included
throughout adolescence annual serial echocardiography is 2129 patients who underwent CPET at the Royal Brompton
recommended in HCM family members.23,25,26 Hospital in London, U.K. They observed that 80 percent of
The second most common cause of sudden cardiac death patients had reduced peak oxygen uptake compared with
in athletes is a coronary artery anomaly. On a good quality normal values. There were significant differences in peak VO2
transthoracic (2-dimensional and color) echocardiogram, between subgroups of adults with CHD. Even adults with
the origin and proximal courses of the anomalous coronary simple CHDs, on an average, had significantly reduced peak
arteries may be visualized in the parasternal short-axis views. VO2 compared with normal values. Adults with Eisenmenger
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 the pulsatile aorta and the pulmonary artery post-exercise and
allowed comparisons in the exercise capacity of individual prove fatal.28,29 These individuals may present with exertional
and their peers. The data obtained from this study should be syncope, chest pain or palpitations and surgical correction is
helpful in interpreting CPET results, guiding therapy, and primarily indicated in symptomatic patients or when ischemia
advising patients on activities of daily living, participation in is demonstrated on imaging.
sports and choice of occupation.27 Another coronary anomaly associated with SCD is the
anomalous left coronary artery arising from the pulmonary
Coronary Computed Tomography Angiography artery (ALCAPA). Long-term outcomes in undiagnosed or
unoperated cases depend on whether or not the degree of
Coronary computed angiography (CTA) is now a popular and collateralization adequately compensates for myocardial
relatively inexpensive imaging tool for definitive identification ischemia, its impact on left ventricular function, the severity
of congenital coronary artery anomalies. Due to the heavy of mitral regurgitation due ischemic papillary muscle and risk
exposure to radiation in a young person and the possibility of of ventricular arrhythmias caused by myocardial scarring
an allergic reaction to the iodine contrast agent, this diagnostic due to ischemia. Surgery to correct this anomaly should be
test is used prudently. performed by implantation of the origin of the left coronary
CTA is usually recommended when congenital coronary artery into the aortic root or a bypass operation. Following
artery anomalies are suspected, as in the case of young revascularization, stress testing is performed periodically to
people presenting with exertional syncope or palpitations evaluate exercise tolerance, ischemia and exercise-induced
due to ventricular arrhythmias. Unfortunately, this diagnosis arrhythmias before recommending level of exercise.
is often missed during life since many young people may be A very rare form of anomalous coronaries are the
asymptomatic with daily activities and have a normal resting congenitally hypoplastic coronary arteries. The risk of
ECG. sudden death increases during the growth phase, as the
More commonly, congenital coronary abnormalities present myocardial demands outstrip the coronary blood supply.
with anomalous origins from the wrong sinuses. The more Unfortunately, an adolescent may suffer sudden cardiac
common type is the anomalous right coronary artery arising death in sleep or during routine activity, with or without any
from the left coronary sinus (ARCA). The most dangerous premonitory symptoms such as palpitations and/or light-
type is the anomalous left main coronary artery (ALMCA) headedness. Sometimes serial electrocardiograms may show
originating from the right (anterior) sinus of Valsalva. The subtle nonspecific ST and T wave abnormalities (Figures 3A
ALMCA takes an acute angled bend with a course between and B). Although not stated in the guidelines, our personal
816 the right ventricular outflow tract/pulmonary trunk and the experience guides us to admit an individual for a complete
anterior aspect of the aorta, that can get compressed between diagnostic work up and potential treatment, if there are
57
a
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/ desirable imaging tool for several pathologies. Where it is
or mild left ventricular dilatation even when the left (systemic) available and when it is affordable, it may be used judiciously
ventricular systolic function is normal. for clarifying the diagnosis in suspected cases of HCM, by
demonstrating segmental areas of hypertrophy of the left
magnetic Resonance Imaging ventricle (such as in the anterolateral free wall or apex).30,31
Arrhythmogenic right ventricular cardiomyopathy or
Magnetic resonance imaging (MRI) does not expose a person dysplasia (ARVC/ARVD) is among the common causes of 817
to ionizing radiation and provides a good contrast between SCD in the young, with an incidence that is actually higher
the soft tissues of the heart and blood vessels, making it a than previously reported.
10
Figure 4: 50-year-old man with Brugada syndrome (Type 1 pattern) presenting with a history of short episodes of presyncope
It is characterized by a progressive replacement of normal Genetic Testing

right ventricular muscle cells by fibrous tissue and fat, starting
with involvement of specific segments of the right ventricle While genetic testing may be helpful in identifying some
(RV), leading to RV enlargement with wall motion abnormalities inheritable disorders, it is very expensive, not routinely
and then progressing to global RV involvement. The most available in all parts of the world. It is also not comprehensive
common ECG abnormality seen in ARVC is T wave inversion for screening populations for most genetic heart disorders.35
in leads V1 to V3. ECG may sometimes demonstrate epsilon Currently, its use is restricted to limited cases where there is
waves described as a terminal notch in the QRS complex due to high suspicion due to involvement of a family history or when
slowed intraventricular conduction. In suspected cases, MRI is characteristic findings suggestive of a genetic disorder are
the test of choice in identification of adipose tissue replacement detected on other diagnostic modalities.
within the wall of the RV and aneurysm formation of the RV
which are the hallmarks for diagnosing ARVC. Cardiac Catheterization
Despite increased awareness and better cardiac imaging,
the diagnosis of ARVC may be delayed, since echocardiogram Coronary angiography is indicated only when non-invasive
is not always able to detect right ventricular involvement and imaging fails to make a diagnosis or when definitive diagnosis
the sensitivity or specificity of MRI for diagnoses of ARVC is is required prior to interventions/cardiac surgery, especially
limited.32-34 in people who have a higher likelihood of having coronary
Brugada syndrome is an autosomal dominant inheritable artery disease.
cause of sudden cardiac death due to ion channelopathies.
Loss-of-function mutations of sodium channel (SCN5A) GUIDELINES FOR EXERCISE IN pATIENTS WITH
account for nearly one in five cases. Classic ECG abnormalities CONGENITAL HEART DEFECTS
suggestive of Brugada syndrome may sometimes be seen
in a young person presenting with palpitations leading to Guidelines for physical activity, strenuous exercise, sports
presyncope or syncope (Figure 4), while in others the diagnosis and athletics in people with cardiovascular abnormalities,
is made during electrophysiological work up for ventricular especially in those with CHD, were established by the
arrhythmias. Implantation of an automatic implantable cardiac Bethesda Conferences.36,37 With the help of these guidelines,
defibrillator (AICD) is the only treatment proven effective in physicians can make individualized recommendations
preventing sudden death due to ventricular tachycardia and based on each person’s clinical status, physical abilities and
818 fibrillation in these patients. interests. The following discussion provides defect-specific
recommendations based upon the available published data Arrhythmias 57
and the experience in taking care of the adults with CHD.
While arrhythmias can occur with genetic conditions and
GENERAL CONSIDERATIONS ion channel diseases, they commonly occur with CHD
restricting participation in exercise and sports programs.
Adolescents and adults receiving anticoagulation should not There is specific prognostic importance linked with the
participate in any type of contact sport. All sport activities and arrhythmias and CHDs, because the main determinant for
exercise have to be avoided during active infection with fever assessing sports participation in patients with arrhythmias
associated with subacute bacterial endocarditis. is the presence of structural heart disease. The Study
The main determinants of exercise tolerance besides Group on Sports Cardiology, of the European Association
the severity of the underlying CHD lesions are ventricular for Cardiovascular Prevention and Rehabilitation, has
function, pulmonary hypertension, cyanosis and arrhythmias. made comprehensive recommendations for participation
in leisure-time physical activity and competitive sports, in
ventricular Function patients with arrhythmias and potentially arrhythmogenic
conditions.39,40
Cardiovascular conditioning has a positive benefit on the
ventricular function which in turn affects exercise tolerance.
An annual assessment of ventricular function should be DEFECT-SpECIFIC EXERCISE RECOmmENDATIONS
performed for risk stratification of all patients with CHD who
have complex defects, unoperated or operated. Less frequent Shunt Lesions
assessment (every other year) may be performed in those with
simple operated CHD and no significant residua or sequelae. Atrial Septal Defect (ASD)
An ejection fraction (EF) over 50 percent allows full
participation in sports while an EF less than 40 percent limits No exercise restrictions
participation in competitive sports. • Unoperated patient with a small to moderate ASD,
with a left-to-right shunt, without significant right
pulmonary Hypertension heart enlargement and not more than mild pulmonary
hypertension with an estimated right ventricular
In day-to-day practice, the peak pulmonary artery systolic systolic pressure (RVSP) less than 45 mm Hg on
pressure (PASP), is assessed by echocardiography based on the echocardiography.
estimation of the right ventricular systolic pressure (RVSP). • Postsurgical or device closure of an ASD (over 6
In the presence of tricuspid regurgitation (TR) by color-flow months ago) without a residual shunt or significant right
Doppler imaging, the RVSP is calculated from the peak velocity heart enlargement and not more than mild pulmonary
(V) of the TR jet (4 V2 + estimated right atrial pressure). The hypertension (estimated RVSP less than 45 mm Hg).
TR jet can be enhanced by injecting saline through a peripheral
intravenous catheter.38 Severe pulmonary hypertension poses a Restriction for athletics
risk of SCD during sports and heavy exertional activities. ASD—operated or unoperated with associated
While there are no restrictions for participation in sports • Severe RV enlargement or decreased function
based on a PASP of less than 30 mm Hg, those with mild • Moderate to severe pulmonary hypertension (estimated
(30–45 mm Hg), moderate (45–60 mm Hg) or severe (greater RVSP is over 45 to 60 mm Hg)
than 60 mm Hg) pulmonary hypertension should be guided on • Uncontrolled arrhythmias (atrial fibrillation/flutter)
an individual basis regarding exercise. • Ventricular tachyarrhythmias
• High degree (second- or third-degree) atrioventricular
Cyanosis (AV) heart block.
Unoperated patients with cyanotic CHD have self limited Ventricular Septal Defect (VSD)
exercise abilities since the cyanosis worsens with effort due to
increasing hypoxemia (decrease in oxygen saturations measured No exercise restrictions
by pulse oximetry). Even after palliative procedures that relieve • Operated VSD (more than 6 months ago) with no residual
the cyanosis at rest, exercise tolerance may still be depressed shunts
due to hypoxemia with moderate to heavy exercise. In the • Unoperated small restrictive VSD, with normal ventricular
absence of a moderate to severe decrease in ventricular function function and absence of pulmonary hypertension (estimated
or tachyarrhythmias associated with impaired consciousness, RVSP is less than 25 mm Hg)
these patients may perform low intensity exercise as long as the • Absence of any atrial or ventricular arrhythmias or high 819
oxygen saturations are maintained over 80 percent. degree AV heart block.
10 Restriction for athletics cardiac death. A fall in blood pressure during exercise is
VSD with large left-to-right shunt a poor prognostic sign. The risk of developing arrhythmias
• Isometric exercises should be avoided since it may lead to should be assessed by an ECG or Holter study.
increase in left ventricular pressure that potentiates the left-

to-right shunt Restrictions for heavy exercise and athletics
• Mild isotonic exercises are allowed as tolerated • Patients with minimal or mild stenosis (peak gradient less
than 40 mm Hg, mean resting gradient less than 20 mm
Restriction for moderate exercise Hg) at the aortic, subvalvular or supravalvular levels in the
• Nonrestrictive, large VSD with associated moderate to absence of left ventricular hypertrophy or arrhythmias may
severe pulmonary hypertension (Eisenmenger physiology) perform mild-to-moderate isotonic exercises.
– Only mild intensity isotonic activities such as walking • Heavy isometric exercise should be avoided with
for a limited duration are allowed – Bicuspid aortic valve due to associated aortopathy5
– Progressive increase in the gradient across the lesion
Patent Ductus Arteriosus (PDA) – Significant left ventricular outflow tract obstruction
(may cause an increase in left ventricular pressure with
No restrictions isometric exercise)
Surgical-ligation or device-closure of the PDA (over 3 months
ago) with no residual shunt, normal left ventricular size and Aortic Valve Regurgitation
function and absence of pulmonary hypertension
• Best prognosis among all adults with CHD No restrictions
• No exercise restrictions • Mild aortic valve regurgitation
• Normal end diastolic left ventricular size and systolic
Restrictions for heavy exercise and athletics function
• Unoperated patients with a small left-to-right shunt
• Significant left ventricular enlargement and decreased Mitral Stenosis
function
– Mild-to-moderate isotonic exercise as tolerated Most of the information on exercise recommendations in
patients with congenital mitral stenosis are extrapolated from
Restrictions for moderate exercise the guidelines for acquired valvular disease.41 Again it is
Long-standing PDA with reversal of the shunt leading to emphasized that those who need anticoagulation should avoid
moderate to severe pulmonary hypertension/ Eisenmenger contact sports or any sports associated with a high probability
physiology of injury. Exercise limitations depend upon the following
• Only mild intensity isotonic activities such as walking for factors:
a limited duration are allowed • Severity of the valve stenosis
• Size of the left atrium
valvular Diseases • Atrial arrhythmias –atrial fibrillation.
Restrictions for heavy exercise and athletics: Mild mitral

Aortic Stenosis (AS), Subvalvular or
stenosis in normal sinus rhythm.
Supravalvular Stenosis
Most of the sudden deaths in patients with severe AS have been Restrictions for moderate exercise: Moderate to severe
found to occur on during physical exertion.37 Adolescents and mitral stenosis with sinus rhythm or atrial fibrillation.
adults should undergo cardiac testing before being approved
for sports or athletics. Periodic re-evaluation (annually) is Mitral Regurgitation
required since AS may progress. Extrapolation of the data
from valvular AS, allows similar criteria to be applied for Restrictions for heavy exercise and athletics
patients with discrete (membranous) subaortic stenosis and • Mild to moderate mitral valve regurgitation
supravalvular aortic stenosis.37 • Mitral valve prolapse
Those with moderate (peak gradient over 40 mm Hg, mean • Arrhythmias
resting gradient between 20 to 40 mm Hg) and severe stenosis
(peak gradient over 64 mm Hg, mean resting gradient over Pulmonary Stenosis (PS) and Pulmonary
40 mm Hg), left ventricular hypertrophy or arrhythmias are Regurgitation (PR)
restricted from getting involved in athletic training, contact
820 sports and isometric exercise like moderate to heavy weight Congenital PS may be due to a domed-shaped or dysplastic
lifting. They are also at risk of having syncope or sudden valve, the former being associated with pulmonary artery
dilatation.5 Echocardiography allows grading of PS as mild Coarctation of the Aorta (CoA) 57
(less than 40 mm Hg), moderate (40-60 mm Hg) and severe
(greater than 60 mm Hg) by a Doppler peak instantaneous Exercise often causes a marked increase blood pressure in the
gradients. Prior to getting involved with athletics, cardiac aorta (especially proximal to the coarctation) in unoperated and
intervention with balloon valvuloplasty, or cardiac surgery operated patients with CoA. Multiple factors including altered
are indicated in symptomatic patients with a gradient greater vascular biology and reduced precoarctation aortic distensibility
than 50 mm Hg. Postoperatively, the individual should contribute to this phenomenon, despite resolution of the local
resume sports after three months.7 Isolated congenital PR obstruction by surgery or implantation of an endovascular stent.
may occur due to an absent pulmonary valve or in association Ambulatory hypertension is common in this population
with PS. even in individuals who are normotensive at rest. Exercise
stress testing helps in risk stratification before exercise
No restrictions counseling and directing appropriate medical management for
• Mild PS with normal RV function better blood pressure control.43
• Operated PS with less than mild residual PS or PR, normal
RV function and less than moderate pulmonary artery Restriction for heavy exercise and athletics
dilatation. • Mild isotonic exercise with slow warm up and slow cool
down is usually recommended
Restriction for heavy exercise and athletics • Moderate to heavy isometric exercise like weight lifting
• Moderate or severe pulmonary stenosis should be avoided to prevent aortic dilatation/aneurysmal
• Severe pulmonary regurgitation with/without significant formation because of the associated aortopathy.
RV enlargement.
Tetralogy of Fallot (TOF)
Ebstein’s Anomaly
Exercise testing, baseline electrocardiogram and echo-
In Ebstein’s anomaly, the tricuspid valve abnormality and cardiography are essential for risk stratification of patients
its associated regurgitation leads to right heart enlargement with TOF, since exercise-induced QRS widening, more than
that may vary in severity, affecting clinical presentation 3 premature ventricular complexes in a row and ventricular
and exercise tolerance.42 If a patent foramen ovale is also arrhythmias, namely non-sustained ventricular tachycardia
present, there may be an increased right-to-left shunt due are prognostic signs for SCD.44,45
to abnormal diastology, causing cyanosis and decrease
exercise tolerance. The presence of an accessory pathway No restrictions
associated with Wolf-Parkinson-White (WPW) syndrome • Operated patients with good biventricular function, normal
may predispose to supraventricular tachycardia (SVT) right ventricular dimensions, mild pulmonary regurgitation,
during exercise. The progressive right atrial enlargement no significant right ventricular outflow tract obstruction
may contribute to atrial arrhythmias. Individuals at the (peak gradient less than 25 mm Hg), with absence of residual
severe end of the spectra of this defect may be at risk for or very small restrictive VSD on echocardiography, normal
SCD. QRS duration on electrocardiogram and are tolerating
isotonic exercises.
No restrictions
• Mild form of Ebstein’s anomaly with normal right Restrictions for heavy exercise and athletics
ventricular size and function • Operated patients with late repair leading to long-standing
• Absence of atrial or ventricular tachyarrhythmias pressure overload of RV (but with RVSP less than half
• Acyanotic. of systemic pressure), significant RV hypertrophy, RV
diastolic dysfunction
Restriction for heavy exercise and athletics • History of right ventriculotomy with annular patch
• Moderate tricuspid regurgitation repair (associated with risk of monomorphic ventricular
• No arrhythmias other than premature ventricular ectopy tachycardia originating from the RV scar).
• Post-tricuspid valve surgery with less than mild residual • Moderate PR
tricuspid regurgitation or right heart enlargement and no • Residual large VSD.
symptomatic atrial/ventricular arrhythmias.
Restrictions for moderate exercise
Restrictions for moderate exercise • Severe right outflow tract obstruction (risk of sudden
Severe form of Ebstein’s anomaly with significant right heart cardiac death is high when RVSP is between half to two-
enlargement and regurgitation. third of the systolic pressure) 821
10 • Severe PR operation depends on left ventricular function, patency of the
• Marked RV dilatation and decreased RV function coronary arteries and the pulmonary blood flow.50
• Inoperable severe PS or infundibular stenosis. Those with coronary ostial fibrosis or obstructive coronary
artery disease may have exercise-induced ischemia. Varying

Transposition of the Great Arteries degree of residual impaired left ventricular function may limit
exercise performance. Impaired baseline LV contractility and
The impact of the systemic RV function, systemic AV valve reversible myocardial perfusion defects and mild wall motion
regurgitation, aortic regurgitation, small baffle leaks or abnormalities may occur.51 Abnormal pulmonary blood flow
obstructions may take a toll on exercise performance in distribution related to branch pulmonary artery stenosis
these individuals. In addition to sinus node dysfunction, or hypoplasia has been associated with a reduced exercise
conduction defects and propensity for atrial arrhythmias capacity and increased ventilatory drive during exercise in
also compound issues relating to exercise performance these patients.52
in some of these patients.46,47 Incremental increase in
exercise training over years can markedly improve exercise Restriction for heavy exercise and athletics
performance and cardiovascular status. Exercise testing with • Obstructive coronary artery disease
annual re-evaluation should be performed in all patients with • Severely decreased postoperative LV function
transposition complex before allowing involvement in sports. • Severe aortic regurgitation from the neo-aorta
• Branch pulmonary artery stenosis or hypoplasia.
D-Transposition of the Great Arteries (DTGA)
Congenitally Corrected Transposition of the Great
Atrial switch repair Arteries (CCTGA)
Maximal exercise capacity is reduced in adult patient
after a Mustard or Senning procedure.46,48 According to a In CCTGA, where the two wrongs—atrioventricular
study by Buys et al. impaired peak exercise performance discordance (ventricular inversion) and ventriculoarterial
results mainly from the inability to increase stroke volume discordance (transposition of the great arteries)—try to
and heart rate at higher exercise intensities. In this study, make it right by restoring the physiological circulation, but
Senning (rather than Mustard) repair and a well-preserved result in a systemic morphological right ventricle. Impaired
right ventricular function were related to a better peak systemic right ventricular function, decreased contractility of
oxygen consumption. An active lifestyle was noted to have the pulmonic ventricle, presence of associated CHDs such as
a positive effect on exercise capacity and perceived physical a VSD or PS and decreased chronotropic response to exercise
functioning.49 dictate the cardiovascular performance.53
Regular aerobic exercise markedly improves cardiovascular
Restriction for heavy exercise and athletics conditioning with very promising long-term results.
• Reduced systemic RV function
• Limited oxygen uptake due to the atrial baffles limiting No restrictions
ventricular filling at higher heart rates, thereby restricting • Asymptomatic patients with CCTGA without other cardiac
an increase in stroke volume to match the increased abnormalities
myocardial oxygen demands during exercise • No systemic RV enlargement or dysfunction
• Uncontrolled atrial arrhythmias • No evidence of resting or exercise induced atrial or
• Chronotropic incompetence (due to sinus node dysfunction) ventricular tachyarrhythmias (confirmed on ambulatory
before pacemaker implantation. ECG monitoring or exercise testing).
Restrictions for moderate exercise Restrictions for moderate exercise

• Severely decreased systemic RV function • Severely decreased systemic RV function
• Severe subaortic or subpulmonic obstruction. • Severe subaortic or subpulmonic obstruction
• Atrial or ventricular arrhythmias
Arterial switch repair
Individuals who underwent arterial switch operation now have Univentricular Hearts (Single ventricle physiology)
the left ventricle (LV) as their systemic ventricle and nearly
normal physiology. This procedure involves transection and In the univentricular heart, the burden of pumping falls on a
removal of the great arteries above the sinuses of Valsalva large dominant ventricle (usually the left ventricle) since the
followed by reimplantation of the coronaries into the neo- other ventricle is small and rudimentary. Right ventricular
aorta. There can be a few issues impacting exercise capacity hypoplasia with tricuspid atresia is the commonest form
822 and functional status of these patients. The success of this for which most patients undergo the Fontan procedure
(classic right atrium to pulmonary artery conduit or one of functional class and objectively measured exercise capacity, 57
its modifications). Exercise tolerance may be reduced due when used appropriately and cautiously as indicated.61
to impaired ventricular function, increased venous pressure
and congestion and difficulty in increasing preload that leads Syndromes
to low cardiac output. In addition, atrial arrhythmias have a
negative impact on exercise tolerance.54,55 Exercise recommendations for adolescents and adults with
Skeletal muscle function in Fontan patients is abnormal, specific syndromes such as Marfan or Down syndrome, are
which may have an impact in the reduced exercise tolerance discussed in their respective chapters.
encountered in these patients.56 Exercise training has beneficial
impacts on the skeletal muscle function in this population.57 YOGA AND TAI CHI CHUAN
Exercise testing should be performed before allowing
involvement in sports. Oxygen saturation should be tested The integrating mind-body relaxation techniques are
before and after exercise since intracardiac or intrapulmonary well known to have a positive effect on health outcomes,
shunting may reduce exercise tolerance. especially in patients with chronic diseases. More recent
studies have noted beneficial cardiovascular effects and
Restriction for Heavy Exercise and Athletics overall improvement in quality of life.62 By the nature of the
movements involved, it is possible for all people to perform
Patients with univentricular hearts who have had a Fontan certain Yoga and Tai Chi exercises despite the limitations
operation may have very good exercise tolerance and can imposed by other co-morbidities or age. Therefore, these
participate in low intensity sports if the: forms of exercises allow diverse application to people of all
• Systemic ventricular function is normal ages, cultures and infirmities.
• Oxygen saturation is normal. Yoga combines physical and breathing exercises that
have benefited people with many chronic health conditions.
Restrictions for Moderate Exercise Improved exercise tolerance and positive effect on levels of
inflammatory markers have been noted in patients with heart
• Moderate or severe ventricular dysfunction failure.63 Yoga respiratory training improves respiratory
• Arrhythmias function leading to an improvement of both the cardiac
• Reduced pulmonary functional capacity due to thoracic autonomic modulation and the sympathovagal balance
abnormalities (kyphoscoliosis). evaluated by heart rate variability.64 Pranayama, a yogic
exercise related to breathing, significantly reduces the indices
Eisenmenger physiology of ventricular repolarization dispersion in patients with
arrhythmia. Further studies are needed to assess its impact
Restrictions for moderate to heavy exercise and athletics on reducing the risk of malignant ventricular arrhythmias.65
Patients with Eisenmenger physiology have severe pulmonary Melville et al showed that yogic postures or meditation
vascular disease characterized by severe pulmonary performed in the office can acutely improve several
hypertension, due to reversal of shunt associated with an ASD, physiological and psychological markers of stress.66
VSD or PDA. Systemic vascular resistance may fall with Tai Chi is a low-impact, weight-bearing form of exercises
exercise and reduce the pulmonary venous return, leading characterized by gentle movements designed to dissipate
to exercise-induced syncope or SCD. Exercise tolerance is force throughout the body while the subject changes poses.
usually very restricted in this population.58 It involves well-coordinated sequences of both isometric
For risk stratification in the office, a six-minute walk test and isotonic segmental movements in the trunk and
is recommended with blood pressure, heart rhythm and pulse all extremities.67 Several studies have shown multiple
oximetry measurements taken before and after exercise. For cardiovascular benefits including improvements in blood
most patients, only mild isotonic exercise such as walking at pressure, arrhythmias and psychosocial well being.68,69 Like
a tolerable pace for short duration and very light weights (less yoga it appears to be safe and enjoyable for all age groups. For
than one lb/500 mg) with more repetitions to maintain muscle people with CHD, it could be a valuable alternative to both the
and bone strength are recommended. high and low intensity aerobic exercise regimens. Tai Chi is a
Exercise capacity and quality of life improves significantly group activity requiring only one supervising instructor for a
in iron-deficient patients with Einsenmenger syndrome, large number of people and is therefore cost efficient.70
after receiving three months of monitored iron replacement
therapy.59 Chronic nifedipine therapy has shown an increase in CONCLUSION
arterial oxygen saturation on exercise and improved maximal
exercise capacity in these patients.60 Bosentan, an endothelin Exercise and sports recommendations are designed to provide
receptor antagonist, has also shown an improvement in guidance to clinicians so that they can individualize medically 823
10 
table 4 7. Mitchell JH, Haskell WL, Snell P, et al. Task Force 8. 36th
Bethesda Conference: Classification of sports. J Am Coll
Congenital heart defects and genetic disorders commonly
associated with sudden cardiac death during sports Cardiol. 2005;45:1364-7.
8. Maron, BJ. Sudden death in young athletes. N Engl J Med. 349

• Hypertrophic cardiomyopathy (2003). pp. 1064-75.
• Coronary artery anomalies-abnormal origins 9. Driscoll DJ, Edwards WD. Sudden unexpected death in children
and adolescents. J Am Coll Cardiol. 5 (1985). pp. 118B-21B.
• Arrhythmogenic right ventricular cardiomyopathy/dysplasia 10. Garson AJ, McNamara DG. Sudden death in a pediatric cardi-
• Marfan syndrome ology population, 1958 to 1983 relation to prior arrhythmias. J
• Severe/critical aortic stenosis Am Coll Cardiol, 5 (1985). pp. 134B-17B.
11. Campbell RM, Berger S, Drezner J. Sudden cardiac arrest
• Hypoplastic coronaries in children and young athletes: the importance of a detailed
personal and family history in the pre-participation evaluation.
acceptable exercise programs allowing participation in sports Br J Sports Med. 2009;43(5):336-41. Epub 2008 Aug 21.
Review.
for adolescents/adults with CHD. Exercise training and
12. Pelliccia A, Di Paolo FM, Corrado D, et al. Evidence for
physical rehabilitation programs may be recommended when
efficacy of the Italian national pre-participation screening
indicated.71 Appropriate screening should be performed to programme for identification of hypertrophic cardiomyopathy
identify the CHD and genetic disorders commonly associated in competitive athletes.Eur Heart J. 2006;27:2196-200. Epub
with SCD during sports (Table 4). Yoga or Tai Chi complement 2006 Jul 10.
the benefits of routine aerobic exercise and enhance mind- 13. Corrado D, Pelliccia A, Bjørnstad HH, et al. Cardiovascular
body relaxation. The goals of exercise/sports in CHD are to pre-participation screening of young competitive athletes for
enhance physical, mental and psychosocial well being while prevention of sudden death: proposal for a common European
improving long-term clinical outcomes that are so strongly protocol. Consensus Statement of the Study Group of Sport
Cardiology of the Working Group of Cardiac Rehabilitation and
linked with functional capacity.
Exercise Physiology and the Working Group of Myocardial and
Pericardial Diseases of the European Society of Cardiology.
Health is a state of complete harmony of the body, mind and Eur Heart J. 2005;26:516-24. Epub 2005 Feb 2. Review.
spirit. When one is free from physical disabilities and mental 14. Lawless CE, Best TM. Electrocardiograms in athletes:
distractions, the gates of the soul open. interpretation and diagnostic accuracy. Med Sci Sports Exerc.
—B.K.S. Iyengar 2008;40:787-98.
15. Antzelevitch C, Brugada P, Borggrefe M, et al. Brugada
REFERENCES syndrome: report of the second consensus conference. Heart
Rhythm. 2005 Apr;2(4):429-40. Review. Erratum in: Heart
1. Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2007 Rhythm. 2005;2(8):905.
Guidelines on Perioperative Cardiovascular Evaluation and 16. Rodriguez FH, Moodie DS, Neeland M, et al. Identifying
Care for Noncardiac Surgery: Executive Summary. J Am Coll arrhythmias in adults with congenital heart disease by 24-h
Cardiol. 2007;50:1707-32. ambulatory electrocardiography. Pediatr Cardiol. 2012;33:
2. Freed MD. Recreational and sports recommendations for the 591-95. Epub 2012 Feb 9.
child with heart disease. Pediatr Clin North Am. 1984;31: 17. Kenny D, Chakrabarti S, Ranasinghe A, et al. Single-
1307-20. centre use of implantable loop recorders in patients with
3. Mitchell JH, Blomqvist CG, Haskell WL, et al. Classification of congenital heart disease. Europace. 2009;11:303-07. Epub
sports. 16th Bethesda Conference: cardiovascular abnormalities 2009 Jan 18.
in the athlete: recommendations regarding eligibility for 18. Fredriksen PM, Kahrs N, Blaasvaer S, et al. Effect of physical
competition. J Am Coll Cardiol. 6 (1985). pp. 1198-9. training in children and adolescents with congenital heart
4. Mitchell JH, Haskell WL, Raven PB, et al. Classification of disease. Cardiol Young. 2000;10:107-14.
sports. 26th Bethesda Conference: cardiovascular abnormalities 19. Instebø A, Norgård G, Helgheim V, et al. Exercise capacity in
in the athlete: recommendations for determining eligibility for young adults with hypertension and systolic blood pressure
competition in athletes with cardiovascular abnormalities. J difference between right arm and leg after repair of coarctation
Am Coll Cardiol. 24 (1994). pp. 864-6. of the aorta. Eur J Appl Physiol. 2004;93:116-23. Epub 2004
5. Niwa K, Perloff JK, Bhuta SM, et al. Structural abnormalities Jul 28.
of great arterial walls in congenital heart disease: light 20. Freed MD, Rocchini A, Rosenthal A, et al. Exercise-induced
and electron microscopic analyses. Circulation. 2001;103: hypertension after surgical repair of coarctation of the aorta.
393-400. Am J Cardiol, 43 (1979). pp. 253-8.
6. Gutgesell HP, Gessner IH, Vetter VL, et al. Recreational and 21. Child JS. Echo-Doppler and color-flow imaging in congenital
occupational recommendations for young patients with heart heart disease. Cardiol Clin. 1990;8:289-313.
disease. A Statement for Physicians by the Committee on 22. Tede NH, Child JS. Diastolic dysfunction in patients with
Congenital Cardiac Defects of the Council on Cardiovascular congenital heart disease. Cardiol Clin. 2000;18:491-9.
23. Maron BJ. Hypertrophic cardiomyopathy- an important
824 Disease in the Young, American Heart Association. Circulation.
1986;74:1195A-8A. global disease. Am J Med. 2004;116:63-5.
24. Burke AP, Farb A, Virmani R, et al. Sports-related and non-
sports-related sudden cardiac death in young adults. Am Heart
channelopathies and implantable defibrillators. Eur J
Cardiovasc Prev Rehabil. 2006;13:676-86.
57
J. 1991;121:568-75. 41. Mellwig KP, van Buuren F, Gohlke-Baerwolf C, et al.
25. Maron BJ, Gohman TE, Kyle SB, et al. Clinical profile and Recommendations for the management of individuals with
spectrum of commotio cordis. JAMA. 2002;287:1142-6. acquired valvular heart diseases who are involved in leisure-
26. Maron BJ. Hypertrophic cardiomyopathy: a systematic review. time physical activities or competitive sports. Eur J Cardiovasc
JAMA. 2002;287:1308-20. Prev Rehabil. 2008;15:95-103.
27. Kempny A, Dimopoulos K, Uebing A, et al. Reference 42. Trojnarska O, Szyszka A, Gwizdała A, et al. Adults with Ebstein’s
values for exercise limitations among adults with congenital anomaly–Cardiopulmonary exercise testing and BNP levels
heart disease. Relation to activities of daily life–single exercise capacity and BNP in adults with Ebstein’s anomaly. Int
centre experience and review of published data. Eur Heart J. J Cardiol. 2006;111:92-97. Epub 2005 Oct 19.
2012;33:1386-96. Epub 2011 Dec 23. 43. Luijendijk P, Bouma BJ, Vriend JW, et al.Usefulness of
28. Davis JA, Cecchin F., Jones, TK, et al. Major coronary artery exercise-induced hypertension as predictor of chronic
anomalies in a pediatric population: incidence and clinical hypertension in adults after operative therapy for aortic isthmic
importance. J Am Coll Cardiol. 2001;37:593-7. coarctation in childhood. Am J Cardiol. 2011;108:435-39.
29. Basso C, Maron BJ, Corrado D, et al. Clinical profile of Epub 2011 May 6.
congenital coronary artery anomalies with origin from the 44. Gatzoulis MA, Balaji S, Webber SA, et al. Risk factors for
wrong aortic sinus leading to sudden death in young competitive arrhythmia and sudden cardiac death late after repair of
athletes. J Am Coll Cardiol. 2000;35:1493-501. tetralogy of Fallot: a multicentre study. Lancet. 2000;356:
30. Maron BJ, Poliac L, Kaplan JA, et al. Blunt impact to the 975-81.
chest leading to sudden death from cardiac arrest during sports 45. van den Berg J, de Bie S, Meijboom FJ, et al. Changes
activities.N Engl J Med. 333 (1995). pp. 337-42 during exercise of ECG intervals related to increased risk for
31. Maron BJ, Shen WK, Link MS, et al. Efficacy of implantable ventricular arrhythmia in repaired tetralogy of Fallot and their
cardioverter-defibrillators for the prevention of sudden death
relationship to right ventricular size and function. Int J Cardiol.
in patients with hypertrophic cardiomyopathy. N Engl J Med,
2008;124:332-38. Epub 2007 Apr 11.
342.
46. Mathews RA, Fricker FJ, Beerman LB, et al. Exercise studies
32. Vermes E, Strohm O, Otmani A, et al. Impact of the revision
after the Mustard operation in transposition of the great arteries.
of arrhythmogenic right ventricular cardiomyopathy/dysplasia
Am J Cardiol. 1983;51:1526-9.
task force criteria on its prevalence by CMR criteria. JACC
47. Hesslein PS, Gutgesell HP, Gillette PC, et al. Exercise
Cardiovasc Imaging. 2011;4:282-7.
assessment of sinoatrial node function following the Mustard
33. Szymański P, Klisiewicz A, Hoffman P. ARVC/D task force
operation. Am Heart J. 1982;103:351-7.
imaging criteria: it is difficult to get along with the guidelines.
48. Budts W, Scheurwegs C, Stevens A, et al. The future of adult
JACC Cardiovasc Imaging. 2011;4:686.
34. Bluemke DA. ARVC: Imaging diagnosis is still in the eye of patients after Mustard or Senning repair for transposition of
the beholder. JACC Cardiovasc Imaging. 2011;4:288-91. the great arteries. Int J Cardiol. 2006;113:209-14. Epub 2006
35. Maron BJ, Douglas PS, Graham TP, et al. Task Force 1: Jan 10.
preparticipation screening and diagnosis of cardiovascular 49. Buys R, Van De Bruaene A, Budts W, et al. In adults with
disease in athletes. J Am Coll Cardiol. 2005;45:1322-6. atrial switch operation for transposition of the great arteries
36. Graham Jr TP, Bricker, JT, James FW, et al. Task Force 2: low physical activity relates to reduced exercise capacity
Congenital heart disease: 26th Betheda Conference. J Am Coll and decreased perceived physical functioning. Acta Cardiol.
Cardiol, 24.1994:867-73. 2012;67:49-57.
37. Graham Jr TP, Driscoll DJ, Gersony WM, eta al. Task Force 2: 50. Reybrouck T, Eyskens B, Mertens L, et al. Cardiorespiratory
Congenital heart disease. 36th Bethesda Conference. J Am Coll exercise function after the arterial switch operation for
Cardiol. 2005;45:1326-33. transposition of the great arteries. Eur Heart J. 2001; 22: 1052-
38. Waggoner AD, Barzilai B, Pérez JE. Saline contrast enhance- 9.
ment of tricuspid regurgitant jets detected by Doppler color 51. Hui L, Chau AK, Leung MP, et al. Assessment of left
flow imaging. Am J Cardiol. 1990;65:1368-71. ventricular function long term after arterial switch operation
39. Heidbüchel H, Panhuyzen-Goedkoop N, Corrado D, et for transposition of the great arteries by dobutamine stress
al. Study Group on Sports Cardiology of the European echocardiography. Heart. 2005;91:68-72.
Association for Cardiovascular Prevention and Rehabilitation. 52. Giardini A, Khambadkone S, Taylor A, et al. Effect of
Recommendations for participation in leisure-time physical abnormal pulmonary flow distribution on ventilatory efficiency
activity and competitive sports in patients with arrhythmias and and exercise capacity after arterial switch operation for
potentially arrhythmogenic conditions Part I: Supraventricular transposition of great arteries. Am J Cardiol. 2010;106:1023-
arrhythmias and pacemakers.Eur J Cardiovasc Prev Rehabil. 28. Epub 2010 Aug 17.
2006;13:475-84. 53. Fredriksen PM, Chen A, Veldtman G, et al. Exercise capacity
40. Heidbüchel H, Corrado D, Biffi A, et al. Recommendations in adult patients with congenitally corrected transposition of
for participation in leisure-time physical activity and the great arteries. Heart. 2001;85:191-5.
competitive sports of patients with arrhythmias and potentially 54. Ohuchi H. Cardiopulmonary response to exercise in patients
arrhythmogenic conditions. Part II: ventricular arrhythmias, with the Fontan circulation. Cardiol Young. 2005;15:39-44.
825
10 55. Ohuchi H, Hamamichi Y, Hayashi T, et al. Post-exercise heart
rate, blood pressure and oxygen uptake dynamics in pediatric
heart failure. J Card Fail. 2008;14:407-13. Epub 2008
May 27.
patients with Fontan circulation Comparison with patients after 64. Santaella DF, Devesa CR, Rojo MR, et al. Yoga respiratory
right ventricular outflow tract reconstruction. Int J Cardiol. training improves respiratory function and cardiac
2005;101:129-36. sympathovagal balance in elderly subjects: a randomised
56. Brassard P, Poirier P, Martin J, et al. Impact of exercise training controlled trial. BMJ Open. 2011;1:e000085.
on muscle function and ergoreflex in Fontan patients: a pilot 65. Dabhade AM, Pawar BH, Ghunage MS, et al. Effect of
study. Int J Cardiol. 2006;107:85-94. Epub 2005 Jul 19. pranayama (breathing exercise) on arrhythmias in the human
57. Brassard P, Bédard E, Jobin J, et al. Exercise capacity and heart. Explore (NY). 2012;8:12-5.
impact of exercise training in patients after a Fontan procedure: 66. Melville GW, Chang D, Colagiuri B, et al. Fifteen minutes
a review.Can J Cardiol. 2006;22:489-95. Review. of chair-based yoga postures or guided meditation performed
58. Müller J, Hess J, Hager A. Exercise performance and quality in the office can elicit a relaxation response. Evid Based Com-
of life is more impaired in Eisenmenger syndrome than in plement Alternat Med. 2012;2012:501986. Epub 2012 Jan 16.
complex cyanotic congenital heart disease with pulmonary 67. Caminiti G, Volterrani M, Marazzi G, et al. Tai chi enhances
stenosis. Int J Cardiol. 2011;150:177-81. Epub 2010 May 1. the effects of endurance training in the rehabilitation of
59. Tay EL, Peset A, Papaphylactou M, et al. Replacement therapy elderly patients with chronic heart failure. Rehabil Res Pract.
for iron deficiency improves exercise capacity and quality of 2011;2011:761958. Epub 2010 Sep 13.
life in patients with cyanotic congenital heart disease and/or 68. Cheng TO. Tai Chi: the Chinese ancient wisdom of an ideal
the Eisenmenger syndrome. Int J Cardiol. 2011;151:307-12. exercise for cardiac patients. Int J Cardiol. 2007;117:293-95.
Epub 2010 Jul 1. Epub 2006 Aug 9. Review.
60. Wong CK, Yeung DW, Lau CP, et al. Improvement of exercise 69. Yeh GY, Wood MJ, Lorell BH, et al. Effects of Tai Chi mind-body
capacity after nifedipine in patients with Eisenmenger movement therapy on functional status and exercise capacity in
syndrome complicating ventricular septal defect. Clin Cardiol. patients with chronic heart failure: a randomized controlled trial.
1991;14:957-61. American Journal of Medicine. 2004;117:541-8.
61. Fine N, Dias B, Shoemaker G, et al. Endothelin receptor 70. Barrow DE, Bedford A, Ives G, et al. An evaluation of the
antagonist therapy in congenital heart disease with shunt- effects of Tai Chi Chuan and Chi Kung training in patients with
associated pulmonary arterial hypertension: a qualitative symptomatic heart failure: a randomised controlled pilot study.
systematic review. Can J Cardiol. 2009;25:e63-8. Postgraduate Medical Journal. 2007;83:717-21.
62. Brown DR, Wang Y, Ward A, et al. Chronic psychological 71. Balady GJ, Ades PA, Comoss P, et al. Core components of
effects of exercise and exercise plus cognitive strategies. cardiac rehabilitation/secondary prevention programs: a
Medicine and Science in Sports and Exercise. 1995;27:765-75. statement for healthcare professionals from the American Heart
63. Pullen PR, Nagamia SH, Mehta PK, et al. Effects of yoga on Association and the American Association of Cardiovascular
inflammation and exercise capacity in patients with chronic and Pulmonary Rehabilitation. Circulation. 2000;102:1069-73.
826
Psychosocial Challenges and
C hapter
58 Psychiatric Issues while Growing Up

with Congenital Heart Disease
Tracy Kustwan Livecchi*, Reema Chugh**, Nolan Thompson***, Syed T Rizvi****
surgeries, heart failure and risk of sudden cardiac death are

PSYCHOSOCIAL CHALLENGES just some of the medical challenges faced by the adult patients.
The information presented here is not only taken from
Introduction published literature but is also from our own perspectives (as
a patient with complex congenital heart disease who has also
Due to the rapid advances in early diagnosis and cardiac inexperienced being a counselor working with CHD patients*
terventions, today’s estimated survival rate of infants born and as physicians caring for ACHD** and psychiatric
with congenital heart disease (CHD) has improved tremen- issues***, ****). We believe that presenting a combination
dously. According to one study, infants diagnosed with CHD of sources is essential because “when ACHD patients share
today have over a 95 percent chance of reaching adulthood in experiences with each other, many of the issues and challenges
developed countries. This figure is in comparison to the much identified fall outside of the existing published literature”.3
reduced survival rate of 55 years ago, in which only 25 percent
of these infants made it through their first year of life.1 Growing up with Congenital Heart Disease
Medical professionals are now faced with caring for over
1,000,000 adults with CHD in the USA alone.2 With the task of Since there are a wide variety of diagnoses with different
caring for this first generation of adult survivors, many in the levels of complexity, the individual experiences of this patient
field are just beginning to consider the psychosocial aspects of population varies greatly. Furthermore, when looking at
this rapidly growing patient population. We write this chapter psychosocial effects, it is important to note that each individual
in hopes of increasing awareness in health care providers must be taken into consideration in terms of their specific
regarding the unique and often complicated psychiatric and medical history, age, prognosis, personality, social support
psychosocial issues affecting this patient population. We also systems, individual coping style and resources available to
challenge you to consider how some of these described needs them. Even when faced with two individuals with identical
can be better addressed in the facility in which you practice. diagnoses and treatment histories, their overall mental health
In exchange for this promising survival rate, children and and quality of life can be astonishingly different.
adolescents with CHD are often subject to a variety of extreme For many CHD patients, their cardiac defect presents
stress producing events. These life altering experiences often them with great trauma beginning from the day they are born.
include numerous invasive procedures, surgeries, coping Not only do many of them have to learn to live with a life
with life-threatening symptoms and overwhelming medical threatening illness, but they have to cope with numerous
information, repeated hospitalizations, interruptions in traumatic and painful medical procedures. Often patients
education and limitations on extracurricular activities and will describe multiple emergency trips to the hospital,
socialization. unanticipated, pervasive physical symptoms and withheld
Since there is almost no surgical cure for congenital heart medical information and/or uncertain diagnoses. For some
disease, many of these same individuals face a wide spectrum patients with CHD, their illness sometimes feels relentless.
of continued cardiac symptoms and ongoing treatment Loss is often a theme in working with CHD patients.
requirements as adults.1 Cardiac arrhythmias, the adjustment Sometimes it means being forced to cope with facing
to cardiac devices such as automated implantable cardiac mortality at a very early age. It can also mean the loss of
defibrillators (AICD) or pacemakers, the threat of cardiac independence, physical abilities or a change in physical
10 appearance. For the adolescent with CHD, loss may mean On the opposite end of the spectrum, some patients were
never having the opportunity to participate in team sports or told that they had ‘corrective’ surgery and that they were
other physical or social activities. For an adult woman with ‘cured’. I was one of those lucky ‘miracle babies’ and I
CHD, it sometimes means not being able to have a child remember hearing this repeatedly as a child and finally let
of her own (biological and/or adopted). There is often an my ‘emotional guard down’ (after hearing ‘don’t worry, you
enormous sense of grief for these along with other losses, worry too much’ from both physicians and family) only to
which must be worked through in order to move on and end up with multiple cardiac problems as a young adult*.
carve out a meaningful life for oneself. Unfortunately, many CHD patients, after years of clinical
This grief is sometimes complicated by society’s reaction to stability experience deterioration in their health and ability to
these feelings. One example of this is the common belief that function. These patients often feel ‘angry and betrayed by their
the longer one lives with a loss, the easier it is to overcome, i.e. hearts, health, physicians and families’ because no one told
“Since I have lived with this my whole life, I should be over them that they may have to face cardiac difficulties again.5 As
it by now”. Some patients actually have disclosed feelings of a result, shock, anger, denial and fright are different emotional
guilt regarding their intermittent or delayed feelings of loss. reactions that many of these patients can experience. Often
However, for many CHD patients, it is not developmentally the return of cardiac symptoms can propel the individual to
possible for them to realize the full extent of their illness until recount previous hospitalizations which may only contribute
they reach adulthood. to their anxiety, fear and uncertainty about their future.
Struggles with body image and the perception of being Another theme occasionally expressed by patients with
different were mentioned in one study as being significant CHD is awareness that the human heart holds strong symbolic
issues in this patient population.4 Scarring, cyanosis and meaning. For many it signifies emotion, the center of life, love
physical restrictions are just some of the issues many of and the human spirit. For some, this resonates beyond their
these patients must learn to cope with on a daily basis. For a physical cardiac lesion and symptomatology; when one has a
teen struggling to ‘fit in’ with his/her peers, this can often be ‘broken heart’ this in of itself can have tremendous impact on
extremely difficult as peer relationships are such an important one’s psyche. This concept was expressed so well by Fischer
part of individuation process. For adults, this theme is often and Cleveland ‘by producing a rhythm felt throughout the
revisited when deciding how and what to tell a romantic body, the heart plays a fundamental role in the individual’s
partner or employer regarding their CHD and then dealing image of self’.4
with potential negative reactions.
Academic performance and employment choices are also Quality of Life
important issues facing by patients. For some, occupational
success is hampered by lapses in school or work due to their Quality of life “reflects a patient’s life satisfaction and ability to
CHD. Health insurance and the financial ability to support function in a variety of life domains including physical, social,
oneself is a consideration for the young adult transitioning emotional and work-related”.7 A study conducted by Moons
from their parents care. Many of the studies suggest that and colleagues defined quality of life as “the degree of overall
moving into a state of independence can be challenging for life satisfaction that is positively or negatively influenced by
some CHD patients. One study found that 83 percent of individuals’ perception of certain aspects of life important to
their subjects chose to stay close to their family home and them, including matters both related and unrelated to health”.8
medical care.5 Another study found that “among patients with Despite the higher rates of psychological distress and the
congenital heart disease there were significantly more of those psychosocial issues described above, some of the research
who had developed a dependent life style, living with their has shown that CHD patients are thriving in many ways and
parents without a marital or quasi-marital relationship”.6 actually report having a better quality of life than their non-
Verstappen articulately describes how the early messages CHD counterparts.9 Much of the research has shown that this
some CHD patients are given can greatly affect their overall group of individuals perseveres. One study had found that in
perspective with regards to their illness and how they live terms of academic achievement and occupational status “these
their lives.3 One message that was given to some was that they respondents seem clearly beyond what one would expect in a
would not live long. As one can imagine, medically centered normal adult population” and that by various criteria, these
anxiety, fear of death and apprehension regarding important patients seemed ‘successful.’10
decision making are all potential emotional consequences of
such a belief. Many of these same patients, now adults, are Role of the Provider Caring for Patients with
alive and wondering how to play ‘catch up’ in terms of their life Congenital Heart Disease
choices (or lack of). Some may still be living with their parents
while others may wish they had invested in certain academic or As a provider, the following measures have shown positive
career choices. Some may find themselves alone as they were outcomes in our practice**. First of all, communication is
828 never able to build a long-term, intimate relationship. the key. We need to stop, look and understand. One needs to
understand, acknowledge the special needs, then approach CHD especially in those with complex CHD and/or cyanotic 58
the individuals with CHD as well as their families in a kind CHD. We have seen many young girls and boys express
and sensitive manner. Knowing their lifelong struggles, their distress over the teasing that goes on in schools because they
Psychosocial Challenges and Psychiatric Issues while Growing Up with Congenital Heart Disease
challenges and limitations should lead us to individualize have kyphoscoliois, cyanosis, clubbing or visible scars.
management for each person. The clinic and the hospital It is important to encourage ‘positive thinking’ and make
environment should to be warm, friendly and resourceful. the patient and families aware of ‘realistic expectations’. The
When faced with a medical or surgical emergency, it is door should be left open with regards to questions relating to
common for the patient and their family to feel overwhelmed long-term outcomes and possibilities such as “What does the
even if they are health care professionals. At this time of need, future hold for me? The fields of medicine and surgery are
there should be an established support system to help them constantly in evolution and therefore the recommendations
navigate physically, emotionally, mentally and spiritually also change over time.
through the medical system with their difficulties. The Clinical I have several patients who never got married or had
Social Worker and the Clinical Nurse Specialist (Registered families because they were told several decades ago that it
Nurse or Advanced Nurse Practitioner) who are involved in would ‘not be feasible for them’ to do so. However, the
caring for people with chronic disabilities (especially CHD) outcomes are far more positive if the health care provider
are most resourceful. The families should have their contact informs them of their ‘current’ abilities and limitations. They
information in order to reach them promptly. should be given hope by encouraging them to follow-up and
For routine care, the physicians and the Clinical Nurse stay up-to-date with the changing paradigms. Guiding people
Specialist should make sure that there is a sound system to as to how they can experience the best possible outcome in
ensure follow-up appointments, discuss test results, answer every situation heals them from despair over time. Reminding
questions/concerns for the patients and their families. ourselves that we mentally, psychologically and spiritually
Prescriptions should be filled in an efficient and timely fashion. make our own choices is critical to our existence. The World
These measures can help reduce anxiety and lapses in care. Health Organization (WHO) defines health as a state of
We need to have genuine respect for our patients and allow complete physical, mental, social well-being and not merely
them to be ‘active’ participants in their health care. We need the absence of disease or infirmity. For a complete sense of
to ‘empower’ them with the knowledge and understanding well-being, all the aspects of health need to be addressed.
of the routine care relating to their condition. Knowledge is As providers, our task is to provide the best information in
powerful and sharing information is even more powerful. order for the individuals with CHD and their families to make
Health education classes, handouts and online resources help the best decisions from time to time. Facilitating transition
those who are more receptive and the most effective moment through stages of life, especially from childhood to adulthood
for a health care provider to share the key information is at is vital for the continuity of care. The chapter on Transitional
the clinic visit or during the hospitalization. These measures Care in Congenital Heart Disease (Chapter 53) deals with this
promote compliance with preventive care, follow-ups and matter in more detail.
medical/surgical treatments. Counseling for personal needs, advice regarding intimacy,
Denial is noted in many individuals with CHD from early pregnancy and contraception are often ignored aspects of
in life. This may come from parents, the children themselves medical care. Both men and women often have fears of passing
or the health care providers (especially physicians). Denial their congenital heart condition to their children or having them
and minimization can be both adaptive and maladaptive. suffer like they did. They are also worried about living long
Although, denial may help ‘normalize’ functioning with enough to raise a child. Patients are usually too embarrassed
regards to survival (such as with education and employment), to bring up this issue. Many general practitioners are reluctant
it can camouflage serious emotional problems leading to to prescribe oral contraceptives to women with underlying
high rates of undiagnosed or untreated mood and anxiety heart disease.4 On the other side of the spectrum, women with
disorders seen in this population. It has been observed that cyanotic congenital heart disease may face fertility issues and
very rarely patients have requested referrals and been referred are also at higher risk for carrying a pregnancy should they
to a psychiatrist/psychologist. Their happy appearance may conceive. For many women not being able to bear children
cover feelings of fears of decline, premature death, loneliness, because of their cardiovascular condition, can be a devastating
isolation, anxiety and depression. These feelings can be blow to their sense of identity and self worth.5 The Clinical
disabling especially in those who are single, unemployed and Nurse Specialist and the Clinical Social Worker are often
isolated.5 most tactful in laying the groundwork by gently addressing
One of the most common phrases that I hear from my these issues in a one-to-one session with the patients who are
patients is “I want to be normal”. The definition of ‘normal’ is generally too shy or embarrassed to bring these matters up in
relative. It depends on the person and on his or her cultural and front of their families. These patients can then be directed to
environmental expectations. Many studies have shown that their physicians to address the technical aspects in dealing with
feeling ‘different’ is a common experience among patients with these issues. 829
10 Informative discussions on these issues can help allay their when turned around. A positive mindset and optimism can
fears and concerns. Some of these guidelines are discussed help immensely. Most limitations are the ones that we impose
in more detail in the chapter on Pregnancy, Contraception on ourselves.
and Gynecological Issues in Women with Congenital Heart Work is usually highly valued among most people with
Disease (Chapter 56) A significant number of women with CHD and they usually show amazing resilience in continuing
CHD are able to have pregnancies, some choose adoption, to be productive despite their physical limitations. Most of
while others may have accidental pregnancies that they choose them display persistence, perseverance, a tremendous amount
to terminate. of patience in achieving their lifetime dreams and goals. We
The families of the individuals with CHD also need a lot of can see the proof of this in our day to day practice where
support since they too suffer from many psychosocial issues. many of our patients grew up and followed their dreams to
Many mothers feel responsible for their child’s illness and project become emotionally, socially and economically successful.
onto the sick heart all their suffering and sorrow. This may lead Some chose careers in the health care profession and are
to activation of unconscious aggressive feelings in the parents very sensitive to the needs of others. Many rose above
and overprotective behavior towards the child. The family their physical limitations to participate in exercise and
may first react to the diagnosis with shock, discouragement sports beyond expectations. Some were triumphant in the
and depression. This may be followed by a phase of struggle Special Olympics and other physically challenging sports.
against the medical illness or they may end up in denial of the Most survivors with CHD are extraordinarily courageous,
illness. Chronic diseases often lead to a reorganization of the usually determined to work, contribute to society and be as
family system around the illness. Siblings may also be affected ‘normal’ as possible.1 Although, studies have shown that their
and are at increased risk for psychopathological disorders such level of education exceeded the national average, there are
as behavioral and/or psychosomatic issues. Group meetings many who consider themselves disabled and do not pursue
with parents allow involvement of the parents in the treatment higher education or vocational training to gain meaningful
plans. They help them overcome these issues by discussing employment. Career and vocational counseling should be an
their hopes, fears and anxieties.11 Not to be ignored are the integral part of any CHD program.12 The goal is to assist the
family stressors relating to an increased strain and drain on the patients in selecting a career corresponding to their special
family financial situation, from health care expenses. In the needs or clinical limitations, while serving their personal
unfortunate event of a death of the child, adolescent or adult interests and aspirations.
with CHD, family support and bereavement services should be It is important to feel good deep inside and therefore the
made readily available. ‘spirit’ cannot be ignored. The most important goal is to have
Patient driven support groups, national and international love, peace, harmony and balance in life for that is what we all
association programs play an important role for most of strive towards. Encouraging empowerment, offering support
our internet-savvy patients. The Adult Congenital Heart and encouraging realistic, yet positive thinking can assist
Association is very active in its efforts with patient advocacy, patients in having the courage to work towards their goals.
in spreading knowledge, promoting research, offering social
networks and peer support (www.achaheart.org). The National PSYCHIATRIC ISSUES
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.
Introduction
org). The International Society for Adults with Congenital It has been found in a number of studies that this patient
Heart Defects (www.isachd.org) offers many resources to population tends to have a higher incidence of mental health
professionals and the public. A listing of international adult issues than the general public. Brandhagen found that the
congenital heart disease (ACHD) groups is available at www. “General psychologic development in adults with congenital
worldcongenitalheart.org. Individual clinics/centers can heart disease differed from that in a normal population.”10
provide information regarding local resources, support groups To substantiate, one study found that among CHD patients
to the patients/families to meet their personal and cultural “who had been assumed to be ‘well-adjusted’, 36.4 percent
needs more adequately. People with CHD have a unique were experiencing a diagnosable psychiatric disorder,
impact on their healthcare and policies when they speak with anxiety or depressive symptoms being prominent”.13
directly of their own experiences.3 Another found that “Fifty percent of interviewed patients met
Appropriately educating complex CHD survivors requires diagnostic criteria for at least one lifetime mood or anxiety
honesty and humility on the part of the providers. Promoting disorder”,14 Finally another study found that approximately
the connection between the ‘BODY, MIND AND SPIRIT’ 79 percent of the CHD patients interviewed presented either
ultimately helps them the most in their lifelong journey. Both with a diagnosable psychiatric disorder of major depression,
the patient and the provider need to acknowledge the power panic disorder or were found to be suffering from “frequently
830 of the ‘Mind over Matter’. For some, adversity can be a gift endorsed clusters of psychiatric symptoms not meeting criteria
for full disorder (post-traumatic stress disorder, dysthymia, of cardiac lesion and the degree of psychological distress10 58
adjustment disorder with depressed mood and/or anxious but yet another found ‘significant correlations.’13 Finally,
mood, either currently or in the past)”.5 yet another study found that a person’s “social adjustment
One psychiatric diagnosis which is not often mentioned and patient-perceived health status are more predictive of
in the literature is post-traumatic stress disorder (PTSD). depression and anxiety than medical variables”.14
This is despite the fact that ‘childhood illness qualifies as a Could this increase of psychiatric conditions be connected
traumatic stressor’ in the diagnosis of PTSD.15 In one study, it to the entry to adulthood? All of the tasks that this transition
was found that approximately 29 percent of adolescents who requires (choosing and maintaining employment, supporting
had undergone cardiac surgery as children were diagnosed oneself financially, maintaining an intimate relationship) could
with ‘full post-traumatic stress disorder (PTSD) likely’.16 It simply be a reminder of one’s differences and limitations. This
is our recommendation that further research into this topic be would be especially true for those who were never ‘prepared’
conducted as there is “preliminary evidence that PTSD may for entering adulthood. One could also say that the experience
be associated with non-adherence with medication and an of living with a life threatening condition, especially during
increased risk of clinical adverse events”.17 one’s formative years, is in of itself enough to contribute to
It has consistently been found that mental health treatment this increased prevalence. After living with repeated traumatic
for these patients is greatly lacking. Kovacs stated that events, the underlying fear of ‘it’ happening again often stays
“approximately, 70 percent of the patients who met diagnostic with the individual. The effect this has on a person can vary
criteria at the time of study participation were not engaged greatly and can manifest on so many different emotional and
in mental health treatment”.14 Furthermore, none of the psychological levels.
patients with diagnosable psychiatric disorders or clusters of Another possible explanation for this increased prevalence
psychiatric symptoms in both the Bromberg13 and Horner5 of psychiatric presentation is that perhaps there is a more
studies were in mental health treatment of any kind. biological involvement due to lower blood oxygen levels,
The need for improved identification and treatment of limitations in physical activity, and due to the effect of
psychological disorders in this patient population could not be their cardiac medications.13 There is also an association of
more clear or convincing. Yet, as illustrated above, this very psychiatric conditions with other cardiovascular diseases such
important aspect of their care is greatly lacking. This is despite as coronary artery disease and heart failure. A higher incidence
the recommendation of the 32nd Bethesda Conference (“Care of clinical depression and anxiety is noted in patients after
of the Adult with Congenital Heart Disease”) which stated in myocardial infarction, coronary artery bypass surgery and
the summary document: “The emotional health of adults with with chronic heart failure. It is believed to be due to lower
congenital heart disease should be a priority in the overall care blood oxygen levels during a myocardial infarction and the
of this patient population. Appropriate screening and referral cardiac surgery. It is also related to the life style changes
sources for treatment should be available at all regional ACHD people have to make after having a heart attack or following
centers”.18 Additionally, the Task Force on the Management of a heart surgery. Psychiatric conditions worsen the prognosis
Grown Up Congenital Heart Disease of the European Society of heart disease and vice versa, heart diseases have a major
of Cardiology for grown-ups with congenital heart disease adverse impact on mental health and psychiatric issues.21
stated “(Practitioners) must be prepared to help patients and Regardless of what the reasons for the connection to CHD
their families with numerous psychosocial issues and work on and psychiatric prevalence are, as health care professionals
a multidisciplinary basis to provide psychological support.”19 we must examine why CHD patients, for the most part, are
There is some research on the connection between CHD not receiving the mental health treatment that they need. This
and psychiatric prevalence. One study began with a hypothesis brings light to the issue of stigma, which unfortunately prevails
that “improvements in medical care would result in more in many cultures when it comes to the acknowledgement of
favorable behavioral and emotional outcomes for children and mental health conditions and the need for treatment.
adolescents with CHD treated recently”. Could the medical
care patients received in the infancy of CHD treatment have had Stigma
enough of an effect to cause an increased rate of psychological
symptomatology? This group compared patients operated on What is Stigma?
before 1980 with a group of patients operated on 10 to 15
years later. They found that “despite evident improvements in Stigma can be defined as a sign of disgrace or discredit, which
diagnostic and surgical techniques and medical treatment of sets a person apart from other. According to Goffman, the
CHD over the past decades, virtually no changes were found difference between a ‘normal’ and stigmatized person is a
in levels of problem behavior”.20 Another potential contributor question of perspective not reality. There is also a ‘courtesy
that has been examined is the possible connection between stigma’ where family members feel embarrassed or ashamed
medical severity and degree of psychological stress. One study of the illness of their loved ones, whether it is an emotional or
found that there was no correlation found between the severity a physical condition.22 831
10 How do We Deal with Stigma? not enough. There continue to be many obstacles to addressing
the psychological needs of these patients. A lack of funding
Education is the first and most important factor in fighting and a deficiency of psychosocial awareness on the part of
stigma. It helps with the ‘fear of the unknown’ and takes down CHD faculty, as well as patients and families are two areas
the walls that people create to psychologically and at times to of concern. Additionally, our experience shows that there is
physically protect themselves. Education should be provided a fear on the part of some patients of not being understood
to the young patients at a level that they can understand by (mental health) treatment providers. Many patients have
clearly. As more understanding grows, patients become less described the frustration of having to explain their medical
embarrassed about their condition and will hopefully begin to history repeatedly to mental health care providers only
feel less ‘different’. Providing psycho-education can also help to receive a variety of unhelpful responses ranging from
patients and family members spread pertinent information to astonishment to pity. Perhaps, this is why it was found that
the people in their lives and circles. Eliminating the fear of only 35 percent of the CHD patients in one study were found
the unknown relating to a medical condition can be helpful. to be interested in receiving peer support.23
The stigma attached to illnesses like HIV/AIDS has been
successfully challenged by educating people more about Management of Children Growing Up
the facts versus the myths. Educational programs, media, with Chronic Disabilities
and support groups for families can assist in promoting
such efforts. Many health conditions receive positive public Rapprochement is a part of a phase of development in toddlers
attention (therefore reducing stigma) when high profile people postulated by Margaret Mahler.25,26 In this sub-phase, a toddler
or celebrities openly discuss their personal medical conditions. practices being independent and wants to explore ‘the world’.
The child realizes that his physical mobility demonstrates
Role of Mental Health Services psychic separateness from his mother. The child has a fear of
mother (primary caregiver) not being there when she is needed.
Mental Health Services can provide emotional support, This phase can be disturbed in children who are challenged
coping strategies and the opportunity to explore one’s with medical illnesses such as CHD and who are undergoing
thinking for distortions that may adversely affect life goals a medical or surgical procedure. His/her experience with
and relationships. Coping strategies which may have their CHD may cause a child to become clingy to the parents
been appropriate in childhood may no longer serve well in and issues of separation anxiety can arise. It is believed that
adulthood. Distortions of thinking may cause unwarranted adolescents go through the same phase when they want to
sensitivity to rejection, social isolation or deferral of fulfilling practice their independence. It is also a time in their life when
activities. existential questions are raised in the mind. The questions
An important issue in making a referral to mental health such as “Who am I?”, “Why am I in this world?” and “Who
services is the level of comfort and knowledge on the part do I belong to (in the psychological sense)?” These are some
of the health care provider and the patient in addressing of the things that make this phase of life so challenging. It is
psychiatric issues. Discussion of the physiologic processes when the normal developmental challenges of independence
(the role of Serotonin, for example) involved in anxiety or are coupled with the added stressor of a child’s heart disease
depression symptoms may help reduce stigma for the patient that significant psychological issues can arise.
in need of mental health services. This may be why it is common to see some children
Our experience has shown that although many CHD become increasingly non-compliant with treatment during
patients do want mental health treatment, denial, lack of adolescence. Other factors that may affect non-compliance
acknowledging the need, the stigmata and paucity of access are the general attitude of invincibility (in adolescence) and
to care may make it challenging for people based upon their denial used as a way of coping with their illness. Parents
demographics. This is substantiated by a study which found and providers can help by acknowledging and validating
that 51 percent of patients “indicated a high interest in at the adolescent’s health situation, feelings or struggles. They
least one of the seven defined focus areas of psychological can offer psychological education, unconditional love and
treatment”.23 Unfortunately, however, according to Horner, acceptance. Partnering with them, instead of telling them what
“CHD patients in adulthood, as in their childhood, often to do has more chances of success.
suffered silently and worried alone.”5 Denial has been cited as
a common psychological defense in this patient population.5 Management of Depression and Anxiety disorders
The fact that many CHD patients in need are not receiving
treatment is especially concerning since there is “existing The treatment for depression and anxiety should be three-fold:
evidence that social support and emotional expression may be biologic, psychotherapy and lifestyle changes.27 The biologic
associated with better medical outcome” (cancer patients).24 treatments are discussed in the section “Pharmacological
832 Although, many ACHD centers do offer some form of interventions in patients with cardiovascular disease”.
mental health services, the findings above indicate that it is Psychotherapy can help in understanding one's patterns of
thinking, how a person copes with situations and how a chronic failure due to coronary artery disease.28-31 In addition, the 58
medical condition has affected his/her social, occupational or positive impact of exercise training in patients with depression
educational life. Cognitive behavior therapy techniques can and heart failure due to coronary artery disease should be
be used in helping patients focus on “seeing the glass half- extrapolated to other cardiac patients (including those with
full rather than half-empty”. Lifestyle changes relating to congenital heart disease).32
‘Healthy Living’ by eating healthy and incorporating exercise Effexor (Venlafaxine) is an antidepressant and anti-
in their daily routine are advocated. Stress management with anxiety medication that is considered to be a serotonin and
meditation, activities that bring peace, harmony such as music, norepinephrine reuptake inhibitor (SNRI). It can cause an
dancing, gardening and yoga should be a part of everyone’s life. elevation in blood pressure and should be used cautiously with
Patients should also be encouraged to think about their proper monitoring. Benzodiazepines such as lorazepam and
priorities in life and how to take control of the direction of clonazepam are good medications in reducing acute anxiety.
their lives in a realistic way. Finding the enjoyment in the Clinicians have to be very careful in using any psychotropic
little things such as a walk in the park, a stroll by the beach medications that may increase the heart rate, blood pressure
or enjoying a cup of tea over a conversation with a friend can or prolong the corrected QT interval (QTc). For example,
also help in feeling fulfilled in one’s life. We think that it is also stimulant medications commonly used to treat attention-
important for CHD patients to define themselves not by their deficit hyperactivity disorder (ADHD) or lethargy related to
illness but instead as individuals with ideas, interests, goals depression, can increase heart rate and blood pressure. These
and dreams. drugs have potential side-effects including cardiac arrhythmias.
Their use may be contraindicated in patients with CHD who
An Approach to Post-traumatic Stress Disorder have significant electrophysiological issues. Therefore, a
baseline electrocardiogram and a cardiology consultation are
The best approach to post-traumatic stress disorder (PTSD) is needed before prescribing these medications. Because the
to minimize the emotional trauma during the treatment. The benzodiazepines can be habit-forming and may cause memory
health care provider can help by preparing the patient with problems, their use should be for short-term only especially
education about their illness or the procedure that they are during acute phases, until the long-term medications such as
about to have. When it is possible, and especially in the case of SSRIs or SNRIs start working. Most antipsychotic medications
children, being close to a loved one until it is time to go under used to treat psychotic disorders such as schizophrenia or mood
anesthesia is very supportive. Processing the traumatic events disorders such as bipolar disorders can prolong the QTc interval
as early as possible can aid in any situation, so the same would (Figure 1). The worst offenders are Ziprasodone (Geodon) and
be true when dealing with a patient’s medical trauma. After Thioridazine (Mellaril). Weight gain, elevated triglycerides and
the procedure, guiding the patient back to their normal life as cholesterol are potential side-effects of this class of medication.
soon as possible also helps in faster recovery, both emotionally Close monitoring for potential side-effects should be provided.
and physically. Nature created human beings with the ‘flight or The tricyclic antidepressants (TCAs) should be used
fight response’, so that when a danger arises, initially certain with caution. A baseline electrocardiogram should be
hormones get pumped into the blood to allow us to either obtained before starting this class of medications. Follow-up
fight it or get out of it. After a short period of time, the body’s electrocardiograms should be checked annually or if there are
response diminishes and everything goes back to the baseline. any cardiac symptoms. In children, Imipramine in low doses
The challenge in patients with chronic illnesses or stress- can be effective for nocturnal bed wetting and desipramine
related disorders is that their bodies and emotions are in that has shown efficacy in treating attention-deficit hyperactivity
state of ‘flight or fight response’ all the time. This takes a toll disorder (ADHD).33,34
on them, unless they are able to seek help in order to recognize Unfortunately, there are case reports of sudden death
these patterns and learn new healthy coping skills. associated with the use of TCAs. Nortriptyline is used to treat
obsessive compulsive disorder (OCD) in both children and
Pharmacological Interventions in Patients adults. TCAs are also used for controlling severe neurological
with Cardiovascular Disease pain and migraine. With the advent of newer antidepressants,
the use of TCAs is now becoming limited. These agents are
Along with counseling, supportive care, the pharmacological still used in treatment of refractory depression.
interventions play a major role in management of depression,
anxiety disorders and other mental conditions in patients with Drug-drug Interactions
CHD as well as in those with other cardiovascular diseases.
Among biologic therapies, the selective serotonin reuptake Selective serotonin reuptake inhibitors (SSRIs) are widely
inhibitors (SSRI) such as fluoxetine, sertraline, paroxetine, used and since most patients are taking multiple medications,
citalopram, have shown to be very effective in treating both it is very important to be aware of drug-drug interactions.
depression and anxiety. There is a rising interest in the use Like many other drugs, SSRI's are metabolized by 833
of SSRIs in cardiac patients, especially in those with heart cytochrome P450 system. Many drugs may increase or
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
decrease the activity of various cytochrome P450 isoenzymes Conclusion

either by inducing the biosynthesis of an isoenzyme or
by directly inhibiting the activity of the cytochrome P450 Screening for early detection and management of psychosocial
isoenzymes. Special consideration should be applied when challenges and psychiatric issues is vitally important. Timely
using medications for cardiac conditions that are also and appropriate referral should be made to the clinical social
metabolized by this system or by specific isoenzymes such as worker, psychotherapist and psychiatrist. There is a need for
CYP2D6. ongoing in-depth studies in this population.
The SSRIs may increase blood levels and risk of toxicity An integrated approach as described in Box 1 may help
of certain medications such as warfarin (coumadin), digoxin improve psychosocial care in people with CHD. A special
and beta blockers. Certain agents and medications such as relationship develops over the years between the providers
diuretics may increase the toxicity of SSRIs. Alcohol use is and the patients. They rely heavily on their providers for
not advised during treatment with SSRIs since it may increase long-term emotional support. The quality of life while living
834 the toxicity of the SSRIs (Table 1). with CHD can be improved by identifying a purpose to make
Box 1: Recommendations for improved psychosocial
7. Kovacs AH, Silversides C, Saidi A, et al. The role of the
psychologist in adult congenital heart disease. Cardiol Clin.
58
care in people with congenital heart disease 2006;24:607-18.
8. Moons P, Marquet K, Budts W, et al. Validity, reliability and
Integrate mental health care providers into the CHD medical
responsiveness of the “Schedule for the Evaluation of Individual
team and also utilize them as a community referral resource.
Quality of Life-Direct Weighting” (SEIQoL-DW) in congenital
Develop outreach strategies designed to identify mental health heart disease. Health Qual Life Outcomes. 2004;2:27.
care providers (clinical social workers and psychologists) and 9. Moons P, Van Deyk K, De Bleser L, et al. Quality of life and
ideally refer to those who are specially trained in working with health status in adults with congenital heart disease: a direct
patients with CHD. comparison with healthy counterparts. Eur J Cardiovasc Prev
Establish a plan to develop and test ‘tools for screening of Rehabil. 2006;13:407-13.
psychosocial problems’ in this population.18 10. Brandhagen DJ, Feldt RH, Williams DE. Long-term
Provide psychological education to the faculty (at the psychologic implications of congenital heart disease: a 25-year
ACHD and Pediatric Centers), patients and family members follow-up. Mayo Clin Proc. 1991;66:474-9.
regarding identification, treatment and recommendations for 11. Masi G, Brovedani P. Adolescents with congenital heart
psychosocial/psychiatric issues. disease: psychopathological implications. Adolescence. 1999;
34(133):185-91.
Pediatric Centers should offer transitional support to assist 12. Simko LC, McGinnis KA. Quality of life experienced by adults
adolescents with the move to adult care. with congenital heart disease. AACN Clin Issues. 2003;14: 42-
Offer patient support groups and ‘peer to peer’ relationships 53.
locally. 13. Bromberg JI, Beasley PJ, D’Angelo EJ, et al. Depression and
Provide crisis intervention and psychotherapy (talk therapy) anxiety in adults with congenital heart disease: a pilot study.
to patients when indicated. Heart Lung. 2003;32:105-10.
14. Kovacs AH, Saidi AS, Kuhl EA, et al. Depression and anxiety
Short-term psychotherapy administered through the ACHD
in adult congenital heart disease: predictors and prevalence. Int
centers.
J Cardiol. 2009;137:158-64. Epub 2008 Aug 15.
Long-term counseling referred out to appropriate affiliated 15. Manne S. Commentary: Adopting [corrected] a broad per-
mental health programs and community resources. spective on post traumatic stress disorders, childhood medical
Inpatient counseling provided following a cardiac episode or illness and injury. J Pediatr Psychol. 2009;34:22-6. Epub 2008
prior to cardiac procedures and surgery. 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.
life more meaningful. As providers, we should encourage 17. Spindler H, Pedersen SS. Posttraumatic stress disorder in the
wake of heart disease: prevalence, risk factors, and future
the patients to feel more empowered when dealing with their
research directions. Psychosom Med. 2005;67:715-23.
health conditions.
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
To keep the body in good health is a duty, otherwise we shall Coll Cardiol. 2001;37:1176-83.
not be able to keep our mind strong and clear. 19. Baumgartner H, Bonhoeffer P, De Groot NM, et al. Task Force
—Gautama the Buddha, 563 BC on the Management of Grown-up Congenital Heart Disease of
the European Society of Cardiology (ESC). ESC Guidelines
REFERENCES for the management of grown-up congenital heart disease
(new version 2010). Eur Heart J. 2010;31:2915-57. Epub 2010
1. Warnes CA. The adult with congenital heart disease: born to be Aug 27.
bad? J Am Coll Cardiol. National Heart Lung. 2005;46:1-8. 20. Spijkerboer AW, Utens EM, Bogers AJ, et al. A historical
2. What are Congenital Heart Defects? National Heart, Lung comparison of long-term behavioral and emotional outcomes
and Blood Institute, Diseases and Conditions Index, US in children and adolescents after invasive treatment for
Department of Health and Human Services, National Institutes congenital heart disease. J Pediatr Surg. 2008;43:534-39.
of Health, Revised July, 2011 21. Meijer A, Conradi HJ, Bos EH, et al. Prognostic association of
3. Verstappen A, Pearson D, Kovacs AH. Adult congenital heart depression following myocardial infarction with mortality and
disease: the patient’s perspective. Cardiol Clin. 2006;24: cardiovascular events: a meta-analysis of 25 years of research.
515-29. Gen Hosp Psychiatry. 2011;33:203-16. Epub 2011 Mar 31.
4. Gantt LT. Growing up heartsick: the experiences of young 22. Goffman E. In Stigma: Notes on the Management of Spoiled
women with congenital heart disease. Health Care Women Int. Identity. New York, Simon and Schuster, Inc. 1963.
1992;13:241-8. 23. Kovacs AH, Bendell KL, Colman J, et al. Adults with
5. Horner T, Liberthson R, Jellinek MS. Psychosocial profile of congenital heart disease: psychological needs and treatment
adults with complex congenital heart disease. Mayo Clin Proc. preferences. Congenit Heart Dis. 2009;4:139-46.
2000;75:31-6. 24. Spiegel D, Sephton SE, Terr AI, et al. Effects of psychosocial
835
6. Kokkonen J, Paavilainen T. Social adaptation of young adults treatment in prolonging cancer survival may be mediated by
with congenital heart disease. Int J Cardiol. 1992;36:23-9. neuroimmune pathways. Ann N Y Acad Sci. 1998;840:674-83.
10 25. Martin A, Volkmar FR (Editors). In Lewis’s Child and
Adolescent Psychiatry: A comprehensive textbook, 4th edition.
30. Tousoulis D, Antonopoulos AS, Antoniades C, et al. Role of
depression in heart failure—choosing the right antidepressive
Philadephia, Lippincott Williams and Wilkins. 2007. p. 389. treatment. Int J Cardiol. 2010;140:12-8. Epub 2009 Jun 6.
26. Mahler MS. Rapprochement subphase of the separation 31. Watson K, Summers KM. Depression in patients with heart
individualization process. Phychoanal. Q. 1972;41:487-506. failure: clinical implications and management. Pharmacothera-
27. Schotte CK, Van Den Bossche B, De Doncker D, et al. A py. 2009;29:49-63.
biopsychosocial model as a guide for psychoeducation 32. Milani RV, Lavie CJ, Mehra MR, et al. Impact of exercise
and treatment of depression. Depress Anxiety. 2006;23: training and depression on survival in heart failure due to
312-24. coronary heart disease. Am J Cardiol. 2011;107:64-8.
28. O’Connor CM, Jiang W, Kuchibhatla M, et al. SADHART- 33. Spencer T, Biederman J, Coffey B, et al. A double-blind com-
CHF Investigators.Safety and efficacy of sertraline for parison of desipramine and placebo in children and adoles-
depression in patients with heart failure: results of the cents with chronic tic disorder and comorbid attention-deficit/
SADHART-CHF (Sertraline Against Depression and Heart hyperactivity disorder. Arch Gen Psychiatry. 2002;59:649-56.
Disease in Chronic Heart Failure) trial. 25. J Am Coll Cardiol. 34. Swanson JR, Jones GR, Krass elt W, et al. Death of two subjects
2010;56:692-9. due to imipramine and desipramine metabolite accumulation
29. Goodlin SJ. Sadness in heart failure: what is a clinician to do? during chronic therapy: a review of the literature and possible
J Am Coll Cardiol. 2010;56:700-1. mechanisms. J Forensic Sci. 1997;42:335-39.
836
Sec t i on
11
Electrophysiological Issues
in Children
C hapter
Congenital Heart Blocks

59 and Bradyarrhythmias
Abhilash SP, Dinesh Choudhary, Narayanan Namboodiri
IntroduCtIon heart rate can fall to 35 to 40 bpm, especially in adolescents

with marked sinus arrhythmia, sometimes producing pauses
Cardiac rhythm disorders range from benign to life-threatening of two seconds or longer. Increased intracranial pressure due
and bradyarrhythmias are arbitrarily defined as a heart rate below to intracranial space occupying lesions and infections like
60 beats/minute. Children have higher heart rates than adults and meningitis can also cause sinus bradycardia. Treatment of
heart rate tends to decrease across childhood upto adolescence. sinus bradycardia per se is not usually necessary, but a careful
Newborns have heart rates that range from 100 to 160 beats per evaluation to rule out any correctable cause is suggested.
minute. Children aged between 1 and 10 years have heart rates
that range from 60 to 140 bpm. This age-dependency of normal Sinus arrhythmia
heart rates should be considered while interpreting heart rates in
infants and young children. Though uncommon, the presence of Sinus arrhythmia is characterized by a phasic variation in
bradyarrhythmia in children requires special attention, related sinus cycle length during which the maximum sinus cycle
to some special issues. First, a clear differentiation of transient, length minus the minimum sinus cycle length exceeds 120
functional abnormalities such as vagotonia from primary disease milliseconds. The sinus rate increases gradually during
of the conduction system is required. Second, a decision to pace inspiration and decreases with expiration. The variation
needs consideration of issues like selection of optimal pacemaker is attributed to changes in vagal tone as a result of reflex
system, limited venous access options at the younger age and the mechanisms arising from the pulmonary and systemic vascular
anticipated problems in the long years of follow-up to come. systems during respiration. This respiratory sinus arrhythmia
Third, the confounding factors related to associated structural is the most frequent form of sinus arrhythmia and is considered
heart disease if any, both anatomical and hemodynamic, and at to be a normal event. Nonrespiratory sinus arrhythmia is more
acute and long-term, also need to be addressed. likely to be seen in elderly individuals in association with heart
A brief description of clinically relevant bradyarrhythmias disease. Symptoms produced by sinus arrhythmia are rare, but
(common to all age groups) is given below as it would aid if the pauses between beats are excessively long, palpitations
in clear understanding of specific bradyarrhythmia-related or dizziness may result. Generally, sinus arrhythmia does not
issues in children. require any specific treatment.
BradyarrHytHmIaS rElatEd to aBnormal SInuS Wandering Pacemaker

nodE FunCtIon
This variant of sinus arrhythmia involves shift of the dominant
pacemaker focus from the SN to latent pacemakers that have the
Sinus Bradycardia next highest degree of automaticity in atria or atrioventricular
Sinus bradycardia can result from excessive vagal and/ (AV) junction. In contrast with AV dissociation, the change
or decreased sympathetic tone. It can also be an effect of occurs in a gradual fashion over the duration of several beats;
medications, disorders like hypothyroidism or due to anatomical thus, only one pacemaker at a time controls the rhythm.
changes in the sinus node (SN) itself. During sleep, the normal Treatment is usually unnecessary.
11 BradyarrHytHmIa rElatEd to aBnormal
av nodE FunCtIon
ElEctrophysiological issuEs in childrEn
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 First-degree av Block
in automaticity of sinus node (sinus arrest) or conduction from the
node to atrium (sinus exit block)
During first-degree heart block, conduction time across
AV node is prolonged resulting in prolonged PR interval in
Sinus Pause ECG; but all impulses are conducted. Clinically important
PR interval prolongation can result from a conduction delay
Sinus pause or absence of an expected P wave for more in the AV node (A-H interval), in the His-Purkinje system
than 3 seconds, may be due to sinus arrest (failure of the SN (H-V interval) or at both sites. Occasionally, an intra-atrial
pacemaker cells to depolarize) or be the result of sinoatrial conduction delay can also result in PR prolongation. Increase
(SA) exit block (depolarization of the SN but failure to conduct in atrial rate or vagal tone can cause first-degree AV nodal
to the atria). The main feature to look for in electrocardiogram block to progress to type I second-degree AV block. Isolated
(ECG) is P-P interval delimiting the pause does not equal a first-degree AV block warrants no treatment.
multiple of the basic P-P interval. In patients with sick sinus
syndrome, characterized by marked sinus bradycardia or Second-degree av Block (mobitz type I and type II)
sinus arrest, especially if symptomatic, permanent pacing is
necessary (Figure 1). Blocking of some atrial impulses conducted to the ventricle
Electrocardiogram in SA exit block shows a pause resulting at a time when physiological interference is not involved
from absence of the normally expected P wave. The duration constitutes second-degree AV block. Second-degree heart
of the pause is a multiple of the basic P-P interval. Sinoatrial block occurs in two forms, Mobitz type I (Wenckebach) and
exit block is caused by a conduction disturbance during which type II (Figures 2 and 3). Type I heart block is characterized
an impulse formed within the SN fails to depolarize the atria by a progressive lengthening of the conduction time until
or does so with delay. Excessive vagal stimulation, acute an impulse is not conducted. Electrocardiographically,
myocarditis or fibrosis involving the atrium, as well as drugs type I second-degree AV block is characterized by progressive
such as beta blockers or digitalis, can produce SA exit block. PR prolongation culminating in a non-conducted P wave.
Sinoatrial exit block can be of three types. A first-degree SA During a type I block, the increment in conduction time is
block cannot be recognized on the surface ECG. Second- greatest in the second beat of the Wenckebach group and the
degree SA blocks are recognized frequently because of their absolute increase in conduction time decreases progressively
effect on the atrial rhythm. Analogous to second-degree AV over subsequent beats. In type I second degree AV block,
block, there are two types of second-degree SA block: type I the interval between successive beats progressively
(Wenckebach periodicity) and type II, manifested by dropped decreases, although the conduction time increases (but by
P waves during sinus rhythm. Type I block is clinically more a decreasing function). The duration of the pause produced
prevalent than type II block. Sinoatrial exit blocks are usually by the non-conducted impulse is less than twice the interval
transient and usually do not require treatment. preceding the blocked impulse and the cycle following the
non-conducted beat is longer than the cycle preceding the
Sick Sinus Syndrome blocked impulse.
Type II heart block denotes occasional or repetitive
Sick sinus syndrome is a term applied to a syndrome sudden block of conduction of an impulse, without prior
encompassing a number of primary sinus nodal abnormalities, measurable lengthening of conduction time. In ECG, the
including sinus bradycardia, sinus arrest or exit block, PR interval remains constant prior to the blocked P wave.
AV conduction disturbances and alternation of atrial Type II AV block indicates disease in the infra-Hisian
tachyarrhythmias especially atrial fibrillation and periods conduction system and often antedates the development of
of slow atrial and ventricular rates (tachy-brady syndrome). Adams-Stokes syncope and complete AV block, whereas
Permanent pacing for the bradycardia, combined with drug type I AV block with a normal QRS complex is generally
therapy to treat the tachycardia, is required in those with benign and does not progress to advanced heart blocks (Refer
840 symptomatic tachycardia-bradycardia syndrome. 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 occurring above the block with retrograde atrial conduction.
The ventricular focus is located below the region of the block,
The 2:1 AV block can be a form of type I or type II second which can be above, at or below the His bundle bifurcation.
degree AV block (Figure 4). If the QRS complex is normal, the Complete AV block can result from block at the level of the AV
block is more likely to be type I and located in the AV node. If a node; also known as suprahisian (usually congenital), within
bundle branch block is present, the block can be located in the the bundle of His or intrahisian or distal to it in the Purkinje
AV node or His-Purkinje system. An EP study may be required system or infrahisian (usually acquired). The ventricular rate
to localize the exact location of block with certainty. in acquired complete heart block is generally less than 40 bpm,
but can be faster in congenital complete AV block. Ventricular
third-degree (Complete) av Block pacemaker activity that are in or closer to the His bundle result
in a faster escape rate than can those located more distally in
Third-degree or complete AV block occurs, when no atrial the ventricular conduction system. Escape rhythm resulting
activity is conducted to the ventricles and the atria and ventricles from conduction block in infrahisian conduction system is
are controlled by independent pacemakers (Figure 5). The atrial slower and much more unstable (See below for indications for 841
pacemaker can be sinus or ectopic atrial or from AV junction pacing).1
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 block may develop varying degrees of exercise limitation or
In CHIldrEn syncope. Sudden death is uncommon during the first decade,
but increases thereafter. Syncope or sudden cardiac death due
Clinical Presentation to complete AV block may result from bradycardia, per se or
bradycardia-dependent polymorphic ventricular tachycardia
Children presenting with symptoms owing to primary with degeneration to ventricular fibrillation (Figure 6).
bradycardias are relatively uncommon. Symptoms associated
with sinus node dysfunction are caused by inadequate heart Clinical Scenarios
rate response to stress or exertion. Overt symptoms are
relatively uncommon in children with first- and second- The common clinically significant bradyarrhythmias secondary
degree AV block too. However, complete heart block, either to conduction system disturbances and relevant in children can
congenital or acquired, can have a fatal outcome in children be grouped into the following main categories:
and may need more attention. 1. Sinus node dysfunction, which is secondary to surgical
The fetus and infant with congenital complete AV block repair of congenital heart disease (CHD), often with
and no associated heart disease usually are asymptomatic. concomitant atrial tachyarrhythmias.
However, if the escape rate is inadequate, symptoms may 2. Postsurgical atrioventricular block.
range from growth retardation to overt congestive heart failure, 3. Congenital atrioventricular block.
842 including hydrops fetalis. Older patients with congenital AV 4. AV conduction disturbances in Long QT syndrome (LQTS).
59

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 Sinus Node Dysfunction with or without Atrial of an episode of atrial tachycardia may be followed by a very
Tachyarrhythmias prolonged asystolic episode in patients with profound SN
dysfunction, leading to syncope. Drugs such as beta-blockers
Surgery for CHD often involves large incisions in the right and amiodarone generally have only negligible serious
atrium and in certain types of operations, the SN can be adverse effects in the presence of a normal SN. But when they
damaged.2,3 The SN may be damaged directly by incision, are given to patients with pre-existing SN disease, profound
clamping or suturing. Interruption of the blood supply to abnormalities of SN function can result.
the SN during surgery can also cause SN dysfuncion. Both
the Mustard and the Senning procedure for atrial redirection Postsurgical Atrioventricular Block
in d-transposition of the great vessels involve extensive
atrial suture lines and the incidence of SN abnormalities The surgical repair for CHD carries some risk of damage to
progressively increases as these patients grow into adulthood. either AV node or the distal conduction system. For example,
These two classical surgeries are not regularly performed in patients with perimembranous ventricular septal defect
nowadays, as transposition is now managed by the arterial (VSD), the bundle of His perforates the central fibrous body to
switch procedure. Still, thousands of children and adults are emerge on the margin of the defect, before branching into right
alive today following the Mustard or Senning procedure and and left fascicles.5 Placement of the patch requires placing
most have some elements of SN abnormality. deep sutures into myocardium and the conduction system
Another operation that is commonly associated with is at risk. Surgical repair of tetralogy of Fallot and truncus
SN dysfunction is the Fontan procedure. The loss of sinus arteriosus also may injure the AV node or distal conduction
rhythm with subsequent junctional escape rhythm leads to AV system. For all surgery at all ages, this incidence is 1 percent
asynchrony. This loss of AV synchrony certainly has adverse to 2 percent6 but may well be higher in patients operated
consequences in a patient with Fontan circulation. In patient during the first year of life. Patients with endocardial cushion
with borderline hemodynamic function, it is advisable to defects (AV canal defects) are at even higher risk, as are those
consider permanent pacemaker to restore AV synchrony, even who have enlargement of their VSD as part of certain complex
if a more obvious indication such as syncope or chronotropic repairs.
incompetence is not present. Due to the presence of extensive Postoperative AV block may also be seen following repair
atrial incisions and suture lines, such patients are also at risk for of simple defects in the atrium, such as secundum atrial septal
the development of atrial tachyarrhythmias and in particular, defects, but in these situations, it is likely that it is the compact
intra-atrial reentrant tachycardia.4 The coexistence of these AV node which is damaged, rather than the distal conduction
tachyarrhythmias with significant SN dysfunction is especially system. Postoperative AV block often resolves spontaneously
important. Episodes of tachycardia leads to hemodynamic within several days of surgery and such resolution may allow
instability and syncope and moreover, the sudden termination one to avoid placing of the pacemaker,7 even though some
843
11 of them may require temporary pacing support. AV block pacemaker for all, but a consensus is not yet there and many
persisting beyond 14 days is a clear indication for permanent believe this is unnecessary. In real world scenario, large
pacing. This is related to the poor prognosis of such patients prospective randomised studies in children with congenital
and the potential for syncope and sudden death. It should AV block to assess the unintervened natural history may
be noted here that the observation of a seemingly adequate not be possible because of multitude of reasons. Hence, the
heart rate in the presence of postsurgical complete AV block recommendations are often supported only by evidence from
should not be seen as reassuring, as such escape rhythms retrospective observations. It is interesting to note that not a
are notoriously unreliable, particularly those with a wide single recommendation (Class I—III) in the current American
QRS complex. Unlike SN dysfunction, advanced AV block, College of Cardiology (ACC)/American Heart Association
especially with a wide QRS escape is potentially fatal. (AHA) guidelines for pacing in bradycardia is backed up by
level of evidence A.1 However, the older the patient, the more
Congenital Atrioventricular Block reasonable this recommendation would be, due to the easier
and safer implant procedure in larger patients. Most (but not
Patients are considered to have congenital complete AV all) clinicians agree that daytime rates > 50 bpm in children
block, if AV block is present at birth or develops during the older than 1 year or long ventricular pauses (defined recently
first year of life. Anatomical disruption between the atrial as at least twice the basic escape cycle length) are indications
musculature and peripheral parts of the conduction system and for pacemaker implantation in asymptomatic individuals.
nodoventricular discontinuity are two common histological
findings. Most cases of complete congenital AV block are Atrioventricular Conduction Disturbances in LQTS
related to maternal mixed connective tissue disease and/or
systemic lupus erythematosus.8,9 Mothers of affected infants The congenital LQTS is a potentially lethal disease caused by
have abnormally high titers of antibodies to the factors SS-A mutations in specific cardiac ion channels. LQTS is known to
and SS-B (anti-Ro and anti-La). A second group of infants cause 2 : 1 AV block in children when the refractory period
have congenital heart disease, especially l-transposition of the of the His-Purkinje system exceeds sinus cycle length. Rarely,
great vessels (congenitally corrected transposition). Finally, it can manifest as first-degree or second-degree AV blocks as
there is a large group in whom the disease is idiopathic, some well (Figure 7). These episodes of transient AV dissociation
of whom may carry the NKX2.5 mutation.10 or ‘pseudo-AV block’ are due to the oscillations in refractory
Mortality from congenital AV block is highest in the period of infrahisian conduction system that are often initiated
neonatal period, is much lower during childhood and by atrial premature beat. A small subset of patients with LQTS
adolescence, and increases slowly later in life. Stokes-Adams with 2 : 1 AV block clinically manifests in the fetal or neonatal
attacks can occur in patients with congenital heart block at period and has been associated with a lethal prognosis. A
any age. It is difficult to predict the prognosis in an individual mortality rate greater than 50 percent in the first 6 months of life
patient. A persistent heart rate at rest of 50 beats/minute or and up to 67 percent by age 2 years has been reported in some
less correlates with the incidence of syncope and extreme series of patients with LQTS and 2 : 1 AV blocks. Suspicion
bradycardia can contribute to the frequency of Stokes-Adams for and detection of LQTS in children presenting with AV
attacks. The site of block may not distinguish symptomatic conduction disturbances in the immediate neonatal period
children, who have congenital or surgically-induced complete allow for close monitoring of high-risk infants. Shortening and
heart block from those without symptoms. Prolonged homogenization of refractoriness of His-Purkinje system with
recovery times of escape foci following rapid pacing and slow AAI (atrium paced, atrium sensed and pacemaker inhibited in
heart rates on 24-hour ECG recordings and the occurrence of response to sensed beat)pacing, potassium supplementation and
paroxysmal tachycardias may be predisposing factors to the beta blockers or other genotype-specific drugs like mexilitene
development of symptoms. often would be sufficient to prevent life-threatening torsades in
Infants born to mothers with antinuclear antibody majority. In our experience, by this therapeutic approach, we
positivity may progress from second degree to complete could manage even refractory cases with excellent long-term
AV block during infancy. Some infants with complete follow up. The renewed interest in left cardiac sympathetic
congenital AV block will present in utero with hydrops denervation, which can be performed with minimally invasive
fetalis. If they are born alive, pacing is clearly indicated. surgery, is increasingly offered to patients with refractory
Others may present with symptoms related to low heart torsades de pointes (TdP). However, smaller devices and
rates, such as syncope, near-syncope or documented exercise novel defibrillator configurations allow for implantation in
intolerance. Children with congenital complete heart block, the neonatal period in a rare case which would not respond to
who are symptomatic should receive permanent pacemaker the above mentioned measures. The technical feasibility of an
implantation. Indications for pacing and recommendations of epicardial system without incorporation of a large, restricting,
timing of pacing are difficult for those children who are totally epicardial defibrillation patch permits implantation in infants
844 asymptomatic. One school of thought is to implant permanent as small as 3.5 kg.
59

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
IndICatIonS For PaCIng ventricular rate less than 55 bpm or with CHD and a
ventricular rate less than 70 bpm (Level of Evidence: C).
Recommendations for Permanent Pacing in Children,
Adolescents and Patients With Congenital Heart Disease— Class IIa
ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy
of Cardiac Rhythm Abnormalities: Executive Summary: A 1. Permanent pacemaker implantation is reasonable for
Report of the American College of Cardiology/American patients with CHD and sinus bradycardia for the prevention
Heart Association Task Force on Practice Guidelines. of recurrent episodes of intra-atrial re-entrant tachycardia;
SND may be intrinsic or secondary to antiarrhythmic
Class I treatment (Level of Evidence: C).
2. Permanent pacemaker implantation is reasonable for
1. Permanent pacemaker implantation is indicated for congenital third-degree AV block beyond the first year of
advanced second- or third-degree AV block associated with life with an average heart rate less than 50 bpm, abrupt
symptomatic bradycardia, ventricular dysfunction or low pauses in ventricular rate that are 2 or 3 times the basic cycle
cardiac output (Level of Evidence: C). length or associated with symptoms due to chronotropic
2. Permanent pacemaker implantation is indicated for sinus incompetence (Level of Evidence: B).
node dysfunction (SND) with correlation of symptoms 3. Permanent pacemaker implantation is reasonable for sinus
during age-inappropriate bradycardia. The definition of bradycardia with complex CHD with a resting heart rate
bradycardia varies with the patient’s age and expected less than 40 bpm or pauses in ventricular rate longer than 3
heart rate (Level of Evidence: B). seconds (Level of Evidence: C).
3. Permanent pacemaker implantation is indicated for 4. Permanent pacemaker implantation is reasonable for
postoperative advanced second- or third-degree AV block patients with CHD and impaired hemodynamics due
that is not expected to resolve or that persists at least 7 days to sinus bradycardia or loss of AV synchrony (Level of
after cardiac surgery (Level of Evidence: B). Evidence: C).
4. Permanent pacemaker implantation is indicated for 5. Permanent pacemaker implantation is reasonable for
congenital third-degree AV block with a wide QRS unexplained syncope in the patient with prior congenital
escape rhythm, complex ventricular ectopy or ventricular heart surgery complicated by transient complete heart
dysfunction (Level of Evidence: B). block with residual fascicular block after a careful
5. Permanent pacemaker implantation is indicated for evaluation to exclude other causes of syncope (Level of
congenital third-degree AV block in the infant with a Evidence: B). 845
11 Class IIb optimal pacemaker, limited venous access, and the anticipated
problems in long-term follow-up.
1. Permanent pacemaker implantation may be considered for
transient postoperative third-degree AV block that reverts Medicine knows no limits, especially not its own.
to sinus rhythm with residual bifascicular block (Level of —Kocher, Gerhard
Evidence: C).
2. Permanent pacemaker implantation may be considered for rEFErEnCES
congenital third-degree AV block in asymptomatic children or
adolescents with an acceptable rate, a narrow QRS complex 1. Epstein AE, Dimarco JP, Ellenbogen KA, et al. 2012 ACCF/
and normal ventricular function (Level of Evidence: B). AHA/HRS Focused Update Incorporated Into the ACCF/
3. Permanent pacemaker implantation may be considered AHA/HRS 2008 Guidelines for Device-Based Therapy of
Cardiac Rhythm Abnormalities: A Report of the American
for asymptomatic sinus bradycardia after biventricular
College of Cardiology Foundation/American Heart
repair of CHD with a resting heart rate less than 40 bpm or Association Task Force on Practice Guidelines and the
pauses in ventricular rate longer than 3 seconds (Level of Heart Rhythm Society. Circulation. 2013 Jan 22;127:e283-
Evidence: C). 352.
2. Lewis AB, Lindesmith GG, Takahashi M, et al. Cardiac rhythm
Class III following the Mustard procedure for transposition of the great
vessels. J Thorac Cardiovasc Surgery. 1977;73:919-26.
1. Permanent pacemaker implantation is not indicated for 3. Bharati S, Molthan ME, Veasy LG, et al. Conduction system
transient postoperative AV block with return of normal AV in two cases of sudden death two years after the Mustard
procedure. J Thorac Cardiovasc Surgery. 1979;77:101-8.
conduction in the otherwise asymptomatic patient (Level of
4. Kalman JM, VanHare GF, Olgin JE, et al. Ablation of‘incisional’
Evidence: B). reentrant atrial tachycardia complicating surgery for congenital
2. Permanent pacemaker implantation is not indicated for heart disease. Use of entrainment to define a critical isthmus of
asymptomatic bifascicular block with or without first- conduction. Circulation. 1996;93:502-12.
degree AV block after surgery for CHD in the absence of 5. Anderson RH, Wilcox BR. The surgical anatomy of ventricular
prior transient complete AV block (Level of Evidence: C). septal defect. J Card Surgery. 1992;7:17-35.
3. Permanent pacemaker implantation is not indicated for 6. Bonatti V, Agnetti A, Squarcia U. Early and late postoperative
asymptomatic type I second-degree AV block (Level of complete heart block in pediatric patients submitted to open-
Evidence: C). heart surgery for congenital heart disease. Pediatr Med Chir.
1998;20:181-86.
4. Permanent pacemaker implantation is not indicated for
7. Vetter VL, Horowitz LN. Electrophysiologic residua and
asymptomatic sinus bradycardia with the longest relative sequelae of surgery for congenital heart defects. Am J Cardiol.
risk interval less than 3 seconds and a minimum heart rate 1982;50:588-604.
more than 40 bpm (Level of Evidence: C). 8. Chameides L, Truex RC, Vetter V, et al. Association of maternal
systemic lupus erythematosus with congenital complete heart
ConCluSIon block. N Engl J Med. 1977;297:1204-7.
9. Litsey SE, Noonan JA, O’Connor WN, et al. Maternal
The presence of bradyarrhythmia in children requires special connective tissue disease and congenital heart block.
care as symptoms are minimal. The transient, functional Demonstration of immunoglobulin in cardiac tissue. N Engl J
Med. 1985;312:98-100.
abnormalities has to be differentiated from primary disease
10. Benson DW, Silberbach GM, Kavanaugh-McHugh A, et al.
of the conduction system. The confounding factors related to
Mutations in the cardiac transcription factor NKX2.5 affect
associated structural heart disease, also need to be addressed. diverse cardiac developmental pathways. J Clin Invest.
Decision to pace needs consideration of issues like selection of 1999;104:1567-73.
846
C hapter
60 Tachyarrhythmias
Sathish S
EpidEmiology the AV node, there is rapid conduction via the specialized His-
Purkinje system with associated right and left bundle branches
Arrhythmias occur less commonly in childhood, constituting that intercalate to the ventricular myocardium.
5 percent of the emergency admissions in the pediatric
population.1 Majority of these tend to be accessory pathway mEChanism of TaChyCardia
mediated supraventricular tachyarrhythmias such as Wolff-
Parkinson-White (WPW) syndrome.2 The non-accessory re-entry
pathway mediated supraventricular tachyarrhythmias commonly
seen in children are atrioventricular nodal re-entry tachycardia Re-entry is a depolarizing wave traveling through a closed
(AVNRT), junctional ectopic tachycardia (JET) and automatic path.
ectopic atrial tachycardia (AT). JET and AT occur mostly in There are three prerequisites for re-entry:
the postoperative period after intracardiac repair for a structural 1. At least two pathways: Slow and fast AV nodal pathways,
heart defect. Ventricular tachycardia (VT) although uncommon, accessory pathway or the presence of barrier (anatomic:
occurs in the pediatric age group in association with hypertrophic tricuspid valve; pathologic: incisional scars, myocardial
cardiomyopathy, long QT syndrome (LQTS) and Brugada infarction and functional scar).3
syndrome. Occasionally, VT can also present symptomatically 2. Unidirectional block: This block can be physiological,
as incessant idiopathic infant VT, right ventricular outflow caused by a premature complex or increased heart rate or
tract (RVOT) tachycardia, catecholaminic VT, idiopathic left pathological, caused by changes in repolarization gradients.
ventricular tachycardia and in postcardiac surgical patient. 3. Slow conduction to prevent collision of the head and the
Supraventricular tachycardia (SVT) is the most common tail of the depolarizing wave: Physiologic caused by AV
rhythm disturbance in children. It is estimated to occur in as nodal slow pathway in AVNRT; cavotricuspid isthmus
many as 1 in 250 otherwise healthy children. Episodes are in atrial flutter (AFL), slow conduction across the crista
often recurrent although rarely life threatening. Treatment of terminalis in upper loop tachycardia; pathologic—ischemic
this disorder has undergone a remarkable transformation in or remodeled cells in atrium and ventricle (ventricular
the past quarter century with the advent of radiofrequency tachycardia, atrial flutter).
ablation (RFA). Although, SVT accounts for a small proportion In functional re-entry, unidirectional block can be due to
of children treated in an outpatient setting, the prevalence is dispersion of refractoriness (repolarization) or dispersion
high enough that most general pediatric practitioners will at of conduction velocity (anisotropic re-entry).The former
some point, care for a patient with this disorder. can be caused by repolarization gradients due to spatial
In the normal heart, the atrial and ventricular myocardium heterogenicity of repolarization (ischemia, drugs), discordant
are electrically insulated from one another except at the repolarization alternans (T-wave alternans during ischemia,
atrioventricular (AV) node and bundle of His. Impulse autonomic abnormalities) and transmural gradients from cell-
generation typically originates in the sinus node and the to-cell uncoupling (drugs, heart failure).
impulse is conducted through the atrial myocardium to the AV
node. The major role of this structure is to allow conduction Triggered activity
of the impulse to the ventricle; however, equally important is
the inherent delay in the AV node that slows conduction from Triggered activities are caused by after depolarization
the atrium to the ventricle, allowing ventricular filling. From currents. They are classified as early after depolarisation
11 (EAD), occuring inside the action potential (phase 2 and 3) However, the prevalence of structural congenital heart disease
and delayed after depolarisation (DAD) occuring in phase 4 of in patients with SVT has been estimated at 9 to 32 percent,
the action potential.4 These currents can in turn be responsible which is substantially higher than in the general population.
for both focal and reentrant arrhythmias. The former is caused The most common association is noted between WPW
by eliciting an excitatory response exceeding the activation syndrome and the Ebstein anomaly of the tricuspid valve, but
threshold and the latter can develop when these currents a number of defects have been found, including ventricular
cause prolongation in action potential, which facilitates the septal defects (VSDs) or atrial septal defects (ASDs), among
development of a unidirectional block due to dispersion of others.
refractoriness.
EValUaTion
automaticity
history
Automaticity is driven by spontaneous phase 4 depolarization.
Automatic depolarizations in the atria and ventricles are not The clinical presentation of SVT is age and duration dependent.
manifested normally due to overdrive suppression by the faster In infants with paroxysmal SVT, the heart rate is usually 220
depolarization caused by the sinoatrial node. However, during to 320 beats/minute; in older children, it is 160 to 280 beats/
excess catecholaminergic states, phase 4 depolarization may minute. In infants, symptoms are usually nonspecific and
exceed sinus node depolarization, causing depolarization to be include poor feeding, irritability, vomiting, cyanosis and pallid
driven by the abnormal tissue.Ventricular tachycardias during spells. If the symptoms are unrecognized for hours to days, the
the acute ischemic and reperfusion phases are good examples infant can present with significant hemodynamic compromise
of automaticity. They often originate from the border zone or heart failure symptoms.7 It is rare for infants who have SVT
between normal and ischemic cells. for less than 24 hours to develop signs of congestive heart
failure at the time of presentation; however, congestive heart
supraventricular Tachycardia 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
Supraventricular tachycardia is broadly defined as a narrow, than 48 hours.8 Approximately, 20 percent of infants receive
complex tachycardia that requires atrial tissue or the AV a diagnosis during routine. In verbal children with SVT,
node as an integral part of the arrhythmia substrate, with the palpitations and fluttering in the chest are the usual presenting
exceptions of SVT in presence of existing or functional bundle symptoms.9 Because re-entrant arrhythmias are a circuit, they
branch block, antidromic atrioventricular reentry tachycardia tend to be all or nothing and the onset is frequently described
(AVRT), atrial fibrillation (AF) with bystander pathway as being abrupt, similar to a light switch being turned on.
conduction which are broad complex tachycardias. The The offset may be less dramatic because the catecholamine
majority (90%) of the clinically important SVTs in otherwise level is typically elevated, with resultant sinus tachycardia
healthy children are caused by the presence of an additional at the termination of SVT and subsequent gradual slowing.
(or accessory) electrical connection between the atrium and Frequently, lightheadedness and dizziness due to transient
ventricle (i.e. the bundle of Kent) or within the AV node itself. hypotension can occur at the onset, but syncope is rare in SVT
and its presence should raise suspicion of something other
inCidEnCE than SVT. The frequency and duration of the episodes vary
greatly from a few minutes to a few hours and occur as often
The true incidence of SVT in children is unknown, but as daily or as infrequently as once or twice per year. Although,
has been estimated to be 1 in 250 to 1 in 1000 children.5 rare in verbal children, incessant SVT symptoms may go
Approximately, 50 percent of children with SVT will present unrecognized until cardiac dysfunction develops.
with their first episode in the first year of life. After infancy,
the incidence peaks in early childhood (ages 6–9 years) and diagnosis
then again in adolescence.6 In infants, spontaneous resolution
occurs in more than 90 percent by 1 year of age. After a Recording a heart rhythm strip during symptoms remains the
period of quiescence, upto one-third will have recurrence of key to correct diagnosis and management. Options for this
SVT at a mean age of 8 years. Only a small minority (15%) include 24-hour ambulatory monitoring, event recorders and
of patients who are diagnosed after 1 year of age will have electrocardiograms (ECGs). Each of these means of obtaining
spontaneous resolution. Supraventricular tachycardia due a recording have associated advantages and disadvantages.
to concealed or manifest accessory pathways, predominates The Holter monitor provides a continuous multichannel
throughout childhood and adolescence, whereas the relative recording that usually allows the interpreter to see the whole
proportion of patients with AVNRT tends to increase with age. episode, including onset and termination. Most patients,
848 Most individuals with SVT have a structurally normal heart. however, do not have daily symptoms, making the Holter
monitor typically impractical in the evaluation of SVT. Event and 0.3 mg/kg at 5 minutes intervals, if hemodynamically 60
recorders are often the optimal solution for patients who have stable and no response. Up to 90 to 95 percent of AVNRT
symptoms more than once per month. Patients can wear the and AVRT respond and 30 to 35 percent of atrial tachycardias
tachyarrhythmias
monitor (loop recorder) or carry it with them (event monitor). respond to this therapy. In patients with AT, by blocking
In both cases, patients activate the recording device during AV node, AT is uncovered AT as the cause of tachycardia,
symptoms. The advantage of the loop recorder is that the however automatic AT may terminate with adenosine
recording encompasses the time before, during and after the (Figure 1). Verapamil (0.1–0.3 mg/kg over 2 minutes,
monitor activation. Finally, for infrequent episodes lasting may be repeated after 15 minutes with a maximum dose
longer than 10 minutes, patients can often be referred to the 5 mg first and 10 mg second dose) and diltiazem are effective
local emergency department for acute monitoring. in terminating AV node-dependent tachycardias in 90 percent
of cases. Verapamil should not to be used in children < 1 year,
management because it causes profound hypotension. Amiodarone (5 mg/
kg) and procainamide (15 mg/kg) can be infused slowly over
Acute Management 30 to 60 minutes with careful ECG and pressure monitoring
in stable patients not responding to above maneuvers.
Acute management of regular narrow QRS (<90 ms or
<0.09 s) nodal dependent (AVRT and AVNRT) tachycardias Long-term Management
depends on how well the tachycardia is tolerated, presence
of underlying heart disease and the response to therapy The management of SVT has many variables that need to
previously. If hemodynamically unstable, synchronized be considered, including the age of the patient, the duration
cardioversion is done at 1 to 2 Joules/kg with pediatric paddles, and frequency of the episodes and the presence of ventricular
if weight is less than 15 kg. Vagal maneuvers, including dysfunction. For children with rare and mildly symptomatic
carotid sinus message, Valsalva and Muller maneuvers, episodes in whom SVT is easily terminated, the SVT may
gagging and in case of infants exposing the face to ice cold not merit treatment. For children with episodes that are
water is helpful in hemodynamically stable patients. Acute difficult to terminate, occur frequently or occur during athletic
management of AVNRT and orthodromic atrioventricular participation, it may be advisable to offer medical therapy or
reentry tachycardia (OAVRT) is the same, except in case of transcatheter ablation as therapeutic options. Infants with SVT
AF with accessory pathway conduction and in antidromic deserve special recognition in regard to treatment options.
AVRT; drugs which prolong refractory period of pathway Most infants will undergo spontaneous resolution of SVT.
is given along with AV node blocking drugs. Digoxin and When this is combined with the increased risk of transcatheter
calcium channel blockers (CCB), which shorten the refractory ablation in this age group, medical management is preferred;
period are to be avoided. If vagal maneuvers fail, adenosine ablation is preferred in presence of tachycardiomyopathy, or
is the initial drug of choice given at 0.1 mg/kg, 0.2 mg/kg 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; 849
IV = Intravenous; QRS = Ventricular activation on ECG; VT = Ventricular tachycardia
11 medical Therapy • WPW and syncope with a shortest prexcited R-R lesser
Optimal medical management (in terms of whom to treat, with than 250 ms
which medication and for how long) of SVT in infants and • Chronic or recurrent SVT with ventricular dysfunction
children has not been well studied and most current clinical • Recurrent VT associated with hemodynamic compromise
practices are extrapolated from small studies of adults and and is amenable to RFA.
uncontrolled pediatric studies.11-13 The intended effect of anti- Class IIA indications, in which the majority are of the
arrhythmic medications is to slow conduction, preferentially opinion or data favors RFA, include
within one limb of the re-entrant circuit, thereby terminating • Recurrent and/or symptomatic SVT refractory to medical
the tachycardia as the circulating wave front encounters therapy and age greater than 4 years
refractory tissue. Nearly, all classes of antiarrhythmic agents • Impending congenital heart surgery when vascular or
have been used to treat SVT successfully. The approach to chamber access may be limited following surgery
antiarrhythmic therapy includes the daily prophylactic therapy • Chronic (greater than 6 months) or incessant tachycardia
and the single-dose ‘pill-in-the-pocket’ approach, whereby with normal ventricular function
medication is taken only during an acute episode. The pill-in- • Chronic or frequent recurrences of intraatrial reentrant
the-pocket approach requires an immediate-release medication tachycardia
and is appropriate for patients who have infrequent episodes • Palpitations with inducible SVT during an
that are prolonged, but well tolerated.14 In adults combination electrophysiological study (EPS).
of diltiazem (120 mg) and propronolol (80 mg) have had good Class IIB indications, in which there is a clear divergence
results compared to flecanaide. They need however to be of opinion regarding the need for RFA, include:
avoided in antidromic AVRT. • Asymptomatic WPW and age less than 5 years when the
In most cases, first-line therapy is directed at modifying risk/benefits of RFA have been explained to the family
the conduction properties of the AV node and includes • SVT, age less than 5 years, as an alternative to chronic
treatment with beta-blockers (propronolol 2–4 mg/kg, 2–4 medical therapy that has controlled the tachycardia
doses, maximum 16 mg/kg, metoprolol 1–3 mg/kg), CCBs • SVT, age less than 5 years,when medications, including
(diltiazem 1.5–2 mg/kg/24 hours, maximum 3.5 mg/kg/24 sotalol and amiodarone, have not controlled the tachycardia
hours, verapamil 4–8 mg/kg/24 hours, 3 divided doses) and or have resulted in intolerable side effects
digoxin (8–10 mcg/kg in 2 divided doses, from birth to 10 • Intra-atrial re-entrant tachycardia, 1–3 episodes per year
years; greater than 10 years 125 mcg/d) except in WPW requiring medical intervention
syndrome, with antidromic tachycardia when use of CCBs • AV node ablation for intra-atrial re-entrant tachycardia
and digoxin should be avoided.15 With medical therapy, there • One episode of VT with hemodynamic compromise and
is a significant reduction in the number of episodes, although amenable to RFA.
complete suppression is rare. Class III indications, in which there is agreement that RFA
Supraventricular tachycardia refractory to first-line is not indicated, include:
medications can often be controlled with more potent anti- • Asymptomatic WPW, age less than 5 years
arrhythmic agents such as flecainide acetate (2–4 mg/kg, • SVT, controlled with medication, age less than 5 years
tid), amiodarone (5 mg/kg/day), sotalol hydrochloride, pro- • Nonsustained and non incessant VT without ventricular
canamide (15–50 mg/kg, qid) or drug combinations. Sodium dysfunction
channel blockers such as flecainide are particularly effective • Nonsustained, asymptomatic SVT.
in controlling SVT, but these agents are generally avoided in
patients with structural or ischemic heart disease because of prognosis
the risk of proarrhythmia. Sotalol, an agent with beta-
receptor and potassium channel blocking properties, is In the absence of structural heart disease or cardiomyopathy, the
also quite effective, but can lead to QT prolongation and prognosis of SVT is believed to be excellent. WPW syndrome
proarrhythmia.16 Radiofrequency ablation is preferred in deserves special consideration with respect to prognosis
children weighing more than 15 kgs, in view of good success owing to the small, but real risk of SCD associated with this
and similar complication incidents as in adults.17 condition. The principal indicator of risk in adults with WPW
In 2002, a position statement was published by members syndrome is the presence of symptoms (e.g. palpitations and
of the Pediatric Electrophysiology Society and endorsed by syncope). Symptomatic patients with WPW syndrome have
the North American Society of Pacing and Electrophysiology. an estimated 3 to 4 percent lifetime risk (0.25% per year) of
(Friedman RA NASPE). Class I indications, in which there SCD.18 In children and adolescents, however, asymptomatic
is clear and consistent agreement that RFA will benefit the may be better termed as presymptomatic. It has been estimated
patient, included: that 55 percent of asymptomatic children and adolescents will
• WPW following aborted sudden death become symptomatic by 40 years of age. For this reason, all the
850
children or adolescents in whom WPW syndrome is identified 60
on an ECG, regardless of the presence of symptoms, should
be referred to a pediatric electrophysiologist for evaluation.
tachyarrhythmias
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 Figure 2: Atrial tachycardia diagnosed after giving adenosine
not using cavotricuspid isthmus as a part of circuit. Those revealing 2:1 conduction (arrows show P wave). Intially there was 1:1
using cavotricuspid isthmus are called atrial flutter. Atrial conduction and there was difficulty in diagnosing the rhythm.
tachycardia is common at extremes of age constituting 15
percent of arrhythmias in pediatric population.
Atrial tachycardia can present in children as either A negative P wave in lead I or aVL or a positive P wave in
paroxysmal or incessant automatic AT. The anatomic lead V1, favors a left atrial origin, negative P waves in the
distribution is similar to adults—the ostium of pulmonary inferior leads are suggestive of a low atrial origin, whereas
veins, crista from sinus node to coronary sinus, left and right a positive P wave in those leads suggest a high atrial origin.
atrial appendage and less commonly along AV valve annuli.20 Atrial tachycardia from the high crista terminalis or right
It is a common cause for tachycardiomyopathy in pediatric superior pulmonary vein may resemble sinus P wave, but for
age group. the positive P wave in lead V1.
Electrocardiogram management
In ATs, the P waves are in the second half of the tachycardia Acute Treatment
cycle, hence obscured by the T wave of the preceding QRS
complex (Figure 2). The presence of AV block during tachycardia Atrial tachycardias may rarely be terminated with vagal
excludes AVRT and makes AVNRT very unlikely. During ATs, maneuvers and a proportion of focal ATs will terminate with
an isoelectric baseline is usually present between P waves and it administration of adenosine and the common response is AV
is used to distinguish AT from typical or atypical flutter (i.e. saw block, revealing atrial rate more than ventricular rate suggestive
toothed or sinusoidal P wave morphologies), however, it may not of AT. Class Ia or class Ic drugs may suppress automaticity or
hold true in congenital heart disease.The diagnosis of AT can be prolong action potential duration and hence, may be effective
established with certainty only by an electrophysiological study, for some patients with AT. Similarly, DC cardioversion
including mapping and entrainment. seldom terminates automatic ATs, but DC cardioversion may
P-wave morphology on the 12-lead surface ECG is useful be successful for those in whom the tachycardia mechanism 851
for the determination of the site of origin of the focal AT.21 is micro re-entry or triggered automaticity and should be
11 considered for patients with drug-resistant arrhythmia. often by one year of age. After neonatal presentation of
The usual acute therapy for AT consists of intravenous beta tachyarrhythmia, there is second peaking at 8 years of age.This
blockers or CCBs for either termination, which is rare or to may be related to functional changes in conduction properties,
achieve rate control through AV block. Direct suppression of cardiac dimension changes, maturation of autonomic nervous
the tachycardia focus may be achieved by use of class Ia and system and increased physical activity. Those having neonatal
Ic or class III (e.g. sotalol, amiodarone) agents. Intravenous presentation, have recurrence of arrhythmia in 1/3 of cases,
class Ia or Ic agents may be taken by patients without cardiac but those presenting late have less chance of spontaneous
failure, whereas intravenous amiodarone is preferred for those resolution.
with poor ventricular function. Natural history studies are limited. In a study of 184
asymptomatic children, 38 percent developed tachyarrhythmia
Long-term Pharmacologic Therapy in next 2 years, 30 percent of them were life threatening.25 The
electrophysiological characterstics of these were antegrade
The available studies pertaining to long-term pharmacologic refractory period < 240 ms, presence of multiple pathways
therapy are observational and there are problems in discerning and inducibility of tachyarrhythmia. The risk of catastrophic
whether the tachycardias were carefully differentiated from events increased in presence of digoxin, caused by heightened
other mechanisms (i.e. AVRT or AVNRT) or from other forms adrenergic status.It is recommended that those children more
of ATs. Review of the available data supports a recommendation than 5 years of age with asymptomatic pre-excitation required
for initial therapy with CCBs or beta blockers because these to participate in competitive sport, needs the assessment
agents may prove to be effective and have minimal side effects. of antegrade refractory period of pathway by looking for
If these drugs are unsuccessful, then class Ia, class Ic (flecainide intermittent pre-excitation on ECG, Holter and disappearance
and propafenone) in combination with an AV-nodal-blocking of pre-excitation with treadmill test indicating poor antegrade
agent or class III agents (sotalol and amiodarone) may be tried conduction over pathway and low risk of SCD. If non-invasive
because they may prove to be effective. The potential benefit studies suggest good antegrade conduction over the pathway,
should be balanced by the potential risks of proarrhythmia and they may require invasive EPS for risk stratification and RFA,
toxicity.22,23 The infants less than three years are managed by if needed.25,26
medical means in view of spontaneous resolution in around 70
percent after 3 years and limitations of RFA, in view of size of mechanism of Tachycardia
child and complications.24 The preffered drug for arrhythmias
are amiodarone and sotalol. Children more than 3 years are The accessory pathway permits either only antegrade or
managed by RFA, in view of amenability to ablation and need retrograde or bidirectional conduction from the atria to the
for long-term medical management. ventricle. An early atrial extrasystole is conducted slowly
down the AV node to the His–Purkinje system and ventricle; it
Wolff-parkinson- WhiTE syndromE and returns to the atrium over the accessory pathway and then into
orThodromiC aVrT ventricle if AV node has recovered and is no longer refractory,
then a circus movement tachycardia, also known as re-entry
By definition, WPW syndrome means pre-excitation on tachycardia or reciprocating tachycardia, can be established,
ECG with tachycardia, either orthodromic, commonest of termed as OAVRT and antidromic AVRT if circuit is other way
the two where the pathway conducts retrogradely or anti- around. A ventricular extrasystole can also trigger tachycardia
dromic tachycardia, the pathway conducts antegradely. The in this situation, via retrograde conduction up the accessory
presentation may be in fetal life with tachycardia, requiring pathway into the atrium, with the retrograde P wave then
fetal auscultation or ultrasonography and confirmation of being conducted anterograde across the AV node. Following
the tachycardia rate by combination of M-mode, Doppler ventricular depolarization, there is conduction back up of the
and two dimensional echocardiography. These patients may accessory pathway and the tachycardia is initiated.25
present with hydrops fetalis, requiring aggressive treatment.
Medications used include digoxin; beta-blockers; CCBs and Electrocardiogram
classes I and III antiarrhythmics, either alone or in combination.
Variations in transplacental transport of medications complicate The baseline ECG may show delta wave if antegrade conduction
treatment of the fetus, coupled with side effects in the mother, occurs over the pathway, the degree of pre-excitation depends
who must be monitored closely for proarrhythmic effects such on how fast the pathway or the node conducts, septal and
as those seen with the class I and III agents. If the fetus does right-sided pathways show more pre-excitation as the sinus
not respond to medications in a timely manner and hydrops conduction reaches this site fast. The presence of intermittent
persists, premature delivery may be required. pre-excitation suggests weak antegrade conduction across the
Among neonates having WPW syndrome, approximately pathway and low risk of sudden death. The ECG showing
852 25 to 35 percent will experience disappearance of delta wave, different patterns of pre-excitation may indicate presence
of multiple pathways.There are different algorithms for inferior leads suggest inferior location of pathway, if positive 60
localization of the pathway with varing sensitivity and suggesting anterior location), ST depression in lateral leads
specificity, based on initial 20 to 60 ms of delta wave or the and ST elevation in aVR.29
tachyarrhythmias
morphology or polarity of entire QRS complex.27,28 All left
free wall pathways show positive delta in V1, with R greater management
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 Neonates and infants with tachycardia are often very sick,
pathway moves from posterior to lateral and more anterior, presenting with congestive heart failure, in view of the infant’s
the delta waves in inferior leads III and aVF, change from inability to communicate and the family’s lack of awareness
negative to isoelectric to positive. A positive delta wave in V1, that the child could have a significant medical condition and
with R greater than S, suggests left-sided pathway and if R long lasting tachycardia. Parents may note that the infant was
lesser than S suggests either right free wall or minimally pre- acting somewhat different than normal, more irritable or not
excited left-sided pathway. A negative delta in V1 suggests eating well, often interpreted as colic or some other ‘normal’
septal pathway. Right-sided pathways are recognised by small childhood problem. At presentation, these babies often
R in V1, late transition at V3 or more and a positive delta are acidotic from decreased cardiac output and may need
wave in lead I and aVL. As the pathway moves from right aggressive resuscitation including artificial ventilation and
superior to lateral and inferior location, delta wave in III and rapid termination of the tachycardia. Intravenous adenosine
aVF changes from positive to isoelectric to negative. The is effective in the acute termination of SVT in this population,
tachycardia ECG may show regular narrow QRS tachycardia but intravenous access is often difficult in a 3 to 4 kg baby
if antegrade conduction occurs over the AV node, orthodromic in congestive heart failure. Transesophageal overdrive pacing
AVRT (Figure 3) and regular broad complex tachycardia if has proven very helpful. Once the rhythm is restored to normal
antegrade conduction occurs over the pathway, producing and the cardiac function has begun to recover, intravenous
antidromic AVRT. Irregular broad complex tachycardia access becomes easier and intravenous medications can be
occurs in AF with antegrade conduction over the pathway. employed.
The ECG signs to suggest OAVRT are the presence of distinct Digoxin, a first-line medication used in the treatment of
P wave in short RP tachycardia (the morphology of retrograde SVT in infants with decreased myocardial performance,
P depends on the site of pathway, positive in V1 or lead I is contraindicated in patients with WPW syndrome; Other
suggests right- sided pathway, negative P wave in all the three 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 853
in lead aVR and a subtle P wave immediately after QRS suggestive of orthodromic AVRT
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
Figure 4: Explaining the mechanism of typical slow fast AVNRT. The
no recurrences of the SVT, the patient will be weaned from the
atrial premature contraction (APC) is blocked in the fast pathway, due
medication unless WPW syndrome is still present on the ECG.33 to the long refractory period, and conducts through the slow pathway.
Approximately, one-third of all patients who develop SVT in the Once the fast pathway recovers, the impulse from the slow pathway
first 3 months of life will outgrow it by 1 year of age. conducts retrogradely through the fast pathway producing echo beat.
It this impulse continues through the slow pathway it produces slow
fast AVNRT.
aTrioVEnTriCUlar nodal rE-EnTranT TaChyCardia
Atrioventricular nodal re-entrant tachycardia is uncommon procanamide and amiodarone are preferred. For long-term
during infancy accounting only for 4 percent of the arrhythmias. management, beta-blockers, CCBs are preferred. With the
The incidence of this is about 23 percent in the 1 to 5 age group, improvement in the success of RFA in drug refractory cases
34 percent in the 6 to 10 age group and 20 percent in those over and with the use of cryotherapy, with which the incidence of
10 years of age. Most of these do not resolve spontaneously and AV block can be reduced, the proportion of pediatric patients
will require RFA. treated with RFA is increasing. The target for ablation is the
slow pathway area at the posterior part of Kochs triangle
mechanism (Figure 5).36
Three different arrhythmias require consideration in
Presence of two distinct group of AV nodal cells with pediatrics in view of common prevalence in this age group-
different refractory properties, forming the re-entry circuit persistent junctional reciprocating tachycardia (PJRT), JET
(dual AV nodal physiology).34 One of these pathways has a and incessant ectopic atrial tachycardia.
long refractory period and fast conduction, while the second
pathway has a shorter refractory period with slow conduction. pErsisTEnT JUnCTional rECiproCaTing
The classic finding on an ECG is a tachycardia in which TaChyCardia
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 PJRT is an accessory pathway at the posteroseptal location
the fact that the retrograde limb of the pathway conducts very with only retrograde conduction and showing properties
rapidly from the ventricle to the atrium (Figure 4). AVNRT of AV node like decremental conduction, responding to AV
is classified into two types, based on which of the two limbs nodal blocking drugs unlike other pathways. The tachycardia
are used for antegrade and retrograde conduction. In the has slower heart rate, in view of slower and decremental
common type called slow fast AVNRT, antegrade limb is the conduction properties. The tachycardia being incessant and
slow pathway and retrograde limb is the fast pathway. In the at slower heart rate may be asymptomatic and present with
uncommon type, fast-slow AVNRT, it is vice versa.35 tachycardiomyopathy.37
management Electrocardiogram
854 In acute management intravenous adenosine or metoprolol The mechanism of the tachycardia accounts for the ECG
can be used. In drug refractory cases intravenous appearances. The QRS is normal for age and P waves are
management 60
Management of PJRT is influenced by the age and clinical
tachyarrhythmias
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
JUnCTional ECTopiC TaChyCardia

Commonly seen in the postoperative setting and sometimes
Figure 5: Showing anatomy of Koch’s triangle and location of fast and congenital. It is caused by abnormal automaticity around
slow pathway. Slow pathway is the target for radio frequency ablation AV node.39,40 The two differ with respect to duration and
in AVNRT response to therapy.The postoperative form associated with
repair of VSD alone or in combination with complex heart
surgeries, is usually transient (1–4 days) and responds well to
clearly seen with a 1 : 1 AV relationship. The pathway conducts intravenous amiodarone and cooling. In contrast, congenital
slowly retrogradely hence, the P wave is much closer to the JET not associated with congenital heart diseases, is incessant,
following QRS, so this is a type of long RP tachycardia. The associated with strong family history, may spontaneously
P waves are characteristically deeply inverted in leads II, III, resolve over period of months to years. The propensity to
and aVF and V4 to V6 because the atria are activated first in resolve spontaneously, response to amiodarone and the
the low right atrium (Figure 6). 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, Paired ventricular pacing to decrease the ventricular rate
ablation of JET can be attempted in the region of fast pathway, has been used. intravenous amiodarone has been effective
preferably with cryoablation.41 in the treatment of these patients. In using intravenous
antiarrhythmics, one must be aware of the potential negative

Electrocardiogram inotropic effect of these medicines on the postoperative
patient’s heart. If the patient can be stabilized for a period of 48
The ECG findings in JET shows tachycardia with a ventricular to 72 hours, the rhythm disturbance will often spontaneously
rate that is faster than the atrial rate or both equal, if there revert to a normal sinus rhythm.
is 1 : 1 VA conduction, with a narrow QRS complex similar
to that seen in the patient’s normal sinus rhythm with rate of VEnTriCUlar arrhyThmias
180 to 240/min (Figure 7). Rarely, patients with JET develop
rate related aberrancy and some postoperative patients have Ventricular arrhythmias include premature ventricular
a bundle branch block that will lead to a wide complex contractions (PVCs), couplets non-sustained ventricular
tachycardia. If there is a wide complex tachycardia, VT tachycardia (NSVT), sustained VT and ventricular fibrillation
must be ruled out by comparison to the QRS in normal sinus (VF). The PVCs may be seen in 15 percent of normal
rhythm or by pacing the atrium faster than the ventricular rate newborns, one-third of normal adolescents and two-third of
to demonstrate wide complex conduction through the His- adolescents and adults with repaired congenital heart disease,
Purkinje system. with difference in prognosis between PVCs in children with
normal and abnormal hearts.44
Treatment
Evaluation
Treatment strategies for the familial form of JET include using
digoxin to slow the rhythm and provide inotropic support. The evaluation should include a standard ECG for QTc interval
Digoxin alone may not be sufficient to manage this arrhythmia and 24-hour ambulatory monitor for the burden and complexity
and the addition of a class la, class lc or class III antiarrhythmic of the ectopy and also for QTc measurment. In normal heart, less
agent is required. The amount of antiarrhythmic medication than 20 percent ectopy usually does not interfere with cardiac
needed to control the rate to prevent decompensation of function, more than 30 percent ectopy may result in ventricu-
cardiac function may suppress the sinus node sufficiently lar dysfunction over time. An echocardiogram to look for any
to require a pacemaker temporarily. Patients with JET have structural abnormalities, such as hypertrophic cardiomyopathy
been treated with RFA.42 Because of the proximity of the AV and abnormalities in cardiac function that might accompany
node and His-bundle to the area of enhanced automaticity myocarditis or dilated cardiomyopathy. Rarely, cardiac tumors
responsible for JET, RFA in this setting carries a high risk of such as rhabdomyomas are identified. Magnetic resonance
causing complete heart block. It is possible that over time the imaging may be indicated if right ventricular dysplasia is sus-
junctional rate will slow to a point that the patient may be pected, based on ventricular ectopy having left bundle branch
weaned from medications. block pattern and superior axis, basal ECG showing features
In the postoperative setting, treatment involves use of of arrhythmogenic right ventricular dysplasia (ARVD) and in
combination of medications along with surface cooling.43 presence of family history. Generally, suppression of PVCs dur-
ing exercise is a positive finding, development of bidirectional/
polymorphic VT may be suggestive of catecholamine induced
VT (CPVT). Prolongation of the corrected QT interval, espe-
cially in the recovery phase, may be seen in patients with long
QT syndrome. The EPS would rarely be indicated unless symp-
toms of syncope suggesting more complex arrhythmias or the
PVCs are associated with conditions that might predispose the
patient to VT or VF.
prognosis
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
Figure 7: Congenital JET diagnosed in a child of 3 years after giving serious arrhythmias, especially if they are complex-multiform,
856 amiodarone infusion, revealing the onset of tachycardia by a junctional
coupled or associated with VT.
beat
Clinical signs and symptoms VT have been described, torsades de pointes and bidirectional 60
VT. Bidirectional VT shows beat-to-beat variation in the
Children under 5 years of age with PVCs are frequently QRS axis and is associated with digoxin toxicity, familial
tachyarrhythmias
asymptomatic and unaware of their arrhythmias. Older hyperkalemic paralysis or catecholamine sensitivity.46
children may complain of a skipped or hard beat or a fluttering
in their chest, while some perceive PVCs as painful. Clinical signs and symptoms
Treatment The type and degree of symptoms appear to be rate related

and the underlying cardiac function, with symptoms most
The PVCs in structurally normal heart and lesser than 20 common in patients with rates greater than 150 bpm and
percent ectopy burden does not require any intervention, cardiac dysfunction. Patients with VT have symptoms similar
unless they are frequent enough to interfere with the cardiac to those with SVT.
output, are closely coupled or frequently fall on the T wave in
a patient judged to be vulnerable to such occurrences (LQTS). long QT syndromE
The PVCs associated with heart disease such as myocarditis,
cardiomyopathy or congenital heart disease may require The congenital LQTS is an inherited condition characterized
further investigation and treatment, especially if they are by syncope, seizures and sudden death, associated in most
frequent or occur in runs resulting in hemodynamic instability. individuals with a prolongation of the QT interval on the ECG.
In addition to the prolongation of the QTc, these patients often
VEnTriCUlar TaChyCardia have bizarre or notched T wave morphology with prominent
U waves or T wave alternans. They develop life-threatening
Ventricular arrhythmias are less common than supraventricular VT, known as torsades de pointes or VF. This syndrome
arrhythmias, occurring in both acute and chronic situations includes the Jervell and Lange-Nielson syndrome, associated
in children. There is an increase in VT in patients after with congenital deafness and thought to demonstrate an
congenital heart surgery, involving scarring of ventricles and autosomal recessive inheritance and the Romano-Ward
survival after complex surgery. The etiology of VT being the syndrome demonstrating autosomal dominant inheritance,
congenital LQTS, hypertrophic and dilated cardiomyopathies, without hearing deficit.47
ARVD, myocarditis, abnormal foci or circuits in structurally
normal hearts or idiopathic etiologies. prevalence and presentation
Electrocardiographic manifestations The data from the new born from Italy demonstrate that,
among whites, the prevalence of LQTS is at least 1 : 2534
The electrocardiographic diagnosis of VT is made most easily apparently healthy live births.48 In 1993, statistics from a
in the presence of a wide QRS tachycardia with AV dissociation. group of 287 children, the initial presentation was cardiac
Many children have ventriculoatrial (VA) conduction with arrest (9%), syncope (26%), seizures (10%), presyncope or
relatively rapid 1 : 1 retrograde VA conduction, and AV palpitations (6%), with 88 percent having exercise-related
dissociation may not occur. The differential diagnosis of broad symptoms, 39 percent were identified because of family
complex tachycardia is SVT in the presence of existing or history or the identification of other family members with
fuctional bundle branch block, antidromic AVRT, AFIB with the syndrome and 39 percent were asymptomatic.49 Of those
bystander pathway conduction which are broad complex asymptomatic, 4 percent experienced sudden death compared
tachycardias. It must be remembered that the normal QRS to 8 percent overall. The strongest predictors of sudden
duration in infants and young children is 40 to 80 ms, so a death were QTc greater than 0.60 and noncompliance with
wide QRS in an infant might only be > 80 ms. The rates of recommended medication. Bradycardia is commonly seen in
VT in pediatrics vary from 120 to 300 bpm. The presence of these patients, and some may develop or present with second-
PVCs during sinus rhythm with the same configuration as VT degree AV block.50 This is more common in neonates (Figure
is a suggestive sign. AV dissociation is suggestive of VT, but 8) who may have second- or third-degree AV block but it may
1 : 1 VA conduction is common, especially in young children. be seen in older children, especially with exercise.
Fusion beats are commonly noted at the onset or termination The abnormal genes that encode for proteins modulate
of the VT. VT may be sustained (greater than 30 consecutive potassium or sodium ion channels, causing the LQTS by
complexes) or nonsustained (3–30 consecutive complexes). altering cardiac repolarization and increasing the risk for
Further, differentiation is made according to the morphology, ventricular arrhythmias. These genes include KVLQTI,
with VT being described as monomorphic or polymorphic.The HERG, SCN5A, minK and MiRp1. Not all families with known
monomorphic VT classified as LBB or RBB morphology based LQTS have shown linkage to these known loci, suggesting the
on predominant polarity in lead V1. Two types of polymorphic 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 Points
ECG findings
QTc mseca ≥ 480 3
460–470 2
450 (in males) 1
Torsade de pointes 2
T-wave alternans (macroscopic) 1
Notched T wave in three leads 1
Figure 8: Neonate with LQT presenting with CHB Low heart rate for ageb 0.5
Clinical history
Syncopec
repolarization abnormality, imbalance or oversensitivity of the With stress 2
myocardium to sympathetic stimulation appears to play a role Without stress 1
in the development of ventricular arrhythmias. The trigger Congenital deafness 0.5
for arrhythmia in the LQTS is believed to be spontaneous Family historyd
Family members with definite LQTSe 1
secondary depolarizations that arise during or just following
Unexplained sudden cardiac death < age 0.5
the prolonged plateau phase of action potentials, early after 30 years among immediate family members
depolarizations, which is augmented by increased sympathetic
aQTc calculated using Bazett’s formula (QTc = QT/square root of RR).
tone. bMutually exclusive.
cResting heart rate below the second percentile for age.
Clinical associations of genetic findings dThe same family member cannot be counted in both.
eDefinite LQTS is defined by an LQTS score greater than or equal to 3.5.
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 longest QT interval in any lead is divided by the square root
patients (18%). The likelihood of dying during a cardiac event of the preceding R–R interval, values greater than 0.45 in any
was higher among LQT3 patients (20%) than among LQT1 or lead as abnormal on the resting or exercise ECG. In addition
LQT2 (4%) patients. Cardiac events in LQT1 patients occur to QT interval prolongation, the Holter may be helpful in
frequently during exercise (62%), especially swimming, 3 illustrating T wave abnormalities, R on T phenomenon, short
percent occurred during sleep. LQT2 and LQT3 patients runs of nonsustained VT, sustained VT or torsades de pointes.
were less likely to have events during exercise (13%) and
more likely to have events during rest/sleep (29% and 39%). Diagnostic Evaluation
The percentage of patients who were free of recurrence with
beta-blocker therapy was higher and the death rate was lower Schwartz et al proposed the first diagnostic criteria for LQTS
among LQT1 patients (81% and 4%, respectively) than in 1985, which included QTc greater than 440 ms as one of
among LQT2 (59% and 4%) and LQT3 patients (50% and the criteria that has rendered this cutoff value of 440 ms a
17%). LQT3 patients have more cardiac events at rest or major limitation of the original ‘Schwartz criteria’.53 A
during sleep, while LQT2 patients experience more events modified ‘Schwartz score’ (Table 1) containing new criteria
during exercise or stress. LQT2 events are more likely to be and a point system based upon a range of QTc values and
stimulated by loud noises. the clinical/family history was formulated in 1993.54 The
‘Schwartz score,’ recently modified for what concerns the
Evaluation and diagnosis points necessary for a ‘high clinical probability of LQTS,’
ranges from 0 to 9 and contains three diagnostic probabilities:
Diagnosis is made by a careful history, both of the individual’s 1 point, low probability of LQTS; 2 or 3 points, intermediate
episodes and a complete family history looking for sudden probability of LQTS; and greater than 3.5 points, high
unexplained death, syncopal episodes in family members, probability of LQTS. The Schwartz criteria provide a very
unusual seizure disorders or hearing deficits. All patients useful guide for contemplating a clinical diagnosis of LQTS
suspected of LQTS should have a standard ECG with careful with the positive predictive value of a modified ‘Schwartz
QTc measurement, 24-hour ambulatory monitoring and score’ greater than 3.5 approaching 100 percent. Importantly,
exercise stress testing if age is appropriate and provocative however, the Schwartz criteria should be used only for the
858 testing such as isoproterenol or epinephrine infusions.52 The diagnosis of clinically evident LQTS. By definition, these
criteria cannot identify the patients or family members with stimulation of the intact IKs channel and augmentation of a 60
concealed LQTS. late inward Na current. Thus, the epinephrine QT stress test
Provocative testing should include exercise stress provides an in vivo physiological assessment of the integrity
tachyarrhythmias
testing in children able to exercise. Exercise will generally of the IKs pathway.
obliterate sinus arrhythmia and a strip can be obtained in The two major protocols developed for epinephrine infusion
which a reasonable QTc calculation, if a good tracing free include the bolus and brief infusion developed by Shimizu, and
of disturbances be obtained. The recovery period with the escalating-dose protocol (Mayo protocol).59,60 Infusion
heart rates around 120 to130 bpm seems to demonstrate of epinephrine is initiated at 0.025 μg/kg/minute. After 10
the greatest degree of QTc prolongation in many patients. minutes of the infusion, QT/QTc, repeated. The epinephrine
Exercise may uncover abnormal T waves, polymorphic infusion was then increased sequentially every 5 min to 0.05,
PVCs, or VT.55,56 If suspicion for LQTS is high and other 0.1 and 0.2 μg/kg/minute and the measurements were repeated
testing has not been definitive, isoproterenol or epinephrine 5 minutes after each dose increase. The epinephrine infusion
infusion may help to identify these patients. Efforts to identify was then discontinued and measurements were obtained 5
patients at high risk for syncope and sudden death continue. and 10 minutes afterward. The total duration of epinephrine
High-risk electrocardiographic markers have included QTc infusion was 25 minutes. The change in the uncorrected
greater than 0.60, T wave alternans and QTc dispersion. QT QT interval and the change in QTc were calculated by the
dispersion, which indicates heterogeneity of repolarization, difference between the maximal and minimal QT and QTc,
could predispose to the development of torsades de pointes, respectively, at any time during the epinephrine infusion at a
patients not responding to beta-blocker had a significantly dose of 0.1 μg/kg/min. Established stopping criteria included
higher dispersion of repolarization than responders.57,58 T systolic blood pressure 200 mm Hg, NSVT or polymorphic
wave alternans is known to be a high risk factor. VT, ten PVCs per minute, T-wave alternans or patient
intolerance (Figure 9).
Epinephrine Challenge Test
Treatment
Physiological basis: In the normal heart, epinephrine increases
both inotropy and chronotropy. This is achieved in part by Emergent treatment of these patients includes lidocaine and
G-protein/cAMP/protein kinase A–mediated phosphorylation cardioversion. Magnesium may be used to treat torsades de
of IKs (slowly activating delayed rectifier potassium pointes; intravenous propranolol and phenytoin have also
channel) and the Ca activated Cl channel. IKs is one of the been successfully used in these patients.61 The class I agents,
dominant potassium channels responsible for repolarization which are known to prolong the QT interval in normal patients,
(particularly phase 3), which allows potassium ions to exit the should be avoided in these LQTS patients. This is related to
cell and action potential duration to shorten. Activation of this QTc prolongation with associated bradycardia or ventricular
channel explains the observed attenuation of the QT interval arrhythmias or both. Temporary pacing and removal of the
that occurs with epinephrine infusion in normal subjects. offending agent are effective therapies.62
LQT 1 with KCNQ1 mutations (LQT1) have compromised The standard long-term treatment in this condition is
IKs channels that are not as responsive to sympathetic the use of beta-blockers. Those most commonly used are
stimulation and phase 3 repolarization in these individuals propranolol and nadolol.63,64 Some have suggested long-
is retarded. Consequently, during epinephrine infusion, there acting metaprolol or atenolol. A concern about once-daily
are relatively more unopposed depolarizing forces via the dosing relates to the lowest levels being present in early
L-type calcium channel and the sodium calcium exchanger morning hours, a particularly high-risk time for some patients.
that prolong the action potential duration and hence the QT The dose of beta-blocker required is variable and is usually
interval. LQT2 with KCNH2 mutations have dysfunctional greater per kilogram in younger patients. The dose can be
rapidly activating delayed rectifier potassium (IKr) channels, titrated by the heart rate response to maximal exercise testing,
a smaller fraction of the potassium channels responsible aiming for a blunted maximal heart rate response on therapy
for phase 3 repolarization and are not as sympathetically of 150 to 160 bpm. Treatment with beta-blockers can lower
responsive as IKs channels. Therefore, in patients with LQT2, the mortality to less than 4 percent, with greatest benefit in
there may be a transient prolongation of the action potential LQT1.65 Patients are followed with exercise stress tests and
duration during epinephrine infusion, followed by a normal Holter monitoring to look for adequacy of treatment or the
abbreviation of the action potential duration and the absolute development of significant ventricular arrhythmias or both.
QT interval due to the presence of unimpaired IKs channels. Patients who do not respond to beta-blockers may be treated
This transient prolongation of the QT interval followed by with mexiletine, phenytoin or pacing. Mexiletine is more useful
shortening is a characteristic feature of the LQT2 phenotype. in LQT3 patients. Rarely, other antiarrhythmics may be used,
The LQT3 phenotype is characterized by a constant reduction but those known to prolong the QT interval should be avoided.
of the action potential duration with epinephrine due to 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
be helpful. Left stellate ganglionectomy is a treatment which that for most LQT1 grown-up patients, full-dose beta-
should be offered to all patients.66 Permanent pacing has been blockers might be sufficient. On the basis of additional
shown to be an effective adjunctive treatment in these patients, considerations, e.g. duration of the QT interval, this may
especially those with severe bradycardia either from the lead to an open discussion with patients and family
syndrome itself or from the beta-blocker therapy, tachycardias 3. Patients who continue to have syncope despite full-dose
which are triggered by pauses. The rate of the pacing should beta-blockade whenever the option of LCSD either is not
be at least 10 to 20 percent higher than the sinus rate and in available or is discarded after discussion with the patients
severe cases should control the rhythm as much of the time 4. All patients with two mutations who continue to have
as possible.67 Pauses should be avoided. Using this treatment, syncope despite beta-blockade
episodes of torsades de pointes may be reduced or eliminated. 5. Exceptionally, the rare asymptomatic patients with a QTc
In patients known to have had a cardiac arrest or frequent or 550 milliseconds who also manifests signs of high electric
significant syncope associated with ventricular arrhythmias, instability (e.g. T-wave alternans) or other evidence of
on beta blockers and left cardiac sympathetic denervation being at very high risk (e.g. very long sinus pauses that
(LCSD), implantation of an automatic internal cardioverter/ might favor early after depolarizations).
defibrillator device may be necessary. These devices can
recognize VT or VF according to programed criteria and Implantable Cardioverter-Defibrillator Complications
provide a series of shocks to convert the patient to sinus
rhythm. Some can provide backup pacing. Their size led to The relatively high rate of inappropriate shocks and
limited use in smaller children, but improved technology now complications after ICD implantation increases the morbidity
allows even small children to benefit from this technology. of this treatment modality in LQTS patients and worsens its
This is not a therapy to be undertaken lightly at this time, risk benefit ratio. Inappropriate shocks were caused mainly by
as follow-up and possible false discharges can significantly abnormal sensing resulting from either T-wave over sensing or
affect a child’s life and lifestyle. lead failure. The young age at implantation (76% of patients
At present following group of patients merit implantable lesser than 40 years of age, 12 percent lesser than 10 years of
cardioverter-defibrillator (ICD): age) supports the hypothesis that the high rate of lead failure
1. All those who have survived aborted cardiac arrest (ACA) is attributable to the activity-dependent increased strain on
on therapy ICD leads. Another cause of inappropriate shocks was SVT.
2. Many of those who have survived an ACA off therapy, Besides avoiding unnecessary shocks, prolonging the detection
860 except those with a reversible/preventable cause, but noting time and increasing the threshold of tachycardia detection
may reduce inappropriate shocks caused by supraventricular pathophysiology 60
or sinus tachycardia, especially in young patients. In 223
implants, there were 67 adverse events in 58 patients, the more The hypothesis that arrhythmias in CPVT are initiated by
tachyarrhythmias
severe adverse events resulted directly from the implantation DADs and triggered activity had been advanced based on
surgery such as lead placement issues, infections and vascular the observation that the bidirectional VT observed in CPVT
problems. Most of the minor complications were related to patients closely resembles digitalis-induced arrhythmias.
lead issues, including conductor fractures, insulation defects, Digitalis-induced intracellular Ca2 overload leads to the
and changes in electric characteristics.68 These findings activation of sodium–calcium exchanger that, in turn,
substantiate the concerns about the long-term impact of generates a net inward current (the so-called ‘transient inward’
implanting an ICD in young LQTS patients, likely to live ITi current). ITi underlies diastolic membrane depolarizations,
another 7 to 8 decades after initial device implantation and DADs, that may reach threshold for sodium current activation
who would be subject to multiple procedures for generator and trigger abnormal beats. This mechanism for arrhythmia
replacements and lead revisions/extractions with probable initiation is defined as ‘triggered activity.’
complications. This makes the implementation of loose and
non-data-based indications for ICD implantation in LQTS Clinical manifestations
patients no longer preferred.
It is generally recommended that competitive athletics be Syncope, triggered by exercise or emotional stress, is often
avoided by patients with LQTS and especially in those with the first manifestation of CPVT.69 Approximately 30 percent
documented LQTS symptoms or arrhythmias. However, as of patients present with a family history of stress-related
more ‘carriers’ or asymptomatic patients are being discovered, syncope, seizure, or sudden death. Most events occur in the
who have only a prolonged QT interval and no family history first or second decade of life. CPVT diagnosis is established
of sudden death or ventricular arrhythmias, individual exercise after an average delay of 2 years from the first syncope,
and sports participation recommendations may be made. because these events are often attributed to vasovagal events
The most important aspect of the care of these patients is or to neurological factors.70 Increasing evidence shows that
continued surveillance. This is true for young family members SCD can be the first manifestation of the disease.
who appear to have normal QT intervals on initial evaluation.
The QT interval changes with age with periodic ECGs, Electrocardiogram
hence appropriate 24 hours and exercise ECG should be done
in children and adolescent members of LQTS families in The resting ECG of CPVT patients is usually normal
whom the initial evaluation was negative, unless the genetic with the exception of prominent U waves and mild sinus
testing has definitively ruled out LQTS. It is recommended bradycardia in some patients, which is especially abnormal
that patients with LQTS avoid caffeine, adrenergic stimulants for children of this age. There is normal QTc, normal AV
such as epinephrine and over-the-counter stimulants such conduction and no evidence of a Brugada like pattern.
as decongestants. Medications that prolong the QT interval Exercise or acute emotional stress is the typical trigger
should be avoided. of CPVT-related arrhythmias, constantly at heart rate of
110 to 130 beats per minute.71 The complexity and frequency
CaTECholaminE-indUCEd VEnTriCUlar of ventricular arrhythmia progressively worsen with an
TaChyCardia increase in workload, from isolated premature beats to
bigeminy and to ventricular tachyarrhythmia (Figure 10).
Catecholamine-induced VT is a genetic disorder associated When the exercise stops, arrhythmias gradually disappear.
with stress-induced, bidirectional VT that may degenerate The most typical VT observed in CPVT patients presents
into VF and result in sudden death, in the absence of both an alternating QRS axis morphology with a rotation of 180
structural heart disease and a prolonged QT interval. The CPVT degrees on a beat-to-beat basis, the so-called bidirectional
phenotype most often shows an autosomal dominant pattern VT. In view of the role of triggered activity as a mechanism
of transmission, although sporadic cases seem to be rather for arrhythmias in CPVT, it is interesting to note that fast
frequent and a familial history of juvenile sudden death and SVT may act as a trigger for the development of DADs and
stress-induced syncope is present in about 30 percent of cases. triggered activity in the ventricle.
This condition usually occurs in childhood, adolescence or
young adulthood. Reports of mutation in the ryanodine receptor diagnosis
gene RyR1 mapped to 1q42-q43 have been found in families
with catecholamine-induced VT, a recessively inherited CPVT Exercise or emotion-induced syncope in a patient with a
phenotype and the disease locus to a 16-megabase interval normal ECG (normal QT interval) and without structural
on chromosome 1p13–21, calsequestrin 2 (CASQ2) gene abnormalities should always suggest the possibility of
mutation gives rise to a pathological clinical phenotype only in CPVT. An exercise stress test is the most important tool for 861
homozygous carriers, while heterozygous carriers are usually diagnosis since the bidirectional or polymorphic VT may be
silent. reproducibly elicited during physical activity in most of the
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 malformations, sufficient to explain the degree of hypertrophy.75
(and not bidirectional) VT, the progressive worsening of The discovery that many patients with hypertrophic
arrhythmias with exercise is to be considered as diagnostic for cardiomyopathy had familial disease led to a search for the
CPVT. Invasive electrophysiological testing and isoprenaline genetic basis of the disease. In 1989, the first mutation in the
infusion are of not proven value. gene encoding the cardiac β-myosin heavy chain was identified.
Since then, more than 400 mutations have been identified in this
Treatment and other cardiac sarcomeric protein.
Acute intravenous administration of propranolol dose is the Epidemiology

treatment of choice for the acute termination of CPVT-related
arrhythmias. Chronic treatment with beta-blockers can prevent Unexplained left ventricular hypertrophy occurs in approxi-
recurrent syncope in some patients.72,73 Nadolol at a daily mately 1 in every 500 adults. The frequency of left ventricular
dose of 1 to 2.5 mg/kg/day is the preferred drug in view of 24 hypertrophy in children is unknown, but population-based
hours action and can be titrated upto 3.5 to 4 mg/kg/day. Beta- studies from Australia and the United States report an
blockers reduce the occurrence of cardiac events, postpone the incidence between 0.3 and 0.5 cases per 100,000, including
induction of VTs during exercise, stress testing and slow the cardiomyopathies associated with inborn errors of metabolism,
rate of VT; ICD should be considered for primary prevention neuromuscular disease and malformation syndromes.76,77
of cardiac arrest in CPVT patients in whom severe ventricular
arrhythmias (sustained VT or rapid VT) are still observed while natural history
on beta-blocker therapy. The beta blockers can be titrated based
on Holter monitoring and stress test, looking for ventricular Hypertrophic cardiomyopathy can present from infancy
ectopic/VT. to old age. Many patients follow a stable and benign
Catecholamine-induced VT mutant RyR2 proteins cause a course, with a low risk of adverse events, but a large
‘gain of function’ and uncontrolled calcium release from number experience progressive symptoms, caused by
sarcoplasmic reticulum. Verapamil by directly inhibiting the gradual deterioration in left ventricular systolic and
function of the ryanodine receptor may theoretically be an diastolic function and atrial arrhythmias. A proportion of
alternative option for treatment.74 The limited experience with individuals die suddenly, whereas others may die from
amiodarone, mexiletine and magnesium produced unfavorable progressive cardiac failure.Neonatal presentation had
results. severe symptomatic presentation.
hypErTrophiC CardiomyopaThy sudden death

Hypertrophic cardiomyopathy is defined as left ventricular Sudden death occurs most commonly in adolescents and
862 hypertrophy in the absence of abnormal loading conditions young adults. The initial descriptions of the natural history
such as valvar disease, hypertension or other congenital cardiac reported annual rates of sudden death from 3 to 6 percent,
recent studies in adults revealed rates of 1 percent or less per used to prevent sudden death in patients considered at high- 60
year. Similarly, early studies of highly selected populations risk. The drug, however, does not prevent SCD in this group
of children reported rates of sudden death ranging from 2 at high-risk. Amiodarone does, nonetheless, remain useful
tachyarrhythmias
to 8 percent per year, but recent population-based reports for the treatment of atrial fibrillation.
from Australia and the United States report an overall annual
rate of sudden death of 1 to 1.5 percent per year beyond BrUgada syndromE
infancy. The mechanism of sudden death is thought to be
ventricular arrhythmia in the majority and several triggers introduction
are recognised, including atrial arrhythmia, myocardial
ischemia and exercise.The most reliable predictor is a Brugada syndrome has increasingly been recognized worldwide
history of previous cardiac arrest. In patients without such as an important cause of SCD at a young age, in the absence of
a history, the most clinically useful markers of risk are a structural cardiac abnormalities. Patients affected with Brugada
family history of SCD, unexplained syncope unrelated to syndrome are at risk for SCD from fast polymorphic VT/
neurocardiogenic mechanisms, a flat or hypotensive response VF, especially at rest. Brugada syndrome is characterized by
of blood pressure to upright exercise, NSVT on ambulatory a typical ECG pattern consisting of ST segment elevation in
electrocardiographic monitoring or during exercise and the right precordial leads and in leads positioned in the upper
severe left ventricular hypertrophy on echocardiography intercostal spaces.82
defined as a maximal left ventricular wall thickness of 30 It is endemic in East and Southeast Asia, where it underlies
mm or more.78 Importantly, these markers of increased risk the sudden unexplained nocturnal death syndrome (SUNDS),
can all be identified non-invasively. Studies have shown that and is also particularly prevalent in Japan, Philippines and
patients with none of these features have a low risk of sudden Thailand, being the leading cause of sudden death among
death, less than 1 percent per year, whereas those with two young men.83 Arrhythmic events in Brugada syndrome
or more risk factors are at substantially higher risk of dying can occur at all ages, from childhood to the elderly (range
suddenly, with an estimated annual mortality rate of 3 percent 2–77 years), with a peak around the fourth decade, with
for those with two risk factors, rising to 6 percent in those higher disease prevalence in males (70–80% of all affected
with three or more risk factors. The evaluation of risk in subjects), particularly in regions where this syndrome is
these patients, therefore, has to be tailored to the individual, endemic, despite equal genetic transmission among both
taking into account the significance of the risk factor as well genders. However, in pediatric age, no sex predilection
as patient specific variables such as age. A particularly is seen. A role in gender disparity could be played by sex
malignant family history may be sufficient to trigger hormones.84 It is estimated that Brugada syndrome causes 4
primary preventative measures in the absence of a second to 12 percent of all SCD and up to 20 percent among patients
risk factor. Several studies have shown that obstruction of without identifiable structural abnormalities.The clinical
the left ventricular outflow tract is associated with increased presentation is heterogeneous and may include palpitations,
cardiovascular mortality, including sudden death. The dizziness syncope and (aborted) sudden death, but many
absolute risk of sudden death associated with obstruction subjects remain asymptomatic.85
in isolation is low, but it may represent an incremental risk The pathophysiological mechanism underlying this
factor in combination with other conventional markers. The syndrome and the typical ECG features and the genesis of the
extrapolation of data derived from adults may not always be arrhythmias:86
appropriate for children.79 Of the conventional markers of an 1. A repolarization disorder, i.e. unequal expression of the
increased risk for sudden death, unexplained syncope, severe transient outward potassium current Ito between the
left ventricular hypertrophy, and a family history of sudden epicardium and the other transmural layers87 or
death have been reported as being particularly relevant to 2. A depolarization disorder, i.e. a delay in the onset of the
young individuals.80,81 action potential in the region of the RVOT.88
In patients who are considered to be at high risk, insertion Three repolarization patterns of ST segment elevation
of an ICD should be regarded as the treatment of choice. In with two different shapes were recognized as potential
children, appropriate discharge rates are higher at 71 percent manifestations of Brugada syndrome.89 The coved-type
per year in those chosen for secondary prevention and 4 morphology (type I) is characterized by a cove-shaped J wave
percent per year in those having primary prevention. Despite elevation 2 mm, followed by a negative T wave. A type I
the life-saving benefits of ICDs, an increased incidence of ECG is required for the diagnosis, while a saddleback-shaped
complications has been reported in children compared with ST elevation or a coved-type lesser than 1 mm (types II–III)
adults, including a higher rate of inappropriate discharges are indeterminate forms that necessitate pharmacological
for supraventricular or sinus tachycardia, an increased risk challenge (Table 2 and Figure 11).
of infection, complications with leads related to growth and The diagnosis is posed when a type I ECG, spontaneously
the psychological sequels of appropriate and inappropriate or after provocation with sodium channel blockers, is present 863
discharges. Prior to the advent of ICDs, amiodarone was in more than one right precordial lead in the absence of
11 structural abnormalities and in association with one of the α subunit of the cardiac sodium channel protein and a linkage
following conditions: to a second locus on chromosome 3 was demonstrated in a
1. Documented VF or polymorphic VT large Brugada syndrome family and direct sequencing of
2. A family history of SCD at a young age or a type I ECG in that region led very recently to the identification of a novel
family members mutation in the glycerol-3-phosphate dehydrogenase 1-like
3. Otherwise unexplained syncope gene (GPD1L).92
4. Inducibility of VT/VF with programmed electrical Sudden death results from fast polymorphic VT originating
stimulation. Patients with spontaneous Type I ECG are at from the RVOT, degenerating into VF. Ventricular arrhythmias
increased risk for malignant arrhythmias. and aborted sudden death in Brugada syndrome, occurs at
Brugada syndrome is inherited as an autosomal dominant rest when the vagal tone is augmented and often at night.
trait, linked to mutations in the SCN5A gene,91 encoding the 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
table 2 documented VT/VF have a history of syncope.
Diagnostic criteria for Brugada syndrome90
A central characteristic of Brugada syndrome is the absence
ST-segment abnormalities in leads V1-V3 of clear structural abnormalities. The ability to detect slight
Type 1 Type 2 Type 3 structural abnormalities has become greater with electron
J point ≥ 2 mm ≥ 2 mm ≥ 2 mm beam computed tomography (CT) scan and cardiac magnetic
T wave Negative Positive or Positive
resonance imaging (MRI).93,94 These methods have revealed
biphasic right ventricular (RV) wall motion abnormalities and RVOT
ST-T Coved type Saddleback Saddleback
enlargement. These findings demonstrate a link between
configuration functional and structural abnormalities and also support the
hypothesis that sodium channel mutations themselves may
ST segment Gradually Elevated Elevated
(terminal descending ≥ 1 mm < 1 mm induce subtle structural derangements and myocardial cell
portion) death.95
864
Figure 11: Different degrees of electrocardiographic changes seen in the same patient
differential diagnosis risk stratification 60
The conditions that are also accompanied by ST segment The prognosis of Brugada syndrome patients is still being
tachyarrhythmias
elevation should be carefully ruled out before the debated. While it is accepted that patients with aborted sudden
diagnosis of Brugada syndrome is made, which include death or those who have had symptoms such as dizziness,
arrhythmogenic right ventricular cardiomyopathy (ARVC), syncope or nocturnal agonal respiration should receive an
early repolarization syndrome, acute myocardial infarction, ICD, conflicting data exist regarding risk stratification and
isolated right ventricular infarction, Prinzmetal’s angina, therapeutic options in asymptomatic individuals.
electrolyte disturbances such as hyperkalemia and
hypercalcemia, acute pericarditis/myocarditis and ECG posTopEraTiVE TaChyCardia
recorded after electrical cardioversion (Box 1).
Drugs and intoxications can lead to a Brugada-like ST The principal patient groups include patients having had
segment elevation such as CCBs or nitrates, tricyclic or incisions over the atrium or ventricle. Atrial arrhythmias
tetracyclic antidepressant medications as well as selective are seen after incision over right atrium for simple cardiac
serotonin reuptake inhibitors and cocaine.96 repairs such as ASDs, VSDs, tetralogy of Fallot (TOF),
atrioventricular canal defects and related defects or following
Therapy complex surgeries such as Mustard or the Senning procedure
or the Fontan procedure. Ventricular tachycardia is seen in
The most effective prevention of sudden death in patients surgically corrected TOF and with related lesions such as
affected by Brugada syndrome who suffered from (aborted) certain types of double outlet right ventricle.99
cardiac arrest or syncope or are considered at high risk for
ventricular arrhythmias are ICDs.97 Quinidine is the only oral Ventricular Tachycardia in postoperative Tetralogy of fallot
agent that has been proven to normalize the ST segment and to
be effective in suppressing arrhythmic events in patients with Postoperatively, the most common congenital lesion associated
Brugada syndrome (both spontaneous events and inducible with VT is TOF, 10 to 15 percent have VT postoperatively.100
VT/VF during EPS);98 neither beta-blockers nor amiodarone Sudden death occurs in 5 to 10 percent. The risk factors associated
have proven to be effective. 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
Box 1: abnormalities associated with Brugada-like st abnormal signal-averaged electrograms with late potentials and
segment elevation the development of VT. A wide QRS duration of greater than
Conditions that can lead to ST segment elevation, mimicking 180 ms has been associated with VT, correlated with severe
Brugada syndrome pulmonary insufficiency leading to RV dilation. QRS duration
• Early repolarization syndrome and degree of pulmonary regurgitation seem to be the greatest
• Cocaine intoxication risk factors for VT and sudden death.101,102 Valve replacement
• Acute myocardial infarction or isolated right ventricular decreases the incidence of episodes of VT and atrial flutter.The
• Infarction ventriculotomy, myocardial resection, and subsequent scarring
• Prinzmetal’s angina
provide the electrophysiological substrate of slow conduction
• Hyperkalemia and hypercalcemia
• Acute pericarditis/myocarditis and block that predisposes the patient to develop reentrant
• RBBB or LBBB and left ventricular hypertrophy arrhythmias. Ventricular arrhythmias occasionally occur despite
• Acute aortic dissection/acute pulmonary embolism good hemodynamic results, although sudden death occurs most
• Arrhythmogenic right ventricular cardiomyopathy commonly in VT associated with poor hemodynamics. Patients
• Long QT syndrome type III repaired earlier in life seem to have a lower incidence of VT,
• Hypothermia suggest that early repairs may decrease the incidence of VT in
• Duchenne muscular dystrophy these patients.
• Friedreich’s ataxia
• Various central and autonomic nervous system
abnormalities Evaluation
• Mechanical compression of the RVOT by a mediastinal
tumor All postoperative patients, especially those noted earlier at
LBBB =Left bundle branch block; RBBB = Right bundle
highest risk, should have periodic follow-up (usually yearly)
branch block, RVOT = Right ventriclular outflow tract. 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 drug refractory cases. The ICD and pacemakers are valuable
and those treated for arrhythmias may need more frequent tools in the treatment of certain arrhythmias.
monitoring. Those with complex arrhythmias (NSVT,
polymorphic PVCs or polymorphic VT) or monomorphic In nature there are neither rewards nor punishments - there
VT should undergo further testing, requiring an EPS. These are only consequences.
studies have been used to evaluate the propensity of these —Robert G. Ingersol
patients to develop VT, evaluate the efficacy of specific
pharmacologic therapies and locate the site of origin of the aCknoWlEdgmEnT
arrhythmia in patients who are candidates for ablative therapy.
Electrophysiological studies may be helpful in determining I wish to thank Dr Somasekhar for his help in preparing this
the need for implantation of an automatic cardioverter article.
defibrillator, negative study does not guarantee that VT/VF or
sudden death will not occur. rEfErEnCEs
management and Treatment 1. Strasburger JF. Cardiac Arrhythmias in childhood. Diagnostic

considerations and treatment. Drugs. 1991;42:974-83.
The presence of frequent or complex ventricular ectopy 2. Ko JK, Deal BJ, Strasburger JF, Benson DW Jr. Supraventricular
tachycardia mechanisms and their age distribution in pediatric
probably identifies a high-risk group, but at present our ability
patients. Am J Cardiol. 1992;69:1028-32.
to further identify those patients at highest risk is limited. It 3. Spear JF, Moore EN. Mechanisms of cardiac arrhythmias.
appears that patients with QRS duration above 180 ms and Annu Rev Physiol. 1982;44:485-97.
severe pulmonary regurgitation represent high-risk patients. 4. Gilmour RF. Early after depolarization-induced triggered
Because of the high incidence of ventricular arrhythmias in activity: Initiation and reinitiation of reentrant arrhythmias.
postoperative patients, their precise role in the occurrence of Heart Rhythm. 2004;1:449-50.
sudden death is unclear. It is known after tetralogy repair that 5. Losek JD, Endom E, Dietrich A, Stewart G, Zempsky W, Smith
exercise stress testing or ambulatory monitoring will uncover K. Adenosine and pediatric supraventricular tachycardia in the
a 25 to 70 percent incidence of ventricular arrhythmias. emergency department: multicenter study and review. Ann
Emerg Med. 1999;33:185-91.
It appears that patients with QRS duration above 180 ms
6. Perry JC, Garson A Jr. Supraventricular tachycardia due
and severe pulmonary regurgitation represent high-risk to Wolff-Parkinson-White syndrome in children: early
patients. The ICD should definitely be considered in patients disappearance and late recurrence. J Am Coll Cardiol.
with aborted SCD, sustained VT. The treatment should be 1990;16:1215-20.
individualised with combination of drugs, RFA and ICD.103 7. Garson A Jr, Gillette PC, McNamara DG. Supraventricular
tachycardia in children: clinical features, response to
atrial arrhythmias treatment, and long-term follow-up in 217 patients. J Pediatr.
1981;98:875-82.
The late postoperative arrhythmias contribute significantly 8. Nadas AS, Daeschner CW, Roth A, Blumenthal SL.
Paroxysmal tachycardia in infants and children: study of 41
to morbidity and mortality. The treatment options included
cases. Pediatrics. 1952;9:167-81.
medical therapy with antiarrhythmic agents, implantation of 9. Jack CS, Stephen PS. Supraventricular tachycardia, Arch
antitachycardia pacemakers, catheter ablation and surgical Pediatr Adolesc Med. 2009;163:268-74.
ablation. The ablative techniques, potentially offer a curative 10. Blomstrom-Lundqvist C, et al. ACC/AHA/ESC guidelines
treatment. Even in patients having surgical right atrial scar for the management of patients with supraventricular
for surgeries for ASD, VSD, TOF, the common arrhythmia is arrhythmias M—executive summary. European Heart Journal.
atrial flutter rather than incisional AT. 2003;24:1857-97.
11. Winniford MD, Fulton KL, Hillis LD. Long-term therapy
of paroxysmal supraventricular tachycardia: a randomized,
ConClUsion double-blind comparison of digoxin, propranolol and
verapamil. Am J Cardiol. 1984;54:1138-9.
Arrhythmias are an important cause of morbidity and
12. Weindling SN, Saul JP, Walsh EP. Efficacy and risks of medical
mortality in children. It is necessary to determine which therapy for supraventricular tachycardia in neonates and
pediatric ECG findings are normal, which are abnormal, infants. Am Heart J. 1996;131:66-72.
and which must be addressed. A systematic approach to 13. Drago F, et al. Paroxysmal reciprocating supraventricular
the diagnosis of arrhythmias is essential so that appropriate tachycardia in infants: electrophysiologically guided medical
treatment can be given. Medical management remains the treatment and long-term evolution of the re-entry circuit.
mainstay of treatment, RFAs is usually considered in cases of Europace. 2008;10:629-35.
866
14. Alboni P, Tomasi C, Menozzi C, et al. Efficacy and safety
of out-of-hospital self-administered single-dose oral drug
32. Kappenberger LJ, Fromer MA, Steinbrunn W, et al. Efficacy
of amiodarone in the Wolff-Parkinson-White syndrome with
60
treatment in the management of infrequent, well-tolerated rapid ventricular response via accessory pathway during atrial
tachyarrhythmias
paroxysmal supraventricular tachycardia. J Am Coll Cardiol. fibrillation. Am J Cardiol. 1984;54:330-5.
2001;37:548-53. 33. Drago F, Silvetti MS, Santis AD. Paroxysmal reciprocating
15. Wong KK, Potts JE, Etheridge SP, Sanatani S. Medications supraventricular tachycardia in infants: Electrophysiologically
used to manage supraventricular tachycardia in the infant: a guided medical treatment and long-term evolution of the re-
North American Survey. Pediatr Cardiol. 2006;27(2):199-203. entry circuit. Europace. 2008;10:629-35.
16. Tanel RE, Walsh EP, Lulu JA, Saul JP. Sotalol for refractory 34. Akhtar M, Jazayeri MR, Sra J, et al. Atrioventricular nodal
arrhythmias in pediatric and young adult patients: initial re-entry: clinical, electrophysiological, and therapeutic consid-
efficacy and long-term outcome. Am Heart J. 1995;130:791-7. erations. Circulation. 1993;88:282-95.
17. Blaufox AD. “Catheter Ablation of Tachyarrhythmias in Small 35. Lockwood D, Otomo K, Wang Z, et al. Electrophysiological
Children”. Indian Pacing and Electrophysiology Journal. characteristics of atrioventricular nodal reentrant tachycardia:
2005;5:51-62. implications for the reentrant circuit. In: Zipes DP, Jaliffe J
18. Munger TM, Packer DL, Hammill SC, et al. A population study (Eds). Cardiac Electrophysiology: From Cell to Bedside, 4th
of the natural history of Wolff-Parkinson-White syndrome edn. Philadelphia, WB Saunders. 2004, pp. 537-57.
in Olmsted County, Minnesota, 1953-1989. Circulation. 36. Clague JR, Dagres N, Kottkamp H, et al. Targeting the slow
1993;87:866-73. pathway for atrioventricular nodal reentrant tachycardia: Initial
19. Zipes, et al. Focal Atrial Tachycardia. ch 8.Clinical results and long-term follow-up in 379 consecutive patients.
Arrhythmology and Electrophysiology, 1st edn 2009, pp. 157- Eur Heart J. 2001;22:82.
76. Saunders, Elsevier, Philadelphia. 2009. pp.157-76. 37. Lindinger A, Heisel A, Von Bernuth G, et al. Permanent
20. Roberts KC, et al. Focal atrial tachycardia I: Clinical features junctional re-entry tachycardia: a multicenter long-term
diagnosis, mechanisms, and anatomic location. Pac and Clin follow-up study in infants, children and young adults. Eur
Electrophysiology. 2006;29:643. Heart J. 1998;19:936-42.
21. Kistler PM, Roderts KC, Haqanni HM, et al. P wave 38. Aquinaga L, Primo J, Anguera I, et al. Long-term follow-up in
morphology in focal atrial tachycardia: development of an patients with the permanent form of junctional reciprocating
algorithm to predict the anatomic site of origin. J Am Coll tachycardia treated with radiofrequency ablation. Pacing Clin
Cardiol. 2006;48:1010. Electrophysiol. 1998;21:2073-78.
22. Zeigler V, Gillette PC, Ross BA, et al.Flecainide for 39. Garson A Jr, Gillette PC. Junctional ectopic tachycardia in
supraventricular and ventricular arrhythmias in children and children: Electrocardiography, electrophysiology and pharma-
young adults. Am J Cardiol. 1989;14:185-91. cologic response. Am J Cardiol. 1979;44:298.
23. Colloridi V, Perri C, Ventriglia F, Critelli G. Oral sotalol in 40. Case CL, Gillette PC. Automatic atrial and junctional
pediatric atrial ectopic tachycardia. Am Heart J. 1992;123:254- tachycardias in the pediatric patient: Strategies for diagnosis
6. and management. Pacing Clin Electrophysiol. 1993;16:1323-
24. Walsh EP, Saul JP, Hulse JE, et al. Transcatheter ablation 35.
of ectopic atrial tachycardia in young patients using 41. Villain E, Vetter VL, Garcia JM, et al. Evolving concepts in the
radiofrequency current. Circulation. 1992;86:1138-46. management of junctional ectopic tachycardia: A multicenter
25. Santinelli V, Carlo Pappone, et al. Long-Term Prospective study. Circulation. 1990;81:1544.
Follow-Up Study of 184 Asymptomatic Children.The Natural 42. Rychik J, Marchlinski F, Sweeten TL, et al. Transcatheter
History of Asymptomatic Ventricular Pre-Excitation: A JACC. radiofrequency ablation of congenital junctional ectopic
2009;53:275-80. tachycardia in a neonate. Pediatr Cardiol. 1996;17:220-2.
26. Josephson ME. Preexcitation syndromes. In: Josephson ME 43. Balaji S, Sullivan I, Deanfield JE, James I. Moderate
(Ed). Clinical Cardiac Electrophysiology, 3rd edn. Philadelphia, hypothermia in the management of resistant automatic
Lippincott, Williams & Wilkins, 2002. pp. 322-424. tachycardias in children. Br Heart J. 1991;66:224.
27. Katsouras CS, Greakas GF, Goudevenos JA, et al. Localization 44. Alexander ME, Berul CI. Ventricular arrhythmias: When to
of accessory pathways by the electrogram. Pacing Clin worry. Pediatr Cardiol. 2000;21:532-41.
Electrophysiol. 2004;27:189. 45. Tsuji A, Nagashima M, Hasegawa S, et al. Long-term follow-
28. Arruda M, Wang X, McClennand J. ECG algorithm for up of idiopathic ventricular arrhythmias in otherwise normal
predicting sites of successful radiofrequency ablation of children. Jpn Circ J. 1995;59:654-62.
accessory pathways (abstract). Pacing Clin Electrophysiol. 46. Benson DW Jr, Gallagher JJ, Sterba R, et al. Catecholamine
1993;16:865. induced double tachycardia: Case report in a child. Pacing Clin
29. Fitzgerald DM, Hawthorne HR, Crossley GH, et al. P wave Electrophysiol. 1980;3:96-103.
morphology during atrial pacing along the atrioventricular 47. Jervell A, Lange-Nielsen F. Congenital deaf-mutism, functional
ring. ECG localization of the site of origin of retrograde atrial heart diseases, with prolongation of the QT interval and sudden
activation. J Electrocardiol. 1996;29:1. death. Am Heart J. 1957;54:59-68.
30. Epstein MC, Kiel EA, Victoria BE. Cardiac decompensation 48. Crotti L S-BM, Pedrazzini M, Ferrandi C, Insolia R, Goulene
following verapamil therapy in infants with supraventricular K, Salice P, Mannarino S, Schwartz PJ. Prevalence of the long
tachycardia. Pediatrics. 1985;75:737. QT syndrome. Circulation 2005;112(Suppl. II):660.
31. Kunze KP, Schluter M, Kuck KH. Sotalol in patients with 49. Garson A Jr, Macdonald D II, Fournier A, et al. The long QT
867
Wolff-Parkinson-White syndrome. Circulation. 1987;75: syndrome in children: An international study of 287 patients.
1050-7. Circulation. 1993;87:1866-72.
11 50. Scott WA, Macdonald DII. Two:one atrioventricular block in
infants with congenital long Q-T syndrome. Am J Cardiol.
catecholaminergic polymorphic ventricular tachycardia.
Circulation. 2004;110(Suppl. II):552.
1987;60:1409-10. 71. Priori SG, Napolitano C, Memmi M, et al. Clinical and
51. Zareba W, Moss AJ, Schwartz PJ, et al. Influence of genotype molecular characterization of patients with catecholaminergic
on the clinical course of the long-QT syndrome. International polymorphic ventricular tachycardia. Circulation. 2002;106:
Long-QT Syndrome Registry Research Group. N Engl J Med. 69-74.
1998;339:960-5. 72. Sumitomo N, Harada K, Nagashima M, et al. Catecholaminer-
52. Garson A Jr. How to measure the QT interval—what is normal? gic polymorphic ventricular tachycardia: Electrocardiographic-
Am J Cardiol. 1993;72:14B-6B. characteristics and optimal therapeutic strategies to prevent
53. Schwartz PJ. Idiopathic long QT syndrome: progress and sudden death. Heart. 2003;89:66-70.
questions. Am Heart J. 1985;109:399-411. 73. De Rosa G, Delogu AB, Piastra M, et al. Catecholaminergic
54. Schwartz PJ, Moss AJ, Vincent GM, Crampton RS. Diagnostic polymorphic ventricular tachycardia: Successful emergency
criteria for the long QT syndrome: An update. Circulation. treatment with intravenous propranolol. Pediatr Emerg Care.
1993;88:782-4. 2004;20:175-7.
55. Vincent GM, Jaiswal D, Timothy KW. Effects of exercise on 74. Swan H, Laitinen P, Kontula K, et al. Calcium channel
heart rate, QT, QTc and QT/QS2 in the Romano-Ward inherited antagonism reduces exercise-induced ventricular arrhythmias
long QT syndrome. Am J Cardiol. 1991;68:498-503. in catecholaminergic polymorphic ventricular tachycardia
56. Swan H, Toivonen L, Viitasalo M. Rate daptation of QT patients with RyR2 mutations. J Cardiovasc Electrophysiol.
intervals during and after exercise in children with congenital 2005;16:162-6.
long QT syndrome. Eur Heart J. 1998;19:508-13. 75. Elliott P, Andersson B, Arbustini E, et al. Classification of the
57. Malfatto G, Beria G, Sala S, et al. Quantitative analysis of T cardiomyopathies: A position statement from the European
wave abnormalities and their prognostic implications in the Society of Cardiology Working Group on Myocardial and
idiopathic long QT syndrome. J Am Coll Cardiol. 1994;23:296- Pericardial Diseases. Eur Heart J. 2008;29:270-6.
301. 76. Nugent AW, Daubeneny PE, Chondros P, et al. The epidemiol-
58. Priori SG, Napolitano C, Diehl L, et al. Dispersion of QT ogy of childhood cardiomyopathy in Australia. N Engl J Med.
interval. A marker of therapeutic efficacy in the idiopathic long 2003;348:1639-46.
QT syndrome. Circulation. 1994;89:1681-8. 77. Lipshultz SE, Sleeper IA, Towbin JA, et al. The incident of
59. Ackerman MJ, Khositseth A, Tester DJ, Hejlik J, Shen WK, pediatric cardiomyopathy in two regions of the United States.
Porter CJ. Epinephrine-induced QT interval prolongation: N Engl J Med. 2003;348:1647-55.
A gene-specific paradoxical response in congenital long QT 78. McKenna WJ, England D, Doi YL, et al. Arrhythmias in
syndrome. Mayo Clin Proc. 2002;77:413-21. hypertrophic cardiomyopathy: Influence on prognosis. Br
60. Shimizu W, Noda T, Takaki H, et al. Epinephrine unmasks Heart J. 1981;46:168.
latent mutation carriers with LQT1 form of congenital long- 79. Fananapazir L, Chang AC, Epstein SE, McAreavey D. Prog-
QT syndrome. J Am Coll Cardiol. 2003;41:633-42. nostic determinants in hypertrophic cardiomyopathy: Pro-
61. Banai S, Tzivoni D. Drug therapy for torsade de pointes. J spective evaluation of a therapeutic strategy based on clini-
Cardiovasc Electrophysiol. 1993;4:206-10. cal, Holter, hemodynamic, and electrophysiological findings.
62. Crawford MH, Karliner JS, O’Rouke RA, et al. Prolonged Circulation. 1992;86:730-40.
QT interval syndrome: successful treatment with combined 80. McKenna WJ, Franklin RCG, Nihoyannopoulos P, et al.
ventricular pacing and propranolol. Chest. 1975;68:369. Arrhythmia and prognosis in infants, children and adolescents.
63. Moss AJ, Robinson J. Clinical features of the idiopathic long with hypertrophic cardiomyopathy. J Am Coll Cardiol.
QT syndrome. Circulation. 1992;85(suppl):I140-4. 1988;11: 147-53.217.
64. Moss AJ, Zareba W, Hall WJ, et al. Effectiveness and 81. Yetman AT, Hamilton RM, Benson LN, McCrindle BW.
limitations of beta-blocker therapy in congenital long-QT Long-term outcome and prognostic determinants in children
syndrome. Circulation. 2000;101:616-23. with hypertrophic cardiomyopathy. J Am Coll Cardiol.
65. Moss AJ, Robinson J. Clinical features of the idiopathic long 1998;32:1943-50.
QT syndrome. Circulation. 1992;85(suppl):I140-4. 82. Sangwatanaroj S, Prechawat S, Sunsaneewitayakul B, et al.
66. Schwartz PJ, Locati EH, Moss AJ, et al. Left cardiac New electrocardiographic leads and the procainamide test
sympathetic denervation in the therapy of congenital long QT for the detection of the Brugada sign in sudden unexplained
syndrome. A worldwide report. Circulation. 1991;84:503-11. death syndrome survivors and their relatives. Eur Heart J.
67. Moss AJ, Liu JE, Gottlieb S, et al. Efficacy of permanent 2001;22:2290-6.
pacing in the management of high-risk patients with long QT 83. Matsuo K, Akahoshi M, Nakashima E, et al. The prevalence,
syndrome. Circulation. 1991;84:1524-9. incidence and prognostic value of the Brugada-type
68. Schwartz PJ, Priori SG, Brink PA, et al. Who Are the Long-QT electrocardiogram: A population-based study of four decades.
Syndrome Patients Who Receive an Implantable Cardioverter- J Am Coll Cardiol. 2001;38:765-70.
Defibrillator and What Happens to Them? Circulation. 84. Shimizu W, Matsuo K, Kokubo Y, et al. Sex hormone and
2010;122:1272-82. gender difference–role of testosterone on male predominance
69. Leenhardt A, Lucte V, Denjoy I, et al. Catecholaminergic in Brugada syndrome. J Cardiovasc Electrophysiol. 2007;18:
polymorphic ventricular tachycardia in children. A 7-year 415-21.
follow-up of 21 patients. Circulation. 1995;91:1512-9. 85. Hermida JS, Lemoine JL, Aoun FB, et al. Prevalence of the
868
70. Cerrone M, Colombi B, Bloise R, et al. Clinical and molecular Brugada syndrome in an apparently healthy population. Am J
characterization of a large cohort of patients affected with Cardiol. 2000;86:91-4.
86. Meregalli PG, Wilde AAM, Tan HL. Pathophysiological
mechanisms of Brugada syndrome: depolarization disorder,
95. Frustaci A, Priori SG, Pieroni M, et al. Cardiac histological
substrate in patients with clinical phenotype of Brugada
60
repolarization disorder or more? Cardiovasc Res. 2005;67: syndrome. Circulation. 2005;112:3680-7.
tachyarrhythmias
367-78. 96. Rouleau F, Asfar P, Boulet S, et al. Transient ST segment
87. Nabauer M, Beuckelmann DJ, Uberfuhr P, et al. Regional elevation in right precordial leads induced by psychotropic
differences in current density and rate dependent properties of the drugs: Relationship to the Brugada syndrome. J Cardiovasc
transient outward current in subepicardial and subendocardial Electrophysiol. 2001;12:61-5.
myocytes of human left ventricle. Circulation. 1996;93:168-77. 97. Brugada P, Brugada R, Brugada J, Geelen P. Use of the
88. Tukkie R, Sogaard P, Vleugels J, et al. Delay in right ventricular prophylactic implantable cardioverter defibrillator for
activation contributes to Brugada syndrome. Circulation. patients with normal hearts. Am J Cardiol. 1999;83:
2004;109:1272-7. 98D-100D.
89. Wilde AA, Antzelevitch C, Borggrefe M, et al. Proposed 98. Mizusawa Y, Sakurada H, Nishizaki M, Hiraoka M. Effects
diagnostic criteria for the Brugada syndrome: consensus report. of low-dose quinidine on ventricular tachyarrhythmias
Circulation. 2002;106:2514-9. in patients with Brugada syndrome: Low-dose quinidine
90. Wilde AA, Antzelevitch C, Borggrefe M, Brugada J, Brugada therapy as an adjunctive treatment. J Cardiovasc Pharmacol.
R, Brugada P, et al. Proposed diagnostic criteria for the Brugada 2006;47:359-64.
syndrome: consensus report. Eur Heart J. 2002;23:1648-54. 99. Vetter VL, Horowitz LN. Electrophysiologic residua and
91. Chen Q, Kirsch GE, Zhang D, et al. Genetic basis and sequelae of surgery for congenital heart defects. Am J Cardiol.
molecular mechanism for idiopathic ventricular fibrillation. 1982;50:588.
Nature. 1998;392(6673):293-6. 100. Gillette PC, Yeoman MA, Mullins CE, et al. Sudden death after
92. Weiss R, Barmada MM, Nguyen T, Seibel JS, Cavlovich D, repair of tetralogy of Fallot. Circulation. 1977;56:566.
Kornblit CA, et al. Clinical and molecular heterogeneity in 101. Deanfield JE, McKenna WJ, Presbitero P, et al. Ventricular
the Brugada syndrome. A novel gene locus on chromosome 3. arrhythmia in unrepaired tetralogy of Fallot: Relation to
Circulation. 2002;105:707-13. age, timing of repair and hemodynamic status. Br Heart J.
93. Takagi M, Aihara N, Kuribayashi S, et al. Localized right 1984;52:77.
ventricular morphological abnormalities detected by electron- 102. Vaksmann G, Fournier A, Davignon A, et al. Frequency and
beam computed tomography represent arrhythmogenic prognosis of arrhythmias after operative “correction” of
substrates in patients with the Brugada syndrome. Eur Heart J. tetralogy of Fallot. Am J Cardiol. 1990;66:346-9.
2001;22:1032-41. 103. Stevenson WG, Delacretaz E, Friedman PL, Ellison KE.
94. Papavassiliu T, Wolpert C, Fluchter S, et al. Magnetic resonance Identification and ablation of macrore entrant ventricular
imaging findings in patients with Brugada syndrome. J tachycardia with the CARTO electroanatomical mapping
Cardiovasc Electrophysiol. 2004;15:1133-8. system. Pacing Clin Electrophysiol. 1998;21:1448-56.
869
C hapter
Invasive Electrophysiology Testing

61 and Devices in Children
Dinesh Choudhary, Abhilash SP, Narayanan Namboodiri
Introduction Preprocedure Preparation

The invasive management of both bradyarrhythmias and The planning of EP study should include choice of intracardiac
tachyarrhythmias is limited in children, because of technical and/or transesophageal technique and requires some pre-
issues involved in performing safe procedures, lesser procedure studies (e.g. electrocardiography [ECG], Holter
evidence-based recommendations in this population, to monitoring, exercise testing, imaging studies). The child and
substantiate the use of devices and as a consequence, lack of family should be well explained about the procedure and
regulatory approval for performing the procedures. The safety technique including success rate of procedure and potential
and feasibility concerns, especially in ablative procedures are complications. Age-related patient and family preparation
particularly related to the anatomical rather than physiological should begin with the pediatric electrophysiologist and
reasons. Children do have smaller cardiac chambers, thinner continued by nurses and other technical staff. General anesthesia
and perhaps more fragile tissues, smaller coronary arteries should be used for all pediatric and young adolescent patients
and smaller distances between structures, such as the posterior for procedural success and to reduce complications due to
septum and the atrioventricular (AV) node or the AV ring and catheter movements in non-cooperative children. Continuous
the coronary arteries in comparison to adults.1-8 Due to these intravenous propofol acts as a deep sedative with low doses
facts, catheters and devices tailored for use in adults may not and as a general anesthetic with higher doses. It causes less
be ideal for use in children. However, arrhythmia mechanisms postprocedural nausea and vomiting, patients recover faster.
and their management options in children largely overlap However, the electrophysiologic effects of propofol in children
with that in adults and it makes the practice of invasive are no different from isoflurane-based anesthetics.9
electrophysiology unique in many aspects.
Sheath and Catheter Placement
Invasive Electrophysiology in children:
an overview To avoid antiarrhythmic serum concentration,10 0.5 to 1
percent concentration lidocaine given in sufficient amounts
Invasive electrophysiology (EP) in pediatric population can (but not in increased volume) to achieve local anesthesia is
be divided into diagnostic studies and mapping and ablation recommended. The number, size and location of the sheaths
of specific arrhythmias. relates to the age and size of the patient, underlying arrhythmia
and objectives of the study. In most studies, the number of
Diagnostic Electrophysiology Studies sheaths varies between 1 to 5, with the maximum number
consisting of three in the femoral vein, one in the internal
The purpose of a diagnostic EP study is to assess the dynamic jugular vein and one in the femoral artery. Sheath sizes
electrophysiologic properties of the different atrial, AV usually correlate directly with the size of the patient and vary
node, His-Purkinje system (HPS) and ventricular cells and between 4 and 8 French (Fr). The 6 or 7 Fr sheaths are used
eventually try to induce and analyze cardiac arrhythmias with because when intravenous drug administration is required, a
concomitant use of drugs, if necessary (e.g. isoproterenol, side-arm sheath larger than the catheter within it, permits free,
adenosine, atropine, procainamide, epinephrine, etc). unobstructed flow of fluid into the vein.
Transesophageal route as an additional access has been catheters used primarily for recording and mapping contain 61
used traditionally in many situations. Limitations in terms between 6 and 12 electrodes. Short (1–2 mm) interelectrode
of cost, higher risk and application in small infants may distances are important in attaining the goals of maximum-
Invasive Electrophysiology Testing and Devices in Children

dominate in specific situations, making the transesophageal quality electrograms and precise mapping. The number,
technique the best choice for the individual patient. The manipulation and placement of electrode catheters involves
inability to effectively pace the ventricle and fixed site of several factors, including patient size and age, underlying
recording and stimulation are the major limitations to the arrhythmia, objectives of the individual study, size and type
transesophageal technique. The inability to reach the effective of catheters (e.g. steerable), and underlying cardiac and blood
refractory period of the atrium is occasionally overcome by vessel anatomy.
increasing the energy output. This is a potential limitation to
the transesophageal technique, especially when attempting to Mapping and Ablation of Arrhythmias in Children
fully evaluate patients with pre-excitation when the accessory
pathway refractory period is limited by reaching the atrial Ventricular tachycardia (VT) is relatively rare in children
refractory period first. (< 5% of all tachycardias and 20% of wide-complex
The heparin dose varies among laboratories, but the tachycardias).11 Supraventricular tachycardia (SVT) accounts
initial dose is usually 70 to 100 U/kg, to a maximum of for most arrhythmias in children.1 SVT is most likely due
5,000 U. Ongoing heparin anticoagulation can be provided to accessory AV pathway (AP) in this age group and easily
by a continuous intravenous infusion (e.g. 15–20 U/kg/hr) ablatable.1 In the absence of a history of surgery for structural
or by boluses. For the optimal anticoagulation during long congenital heart disease (CHD), accessory pathways (APs)
procedures, the activated clotting time (ACT) is measured probably underlie about 75 percent of all SVTs in children1
one to three times per hour to achieve a desired value of 200 and 95 percent in neonates,12 compared with 30 to 40 percent
to 300 seconds except higher values of 300 to 400 seconds of SVTs in adults. Atrioventricular nodal reentrant tachycardia
when 3-D balloon array mapping systems are used within the (AVNRT) and primary atrial tachycardias (both reentrant
left atrium or ventricle. Other pharmacological agents may and automatic) each appear to account for about half of the
be required for a complete study, depending on the goal of remaining SVTs.1
the EP study, e.g. use of adenosine to block conduction in Some arrhythmias like ectopic atrial tachycardia (EAT),
the AV node, provocative arrhythmic drug like isoproterenol, junctional ectopic tachycardia (JET) and the permanent form
epinephrine, caffeine, atropine, procainamide or flecainide. of junctional reciprocating tachycardia (PJRT) are unique to
The doses of isoproterenol and epinephrine continuous drip pediatric patients.
infusions are similar and range from 0.01 to 0.1 mg/kg/min. Ectopic atrial tachycardia accounts for 5 to 20 percent
Atropine (0.01–0.04 mg/kg) is infrequently used, because it of SVTs in children (< 2% of SVTs in adult).13,14 It is
cannot be administered as a continuous drip and because of its usually due to automatic single atrial focus outside the sinus
longer-lasting effects. Invasive pressure monitoring is done node. It is frequently incessant and presents usually with
during the procedure for safety reasons with radial or femoral tachycardiomyopathy in 50 to 75 percent of cases.15,16
artery access in indicated cases. EAT may resolve spontaneously, if patient is younger than
A standard diagnostic EP study involves use of 4 catheter 6 months, but in many cases it is resistant to drug therapy
electrodes in high right atrium (RA) at lateral wall, right and arrhythmia surgery. Ventricular function usually returns
ventricular apex, coronary sinus and His bundle location. The to normal after control of arrhythmia.15 This has led to an
coronary sinus catheter (decapolar) allows recording of left aggressive approach with catheter ablation. Radiofrequency
atrial and ventricular electrograms. The other catheters (Halo (RF) catheter ablation for EAT arising from a single focus
catheter, Lasso catheter, basket catheter, etc.) are for specific has been acutely successful in 90 to 100 percent of cases
use. without significant complications.13 Most incessant EATs can
The catheter sizes vary between 2 and 7 Fr. Formerly, the 4 be successfully mapped. Map signals that precede the surface
Fr catheters were used virtually only for infants, whereas the P wave by more than 20 ms are most likely to indicate a
5 Fr catheters most often were used in young children and 6 successful location.16
and 7 Fr catheters were used for adolescents and adult-sized Junctional ectopic tachycardia is seen in two settings in
patients. Smaller (2–3 Fr) catheters are used for intracardiac children: postoperative and congenital.17,18 Both are caused
recordings as well as for epicardial mapping (by advancing by abnormal automaticity, from either low in the AV node
the catheters from the coronary sinus into the very small or high in the HPS. Postoperative JET is strongly associated
branches throughout the epicardial surface). These small with ventricular septal defect repair, is usually transient,
catheters can be used in any size patients with the advantage lasting between 1 to 4 days and responds well to cooling and
of minimizing the venous puncture site and therefore skin, intravenous amiodarone or propafenone.19 These observations
muscle and vein trauma. Most catheters used for recording suggest that the tachycardia may be due to trauma and
and pacing are in a quadripolar configuration, whereas inflammation induced at the time of the repair. Congenital JET 871
11 is typically not associated with structural CHD; is incessant; in smaller patients. The reported incidences of coronary
has a positive family history in 50 percent of cases; usually injury4,6 are 0.03 percent in children29 and 0.06 to 0.1 percent
does not respond to cooling; is associated with the maternal in adults30 during AVNRT and APs ablation. Cryoablation is
Electrophysiological Issues in Children
lupus anti-SSA and anti-SSB antibodies in some cases20 and a good alternative therapy in children with a 97 percent acute
may spontaneously resolve. Both JET types appear to be success rate and 2 percent recurrence with cryoablation.31
exacerbated by adrenergic stimulation,17 and respond well There are no reports of permanent AV block with cryoablation.
to intravenous amiodarone. JET may initially be best treated Accessory pathway function may spontaneously disappear
medically by minimizing adrenergic stimulation and starting by 1 year of age.32 Aggressive pharmacologic control should
amiodarone, particularly in infants because of potential risk be attempted first before ablation, because of known risks of
of AV block from either catheter21 or surgical17 ablation of catheterization and ablation in this age group. Radiofrequency
the JET focus (no clear site of ablation) in the AV junction. ablation lesions may increase in size during development and
Cryotherapy is the treatment of first choice for ablation. may lead to sudden cardiac death.3 Coronary artery damage is
Permanent form of junctional reciprocating tachycardia also a heightened risk in infants due to close proximity of the
is caused by an orthodromic reciprocating tachycardia coronaries (RCA and LCX) to the ablation catheter.4-6 Despite
involving a slow and decremental retrogradely conducting these, ablation is still needed in a small subset of infants with
concealed AP. It may resolve spontaneously.22 Catheter AP-mediated tachycardia. Lesion size is related to catheter-tip
ablation is highly effective technique in difficult to control size, RF power, tip temperature and lesion duration. Therefore
patients with PJRT, with minimal risk for AV block.23,24 Most ablation should be done on atrial side with low temperature
common site of these APs is posteroseptal, but may occur in (55°C–60°C) and of shorter duration burns with 5F catheter
any location along the AV groove. Electrogram characteristics, tip. Cryotherapy is much less harmful to coronary arteries.
electrophysiologic techniques and mapping techniques are The pre-excitation syndromes are statistically increased
somewhat different for PJRT pathways than for typical non- in patients with Ebstein malformation, l-transposition of
decremental APs. It is often impossible to confirm an AP the great arteries or hypertrophic cardiomyopathy. Multiple
as the retrograde conduction pathway using the standard pathways are present in 30 to 80 percent of patients33-37
technique of His refractory ventricular premature beat compared with 5 to 10 percent of patients without CHD.30,34,36
because the retrograde conduction decrements after premature Accessory atrioventricular connections in Ebstein
ventricular stimulation. The VA interval is usually long and anomaly pose special problems. Differentiation of atrial
an AP potential may be present in as many as 75 percent of and ventricular signals and precise localization of the AV
cases.25 The pathways must usually be mapped and ablated in groove can be difficult in Ebstein anomaly, leading to a
tachycardia, because it is often not possible to achieve reliable lack of specificity for what appear to be excellent signals
exclusive AP conduction during ventricular pacing, owing to in predicting a successful ablation site. The true AV groove
either AV node conduction or retrograde block at any cycle (site of AP potentials) is best identified by a right coronary
length longer than that of the tachycardia. Success rate of electrode wire. Catheter stabilization for free wall pathways in
radiofrequency ablation (RFA) is more than 95 percent, but the largest hearts is difficult and is not sufficiently improved
recurrence rates are higher than for typical APs. AV block and through the use of a long sheath or a variety of approaches.2
coronary damage are the potential complications.4 Coronary damage is common, probably because of the thin
Dual AV node physiology in pediatric patients is seen right ventricular wall and often diminutive right coronary
in only 60 percent of cases26,27 in comparison to adults artery. The success rate is 80 to 90 percent with infrequent
(90–100%)28 with inducible AVNRT. The difference in the major complications such as permanent AV block.33-35
baseline conduction properties of the two pathways does not Recurrence rates have been reported to be as high as 40
reach the threshold for dual physiology in about 40 percent of percent, particularly, if multiple pathways are present.33-37
children. Magnitude of the AH (atrium-His bundle) change at Ablation procedures in patients with heterotaxy or
the transition from the fast to the slow pathway is related to AV discordance require detailed echocardiography and
heart size and therefore to age, because AH or the PR interval angiography for defining the complex anatomy of the atria, the
increases with age. Younger children have faster conduction in AV ring and the coronary sinus. Careful attention must be given
the slow pathway than older children and adults.27 In children, to locate the normal conduction system thereafter. In most of
the slope change of AH versus AA (atrium-atrium) is a more the patients with AV discordance, the AP has been associated
reliable and specific measure of the transition between the fast with the tricuspid valve, whereas the His bundle has been
and slow pathways than the AH jump alone. For ablation of associated more closely with the mitral valve. After locating
AVNRT, smaller catheter should be used in smaller children the normal and abnormal conduction, electrophysiologic study
(< 20 kg), to minimize the lesion size. Success rate is more and RFA of the APs can proceed with less risk for damage
than 95 percent.26 The risk for heart block is higher because to the normal conduction system. The AV node in corrected
of relatively large lesion size compared with the size of the transposition is typically situated superior and anterior in the
872 heart and closeness of ‘smaller’ AV node to the slow pathway atrial wall. The penetrating bundle then runs in the fibrous
continuity between the right sided mitral valve and the anterior in animals, children or adults. Isolated case reports of late 61
cusp of the posterior great artery and continues as left bundle coronary stenosis have also been described, especially in
branch on the right side of the ventricular septum. The right children who had extensive ablation of transannular pathways

bundle branch then penetrates the ventricular septum to emerge in conditions like Ebstein anomaly. Virtually all pediatric
in the inferior left-sided right ventricle. A second AV node is programs use general anesthesia for ablation cases and most
often present more inferiorly (in the normal area of the triangle non-electrophysiologic catheter interventions.
of Koch).This can also link to the ventricular conduction fibers Safety concerns dominate the decision to ablate in many
posteriorly (inferior to a ventricular septal defect). Conduction pediatric arrhythmias. Myocardial injury3 and potentially
sling,38 which joins these posterior and anterior ventricular severe coronary injury4-6 are more likely with RFA in this age
bundle branches together, is known as Mönckeberg sling. These group with AP ablation. Radiofrequency abalation lesion may
anatomic findings provide the substrate for different types of grow with age and may lead to sudden cardiac death.3 About
ventricular excitation or preexcitation and AV reciprocating 40 percent of APs in infants spontaneously stop functioning
tachycardias. during the first year of life32 and an additional one-third of
Despite all these limitations, most APs in patients with CHD patients are unlikely to have symptoms between infancy
can be safely and effectively ablated despite the difficulties of and early childhood,41 so ablation should be planned when
unusual anatomy and abnormal course of conduction fibers. safety and benefits edge over complications. In contrast to
In children, atrial re-entrant tachycardias are relatively the situation in infants, even asymptomatic Wolff-Parkinson-
rare in the absence of either structural or functional heart White (WPW) patients between the ages of 10 and 18 years
disease. Age presentation is bimodal. Most common is during may be managed more aggressively than adults. Unlike
the third trimester of fetal life, when atrial flutter accounts for asymptomatic adults older than age 28 years, who are unlikely
up to 33 percent of fetal tachycardias.1 Neonatal atrial flutter to ever have symptoms, the older child with a high-risk
almost universally resolves without recurrence, if it can be pathway is exactly the type of patient who may present with
managed successfully during fetal and early neonatal life.39 So sudden arrhythmic death as their initial symptom, leading to
ablation therapy for such infants is usually not necessary and the recommendation that such patients should undergo risk
has never been reported. A second presentation peak occurs stratification and RFA accordingly.
during adolescence, when both atrial flutter and fibrillation
may occur in the absence of any identifiable structural, Safety of radiofrequency and potential
hormonal or chemical cause. Initial management should be use of cryoablation
conservative. But ablation is usually needed in this age group
because of high recurrence rate despite medical therapy. Electrophysiologic procedures cause major complications
Success rate is more than 90 percent for the flutter subgroup.40 in 0.7 (diagnostic EP study) to 2.0 percent (if ablation
Techniques for ablation of atrial flutter or fibrillation is included). Myocardial injury and potentially severe
in the larger child are not much different than in adults. The coronary injury are more likely with RFA in the pediatric
timing (when to ablate) and technique chosen should be the population. Cryoablation has several potential advantages
most conservative in terms of safety because complications over RFA, including reversible cryomapping before the
such as pulmonary vein stenosis and stroke can be devastating production of a permanent lesion, adherence of the catheter
to a child. tip to the endocardium on freezing, a well-defined edge of
Radiofrequency ablation of atrial tachycardia in post the cryolesion, minimal effects on adjacent coronary arteries
operative CHD patients has many unique challenges, because and a lower incidence of thrombus. Only disadvantage of
of anatomic complexity, atypical tachycardia substrates and cryoablation is that lesion size is less and data regarding this
abnormally thick atrial muscle, which is difficult to ablate. therapy in pediatric population are less.
Technologic advances in 3D mapping and the broader
availability of ablation catheters designed to make more Pacemakers in Children
effective RF lesions have significantly improved outcomes.
About one percent of all pacemakers are implanted in the
Safety vs Efficacy of RADIOFREQUENCY Ablation children.42 Though there is not much difference in surgical
technique in children and adults for pacemaker implanation,
Risk for vascular injury, secondary to thrombus or embolus still it requires an experienced and skilled surgeon to evaluate
formation, exists with any catheterization and ablation in the problems in the smaller babies regarding implantation and
smaller children. To minimize these, a tendency is not to use life long consequences.
the retrograde arterial approach in children. New or increased
valvular regurgitation also has been reported in pediatric Indications
patients after use of the retrograde arterial approach. The
risk for acute coronary damage is also increased in smaller Indications for pacing in newborns and infants are divided 873
children. Data on late coronary function are not available predominantly into three groups based on American College
11 of Cardiolgoy/American Heart Association (ACC/AHA) Vessel recanalisation with balloon dilatation should be
guidelines:43 considered in case of severe obstruction or occlusion of the
1. Congenital abnormalities of the conduction system. subclavian vein or the superior vena cava combined with
2. Acquired heart blocks after cardiac surgery for correction surgical treatment before planning an epicardial or alternative
of congenital defects. approach.
3. Sinus node diseases. Epicardial pacing indications in newborns or infants are:
Rare indications include the therapy of tachyarrhythmias, 1. Too small baby.
hypertrophic obstructive cardiomyopathy and of the long- 2. Venous abnormalities or congenital malformations, which
QT-syndrome. make a venous lead implantation impossible: discordant
atrioventricular connection, tricuspid atresia or after
Implantation Fontan surgery.
3. If all upper venous vessels have thrombotic occlusions and
Implantation of a pacemaker in infants requires the individual alternative approaches are not possible.
assessment of: 4. If a right-to-left shunt with the risk of systemic embolization
1. Access (endovenous versus epicardial). exists.
2. Leads. 5. If one wants to prevent the endovenous problems regarding
3. Implantation site (infraclavicular versus abdominal). growth. Epicardial leads (cork-screw mechanism or only
4. Selection between subcutaneous versus submuscular plane. a suture fixed) should be steroid-eluting and bipolar.
The expected growth of the child, lifelong dependency Disadvantage of epicardial pacing leads are higher
on pacing therapy and multiple revisions in future have to be threshold and slightly higher fracture rate because of the
taken into consideration during implantation. higher mechanical stress compared to endovenous leads.
Currently it is recommended to use the epicardial approach Another alternative for endocardial pacing is the transatrial
in infants until the age of 3 to 4 years in order to prevent a approach. Indications for this more invasive approach are
lesion of the subclavian vein. With advancement in technique occluded, obstructed, hypoplastic central veins or disconnected
and hardwares, the trend from epicardial towards endovenous superior vena cava from the RA (either congenital or post
leads is increasing. surgical). A transatrial approach can replace the epicardial
Lead revision due to growth of children remains a potential stimulation, which would normally be used in these situations
problem in pacing therapy until puberty. Fibrotic attachment and prevents its potential complications.
to the vessel wall (mostly at the junction of the subclavian Pulse generators are usually implanted subpectorally (sub
and brachiocephalic vein with the superior vena cava) can muscularly) to prevent pocket related problems in small
compromise a later advancement of the lead. This results in children. This requires bipolar leads to prevent pectoral muscle
implantation of an additional new lead in a relatively short stimulation. The cosmetic aspect is much more favorable
period of time after the first implantation despite the normal with this approach. It also prevents Twiddler syndrome. For
lead parameters. Keeping the large loop in the RA to reduce using epicardial systems (mostly in babies), pocket is created
this increases the chances of displacement (due to tension abdominally behind the anterior sheet of the rectus muscle
of the floating loop on the tip of the endocardial electrode), (subxiphoidal approach).
arrhythmias (if migrating to right ventricle) and significant In view of multiple lead implantations during lifetime,
pulmonary valve insufficiency (if migrating to pulmonary pediatric pacing therapy should only be carried out by
artery). Every year approximately 10 millimeters of lead length experienced surgeons and in well equipped cath labs to prevent
is necessary to compensate body growth, thus 80 millimeter or to minimize complications. Prior to every single lead
right atrial lead loop allows 6 to 12 years (mean 8 years) of insertion, physician should judge the central venous access in
growth without need of lead replacement.44 Redundant lead terms of stenosis or occlusion sonographically and then try to
loop within the inferior vena cava or sliding technique of lead plan the operation. If a new pacing lead has to be implanted
fixation at the site of venous entrance with slowly absorbable endovenously, the old screw-in lead should be extracted
sutures are of questionable value in view of lead adherence to during the same session. An additional endovenous lead
vascular wall. loop for further growth has to be considered preoperatively.
The isodiametric construction of leads allows an easier and The latest rate adaptive pacemakers should be implanted to
safer elective extraction. Active fixation allows an anchorage provide most physiological pacing mode.
at every desired position, which is helpful in anatomic Left ventricular systolic or diastolic dysfunction can
variations or complex cardiac malformations. Continuous result after long-term right ventricular apical pacing in
release of steroid in the first phase after implantation ensures the young. This can be reduced by pacing at septal or
stable low chronic stimulation thresholds. Severe tricuspid high right ventricular outflow tract. With these positions,
regurgitation and atrial or ventricular perforation are the echocardiographic findings show markedly normalized
874 potential complications after lead placement. ventricular contraction patterns.
The implantable cardioverter-defibrillator (ICD) is now 4. Blaufox AD, Saul JP. Acute coronary artery stenosis during
slow pathway ablation for atrioventricular nodal re-entrant
61
established as safe and effective for preventing sudden cardiac
death (SCD) in children. The continued miniaturization of tachycardia in a child. J Cardiovasc Electrophysiol. 2004;15:

97-100.
devices and leads have allowed their use in smaller patients,
5. Paul T, Kakavand B, Blaufox AD, et al. Complete occlusion
including children, infants and even neonates. However, the of the left circumflex coronary artery after radiofrequency
proper indications, implantation methods, programing and catheter ablation in an infant. J Cardiovasc Electrophysiol.
long-term follow-up issues continue to evolve. Individualized 2003;14:1004-06.
implant techniques are necessary for the smallest children and 6. Bertram H, Bokenkamp R, Peuster M, et al. Coronary
those with complex CHD. artery stenosis after radiofrequency catheter ablation of
Cardiac resynchronization therapy (CRT) has been accessory atrioventricular pathways in children with Ebstein’s
extensively studied in adult heart failure patients. There malformation. Circulation. 2001;103:538-43.
are less trial of CRT in patients with CHD who make up a 7. Hope EJ, Haigney MC, Calkins H, et al. Left main coronary
thrombosis after radiofrequency ablation: Successful treatment
substantially different population that is characterized by
with percutaneous transluminal angioplasty. Am Heart J.
unusual anatomy including univentricular heart, systemic right 1995;129:1217-9.
ventricles and other anomalies. CRT has been demonstrated 8. Nakagawa H, Chandrasekaren K, Pitha J, et al. Early detection
to benefit certain CHD patients, but significantly varies by of coronary artery injury produced by radiofrequency ablation
substrate. within the coronary sinus using intravascular ultrasound
imaging. Circulation. 1995;92:I-610.
Conclusion 9. Erb TO, Kanter RJ, Hall JM, et al. Comparison of
electrophysiologic effects of propofol and isoflurane-based
Arrhythmia mechanisms, ongoing myocardial development, anesthetics in children undergoing radiofrequency catheter
ablation for supraventricular tachycardia. Anesthesiology.
increased risk for vascular injury, AV node damage, smaller
2002;96:1386-94.
cardiac size and presence of CHDs should be considered 10. Pass RH, Walsh EP. Intracardiac electrophysiologic testing in
prior to ablation in children. In a child, safety should be a pediatric patients. In: Walsh EP, Saul JP, Triedman JK (Eds).
priority over efficacy. Therefore, variations of technique Cardiac Arrhythmias in Children and Young Adults with
should be applied to the decision to ablate the energy source Congenital Heart Disease. Philadelphia: Lippincott Williams
and its delivery, the catheter approach to the heart and the and Wilkins; 2001. pp. 57-94.
AV ring and the follow-up. Still it seems clear that a variety 11. Benson DW, Smith WM, Dunnigan A. Mechanisms of regular
of techniques and approaches are necessary to successfully wide QRS tachycardia in infants and children. Am J Cardiol.
ablate substrates in all locations of the heart, including the AV 1982;49:1776-88.
12. Weindling SN, Walsh EP, Saul JP. Management of supra
groove in children.
ventricular tachycardia in infants. J Am Coll Cardiol. 2000;21:
Pacemaker implantation into children does not differ 294a.
substantially from operations in adults. As most of these 13. Walsh EP, Saul JP, Hulse JE, et al. Transcatheter ablation
children remain pacemaker dependent for lifetime, it is of of ectopic atrial tachycardia in young patients using radio-
tremendous importance to minimize all revisions regarding frequency current [see comments]. Circulation. 1992;86:1138-46.
the implanted systems and to enable small patients a nearly 14. Weindling SN, Saul JP, Walsh EP. Efficacy and risks of medical
normal quality of life. For ICD and CRT in pediatric patients therapy for supraventricular tachycardia in neonates and
data regarding indications and outcomes are limited and are infants. Am Heart J. 1996;131:66-72.
continuously evolving. 15. Gillette PC, Smith RT, Garson A Jr, et al. Chronic
supraventricular tachycardia: a curable cause of congestive
cardiomyopathy. JAMA. 1985;253:391-2.
Declare the past, diagnose the present, foretell the future. 16. Walsh EP. Ablation of ectopic atrial tachycardia in children. In:
―Hippocrates Huang SK (Ed). Radiofrequency Catheter Ablation of Cardiac
Arrhythmias: Basic Concepts and Clinical Applications. Mt.
References Kisko, NY: Futura; 1994. pp. 421-43.
17. Villain E, Vetter VL, Garcia JM, et al. Evolving concepts in
1. Ko JK, Deal BJ, Strasburger JF, et al. Supraventricular the management of congenital junctional ectopic tachycardia:
tachycardia mechanisms and their age distribution in pediatric a multicenter study [see comments][review]. Circulation.
patients. Am J Cardiol. 1992;69:1028-32. 1990;81:1544-9.
2. Saul JP, Hulse JE, De W, et al. Catheter ablation of accessory 18. Walsh EP, Saul JP, Sholler GF, et al. Evaluation of a staged
atrioventricular pathways in young patients: use of long vascular treatment protocol for rapid automatic junctional tachycardia
sheaths, the transseptal approach and a retrograde left posterior after operation for congenital heart disease. J Am Coll Cardiol.
parallel approach. J Am Coll Cardiol. 1993;21:571-83. 1997;29:1046-53.
3. Saul JP, Hulse JE, Papagiannis J, et al. Late enlargement of 19. Sholler GF, Walsh EP, Saul JP, et al. Evaluation of a staged
radiofrequency lesions in infant lambs: Implications for ablation treatment protocol for postoperative rapid junctional ectopic
tachycardia. Circulation. 1988;78:II-597. 875
procedures in small children.Circulation. 1994;90:492-9.
11 20. Dubin AM, Cuneo B, Strasburger J, et al. Congenital junctional
tachycardia and congenital complete AV block: a shared
33. Levine JC, Walsh EP, Saul JP. Radiofrequency ablation of
accessory pathways associated with congenital heart disease
etiology? Heart Rhythm. 2005;2:313-5. including heterotaxy syndrome. Am J Cardiol. 1993;72:689-93.
21. Gillette PC, Garson A Jr, Porter CJ, et al. Junctional automatic 34. Jackman WM, Wang XZ, Friday KJ, et al. Catheter ablation of
ectopic tachycardia: New proposed treatment by transcatheter accessory atrioventricular pathways (Wolff-Parkinson-White
His bundle ablation. Am Heart J. 1983;106:619-23. syndrome) by radiofrequency current [see comments]. N Engl
22. Guarnieri T, German LD, Gallagher JJ. The long RP’ tachycar- J Med. 1991;324:1605-11.
dias [review]. Pacing Clin Electrophysiol. 1987;10: 103-17. 35. Van Hare GF, Lesh MD, Stanger P. Radiofrequency catheter
23. Ticho BS, Walsh EP, Saul JP. Ablation of permanent junctional ablation of supraventricular arrhythmias in patients with
reciprocating tachycardia. In: Huang SK, (Ed). Radiofrequency congenital heart disease: results and technical considerations. J
Catheter Ablation of Cardiac Arrhythmias: Basic Concepts and Am Coll Cardiol. 1993;22:883-90.
Clinical Applications. Mt. Kisko, NY: Futura; 1994. pp. 397- 36. Smith WM, Gallagher JJ, Kerr CR, et al. The electrophysiologic
409. basis and management of symptomatic recurrent tachycardia in
24. Gaita F, Haïssaguerre M, Giustetto C, et al. Catheter ablation patients with Ebstein’s anomaly of the tricuspid valve. Am J
of permanent junctional reciprocating tachycardia with Cardiol. 1982;49:1223-34.
radiofrequency current. J Am Coll Cardiol. 1995;25:648-54. 37. Twidale N, Wang X, Beckman KJ, et al. Factors associated
25. Haïssaguerre M, Montserrat P, Warin JF, et al. Catheter with recurrence of accessory pathway conduction after
ablation of left posteroseptal accessory pathways and of long radiofrequency catheter ablation. Pacing Clin Electrophysiol.
RP’ tachycardias with a right endocardial approach. Eur Heart 1991;14:2042-8.
J. 1991;12:845-59. 38. Symons JC, Shinebourne EA, Joseph MC, et al. Criss-cross
26. Van Hare GF, Chiesa NA, Campbell RM, et al. Pediatric heart with congenitally corrected transposition: Report of a
Electrophysiology Society. Atrioventricular nodal reentrant case with d-transposed aorta and ventricular preexcitation. Eur
tachycardia in children: effect of slow pathway ablation on fast J Cardiol. 1977;5:493.
pathway function [comment]. J Cardiovasc Electrophysiol. 39. Dunnigan A, Benson DW, Benditt DG. Atrial flutter in
2002;13:203-9. infancy: diagnosis, clinical features and treatment. Pediatrics.
27. Blaufox AD, Rhodes JF, Fishberger SB. Age related changes 1985;75:725-9.
in dual AV nodal physiology. Pacing Clin Electrophysiol. 40. Kugler JD, Danford DA, Houston K, et al. Radiofrequency
2000;23:477-80. catheter ablation for paroxysmal supraventricular tachycardia
28. Rosen KM, Bauernfeind RA, Swiryn S, et al. Dual AV nodal in children and adolescents without structural heart disease.
pathways and AV nodal reentrant paroxysmal tachycardia. Am Pediatric EP Society, Radiofrequency Catheter Ablation
Heart J. 1981;101:691-5. Registry. Am J Cardiol. 1997;80:1438-43.
29. Kugler JD, Danford DA, Deal BJ, et al. Radiofrequency 41. Perry JC, Garson A, Jr. Supraventricular tachycardia due
catheter ablation for tachyarrhythmias in children and to Wolff-Parkinson-White syndrome in children: early
adolescents. The Pediatric Electrophysiology Society. N Engl J disappearance and late recurrence [see comments]. J Am Coll
Med. 1994;330:1481-7. Cardiol. 1990;16:1215-20.
30. Calkins H, Langberg J, Sousa J, et al. Radiofrequency catheter 42. Bink-Boelkens MTHE. Cardiac pacing in infants and children.
ablation of accessory atrioventricular connections in 250 Neth J Cardiol 1992;5:199-202.
patients: abbreviated therapeutic approach to Wolff-Parkinson- 43. Recommendations for Permanent Pacing in Children,
White syndrome. Circulation. 1992;85:1337-46. Adolescents and Patients With Congenital Heart Disease-
31. Avari JN, Jay KS, Rhee EK. Experience and results during ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy
transition from radiofrequency ablation to cryoablation of Cardiac Rhythm Abnormalities: Executive Summary: A
for treatment of pediatric atrioventricular nodal reentrant Report of the American College of Cardiology/American Heart
tachycardia. Pacing Clin Electrophysiol. 2008;31:454-60. Association Task Force on Practice Guidelines.
32. Deal BJ, Keane JF, Gillette PC, et al. Wolff-Parkinson-White 44. Gheissari A, Hordof AJ, Spotnitz HM. Transvenous pacemaker
syndrome and supraventricular tachycardia during infancy: in children: relation of lead length to anticipated growth. Ann
management and follow-up. J Am Coll Cardiol. 1985;5:130-5. Thorac Surg. 1991;52:118-21.
876
Sec t i on
12
Miscellaneous
C hapter
Congenital Coronary Artery

62 Anomalies
Nick Hayes, Shakeel Qureshi
Congenital coronary artery anomalies encompass a constellation Anatomy

of conditions where there is a variation in the origin, course,
intrinsic anatomy or termination of one or both the coronary The coronary arterial circulation has been extensively described3
arteries. Although the prevalence of these conditions are low and in essence is similar to any systemic arterial network,
compared to that of other congenital heart defects (CHD), consisting of large proximal epicardial conductive arteries
their pathophysiological effects can be of critical importance. leading to an extensive distal myocardial arteriolar-capillary
In this chapter we will focus on isolated congenital coronary bed.4 Typically there are two major coronary arteries: the right
artery abnormalities (i.e. those occurring in the absence of coronary artery and the left main stem, which take origin from
other structural cardiac defects), for whilst coronary anoma- the two correspondingly named right and left aortic sinuses of
lies can often be found in association with other CHD (e.g. Valsalva, adjacent to the pulmonary artery (Figure 1). These
transposition of the great arteries or pulmonary atresia), these sinuses are small bulbous out pouchings between the aortic
conditions are addressed specifically elsewhere. valve and sinotubular junction. There are usually three aortic
sinuses, with the third most distant from the pulmonary trunk
Normal Coronary Arteries termed the non-coronary sinus as it is extremely unusual for a
major coronary artery to take origin from this sinus. Whilst the
Before considering coronary anomalies it is important to coronary artery ostia are usually located fairly centrally within
review the anatomical structure, physiological function the aortic sinus and just below the sinotubular junction, there is
and embryogenesis of normal coronary arteries. Defining considerable variation both in proximity to valvar commissures
‘normal’ coronary arrangement is not however as straight and height of take off, with ostia up to 1 cm above the sinotubular
forward as it may seem. It would be simple to take a junction still considered within the normal variation.5,6
definition of normality as the pattern occurring in the majority
(i.e. > 50%) of the population and consequently any deviation Left Coronary Artery
from this as an anomaly. However, certain variations in
coronary arrangements with no physiological significance The left main stem arises from the left sinus of Valsalva
can occur in large proportions of the population. For and courses laterally, posterior to the pulmonary artery and
example, a separate origin of the conal artery direct from the anterior to the left atrial appendage, a short distance (1–2 cm
right sinus of Valsalva, resulting in three distinct coronary in adult) before dividing into the circumflex and left anterior
ostia, is observed in close to 50 percent of the population.1 descending (also termed the anterior interventricular)7 arteries.
It seems incongruous to classify such benign ‘normal The diameter is usually larger than the right coronary artery
variations’ as anomalous, which has led to the proposal that (RCA) as it typically supplies a larger area of myocardium
an anomaly be defined as occurring in less than 1 percent including the majority of the left ventricle. In around 1 percent
of an unselected population.2 This of course assumes that of the population there are separate origins of the circumflex
the true prevalence of each pattern is known and does not and left anterior descending arteries direct from the left aortic
incorporate pathophysiological significance, but does sinus with no left main stem.6
provide a useful platform on which to base a definition, with The left circumflex (LCx) artery runs under the left
subsequent further classification. atrial appendage and then travels posterior-inferiorly in left
12
Miscellaneous
Figure 1: Aortic root angiogram and cardiac MRI demonstrating normal coronary arrangement
atrioventricular groove. A number of marginal branches, the branch of the right coronary artery, although as previously
largest of which is termed the obtuse marginal, arise along mentioned, in the rest the conal artery takes origin directly from
the course of the circumflex and supply the lateral wall of the aortic root with a separate ostial orifice. The next branch
the left ventricle and the anterolateral papillary muscle. The is usually the sinus node artery, although again in around 50
sinus node artery arises from the circumflex in 50 percent of percent this originates from the circumflex. Several marginal
individuals. Around 10 percent of the population display a branches, the largest of which is termed the acute marginal,
‘left-dominant’ pattern,3 where the posterior descending (also supply the right ventricular free wall. Around 90 percent of the
termed the inferior interventricular)7 artery arises from the population have a ‘right-dominant’ pattern, with the posterior
circumflex and proceeds to supply the atrioventricular node descending artery originating from the right coronary artery.3
and inferior right ventricular surface. In these individuals, the It is important to note that the term ‘dominance’ is merely a
circumflex artery is considerably larger in diameter. descriptive term reflecting this pattern and does not refer to
The left anterior descending (LAD) artery descends along the coronary artery supplying the majority of the myocardium,
the anterior surface of the heart in the anterior interventricular which is nearly always the left coronary artery, irrespective
groove and can continue beyond the apex to anastamose with of the origin of the posterior descending artery. The posterior
the posterior descending artery. The left conal artery is the first descending artery supplies the inferior surface of the left and
branch and may form the circle of Vieussens by anastomosing right ventricles, has posterior septal perforators that penetrate
with the right conal artery.8 Diagonal branches supply the the interventricular septum and also has a branch supplying
anterior surface of the left and right ventricles and around the atrioventricular node.
four septal perforators enter the interventricular septum
and anastamose with septal branches from the posterior Physiology
descending artery.
The coronary arteries are responsible for the supply of oxygen
Right Coronary Artery to the highly aerobic myocardium. This supply is determined
by the oxygen content of the blood (which is primarily
Originates from the right sinus of Valsalva and initially courses related to amount of saturated hemoglobin) and the amount
anteriorly between the pulmonary trunk and right atrial of coronary flow, which in turn is determined by coronary
appendage to the right atrioventricular groove. In around 50 perfusion pressure (the difference between the coronary artery
880 percent of the population the right conal artery forms the first pressure and ventricular end diastolic pressure) and coronary
arterial vascular resistance. During ventricular systole, Abnormalities 62
the myocardial compressive forces cause almost complete
obstruction of the arterioles, resulting in an extremely high
Classification
Congenital Coronary Artery Anomalies

vascular resistance. Consequently, coronary blood flow,
particularly to the left ventricle, occurs virtually exclusively in Earlier classification systems tended to group anomalies into
diastole. Usually, coronary blood flow far exceeds myocardial major and minor variations depending on clinical relevance,
oxygen demand and there is sufficient coronary flow reserve but a more recent and comprehensive classification system
even at peak exertion. However, reduced coronary perfusion has categorized the various anomalies based on the underlying
pressure (for example, from coronary stenosis and/or elevated morphology and is displayed in Box 1.15 As can be seen, the
end diastolic pressure) results in absence of coronary flow range of possible coronary anomalies is vast and further
reserve and ensuing myocardial ischemia to which the discussion will focus on the more important conditions.
subendocardium is particularly susceptible. It is of no surprise
that transient periods of ischemia occur with more mild Abnormalities of Origin and Course
stenosis only at times of high myocardial oxygen demand
(i.e. on exertion). As the stenosis progresses and the impact
Anomalous Left Coronary Artery from the
on coronary perfusion increases, ischemia becomes more
apparent. Ultimately, critical lack of oxygen supply results in
Pulmonary Artery
myocardial cell infarction. Anomalous origin of the left coronary artery from the
pulmonary artery (ALCAPA) is also known by the eponymous
Embryogenesis name Bland-White-Garland syndrome following the original
clinical description by these authors in 1933.16 This is a
Initial theories regarding embryological coronary artery rare anomaly with an estimated incidence of 1:300,000 live
development focused on a supposed fusion of a subepicardial births,17,18 but is of critical clinical importance as it represents
vascular network with endothelial buds that grew out from one of the most common causes of myocardial ischemia in
the base of the truncus arteriosus.9 However, in 1989 Bogers infants and children.19
identified major coronary arteries in the aortic wall prior to
the emergence of coronary ostia, suggesting in-growth, rather Morphology and Pathophysiology
than out-growth of these vessels10,11 and definitive evidence of
this has been demonstrated in chick embryos.12,13 Whilst the Anomalous left coronary artery from the pulmonary artery
myocardium is formed from an endothelial and muscular tube typically occurs in isolation, although can be associated
derived from lateral plate mesoderm, the cells that generate the with other CHD such as ventricular septal defects, tetralogy
epicardium that appears crucial to coronary vessel development, of Fallot and aortic coarctation.9 Usually the anomalous left
originate from a component of mesothelium that arises near coronary artery originates from the right pulmonary sinus,
the liver primordium, termed the proepicardial organ (PEO). which is in closest proximity to the left aortic sinus, although
This grows towards the heart and then gradually spreads out, occasionally there is take off from the other pulmonary
encasing the entire myocardium and pericardial cavity.11 These sinuses or even more distal in the main or proximal branch
epicardial cells then undergo tansformation under the control pulmonary arteries.20,21 The pathophysiology depends on the
of various growth and transcription factors and differentiate status of the blood flow in the left coronary artery.22 In the
to form vascular progenitor cells, which migrate deep into the initial neonatal period, the pulmonary vascular resistance
myocardium and coalesce to form channels.13 (PVR) and pressures are high and there is antegrade perfusion
The vascular tubes undergo branching and fusion to form a of the left coronary myocardial territory, albeit with slightly
complex subepicardial vascular network, part of which forms a desaturated blood from the pulmonary artery. This generally
peritruncal ring, from which capillary plexi penetrate the aortic allows adequate myocardial perfusion to meet oxygen demand
root to form the beginnings of the major coronary arteries.11 This and there is no ischemia.
appears to occur at multiple sites (including the non-coronary As the PVR begins to fall, coronary perfusion pressure falls
sinus), but subsequent fusion and apoptosis occurs14 leading and myocardial oxygen delivery depends on collateral flow
to a definitive coronary circulation around 45 days gestation.9 from the right coronary artery. Occasionally there is extensive
Ongoing vascular remodelling then takes place in the presence of intercoronary collateralization or persistent elevation in
blood flow through the arterial tree. The molecular mechanisms the pulmonary artery pressures and myocardial perfusion is
behind many of these processes are poorly understood and maintained, but typically this is not the case and significant
currently under investigation, but an appreciation of the complex LV myocardial ischemia ensues. With further reduction in
nature of coronary angiogenesis in fact makes it remarkable that the PVR, flow in the left coronary artery becomes retrograde,
congenital coronary anomalies are so rare. resulting in ‘steal’ from the right coronary circulation as it is
881
12 Box 1: Classification of coronary anomalies from Angelini15
A. Anomalies of origination and course. – Posterior atrioventricular groove

Miscellaneous
1. Absent left main trunk (split origination of LCA). – Retroaortic.

2. Anomalous location of coronary ostium within aortic root • LCA that arises from right anterior sinus, with
or near: anomalous course
• High – Posterior atrioventricular groove
• Low – Retroaortic
• Commissural. – Between aorta and pulmonary artery
3. Anomalous location of coronary ostium outside normal – Intraseptal
‘coronary’: – Anterior to pulmonary outflow
• Right posterior aortic sinus – Posteroanterior interventricular groove.
• Ascending aorta 5. Single coronary artery (see A4)
• Left ventricle B. Anomalies of intrinsic coronary arterial anatomy
• Right ventricle 1. Congenital ostial stenosis or atresia (LCA, LAD, RCA,
• Pulmonary artery Cx).
– LCA that arises from posterior facing sinus 2. Coronary ostial dimple.
– Cx that arises from posterior facing sinus 3. Coronary ectasia or aneurysm.
– LAD that arises from posterior facing sinus 4. Absent coronary artery.
– RCA that arises from anterior right facing sinus 5. Coronary hypoplasia.
– Ectopic location (outside facing sinuses) of any 6. Intramural coronary artery (muscular bridge).
coronary 7. Subendocardial coronary course.
- From anterior left sinus 8. Coronary crossing.
- From pulmonary trunk 9. Anomalous origination of posterior descending artery
- From pulmonary branch from the anterior.
• Aortic arch 10. Split RCA:
• Innominate artery • Proximal + distal PDs that both arise from RCA
• Right carotid artery • Proximal PD that arises from RCA, distal PD that
• Internal mammary artery arises from LAD
• Bronchial artery • Parallel PDs × 2 (arising from RCA, Cx) or
• Subclavian artery ‘codominant’.
• Descending thoracic aorta. 11. Split LAD:
4. Anomalous location of coronary ostium at improper sinus • LAD + first large septal branch
(which may involve joint origination or ‘single’ coronary • LAD, double (parallel LADs).
pattern): 12. Ectopic origination of first septal branch:
• RCA that arises from left anterior sinus, with • RCA
anomalous course: • Right sinus
– Posterior atrioventricular groove or retrocardiac • Diagonal
– Retroaortic • Ramus
– Between aorta and pulmonary artery (intramural) • Cx
– Intraseptal C. Anomalies of coronary termination
– Anterior to pulmonary outflow 1. Inadequate arteriolar/capillary ramifications.
– Posteroanterior interventricular groove (wrap 2. Fistulas from RCA, LCA, or infundibular artery to:
around). • Right ventricle
• LAD that arises from right anterior sinus, with • Right atrium
anomalous course • Coronary sinus
– Between aorta and pulmonary artery (intramural) • Superior vena cava
Contd...
– Intraseptal • Pulmonary artery
– Anterior to pulmonary outflow • Pulmonary vein
– Posteroanterior interventricular groove (wrap • Left atrium
around). • Left ventricle
• Cx that arises from right anterior sinus, with • Multiple, right + left ventricles.
anomalous course D. Anomalous anastomotic vessels
Cx = Circumflex; LAD = Left descending coronary artery; LCA = Left coronary artery; RCA = Right coronary artery; PD = Posterior descending branch.
882
shunted into the pulmonary artery, further aggravating the is around 30 years of age, although for patients surviving 62
ischemia. Stenosis of the origin of the left coronary artery may beyond 50, the risk of sudden death appears to decline.17
at this point reduce the degree of ‘steal’ and confer a degree of

protection. Investigation
Clinical Features The main aim of investigation is to differentiate ALCAPA

from other causes of a dilated poorly functioning left ventricle,
Patients predominantly present in early infancy with such as dilated cardiomyopathy and a high index of suspicion
symptoms of congestive heart failure, such as breathlessness, is required in such patients.
failure to thrive, sweating and wheezing. The classic history
includes acute episodes of irritability with associated pallor Chest X-ray
secondary to myocardial ischemia, typically during feeding
or distress, when infant myocardial oxygen demand is at its Chest X-ray is non-specific with cardiomegaly from an
highest. Clinically patients have signs of left heart failure, enlarged left heart and evidence of pulmonary congestion.
with reduced perfusion, displaced apex beat, 3rd or 4th
heart sounds and possibly a murmur secondary to mitral ECG
regurgitation (which can be secondary to left ventricular
dilation or papillary muscle ischemia/rupture). Without Classical signs of ischemia include pathological Q waves
treatment around 90 percent of infants die within the first in the inferolateral leads with poor R wave progression, ST
year of life.23 Around 10 percent of patients with extensive elevation and T wave inversion (Figure 2). However, not all
collateralization present later in childhood or adulthood patients with ALCAPA have classical patterns of ischemia
with a continuous murmur, angina, ventricular arrhythmia on 12 lead ECG and although non-specific ST and T wave
or sudden death. The average life expectancy in this group 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 883
and T wave inversion in I, aVL and V4-6, along with ST elevation in V2-3
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
Miscellaneous
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,
Figure 4: Echocardiogram in parasternal short axis clearly demon-
the papillary muscles tend to be bright and echogenic as a strating the connection of the left coronary artery to the pulmonary
result of infarction and fibrosis, although this is non-specific artery on 2D, with retrograde flow from the coronary artery into the
(Figure 3). There is often significant mitral regurgitation pulmonary artery, noted on color flow mapping
(MR) (from annular dilation, papillary muscle shortening and
also possible papillary muscle rupture) and the left atrium
is dilated. Advances in echocardiographic technology and and occasionally collateral flow can be seen. In cases where
resolution now means that it is technically feasible to confirm the diagnosis remains uncertain following echocardiography,
the diagnosis with 2D imaging of the coronary arteries, with more definitive imaging is required.
the left coronary artery demonstrated originating from the
pulmonary artery (Figure 4), but as the left coronary artery often CT/MRI
takes a course very close to the left aortic sinus, the connection
can easily be misinterpreted as normal (in as many as 70% in Improved spatial resolution of cardiac computed tomography
some reports).24 Doppler assessment with color flow mapping (CT) and magnetic resonance (MRI) imaging has led to their
of the coronary flow is therefore essential for both confirming increasing use in coronary assessment and a number of reports
and excluding the diagnosis with abnormal retrograde flow confirm accurate diagnosis of ALCAPA particularly in the adult
noted in the left coronary artery and a retrograde jet of flow population where acoustic windows for echocardiography
noted in the pulmonary artery.27 The right coronary artery tend to be poor.17,29-31 The CT demonstrates better spatial
tends to be dilated (with an RCA: aortic ratio often ≥ 0.14)28 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.
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
Figure 3: 2-D Echocardiogram from the apical four-chamber view artery tend to be small and may not be identified on a
in a patient with ALCAPA. The left ventricle is dilated, with severely
saturation run, but this is rarely required with diagnostic
884 impaired ventricular function and in particular note the highly echogenic
appearance of the papillary muscles secondary to ischemic fibrosis. angiography. Either root angiography or selective right
A left atrial line is also seen crossing the atrial septum coronary angiography should clearly delineate the anomalous
62

A B
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 in adults, reduced vessel elasticity, increased friability and
5A and B). excessive collateralization make direct reimplantation more
hazardous and internal mammary artery bypass grafting may
Management be safer,39,40 There is, however, little data on long-term patency
of internal mammary grafts in ALCAPA patients and direct
Supportive medical management including ventilation, reimplantation is still advocated in the majority of patients.41
inotropes, afterload reduction and diuretics can be used to If bypass grafting is performed, it is recommended that the
stabilise a sick patient, but the key to management is urgent left coronary origin is ligated to prevent graft thrombosis from
surgical repair to improve myocardial perfusion. Early surgical competitive flow.
techniques prior to the introduction of cardiopulmonary bypass Overall mortality rates have fallen from 75 percent to 80
aimed to reduce pulmonary artery steal by either increasing percent in the early 1980s to 0 percent to 23 percent in the
proximal pulmonary artery pressures with pulmonary artery current era,20 with most mortality in the immediate post-
banding32 or ligating the pulmonary origin of the anomalous operative period. Risk factors identified for 30 day mortality
left coronary artery.33 Subsequently establishment of a two- include young age at operation and reduced pre-operative left
coronary system was reported with saphenous vein grafting34 ventricular function, with the degree of MR not consistently
or direct anastomosis of the left subclavian artery to the left found to influence early mortality.42-44 The degree of MR tends
coronary artery.35 Direct reimplantation of the left coronary to improve with time and there is generally a consensus that
artery was first reported in 197436 and with growing expertise concomitant mitral valve surgery at the time of ALCPA repair
in neonatal coronary surgery as a result of the arterial switch is not necessary (unless there is papillary muscle rupture).
operation, has become established as the procedure of choice This also increases cardiopulmonary bypass time in an already
in the majority. It is technically feasible in most patients and compromised and ischemic ventricle.20,42-44 Mechanical
affords high long-term patency rates.37 If the position or length circulatory support may be required in the immediate
of the left coronary artery makes direct transfer unfeasible, postoperative period to bridge to recovery and it is mandatory
creation of an intrapulmonary coronary baffle (Takeuchi that this is available to units performing surgical repair.
operation)38 is an alternative to direct coronary transfer, but Mid- to long-term results following repair are excellent
future interventions for complications such as suprapulmonary with steady improvement and often normalization in left
stenosis, baffle leaks and aortic regurgitation are required ventricular function within 1 to 2 years and low long-term
in up to 30 percent of patients.20 It has been suggested that mortality.20,43-46 Medical therapy to help off-load the ventricle 885
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
Miscellaneous
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
Figure 6: Echocardiogram in the parasternal short axis demonstrating
than ALCAPA, although on the whole ARCAPA appears a retroaortic course of the left coronary artery, having originated from
to be less severe and it is likely that the true incidence is the right aortic sinus
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 non-
specific ECG findings. Nonetheless some patients do present Following origin from the right aortic sinus, the left coronary
with myocardial ischemia and sudden death, particularly artery takes one of four possible routes back to the left side of
if there is a right dominant coronary pattern. Interestingly the heart:51
associated cardiac lesions appear to be more common than 1. Anteriorly around the pulmonary artery.
with ALCAPA and are reported in up to 1/3 of cases,47 2. Between the great arteries (intra-arterial).
although again this may reflect identification bias. Clearly 3. Within the subpulmonary muscular infundibulum.
surgical repair, usually with coronary artery reimplantation, 4. Posteriorly around the aorta (retroaortic)—Figure 6.
is indicated in patients with evidence of myocardial ischemia. There may also be an associated proximal intramural
There remains uncertainty as to whether surgery is indicated course, slit like opening of the coronary ostium and/or kinking
in asymptomatic patients without evidence of myocardial of the coronary artery of with acute angle take off.
ischemia, but with dramatically improved operative mortality, This lesion has been noted in up to 20 percent of cases of
surgical repair is generally advocated to reduce the risk of SCD in young adults, typically occurring during exertion,52 with
future sudden cardiac death (SCD). an interarterial coronary course conveying a particularly high
risk.51-54 Sudden death can frequently be the first presentation
Isolated Circumflex or Left Anterior Descending Artery with only about 1/3 of patients reporting previous symptoms
from the Pulmonary Artery attributable to ischemia.52,53 Proposed mechanisms for
myocardial ischemia include: flap closure of a slit like coronary
Both these anomalies are extremely rare, but can present with ostium, compression of the intramural segment, kinking of
signs of myocardial ischemia and there is a high incidence of the coronary artery with acute angle take-off and compression
associated CHD.48 Experience is lacking regarding surgical of the coronary artery as it passes between the great arteries
repair, but seems advisable, especially if there is evidence of aggravated by increased stroke volume and arterial distension
ischemia. during exertion, just as myocardial oxygen demand is highest.55
Why comparatively few patients report preceding symptoms
Total Anomalous Coronary Circulation of ischemia despite multiple previous episodes of exertion is
from the Pulmonary Artery unclear. Even when patients report ischemic symptoms, such
as angina or syncope on exertion, the diagnosis still requires
Either with both coronary arteries or a single coronary a high index of suspicion. Resting ECG, exercise stress tests
circulation originating from the pulmonary artery. Extremely and baseline ventricular function are often normal52 and the
rare and generally lethal, although successful repair in an anomaly may be missed on echocardiography.
infant has been reported.49 If echocardiography cannot exclude the diagnosis, further
investigation should be undertaken. Traditionally this involved
Left Coronary Artery from the Right Aortic Sinus cardiac catheterization, but the three dimensional nature of
cardiac CT and MRI have been shown to clearly identify
886 The true prevalence of this anomaly is unknown, but estimates the proximal course of anomalous coronary arteries with
range from 0.1 to 0.3 percent of the general population,50 even more accuracy than invasive angiography.56,57 Surgery
which if true, represents a significant number of individuals. is warranted in symptomatic patients and there is general
consensus that asymptomatic patients with high risk lesions, is extremely unusual.52,60 As with ARCAPA, right coronary 62
such as intra-arterial course, ostial narrowing or an intramural dominance may play a role in clinical presentation and risk. As
segment should also undergo surgery to reduce the risk of the risk of sudden death appears lower, surgical repair is generally

sudden death, although patients without these features can be only undertaken in symptomatic patients or asymptomatic
managed conservatively as the risk of coronary insufficiency patients with documented ischemia on stress testing.59
appears low.58 Surgical options depend on the underlying
morphology, but include coronary reimplantation into the Left or Right Coronary Artery from Non-coronary Sinus
left aortic sinus, ostial enlargement, unroofing if there is an
intramural course or translocation of the pulmonary artery in This pattern is extremely unusual with only a few reports.61
cases of interarterial course if reimplantation is not feasible In general the risk of myocardial ischemia appears low and
(for example, if there is a single coronary ostia).50,55,58 Bypass surgical correction has not been performed, although patients
grafting is generally reserved for patients with concomitant should be assessed for the associated higher risk features such
atherosclerotic disease, as competitive flow from the coronary as ostial stenosis and intramural course.
artery can result in poor long-term graft patency.55,59 Short to
mid-term results are encouraging with no late postoperative Single Coronary Artery
ventricular arrhythmias or sudden death reported, but aortic
regurgitation is a recognized complication and longer term Occurs in approximately 0.024 to 0.066 percent of the
follow-up is required.50,55 population62 with around 40 percent associated with other
CHD.63 Many patients are asymptomatic although a subsection
RCA from the Left Aortic Sinus with higher risk patterns (such as inter-arterial course) can
suffer with myocardial ischemia63 and may warrant surgery.
Less commonly reported in the literature than anomalous origin Clearly the consequences of atherosclerotic disease affecting
of the left coronary artery from the right sinus, but this likely the single coronary artery can be catastrophic and early
reflects a lower incidence of SCD than true prevalence of the intervention is advised for symptomatic patients.
anomaly. Analysis of 1950 angiograms by Angelini actually
demonstrated the prevalence of RCA origin from the left sinus Abnormalities of Intrinsic Coronary
(0.92%) to be higher than left coronary artery origin from the Arterial Anatomy
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
Left Main Coronary Artery Atresia
7), although this again may reflect presentation bias. Although A rare condition where the left coronary ostium and left
mechanisms for myocardial ischemia are presumably the same main coronary artery are absent (sometimes a remnant
as for the left coronary artery, patients very rarely complain fibrous cord is present) with the distal left coronary system
of symptoms and presentation with SCD, whilst reported, filling via collateral flow from the right coronary artery.
887
Figure 7: The right coronary artery is noted to take origin from a high position of the left aortic sinus on this cardiac MRI
12 As with ALCAPA, patients can present in infancy with critical Abnormalities of Coronary Termination
myocardial ischemia, although interestingly and perhaps due
to the lack of pulmonary artery ‘steal’ a much larger proportion Coronary Artery Fistulae
Miscellaneous
of patients appear to present in later childhood or adulthood

with symptoms of myocardial ischemia or occasionally Coronary artery fistulae comprise of an abnormal direct
sudden death.64 Surgical therapy generally consists of internal vascular communication between the coronary arteries and
mammary artery bypass grafting. cardiac chambers (coronary-cameral fistulae), major veins
(coronary-arteriovenous fistulae) or pulmonary arteries
Congenital Ostial Stenosis of the Left Main (coronary-pulmonary fistulae). They can vary from short
Coronary Artery direct communications to large tortuous vessels and represent
one of the more common congenital abnormalities of coronary
Left main stem ostial stenosis is usually associated with arteries with a reported prevalence of 0.13 to 0.22 percent of
atheromatous plaque formation or other forms of systemic or adults undergoing coronary angiography.72
vasculitic disease, however case reports exist where isolated
ostial stenosis does appear to be congenital in origin often Morphology and Pathophysiology
with hypoplasia of the left main coronary artery.65,66 Again,
these patients have generally undergone internal mammary The fistulae appear to represent persistence of intratrabecular
bypass grafting. spaces73 and can arise from any part of the coronary system.
Earlier studies prior to echocardiography suggested that
Myocardial Bridging origination from the right coronary artery was slightly more
common (in around 60%), although it appears that small,
A myocardial bridge is formed when an area of myocardial clinically insignificant fistulae more commonly originate from
muscle overlies a major epicardial coronary artery (most com the left.72 A recent review concluded that overall around 55
monly the middle segment of the LAD), producing a tunnelled percent originated form the left coronary artery, 37 percent
intramyocardial segment of coronary artery. Prevalence varies from the right and 8 percent had multiple origins from both.74
with lower rates noted in angiographic compared to autopsy Most fistulae terminated in the right heart (65%), followed
studies, but on average myocardial bridges are present in around by the pulmonary arteries (23%), the left heart (11%) and
1/3 adults67 and are reported even more frequently in patients rarely multiple sites. Associated cardiac anomalies have been
with hypertrophic obstructive cardiomyopathy.68 The muscle reported in around a quarter of cases, most frequently tetralogy
bridge contracts during ventricular systole causing coronary of Fallot or pulmonary atresia. The underlying pathophysiology
compression. Although coronary flow predominantly occurs in depends on the size of the shunt and site of drainage. Many
diastole, significant compression in a proximal segment of the shunts are small and of little hemodynamic significance. Large
coronary system can still result in reduced overall mean flow left to right shunts will result in pressure and volume loading of
and reduced coronary flow reserve.69 The segment proximal the right heart and pulmonary circulation, while drainage to the
to the bridge also frequently shows atheromatous plaque left atrium or ventricle will produce similar effects to mitral or
formation,70 possibly due to altered flow dynamics. Angina, aortic regurgitation respectively. Significant flow through the
myocardial ischemia, exercise induced arrhythmia and sudden fistula also tends to result in dilation of the proximal coronary
death have all been reported as a result of myocardial bridging, artery and if the shunt is large, there is potential for coronary
although it appears only an extremely small proportion of artery steal and myocardial ischemia.
these anomalies are functionally significant given the overall
prevalence in the population.67 Resting ECG is frequently Clinical Features
normal with non-specific signs of ischemia on stress testing.
The diagnosis was traditionally made by coronary As with the pathophysiology, the clinical symptoms depends
angiography with a lumen diameter reduction of 70 percent on the degree of shunting and site of drainage. Large shunts
in systole and 35 percent in diastole defined as significant,71 may present in infancy with congestive cardiac failure
although newer imaging modalities such as intravascular and improving ultrasound technology has even permitted
ultrasound (IVUS) and MRI may provide more functional prenatal diagnosis, particularly when the shunt is large
information. Medical therapy with beta-blockers or calcium enough to produce chamber enlargement.75 These cases
antagonists is used as the first line, although nitrates should are relatively unusual however, and within the pediatric
be avoided as they can increase the degree of angiographic population most patients are asymptomatic and present with
narrowing and worsen symptoms.69 Surgical myotomy is an incidental murmur, which is classically continuous and
reserved for patients with objective evidence of regional louder in diastole.74,76,77 The exact location of the maximal
ischemia refractive to medical therapy and has been shown intensity of the murmur depends on the site of fistula
888 to improve symptoms. Restenosis or major periprocedural drainage. Interestingly symptoms (such as dyspnea, exercise
complications have been reported in up to 50 percent patients intolerance and chest pain) and complications (including
who have undergone coronary stenting.67 coronary ischemia, myocardial infarction, heart failure,
arrhythmias, endocarditis, pulmonary hypertension and very intervention is best delayed until the patient is slightly larger in 62
rarely rupture)78 appear increasingly common in adulthood order to minimise procedural risk and because some neonates
and have been reported in up to 2/3 of patients.76 It would may become asymptomatic with a relative reduction in the size

therefore appear that fistulae have the potential to dilate over of the fistula over time.80 Equally, fistulae in symptomatic older
time with a progressive increase in the degree of shunting, children and adults warrant occlusion, but debate still exists as
although the exact time-course of this is not well understood to when to intervene in asymptomatic patients. Traditionally
and conversely small fistulae can also close spontaneously.74 closure has been advocated for all patients diagnosed with a
coronary artery fistula in order to prevent future complications.9
Investigation However, complications in children appear uncommon and as
already mentioned, small fistulae have been reported to close
Twelve lead ECG is nearly always normal in small fistulae, spontaneously.72,74 Conservative follow-up has therefore been
although may show signs of chamber enlargement, hypertrophy proposed for small fistulae, although given complications are
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
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 Figure 9: Cardiac MRI in the same patient as Figure 8 confirming
require intervention. However, symptoms of congestive cardiac the proximal right coronary artery dilation and fistula connecting to the
failure in infancy may respond to medical therapy in which case 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
12 increasingly apparent in adulthood, elective closure of medium arteriosus, atrial septal defect and ventricular septal defect
to large asymptomatic fistulas should be considered.72 devices.72,74 Whilst techniques vary according to the position
Surgical closure of the fistula, either by external ligation and drainage of the fistula the key principle is to ensure there
Miscellaneous
or intracardiac closure on cardiopulmonary bypass was is no coronary supply to the myocardium distal to the point
the mainstay of treatment until the first reported catheter of occlusion. If uncertain, this can be tested by observing
occlusion in 1983.81 Since then percutaneous interventional the ECG during temporary balloon occlusion of the fistula
occlusion has gradually become the procedure of choice in the (Figures 10A to D). Results following device occlusion have
vast majority of patients. Reports exist with devices ranging been comparable to surgical results with an expected mortality
from detachable balloons, coils, vascular plugs, patent ductus of < 1 percent. Complications such as device embolisation,
A B
C D
890 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 o’clock. 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
ST changes and coronary occlusion have been reported, matter of ingrowth or outgrowth? Anatomy and Embryology.
1989;180(5):437-41.
62
but are uncommon and small residual shunts appear to be
present in around 10 percent of patients, which is similar to 11. Reese DE, Mikawa T, Bader DM. Development of the coronary

vessel system. Circ Res. 2002;91(9):761-8.
that seen after surgical closure.72 Surgery may be necessary if
12. Waldo KL, Willner W, Kirby ML. Origin of the proximal
close proximity of normal coronary vessels prevent selective coronary artery stems and a review of ventricular vascular
occlusion. There is relatively limited information on long- ization in the chick embryo. American Journal of Anatomy.
term follow-up of this very heterogeneous patient population 1990;188(2):109-20.
and whilst most patients appear to do well, the proximal 13. Tomanek RJ. Formation of the coronary vasculature during
coronary artery can remain persistently dilated with possible development. Angiogenesis. 2005;8(3):273-84.
thrombotic occlusion. As a result, long-term antiplatelet 14. Velkey JM, Bernanke DH. Apoptosis during coronary artery
therapy appears advisable and formal anticoagulation has orifice development in the chick embryo. The Anatomical
been proposed for patients with more than moderate persistent Record. 2001;262(3):310-7.
15. Angelini P. Coronary artery anomalies; an entity in search of an
aneurysmal dilation.72
identity. Circulation. 2007;115:1296-1305.
16. Bland EF, White PD, Garland J. Congenital anomalies of the
Conclusion coronary arteries: report of an unusual case associated with
cardiac hypertrophy. American Heart Journal. 1933;8:787-
As this chapter demonstrates, the range of possible coronary 801.
artery anomalies is vast, but a thorough knowledge of the more 17. Yau JM, Singh R, Halpern EJ, et al. Anomalous origin of the
severe and frequently encountered abnormalities is vital. Not left coronary artery from the pulmonary artery in adults: a
only can the pathophysiological consequences be devastating, comprehensive review of 151 adult cases and a new diagnosis
but also definitive diagnosis may be difficult and a high level in a 53-year-old woman. Clin Cardiol. 2011;34(4):204-10.
18. Keith JD. The anomalous origin of the left coronary artery
of suspicion is required for appropriate further investigation.
from the pulmonary artery. British Heart Journal. 1959;21:
With advances in both surgical and transcatheter therapies the 149-61.
vast majority of these abnormalities can be successful treated 19. Driscoll DJ, Nihill MR, Mullins CE, et al. Management
with low mortality and long term morbidity. of symptomatic infants with anomalous origin of the left
coronary artery from the pulmonary artery. American Journal
The diseases which destroy a man are no less natural than of Cardiology. 1981;75:71-4.
the instincts which preserve him. 20. Dodge-Khatami A, Mavroudis C, Backer CL. Anomalous
— George Santayana origin of the left coronary artery from the pulmonary artery:
collective review of surgical therapy. Ann Thorac Surg. 2002;
74(3):946-55.
References 21. Angelini P. Anomalous origin of the left coronary artery from
the pulmonary artery: the location of the ectopic ostium and the
1. Schlesinger MJ, Zoll PM, Wessler S. The conus artery; a third
course of the proximal left coronary artery make a difference.
coronary artery. Am Heart J. 1949;38(6):823-36, illust.
Tex Heart Inst J. 2008;35(1):36-7.
2. Angelini P. Normal and anomalous coronary arteries:
22. Edwards JE. Anomalous coronary arteries with special
definitions and classification. Am Heart J. 1989;117(2):418-34.
reference to arteriovenous-like communications. Circulation.
3. James TN. Anatomy of the coronary arteries. New York:
1958;17:1001-6.
Hoeber, 1961.
23. Wesselhoeft H, Fawcett JS, Johnson AL. Anomalous origin of the
4. Angelini P. Coronary artery anomalies—current clinical issues:
left coronary artery from the pulmonary trunk. Its clinical spec-
definitions, classification, incidence, clinical relevance, and
trum, pathology, and pathophysiology, based on a review of 140
treatment guidelines. Tex Heart Inst J. 2002;29(4):271-8.
cases with seven further cases. Circulation. 1968;38: 403-25.
5. Muriago M, Sheppard MN, Ho SY, Anderson RH. Location
24. Chang RR, Allada V. Electrocardiographic and echocardio
of the coronary arterial orifices in the normal heart. Clin Anat.
graphic features that distinguish anomalous origin of the left
1997;10(5):297-302.
coronary artery from pulmonary artery from idiopathic dilated
6. Vlodaver Z, Neufeld HN, Edwards JE. Coronary arterial
cardiomyopathy. Pediatr Cardiol. 2001;22(1):3-10.
variations in the normal heart and in congenital heart disease.
25. Kurup RP, Daniel R, Kumar RK. Anomalous origin of the left
New York: Academic Press, 1975.
coronary artery from the pulmonary artery in infancy with
7. Cook AC, Anderson RH. Attitudinally correct nomenclature.
preserved left ventricular function: Potential pitfalls and clues
Heart. 2002;87:503-6.
to diagnosis. Ann Pediatr Cardiol. 2008;1(1):65-7.
8. Loukas M, Groat C, Khangura R, et al. The normal and abnormal
26. Iriart X, Jalal Z, Derval N, et al. Two-dimensional strain as
anatomy of the coronary arteries. Clin Anat. 2009;22(1):114-28.
a marker of subclinical anterior ischemia in anomaly of
9. Rene Herlong J. Congenital Coronary Artery Anomalies. In:
left coronary artery arising from pulmonary artery. Eur J
Garson A, Bricker JT, Fisher DJ, Neish SR, (Eds). The Science
Echocardiogr. 2009;10(5):732-5.
and Practice of Pediatric Cardiology. 2nd edition. Baltimore:
27. Kudo Y, Suda K, Koteda Y. Pitfalls of echocardiographic
Lippincott Williams and Wilkins; 1998.pp.1647-66.
evaluation of anomalous origin of the left coronary artery from
10. Brogers AJJC, Gittenberger-de Groot AC, Poelmann RE,
the pulmonary trunk. Cardiol Young. 2008;18(5):537-8. 891
et al. Development of the origin of the coronary arteries, a
12 28. Koike K, Musewe NN, Smallhorn JF, et al. Distinguishing be-
tween anomalous origin of the left coronary artery from the
with special attention to the mitral valve. Eur J Cardiothorac
Surg. 2009;36(2):244-8.
pulmonary trunk and dilated cardiomyopathy: role of echocar- 45. Schwartz ML, Jonas RA, Colan SD. Anomalous origin of
Miscellaneous
diographic measurement of the right coronary artery diameter. left coronary artery from pulmonary artery: recovery of left
British Heart Journal. 1989;61:192-7. ventricular function after dual coronary repair. J Am Coll
29. Castorina S, Mignosa C, Degno S, et al. Demonstration of an Cardiol. 1997;1997:547-53.
anomalous connection between the left coronary artery and 46. Ojala T, Salminen J, Happonen JM, et al. Excellent functional
the pulmonary artery using a multislice CT 64. Clin Anat. result in children after correction of anomalous origin of left
2008;21(4):319-24. coronary artery from the pulmonary artery—a population-
30. Komocsi A, Simor T, Toth L, et al. Magnetic resonance studies based complete follow-up study. Interact Cardiovasc Thorac
in management of adult cases with Bland-White-Garland Surg. 2010;10(1):70-5.
syndrome. Int J Cardiol. 2007;123(1):e8-11. 47. Williams IA, Gersony WM, Hellenbrand WE. Anomalous right
31. Greer ML, Mondal TK, Yoo SJ. Late presentation of anomalous coronary artery arising from the pulmonary artery: a report of 7
origin of the left coronary artery from the pulmonary artery: the cases and a review of the literature. Am Heart J. 2006;152(5):
definitive role of cardiovascular magnetic resonance imaging. 1004-17.
Cardiol Young. 2011;21(2):225-6. 48. Alexi-Meskishvili V, Dahnert I, Hetzer R, et al. Origin of
32. Case RB, Morrow AG, Stainsby W, et al. Anomalous origin of the circumflex coronary artery from the pulmonary artery in
the left coronary artery. Circulation. 1958;17:1062-8. infants. Ann Thorac Surg. 1998;66(4):1406-9.
33. Sabiston DC, Neil CA, Taussig HB. The direction of blood flow 49. Ochoa-Ramirez E, Valdez-Garza HE, Reyes-Gonzalez R, et al.
in anomalous left coronary artery arising from the pulmonary Double anomalous coronary origin from the pumonary artery:
artery. Circulation. 1960;22:591-7. successful surgical correction in an infant. Tex Heart Inst J.
34. Cooley DA, Hallman GL, Bloodwell RD. Definitive surgical 2005;32(3):348-50.
treatment of anomalous origin of the left coronary artery from 50. Said SM, Dearani JA, Burkhart HM, Schaff HV. Surgical
pulmonary artery: indications and results. J Thorac Cardiovasc management of congenital coronary arterial anomalies in
Surg. 1966;52:798-808. adults.Cardiol Young 2010;20(Suppl. 3):68-85.
35. Meyer BW, Stefanik G, Stiles QR, et al. A method of definitive 51. Roberts WC, Shirani J. The four subtypes of anomalous origin
surgical treatment of anomalous origin of the left coronary of the left main coronary artery from the right aortic sinus
artery. A case report. J Thorac Cardiovasc Surg. 1968;56: (or from the right coronary artery). Am J Cardiol. 1992;70(1):
104-7. 119-21.
36. Neches WH, Mathews RA, Park SC, et al. Anomalous origin 52. Basso C, Maron BJ, Corrado D, et al. Clinical profile of con-
of the left coronary artery from the pulmonary artery. A new genital coronary artery anomalies with origin from the wrong
method of surgical repair. Circulation. 1974;50:582-7. aortic sinus leading to sudden death in young competitive
37. Vouhe PR, Tamisier D, Sidi D, et al. Anomalous left coronary athletes. J Am Coll Cardiol. 2000;35(6):1493-501.
artery from the pulmonary artery: results of isolated aortic 53. Liberthson RR. Sudden death from cardiac causes in children
reimplantation. Ann Thorac Surg. 1992;54:621-7. and young adults. N Engl J Med. 1996;334:1039-44.
38. Takeuchi S, Imamura H, Katsumoto K, et al. New surgical 54. Moustafa SE, Zehr K, Mookadam M, et al. Anomalous
method for repair of anomalous left coronary artery from interarterial left coronary artery: an evidence based systematic
pulmonary artery. J Thorac Cardiovasc Surg. 1979;78:7-11. overview. Int J Cardiol. 2008;126(1):13-20.
39. Kitamura S, Kawachi K, Nishii T, et al. Internal thoracic artery 55. Alphonso N, Anagnostopoulos PV, Nolke L, et al.
grafting for congenital coronary malformations. Ann Thorac Anomalous coronary artery from the wrong sinus of
Surg. 1992;53:513-6. Valsalva: a physiologic repair strategy. Ann Thorac Surg.
40. Chan RK, Hare DL, Buxton BF. Anomalous left main coronary 2007;83(4):1472-6.
artery arising from the pulmonary artery in an adult: treatment 56. Soon KH, Chaitowitz I, Selvanayagam JB, et al. Comparison
by internal mammary artery grafting. J Thorac Cardiovasc of fluoroscopic coronary angiography and multislice coronary
Surg. 1995;109:393-4. angiography in the characterization of anomalous coronary
41. Kottayil BP, Jayakumar K, Dharan BS, et al. Anomalous origin artery. Int J Cardiol. 2008;130(1):96-8.
of left coronary artery from pulmonary artery in older children 57. Post JC, van Rossum AC, Bronzwaer JGF, et al. Magnetic
and adults: direct aortic implantation. Ann Thorac Surg. resonance angiography of anomalous coronary arteries: a new
2011;91(2):549-53. gold standard for delineating the proximal course? Circulation.
42. Lange R, Vogt M, Horer J, et al. Long-term results of repair 1995;92:3163-71.
of anomalous origin of the left coronary artery from the 58. Gulati R, Reddy VM, Culbertson C, et al. Surgical management
pulmonary artery. Ann Thorac Surg. 2007;83(4):1463-71. of coronary artery arising from the wrong coronary sinus, using
43. Brown JW, Ruzmetov M, Parent JJ, et al. Does the degree standard and novel approaches. J ThoracCardiovascSurg.
of preoperative mitral regurgitation predict survival 2007;134(5):1171-8.
or the need for mitral valve repair or replacement in 59. Davies JE, Burkhart HM, Dearani JA, et al. Surgical manage
patients with anomalous origin of the left coronary artery ment of anomalous aortic origin of a coronary artery. Ann
from the pulmonary artery? J Thorac Cardiovasc Surg. ThoracSurg. 2009;88(3):844-7.
2008;136(3):743-8. 60. Duran AC, Angelini A, Frescura C, et al. Anomalous origin of
44. Ali WB, Metton O, Roubertie F, et al. Anomalous origin of the right coronary artery from the left aortic sinus and sudden
892
the left coronary artery from the pulmonary artery: late results infant death. Int J Cardiol. 1994;45(2):147-9.
61. Liberman L, Pass RH, Kaufman S, et al. Left coronary artery
arising from the non-coronary sinus: a rare congenital coronary
72. Latson L. Coronary artery fistulas: how to manage them.
Catheter CardiovascInterv. 1997;70:110-16.
62
anomaly. Pediatr Cardiol. 2005;26(5):672-4. 73. Levin DC, Fellows KE, Abrams HL. Hemodynamically

62. Desmet W, Vanhaecke J, Vrolix M, et al. Isolated single significant primary anomalies of the coronary arteries:
coronary artery: a review of 50,000 consecutive coronary angiographic aspects. Circulation. 1978;58:25-34.
angiographies. Eur Heart J. 1992;13(12):1637-40. 74. Holzer R, Johnson R, Ciotti G, et al. Review of an institutional
63. Akcay A, Tuncer C, Batyraliev T, et al. Isolated single coronary experience of coronary arterial fistulas in childhood set in context
artery: a series of 10 cases. Circ J. 2008;72(8):1254-8. of review of the literature. Cardiol Young. 2004;14:380-5.
64. Musiani A, Cernigliaro C, Sansa M, et al. Left main coronary 75. Sharland GK, Tynan M, Qureshi SA. Prenatal detection and
artery atresia: literature review and therapeutical considerations. progression of right coronary artery to right ventricle fistula.
Eur J CardiothoracSurg. 1997;11(3):505-14. Heart. 1996;76:79-81.
65. Knobel B, Rosman P, Kriwisky M, et al. Sudden death and 76. Liberthson RR, Sagar K, Berkoben JP, et al. Congenital coronary
cerebral anoxia in a young woman with congenital ostial stenosis artery fistula: report of 13 patients, review of the literature and
of the left main coronary artery. Catheter CardiovascInterv. delineation of management. Circulation. 1979;59(5):849-54.
1999;48(1):67-70. 77. Tavora F, Burke A, Kutys R, et al. Total anomalous origin
66. Satran A, Dawn B, Leesar MA. Congenital ostial left main of the coronary circulation from the right pulmonary artery.
coronary artery stenosis associated with a bicuspid aortic valve Cardiovasc Pathol. 2008;17(4):246-9.
in a young woman. J Invasive Cardiol. 2006;18(3):E114-E116. 78. Misumi T, Nishikawa K, Yasudo M, et al. Rupture of an
67. Mohlenkamp S, Hort W, Ge J, Erbel R. Update on myocardial aneurysm of a coronary arteriovenous fistula. Ann Thorac
bridging. Circulation. 2002;106(20):2616-22. Surg. 2001;71:2026-7.
68. Achrafi H. Hypertrophic cardiomyopathy and myocardial 79. Zenooz NA, Habibi R, Mammen L, et al. Coronary artery
bridging. Int J Cardiol. 1992;37:111-2. fistulas: CT findings. Radiographics. 2009;29(3):781-9.
69. Alegria JR, Herrmann J, Holmes DR, et al. Myocardial 80. Hsieh KS, Huang TC, Lee CL. Coronary artery fistulas in
bridging. Eur Heart J. 2005;26(12):1159-68. neonates, infants and children: Clinical findings and outcome.
70. Angelini P, Tivellato M, Donis J, et al. Myocardial bridges: a Pediatr Cardiol. 2002;23:415-19.
review. Prog Cardiovasc Dis. 1983;26(1):75-88. 81. Reidy JF, Sowton E, Ross DN. Transcatheter occlusion of
71. Schwartz ER, Klues HG, vom Dahl J, et al. Functional character- coronary to bronchial anastomosis by detachable balloon
istics of myocardial bridging: a combined angiographic and intra- combined with coronary angioplasty at same procedure. British
coronary Doppler flow study. Eur Heart J. 1997;18(3):434-42. Heart Journal. 1983;49:284-7.
893
C hapter
63 Cardiac and Extracardiac Masses
Bhanu Duggal, Vijayalakshmi IB, Nirav Panchani
Cardiac masses have been classified as either secondary or Table 1


primary. Secondary or metastatic tumors of the heart are 20 General manifestations of cardiac tumors
to 40 times more common than primary tumors and should
be suspected, when a patient with an underlying malignancy Pericardial involvement
develops signs and symptoms of cardiovascular disease.1 • Pericarditis
Primary cardiac tumors are extremely rare. Autopsy incidence • Pericardial effusion
• Radiographic enlargement
is only 0.02 percent. They may be classified by location or by • Arrhythmia, predominantly atrial
histology.1-3 • Tamponade
• Constriction and compression of various cardiac structures
Clinical Features Myocardial involvement
• Arrhythmias, ventricular and atrial
Cardiac tumors produce no characteristic signs and symptoms • Electrocardiographic changes
unless they interfere with cardiac function. Hence only 5 to • Radiographic enlargement—generalized, localized
10 percent may be diagnosed clinically, while some may be • Conduction disturbances and heart block
found incidentally during evaluation for a seemingly unrelated • Congestive heart failure
problem or physical finding. Because symptoms mimic other • Coronary involvement—angina, infarction
cardiac conditions, the clinical challenge is to consider the Intracavitary tumor
possibility of a cardiac tumor so that the appropriate diagnostic • Cavity obliteration
test(s) can be conducted.4 • Valve obstruction and valve damage
The symptoms depend on the anatomic location of the tumor • Embolic phenomena—systemic, neurologic, coronary
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 Occasionally, a large mobile tumor can completely obstruct
pericardium (Table 1). The clinical presentation is determined an inflow/outflow leading to transient syncope and even
by many factors including presence of the tumor on the left/ sudden cardiac death (SCD). As the cardiac output is severely
right side of the heart, size (mass effect), growth rate, friability, reduced it may result in the development of angina. Systolic
mobility and degree of invasiveness. blood pressure may be low. Fragmentation of the tumor may
cause embolization.
Intracavitary tumors
Left Atrial Tumors
Intracavitary tumors are most commonly located in the atria
and produce clinical manifestations by interfering with cardiac Tumors arising in the left atrium (LA) tend to grow into the
filling or ejection (Table 2). Exertional dyspnea is common atrial lumen and cause symptoms of mitral stenosis or mitral
and when cardiac failure develops it is intractable because of regurgitation (damaged valve by tumor prolapse termed
the mechanical obstruction to the atrial or ventricular filling. ‘wrecking ball’ phenomenon). Left atrial tumors thus may
This obstruction may be progressive as the size of the tumor simulate mitral valve disease and produce heart failure and/or
increases or intermittent in pedunculated, mobile tumors. secondary pulmonary hypertension.
Table 2
 63
Clinical features in intracavitary tumors
Cardiac and Extracardiac Masses

Location Clinical features Symptoms Examples
Left atrial Left ventricular inflow Dyspnea, paroxysmal nocturnal dyspnea, Myxoma
obstruction orthopnea, syncope, sudden cardiac death Fibroma
(SCD) (may have postural variation) Undifferentiated
especially myxomas sarcoma
Osteosarcoma
Embolism—central nervous Stroke, myocardial infarction (MI)
system, coronary,
peripheral, retinal
Left ventricle Left ventricular outflow Angina, syncope, SCD,

obstruction murmur on examination
Systemic embolism Stroke, SCD, MI Papillary fibroelastoma
Intramural—arrhythmias Ventricular tachycardia, ventricular fibrillation, Fibroma

atrioventricular blocks
Right atrium Benign superior vena cava Right heart failure, i.e. peripheral Myxoma
syndrome (obstruction) edema, ascites
Tricuspid stenosis/regurgitation Murmur increasing with respiration Angiosarcoma
Cyanosis, R-L shunt through patent foramen

ovale
Right ventricle Right ventricular inflow and Dyspnea, appropriate murmurs, Fibroma
outflow obstruction syncope
Pulmonary embolism Right heart failure Rhabdomyoma
Pulmonary hypertension Hamartoma
Commonly observed symptoms and signs include dyspnea, angiosarcomas are the commonest malignant primary tumors
orthopnea, paroxysmal nocturnal dyspnea, pulmonary edema, and have a predilection to arise in the RA. Tumors arising in
cough, hemoptysis, edema and fatigue. Symptoms may be the RA grow into the atrial lumen and obstruct blood flow,
worse in certain body positions in mobile pedunculated producing hemodynamic changes that are similar to those seen
tumors as in the left atrial myxoma. Respiratory symptoms with triscuspid stenosis/regurgitation. Typical cardiovascular
due to pulmonary venous hypertension that worsen rather than signs and symptoms are those of right heart failure (i.e. fatigue,
improve in the upright position are a clue to the diagnosis of peripheral edema, hepatomegaly, ascites and prominent ‘a
this tumor. The characteristics of the clinical findings vary waves’ in the jugular veins). On physical examination, a
on repeat examinations. On physical examination along diastolic murmur along with the ‘tumor plop’ may be heard.
with the diastolic murmur, a characteristic ‘tumor plop’ Occasionally patients present with recurrent arrhythmias. In
may be heard in early diastole (only in 15% of the cases). A addition to obstructing circulation through the right side of the
fixed tumor does not produce a positional alteration in signs heart, tumor fragments may be released into the pulmonary
and symptoms. The patients along with clinical features of circulation, causing symptoms consistent with pulmonary
pulmonary venous hypertension often have a history of atrial embolism. Right atrial hypertension can result in shunting of
arrhythmia. In addition to interfering with the circulation, left venous blood into the systemic circulation if a patent foramen
atrial tumors may release tumor fragments or thrombi into the ovale is present, resulting in hypoxemia or systemic emboli.
systemic circulation. The most serious complications of such
embolization are neurologic. Right Ventricular Tumors
Right Atrial Tumors Tumors arising in the right ventricle (RV) can be mis-
diagnosed as pulmonic stenosis, restrictive cardiomyopathy 895
Similar to left atrial tumors, myxomas are the most common or tricuspid regurgitation. Lesions arising in the RV may
tumors of the right atrium (RA). Sarcomas and in particular, result in right-sided heart failure or right ventricular outflow
12 obstruction leading to shortness of breath, syncope and sudden Table 3

death. Prevalence of primary cardiac tumors
Miscellaneous
Benign Myxoma 27%

Left Ventricular Tumors
Rhabdomyomas 20%
Intracavitary left ventricular tumors often result in narrowing
of the left ventricular outflow tract and present as aortic Lipoma 10%
stenosis or hypertrophic obstructive cardiomyopathy. Papillary fibroelastoma 8%
Hemangioma 5%
Intramural tumors
Mesothelioma of the atrioventricular
Intramural tumors may remain completely asymptomatic (AV) node/paragangliomas/ 1%
Pheochromocytoma
for a long-time and cause symptoms at a late stage due to
myocardial damage or compression of the cardiac conduction Malignant Angiosarcoma 9%
system with tumor expansion. Small but strategically placed Rhabdomyosarcoma 5%
tumors can cause an earlier development of symptoms.
Patients may present with Stokes-Adams syncope due Mesothelioma 4%
to complete heart block or palpitations due to ventricular Fibrosarcoma 3%
arrhythmias. Symptoms and signs of left and/or right ventricular
Malignant lymphoma 2%
decompensation are together important clinical manifestations
of myocardial tumors. Clinical signs may be subtle and consist Extraskeletal osteosarcoma 1%
only of gallop rhythm and sinus tachycardia. With more severe Cysts Pericardial 18%
degree of myocardial involvement cardiomegaly, pulmonary
Bronchogenic 2%
congestion and peripheral edema may occur.
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 A B
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
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 C
Histologically, these tumors are composed of scattered Figures 1A to C: A. Solid, polypoidal, smooth-surfaced mass lesion
cells within a mucopolysaccharide stroma (Figures 1A to C). attached to the inter-atrial septum on left atrial aspect; B. Cut surface
The cells originate from a multipotent mesenchyme that is shows myxoid, greenish yellow appearance with foci of hemorrhage;
C. Stellate to spindle shaped cells in myxoid background. Note
capable of neural and endothelial differentiation. Myxomas perivascular arrangement of cells (H&E x 400). Courtesy: Dr Pradeep
896 produce vascular endothelial growth factor (VEGF) which Vaideeswar
probably contributes to the induction of angiogenesis and the occur due to the release of vasoactive substances including 63
early stages of tumor growth. interleukin-6. Hemolytic anemia is associated with calcified
Macroscopically, typical myxomas are pedunculated and myxomas in a right atrial location.
Cardiac and Extracardiac Masses

gelatinous in consistency; the surface may be smooth, villous, Familial myxomas constitute 4.5 to 10 percent of all
or friable. Tumors vary widely in size, ranging from 1 to 15 myxomas and a significant portion of them are related to
cm (mean 5 cm) in diameter and weight between 15 and 180 g. Carney complex, a familial autosomal dominant syndrome.
About 35 percent of myxomas are friable or villous and these They are likely to have a earlier presentation (median 20
tend to present with emboli. Larger tumors are more likely to years), atypical location, multiple tumors and higher chances
have a smooth surface and are associated with cardiovascular of recurrence. They also have one or more of the following
symptoms. features: cutaneous lentiginosis or unusual hyperpigmented
skin lesions (excessive freckling), neurofibromas or a rare
Clinical Features endocrine neoplasm. Patient with cardiac myxomas and
pigmentary abnormality has been described as NAME (naevi,
The patient is usually 30-60 years old and may be asymptomatic atrial myxoma, myxoid, neurofibroma, ephelids) and LAMB
(20%) or present with a clinical triad of embolic events, (lentigines, atrial myxoma and blue naevi) syndrome.8
cardiac symptoms and constitutional symptoms.7 In nearly
one-third of the cases the cardiac myxoma can present with Investigations
embolic symptoms of which the central nervous system is the
commonest (83%). The other embolic locations are the retinal Two-dimensional echocardiography is the imaging modality
artery (3%), the upper and lower extremities (45%) and the of choice, which is used to identify the tumor (Figures 2A
coronary arteries (12%). Ischemic stroke and acute myocardial and B), its location, size, functional valvar obstruction
infarction are the dreaded complications of embolism. (Doppler gradient) and exclusion of multiple mass.9 The
Recurrent emboli to the central nervous system may lead to myxoma is a polypoid, mobile structure with a heterogenous
formation of intracranial aneurysms as tumor emboli infiltrate echogenicity. Its attachment to the IAS helps to differentiate
and weaken the vessel wall and 12 percent of the cases can have it from a thrombus. A careful search for multiple cardiac
intracerebral hemorrhage or subarachnoid hemorrhage (5%). tumors should be made to differentiate sporadic from familial
The myxoma is attached by a stalk to the interatrial septum myxomas. If transthoracic echocardiography (TTE) has poor
(IAS) and may be large enough to cause atrioventricular acoustics, transesophageal echocardiography (TEE) may be
(AV) valve obstruction (less often regurgitation) due to used for the diagnosis. LA being a posterior structure, TEE
prolapse of the tumor across the annulus during ventricular permits superior imaging of LA myxomas. Computerized
filling in diastole. A highly mobile tumor in the LA can cause tomography (CT) (Figure 2C) and magnetic resonace imaging
intermittent obstruction and positional symptoms. Left atrial (MRI) have no incremental value in the diagnostic workup
myxomas can cause mitral valve obstruction with dyspnea of a classical myxoma unless it has an unusual location or
and orthopnea from pulmonary edema or heart failure. Right attachment. Due to the autosomal dominant transmission of
atrial myxoma may obstruct the tricuspid valve and cause Carney complex, identification of multiple cardiac myxomas
symptoms of right heart failure. Constitutional symptoms in a young individual should prompt echocardiographic
of fever, malaise with raised inflammatory markers may screening of first-degree relatives.
A B C
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 IAS—classical 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 897
Madhav Hegde
12 Treatment and Prognosis signal intensity of lipomas on T1-weighed images on MRI
shows the superior diagnostic ability of this modality. For the
Once a presumptive diagnosis of myxoma has been made on atrial arrhythmias, medical management with antiarrhythmics
Miscellaneous
imaging studies, prompt resection for complete removal of the should be given, but if the patient fails to respond , surgical
myxoma is required because of the risk of embolization or resection is indicated. Because of the symptoms they cause
cardiovascular complications, including sudden death. The atrial and their progressive growth, myocardial lipomas usually
septum to which the myxoma is attached should be excised and require resection.
if this is a substantial portion of the septum, a Dacron patch Lipomatous hypertrophy of the IAS is an exaggerated
is used for the repair. This leads to normalization of serum growth of non-encapsulated normal fat existing within the
interleukin-6 levels and resolution of constitutional symptoms septum at the level of fossa ovalis and is not a true tumor.12
and the intracranial aneurysms may regress and resolve. Cardiac The septal hypertrophy is greater than 2 cm in thickness
transplantation has been reported for other tumors and might be (normal < 1 cm) and is seen primarily in older patients and
considered for multiple recurrent atrial myxomas. in those who are obese. In the absence of symptoms of atrial
Postoperative recovery is generally rapid. However, atrial arrhythmias or heart block, they do not require resection. It is
arrhythmias or AV conduction abnormalities were present often necessary to differentiate lipomatous hypertrophy of the
postoperatively in 26 percent of patients in one series. In IAS from lipomas. This is often seen in obese elderly people
addition, patients are at risk for recurrence of the myxoma, and a TEE is required to show the hour glass septum with fatty
which may occur in 2 to

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A Comprehensive Approach to

Professor of Pediatric Cardiology

JAYPEE BROTHERS MEDICAL PUBLISHERS (P) LTD

Jaypee Brothers Medical Publishers (P) Ltd

Jaypee Brothers Medical Publishers (P) Ltd

© 2013, Jaypee Brothers Medical Publishers

Inquiries for bulk sales may be solicited at: jaypee@jaypeebrothers.com

A Comprehensive Approach to Congenital Heart Diseases

First Edition: 2013

—Dr P Syamasundar Rao

—Dr Reema Chugh

Monroe Carell Jr Children’s Hospital Bangaluru, India Congenital Heart Centre

S Padmavati FRCP (Lond), FRCPE, FAMS, FACC, FAHA,

School, Houston, Texas, USA.

1. Development of the Cardiovascular System 3

7. Examination of the Heart—A Comparative External and Internal Anatomy 119

15. Anomalies of Systemic Veins 213

Section 4: Shunt Defects

18. Interatrial Defects 253

Section 5: Right and Left Ventricular Obstructive Lesions

25. Right Ventricular Outflow Tract Obstructions 357

Section 6: Congenital Valvar Lesions

28. Tricuspid Atresia 397

Section 7: Diseases of the Aorta

34. Coarctation of the Aorta 505

Section 8: Cyanotic Heart Diseases

37. Tetralogy of Fallot 547

47. Hypoplastic Left Heart Syndrome 665

48. Dilated Cardiomyopathy 685

Section 10: Congenital Heart Disease in Adults

53. Transitional Care in Congenital Heart Disease 745

Section 11: Electrophysiological Issues in Children

59. Congenital Heart Blocks and Bradyarrhythmias 839

Section 13: General Issues

69. Prevention of Congenital Heart Diseases 971

Epilogue—IB Vijayalakshmi 1089

Embryo to the Neonate

Varsha Kaulgud Mokhasi

DEvElopmENt oF thE CArDiovAsCulAr systEm

DEvElopmENt oF thE CArDiovAsCulAr systEm

DEvElopmENt oF thE CArDiovAsCulAr systEm

Figures 8A to C: Formation of atrioventricular valves and chordae tendinae

DEvElopmENt oF thE CArDiovAsCulAr systEm

DEvElopmENt oF thE CArDiovAsCulAr systEm

return poorly oxygenated blood from the body of the embryo

DEvElopmENt oF thE CArDiovAsCulAr systEm

Chitra Narasimhan, Vijayalakshmi IB

Introduction ventricles work in parallel instead of in series as in the adult,

Percentage of combined cardiac output Control of the Fetal Circulation

Introduction There are six supposed pathogenetic mechanisms of CHD

Pathogenetic Mechanisms Infections

ductus arteriosus (20%) and peripheral pulmonic stenosis

Therapeutic Drug Exposure Fluconazole

Etiopathogenesis of Congenital Heart Diseases

The incidence of CHD was increased among infants of Female Hormones

Non-steroidal Anti-inflammatory Drugs Chemotherapy

Diabetes Mellitus Defects

Etiopathogenesis of Congenital Heart Diseases

Etiopathogenesis of Congenital Heart Diseases

Vitamins Indirect Evidence

Herbicides, Pesticides and Rodenticides Ionizing Radiation

Etiopathogenesis of Congenital Heart Diseases

non-chromosomal atrioventricular septal defects, atrial septal